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Conserved domains on  [gi|30027621|gb|AAP13442|]
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nonstructural polyprotein pp1ab [SARS coronavirus Urbani]

Protein Classification

Graphical summary

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List of domain hits

Name Accession Description Interval E-value
SARS-CoV-like_RdRp cd21591
Severe acute respiratory syndrome coronavirus RNA-dependent RNA polymerase, also known as ...
4375-5301 0e+00

Severe acute respiratory syndrome coronavirus RNA-dependent RNA polymerase, also known as non-structural protein 12, and similar proteins from betacoronaviruses in the B lineage: responsible for replication and transcription of the viral RNA genome; This group contains the RNA-dependent RNA polymerase (RdRp) of Severe acute respiratory syndrome coronavirus (SARS-CoV), SARS-CoV-2 (also known as 2019 novel CoV (2019-nCoV) or COVID-19 virus), and similar proteins from betacoronaviruses in the sarbecovirus subgenera (B lineage). CoVs utilize a multi-subunit replication/transcription machinery. A set of non-structural proteins (Nsps) generated as cleavage products of the ORF1a and ORF1ab viral polyproteins assemble to facilitate viral replication and transcription. A key component, the RNA-dependent RNA polymerase (RdRp, also known as Nsp12), catalyzes the synthesis of viral RNA and thus plays a central role in the replication and transcription cycle of CoV, possibly interacting with its co-factors, Nsp7 and Nsp8. RdRp is therefore considered a primary target for nucleotide analog antiviral inhibitors such as remdesivir, which shows potential for the treatment of SARS-CoV-2 viral infections. The structure of SARS-CoV-2 Nsp12 contains a RdRp domain as well as a large N-terminal extension that adopts a nidovirus RdRp-associated nucleotidyltransferase (NiRAN) architecture. Recent studies have shown that the SARS-CoV-2 RdRp requires two iron-sulfur clusters to function optimally. Earlier studies had mistakenly identified these iron-sulfur cluster binding sites for zinc-binding sites, likely because iron-sulfur clusters degrade easily under standard experimental conditions.The RdRp domain displays a right hand with three functional subdomains, called fingers, palm, and thumb. All RdRps contain conserved polymerase motifs (A-G), located in the palm (A-E motifs) and finger (F-G) subdomains. All these motifs have been implicated in RdRp fidelity such as processes of correct incorporation and reorganization of nucleotides.


:

Pssm-ID: 394895  Cd Length: 928  Bit Score: 1903.66  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 4375 TFLNRVCGVSAARLTPCGTGTSTDVVYRAFDIYNEKVAGFAKFLKTNCCRFQEKDEEGNLLDSYFVVKRHTMSNYQHEET 4454
Cdd:cd21591    2 SFLNRVCGVSAARLTPCGTGTSTDVVYRAFDIYNDKVAGFAKFLKTNCCRFQEKDEDGNLIDSYFVVKRHTFSNYQHEET 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 4455 IYNLVKDCPAVAVHDFFKFRVDGDMVPHISRQRLTKYTMADLVYALRHFDEGNCDTLKEILVTYNCCDDDYFNKKDWYDF 4534
Cdd:cd21591   82 IYNLLKDCPAVAVHDFFKFRVDGDMVPHISRQRLTKYTMADLVYALRHFDEGNCDTLKEILVTYNCCDDDYFNKKDWYDF 161
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 4535 VENPDILRVYANLGERVRQSLLKTVQFCDAMRDAGIVGVLTLDNQDLNGNWYDFGDFVQVAPGCGVPIVDSYYSLLMPIL 4614
Cdd:cd21591  162 VENPDILRVYANLGERVRQALLKTVQFCDAMRDAGIVGVLTLDNQDLNGNWYDFGDFIQTTPGSGVPIVDSYYSLLMPIL 241
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 4615 TLTRALAAESHMDADLAKPLIKWDLLKYDFTEERLCLFDRYFKYWDQTYHPNCINCLDDRCILHCANFNVLFSTVFPPTS 4694
Cdd:cd21591  242 TLTRALTAESHVDTDLTKPYIKWDLLKYDFTEERLKLFDRYFKYWDQTYHPNCVNCLDDRCILHCANFNVLFSTVFPPTS 321
                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 4695 FGPLVRKIFVDGVPFVVSTGYHFRELGVVHNQDVNLHSSRLSFKELLVYAADPAMHAASGNLLLDKRTTCFSVAALTNNV 4774
Cdd:cd21591  322 FGPLVRKIFVDGVPFVVSTGYHFRELGVVHNQDVNLHSSRLSFKELLVYAADPAMHAASGNLLLDKRTTCFSVAALTNNV 401
                        410       420       430       440       450       460       470       480
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 4775 AFQTVKPGNFNKDFYDFAVSKGFFKEGSSVELKHFFFAQDGNAAISDYDYYRYNLPTMCDIRQLLFVVEVVDKYFDCYDG 4854
Cdd:cd21591  402 AFQTVKPGNFNKDFYDFAVSKGFFKEGSSVELKHFFFAQDGNAAISDYDYYRYNLPTMCDIRQLLFVVEVVDKYFDCYDG 481
                        490       500       510       520       530       540       550       560
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 4855 GCINANQVIVNNLDKSAGFPFNKWGKARLYYDSMSYEDQDALFAYTKRNVIPTITQMNLKYAISAKNRARTVAGVSICST 4934
Cdd:cd21591  482 GCINANQVIVNNLDKSAGFPFNKWGKARLYYDSMSYEDQDALFAYTKRNVIPTITQMNLKYAISAKNRARTVAGVSICST 561
                        570       580       590       600       610       620       630       640
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 4935 MTNRQFHQKLLKSIAATRGATVVIGTSKFYGGWHNMLKTVYSDVETPHLMGWDYPKCDRAMPNMLRIMASLVLARKHNTC 5014
Cdd:cd21591  562 MTNRQFHQKLLKSIAATRGATVVIGTSKFYGGWHNMLKTVYSDVENPHLMGWDYPKCDRAMPNMLRIMASLVLARKHTTC 641
                        650       660       670       680       690       700       710       720
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 5015 CNLSHRFYRLANECAQVLSEMVMCGGSLYVKPGGTSSGDATTAYANSVFNICQAVTANVNALLSTDGNKIADKYVRNLQH 5094
Cdd:cd21591  642 CSLSHRFYRLANECAQVLSEMVMCGGSLYVKPGGTSSGDATTAYANSVFNICQAVTANVNALLSTDGNKIADKYVRNLQH 721
                        730       740       750       760       770       780       790       800
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 5095 RLYECLYRNRDVDHEFVDEFYAYLRKHFSMMILSDDAVVCYNSNYAAQGLVASIKNFKAVLYYQNNVFMSEAKCWTETDL 5174
Cdd:cd21591  722 RLYECLYRNRDVDTDFVNEFYAYLRKHFSMMILSDDAVVCFNSTYASQGLVASIKNFKSVLYYQNNVFMSEAKCWTETDL 801
                        810       820       830       840       850       860       870       880
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 5175 TKGPHEFCSQHTMLVKQGDDYVYLPYPDPSRILGAGCFVDDIVKTDGTLMIERFVSLAIDAYPLTKHPNQEYADVFHLYL 5254
Cdd:cd21591  802 TKGPHEFCSQHTMLVKQGDDYVYLPYPDPSRILGAGCFVDDIVKTDGTLMIERFVSLAIDAYPLTKHPNQEYADVFHLYL 881
                        890       900       910       920
                 ....*....|....*....|....*....|....*....|....*..
gi 30027621 5255 QYIRKLHDELTGHMLDMYSVMLTNDNTSRYWEPEFYEAMYTPHTVLQ 5301
Cdd:cd21591  882 QYIRKLHDELTGHMLDMYSVMLTNDNTSRYWEPEFYEAMYTPHTVLQ 928
betaCoV_Nsp2_SARS-like cd21516
betacoronavirus non-structural protein 2 (Nsp2) similar to SARS-CoV Nsp2, and related proteins ...
182-818 0e+00

betacoronavirus non-structural protein 2 (Nsp2) similar to SARS-CoV Nsp2, and related proteins from betacoronaviruses in the B lineage; Non-structural proteins (Nsps) from Severe acute respiratory syndrome coronavirus (SARS-CoV) and betacoronaviruses in the sarbecovirus subgenus (B lineage) are encoded in ORF1a and ORF1b. Post infection, the SARS-CoV genomic RNA is released into the cytoplasm of the cell and translated into two long polyproteins (pp), pp1a and pp1ab, which are then autoproteolytically cleaved by two viral proteases Nsp3 and Nsp5 into smaller subunits. Nsp2 is one of these subunits. The function of Nsp2 remains unknown. Deletion of Nsp2 from the SARS-CoV genome results in only a modest reduction in viral titers. Rather than playing a role in viral replication, SARS-CoV Nsp2 may be involved in altering the host cell environment; it has been shown to interact with two host proteins, prohibitin 1 (PHB1) and PHB2 which have been implicated in cellular functions, including cell-cycle progression, cell migration, cellular differentiation, apoptosis, and mitochondrial biogenesis.


:

Pssm-ID: 439199  Cd Length: 637  Bit Score: 1238.88  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621  182 VTRYVDNNFCGPDGYPLDCIKDFLARAGKSMCTLSEQLDYIESKRGVYCCRDHEHEIAWFTERSDKSYEHQTPFEIKSAK 261
Cdd:cd21516    1 YTRYVDNNFCGPDGYPLECIKDLLARAGKSSCPLSEQLDFIGLKRGVYCCREHEHEIAWYTERSEKSYELQTPFEIKSAK 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621  262 KFDTFKGECPKFVFPLNSKVKVIQPRVEKKKTEGFMGRIRSVYPVASPQECNNMHLSTLMKCNHCDEVSWQTCDFLKATC 341
Cdd:cd21516   81 KFDTFKGECPHFVFPLNSTVKVIQPRVEKKKTEGFMGRIRSVYPVASPGECNPMALSTLMKCNHCGETSWQTSDFLKATC 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621  342 EHCGTENLVIEGPTTCGYLPTNAVVKMPCPACQDPEIGPEHSVADYHNHSNIETRLRKGGRTRCFGGCVFAYVGCYNKRA 421
Cdd:cd21516  161 EFCGTENLTKEGPTTCGYLPQNAVVKMPCPACKNDEVGPEHSLADYHNHSGIETRLRKGGRTVCFGGCVFAYVGCYNKCA 240
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621  422 YWVPRASADIGSGHTGITGDNVETLNEDLLEILSRERVNINIVGDFHLNEEVAIILASFSASTSAFIDTIKSLDYKSFKT 501
Cdd:cd21516  241 YWVPRASANIGSNHTGVVGEDVETLNDDLLEILQREKVNINIVGDFKLNEEVAIILASFSASTSAFIETVKGLDYKTFKQ 320
                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621  502 IVESCGNYKVTKGKPVKGAWNIGQQRSVLTPLCGFPSQAAGVIRSIFARTLDAANHSIPDLQRAAVTILDGISEQSLRLV 581
Cdd:cd21516  321 IVESCGNFKVTKGKAKKGAWNIGTQKSVLTPLLAFPSQAAGVVRSIFSRTLDTAGHSLRALQRAAITILDGISPQSLRLL 400
                        410       420       430       440       450       460       470       480
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621  582 DAMVYTSDLLTNSVIIMAYVTGGLVQQTSQWLSNLLGTTVEKLRPIFEWIEAKLSAGVEFLKDAWEILKFLITGVFDIVK 661
Cdd:cd21516  401 DAMVFTSDLATNSVLVMAYDTGGLVQVTSQWLDNLFGTCADKLKPVLTWLEEKLKEGVDFLRDAWEILKFLVTGAYKIVK 480
                        490       500       510       520       530       540       550       560
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621  662 GQIQVASDNIKDCVKCFIDVVNKALEMCIDQVTIAGAKLRSLNLGEVFIAQSKGLYRQCIRGKEQLQLLMPLKAPKEVTF 741
Cdd:cd21516  481 GQIVLAAKNIKECVQSFVAVVNKVLSLCYDQIQIAGAKVGALNLGETFIAQSKGLYRVCVRAREIQQLLMPLKAPKELTF 560
                        570       580       590       600       610       620       630
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 30027621  742 LEGDSHDTVLTSEEVVLKNGELEALETPVDSFTNGAIVGTPVCVNGLMLLEIKDKEQYCALSPGLLATNNVFRLKGG 818
Cdd:cd21516  561 LEGDTLDTELTSEEVVLKTGTLEALDTPTSEVVNGPVEGTPVCVNGLMLLEIKDKEQYCALSPDCQATNNVFTLKGG 637
TM_Y_SARS-CoV-like_Nsp3_C cd21717
C-terminus of non-structural protein 3, including transmembrane and Y domains, from Severe ...
2209-2739 0e+00

C-terminus of non-structural protein 3, including transmembrane and Y domains, from Severe acute respiratory syndrome-related coronavirus and betacoronavirus in the B lineage; This model represents the C-terminus of non-structural protein 3 (Nsp3) from betacoronavirus in the sarbecovirus subgenus (B lineage), including highly pathogenic human coronaviruses such as Severe acute respiratory syndrome-related coronavirus (SARS-CoV) and SARS-CoV2 (also called 2019 novel CoV or 2019-nCoV). This conserved C-terminus includes two transmembrane (TM) regions TM1 and TM2, an ectodomain (3Ecto) between the TM1 and TM2 that is glycosylated and located on the lumenal side of the ER, an amphiphatic region (AH1) that is not membrane-spanning, and a large Y domain of approximately 370 residues. Nsp3 is a large multi-functional multi-domain protein that is an essential component of the replication/transcription complex (RTC), which carries out RNA synthesis, RNA processing, and interference with the host cell innate immune system. In SARS-CoV and the related murine hepatitis virus (MHV), the TM1, 3Ecto and TM2 domains are important for the papain-like protease (PL2pro) domain to process Nsp3-Nsp4 cleavage. It has also been shown that the interaction of 3Ecto with the lumenal loop of Nsp4 is essential for ER rearrangements in cells infected with SARS-CoV or MHV. The Y domain, located at the cytosolic side of the ER, consists of the Y1 and CoV-Y subdomains, which are conserved in nidovirus and coronavirus, respectively. Functional information about the Y domain is limited; it has been shown that Nsp3 binding to Nsp4 is less efficient without the Y domain.


:

Pssm-ID: 409665  Cd Length: 531  Bit Score: 1169.76  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 2209 WLLLLSICLGSLICVTAAFGVLLSNFGAPSYCNGVRELYLNSSNVTTMDFCEGSFPCSICLSGLDSLDSYPALETIQVTI 2288
Cdd:cd21717    1 WLLLLSICLGSLIYVTAALGVLLSNLGAPSYCDGVRESYLNSSNVTTMDFCEGSFPCSVCLSGLDSLDSYPALETIQVTI 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 2289 SSYKLDLTILGLAAEWVLAYMLFTKFFYLLGLSAIMQVFFGYFASHFISNSWLMWFIISIVQMAPVSAMVRMYIFFASFY 2368
Cdd:cd21717   81 SSYKLDLTILGLAAEWFLAYMLFTKFFYLLGLSAIMQVFFGYFASHFISNSWLMWFIISIVQMAPVSAMVRMYIFFASFY 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 2369 YIWKSYVHIMDGCTSSTCMMCYKRNRATRVECTTIVNGMKRSFYVYANGGRGFCKTHNWNCLNCDTFCTGSTFISDEVAR 2448
Cdd:cd21717  161 YIWKSYVHIMDGCTSSTCMMCYKRNRATRVECTTIVNGMKRSFYVYANGGRGFCKTHNWNCLNCDTFCAGSTFISDEVAR 240
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 2449 DLSLQFKRPINPTDQSSYIVDSVAVKNGALHLYFDKAGQKTYERHPLSHFVNLDNLRANNTKGSLPINVIVFDGKSKCDE 2528
Cdd:cd21717  241 DLSLQFKRPINPTDQSSYVVDSVAVKNGALHLYFDKAGQKTYERHPLSHFVNLDNLRANNTKGSLPINVIVFDGKSKCDE 320
                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 2529 SASKSASVYYSQLMCQPILLLDQVLVSDVGDSTEVSVKMFDAYVDTFSATFSVPMEKLKALVATAHSELAKGVALDGVLS 2608
Cdd:cd21717  321 SAAKSASVYYSQLMCQPILLLDQALVSDVGDSTEVSVKMFDAYVDTFSATFSVPMEKLKALVATAHSELAKGVALDGVLS 400
                        410       420       430       440       450       460       470       480
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 2609 TFVSAARQGVVDTDVDTKDVIECLKLSHHSDLEVTGDSCNNFMLTYNKVENMTPRDLGACIDCNARHINAQVAKSHNVSL 2688
Cdd:cd21717  401 TFVSAARQGVVDTDVDTKDVIECLKLSHHSDLEVTGDSCNNFMLTYNKVENMTPRDLGACIDCNARHINAQVAKSHNVSL 480
                        490       500       510       520       530
                 ....*....|....*....|....*....|....*....|....*....|.
gi 30027621 2689 IWNVKDYMSLSEQLRKQIRSAAKKNNIPFRLTCATTRQVVNVITTKISLKG 2739
Cdd:cd21717  481 IWNVKDYMSLSEQLRKQIRSAAKKNNIPFRLTCATTRQVVNVITTKISLKG 531
betaCoV_Nsp14 cd21659
nonstructural protein 14 of betacoronavirus; Nonstructural protein 14 (Nsp14) of coronavirus ...
5907-6427 0e+00

nonstructural protein 14 of betacoronavirus; Nonstructural protein 14 (Nsp14) of coronavirus (CoV) plays an important role in viral replication and transcription. It consists of 2 domains with different enzymatic activities: an N-terminal exoribonuclease (ExoN) domain and a C-terminal cap (guanine-N7) methyltransferase (N7-MTase) domain. ExoN is important for proofreading and therefore, the prevention of lethal mutations. The association of Nsp14 with Nsp10 stimulates its ExoN activity; the complex hydrolyzes double-stranded RNA in a 3' to 5' direction as well as a single mismatched nucleotide at the 3'-end mimicking an erroneous replication product. The Nsp10/Nsp14 complex may function in a replicative mismatch repair mechanism. N7-MTase functions in mRNA capping. Nsp14 can methylate GTP, dGTP as well as cap analogs GpppG, GpppA and m7GpppG. The accumulation of m7GTP or Nsp14 has been found to interfere with protein translation of cellular mRNAs.


:

Pssm-ID: 394958  Cd Length: 519  Bit Score: 1085.52  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 5907 TGLFKDCSKIITGLHPTQAPTHLSVDIKFKTEG-LCVDIPGIPKDMTYRRLISMMGFKMNYQVNGYPNMFITREEAIRHV 5985
Cdd:cd21659    1 TGLFKDCSKSYVGLHPAYAPTFLSVDDKYKTNGdLCVCLNIIDSVVTYSRLISLMGFKLDLTLPGYPKLFITREEAIKRV 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 5986 RAWIGFDVEGCHATRDAVGTNLPLQLGFSTGVNLVAVPTGYVDTENNTEFTRVNAKPPPGDQFKHLIPLMYKGLPWNVVR 6065
Cdd:cd21659   81 RAWIGFDVEGAHATRDAIGTNFPLQLGFSTGVNFVVEPTGLVDTEDGYMFTKIVAKAPPGEQFKHLIPLMSKGQPWDVVR 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 6066 IKIVQMLSDTLKGLSDRVVFVLWAHGFELTSMKYFVKIGPERTCCLCDKRATCFSTSSDTYACWNHSVGFDYVYNPFMID 6145
Cdd:cd21659  161 IRIVQMLSDTLDDLSDSVVFVTWAHGFELTSLRYFAKIGKERTCCMCTKRATCYSSRTGYYGCWRHSVGCDYVYNPFIVD 240
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 6146 VQQWGFTGNLQSNHDQHCQVHGNAHVASCDAIMTRCLAVHECFVKRVDWSVEYPIIGDELRVNSACRKVQHMVVKSALLA 6225
Cdd:cd21659  241 VQQWGYTGNLQSNHDRYCSVHKGAHVASSDAIMTRCLAVHDCFCKRVNWDVEYPIISNELSINSSCRLVQRVVLKAALLA 320
                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 6226 DKFPVLHDIGNPKAIKCVPQAEVEWKFYDAQPCsdkAYKIEELFYSYATHHDKFTDGVCLFWNCNVDRYPANAIVCRFDT 6305
Cdd:cd21659  321 NRFDLCYDIGNPKGIACVKDPVVDWKFYDAQPV---VKSVKQLFYTYEAHKDQFKDGLCMFWNCNVDKYPANAIVCRFDT 397
                        410       420       430       440       450       460       470       480
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 6306 RVLSNLNLPGCDGGSLYVNKHAFHTPAFDKSAFTNLKQLPFFYYSDSPCESHGKQVVSDIDYVPLKSATCITRCNLGGAV 6385
Cdd:cd21659  398 RVLSKLNLPGCNGGSLYVNKHAFHTPAFDKSAFENLKPLPFFYYSDTPCEYHGGNDVKDVDYVPLKSATCITRCNLGGAV 477
                        490       500       510       520
                 ....*....|....*....|....*....|....*....|..
gi 30027621 6386 CRHHANEYRQYLDAYNMMISAGFSLWIYKQFDTYNLWNTFTR 6427
Cdd:cd21659  478 CRKHAEEYREYLEAYNTATTAGFTLWVYKTFDFYNLWNTFTK 519
betaCoV_Nsp13-helicase cd21722
helicase domain of betacoronavirus non-structural protein 13; This model represents the ...
5552-5891 0e+00

helicase domain of betacoronavirus non-structural protein 13; This model represents the helicase domain of non-structural protein 13 (Nsp13) from betacoronavirus, including pathogenic human viruses such as Severe acute respiratory syndrome coronavirus (SARS-CoV), SARS-CoV2 (also called 2019 novel CoV or 2019-nCoV), and Middle East respiratory syndrome-related (MERS) CoV. Helicases catalyze NTP-dependent unwinding of nucleic acid duplexes into single strands and are classified based on the arrangement of conserved motifs into six superfamilies. CoV Nsp13 is a member of the helicase superfamily 1 (SF1); SF1 and SF2 helicases do not form toroidal structures, while SF3-6 helicases do. Nsp13 is a component of the viral RNA synthesis replication and transcription complex (RTC). It is a multidomain protein containing a Cys/His rich zinc-binding domain (CH/ZBD), a stalk domain, a 1B domain involved in nucleic acid substrate binding, and a SF1 helicase core.


:

Pssm-ID: 409655 [Multi-domain]  Cd Length: 340  Bit Score: 707.72  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 5552 GLYPTLNISDEFSSNVANYQKVGMQKYSTLQGPPGTGKSHFAIGLALYYPSARIVYTACSHAAVDALCEKALKYLPIDKC 5631
Cdd:cd21722    1 GLYPTYNVPEEFQNNVVNYQKIGMKRYCTVQGPPGTGKSHLAIGLAVYYPTARVVYTACSHAAVDALCEKAFKFLNINKC 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 5632 SRIIPARARVECFDKFKVNSTLEQYVFCTVNALPETTADIVVFDEISMATNYDLSVVNARLRAKHYVYIGDPAQLPAPRT 5711
Cdd:cd21722   81 SRIIPAKARVECYDKFKVNDTSRQYVFSTINALPETVTDILVVDEVSMCTNYDLSVINARVRAKHIVYIGDPAQLPAPRT 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 5712 LLTKGTLEPEYFNSVCRLMKTIGPDMFLGTCRRCPAEIVDTVSALVYDNKLKAHKDKSAQCFKMFYKGVITHDVSSAINR 5791
Cdd:cd21722  161 LLTKGTLEPEYFNSVTRLMCCLGPDIFLGTCYRCPKEIVDTVSALVYDNKLKAKKDNSGQCFKVYYKGSVTHDSSSAINR 240
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 5792 PQIGVVREFLTRNPAWRKAVFISPYNSQNAVASKILGLPTQTVDSSQGSEYDYVIFTQTTETAHSCNVNRFNVAITRAKI 5871
Cdd:cd21722  241 PQIYLVKKFLKANPAWSKAVFISPYNSQNAVARRVLGLQTQTVDSSQGSEYDYVIYCQTAETAHSVNVNRFNVAITRAKK 320
                        330       340
                 ....*....|....*....|
gi 30027621 5872 GILCIMSDRDLYDKLQFTSL 5891
Cdd:cd21722  321 GILCVMSSMQLFESLQFTEL 340
NSP13 pfam06460
Coronavirus NSP13; This family covers the NSP13 region of the coronavirus polyprotein. This ...
6777-7072 0e+00

Coronavirus NSP13; This family covers the NSP13 region of the coronavirus polyprotein. This protein has the predicted function of an mRNA cap-1 methyltransferase function.


:

Pssm-ID: 399456  Cd Length: 297  Bit Score: 596.02  E-value: 0e+00
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621   6777 SQAWQPGVAMPNLYKMQRMLLEKCDLQNYGENAVIPKGIMMNVAKYTQLCQYLNTLTLAVPYNMRVIHFGAGSDKGVAPG 6856
Cdd:pfam06460    1 SAAWKPGYSMPNLYKMQRMCLEPCNLYNYGAGITLPSGIMMNVAKYTQLCQYLNTTTLCVPHNMRVLHLGAGSDKGVAPG 80
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621   6857 TAVLRQWLPTGTLLVDSDLNDFVSDADSTLIGDCATVHTANKWDLIISDMYDPRTKHVTKENDSKEGFFTYLCGFIKQKL 6936
Cdd:pfam06460   81 SAVLRQWLPTGTILVDNDLNDYVSDADFSVTGDCATVYTEDKFDLIISDMYDPRTKHIDGENVSKDGFFTYLCGFIKEKL 160
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621   6937 ALGGSIAVKITEHSWNADLYKLMGHFSWWTAFVTNVNASSSEAFLIGANYLGK-PKEQIDGYTMHANYIFWRNTNPIQLS 7015
Cdd:pfam06460  161 ALGGSIAIKITEFSWNADLYELMQRFSWWTMFCTNVNASSSEAFLIGINYLGKsPKEQIDGKTMHANYIFWRNSTPMQLS 240
                          250       260       270       280       290
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 30027621   7016 SYSLFDMSKFPLKLRGTAVMSLKENQINDMIYSLLEKGRLIIRENNRVVVSSDILVN 7072
Cdd:pfam06460  241 AYSLFDMSKFPLKLKGTAVVSLKENQINDMVLSLLEKGKLLVRDNGKVVFFSDSLVN 297
betaCoV_Nsp5_Mpro cd21666
betacoronavirus non-structural protein 5, also called Main protease (Mpro); This subfamily ...
3244-3540 0e+00

betacoronavirus non-structural protein 5, also called Main protease (Mpro); This subfamily contains the coronavirus (CoV) non-structural protein 5 (Nsp5) also called the Main protease (Mpro), or 3C-like protease (3CLpro), found in betacoronaviruses. CoVs utilize a multi-subunit replication/transcription machinery. A set of non-structural proteins (Nsps) generated as cleavage products of the ORF1a and ORF1ab viral polyproteins assemble to facilitate viral replication and transcription. Mpro/Nsp5 is a key enzyme in this process, making it a high value target for the development of anti-coronavirus therapeutics. These enzymes belong to the MEROPS peptidase C30 family, where the active site residues His and Cys form a catalytic dyad. The structures of Mpro/Nsp5 consist of three domains with the first two containing anti-parallel beta barrels and the third consisting of an arrangement of alpha-helices. The catalytic residues are found in a cleft between the first two domains. Mpro requires a Gln residue in the P1 position of the substrate and space for only small amino-acid residues such as Gly, Ala, or Ser in the P1' position; since there is no known human protease with a specificity for Gln at the cleavage site of the substrate, these viral proteases are suitable targets for the development of antiviral drugs.


:

Pssm-ID: 394887  Cd Length: 297  Bit Score: 577.43  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 3244 RKMAFPSGKVEGCMVQVTCGTTTLNGLWLDDTVYCPRHVICTAEDMLNPNYEDLLIRKSNHSFLVQAGNVQLRVIGHSMQ 3323
Cdd:cd21666    1 RKMAFPSGKVEGCMVQVTCGTMTLNGLWLDDTVYCPRHVICTAEDMLNPNYEDLLIRKTNHSFLVQAGNVQLRVIGHSMQ 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 3324 NCLLRLKVDTSNPKTPKYKFVRIQPGQTFSVLACYNGSPSGVYQCAMRPNHTIKGSFLNGSCGSVGFNIDYDCVSFCYMH 3403
Cdd:cd21666   81 GCLLRLTVDTSNPKTPKYKFVRVKPGQTFSVLACYNGSPSGVYQCAMRPNHTIKGSFLCGSCGSVGYNIDGDCVSFCYMH 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 3404 HMELPTGVHAGTDLEGKFYGPFVDRQTAQAAGTDTTITLNVLAWLYAAVINGDRWFLNRFTTTLNDFNLVAMKYNYEPLT 3483
Cdd:cd21666  161 QMELPTGVHTGTDLEGKFYGPFVDRQTAQAAGTDTTITLNVLAWLYAAVLNGDRWFVNRFTTTLNDFNLWAMKYNYEPLT 240
                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 30027621 3484 QDHVDILGPLSAQTGIAVLDMCAALKELLQNGMNGRTILGSTILEDEFTPFDVVRQC 3540
Cdd:cd21666  241 QDHVDILDPLAAQTGIAVEDMLAALKELLQGGMQGRTILGSTILEDEFTPFDVVRQC 297
betaCoV_PLPro cd21732
betacoronavirus papain-like protease; This model represents the papain-like protease (PLPro) ...
1543-1845 1.12e-159

betacoronavirus papain-like protease; This model represents the papain-like protease (PLPro) found in non-structural protein 3 (Nsp3) of betacoronavirus, including highly pathogenic betacoronaviruses such as Severe acute respiratory syndrome-related coronavirus (SARS-CoV), SARS-CoV2 (also called 2019 novel CoV or 2019-nCoV), and Middle East respiratory syndrome-related (MERS) CoV. CoVs utilize a multi-subunit replication/transcription machinery. A set of non-structural proteins (Nsps) generated as cleavage products of the ORF1a and ORF1ab viral polyproteins assemble to facilitate viral replication and transcription. PLPro is a key enzyme in this process, making it a high value target for the development of anti-coronavirus therapeutics. PLPro, which belongs to the MEROPS peptidase C16 family, participates in the proteolytic processing of the N-terminal region of the replicase polyprotein; it can cleave Nsp1|Nsp2, Nsp2|Nsp3, and Nsp3|Nsp4 sites and its activity is dependent on zinc. In SARS-CoV and murine hepatitis virus (MHV), the C-terminal non-structural protein 3 region spanning transmembrane regions TM1 and TM2 with 3Ecto domain in between, are important for the PL2pro domain to process Nsp3-Nsp4 cleavage. Besides cleaving the polyproteins, PLPro also possesses a related enzymatic activity to promote virus replication: deubiquitinating (DUB) and de-ISGylating activities. Both, ubiquitin (Ub) and Ub-like interferon-stimulated gene product 15 (ISG15), are involved in preventing viral infection; coronaviruses utilize Ubl-conjugating pathways to counter the pro-inflammatory properties of Ubl-conjugated host proteins via the action of PLPro, which processes both 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains from cellular substrates. The Nsp3 PLPro domain of many of these CoVs has also been shown to antagonize host innate immune induction of type I interferon by interacting with IRF3 and blocking its activation. Interactions of SARS-CoV and MERS-CoV with antiviral interferon (IFN) responses of human cells are remarkably different; high-dose IFN treatment (type I and type III) shows MERS-CoV was substantially more IFN sensitive than SARS-CoV. This may be due to differences in the architecture of the oxyanion hole and of the S3 as well as the S5 specificity sites, despite the overall structures of SARS-CoV and MERS-CoV PLPro being similar.


:

Pssm-ID: 409649  Cd Length: 304  Bit Score: 496.72  E-value: 1.12e-159
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 1543 KTIKVFTTVDNTNLHTQLVDMSMTYGQQFGPTYLDGADVTKIKPHVNHEGKTFFVLPSDDTLRSEAFEY-YHTLDESFLG 1621
Cdd:cd21732    1 KTIEVLTTVDGVNFRTVLVNNGETFGKQLGNVFCDGVDVTKTKPSAKYEGKVLFQADNLSAEELEAVEYyYGFDDPTFLL 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 1622 RYMSALNHTKKWKFPQVGGLTSIKWADNNCYLSSVLLALQQLEVKFNAPALQEAYYRARAGDAANFCALILAYSNKTVGE 1701
Cdd:cd21732   81 RYYSALAHVKKWKFVVVDGYFSLKQADNNCYLNAACLMLQQLDLKFNTPALQEAYYEFRAGDPLRFVALVLAYGNFTFGE 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 1702 LGDVRETMTHLLQHANLESAKRVLNVVCKHCGQKTTTLTGVEAVMYMGTLSYDNLKTGVSIPCVCGRDATQYLVQQESSF 1781
Cdd:cd21732  161 PDDARDFLRVVLSHADLVSARRVLEEVCKVCGVKQEQRTGVDAVMYFGTLSLDDLYKGYTIDCSCGRKAIRYLVEQVPPF 240
                        250       260       270       280       290       300
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 30027621 1782 VMMSAPPAEYKLQQGTFLCANEYTGNYQCGHYTHITAKETLYRIDGAHLTKMSEYKGPVTDVFY 1845
Cdd:cd21732  241 LLMSNTPTEVPLPTGDFVAANVFTGDESVGHYTHVKNKSLLYLYDAGNVKKTSDLKGPVTDVLY 304
cv_Nsp4_TM cd21473
coronavirus non-structural protein 4 (Nsp4) transmembrane domain; Nsp4 may be involved in ...
2754-3134 1.99e-149

coronavirus non-structural protein 4 (Nsp4) transmembrane domain; Nsp4 may be involved in coronavirus-induced membrane remodeling. In order to assemble the replication-transcription complex (RTC), coronavirus induces the rearrangement of host endoplasmic reticulum (ER) membrane into double membrane vesicles (DMVs), zippered ER, or ER spherules. DMV formation has been observed in SARS-CoV cells overexpressing the three transmembrane-containing non-structural proteins of viral replicase polyprotein 1ab: Nsp3, Nsp4 and Nsp6. Together, Nsp3, Nsp4, and Nsp6 have the ability to induce the formation of DMVs that are similar to those seen in SARS-CoV-infected cells.


:

Pssm-ID: 394836  Cd Length: 376  Bit Score: 470.92  E-value: 1.99e-149
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 2754 TLLCVLAALVCYIVMPVHTLSIHDGYTNEIIGYKAIQDGVTRDIISTDDCFANKHAGFDAWFSQRGGS-YKNDKSCPVVA 2832
Cdd:cd21473    1 FLWLLLAAILLYAFLPSYSVFTVTVSSFPGYDFKVIENGVLRDIRSTDTCFANKFVNFDSWYQAKYGSvPTNSKSCPIVV 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 2833 AIITREIGFiVPGLPGTVLRaINGDFLHFLPRVFSAVGNICYTPSKLIEYSDFATSACVLAAECTIFKDaMGKPVPYCYD 2912
Cdd:cd21473   81 GVIDDVRGS-VPGVPAGVLL-VGKTLVHFVQTVFFGDTVVCYTPDGVITYDSFYTSACVFNSACTYLTG-LGGRQLYCYD 157
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 2913 TNLLEGSISYSELRPDTRYVLMDGSIIQFPNTYLEGSVRVVTTFDAEYCRHGTCERSEVGICLSTSGRWVLNNEHYRalS 2992
Cdd:cd21473  158 TGLVEGAKLYSDLLPHVRYKLVDGNYIKFPEVILEGGPRIVRTLATTYCRVGECEDSKAGVCVSFDGFWVYNNDYYG--P 235
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 2993 GVFCGVDAMNLIANIFTPLVQPVGALDVSASVVAGGIIAILVTCAAYYFMKFRRVFGEyNHVVAANALLFLMSFTILCLV 3072
Cdd:cd21473  236 GVYCGDGLFDLLTNLLSGFFQPVSVFALSGQLLFNTIVAILAVLACYYVQKFKRAFGD-MSVVVVTVVAAALVNNVLYVV 314
                        330       340       350       360       370       380
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 30027621 3073 PAYSFLPGVYSVFYLYLTFYFTNDVSFLAHLQWFAMFSPIVPFWITAIYVFCISLKHCHWFF 3134
Cdd:cd21473  315 TQNPLLMIVYAVLYFYATLYLTYERAWIMHLGWVVAYGPIAPWWLLALYVVAVLYDYLPWFF 376
betaCoV-Nsp6 cd21560
betacoronavirus non-structural protein 6; Coronaviruses (CoV) redirect and rearrange host cell ...
3547-3836 8.03e-149

betacoronavirus non-structural protein 6; Coronaviruses (CoV) redirect and rearrange host cell membranes as part of the viral genome replication and transcription machinery; they induce the formation of double-membrane vesicles in infected cells. CoV non-structural protein 6 (Nsp6), a transmembrane-containing protein, together with Nsp3 and Nsp4, have the ability to induce double-membrane vesicles that are similar to those observed in severe acute respiratory syndrome (SARS) coronavirus-infected cells. By itself, Nsp6 can generate autophagosomes from the endoplasmic reticulum. Autophagosomes are normally generated as a cellular response to starvation to carry cellular organelles and long-lived proteins to lysosomes for degradation. Degradation through autophagy may provide an innate defense against virus infection, or conversely, autophagosomes can promote infection by facilitating the assembly of replicase proteins. In addition to initiating autophagosome formation, Nsp6 also limits autophagosome expansion regardless of how they were induced, i.e. whether they were induced directly by Nsp6, or indirectly by starvation or chemical inhibition of MTOR signaling. This may favor coronavirus infection by compromising the ability of autophagosomes to deliver viral components to lysosomes for degradation.


:

Pssm-ID: 394846  Cd Length: 290  Bit Score: 465.18  E-value: 8.03e-149
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 3547 GKFKKIVKGTHHWMLLTFLTSLLILVQSTQWSLFFFVYENAFLPFTLGIMAIAACAMLLVKHKHAFLCLFLLPSLATVAY 3626
Cdd:cd21560    1 SKVKRVVKGTLHWLLATFVLFYLIILQLTKWTMFMYLTETMLLPLTPALCCVSACVMLLVKHKHTFLTLFLLPVLLTLAY 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 3627 FNMVYMPA-SWVMRIMTWLELADTSlSGYRLKDCVMYASALVLLILMTARTVYDDAARRVWTLMNVITLVYKVYYGNALD 3705
Cdd:cd21560   81 YNYVYVPKsSFLGYVYNWLNYVNPY-VDYTYTDEVTYGSLLLVLMLVTMRLVNHDAFSRVWAVCRVITWVYMWYTGSLEE 159
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 3706 QAISMWALVISVTSNYSGVVTTIMFLARAIVFVCVEYYPLLFITGNTLQCIMLVYCFLGYCCCCYFGLFCLLNRYFRLTL 3785
Cdd:cd21560  160 SALSYLTFLFSVTTNYTGVVTVSLALAKFITALWLAYNPLLFLDIPEVKCVLLVYLFIGYICTCYFGVFSLLNRLFRCPL 239
                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|.
gi 30027621 3786 GVYDYLVSTQEFRYMNSQGLLPPKSSIDAFKLNIKLLGIGGKPCIKVATVQ 3836
Cdd:cd21560  240 GVYDYKVSTQEFRYMNANGLRPPRNSWEALMLNFKLLGIGGVPCIKVSTVQ 290
nsp8 pfam08717
nsp8 replicase; Viral nsp8 (non structural protein 8) forms a hexadecameric supercomplex with ...
3920-4116 4.68e-115

nsp8 replicase; Viral nsp8 (non structural protein 8) forms a hexadecameric supercomplex with nsp7 that adopts a hollow cylinder-like structure. The dimensions of the central channel and positive electrostatic properties of the cylinder imply that it confers processivity on RNA-dependent RNA polymerase.


:

Pssm-ID: 400866  Cd Length: 197  Bit Score: 364.17  E-value: 4.68e-115
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621   3920 AIASEFSSLPSYAAYATAQEAYEQAVANGDSEVVLKKLKKSLNVAKSEFDRDAAMQRKLEKMADQAMTQMYKQARSEDKR 3999
Cdd:pfam08717    1 SVASEFSSLPSYAAYETAKEAYEEAVANGSSQQVLKQLKKACNIAKSEFDRDAAVQKKLEKMAEQAMTQMYKEARAVDRK 80
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621   4000 AKVTSAMQTMLFTMLRKLDNDALNNIINNARDGCVPLNIIPLTTAAKLMVVVPDYGTYKNTCDGNTFTYASALWEIQQVV 4079
Cdd:pfam08717   81 SKVVSAMHTLLFSMLRKLDNSALNTIINNARNGVVPLNIIPATTAAKLTVVVPDYETFVKVVDGNTVTYAGAVWEIQEVK 160
                          170       180       190
                   ....*....|....*....|....*....|....*..
gi 30027621   4080 DADSKIVQLSEINMDNSPNLAWPLIVTALRANSAVKL 4116
Cdd:pfam08717  161 DADGKIVHLKEITMDNSPNLAWPLIVTAERANSAVKL 197
DUF3655 super family cl13772
Protein of unknown function (DUF3655); This domain family is found in viruses, and is ...
881-1029 4.67e-108

Protein of unknown function (DUF3655); This domain family is found in viruses, and is approximately 70 amino acids in length. The family is found in association with pfam08716, pfam01661, pfam05409, pfam06471, pfam08717, pfam06478, pfam09401, pfam06460, pfam08715, pfam08710.


The actual alignment was detected with superfamily member pfam12379:

Pssm-ID: 432517  Cd Length: 149  Bit Score: 342.16  E-value: 4.67e-108
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621    881 VKTLQPVSDLLTNMGIDLDEWSVATFYLFDDAGEENFSSRMYCSFYPPDEEEEDDAECEEEEIDETCEHEYGTEDDYQGL 960
Cdd:pfam12379    1 VKTLQPVSDLLTNMGIDLDEWSVATFYLFDDAGEENFSSRMYCSFYPPDEEEEDDAECEEEEIDETCEHEYGTEDDYQGL 80
                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 30027621    961 PLEFGASAETVRVEEEEEEDWLDDTTEQSEIEPEPEPTPEEPVNQFTGYLKLTDNVAIKCVDIVKEAQS 1029
Cdd:pfam12379   81 PLEFGASAETVRVEEEEEEDWLDDTTEQSEIEPEPEPTPEEPVNQFTGYLKLTDNVAIKCVDIVKEAQS 149
NendoU_cv_Nsp15-like cd21161
Nidoviral uridylate-specific endoribonuclease (NendoU) domain of coronavirus Nonstructural ...
6623-6773 2.52e-90

Nidoviral uridylate-specific endoribonuclease (NendoU) domain of coronavirus Nonstructural Protein 15 (Nsp15) and related proteins; Nidovirus endoribonucleases (NendoUs) are uridylate-specific endoribonucleases, which release a cleavage product containing a 2',3'-cyclic phosphate at the 3' terminal end. NendoUs include Nsp15 from coronaviruses and Nsp11 from arteriviruses, both of which may participate in the viral replication process and in the evasion of the host immune system. Except for turkey coronavirus (TCoV) Nsp15, Mn2+ is generally essential for the catalytic activity of coronavirus Nsp15. Coronavirus Nsp15 from Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV), human Coronavirus 229E (HCoV229E), and murine hepatitis virus (MHV) form a functional hexamer while Porcine DeltaCoronavirus (PDCoV) Nsp15 has been shown to exist as a dimer and a monomer in solution. NendoUs are distantly related to Xenopus laevis Mn(2+)-dependent uridylate-specific endoribonuclease (XendoU) which is involved in the processing of intron-encoded box C/D U16 small, nucleolar RNA.


:

Pssm-ID: 439158  Cd Length: 151  Bit Score: 291.47  E-value: 2.52e-90
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 6623 FTQSRDLEDFKPRSQMETDFLELAMDEFIQRYKLEGYAFEHIVYGDFSHGQLGGLHLMIGLAKRSQDSPLKLEDFIPMDS 6702
Cdd:cd21161    1 FTQGRSLEDFKPRSQMERDFLSMDQDVFIQKYGLEDLGFEHIVYGDFSKPTIGGLHLLIGLVRLKKEGKLYVEEFHNSDS 80
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 30027621 6703 TVKNYFITDAQTGSSKCVCSVIDLLLDDFVEIIKSQDLSVISKVVKVTIDYAEISFMLWCKDGHVETFYPK 6773
Cdd:cd21161   81 TVQNYFVTDANNGSSKQVCTVVDLLLDDFVDILKSQDLSVVSKVVTVSIDYKPIRFMLWCKDGKVKTFYPQ 151
CoV_Nsp10 cd21872
coronavirus non-structural protein 10; This model represents the non-structural protein 10 ...
4231-4361 1.32e-82

coronavirus non-structural protein 10; This model represents the non-structural protein 10 (Nsp10) of alpha-, beta-, gamma- and deltacoronaviruses, including highly pathogenic betacoronaviruses such as Severe acute respiratory syndrome-related coronavirus (SARS-CoV), SARS-CoV2 (also called 2019 novel CoV or 2019-nCoV), and Middle East respiratory syndrome-related (MERS) CoV. CoVs utilize a multi-subunit replication/transcription machinery. A set of non-structural proteins (Nsps) generated as cleavage products of the ORF1a and ORF1ab viral polyproteins assemble to facilitate viral replication and transcription. Upon processing of the Nsp7-10 region by protease M (Mpro), the released four small proteins Nsp7, Nsp8, Nsp9, and Nsp10 form functional complexes with CoV core enzymes and thereby stimulate replication. Coronaviruses cap their mRNAs; RNA cap methylation may involve at least three proteins: Nsp10, Nsp14, and Nsp16. Nsp10 serves as a cofactor for both Nsp14 and Nsp16. Nsp14 consists of 2 domains with different enzymatic activities: an N-terminal ExoN domain and a C-terminal cap (guanine-N7) methyltransferase (N7-MTase) domain. The association of Nsp10 with Nsp14 enhances Nsp14's exoribonuclease (ExoN) activity, and not its N7-Mtase activity. ExoN is important for proofreading and therefore, the prevention of lethal mutations. The Nsp10/Nsp14 complex hydrolyzes double-stranded RNA in a 3' to 5' direction as well as a single mismatched nucleotide at the 3'-end, mimicking an erroneous replication product, and may function in a replicative mismatch repair mechanism. Nsp16 Cap-0 specific (nucleoside-2'-O-)-methyltransferase (2'OMTase) acts sequentially to Nsp14 MTase in RNA capping methylation, and methylates the RNA cap at the ribose 2'-O position; it catalyzes the conversion of the cap-0 structure on m7GpppA-RNA to a cap-1 structure. The association of Nsp10 with Nsp16 enhances Nsp16's 2'OMTase activity, possibly through enhanced RNA binding affinity. Additionally, transmissible gastroenteritis virus (TGEV) Nsp10, Nsp16, and their complex can interact with DII4, which normally binds to Notch receptors; this interaction may disturb Notch signaling. Nsp10 also binds 2 zinc ions with high affinity.


:

Pssm-ID: 409325  Cd Length: 131  Bit Score: 268.57  E-value: 1.32e-82
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 4231 AGNATEVPANSTVLSFCAFAVDPAKAYKDYLASGGQPITNCVKMLCTHTGTGQAITVTPEANMDQESFGGASCCLYCRCH 4310
Cdd:cd21872    1 AGNATEVPANSTVLSFCAFAVDPAKAYKDYLASGGQPITNCVKMLCTHTGTGQAITVKPEANMDQESFGGASVCLYCRAH 80
                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|.
gi 30027621 4311 IDHPNPKGFCDLKGKYVQIPTTCANDPVGFTLRNTVCTVCGMWKGYGCSCD 4361
Cdd:cd21872   81 IDHPNPDGFCDYKGKFVQIPTTCANDPVGFTLRNTVCTVCQMWKGYGCSCD 131
SUD-M pfam11633
Single-stranded poly(A) binding domain; This family of proteins represents Nsp3c, the product ...
1344-1469 1.78e-82

Single-stranded poly(A) binding domain; This family of proteins represents Nsp3c, the product of ORF1a in group 2 coronavirus. The domain exhibits a macrodomain fold containing the nsp3 residues 528 to 648, with a flexibly extended N-terminal tail from residues 513 to 527 and a C-terminal flexible tail of residues 649 to 651. SUD-M(527-651) binds single-stranded poly(A); the contact area with this RNA on the protein surface, and the electrophoretic mobility shift assays confirm that SUD-M has higher affinity for purine bases than for pyrimidine bases.


:

Pssm-ID: 431970  Cd Length: 126  Bit Score: 267.77  E-value: 1.78e-82
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621   1344 LGTVSWNLREMLAHAEETRKLMPICMDVRAIMATIQRKYKGIKIQEGIVDYGVRFFFYTSKEPVASIITKLNSLNEPLVT 1423
Cdd:pfam11633    1 LGTVSWNLREMLAHAEETRKLMPICMDVRAIMATIQRKYKGIKIQEGIVDYGVRFFFYTSKEPVASIITKLNSLNEPLVT 80
                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*.
gi 30027621   1424 MPIGYVTHGFNLEEAARCMRSLKAPAVVSVSSPDAVTTYNGYLTSS 1469
Cdd:pfam11633   81 MPIGYVTHGFNLEEAARCMRSLKAPAVVSVSSPDAVTTYNGYLTSS 126
SARS-CoV-like_Nsp1_N cd21796
N-terminal domain of non-structural protein 1 from Severe acute respiratory syndrome-related ...
13-127 1.96e-79

N-terminal domain of non-structural protein 1 from Severe acute respiratory syndrome-related coronavirus and betacoronavirus in the B lineage; This model represents the N-terminal domain of non-structural protein 1 (Nsp1) from betacoronaviruses in the sarbecovirus subgenus (B lineage), including highly pathogenic coronaviruses such as Severe acute respiratory syndrome-related coronavirus (SARS-CoV) and SARS-CoV2 (also called 2019 novel CoV or 2019-nCoV). CoVs utilize a multi-subunit replication/transcription machinery assembled from a set of non-structural proteins (Nsps) generated as cleavage products of the ORF1a and ORF1ab viral polyproteins. Nsp1 is the N-terminal cleavage product released from the ORF1a polyprotein by the action of papain-like protease (PLpro). Though Nsp1s of alphaCoVs and betaCoVs share structural similarity, they show no significant sequence similarity and may be considered as genus-specific markers. Despite low sequence similarity, the Nsp1s of alphaCoVs and betaCoVs exhibit remarkably similar biological functions, and are involved in the regulation of both host and viral gene expression. CoV Nsp1 induces suppression of host gene expression and interferes with host immune response. It inhibits host gene expression in two ways: by targeting the translation and stability of cellular mRNAs, and by inhibiting mRNA translation and inducing an endonucleolytic RNA cleavage in the 5'-UTR of cellular mRNAs through its tight association with the 40S ribosomal subunit, a key component of the cellular translation machinery. Inhibition of host mRNA translation includes that of type I interferons, major components of the host innate immune response. Nsp1 is critical in regulating viral replication and gene expression, as shown by multiple evidences, including: mutations in the Nsp1 coding region of the transmissible gastroenteritis virus (TGEV) and murine hepatitis virus (MHV) genomes cause drastic reduction or elimination of infectious virus; bovine coronavirus (BCoV) Nsp1 is an RNA-binding protein that interacts with cis-acting replication elements in the 5'-UTR of the BCoV genome, implying its potential role in the regulation of viral translation or replication; and SARS-CoV Nsp1 enhances virus replication by binding to a stem-loop structure in the 5'-UTR of its genome.


:

Pssm-ID: 439285  Cd Length: 115  Bit Score: 258.67  E-value: 1.96e-79
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621   13 HVQLSLPVLQVRDVLVRGFGDSVEEALSEAREHLKNGTCGLVELEKGVLPQLEQPYVFIKRSDALSTNHGHKVVELVAEM 92
Cdd:cd21796    1 HVQLSLPVLQVRDVLVRGFGDSVEEALSEAREHLKNGTCGLVELEKGVLPQLEQPYVFIKRSDALSTNHGHKVVELVAEL 80
                         90       100       110
                 ....*....|....*....|....*....|....*
gi 30027621   93 DGIQYGRSGITLGVLVPHVGETPIAYRNVLLRKNG 127
Cdd:cd21796   81 DGIQYGRSGITLGVLVPHVGETPIAYRNVLLRKNG 115
SARS-CoV-like_Nsp3_betaSM cd21814
betacoronavirus-specific marker of non-structural protein 3 from Severe acute respiratory ...
2021-2136 2.40e-78

betacoronavirus-specific marker of non-structural protein 3 from Severe acute respiratory syndrome-related coronavirus and betacoronavirus in the B lineage; This model represents the betacoronavirus-specific marker (betaSM), also called group 2-specific marker (G2M), of non-structural protein 3 (Nsp3) from betacoronavirus in the sarbecovirus subgenus (B lineage), including highly pathogenic human coronaviruses such as Severe acute respiratory syndrome-related coronavirus (SARS-CoV) and SARS-CoV2 (also called 2019 novel CoV or 2019-nCoV). The betaSM/G2M is located C-terminal to the nucleic acid-binding (NAB) domain. This region is absent in alpha- and deltacoronavirus Nsp3; there is a gammacoronavirus-specific marker (gammaSM) at this position in gammacoronavirus Nsp3. Nsp3 is a large multi-functional multi-domain protein that is an essential component of the replication/transcription complex (RTC), which carries out RNA synthesis, RNA processing, and interference with the host cell innate immune system. Little is known about the betaSM/G2M domain; it is predicted to be non-enzymatic and may be an intrinsically disordered region. The betaSM/G2M domain is part of the predicted PLnc domain (made up of 385 amino acids) of SARS-CoV Nsp3 that may function as a replication/transcription scaffold, with interactions to Nsp5, Nsp12, Nsp13, Nsp14, and Nsp16.


:

Pssm-ID: 409629  Cd Length: 116  Bit Score: 255.57  E-value: 2.40e-78
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 2021 QQPTSEEVVENPTIQKEVIECDVKTTEVVGNVILKPSDEGVKVTQELGHEDLMAAYVENTSITIKKPNELSLALGLKTIA 2100
Cdd:cd21814    1 QQPTSEEVVENPTIQKEVIECDVKTTEVVGNVILKPSDEGVKVTQELGHEDLMAAYVENTSITIKKPNELSLALGLKTLA 80
                         90       100       110
                 ....*....|....*....|....*....|....*.
gi 30027621 2101 THGIAAINSVPWSKILAYVKPFLGQAAITTSNCAKR 2136
Cdd:cd21814   81 THGAAAINSVPWSKILAYVKPFLGQAAVTTSNCAKR 116
Macro_cv_SUD-N_Nsp3-like cd21562
SUD-N macrodomain (or Mac2 domain) of the SARS Unique Domain (SUD) of SARS-CoV non-structural ...
1209-1334 7.87e-76

SUD-N macrodomain (or Mac2 domain) of the SARS Unique Domain (SUD) of SARS-CoV non-structural protein 3 and related macrodomains; This subfamily includes the macrodomain referred to as SUD-N (N-terminal subdomain) of the SARS-unique domain (SUD) which binds G-quadruplexes (unusual nucleic-acid structures formed by consecutive guanosine nucleotides). It is found in the non-structural protein 3 (Nsp3) of Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) and highly related coronaviruses. SUD consists of three globular domains separated by short linker peptide segments: SUD-N, SUD-M, and SUD-C. Among these, SUD-N and SUD-M are macrodomains: the SUD-M domain (not represented in this subfamily) is a related macrodomain which also binds G-quadruplexes. SUD-N (also called Mac2) is specific to the Nsp3 of SARS and betacoronaviruses of the sarbecovirus subgenera (B lineage), while SUD-M (also called Mac3) is present in most Nsp3 proteins except the Nsp3 from betacoronaviruses of the embecovirus subgenera (A lineage). SUD-C adopts a frataxin-like fold, has structural similarity to DNA-binding domains of DNA-modifying enzymes, binds single-stranded RNA, and regulates the RNA binding behavior of the SUD-M macrodomain. SARS-CoV Nsp3 contains a third macrodomain (the X-domain or Mac1) which is also not represented in this subfamily. The X-domain may function as a module binding poly(ADP-ribose); however, SUD-N and SUD-M do not bind ADP-ribose, as the triple glycine sequence involved in its binding is not conserved in these.


:

Pssm-ID: 394883  Cd Length: 126  Bit Score: 248.98  E-value: 7.87e-76
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 1209 KACIDEVTTTLEETKFLTNKLLLFADINGKLYHDSQNMLRGEDMSFLEKDAPYMVGDVITSGDITCVVIPSKKAGGTTEM 1288
Cdd:cd21562    1 KACIEEVTTTLEETKFLTNKLLLYADINGNLHEDSKNLLRGEDMSFLKKDAPYIVGDVITEGDITCVVIPSKKAGGTTEM 80
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*.
gi 30027621 1289 LSRALKKVPVDEYITTYPGQGCAGYTLEEAKTALKKCKSAFYVLPS 1334
Cdd:cd21562   81 LTRALKKVPTDEYITTYPGQGCAGYTLEEAKTALKKCKSAFYVLPS 126
SARS-CoV-like_Nsp3_NAB cd21822
nucleic acid binding domain of non-structural protein 3 from Severe acute respiratory ...
1890-1996 4.77e-71

nucleic acid binding domain of non-structural protein 3 from Severe acute respiratory syndrome-related coronavirus and betacoronavirus in the B lineage; This model represents the nucleic acid binding (NAB) domain of non-structural protein 3 (Nsp3) from betacoronavirus in the sarbecovirus subgenus (B lineage) and hibecovirus subgenus, including highly pathogenic human coronaviruses (CoVs) such as Severe acute respiratory syndrome-related coronavirus (SARS-CoV) and SARS-CoV2 (also called 2019 novel CoV or 2019-nCoV). The NAB domain represents a new fold, with a parallel four-strand beta-sheet holding two alpha-helices of three and four turns that are oriented antiparallel to the beta-strands. NAB is a cytoplasmic domain located between the papain-like protease (PLPro) and betacoronavirus-specific marker (betaSM) domains of CoV Nsp3. Nsp3 is a large multi-functional multi-domain protein that is an essential component of the replication/transcription complex (RTC), which carries out RNA synthesis, RNA processing, and interference with the host cell innate immune system. The NAB domain both binds ssRNA and unwinds dsDNA. It prefers to bind ssRNA containing repeats of three consecutive guanines. A group of residues that form a positively charged patch on the protein surface of SARS-CoV Nsp3 NAB serves as the binding site of nucleic acids. This site is conserved in the NAB of Nsp3 from betacoronavirus in the B lineage.


:

Pssm-ID: 409348  Cd Length: 107  Bit Score: 234.35  E-value: 4.77e-71
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 1890 DLVPTQPLPNASFDNFKLTCSNTKFADDLNQMTGFTKPASRELSVTFFPDLNGDVVAIDYRHYSASFKKGAKLLHKPIVW 1969
Cdd:cd21822    1 DLVPTQPLPNASFDNFKLTCSNTKFADDLNQMTGFTKPASRELSVTFFPDLNGDVVAIDYRHYSPSFKKGAKLLHKPIVW 80
                         90       100
                 ....*....|....*....|....*..
gi 30027621 1970 HINQATTKTTFKPNTWCLRCLWSTKPV 1996
Cdd:cd21822   81 HINQATTKTTYKPNTWCLRCLWSTKPV 107
ZBD_cv_Nsp13-like cd21401
Cys/His rich zinc-binding domain (CH/ZBD) of coronavirus SARS NSP13 helicase and related ...
5302-5396 1.22e-60

Cys/His rich zinc-binding domain (CH/ZBD) of coronavirus SARS NSP13 helicase and related proteins; Helicases catalyze NTP-dependent unwinding of nucleic acid duplexes into single strands and are classified based on the arrangement of conserved motifs into six superfamilies. This coronavirus family includes Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) non-structural protein 13 (SARS-Nsp13) and belongs to helicase superfamily 1 (SF1) and to a family of nindoviral replication helicases. SARS-Nsp13 has an N-terminal CH/ZBD, a stalk domain, a 1B regulatory domain, and SF1 helicase core. The CH/ZBD has 3 zinc-finger (ZnF1-3) motifs. SARS-Nsp13 is a component of the viral RNA synthesis replication and transcription complex (RTC). The SARS-Nsp13 CH/ZBD is indispensable for helicase activity and interacts with SARS-Nsp12, the RNA-dependent RNA polymerase (RdRp). Structural studies of a stable SARS-CoV-2 RTC which included two molecules of Nsp13, the RdRp holoenzyme (Nsp7, two molecules of Nsp8, Nsp12), and an RNA template product, show that one Nsp13 CH/ZBD domain interacts with Nsp12, and both Nsp13-CH/ZBD domains interact with the Nsp8. This stable SARS-CoV-2 RTC suggests that the Nsp13 helicase may drive RTC backtracking, affecting proofreading and template switching.


:

Pssm-ID: 439168  Cd Length: 95  Bit Score: 204.16  E-value: 1.22e-60
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 5302 AVGACVLCNSQTSLRCGACIRRPFLCCKCCYDHVISTSHKLVLSVNPYVCNAPGCDVTDVTQLYLGGMSYYCKSHKPPIS 5381
Cdd:cd21401    1 AVGLCVVCNSQTVLRCGDCIRRPFLCCKCCYDHVMSTSHKFILSINPYVCNAPGCGVSDVTKLYLGGMSYYCEDHKPSLS 80
                         90
                 ....*....|....*
gi 30027621 5382 FPLCANGQVFGLYKN 5396
Cdd:cd21401   81 FPLCANGFVFGLYKN 95
betaCoV_Nsp9 cd21898
betacoronavirus non-structural protein 9; This model represents the non-structural protein 9 ...
4118-4230 2.58e-59

betacoronavirus non-structural protein 9; This model represents the non-structural protein 9 (Nsp9) from betacoronaviruses including highly pathogenic Severe acute respiratory syndrome-related coronavirus (SARS-CoV), SARS-CoV2 (also called 2019 novel CoV or 2019-nCoV), and Middle East respiratory syndrome-related (MERS) CoV. CoVs utilize a multi-subunit replication/transcription machinery assembled from a set of non-structural proteins (Nsps) generated as cleavage products of the ORF1a and ORF1ab viral polyproteins. All of these Nsps, except for Nsp1 and Nsp2, are considered essential for transcription, replication, and translation of the viral RNA. Nsp9, with Nsp7, Nsp8, and Nsp10, localizes within the replication complex. Nsp9 is an essential single-stranded RNA-binding protein for coronavirus replication; it shares structural similarity to the oligosaccharide-binding (OB) fold, which is characteristic of proteins that bind to ssDNA or ssRNA. Nsp9 requires dimerization for binding and orienting RNA for subsequent use by the replicase machinery. CoV Nsp9s have diverse forms of dimerization that promote their biological function, which may help elucidate the mechanism underlying CoVs replication and contribute to the development of antiviral drugs. Generally, dimers are formed via interaction of the parallel alpha-helices containing the protein-protein interaction motif GXXXG; additionally, the N-finger region may also play a critical role in dimerization as seen in porcine delta coronavirus (PDCoV) Nsp9. As a member of the replication complex, Nsp9 may not have a specific RNA-binding sequence but may act in conjunction with other Nsps as a processivity factor, as shown by mutation studies indicating that Nsp9 is a key ingredient that intimately engages other proteins in the replicase complex to mediate efficient virus transcription and replication.


:

Pssm-ID: 409331  Cd Length: 111  Bit Score: 201.09  E-value: 2.58e-59
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 4118 NNELSPVALRQMSCAAGTTQTACtDDNALAYYNNSKGGRFVLALLSDHQDLKWARFPKSDGtGTIYTELEPPCRFVTDTP 4197
Cdd:cd21898    1 NNELMPQGLKTMVVTAGPDQTAC-NTPALAYYNNVQGGRMVMAILSDVDGLKYAKVEKSDG-GFVVLELDPPCKFLVQTP 78
                         90       100       110
                 ....*....|....*....|....*....|...
gi 30027621 4198 KGPKVKYLYFIKGLNNLNRGMVLGSLAATVRLQ 4230
Cdd:cd21898   79 KGPKVKYLYFVKGLNNLHRGQVLGTIAATVRLQ 111
M_alpha_beta_cv_Nsp15-like cd21167
middle domain of alpha- and beta-coronavirus Nonstructural protein 15 (Nsp15), and related ...
6494-6625 1.98e-55

middle domain of alpha- and beta-coronavirus Nonstructural protein 15 (Nsp15), and related proteins; Nidovirus endoribonucleases (NendoUs) are uridylate-specific endoribonucleases, which release a cleavage product containing a 2',3'-cyclic phosphate at the 3' terminal end. NendoUs include Nsp15 from coronaviruses and Nsp11 from arteriviruses, both of which may participate in the viral replication process and in the evasion of the host immune system. Coronavirus Nsp15 NendoUs have an N-terminal domain, a middle (M) domain and a C-terminal catalytic (NendoU) domain. Coronavirus Nsp15 from Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV), human Coronavirus 229E (HCoV229E), and Murine Hepatitis Virus (MHV) form a functional hexamer. This middle domain harbors residues involved in hexamer formation and in trimer stability. Oligomerization of Porcine DeltaCoronavirus (PDCoV) Nsp15 differs from that of the other coronaviruses; it has been shown to exist as a dimer and a monomer in solution.


:

Pssm-ID: 439161  Cd Length: 127  Bit Score: 190.62  E-value: 1.98e-55
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 6494 PVPEIKILNNLGVDIAANTVIWDYKREAPAHVSTIGVCTMTDIAKKptesacSSLTVLFDGRVEGQVDLFRNARNGVLIT 6573
Cdd:cd21167    1 PVPELKLLRNLGVDICYKFVLWDYEREAPFTSSTIGVCKYTDIDKK------SDLNVLFDGRDPGSLERFRSARNAVLIS 74
                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|...
gi 30027621 6574 EGSVKGLTPSKGPAQASVNGVTLIGES-VKTQFNYFKKVDGIIQQLPETYFTQ 6625
Cdd:cd21167   75 TTKVKGLKPIKGPNYASLNGVVVESVDkKKVKFYYYVRKDGEFVDLTDTYFTQ 127
1B_cv_Nsp13-like cd21409
1B domain of coronavirus SARS NSP13 helicase and related proteins; Helicases catalyze ...
5451-5529 8.33e-48

1B domain of coronavirus SARS NSP13 helicase and related proteins; Helicases catalyze NTP-dependent unwinding of nucleic acid duplexes into single strands and are classified based on the arrangement of conserved motifs into six superfamilies. Members of this subfamily belong to helicase superfamily 1 (SF1) and include coronavirus helicases such as Severe Acute Respiratory Syndrome coronavirus (SARS) non-structural protein 13 (SARS-Nsp13). SARS-Nsp13 is a component of the viral RNA synthesis replication and transcription complex (RTC). Structural studies of a stable RTC which included the RNA-dependent RNA polymerase holoenzyme (Nsp7, two molecules of Nsp82, Nsp12), two molecules of Nsp13 helicase accessory factor and an RNA template product suggests that the Nsp13 helicase may drive RTC backtracking, affecting proofreading and template switching. SARS-Nsp13 is a multidomain protein; its other domains include an N-terminal Cys/His rich zinc-binding domain (CH/ZBD) and a SF1 helicase core. The 1B domain is involved in nucleic acid substrate binding; the 1B domain of the related Equine arteritis virus (EAV) Nsp10 undergoes large conformational change upon substrate binding, and together with the 1A and 2A domains of the helicase core form a channel that accommodates the single stranded nucleic acids.


:

Pssm-ID: 394817  Cd Length: 79  Bit Score: 166.75  E-value: 8.33e-48
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 30027621 5451 GIATVREVLSDRELHLSWEVGKPRPPLNRNYVFTGYRVTKNSKVQIGEYTFEKGDYGDAVVYRGTTTYKLNVGDYFVLT 5529
Cdd:cd21409    1 ASATVKEVVGPRELVLSWEAGKTKPPLNRNYVFTGYHITKNSKTQLGEYTFEKSDYSDSVYYKSTTTYKLQPGDIFVLT 79
Macro_X_Nsp3-like cd21557
X-domain (or Mac1 domain) of viral non-structural protein 3 and related macrodomains; The ...
1034-1155 9.84e-48

X-domain (or Mac1 domain) of viral non-structural protein 3 and related macrodomains; The X-domain, also called Mac1, is the macrodomain found in riboviral non-structural protein 3 (Nsp3), including the Nsp3 of Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) as well as SARS-CoV-2, and other coronaviruses (alpha-, beta-, gamma-, and deltacoronavirus), among others. The SARS-CoV-2 Nsp3 Mac1 is highly conserved among all CoVs, and binds to and hydrolyzes mono-ADP-ribose (MAR) from target proteins. It appears to counter host-mediated antiviral ADP-ribosylation, a post-translational modification that is part of the host response to viral infections. Mac1 is essential for pathogenesis in multiple animal models of CoV infection, implicating it as a virulence factor and potential therapeutic target. Assays show that the de-MARylating activity leads to a rapid loss of substrate, and that Mac1 could not hydrolyze poly-ADP-ribose; thus, Mac1 is a MAR-hydrolase (mono-ADP ribosylhydrolase). Mac1 was originally named ADP-ribose-1"-phosphatase (ADRP) based on data demonstrating that it could remove the phosphate group from ADP-ribose-1"-phosphate; however, activity was modest and was unclear why this would impact a virus infection. This family also includes the X-domain of Avian infectious bronchitis virus (IBV) strain Beaudette coronavirus that does not bind ADP-ribose; the triple glycine sequence found in the X-domains of SARS-CoV and human coronavirus 229E (HCoV229E), which are involved in ADP-ribose binding, is not conserved in the IBV X-domain. SARS-CoVs have two other macrodomains referred to as the SUD-N (N-terminal subdomain, or Mac2) and SUD-M (middle SUD subdomain, or Mac3) of the SARS-unique domain (SUD), which also do not bind ADP-ribose; these bind G-quadruplexes (unusual nucleic-acid structures formed by consecutive guanosine nucleotides). SARS-CoV SUD-N and SUD-M are not included in this group.


:

Pssm-ID: 438957  Cd Length: 127  Bit Score: 168.50  E-value: 9.84e-48
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 1034 VIVNAANIHLKHGGGVAGALNKATNGAMQKESDdYIKLNGPLTVGGSCLLSGHNLAKKCLHVVGPNLNAGEDIQLLKAAY 1113
Cdd:cd21557    3 VVVNAANENLKHGGGVAGAIYKATGGAFQKESD-YIKKNGPLKVGTAVLLPGHGLAKNIIHVVGPRKRKGQDDQLLAAAY 81
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*.
gi 30027621 1114 ENFNS-QDILLAPLLSAGIFGAKPLQSLQVCVQTVRT---QVYIAV 1155
Cdd:cd21557   82 KAVNKeYGSVLTPLLSAGIFGVPPEQSLNALLDAVDTtdaDVTVYC 127
Corona_NSP4_C pfam16348
Coronavirus nonstructural protein 4 C-terminus; This is the C-terminal domain of the ...
3146-3238 6.12e-44

Coronavirus nonstructural protein 4 C-terminus; This is the C-terminal domain of the coronavirus nonstructural protein 4 (NSP4). NSP4 is a membrane-spanning protein which is thought to anchor the viral replication-transcription complex (RTC) to modified endoplasmic reticulum membranes. This predominantly alpha-helical domain may be involved in protein-protein interactions.


:

Pssm-ID: 406690  Cd Length: 92  Bit Score: 156.14  E-value: 6.12e-44
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621   3146 GVTF-STFEEAALCTFLLNKEMYLKLRSEtlLPLTQYNRYLALYNKYKYFSGALDTTSYREAACCHLAKALNDFSNSGAD 3224
Cdd:pfam16348    1 GDEFvGTFEEAALGTFVIDKESYEKLTNS--ISLDKFNRYLSLYNKYKYYSGTMDEADYREACCAHLAKALDDFSNSGND 78
                           90
                   ....*....|....
gi 30027621   3225 VLYQPPQTSITSAV 3238
Cdd:pfam16348   79 ILYTPPTVSIGSSL 92
betaCoV_Nsp7 cd21827
betacoronavirus non-structural protein 7; This model represents the non-structural protein 7 ...
3837-3919 2.89e-41

betacoronavirus non-structural protein 7; This model represents the non-structural protein 7 (Nsp7) of betacoronaviruses including the highly pathogenic Severe acute respiratory syndrome-related coronavirus (SARS-CoV), SARS-CoV2 (also called 2019 novel CoV or 2019-nCoV), and Middle East respiratory syndrome-related (MERS) CoV. CoVs utilize a multi-subunit replication/transcription machinery. A set of non-structural proteins (Nsps) generated as cleavage products of the ORF1a and ORF1ab viral polyproteins assemble to facilitate viral replication and transcription. Upon processing of the Nsp7-10 region by protease M (Mpro), the released four small proteins Nsp7, Nsp8, Nsp9 and Nsp10 form functional complexes with CoV core enzymes and stimulate replication. Most importantly, a complex of Nsp7 with Nsp8 has been shown to activate and confer processivity to the RNA-synthesizing activity of Nsp12, the RNA-dependent RNA-polymerase (RdRp); in SARS-CoV, point mutations in the NSP7- or NSP8-coding region have been shown to delay virus growth. Nsp7 and Nsp8 cooperate in activating the primer-dependent activity of the Nsp12 RdRp such that the level of their association may constitute a limiting factor for obtaining a high RNA polymerase activity. The subsequent Nsp7/Nsp8/Nsp12 polymerase complex is then able to associate with an active bifunctional Nsp14, which includes N-terminal 3' to 5' exoribonuclease (ExoN) and C-terminal N7-guanine cap methyltransferase (N7-MTase) activities, thus representing a unique coronavirus Nsp assembly that incorporates RdRp, exoribonuclease, and N7-MTase activities. Interaction of Nsp7 with Nsp8 appears to be conserved across the coronavirus family, making these proteins interesting drug targets. Nsp7 has a 4-helical bundle conformation which is strongly affected by its interaction with Nsp8, especially where it concerns alpha-helix 4. SARS-CoV Nsp7 forms a 8:8 hexadecameric supercomplex with Nsp8 that adopts a hollow cylinder-like structure with a large central channel and positive electrostatic properties in the cylinder; the Nsp7/Nsp8 complex functions as a noncanonical RNA polymerase capable of synthesizing RNA of up to template length.


:

Pssm-ID: 409253  Cd Length: 83  Bit Score: 148.36  E-value: 2.89e-41
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 3837 SKMSDVKCTSVVLLSVLQQLRVESSSKLWAQCVQLHNDILLAKDTTEAFEKMVSLLSVLLSMQGAVDINRLCEEMLDNRA 3916
Cdd:cd21827    1 SKLTDVKCTSVVLLSVLQQLHVESNSKLWAYCVKLHNDILAAKDPTEAFEKFVSLLSVLLSFPGAVDLDALCSELLDNPT 80

                 ...
gi 30027621 3917 TLQ 3919
Cdd:cd21827   81 VLQ 83
SUD_C_SARS-CoV_Nsp3 cd21525
C-terminal SARS-Unique Domain (SUD) of non-structural protein 3 (Nsp3) from Severe Acute ...
1472-1538 3.45e-41

C-terminal SARS-Unique Domain (SUD) of non-structural protein 3 (Nsp3) from Severe Acute Respiratory Syndrome coronavirus and related betacoronaviruses in the B lineage; This subfamily contains the SUD-C of Severe Acute Respiratory Syndrome (SARS) coronavirus (CoV) non-structural protein 3 (Nsp3) and other Nsp3s from betacoronaviruses in the sarbecovirus subgenera (B lineage), such as SARS-CoV-2 and related bat CoVs. Non-structural protein 3 (Nsp3) is a large multi-functional multi-domain protein that is an essential component of the replication/transcription complex (RTC), which carries out RNA synthesis, RNA processing, and interference with the host cell innate immune system. Nsp3 of the Severe Acute Respiratory Syndrome (SARS) coronavirus includes a SARS-unique domain (SUD) consisting of three globular domains separated by short linker peptide segments: SUD-N, SUD-M, and SUD-C. SUD-N and SUD-M are macro domains which bind G-quadruplexes (unusual nucleic-acid structures formed by consecutive guanosine nucleotides). The SUD-C domain adopts a frataxin-like fold and has structural similarity to DNA-binding domains of DNA-modifying enzymes. It binds to single-stranded RNA and recognizes purine bases more strongly than pyrimidine bases. SUD-C also regulates the RNA binding behavior of the SUD-M macrodomain.


:

Pssm-ID: 394841  Cd Length: 67  Bit Score: 147.31  E-value: 3.45e-41
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 30027621 1472 TSEEHFVETVSLAGSYRDWSYSGQRTELGVEFLKRGDKIVYHTLESPVEFHLDGEVLSLDKLKSLLS 1538
Cdd:cd21525    1 TPEEHFVETVSLAGSYRDWSYSGQRTELGVEFLKRGDKIVYHTLESPVEFHLDGEVLPLDKLKSLLS 67
SARS-CoV-like_Nsp1_C cd22662
C-terminal domain of non-structural protein 1 from Severe acute respiratory syndrome-related ...
128-180 6.79e-34

C-terminal domain of non-structural protein 1 from Severe acute respiratory syndrome-related coronavirus and betacoronavirus in the B lineage; This model represents the C-terminal domain of non-structural protein 1 (Nsp1) from betacoronaviruses in the sarbecovirus subgenus (B lineage), including highly pathogenic coronaviruses such as Severe acute respiratory syndrome-related coronavirus (SARS-CoV) and SARS-CoV2 (also called 2019 novel CoV or 2019-nCoV). CoVs utilize a multi-subunit replication/transcription machinery assembled from a set of non-structural proteins (Nsps) generated as cleavage products of the ORF1a and ORF1ab viral polyproteins. Nsp1 is the N-terminal cleavage product released from the ORF1a polyprotein by the action of papain-like protease (PLpro). Though Nsp1s of alphaCoVs and betaCoVs share structural similarity, they show no significant sequence similarity and may be considered as genus-specific markers. Despite low sequence similarity, the Nsp1s of alphaCoVs and betaCoVs exhibit remarkably similar biological functions, and are involved in the regulation of both host and viral gene expression. CoV Nsp1 induces suppression of host gene expression and interferes with host immune response. It inhibits host gene expression in two ways: by targeting the translation and stability of cellular mRNAs, and by inhibiting mRNA translation and inducing an endonucleolytic RNA cleavage in the 5'-UTR of cellular mRNAs through its tight association with the 40S ribosomal subunit, a key component of the cellular translation machinery. Inhibition of host mRNA translation includes that of type I interferons, major components of the host innate immune response. Nsp1 is critical in regulating viral replication and gene expression. SARS-CoV Nsp1 enhances virus replication by binding to a stem-loop structure in the 5'-UTR of its genome. When the SARS-CoV-2 5' UTR is bound to the Nsp1 N-terminus, the covalently linked Nsp1 C-terminus cannot bind the 40S ribosome, suggesting a bipartite mechanism whereby SARS-CoV-2 Nsp1 suppresses host but not viral translation.


:

Pssm-ID: 439355  Cd Length: 53  Bit Score: 126.14  E-value: 6.79e-34
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 30027621  128 NKGAGGHSYGIDLKSYDLGDELGTDPIEDYEQNWNTKHGSGALRELTRELNGG 180
Cdd:cd22662    1 NKGAGGHSYGIDLKSYDLGDELGTDPIEDYEQNWNTKHGSGALRELTRELNGG 53
NTD_alpha_betaCoV_Nsp15-like cd21171
N-terminal domain of alpha- and beta-coronavirus Nonstructural protein 15 (Nsp15), and related ...
6430-6490 3.55e-33

N-terminal domain of alpha- and beta-coronavirus Nonstructural protein 15 (Nsp15), and related proteins; Coronavirus (CoV) Nsp15 is a nidovirus endoribonuclease (NendoU). NendoUs are uridylate-specific endoribonucleases, which release a cleavage product containing a 2',3'-cyclic phosphate at the 3' terminal end. NendoUs include CoV Nsp15 and arterivirus Nsp11, both of which may participate in the viral replication process and in the evasion of the host immune system. This small NTD structure, present in coronavirus Nsp15, is missing in Nsp11. CoV Nsp15 has an N-terminal domain, a middle (M) domain, and a C-terminal catalytic (NendoU) domain. Nsp15 from Severe Acute Respiratory Syndrome (SARS)-CoV, human CoV229E (HCoV229E), and Murine Hepatitis Virus (MHV) form a functional hexamer. Residues in this N-terminal domain are important for hexamer (dimer of trimers) formation.


:

Pssm-ID: 439163  Cd Length: 61  Bit Score: 124.22  E-value: 3.55e-33
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 30027621 6430 SLENVAYNVVNKGHFDGHAGEAPVSIINNAVYTKVDGIDVEIFENKTTLPVNVAFELWAKR 6490
Cdd:cd21171    1 SLENVAYNVVKKGHFVGVEGELPVAIVNDKVFVKDGGVDVLVFTNKTSLPTNVAFELYAKR 61
stalk_CoV_Nsp13-like cd21689
stalk domain of coronavirus Nsp13 helicase and related proteins; This model represents the ...
5400-5447 6.70e-25

stalk domain of coronavirus Nsp13 helicase and related proteins; This model represents the stalk domain of coronavirus non-structural protein 13 (Nsp13) helicase, found in the Nsp3s of alpha-, beta-, gamma-, and deltacoronaviruses, including Severe Acute Respiratory Syndrome coronavirus (SARS-CoV), SARS-CoV-2 (also called 2019 novel CoV or 2019-nCoV), and Middle East respiratory syndrome coronavirus (MERS-CoV). Helicases are classified based on the arrangement of conserved motifs into six superfamilies; coronavirus helicases in this family belong to superfamily 1 (SF1). Helicases catalyze NTP-dependent unwinding of nucleic acid duplexes into single strands. Nsp13 is a component of the viral RNA synthesis replication and transcription complex (RTC). It consists of an N-terminal ZBD (Cys/His rich zinc-binding domain), a stalk domain, a 1B regulatory domain, and SF1 helicase core. The stalk domain lies between the ZBD domain and the 1B domain; a short loop connects the ZBD to the stalk domain. The stalk domain is comprised of three tightly-interacting alpha-helices connected to the 1B domain, transferring the effect from the ZBD domain onto the helicase core domains. The ZBD and stalk domains are critical for the helicase activity of SARS-CoV Nsp13.


:

Pssm-ID: 410205  Cd Length: 48  Bit Score: 100.38  E-value: 6.70e-25
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*...
gi 30027621 5400 GSDNVTDFNAIATCDWTNAGDYILANTCTERLKLFAAETLKATEETFK 5447
Cdd:cd21689    1 GSPDVDDFNRLATSDWSDVEDYKLANTCKDSLKLFAAETIKAKEESVK 48
 
Name Accession Description Interval E-value
SARS-CoV-like_RdRp cd21591
Severe acute respiratory syndrome coronavirus RNA-dependent RNA polymerase, also known as ...
4375-5301 0e+00

Severe acute respiratory syndrome coronavirus RNA-dependent RNA polymerase, also known as non-structural protein 12, and similar proteins from betacoronaviruses in the B lineage: responsible for replication and transcription of the viral RNA genome; This group contains the RNA-dependent RNA polymerase (RdRp) of Severe acute respiratory syndrome coronavirus (SARS-CoV), SARS-CoV-2 (also known as 2019 novel CoV (2019-nCoV) or COVID-19 virus), and similar proteins from betacoronaviruses in the sarbecovirus subgenera (B lineage). CoVs utilize a multi-subunit replication/transcription machinery. A set of non-structural proteins (Nsps) generated as cleavage products of the ORF1a and ORF1ab viral polyproteins assemble to facilitate viral replication and transcription. A key component, the RNA-dependent RNA polymerase (RdRp, also known as Nsp12), catalyzes the synthesis of viral RNA and thus plays a central role in the replication and transcription cycle of CoV, possibly interacting with its co-factors, Nsp7 and Nsp8. RdRp is therefore considered a primary target for nucleotide analog antiviral inhibitors such as remdesivir, which shows potential for the treatment of SARS-CoV-2 viral infections. The structure of SARS-CoV-2 Nsp12 contains a RdRp domain as well as a large N-terminal extension that adopts a nidovirus RdRp-associated nucleotidyltransferase (NiRAN) architecture. Recent studies have shown that the SARS-CoV-2 RdRp requires two iron-sulfur clusters to function optimally. Earlier studies had mistakenly identified these iron-sulfur cluster binding sites for zinc-binding sites, likely because iron-sulfur clusters degrade easily under standard experimental conditions.The RdRp domain displays a right hand with three functional subdomains, called fingers, palm, and thumb. All RdRps contain conserved polymerase motifs (A-G), located in the palm (A-E motifs) and finger (F-G) subdomains. All these motifs have been implicated in RdRp fidelity such as processes of correct incorporation and reorganization of nucleotides.


Pssm-ID: 394895  Cd Length: 928  Bit Score: 1903.66  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 4375 TFLNRVCGVSAARLTPCGTGTSTDVVYRAFDIYNEKVAGFAKFLKTNCCRFQEKDEEGNLLDSYFVVKRHTMSNYQHEET 4454
Cdd:cd21591    2 SFLNRVCGVSAARLTPCGTGTSTDVVYRAFDIYNDKVAGFAKFLKTNCCRFQEKDEDGNLIDSYFVVKRHTFSNYQHEET 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 4455 IYNLVKDCPAVAVHDFFKFRVDGDMVPHISRQRLTKYTMADLVYALRHFDEGNCDTLKEILVTYNCCDDDYFNKKDWYDF 4534
Cdd:cd21591   82 IYNLLKDCPAVAVHDFFKFRVDGDMVPHISRQRLTKYTMADLVYALRHFDEGNCDTLKEILVTYNCCDDDYFNKKDWYDF 161
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 4535 VENPDILRVYANLGERVRQSLLKTVQFCDAMRDAGIVGVLTLDNQDLNGNWYDFGDFVQVAPGCGVPIVDSYYSLLMPIL 4614
Cdd:cd21591  162 VENPDILRVYANLGERVRQALLKTVQFCDAMRDAGIVGVLTLDNQDLNGNWYDFGDFIQTTPGSGVPIVDSYYSLLMPIL 241
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 4615 TLTRALAAESHMDADLAKPLIKWDLLKYDFTEERLCLFDRYFKYWDQTYHPNCINCLDDRCILHCANFNVLFSTVFPPTS 4694
Cdd:cd21591  242 TLTRALTAESHVDTDLTKPYIKWDLLKYDFTEERLKLFDRYFKYWDQTYHPNCVNCLDDRCILHCANFNVLFSTVFPPTS 321
                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 4695 FGPLVRKIFVDGVPFVVSTGYHFRELGVVHNQDVNLHSSRLSFKELLVYAADPAMHAASGNLLLDKRTTCFSVAALTNNV 4774
Cdd:cd21591  322 FGPLVRKIFVDGVPFVVSTGYHFRELGVVHNQDVNLHSSRLSFKELLVYAADPAMHAASGNLLLDKRTTCFSVAALTNNV 401
                        410       420       430       440       450       460       470       480
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 4775 AFQTVKPGNFNKDFYDFAVSKGFFKEGSSVELKHFFFAQDGNAAISDYDYYRYNLPTMCDIRQLLFVVEVVDKYFDCYDG 4854
Cdd:cd21591  402 AFQTVKPGNFNKDFYDFAVSKGFFKEGSSVELKHFFFAQDGNAAISDYDYYRYNLPTMCDIRQLLFVVEVVDKYFDCYDG 481
                        490       500       510       520       530       540       550       560
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 4855 GCINANQVIVNNLDKSAGFPFNKWGKARLYYDSMSYEDQDALFAYTKRNVIPTITQMNLKYAISAKNRARTVAGVSICST 4934
Cdd:cd21591  482 GCINANQVIVNNLDKSAGFPFNKWGKARLYYDSMSYEDQDALFAYTKRNVIPTITQMNLKYAISAKNRARTVAGVSICST 561
                        570       580       590       600       610       620       630       640
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 4935 MTNRQFHQKLLKSIAATRGATVVIGTSKFYGGWHNMLKTVYSDVETPHLMGWDYPKCDRAMPNMLRIMASLVLARKHNTC 5014
Cdd:cd21591  562 MTNRQFHQKLLKSIAATRGATVVIGTSKFYGGWHNMLKTVYSDVENPHLMGWDYPKCDRAMPNMLRIMASLVLARKHTTC 641
                        650       660       670       680       690       700       710       720
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 5015 CNLSHRFYRLANECAQVLSEMVMCGGSLYVKPGGTSSGDATTAYANSVFNICQAVTANVNALLSTDGNKIADKYVRNLQH 5094
Cdd:cd21591  642 CSLSHRFYRLANECAQVLSEMVMCGGSLYVKPGGTSSGDATTAYANSVFNICQAVTANVNALLSTDGNKIADKYVRNLQH 721
                        730       740       750       760       770       780       790       800
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 5095 RLYECLYRNRDVDHEFVDEFYAYLRKHFSMMILSDDAVVCYNSNYAAQGLVASIKNFKAVLYYQNNVFMSEAKCWTETDL 5174
Cdd:cd21591  722 RLYECLYRNRDVDTDFVNEFYAYLRKHFSMMILSDDAVVCFNSTYASQGLVASIKNFKSVLYYQNNVFMSEAKCWTETDL 801
                        810       820       830       840       850       860       870       880
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 5175 TKGPHEFCSQHTMLVKQGDDYVYLPYPDPSRILGAGCFVDDIVKTDGTLMIERFVSLAIDAYPLTKHPNQEYADVFHLYL 5254
Cdd:cd21591  802 TKGPHEFCSQHTMLVKQGDDYVYLPYPDPSRILGAGCFVDDIVKTDGTLMIERFVSLAIDAYPLTKHPNQEYADVFHLYL 881
                        890       900       910       920
                 ....*....|....*....|....*....|....*....|....*..
gi 30027621 5255 QYIRKLHDELTGHMLDMYSVMLTNDNTSRYWEPEFYEAMYTPHTVLQ 5301
Cdd:cd21591  882 QYIRKLHDELTGHMLDMYSVMLTNDNTSRYWEPEFYEAMYTPHTVLQ 928
betaCoV_Nsp2_SARS-like cd21516
betacoronavirus non-structural protein 2 (Nsp2) similar to SARS-CoV Nsp2, and related proteins ...
182-818 0e+00

betacoronavirus non-structural protein 2 (Nsp2) similar to SARS-CoV Nsp2, and related proteins from betacoronaviruses in the B lineage; Non-structural proteins (Nsps) from Severe acute respiratory syndrome coronavirus (SARS-CoV) and betacoronaviruses in the sarbecovirus subgenus (B lineage) are encoded in ORF1a and ORF1b. Post infection, the SARS-CoV genomic RNA is released into the cytoplasm of the cell and translated into two long polyproteins (pp), pp1a and pp1ab, which are then autoproteolytically cleaved by two viral proteases Nsp3 and Nsp5 into smaller subunits. Nsp2 is one of these subunits. The function of Nsp2 remains unknown. Deletion of Nsp2 from the SARS-CoV genome results in only a modest reduction in viral titers. Rather than playing a role in viral replication, SARS-CoV Nsp2 may be involved in altering the host cell environment; it has been shown to interact with two host proteins, prohibitin 1 (PHB1) and PHB2 which have been implicated in cellular functions, including cell-cycle progression, cell migration, cellular differentiation, apoptosis, and mitochondrial biogenesis.


Pssm-ID: 439199  Cd Length: 637  Bit Score: 1238.88  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621  182 VTRYVDNNFCGPDGYPLDCIKDFLARAGKSMCTLSEQLDYIESKRGVYCCRDHEHEIAWFTERSDKSYEHQTPFEIKSAK 261
Cdd:cd21516    1 YTRYVDNNFCGPDGYPLECIKDLLARAGKSSCPLSEQLDFIGLKRGVYCCREHEHEIAWYTERSEKSYELQTPFEIKSAK 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621  262 KFDTFKGECPKFVFPLNSKVKVIQPRVEKKKTEGFMGRIRSVYPVASPQECNNMHLSTLMKCNHCDEVSWQTCDFLKATC 341
Cdd:cd21516   81 KFDTFKGECPHFVFPLNSTVKVIQPRVEKKKTEGFMGRIRSVYPVASPGECNPMALSTLMKCNHCGETSWQTSDFLKATC 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621  342 EHCGTENLVIEGPTTCGYLPTNAVVKMPCPACQDPEIGPEHSVADYHNHSNIETRLRKGGRTRCFGGCVFAYVGCYNKRA 421
Cdd:cd21516  161 EFCGTENLTKEGPTTCGYLPQNAVVKMPCPACKNDEVGPEHSLADYHNHSGIETRLRKGGRTVCFGGCVFAYVGCYNKCA 240
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621  422 YWVPRASADIGSGHTGITGDNVETLNEDLLEILSRERVNINIVGDFHLNEEVAIILASFSASTSAFIDTIKSLDYKSFKT 501
Cdd:cd21516  241 YWVPRASANIGSNHTGVVGEDVETLNDDLLEILQREKVNINIVGDFKLNEEVAIILASFSASTSAFIETVKGLDYKTFKQ 320
                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621  502 IVESCGNYKVTKGKPVKGAWNIGQQRSVLTPLCGFPSQAAGVIRSIFARTLDAANHSIPDLQRAAVTILDGISEQSLRLV 581
Cdd:cd21516  321 IVESCGNFKVTKGKAKKGAWNIGTQKSVLTPLLAFPSQAAGVVRSIFSRTLDTAGHSLRALQRAAITILDGISPQSLRLL 400
                        410       420       430       440       450       460       470       480
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621  582 DAMVYTSDLLTNSVIIMAYVTGGLVQQTSQWLSNLLGTTVEKLRPIFEWIEAKLSAGVEFLKDAWEILKFLITGVFDIVK 661
Cdd:cd21516  401 DAMVFTSDLATNSVLVMAYDTGGLVQVTSQWLDNLFGTCADKLKPVLTWLEEKLKEGVDFLRDAWEILKFLVTGAYKIVK 480
                        490       500       510       520       530       540       550       560
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621  662 GQIQVASDNIKDCVKCFIDVVNKALEMCIDQVTIAGAKLRSLNLGEVFIAQSKGLYRQCIRGKEQLQLLMPLKAPKEVTF 741
Cdd:cd21516  481 GQIVLAAKNIKECVQSFVAVVNKVLSLCYDQIQIAGAKVGALNLGETFIAQSKGLYRVCVRAREIQQLLMPLKAPKELTF 560
                        570       580       590       600       610       620       630
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 30027621  742 LEGDSHDTVLTSEEVVLKNGELEALETPVDSFTNGAIVGTPVCVNGLMLLEIKDKEQYCALSPGLLATNNVFRLKGG 818
Cdd:cd21516  561 LEGDTLDTELTSEEVVLKTGTLEALDTPTSEVVNGPVEGTPVCVNGLMLLEIKDKEQYCALSPDCQATNNVFTLKGG 637
TM_Y_SARS-CoV-like_Nsp3_C cd21717
C-terminus of non-structural protein 3, including transmembrane and Y domains, from Severe ...
2209-2739 0e+00

C-terminus of non-structural protein 3, including transmembrane and Y domains, from Severe acute respiratory syndrome-related coronavirus and betacoronavirus in the B lineage; This model represents the C-terminus of non-structural protein 3 (Nsp3) from betacoronavirus in the sarbecovirus subgenus (B lineage), including highly pathogenic human coronaviruses such as Severe acute respiratory syndrome-related coronavirus (SARS-CoV) and SARS-CoV2 (also called 2019 novel CoV or 2019-nCoV). This conserved C-terminus includes two transmembrane (TM) regions TM1 and TM2, an ectodomain (3Ecto) between the TM1 and TM2 that is glycosylated and located on the lumenal side of the ER, an amphiphatic region (AH1) that is not membrane-spanning, and a large Y domain of approximately 370 residues. Nsp3 is a large multi-functional multi-domain protein that is an essential component of the replication/transcription complex (RTC), which carries out RNA synthesis, RNA processing, and interference with the host cell innate immune system. In SARS-CoV and the related murine hepatitis virus (MHV), the TM1, 3Ecto and TM2 domains are important for the papain-like protease (PL2pro) domain to process Nsp3-Nsp4 cleavage. It has also been shown that the interaction of 3Ecto with the lumenal loop of Nsp4 is essential for ER rearrangements in cells infected with SARS-CoV or MHV. The Y domain, located at the cytosolic side of the ER, consists of the Y1 and CoV-Y subdomains, which are conserved in nidovirus and coronavirus, respectively. Functional information about the Y domain is limited; it has been shown that Nsp3 binding to Nsp4 is less efficient without the Y domain.


Pssm-ID: 409665  Cd Length: 531  Bit Score: 1169.76  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 2209 WLLLLSICLGSLICVTAAFGVLLSNFGAPSYCNGVRELYLNSSNVTTMDFCEGSFPCSICLSGLDSLDSYPALETIQVTI 2288
Cdd:cd21717    1 WLLLLSICLGSLIYVTAALGVLLSNLGAPSYCDGVRESYLNSSNVTTMDFCEGSFPCSVCLSGLDSLDSYPALETIQVTI 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 2289 SSYKLDLTILGLAAEWVLAYMLFTKFFYLLGLSAIMQVFFGYFASHFISNSWLMWFIISIVQMAPVSAMVRMYIFFASFY 2368
Cdd:cd21717   81 SSYKLDLTILGLAAEWFLAYMLFTKFFYLLGLSAIMQVFFGYFASHFISNSWLMWFIISIVQMAPVSAMVRMYIFFASFY 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 2369 YIWKSYVHIMDGCTSSTCMMCYKRNRATRVECTTIVNGMKRSFYVYANGGRGFCKTHNWNCLNCDTFCTGSTFISDEVAR 2448
Cdd:cd21717  161 YIWKSYVHIMDGCTSSTCMMCYKRNRATRVECTTIVNGMKRSFYVYANGGRGFCKTHNWNCLNCDTFCAGSTFISDEVAR 240
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 2449 DLSLQFKRPINPTDQSSYIVDSVAVKNGALHLYFDKAGQKTYERHPLSHFVNLDNLRANNTKGSLPINVIVFDGKSKCDE 2528
Cdd:cd21717  241 DLSLQFKRPINPTDQSSYVVDSVAVKNGALHLYFDKAGQKTYERHPLSHFVNLDNLRANNTKGSLPINVIVFDGKSKCDE 320
                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 2529 SASKSASVYYSQLMCQPILLLDQVLVSDVGDSTEVSVKMFDAYVDTFSATFSVPMEKLKALVATAHSELAKGVALDGVLS 2608
Cdd:cd21717  321 SAAKSASVYYSQLMCQPILLLDQALVSDVGDSTEVSVKMFDAYVDTFSATFSVPMEKLKALVATAHSELAKGVALDGVLS 400
                        410       420       430       440       450       460       470       480
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 2609 TFVSAARQGVVDTDVDTKDVIECLKLSHHSDLEVTGDSCNNFMLTYNKVENMTPRDLGACIDCNARHINAQVAKSHNVSL 2688
Cdd:cd21717  401 TFVSAARQGVVDTDVDTKDVIECLKLSHHSDLEVTGDSCNNFMLTYNKVENMTPRDLGACIDCNARHINAQVAKSHNVSL 480
                        490       500       510       520       530
                 ....*....|....*....|....*....|....*....|....*....|.
gi 30027621 2689 IWNVKDYMSLSEQLRKQIRSAAKKNNIPFRLTCATTRQVVNVITTKISLKG 2739
Cdd:cd21717  481 IWNVKDYMSLSEQLRKQIRSAAKKNNIPFRLTCATTRQVVNVITTKISLKG 531
betaCoV_Nsp14 cd21659
nonstructural protein 14 of betacoronavirus; Nonstructural protein 14 (Nsp14) of coronavirus ...
5907-6427 0e+00

nonstructural protein 14 of betacoronavirus; Nonstructural protein 14 (Nsp14) of coronavirus (CoV) plays an important role in viral replication and transcription. It consists of 2 domains with different enzymatic activities: an N-terminal exoribonuclease (ExoN) domain and a C-terminal cap (guanine-N7) methyltransferase (N7-MTase) domain. ExoN is important for proofreading and therefore, the prevention of lethal mutations. The association of Nsp14 with Nsp10 stimulates its ExoN activity; the complex hydrolyzes double-stranded RNA in a 3' to 5' direction as well as a single mismatched nucleotide at the 3'-end mimicking an erroneous replication product. The Nsp10/Nsp14 complex may function in a replicative mismatch repair mechanism. N7-MTase functions in mRNA capping. Nsp14 can methylate GTP, dGTP as well as cap analogs GpppG, GpppA and m7GpppG. The accumulation of m7GTP or Nsp14 has been found to interfere with protein translation of cellular mRNAs.


Pssm-ID: 394958  Cd Length: 519  Bit Score: 1085.52  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 5907 TGLFKDCSKIITGLHPTQAPTHLSVDIKFKTEG-LCVDIPGIPKDMTYRRLISMMGFKMNYQVNGYPNMFITREEAIRHV 5985
Cdd:cd21659    1 TGLFKDCSKSYVGLHPAYAPTFLSVDDKYKTNGdLCVCLNIIDSVVTYSRLISLMGFKLDLTLPGYPKLFITREEAIKRV 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 5986 RAWIGFDVEGCHATRDAVGTNLPLQLGFSTGVNLVAVPTGYVDTENNTEFTRVNAKPPPGDQFKHLIPLMYKGLPWNVVR 6065
Cdd:cd21659   81 RAWIGFDVEGAHATRDAIGTNFPLQLGFSTGVNFVVEPTGLVDTEDGYMFTKIVAKAPPGEQFKHLIPLMSKGQPWDVVR 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 6066 IKIVQMLSDTLKGLSDRVVFVLWAHGFELTSMKYFVKIGPERTCCLCDKRATCFSTSSDTYACWNHSVGFDYVYNPFMID 6145
Cdd:cd21659  161 IRIVQMLSDTLDDLSDSVVFVTWAHGFELTSLRYFAKIGKERTCCMCTKRATCYSSRTGYYGCWRHSVGCDYVYNPFIVD 240
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 6146 VQQWGFTGNLQSNHDQHCQVHGNAHVASCDAIMTRCLAVHECFVKRVDWSVEYPIIGDELRVNSACRKVQHMVVKSALLA 6225
Cdd:cd21659  241 VQQWGYTGNLQSNHDRYCSVHKGAHVASSDAIMTRCLAVHDCFCKRVNWDVEYPIISNELSINSSCRLVQRVVLKAALLA 320
                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 6226 DKFPVLHDIGNPKAIKCVPQAEVEWKFYDAQPCsdkAYKIEELFYSYATHHDKFTDGVCLFWNCNVDRYPANAIVCRFDT 6305
Cdd:cd21659  321 NRFDLCYDIGNPKGIACVKDPVVDWKFYDAQPV---VKSVKQLFYTYEAHKDQFKDGLCMFWNCNVDKYPANAIVCRFDT 397
                        410       420       430       440       450       460       470       480
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 6306 RVLSNLNLPGCDGGSLYVNKHAFHTPAFDKSAFTNLKQLPFFYYSDSPCESHGKQVVSDIDYVPLKSATCITRCNLGGAV 6385
Cdd:cd21659  398 RVLSKLNLPGCNGGSLYVNKHAFHTPAFDKSAFENLKPLPFFYYSDTPCEYHGGNDVKDVDYVPLKSATCITRCNLGGAV 477
                        490       500       510       520
                 ....*....|....*....|....*....|....*....|..
gi 30027621 6386 CRHHANEYRQYLDAYNMMISAGFSLWIYKQFDTYNLWNTFTR 6427
Cdd:cd21659  478 CRKHAEEYREYLEAYNTATTAGFTLWVYKTFDFYNLWNTFTK 519
NSP11 pfam06471
NSP11; This region of coronavirus polyproteins encodes the NSP11 protein.
5905-6427 0e+00

NSP11; This region of coronavirus polyproteins encodes the NSP11 protein.


Pssm-ID: 399465  Cd Length: 515  Bit Score: 990.04  E-value: 0e+00
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621   5905 NVTGLFKDCSKIITGLHPTQAPTHLSVDIKFKTEG---LCVDIPgiPKDMTYRRLISMMGFKMNYQVNGYPNMFITREEA 5981
Cdd:pfam06471    1 NTTGLFKDCSKEYSGLHPAHAPTYLSLDDKFKTSGdlaVCVGVS--DKDVTYKRLISLMGFKMSLNVEGYHNMFITRDEA 78
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621   5982 IRHVRAWIGFDVEGCHATRDAVGTNLPLQLGFSTGVNLVAVPTGYVDTENNTEFTRVNAKPPPGDQFKHLIPLMYKGLPW 6061
Cdd:pfam06471   79 IRHVRAWIGFDVEGAHATGDNVGTNLPLQLGFSTGVDFVVTPEGCVDTENGSVFEPVNAKAPPGEQFKHLIPLMRKGQPW 158
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621   6062 NVVRIKIVQMLSDTLKGLSDRVVFVLWAHGFELTSMKYFVKIGPERTCClCDKRATCFSTSSDTYACWNHSVGFDYVYNP 6141
Cdd:pfam06471  159 HVVRIRIVQMLADTLAGLSDRVVFVLWAHGLELTTMRYFVKIGREQVCS-CGKRATCFNSSTDTYACWKHSLGCDYVYNP 237
                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621   6142 FMIDVQQWGFTGNLQSNHDQHCQVHGNAHVASCDAIMTRCLAVHECFVKRVDWSVEYPIIGDELRVNSACRKVQHMVVKS 6221
Cdd:pfam06471  238 FLIDIQQWGYTGSLSSNHDEHCNVHGNAHVASGDAIMTRCLAVHDCFVKRVDWSLEYPIIANELRVNKACRLVQRMVLKA 317
                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621   6222 ALLADKFPVLHDIGNPKAIKCVPQAEVEWKFYDAQPCSDkayKIEELFYSYATHHDkFTDGVCLFWNCNVDRYPANAIVC 6301
Cdd:pfam06471  318 ALLADKPPVVHDIGNPKGIKCVRRAGVKWKFYDANPIVK---NVKQLEYDYETHKD-KMDGLCLFWNCNVDMYPANAIVC 393
                          410       420       430       440       450       460       470       480
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621   6302 RFDTRVLSNLNLPGCDGGSLYVNKHAFHTPAFDKSAFTNLKQLPFFYYSDSPCESHGKQVvsdiDYVPLKSATCITRCNL 6381
Cdd:pfam06471  394 RFDTRVLSKLNLPGCNGGSLYVNKHAFHTPAFDRRAFANLKPMPFFYYSDSPCESVGKQV----DYVPLKSATCITRCNI 469
                          490       500       510       520
                   ....*....|....*....|....*....|....*....|....*.
gi 30027621   6382 GGAVCRHHANEYRQYLDAYNMMISAGFSLWIYKQFDTYNLWNTFTR 6427
Cdd:pfam06471  470 GGAVCKKHANEYREYVESYNMMTTAGFTFWVPKNFDTYNLWNTFTR 515
Corona_RPol_N pfam06478
Coronavirus RPol N-terminus; This family covers the N-terminal region of the coronavirus ...
4383-4735 0e+00

Coronavirus RPol N-terminus; This family covers the N-terminal region of the coronavirus RNA-directed RNA Polymerase.


Pssm-ID: 428967  Cd Length: 353  Bit Score: 715.78  E-value: 0e+00
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621   4383 VSAARLTPCGTGTSTDVVYRAFDIYNEKVAGFAKFLKTNCCRFQEKDEEGNLLDSYFVVKRHTMSNYQHEETIYNLVKDC 4462
Cdd:pfam06478    1 SSAARLEPCASGTDPDVVYRAFDIYNKDVAGIGKFLKTNCCRFQEVDKDGNLLDSYFVVKRCTKSVYEHEESCYNLLKDC 80
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621   4463 PAVAVHDFFKFRVDGDMVPHISRQRLTKYTMADLVYALRHFDEGNCDTLKEILVTYNCCDDDYFNKKDWYDFVENPDILR 4542
Cdd:pfam06478   81 GVVAEHDFFKFDKGGDMVPNISRQDLTKYTMMDLCYALRHFDEKDCEVLKEILVTYGCCEEDYFEKKDWYDPVENPDIYR 160
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621   4543 VYANLGERVRQSLLKTVQFCDAMRDAGIVGVLTLDNQDLNGNWYDFGDFVQVAPGCGVPIVDSYYSLLMPILTLTRALAA 4622
Cdd:pfam06478  161 VYAKLGPIVRRALLKTVAFCDAMVEAGLVGVLTLDNQDLNGNFYDFGDFVKTAPGCGVPVVDSYYSYMMPIMTMTHALAS 240
                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621   4623 ESHMDADLAKPLIKWDLLKYDFTEERLCLFDRYFKYWDQTYHPNCINCLDDRCILHCANFNVLFSTVFPPTSFGPLVRKI 4702
Cdd:pfam06478  241 ECFVDSDLGKDYKKYDLLKYDFTEEKLELFDKYFKYWDQTYHPNCVDCLDDRCILHCANFNVLFSTVIPNTAFGPLVRKV 320
                          330       340       350
                   ....*....|....*....|....*....|...
gi 30027621   4703 FVDGVPFVVSTGYHFRELGVVHNQDVNLHSSRL 4735
Cdd:pfam06478  321 FVDGVPFVVTAGYHFKELGVVMNQDVNTHSSRL 353
betaCoV_Nsp13-helicase cd21722
helicase domain of betacoronavirus non-structural protein 13; This model represents the ...
5552-5891 0e+00

helicase domain of betacoronavirus non-structural protein 13; This model represents the helicase domain of non-structural protein 13 (Nsp13) from betacoronavirus, including pathogenic human viruses such as Severe acute respiratory syndrome coronavirus (SARS-CoV), SARS-CoV2 (also called 2019 novel CoV or 2019-nCoV), and Middle East respiratory syndrome-related (MERS) CoV. Helicases catalyze NTP-dependent unwinding of nucleic acid duplexes into single strands and are classified based on the arrangement of conserved motifs into six superfamilies. CoV Nsp13 is a member of the helicase superfamily 1 (SF1); SF1 and SF2 helicases do not form toroidal structures, while SF3-6 helicases do. Nsp13 is a component of the viral RNA synthesis replication and transcription complex (RTC). It is a multidomain protein containing a Cys/His rich zinc-binding domain (CH/ZBD), a stalk domain, a 1B domain involved in nucleic acid substrate binding, and a SF1 helicase core.


Pssm-ID: 409655 [Multi-domain]  Cd Length: 340  Bit Score: 707.72  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 5552 GLYPTLNISDEFSSNVANYQKVGMQKYSTLQGPPGTGKSHFAIGLALYYPSARIVYTACSHAAVDALCEKALKYLPIDKC 5631
Cdd:cd21722    1 GLYPTYNVPEEFQNNVVNYQKIGMKRYCTVQGPPGTGKSHLAIGLAVYYPTARVVYTACSHAAVDALCEKAFKFLNINKC 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 5632 SRIIPARARVECFDKFKVNSTLEQYVFCTVNALPETTADIVVFDEISMATNYDLSVVNARLRAKHYVYIGDPAQLPAPRT 5711
Cdd:cd21722   81 SRIIPAKARVECYDKFKVNDTSRQYVFSTINALPETVTDILVVDEVSMCTNYDLSVINARVRAKHIVYIGDPAQLPAPRT 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 5712 LLTKGTLEPEYFNSVCRLMKTIGPDMFLGTCRRCPAEIVDTVSALVYDNKLKAHKDKSAQCFKMFYKGVITHDVSSAINR 5791
Cdd:cd21722  161 LLTKGTLEPEYFNSVTRLMCCLGPDIFLGTCYRCPKEIVDTVSALVYDNKLKAKKDNSGQCFKVYYKGSVTHDSSSAINR 240
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 5792 PQIGVVREFLTRNPAWRKAVFISPYNSQNAVASKILGLPTQTVDSSQGSEYDYVIFTQTTETAHSCNVNRFNVAITRAKI 5871
Cdd:cd21722  241 PQIYLVKKFLKANPAWSKAVFISPYNSQNAVARRVLGLQTQTVDSSQGSEYDYVIYCQTAETAHSVNVNRFNVAITRAKK 320
                        330       340
                 ....*....|....*....|
gi 30027621 5872 GILCIMSDRDLYDKLQFTSL 5891
Cdd:cd21722  321 GILCVMSSMQLFESLQFTEL 340
NSP13 pfam06460
Coronavirus NSP13; This family covers the NSP13 region of the coronavirus polyprotein. This ...
6777-7072 0e+00

Coronavirus NSP13; This family covers the NSP13 region of the coronavirus polyprotein. This protein has the predicted function of an mRNA cap-1 methyltransferase function.


Pssm-ID: 399456  Cd Length: 297  Bit Score: 596.02  E-value: 0e+00
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621   6777 SQAWQPGVAMPNLYKMQRMLLEKCDLQNYGENAVIPKGIMMNVAKYTQLCQYLNTLTLAVPYNMRVIHFGAGSDKGVAPG 6856
Cdd:pfam06460    1 SAAWKPGYSMPNLYKMQRMCLEPCNLYNYGAGITLPSGIMMNVAKYTQLCQYLNTTTLCVPHNMRVLHLGAGSDKGVAPG 80
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621   6857 TAVLRQWLPTGTLLVDSDLNDFVSDADSTLIGDCATVHTANKWDLIISDMYDPRTKHVTKENDSKEGFFTYLCGFIKQKL 6936
Cdd:pfam06460   81 SAVLRQWLPTGTILVDNDLNDYVSDADFSVTGDCATVYTEDKFDLIISDMYDPRTKHIDGENVSKDGFFTYLCGFIKEKL 160
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621   6937 ALGGSIAVKITEHSWNADLYKLMGHFSWWTAFVTNVNASSSEAFLIGANYLGK-PKEQIDGYTMHANYIFWRNTNPIQLS 7015
Cdd:pfam06460  161 ALGGSIAIKITEFSWNADLYELMQRFSWWTMFCTNVNASSSEAFLIGINYLGKsPKEQIDGKTMHANYIFWRNSTPMQLS 240
                          250       260       270       280       290
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 30027621   7016 SYSLFDMSKFPLKLRGTAVMSLKENQINDMIYSLLEKGRLIIRENNRVVVSSDILVN 7072
Cdd:pfam06460  241 AYSLFDMSKFPLKLKGTAVVSLKENQINDMVLSLLEKGKLLVRDNGKVVFFSDSLVN 297
betaCoV_Nsp5_Mpro cd21666
betacoronavirus non-structural protein 5, also called Main protease (Mpro); This subfamily ...
3244-3540 0e+00

betacoronavirus non-structural protein 5, also called Main protease (Mpro); This subfamily contains the coronavirus (CoV) non-structural protein 5 (Nsp5) also called the Main protease (Mpro), or 3C-like protease (3CLpro), found in betacoronaviruses. CoVs utilize a multi-subunit replication/transcription machinery. A set of non-structural proteins (Nsps) generated as cleavage products of the ORF1a and ORF1ab viral polyproteins assemble to facilitate viral replication and transcription. Mpro/Nsp5 is a key enzyme in this process, making it a high value target for the development of anti-coronavirus therapeutics. These enzymes belong to the MEROPS peptidase C30 family, where the active site residues His and Cys form a catalytic dyad. The structures of Mpro/Nsp5 consist of three domains with the first two containing anti-parallel beta barrels and the third consisting of an arrangement of alpha-helices. The catalytic residues are found in a cleft between the first two domains. Mpro requires a Gln residue in the P1 position of the substrate and space for only small amino-acid residues such as Gly, Ala, or Ser in the P1' position; since there is no known human protease with a specificity for Gln at the cleavage site of the substrate, these viral proteases are suitable targets for the development of antiviral drugs.


Pssm-ID: 394887  Cd Length: 297  Bit Score: 577.43  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 3244 RKMAFPSGKVEGCMVQVTCGTTTLNGLWLDDTVYCPRHVICTAEDMLNPNYEDLLIRKSNHSFLVQAGNVQLRVIGHSMQ 3323
Cdd:cd21666    1 RKMAFPSGKVEGCMVQVTCGTMTLNGLWLDDTVYCPRHVICTAEDMLNPNYEDLLIRKTNHSFLVQAGNVQLRVIGHSMQ 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 3324 NCLLRLKVDTSNPKTPKYKFVRIQPGQTFSVLACYNGSPSGVYQCAMRPNHTIKGSFLNGSCGSVGFNIDYDCVSFCYMH 3403
Cdd:cd21666   81 GCLLRLTVDTSNPKTPKYKFVRVKPGQTFSVLACYNGSPSGVYQCAMRPNHTIKGSFLCGSCGSVGYNIDGDCVSFCYMH 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 3404 HMELPTGVHAGTDLEGKFYGPFVDRQTAQAAGTDTTITLNVLAWLYAAVINGDRWFLNRFTTTLNDFNLVAMKYNYEPLT 3483
Cdd:cd21666  161 QMELPTGVHTGTDLEGKFYGPFVDRQTAQAAGTDTTITLNVLAWLYAAVLNGDRWFVNRFTTTLNDFNLWAMKYNYEPLT 240
                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 30027621 3484 QDHVDILGPLSAQTGIAVLDMCAALKELLQNGMNGRTILGSTILEDEFTPFDVVRQC 3540
Cdd:cd21666  241 QDHVDILDPLAAQTGIAVEDMLAALKELLQGGMQGRTILGSTILEDEFTPFDVVRQC 297
Peptidase_C30 pfam05409
Coronavirus endopeptidase C30; Corresponds to Merops family C30. These peptidases are involved ...
3269-3546 1.80e-164

Coronavirus endopeptidase C30; Corresponds to Merops family C30. These peptidases are involved in viral polyprotein processing in replication.


Pssm-ID: 398852  Cd Length: 274  Bit Score: 509.29  E-value: 1.80e-164
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621   3269 GLWLDDTVYCPRHVICTAEDMLnPNYEDLLIRKSNHSFLVQAGNVQLRVIGHSMQNCLLRLKVDTSNPKTPKYKFVRIQP 3348
Cdd:pfam05409    1 GLWLGDTVYCPRHVIGSFTGML-PQYEHLLSIARNHDFCVVSGGVQLTVVSAKMQGAILVLKVHTNNPNTPKYKFVRLKP 79
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621   3349 GQTFSVLACYNGSPSGVYQCAMRPNHTIKGSFLNGSCGSVGFNIDYDCVSFCYMHHMELPTGVHAGTDLEGKFYGPFVDR 3428
Cdd:pfam05409   80 GESFTILAAYDGCPQGVYHVTMRSNHTIKGSFLNGACGSVGYNLKGGTVCFVYMHHLELPNGSHTGTDLEGVFYGPYVDE 159
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621   3429 QTAQAAGTDTTITLNVLAWLYAAVINGDRWFLNRFTTTLNDFNLVAMKYNYEPLTQDHVdiLGPLSAQTGIAVLDMCAAL 3508
Cdd:pfam05409  160 EVAQLEGTDQTYTDNVVAWLYAAIINGPRWFLASTTVSLEDFNAWAMTNGFTPFPCEDA--ILGLAAKTGVSVERLLAAI 237
                          250       260       270
                   ....*....|....*....|....*....|....*...
gi 30027621   3509 KElLQNGMNGRTILGSTILEDEFTPFDVVRQCSGVTFQ 3546
Cdd:pfam05409  238 KV-LNNGFGGRTILGSPSLEDEFTPEDVYNQMAGVTLQ 274
betaCoV_PLPro cd21732
betacoronavirus papain-like protease; This model represents the papain-like protease (PLPro) ...
1543-1845 1.12e-159

betacoronavirus papain-like protease; This model represents the papain-like protease (PLPro) found in non-structural protein 3 (Nsp3) of betacoronavirus, including highly pathogenic betacoronaviruses such as Severe acute respiratory syndrome-related coronavirus (SARS-CoV), SARS-CoV2 (also called 2019 novel CoV or 2019-nCoV), and Middle East respiratory syndrome-related (MERS) CoV. CoVs utilize a multi-subunit replication/transcription machinery. A set of non-structural proteins (Nsps) generated as cleavage products of the ORF1a and ORF1ab viral polyproteins assemble to facilitate viral replication and transcription. PLPro is a key enzyme in this process, making it a high value target for the development of anti-coronavirus therapeutics. PLPro, which belongs to the MEROPS peptidase C16 family, participates in the proteolytic processing of the N-terminal region of the replicase polyprotein; it can cleave Nsp1|Nsp2, Nsp2|Nsp3, and Nsp3|Nsp4 sites and its activity is dependent on zinc. In SARS-CoV and murine hepatitis virus (MHV), the C-terminal non-structural protein 3 region spanning transmembrane regions TM1 and TM2 with 3Ecto domain in between, are important for the PL2pro domain to process Nsp3-Nsp4 cleavage. Besides cleaving the polyproteins, PLPro also possesses a related enzymatic activity to promote virus replication: deubiquitinating (DUB) and de-ISGylating activities. Both, ubiquitin (Ub) and Ub-like interferon-stimulated gene product 15 (ISG15), are involved in preventing viral infection; coronaviruses utilize Ubl-conjugating pathways to counter the pro-inflammatory properties of Ubl-conjugated host proteins via the action of PLPro, which processes both 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains from cellular substrates. The Nsp3 PLPro domain of many of these CoVs has also been shown to antagonize host innate immune induction of type I interferon by interacting with IRF3 and blocking its activation. Interactions of SARS-CoV and MERS-CoV with antiviral interferon (IFN) responses of human cells are remarkably different; high-dose IFN treatment (type I and type III) shows MERS-CoV was substantially more IFN sensitive than SARS-CoV. This may be due to differences in the architecture of the oxyanion hole and of the S3 as well as the S5 specificity sites, despite the overall structures of SARS-CoV and MERS-CoV PLPro being similar.


Pssm-ID: 409649  Cd Length: 304  Bit Score: 496.72  E-value: 1.12e-159
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 1543 KTIKVFTTVDNTNLHTQLVDMSMTYGQQFGPTYLDGADVTKIKPHVNHEGKTFFVLPSDDTLRSEAFEY-YHTLDESFLG 1621
Cdd:cd21732    1 KTIEVLTTVDGVNFRTVLVNNGETFGKQLGNVFCDGVDVTKTKPSAKYEGKVLFQADNLSAEELEAVEYyYGFDDPTFLL 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 1622 RYMSALNHTKKWKFPQVGGLTSIKWADNNCYLSSVLLALQQLEVKFNAPALQEAYYRARAGDAANFCALILAYSNKTVGE 1701
Cdd:cd21732   81 RYYSALAHVKKWKFVVVDGYFSLKQADNNCYLNAACLMLQQLDLKFNTPALQEAYYEFRAGDPLRFVALVLAYGNFTFGE 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 1702 LGDVRETMTHLLQHANLESAKRVLNVVCKHCGQKTTTLTGVEAVMYMGTLSYDNLKTGVSIPCVCGRDATQYLVQQESSF 1781
Cdd:cd21732  161 PDDARDFLRVVLSHADLVSARRVLEEVCKVCGVKQEQRTGVDAVMYFGTLSLDDLYKGYTIDCSCGRKAIRYLVEQVPPF 240
                        250       260       270       280       290       300
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 30027621 1782 VMMSAPPAEYKLQQGTFLCANEYTGNYQCGHYTHITAKETLYRIDGAHLTKMSEYKGPVTDVFY 1845
Cdd:cd21732  241 LLMSNTPTEVPLPTGDFVAANVFTGDESVGHYTHVKNKSLLYLYDAGNVKKTSDLKGPVTDVLY 304
Viral_protease pfam08715
Papain like viral protease; This family of viral proteases are similar to the papain protease ...
1541-1859 3.37e-156

Papain like viral protease; This family of viral proteases are similar to the papain protease and are required for proteolytic processing of the replicase polyprotein. The structure of this protein has shown it adopts a fold similar that of de-ubiquitinating enzymes.


Pssm-ID: 430171  Cd Length: 318  Bit Score: 487.57  E-value: 3.37e-156
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621   1541 EVKTIKVFTTVDNTNLHTQLVDMSMTYGQQFGPTYLDGADVTKIKPHVNHEGKTFFVLPSDDTLRSEAFE---YYHTLDE 1617
Cdd:pfam08715    1 ECKQITIYLTEDGVNYHSIVVKPGDSLGQQFGQVYAKNKDLSGVFPADDVEDKEILYVPTTDWVEFYGFKsilEYYTLDA 80
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621   1618 SFLGRYMSALnhtkKWKFPQVGGLTSIKWADNNCYLSSVLLALQQLEVKFNAPALQEAYYRARAGDAANFCALILAYSNK 1697
Cdd:pfam08715   81 SKYVIYLSAL----TKNVQYVDGFLILKWRDNNCWISSVIVALQAAKIRFKGQFLTEAWAKLLGGDPTDFVAWCYASCTA 156
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621   1698 TVGELGDVRETMTHLLQHANLESAKRVLN-VVCKHCGQKTTTLTGVEAVMYMGTLSYDNLKTGVSIPCVCGRDATQYLVQ 1776
Cdd:pfam08715  157 KVGDFGDANWTLTNLAEHFDAEYTNAFLKkRVCCNCGIKSYELRGLEACIQVRATNLDHFKTGYSNCCVCGANNTDEVIE 236
                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621   1777 QESSFVMMSA---PPAEYKLQQGTFLCAneYTGNYQCGHYTHITAKETLYriDGAHLTKMSEYKGPVTDVFYKETSYTTT 1853
Cdd:pfam08715  237 ASLPYLLLSAtdgPAAVDCLEDGVGTVA--FVGSTNSGHYTYQTAKQAFY--DGAKDRKFGKKSPYVTAVYTRFAFKNET 312

                   ....*.
gi 30027621   1854 IKPVSY 1859
Cdd:pfam08715  313 SLPVAK 318
CoV_NSP3_C pfam19218
Coronavirus replicase NSP3, C-terminal; This family represents the C-terminal region of ...
2240-2726 4.38e-155

Coronavirus replicase NSP3, C-terminal; This family represents the C-terminal region of non-structural protein NSP3 (also known as nsp3). NSP3 is the product of ORF1a. It is found in human SARS coronavirus polyprotein 1a and 1ab, and in related coronavirus polyproteins. It is a multifunctional protein comprising up to 16 different domains and regions. NSP3 binds to viral RNA, nucleocapsid protein, as well as other viral proteins and participates in polyprotein processing.


Pssm-ID: 437055  Cd Length: 463  Bit Score: 490.68  E-value: 4.38e-155
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621   2240 CNGVRELYLNSSNVTTmDFCEGSFPCSICLSGLDSLDSYPALETIQVTISSYKLD--LTILGLAAEWVLAYMLFTKFFYL 2317
Cdd:pfam19218    4 CDGYVDGYSNSSFDKS-DYCNGSLLCKACLSGYDSLHDYPHLKVVQQHVKDPLFFdyTPLAYFAFELFVALALFGGTFVR 82
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621   2318 LGLSAIMQVFFGYFaSHFISNSWLMWFiisiVQMAPVSAMVRMYIFFASFYYIWKSYVHIMDGCTSSTCMMCYKRNRATR 2397
Cdd:pfam19218   83 LFLLYFLQQFVNFF-GVYLGLQDLSWF----LTLIPFDVFLREYVVVFYVIKLYRFFKHVVFGCKKPSCLACSKRARLTR 157
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621   2398 VECTTIVNGMKRSFYVYANGGRGFCKTHNWNCLNCDTFCTGSTFISDEVARDLSLQFKRPINPTDQSSYIVDSVAVKNGA 2477
Cdd:pfam19218  158 VPVSTVVNGSKKSFYVNANGGTKFCKKHNFFCVNCDSYGPGNTFINDEVAEDLSNVTKRSVKPTDPAYYEVDKVEFQDGF 237
                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621   2478 LHLYFDKAGQKTYERHPLSHFVNLDNLRANNTKGSLPINVIVFDgKSKCDESASKSASVYYSQLMCQPILLLDQVLVSDV 2557
Cdd:pfam19218  238 YYLYYGREFWRYYFDVTVSKFSDKEVLKNCNVTGYPLDNFIVYD-NNGSNLANAKNACVYYSQLLCKPIKLVDSNLLSTL 316
                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621   2558 GDSTEVSVKMFDAYVDTFSATFSVPMEKLKALVATAHSelakgvaldgvlstfvsaarqgvVDTDVDTKDVIECLKLSHH 2637
Cdd:pfam19218  317 GDSVDVNGALFDAFVDVLLNSFNVDLSKCKTLIECAKD-----------------------LGSDVDTDSFVNAVQNAHR 373
                          410       420       430       440       450       460       470       480
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621   2638 SDLEVTGDSCNNFMLTYNKV-ENMTPRDLGACIDCNARHINAQVAKSHNVSLIWNVKDYMSLSEQLRKQIRSAAKKNNIP 2716
Cdd:pfam19218  374 YDLLLTDDSFNNFVPTYAKPeDSLSTHDLAVCIRFGAKIVNHNVLKKENVSVVWSADDFNKLSEEARRYIVKAAKKKGVT 453
                          490
                   ....*....|
gi 30027621   2717 FRLTCATTRQ 2726
Cdd:pfam19218  454 FKLTFNKLRA 463
cv_Nsp4_TM cd21473
coronavirus non-structural protein 4 (Nsp4) transmembrane domain; Nsp4 may be involved in ...
2754-3134 1.99e-149

coronavirus non-structural protein 4 (Nsp4) transmembrane domain; Nsp4 may be involved in coronavirus-induced membrane remodeling. In order to assemble the replication-transcription complex (RTC), coronavirus induces the rearrangement of host endoplasmic reticulum (ER) membrane into double membrane vesicles (DMVs), zippered ER, or ER spherules. DMV formation has been observed in SARS-CoV cells overexpressing the three transmembrane-containing non-structural proteins of viral replicase polyprotein 1ab: Nsp3, Nsp4 and Nsp6. Together, Nsp3, Nsp4, and Nsp6 have the ability to induce the formation of DMVs that are similar to those seen in SARS-CoV-infected cells.


Pssm-ID: 394836  Cd Length: 376  Bit Score: 470.92  E-value: 1.99e-149
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 2754 TLLCVLAALVCYIVMPVHTLSIHDGYTNEIIGYKAIQDGVTRDIISTDDCFANKHAGFDAWFSQRGGS-YKNDKSCPVVA 2832
Cdd:cd21473    1 FLWLLLAAILLYAFLPSYSVFTVTVSSFPGYDFKVIENGVLRDIRSTDTCFANKFVNFDSWYQAKYGSvPTNSKSCPIVV 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 2833 AIITREIGFiVPGLPGTVLRaINGDFLHFLPRVFSAVGNICYTPSKLIEYSDFATSACVLAAECTIFKDaMGKPVPYCYD 2912
Cdd:cd21473   81 GVIDDVRGS-VPGVPAGVLL-VGKTLVHFVQTVFFGDTVVCYTPDGVITYDSFYTSACVFNSACTYLTG-LGGRQLYCYD 157
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 2913 TNLLEGSISYSELRPDTRYVLMDGSIIQFPNTYLEGSVRVVTTFDAEYCRHGTCERSEVGICLSTSGRWVLNNEHYRalS 2992
Cdd:cd21473  158 TGLVEGAKLYSDLLPHVRYKLVDGNYIKFPEVILEGGPRIVRTLATTYCRVGECEDSKAGVCVSFDGFWVYNNDYYG--P 235
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 2993 GVFCGVDAMNLIANIFTPLVQPVGALDVSASVVAGGIIAILVTCAAYYFMKFRRVFGEyNHVVAANALLFLMSFTILCLV 3072
Cdd:cd21473  236 GVYCGDGLFDLLTNLLSGFFQPVSVFALSGQLLFNTIVAILAVLACYYVQKFKRAFGD-MSVVVVTVVAAALVNNVLYVV 314
                        330       340       350       360       370       380
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 30027621 3073 PAYSFLPGVYSVFYLYLTFYFTNDVSFLAHLQWFAMFSPIVPFWITAIYVFCISLKHCHWFF 3134
Cdd:cd21473  315 TQNPLLMIVYAVLYFYATLYLTYERAWIMHLGWVVAYGPIAPWWLLALYVVAVLYDYLPWFF 376
betaCoV-Nsp6 cd21560
betacoronavirus non-structural protein 6; Coronaviruses (CoV) redirect and rearrange host cell ...
3547-3836 8.03e-149

betacoronavirus non-structural protein 6; Coronaviruses (CoV) redirect and rearrange host cell membranes as part of the viral genome replication and transcription machinery; they induce the formation of double-membrane vesicles in infected cells. CoV non-structural protein 6 (Nsp6), a transmembrane-containing protein, together with Nsp3 and Nsp4, have the ability to induce double-membrane vesicles that are similar to those observed in severe acute respiratory syndrome (SARS) coronavirus-infected cells. By itself, Nsp6 can generate autophagosomes from the endoplasmic reticulum. Autophagosomes are normally generated as a cellular response to starvation to carry cellular organelles and long-lived proteins to lysosomes for degradation. Degradation through autophagy may provide an innate defense against virus infection, or conversely, autophagosomes can promote infection by facilitating the assembly of replicase proteins. In addition to initiating autophagosome formation, Nsp6 also limits autophagosome expansion regardless of how they were induced, i.e. whether they were induced directly by Nsp6, or indirectly by starvation or chemical inhibition of MTOR signaling. This may favor coronavirus infection by compromising the ability of autophagosomes to deliver viral components to lysosomes for degradation.


Pssm-ID: 394846  Cd Length: 290  Bit Score: 465.18  E-value: 8.03e-149
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 3547 GKFKKIVKGTHHWMLLTFLTSLLILVQSTQWSLFFFVYENAFLPFTLGIMAIAACAMLLVKHKHAFLCLFLLPSLATVAY 3626
Cdd:cd21560    1 SKVKRVVKGTLHWLLATFVLFYLIILQLTKWTMFMYLTETMLLPLTPALCCVSACVMLLVKHKHTFLTLFLLPVLLTLAY 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 3627 FNMVYMPA-SWVMRIMTWLELADTSlSGYRLKDCVMYASALVLLILMTARTVYDDAARRVWTLMNVITLVYKVYYGNALD 3705
Cdd:cd21560   81 YNYVYVPKsSFLGYVYNWLNYVNPY-VDYTYTDEVTYGSLLLVLMLVTMRLVNHDAFSRVWAVCRVITWVYMWYTGSLEE 159
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 3706 QAISMWALVISVTSNYSGVVTTIMFLARAIVFVCVEYYPLLFITGNTLQCIMLVYCFLGYCCCCYFGLFCLLNRYFRLTL 3785
Cdd:cd21560  160 SALSYLTFLFSVTTNYTGVVTVSLALAKFITALWLAYNPLLFLDIPEVKCVLLVYLFIGYICTCYFGVFSLLNRLFRCPL 239
                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|.
gi 30027621 3786 GVYDYLVSTQEFRYMNSQGLLPPKSSIDAFKLNIKLLGIGGKPCIKVATVQ 3836
Cdd:cd21560  240 GVYDYKVSTQEFRYMNANGLRPPRNSWEALMLNFKLLGIGGVPCIKVSTVQ 290
CoV_NSP4_N pfam19217
Coronavirus replicase NSP4, N-terminal; This is the N-terminal domain of the coronavirus ...
2765-3119 3.79e-116

Coronavirus replicase NSP4, N-terminal; This is the N-terminal domain of the coronavirus nonstructural protein 4 (NSP4). NSP4 is encoded by ORF1a/1ab and proteolytically released from the pp1a/1ab polyprotein. NSP4 is a membrane-spanning protein which is thought to anchor the viral replication-transcription complex to modified endoplasmic reticulum membranes. This N-terminal region represents the membrane spanning region, covering four transmembrane regions.


Pssm-ID: 437054  Cd Length: 351  Bit Score: 374.29  E-value: 3.79e-116
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621   2765 YIVMPVHTLSIHDGYTNEIIGYKAIQDGVTRDIISTDDCFANKHAGFDAWFSQRGGSYKNDKSCPVVAAIITREIGFIVP 2844
Cdd:pfam19217    1 YALSPSFFNTKVYFVSDPVYDFKVIENGVLRDFDSTDTCFHNKFDNFDQWHQAKFGTPTNSRSCPIVVGVVDGVVGRTVP 80
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621   2845 GLPGTVLRAiNGDFLHFLPRVFSAVGNICYTPSKLIEYSDFATSACVLAAECTIFKDAMGKPVPYCYDTNLLEGSISYSE 2924
Cdd:pfam19217   81 GVPAGVALV-GGTILHFVTRVFFGAGNVCYTPSGVISYEDFSASACVFNSACTTLTGLGGTRVLYCYDDGLVPGAKLYSD 159
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621   2925 LRPDTRYVLMDGSIIQFPNTYLEGSVRVVTTFDAEYCRHGTCERSEVGICLSTSGRWVLNNEHYralSGVFCGVDAMNLI 3004
Cdd:pfam19217  160 LKPHVRYKLVDGNYVKFPEVLFRGGFRIVRTLATTYCRVGECEDSKAGVCVGFDGSFVYNNDFG---PGVYCGDDFLDLV 236
                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621   3005 ANIFTPLVQPVGALDVSASVVAGGIIAILVTCAAYYFMKFRRVFGEYNHVVAANALLFLMSFTILCLVPAYSFLPGVYSV 3084
Cdd:pfam19217  237 RNVFSGFNTPISVFALTGQLMFNCVLALIAVCVCYYVLKFKRAFGDYTTGVLTVVLAALVNNLSYFVTQVNPVLMIVYAV 316
                          330       340       350
                   ....*....|....*....|....*....|....*
gi 30027621   3085 FYLYLTFYFTNDVSFLAHLQWFAMFSPIVPFWITA 3119
Cdd:pfam19217  317 LYFYATLYVTPEYAWIMHLSFLVAYVPVAPWWVLL 351
nsp8 pfam08717
nsp8 replicase; Viral nsp8 (non structural protein 8) forms a hexadecameric supercomplex with ...
3920-4116 4.68e-115

nsp8 replicase; Viral nsp8 (non structural protein 8) forms a hexadecameric supercomplex with nsp7 that adopts a hollow cylinder-like structure. The dimensions of the central channel and positive electrostatic properties of the cylinder imply that it confers processivity on RNA-dependent RNA polymerase.


Pssm-ID: 400866  Cd Length: 197  Bit Score: 364.17  E-value: 4.68e-115
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621   3920 AIASEFSSLPSYAAYATAQEAYEQAVANGDSEVVLKKLKKSLNVAKSEFDRDAAMQRKLEKMADQAMTQMYKQARSEDKR 3999
Cdd:pfam08717    1 SVASEFSSLPSYAAYETAKEAYEEAVANGSSQQVLKQLKKACNIAKSEFDRDAAVQKKLEKMAEQAMTQMYKEARAVDRK 80
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621   4000 AKVTSAMQTMLFTMLRKLDNDALNNIINNARDGCVPLNIIPLTTAAKLMVVVPDYGTYKNTCDGNTFTYASALWEIQQVV 4079
Cdd:pfam08717   81 SKVVSAMHTLLFSMLRKLDNSALNTIINNARNGVVPLNIIPATTAAKLTVVVPDYETFVKVVDGNTVTYAGAVWEIQEVK 160
                          170       180       190
                   ....*....|....*....|....*....|....*..
gi 30027621   4080 DADSKIVQLSEINMDNSPNLAWPLIVTALRANSAVKL 4116
Cdd:pfam08717  161 DADGKIVHLKEITMDNSPNLAWPLIVTAERANSAVKL 197
betaCoV_Nsp8 cd21831
betacoronavirus non-structural protein 8; This model represents the non-structural protein 8 ...
3923-4117 2.01e-110

betacoronavirus non-structural protein 8; This model represents the non-structural protein 8 (Nsp8) the highly pathogenic betacoronaviruses that include Severe acute respiratory syndrome-related coronavirus (SARS-CoV), SARS-CoV2 (also called 2019 novel CoV or 2019-nCoV), and Middle East respiratory syndrome-related (MERS) CoV. CoVs utilize a multi-subunit replication/transcription machinery. A set of non-structural proteins (Nsps) generated as cleavage products of the ORF1a and ORF1ab viral polyproteins assemble to facilitate viral replication and transcription. Upon processing of the Nsp7-10 region by protease M (Mpro), the released four small proteins Nsp7, Nsp8, Nsp9, and Nsp10 form functional complexes with CoV core enzymes and thereby stimulate replication. Most importantly, a complex of Nsp8 with Nsp7 has been shown to activate and confer processivity to the RNA-synthesizing activity of Nsp12, the RNA-dependent RNA-polymerase (RdRp); in SARS-CoV, point mutations in the genes encoding Nsp8 and Nsp7 have been shown to delay virus growth. Nsp8 and Nsp7 cooperate in activating the primer-dependent activity of the Nsp12 RdRp such that the level of their association may constitute a limiting factor for obtaining a high RNA polymerase activity. The subsequent Nsp7/Nsp8/Nsp12 polymerase complex is then able to associate with an active bifunctional Nsp14, which includes N-terminal 3' to 5' exoribonuclease (ExoN) and C-terminal N7-guanine cap methyltransferase (N7-MTase) activities, thus representing a unique coronavirus Nsp assembly that incorporates RdRp, exoribonuclease, and N7-MTase activities. Interaction of Nsp8 with Nsp7 appears to be conserved across the coronavirus family, making these proteins interesting drug targets. Nsp8 has a novel 'golf-club' fold composed of an N-terminal 'shaft' domain and a C-terminal 'head' domain. The shaft domain contains three helices, one of which is very long, while the head domain contains another three helices and seven beta-strands, forming an alpha/beta fold. SARS-CoV Nsp8 forms a 8:8 hexadecameric supercomplex with Nsp7 that adopts a hollow cylinder-like structure with a large central channel and positive electrostatic properties in the cylinder; the Nsp7/Nsp8 complex functions as a noncanonical RNA polymerase capable of synthesizing RNA of up to the template length.


Pssm-ID: 409258  Cd Length: 196  Bit Score: 351.01  E-value: 2.01e-110
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 3923 SEFSSLPSYAAYATAQEAYEQAVANGD-SEVVLKKLKKSLNVAKSEFDRDAAMQRKLEKMADQAMTQMYKQARSEDKRAK 4001
Cdd:cd21831    1 SEFSNLASYAEYETAQKAYDEAVASGDaSPQVLKALKKAVNVAKSAYEKDKAVARKLERMADQAMTSMYKQARAEDKKSK 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 4002 VTSAMQTMLFTMLRKLDNDALNNIINNARDGCVPLNIIPLTTAAKLMVVVPDYGTYKNTCDGNTFTYASALWEIQQVVDA 4081
Cdd:cd21831   81 VVSAMQTMLFGMIRKLDNDALNNIINNARNGCVPLSIIPLTAANKLRVVVPDYSVYKQVVDGPTLTYAGALWDIQQINDA 160
                        170       180       190
                 ....*....|....*....|....*....|....*..
gi 30027621 4082 DSKIVQLSEINMDNsPNLAWPLIVTALRAN-SAVKLQ 4117
Cdd:cd21831  161 DGKIVQLSDITEDS-ENLAWPLVVTATRANsSAVKLQ 196
DUF3655 pfam12379
Protein of unknown function (DUF3655); This domain family is found in viruses, and is ...
881-1029 4.67e-108

Protein of unknown function (DUF3655); This domain family is found in viruses, and is approximately 70 amino acids in length. The family is found in association with pfam08716, pfam01661, pfam05409, pfam06471, pfam08717, pfam06478, pfam09401, pfam06460, pfam08715, pfam08710.


Pssm-ID: 432517  Cd Length: 149  Bit Score: 342.16  E-value: 4.67e-108
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621    881 VKTLQPVSDLLTNMGIDLDEWSVATFYLFDDAGEENFSSRMYCSFYPPDEEEEDDAECEEEEIDETCEHEYGTEDDYQGL 960
Cdd:pfam12379    1 VKTLQPVSDLLTNMGIDLDEWSVATFYLFDDAGEENFSSRMYCSFYPPDEEEEDDAECEEEEIDETCEHEYGTEDDYQGL 80
                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 30027621    961 PLEFGASAETVRVEEEEEEDWLDDTTEQSEIEPEPEPTPEEPVNQFTGYLKLTDNVAIKCVDIVKEAQS 1029
Cdd:pfam12379   81 PLEFGASAETVRVEEEEEEDWLDDTTEQSEIEPEPEPTPEEPVNQFTGYLKLTDNVAIKCVDIVKEAQS 149
NendoU_cv_Nsp15-like cd21161
Nidoviral uridylate-specific endoribonuclease (NendoU) domain of coronavirus Nonstructural ...
6623-6773 2.52e-90

Nidoviral uridylate-specific endoribonuclease (NendoU) domain of coronavirus Nonstructural Protein 15 (Nsp15) and related proteins; Nidovirus endoribonucleases (NendoUs) are uridylate-specific endoribonucleases, which release a cleavage product containing a 2',3'-cyclic phosphate at the 3' terminal end. NendoUs include Nsp15 from coronaviruses and Nsp11 from arteriviruses, both of which may participate in the viral replication process and in the evasion of the host immune system. Except for turkey coronavirus (TCoV) Nsp15, Mn2+ is generally essential for the catalytic activity of coronavirus Nsp15. Coronavirus Nsp15 from Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV), human Coronavirus 229E (HCoV229E), and murine hepatitis virus (MHV) form a functional hexamer while Porcine DeltaCoronavirus (PDCoV) Nsp15 has been shown to exist as a dimer and a monomer in solution. NendoUs are distantly related to Xenopus laevis Mn(2+)-dependent uridylate-specific endoribonuclease (XendoU) which is involved in the processing of intron-encoded box C/D U16 small, nucleolar RNA.


Pssm-ID: 439158  Cd Length: 151  Bit Score: 291.47  E-value: 2.52e-90
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 6623 FTQSRDLEDFKPRSQMETDFLELAMDEFIQRYKLEGYAFEHIVYGDFSHGQLGGLHLMIGLAKRSQDSPLKLEDFIPMDS 6702
Cdd:cd21161    1 FTQGRSLEDFKPRSQMERDFLSMDQDVFIQKYGLEDLGFEHIVYGDFSKPTIGGLHLLIGLVRLKKEGKLYVEEFHNSDS 80
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 30027621 6703 TVKNYFITDAQTGSSKCVCSVIDLLLDDFVEIIKSQDLSVISKVVKVTIDYAEISFMLWCKDGHVETFYPK 6773
Cdd:cd21161   81 TVQNYFVTDANNGSSKQVCTVVDLLLDDFVDILKSQDLSVVSKVVTVSIDYKPIRFMLWCKDGKVKTFYPQ 151
CoV_NSP15_C pfam19215
Coronavirus replicase NSP15, uridylate-specific endoribonuclease; This entry represents the ...
6620-6773 4.99e-84

Coronavirus replicase NSP15, uridylate-specific endoribonuclease; This entry represents the C-terminal domain of coronavirus non-structural protein 15 (NSP15 or nsp15). NSP15 is encoded by ORF1a/1ab and proteolytically released from the pp1a/1ab polyprotein. This domain exhibits endoribonuclease activity designated EndoU, highly conserved in all known CoVs and is part of the replicase-transcriptase complex that plays important roles in virus replication and transcription. NSP15 is a Uridylate-specific endoribonuclease that cleaves the 5'-polyuridines from negative-sense viral RNA, termed PUN RNA either upstream or downstream of uridylates, at GUU or GU to produce molecules with 2',3'-cyclic phosphate ends. PUN RNA is a CoV MDA5-dependent pathogen-associated molecular pattern (PAMP).


Pssm-ID: 437052  Cd Length: 154  Bit Score: 273.42  E-value: 4.99e-84
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621   6620 ETYFTQSRDLEDFKPRSQMETDFLELAMDEFIQRYKLEGYAFEHIVYGDFSHGQLGGLHLMIGLAKRSQDSPLKLEDFIP 6699
Cdd:pfam19215    1 DTLFTQGRTLEDFVPRSTMEKDFLNMDQDVFIQKYGLEDYGFEHIVYGDFSKTTIGGLHLLISLVRLSQEGILKVEEFVP 80
                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 30027621   6700 MDSTVKNYFITDAQTGSSKCVCSVIDLLLDDFVEIIKSQDLSVISKVVKVTIDYAEISFMLWCKDGHVETFYPK 6773
Cdd:pfam19215   81 NDSTVKNCFVTYANDGSSKAVCTVIDLLLDDFVDIIKSLDLSVVSKVVTVNIDFQPIRFMLWCKDGKVQTFYPQ 154
CoV_Nsp10 cd21872
coronavirus non-structural protein 10; This model represents the non-structural protein 10 ...
4231-4361 1.32e-82

coronavirus non-structural protein 10; This model represents the non-structural protein 10 (Nsp10) of alpha-, beta-, gamma- and deltacoronaviruses, including highly pathogenic betacoronaviruses such as Severe acute respiratory syndrome-related coronavirus (SARS-CoV), SARS-CoV2 (also called 2019 novel CoV or 2019-nCoV), and Middle East respiratory syndrome-related (MERS) CoV. CoVs utilize a multi-subunit replication/transcription machinery. A set of non-structural proteins (Nsps) generated as cleavage products of the ORF1a and ORF1ab viral polyproteins assemble to facilitate viral replication and transcription. Upon processing of the Nsp7-10 region by protease M (Mpro), the released four small proteins Nsp7, Nsp8, Nsp9, and Nsp10 form functional complexes with CoV core enzymes and thereby stimulate replication. Coronaviruses cap their mRNAs; RNA cap methylation may involve at least three proteins: Nsp10, Nsp14, and Nsp16. Nsp10 serves as a cofactor for both Nsp14 and Nsp16. Nsp14 consists of 2 domains with different enzymatic activities: an N-terminal ExoN domain and a C-terminal cap (guanine-N7) methyltransferase (N7-MTase) domain. The association of Nsp10 with Nsp14 enhances Nsp14's exoribonuclease (ExoN) activity, and not its N7-Mtase activity. ExoN is important for proofreading and therefore, the prevention of lethal mutations. The Nsp10/Nsp14 complex hydrolyzes double-stranded RNA in a 3' to 5' direction as well as a single mismatched nucleotide at the 3'-end, mimicking an erroneous replication product, and may function in a replicative mismatch repair mechanism. Nsp16 Cap-0 specific (nucleoside-2'-O-)-methyltransferase (2'OMTase) acts sequentially to Nsp14 MTase in RNA capping methylation, and methylates the RNA cap at the ribose 2'-O position; it catalyzes the conversion of the cap-0 structure on m7GpppA-RNA to a cap-1 structure. The association of Nsp10 with Nsp16 enhances Nsp16's 2'OMTase activity, possibly through enhanced RNA binding affinity. Additionally, transmissible gastroenteritis virus (TGEV) Nsp10, Nsp16, and their complex can interact with DII4, which normally binds to Notch receptors; this interaction may disturb Notch signaling. Nsp10 also binds 2 zinc ions with high affinity.


Pssm-ID: 409325  Cd Length: 131  Bit Score: 268.57  E-value: 1.32e-82
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 4231 AGNATEVPANSTVLSFCAFAVDPAKAYKDYLASGGQPITNCVKMLCTHTGTGQAITVTPEANMDQESFGGASCCLYCRCH 4310
Cdd:cd21872    1 AGNATEVPANSTVLSFCAFAVDPAKAYKDYLASGGQPITNCVKMLCTHTGTGQAITVKPEANMDQESFGGASVCLYCRAH 80
                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|.
gi 30027621 4311 IDHPNPKGFCDLKGKYVQIPTTCANDPVGFTLRNTVCTVCGMWKGYGCSCD 4361
Cdd:cd21872   81 IDHPNPDGFCDYKGKFVQIPTTCANDPVGFTLRNTVCTVCQMWKGYGCSCD 131
SUD-M pfam11633
Single-stranded poly(A) binding domain; This family of proteins represents Nsp3c, the product ...
1344-1469 1.78e-82

Single-stranded poly(A) binding domain; This family of proteins represents Nsp3c, the product of ORF1a in group 2 coronavirus. The domain exhibits a macrodomain fold containing the nsp3 residues 528 to 648, with a flexibly extended N-terminal tail from residues 513 to 527 and a C-terminal flexible tail of residues 649 to 651. SUD-M(527-651) binds single-stranded poly(A); the contact area with this RNA on the protein surface, and the electrophoretic mobility shift assays confirm that SUD-M has higher affinity for purine bases than for pyrimidine bases.


Pssm-ID: 431970  Cd Length: 126  Bit Score: 267.77  E-value: 1.78e-82
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621   1344 LGTVSWNLREMLAHAEETRKLMPICMDVRAIMATIQRKYKGIKIQEGIVDYGVRFFFYTSKEPVASIITKLNSLNEPLVT 1423
Cdd:pfam11633    1 LGTVSWNLREMLAHAEETRKLMPICMDVRAIMATIQRKYKGIKIQEGIVDYGVRFFFYTSKEPVASIITKLNSLNEPLVT 80
                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*.
gi 30027621   1424 MPIGYVTHGFNLEEAARCMRSLKAPAVVSVSSPDAVTTYNGYLTSS 1469
Cdd:pfam11633   81 MPIGYVTHGFNLEEAARCMRSLKAPAVVSVSSPDAVTTYNGYLTSS 126
SARS-CoV-like_Nsp1_N cd21796
N-terminal domain of non-structural protein 1 from Severe acute respiratory syndrome-related ...
13-127 1.96e-79

N-terminal domain of non-structural protein 1 from Severe acute respiratory syndrome-related coronavirus and betacoronavirus in the B lineage; This model represents the N-terminal domain of non-structural protein 1 (Nsp1) from betacoronaviruses in the sarbecovirus subgenus (B lineage), including highly pathogenic coronaviruses such as Severe acute respiratory syndrome-related coronavirus (SARS-CoV) and SARS-CoV2 (also called 2019 novel CoV or 2019-nCoV). CoVs utilize a multi-subunit replication/transcription machinery assembled from a set of non-structural proteins (Nsps) generated as cleavage products of the ORF1a and ORF1ab viral polyproteins. Nsp1 is the N-terminal cleavage product released from the ORF1a polyprotein by the action of papain-like protease (PLpro). Though Nsp1s of alphaCoVs and betaCoVs share structural similarity, they show no significant sequence similarity and may be considered as genus-specific markers. Despite low sequence similarity, the Nsp1s of alphaCoVs and betaCoVs exhibit remarkably similar biological functions, and are involved in the regulation of both host and viral gene expression. CoV Nsp1 induces suppression of host gene expression and interferes with host immune response. It inhibits host gene expression in two ways: by targeting the translation and stability of cellular mRNAs, and by inhibiting mRNA translation and inducing an endonucleolytic RNA cleavage in the 5'-UTR of cellular mRNAs through its tight association with the 40S ribosomal subunit, a key component of the cellular translation machinery. Inhibition of host mRNA translation includes that of type I interferons, major components of the host innate immune response. Nsp1 is critical in regulating viral replication and gene expression, as shown by multiple evidences, including: mutations in the Nsp1 coding region of the transmissible gastroenteritis virus (TGEV) and murine hepatitis virus (MHV) genomes cause drastic reduction or elimination of infectious virus; bovine coronavirus (BCoV) Nsp1 is an RNA-binding protein that interacts with cis-acting replication elements in the 5'-UTR of the BCoV genome, implying its potential role in the regulation of viral translation or replication; and SARS-CoV Nsp1 enhances virus replication by binding to a stem-loop structure in the 5'-UTR of its genome.


Pssm-ID: 439285  Cd Length: 115  Bit Score: 258.67  E-value: 1.96e-79
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621   13 HVQLSLPVLQVRDVLVRGFGDSVEEALSEAREHLKNGTCGLVELEKGVLPQLEQPYVFIKRSDALSTNHGHKVVELVAEM 92
Cdd:cd21796    1 HVQLSLPVLQVRDVLVRGFGDSVEEALSEAREHLKNGTCGLVELEKGVLPQLEQPYVFIKRSDALSTNHGHKVVELVAEL 80
                         90       100       110
                 ....*....|....*....|....*....|....*
gi 30027621   93 DGIQYGRSGITLGVLVPHVGETPIAYRNVLLRKNG 127
Cdd:cd21796   81 DGIQYGRSGITLGVLVPHVGETPIAYRNVLLRKNG 115
SARS-CoV-like_Nsp3_betaSM cd21814
betacoronavirus-specific marker of non-structural protein 3 from Severe acute respiratory ...
2021-2136 2.40e-78

betacoronavirus-specific marker of non-structural protein 3 from Severe acute respiratory syndrome-related coronavirus and betacoronavirus in the B lineage; This model represents the betacoronavirus-specific marker (betaSM), also called group 2-specific marker (G2M), of non-structural protein 3 (Nsp3) from betacoronavirus in the sarbecovirus subgenus (B lineage), including highly pathogenic human coronaviruses such as Severe acute respiratory syndrome-related coronavirus (SARS-CoV) and SARS-CoV2 (also called 2019 novel CoV or 2019-nCoV). The betaSM/G2M is located C-terminal to the nucleic acid-binding (NAB) domain. This region is absent in alpha- and deltacoronavirus Nsp3; there is a gammacoronavirus-specific marker (gammaSM) at this position in gammacoronavirus Nsp3. Nsp3 is a large multi-functional multi-domain protein that is an essential component of the replication/transcription complex (RTC), which carries out RNA synthesis, RNA processing, and interference with the host cell innate immune system. Little is known about the betaSM/G2M domain; it is predicted to be non-enzymatic and may be an intrinsically disordered region. The betaSM/G2M domain is part of the predicted PLnc domain (made up of 385 amino acids) of SARS-CoV Nsp3 that may function as a replication/transcription scaffold, with interactions to Nsp5, Nsp12, Nsp13, Nsp14, and Nsp16.


Pssm-ID: 409629  Cd Length: 116  Bit Score: 255.57  E-value: 2.40e-78
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 2021 QQPTSEEVVENPTIQKEVIECDVKTTEVVGNVILKPSDEGVKVTQELGHEDLMAAYVENTSITIKKPNELSLALGLKTIA 2100
Cdd:cd21814    1 QQPTSEEVVENPTIQKEVIECDVKTTEVVGNVILKPSDEGVKVTQELGHEDLMAAYVENTSITIKKPNELSLALGLKTLA 80
                         90       100       110
                 ....*....|....*....|....*....|....*.
gi 30027621 2101 THGIAAINSVPWSKILAYVKPFLGQAAITTSNCAKR 2136
Cdd:cd21814   81 THGAAAINSVPWSKILAYVKPFLGQAAVTTSNCAKR 116
Macro_cv_SUD-N_Nsp3-like cd21562
SUD-N macrodomain (or Mac2 domain) of the SARS Unique Domain (SUD) of SARS-CoV non-structural ...
1209-1334 7.87e-76

SUD-N macrodomain (or Mac2 domain) of the SARS Unique Domain (SUD) of SARS-CoV non-structural protein 3 and related macrodomains; This subfamily includes the macrodomain referred to as SUD-N (N-terminal subdomain) of the SARS-unique domain (SUD) which binds G-quadruplexes (unusual nucleic-acid structures formed by consecutive guanosine nucleotides). It is found in the non-structural protein 3 (Nsp3) of Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) and highly related coronaviruses. SUD consists of three globular domains separated by short linker peptide segments: SUD-N, SUD-M, and SUD-C. Among these, SUD-N and SUD-M are macrodomains: the SUD-M domain (not represented in this subfamily) is a related macrodomain which also binds G-quadruplexes. SUD-N (also called Mac2) is specific to the Nsp3 of SARS and betacoronaviruses of the sarbecovirus subgenera (B lineage), while SUD-M (also called Mac3) is present in most Nsp3 proteins except the Nsp3 from betacoronaviruses of the embecovirus subgenera (A lineage). SUD-C adopts a frataxin-like fold, has structural similarity to DNA-binding domains of DNA-modifying enzymes, binds single-stranded RNA, and regulates the RNA binding behavior of the SUD-M macrodomain. SARS-CoV Nsp3 contains a third macrodomain (the X-domain or Mac1) which is also not represented in this subfamily. The X-domain may function as a module binding poly(ADP-ribose); however, SUD-N and SUD-M do not bind ADP-ribose, as the triple glycine sequence involved in its binding is not conserved in these.


Pssm-ID: 394883  Cd Length: 126  Bit Score: 248.98  E-value: 7.87e-76
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 1209 KACIDEVTTTLEETKFLTNKLLLFADINGKLYHDSQNMLRGEDMSFLEKDAPYMVGDVITSGDITCVVIPSKKAGGTTEM 1288
Cdd:cd21562    1 KACIEEVTTTLEETKFLTNKLLLYADINGNLHEDSKNLLRGEDMSFLKKDAPYIVGDVITEGDITCVVIPSKKAGGTTEM 80
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*.
gi 30027621 1289 LSRALKKVPVDEYITTYPGQGCAGYTLEEAKTALKKCKSAFYVLPS 1334
Cdd:cd21562   81 LTRALKKVPTDEYITTYPGQGCAGYTLEEAKTALKKCKSAFYVLPS 126
NSP10 pfam09401
RNA synthesis protein NSP10; Non-structural protein 10 (NSP10) is involved in RNA synthesis. ...
4242-4361 2.63e-73

RNA synthesis protein NSP10; Non-structural protein 10 (NSP10) is involved in RNA synthesis. it is synthesized as a polyprotein whose cleavage generates many non-structural proteins. NSP10 contains two zinc binding motifs and forms two anti-parallel helices which are stacked against an irregular beta sheet. A cluster of basic residues on the protein surface suggests a nucleic acid-binding function.


Pssm-ID: 286486  Cd Length: 119  Bit Score: 241.20  E-value: 2.63e-73
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621   4242 TVLSFCAFAVDPAKAYKDYLASGGQPITNCVKMLCTHTGTGQAITVTPEANMDQESFGGASCCLYCRCHIDHPNPKGFCD 4321
Cdd:pfam09401    1 GLLSLCAFAVDPAKAYLDYLAQGGQPVTNCVKMLCNHAGTGQAITVKPEANTDQDSYGGASVCLYCRAHIEHPNPDGFCQ 80
                           90       100       110       120
                   ....*....|....*....|....*....|....*....|
gi 30027621   4322 LKGKYVQIPTTcANDPVGFTLRNTVCTVCGMWKGYGCSCD 4361
Cdd:pfam09401   81 LKGKFVQIPTG-TKDPVGFCLRNTVCTVCGCWLGYGCSCD 119
capping_2-OMTase_Nidovirales cd20762
Cap-0 specific (nucleoside-2'-O-)-methyltransferase of nidovirales; Cap-0 specific ...
6818-7008 4.66e-72

Cap-0 specific (nucleoside-2'-O-)-methyltransferase of nidovirales; Cap-0 specific (nucleoside-2'-O-)-methyltransferase (2'OMTase) catalyzes the methylation of Cap-0 (m7GpppNp) at the 2'-hydroxyl of the ribose of the first nucleotide, using S-adenosyl-L-methionine (AdoMet) as the methyl donor. This reaction is the fourth and last step in mRNA capping, the creation of the stabilizing five-prime cap (5' cap) on mRNA. Nidovirales, a family of ss(+)RNA viruses, cap their mRNAs. For one member, Coronavirus, the 2'OMTase activity is located in the nonstructural protein 16 (NSP16). For others, the 2'OMTase activity may be located in replicase polyprotein 1ab.


Pssm-ID: 394921  Cd Length: 176  Bit Score: 240.30  E-value: 4.66e-72
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 6818 NVAKYTQLCQYLNTLTLaVPYNMRVIHFGAGSDKGVAPGTAVLRQWLptGTLLVDSDLNDFVSDADSTLIGDCATVHTaN 6897
Cdd:cd20762    1 NISKYVQLCQYINDHLK-LPINPRVLHLGAASDKGYSPGDEVLRQPF--GGIVLDYDLNDFVSHSDIRHINDCNNVFS-G 76
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 6898 KWDLIISDMYDPRTkhvtkenDSKEGFFTYLCGFIKqklaLGGSIAVKITEHSWNADLYKLMGHFSWWTAFVTNVNASSS 6977
Cdd:cd20762   77 KYDLIISDIYAPDT-------DNTELLFDYLNNHLK----LGGSIIWKTTERSTSDNLYQIAKYFGSWTFFTTRVNASSS 145
                        170       180       190
                 ....*....|....*....|....*....|.
gi 30027621 6978 EAFLIGANYLGKPKEQIDGYTMHANYIFWRN 7008
Cdd:cd20762  146 EVFLVFKYYLGTYKEQIDYNDIHALLIAYRN 176
SARS-CoV-like_Nsp3_NAB cd21822
nucleic acid binding domain of non-structural protein 3 from Severe acute respiratory ...
1890-1996 4.77e-71

nucleic acid binding domain of non-structural protein 3 from Severe acute respiratory syndrome-related coronavirus and betacoronavirus in the B lineage; This model represents the nucleic acid binding (NAB) domain of non-structural protein 3 (Nsp3) from betacoronavirus in the sarbecovirus subgenus (B lineage) and hibecovirus subgenus, including highly pathogenic human coronaviruses (CoVs) such as Severe acute respiratory syndrome-related coronavirus (SARS-CoV) and SARS-CoV2 (also called 2019 novel CoV or 2019-nCoV). The NAB domain represents a new fold, with a parallel four-strand beta-sheet holding two alpha-helices of three and four turns that are oriented antiparallel to the beta-strands. NAB is a cytoplasmic domain located between the papain-like protease (PLPro) and betacoronavirus-specific marker (betaSM) domains of CoV Nsp3. Nsp3 is a large multi-functional multi-domain protein that is an essential component of the replication/transcription complex (RTC), which carries out RNA synthesis, RNA processing, and interference with the host cell innate immune system. The NAB domain both binds ssRNA and unwinds dsDNA. It prefers to bind ssRNA containing repeats of three consecutive guanines. A group of residues that form a positively charged patch on the protein surface of SARS-CoV Nsp3 NAB serves as the binding site of nucleic acids. This site is conserved in the NAB of Nsp3 from betacoronavirus in the B lineage.


Pssm-ID: 409348  Cd Length: 107  Bit Score: 234.35  E-value: 4.77e-71
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 1890 DLVPTQPLPNASFDNFKLTCSNTKFADDLNQMTGFTKPASRELSVTFFPDLNGDVVAIDYRHYSASFKKGAKLLHKPIVW 1969
Cdd:cd21822    1 DLVPTQPLPNASFDNFKLTCSNTKFADDLNQMTGFTKPASRELSVTFFPDLNGDVVAIDYRHYSPSFKKGAKLLHKPIVW 80
                         90       100
                 ....*....|....*....|....*..
gi 30027621 1970 HINQATTKTTFKPNTWCLRCLWSTKPV 1996
Cdd:cd21822   81 HINQATTKTTYKPNTWCLRCLWSTKPV 107
NAR pfam16251
Nucleic acid-binding domain (NAR); This domain, approximately 100 residues in length, is ...
1884-1996 4.84e-63

Nucleic acid-binding domain (NAR); This domain, approximately 100 residues in length, is mainly found in Orf1a polyproteins in severe acute respiratory syndrome coronavirus. The global domain of the NAR represents a new fold, with a parallel four-strand beta-sheet holding two alpha-helices of three and four turns that are oriented antiparallel to the beta-strands and a group of residues form a positively charged patch on the protein surface as the binding site responsible for binding affinity for nucleic acids.


Pssm-ID: 406621  Cd Length: 129  Bit Score: 212.41  E-value: 4.84e-63
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621   1884 YTEQPIDLVPTQPLPNASF----------DNFKLTCSNTKFADDLNQMTGF--TKPASRELSVTFFPDLNGDVVAIDYRH 1951
Cdd:pfam16251    1 YTEQPIDLVPTKPIIKAQFrtfekvdgvyDNFKLTCSGHKFADDLNAKLGFdcNKPASRELKITEFPDANGDVVAADDDH 80
                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*....
gi 30027621   1952 YSASFKKGAKLLHKPIVW--HINQATTKTTF--KPNTWCLRCLWSTKPV 1996
Cdd:pfam16251   81 YSARFKKGAILFGKPIVWlgHEEAALKKLTFfnKPNTVCLECKFNTKPV 129
CoV_NSP6 pfam19213
Coronavirus replicase NSP6; This entry represents proteins found in Coronaviruses and includes ...
3575-3836 3.13e-62

Coronavirus replicase NSP6; This entry represents proteins found in Coronaviruses and includes the Non-structural Protein 6 (NSP6). Coronaviruses encode large replicase polyproteins which are proteolytically processed by viral proteases to generate mature Nonstructural Proteins (NSPs). NSP6 is a membrane protein containing 6 transmembrane domains with a large C-terminal tail. NSP6 from the avian coronavirus, infectious bronchitis virus (IBV) and the mouse hepatitis virus (MHV) have been shown to localize to the ER and to generate autophagosomes. Coronavirus NSP6 proteins have also been shown to limit autophagosome expansion. This may favour coronavirus infection by reducing the ability of autophagosomes to deliver viral components to lysosomes for degradation. NSP6 from IBV, MHV and severe acute respiratory syndrome coronavirus (SARS-CoV) have also been found to activate autophagy.


Pssm-ID: 437050  Cd Length: 260  Bit Score: 215.57  E-value: 3.13e-62
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621   3575 TQWSLFFFVYENAFLPFTLGIMAIAACAMLLVKHKHAFLCLFLLPSLATVAYFNM--VYMPASWVMRIMTWlelaDTSLS 3652
Cdd:pfam19213    2 LMYTAFYWLPPNLITPVLPVLLCVSAILMLFIKHKHLFLTTFLLPSVVVLAYYNFtwDYYVNSFLRYVYDY----HMSLT 77
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621   3653 GYRLKDCVMYASALVLLILMTARTVYDDAARrVWTLMNVITLVYKVYYGNALDQA---ISMWALVISVTSNYSGVVTTIM 3729
Cdd:pfam19213   78 SFDLQGYFNIASCVFVNVLHTYRFVRSKSSI-ATYLVSLVVVVYMYVYGYALGTAsdpLSLLMMVLSLLTSYWYTGAIAY 156
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621   3730 FLARAIVFVCVEYYPLLFitgNTLQCIMLVYCFLGYCCCCYFGLFCLLNRYFRLTLGVYDYLVSTQEFRYMNSQGLLPPK 3809
Cdd:pfam19213  157 KLAKYIALYYPPSLIAVF---GDVKVVLLVYLCLGYVCCVYFGVLYWINRFTRLPLGVYDFKVSAAEFKYMVANGLSAPR 233
                          250       260
                   ....*....|....*....|....*..
gi 30027621   3810 SSIDAFKLNIKLLGIGGKPCIKVATVQ 3836
Cdd:pfam19213  234 NVFEALILNFKLLGIGGNRTIKISTVQ 260
ZBD_cv_Nsp13-like cd21401
Cys/His rich zinc-binding domain (CH/ZBD) of coronavirus SARS NSP13 helicase and related ...
5302-5396 1.22e-60

Cys/His rich zinc-binding domain (CH/ZBD) of coronavirus SARS NSP13 helicase and related proteins; Helicases catalyze NTP-dependent unwinding of nucleic acid duplexes into single strands and are classified based on the arrangement of conserved motifs into six superfamilies. This coronavirus family includes Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) non-structural protein 13 (SARS-Nsp13) and belongs to helicase superfamily 1 (SF1) and to a family of nindoviral replication helicases. SARS-Nsp13 has an N-terminal CH/ZBD, a stalk domain, a 1B regulatory domain, and SF1 helicase core. The CH/ZBD has 3 zinc-finger (ZnF1-3) motifs. SARS-Nsp13 is a component of the viral RNA synthesis replication and transcription complex (RTC). The SARS-Nsp13 CH/ZBD is indispensable for helicase activity and interacts with SARS-Nsp12, the RNA-dependent RNA polymerase (RdRp). Structural studies of a stable SARS-CoV-2 RTC which included two molecules of Nsp13, the RdRp holoenzyme (Nsp7, two molecules of Nsp8, Nsp12), and an RNA template product, show that one Nsp13 CH/ZBD domain interacts with Nsp12, and both Nsp13-CH/ZBD domains interact with the Nsp8. This stable SARS-CoV-2 RTC suggests that the Nsp13 helicase may drive RTC backtracking, affecting proofreading and template switching.


Pssm-ID: 439168  Cd Length: 95  Bit Score: 204.16  E-value: 1.22e-60
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 5302 AVGACVLCNSQTSLRCGACIRRPFLCCKCCYDHVISTSHKLVLSVNPYVCNAPGCDVTDVTQLYLGGMSYYCKSHKPPIS 5381
Cdd:cd21401    1 AVGLCVVCNSQTVLRCGDCIRRPFLCCKCCYDHVMSTSHKFILSINPYVCNAPGCGVSDVTKLYLGGMSYYCEDHKPSLS 80
                         90
                 ....*....|....*
gi 30027621 5382 FPLCANGQVFGLYKN 5396
Cdd:cd21401   81 FPLCANGFVFGLYKN 95
betaCoV_Nsp9 cd21898
betacoronavirus non-structural protein 9; This model represents the non-structural protein 9 ...
4118-4230 2.58e-59

betacoronavirus non-structural protein 9; This model represents the non-structural protein 9 (Nsp9) from betacoronaviruses including highly pathogenic Severe acute respiratory syndrome-related coronavirus (SARS-CoV), SARS-CoV2 (also called 2019 novel CoV or 2019-nCoV), and Middle East respiratory syndrome-related (MERS) CoV. CoVs utilize a multi-subunit replication/transcription machinery assembled from a set of non-structural proteins (Nsps) generated as cleavage products of the ORF1a and ORF1ab viral polyproteins. All of these Nsps, except for Nsp1 and Nsp2, are considered essential for transcription, replication, and translation of the viral RNA. Nsp9, with Nsp7, Nsp8, and Nsp10, localizes within the replication complex. Nsp9 is an essential single-stranded RNA-binding protein for coronavirus replication; it shares structural similarity to the oligosaccharide-binding (OB) fold, which is characteristic of proteins that bind to ssDNA or ssRNA. Nsp9 requires dimerization for binding and orienting RNA for subsequent use by the replicase machinery. CoV Nsp9s have diverse forms of dimerization that promote their biological function, which may help elucidate the mechanism underlying CoVs replication and contribute to the development of antiviral drugs. Generally, dimers are formed via interaction of the parallel alpha-helices containing the protein-protein interaction motif GXXXG; additionally, the N-finger region may also play a critical role in dimerization as seen in porcine delta coronavirus (PDCoV) Nsp9. As a member of the replication complex, Nsp9 may not have a specific RNA-binding sequence but may act in conjunction with other Nsps as a processivity factor, as shown by mutation studies indicating that Nsp9 is a key ingredient that intimately engages other proteins in the replicase complex to mediate efficient virus transcription and replication.


Pssm-ID: 409331  Cd Length: 111  Bit Score: 201.09  E-value: 2.58e-59
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 4118 NNELSPVALRQMSCAAGTTQTACtDDNALAYYNNSKGGRFVLALLSDHQDLKWARFPKSDGtGTIYTELEPPCRFVTDTP 4197
Cdd:cd21898    1 NNELMPQGLKTMVVTAGPDQTAC-NTPALAYYNNVQGGRMVMAILSDVDGLKYAKVEKSDG-GFVVLELDPPCKFLVQTP 78
                         90       100       110
                 ....*....|....*....|....*....|...
gi 30027621 4198 KGPKVKYLYFIKGLNNLNRGMVLGSLAATVRLQ 4230
Cdd:cd21898   79 KGPKVKYLYFVKGLNNLHRGQVLGTIAATVRLQ 111
nsp9 pfam08710
nsp9 replicase; nsp9 is a single-stranded RNA-binding viral protein likely to be involved in ...
4118-4230 1.23e-56

nsp9 replicase; nsp9 is a single-stranded RNA-binding viral protein likely to be involved in RNA synthesis. Its structure comprises of a single beta barrel.


Pssm-ID: 285872  Cd Length: 111  Bit Score: 193.46  E-value: 1.23e-56
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621   4118 NNELSPVALRQMSCAAGTTQtACTDDNALAYYNNSKGGRFVLALLSDHQDLKWARFPKSDGTgTIYTELEPPCRFVTDTP 4197
Cdd:pfam08710    1 NNELMPGKLKTKACKAGVTD-AHCSVEGKAYYNNEGGGSFVYAILSSNPNLKYAKFEKEDGN-VIYVELEPPCRFVVDTP 78
                           90       100       110
                   ....*....|....*....|....*....|...
gi 30027621   4198 KGPKVKYLYFIKGLNNLNRGMVLGSLAATVRLQ 4230
Cdd:pfam08710   79 KGPEVKYLYFVKNLNNLRRGMVLGYISATVRLQ 111
M_alpha_beta_cv_Nsp15-like cd21167
middle domain of alpha- and beta-coronavirus Nonstructural protein 15 (Nsp15), and related ...
6494-6625 1.98e-55

middle domain of alpha- and beta-coronavirus Nonstructural protein 15 (Nsp15), and related proteins; Nidovirus endoribonucleases (NendoUs) are uridylate-specific endoribonucleases, which release a cleavage product containing a 2',3'-cyclic phosphate at the 3' terminal end. NendoUs include Nsp15 from coronaviruses and Nsp11 from arteriviruses, both of which may participate in the viral replication process and in the evasion of the host immune system. Coronavirus Nsp15 NendoUs have an N-terminal domain, a middle (M) domain and a C-terminal catalytic (NendoU) domain. Coronavirus Nsp15 from Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV), human Coronavirus 229E (HCoV229E), and Murine Hepatitis Virus (MHV) form a functional hexamer. This middle domain harbors residues involved in hexamer formation and in trimer stability. Oligomerization of Porcine DeltaCoronavirus (PDCoV) Nsp15 differs from that of the other coronaviruses; it has been shown to exist as a dimer and a monomer in solution.


Pssm-ID: 439161  Cd Length: 127  Bit Score: 190.62  E-value: 1.98e-55
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 6494 PVPEIKILNNLGVDIAANTVIWDYKREAPAHVSTIGVCTMTDIAKKptesacSSLTVLFDGRVEGQVDLFRNARNGVLIT 6573
Cdd:cd21167    1 PVPELKLLRNLGVDICYKFVLWDYEREAPFTSSTIGVCKYTDIDKK------SDLNVLFDGRDPGSLERFRSARNAVLIS 74
                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|...
gi 30027621 6574 EGSVKGLTPSKGPAQASVNGVTLIGES-VKTQFNYFKKVDGIIQQLPETYFTQ 6625
Cdd:cd21167   75 TTKVKGLKPIKGPNYASLNGVVVESVDkKKVKFYYYVRKDGEFVDLTDTYFTQ 127
Macro_cv_SUD-M_Nsp3-like cd21563
SUD-M macrodomain (or Mac3 domain) of the SARS Unique Domain (SUD) of SARS-CoV non-structural ...
1345-1465 1.06e-54

SUD-M macrodomain (or Mac3 domain) of the SARS Unique Domain (SUD) of SARS-CoV non-structural protein 3 and related macrodomains; This subfamily includes the macrodomain referred to as SUD-M (middle SUD subdomain) of the SARS-unique domain (SUD) which binds G-quadruplexes (unusual nucleic-acid structures formed by consecutive guanosine nucleotides). It is found in non-structural protein 3 (Nsp3) of Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) and related coronaviruses. SUD consists of three globular domains separated by short linker peptide segments: SUD-N, SUD-M, and SUD-C. Among these, SUD-N and SUD-M are macrodomains: The SUD-N domain (not represented in this subfamily) is a related macrodomain which also binds G-quadruplexes. While SUD-N (also called Mac2) is specific to the Nsp3 of SARS and betacoronaviruses of the sarbecovirus subgenera (B lineage), SUD-M (also called Mac3) is present in most Nsp3 proteins except the Nsp3 from betacoronaviruses of the embecovirus subgenera (A lineage). SUD-M, despite its name, is not specific to SARS. SUD-C adopts a frataxin-like fold, has structural similarity to DNA-binding domains of DNA-modifying enzymes, binds single-stranded RNA, and regulates the RNA binding behavior of the SUD-M macrodomain. SARS-CoV Nsp3 contains a third macrodomain (the X-domain or Mac1) which is also not represented in this subfamily. The X-domain may function as a module binding poly(ADP-ribose); however, SUD-N and SUD-M do not bind ADP-ribose, as the triple glycine sequence involved in its binding is not conserved in these.


Pssm-ID: 394884  Cd Length: 120  Bit Score: 188.27  E-value: 1.06e-54
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 1345 GTVSWNLREMLAHAEETRKLMPICMDVRAIMATIQRKYKGIKIQEGIVDyGVRFFFYTSKEPVASIITKLNSLNEPLVTM 1424
Cdd:cd21563    1 LTVSFNLRQMLAHAKEYGLLMPVCIDYKAFTKVLRRKGVDPKKGFQTVD-GVRFYFYSSKDPLADVIAALNSLGKPIITM 79
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|.
gi 30027621 1425 PIGYVTHGFNLEEAARCMRSLKAPAVVSVSSPDAVTTYNGY 1465
Cdd:cd21563   80 PLGYITHGLDLAEAAAIMRMLTVPYVVVLASPDAVPLYNGY 120
CoV_NSP2_N pfam19211
Coronavirus replicase NSP2, N-terminal; This entry corresponds to the N-terminal region of ...
182-423 1.06e-52

Coronavirus replicase NSP2, N-terminal; This entry corresponds to the N-terminal region of coronavirus non-structural protein 2. NSP2 is encoded by ORF1a/1ab and proteolytically released from the pp1a/1ab polyprotein. The function of this protein is uncertain. This region contains numerous conserved and semi-conserved cysteine residues.


Pssm-ID: 437048 [Multi-domain]  Cd Length: 199  Bit Score: 185.59  E-value: 1.06e-52
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621    182 VTRYVDNNFCGPDGYPLD-----CIKDFLARAGKsmctlseqldyIESKRGVYCCrdheheiAWFTERSDKSYEHQTPFE 256
Cdd:pfam19211    1 DVIPVDQYMCGADGKPVLpedtwCFKDYFGDDGE-----------IVLNGGTYRK-------AWNVERKDVPYEKQSLFT 62
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621    257 IKSAKKFdtfkGECPKFVfpLNSKVKVIQPRVEKKKTEGFMGRIRSVYPVASPQECNN---MHLSTLMKCNHCDEVSWQT 333
Cdd:pfam19211   63 INSIEYL----GDVPHVL--PNGAVLVVAPRVKKSKKVVLSEKYKSLYDTYGSPFVTNpkpIFLHALVKCSSCGKESWTV 136
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621    334 CDFLKATCEHCGTENLVIeGPTTCGYLPTNAVVkmpcpacqdpeigpehsvadyhnhsnIETRLRKGGRTRCFGGCVFAY 413
Cdd:pfam19211  137 GDWSGFKCLCCGVYGNPV-CVQSAGLVKPGAVM--------------------------LITKAPVGAGTKFFGGAVLKY 189
                          250
                   ....*....|
gi 30027621    414 VGCYNKRAYW 423
Cdd:pfam19211  190 VGCVEGVAVW 199
1B_cv_Nsp13-like cd21409
1B domain of coronavirus SARS NSP13 helicase and related proteins; Helicases catalyze ...
5451-5529 8.33e-48

1B domain of coronavirus SARS NSP13 helicase and related proteins; Helicases catalyze NTP-dependent unwinding of nucleic acid duplexes into single strands and are classified based on the arrangement of conserved motifs into six superfamilies. Members of this subfamily belong to helicase superfamily 1 (SF1) and include coronavirus helicases such as Severe Acute Respiratory Syndrome coronavirus (SARS) non-structural protein 13 (SARS-Nsp13). SARS-Nsp13 is a component of the viral RNA synthesis replication and transcription complex (RTC). Structural studies of a stable RTC which included the RNA-dependent RNA polymerase holoenzyme (Nsp7, two molecules of Nsp82, Nsp12), two molecules of Nsp13 helicase accessory factor and an RNA template product suggests that the Nsp13 helicase may drive RTC backtracking, affecting proofreading and template switching. SARS-Nsp13 is a multidomain protein; its other domains include an N-terminal Cys/His rich zinc-binding domain (CH/ZBD) and a SF1 helicase core. The 1B domain is involved in nucleic acid substrate binding; the 1B domain of the related Equine arteritis virus (EAV) Nsp10 undergoes large conformational change upon substrate binding, and together with the 1A and 2A domains of the helicase core form a channel that accommodates the single stranded nucleic acids.


Pssm-ID: 394817  Cd Length: 79  Bit Score: 166.75  E-value: 8.33e-48
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 30027621 5451 GIATVREVLSDRELHLSWEVGKPRPPLNRNYVFTGYRVTKNSKVQIGEYTFEKGDYGDAVVYRGTTTYKLNVGDYFVLT 5529
Cdd:cd21409    1 ASATVKEVVGPRELVLSWEAGKTKPPLNRNYVFTGYHITKNSKTQLGEYTFEKSDYSDSVYYKSTTTYKLQPGDIFVLT 79
Macro_X_Nsp3-like cd21557
X-domain (or Mac1 domain) of viral non-structural protein 3 and related macrodomains; The ...
1034-1155 9.84e-48

X-domain (or Mac1 domain) of viral non-structural protein 3 and related macrodomains; The X-domain, also called Mac1, is the macrodomain found in riboviral non-structural protein 3 (Nsp3), including the Nsp3 of Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) as well as SARS-CoV-2, and other coronaviruses (alpha-, beta-, gamma-, and deltacoronavirus), among others. The SARS-CoV-2 Nsp3 Mac1 is highly conserved among all CoVs, and binds to and hydrolyzes mono-ADP-ribose (MAR) from target proteins. It appears to counter host-mediated antiviral ADP-ribosylation, a post-translational modification that is part of the host response to viral infections. Mac1 is essential for pathogenesis in multiple animal models of CoV infection, implicating it as a virulence factor and potential therapeutic target. Assays show that the de-MARylating activity leads to a rapid loss of substrate, and that Mac1 could not hydrolyze poly-ADP-ribose; thus, Mac1 is a MAR-hydrolase (mono-ADP ribosylhydrolase). Mac1 was originally named ADP-ribose-1"-phosphatase (ADRP) based on data demonstrating that it could remove the phosphate group from ADP-ribose-1"-phosphate; however, activity was modest and was unclear why this would impact a virus infection. This family also includes the X-domain of Avian infectious bronchitis virus (IBV) strain Beaudette coronavirus that does not bind ADP-ribose; the triple glycine sequence found in the X-domains of SARS-CoV and human coronavirus 229E (HCoV229E), which are involved in ADP-ribose binding, is not conserved in the IBV X-domain. SARS-CoVs have two other macrodomains referred to as the SUD-N (N-terminal subdomain, or Mac2) and SUD-M (middle SUD subdomain, or Mac3) of the SARS-unique domain (SUD), which also do not bind ADP-ribose; these bind G-quadruplexes (unusual nucleic-acid structures formed by consecutive guanosine nucleotides). SARS-CoV SUD-N and SUD-M are not included in this group.


Pssm-ID: 438957  Cd Length: 127  Bit Score: 168.50  E-value: 9.84e-48
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 1034 VIVNAANIHLKHGGGVAGALNKATNGAMQKESDdYIKLNGPLTVGGSCLLSGHNLAKKCLHVVGPNLNAGEDIQLLKAAY 1113
Cdd:cd21557    3 VVVNAANENLKHGGGVAGAIYKATGGAFQKESD-YIKKNGPLKVGTAVLLPGHGLAKNIIHVVGPRKRKGQDDQLLAAAY 81
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*.
gi 30027621 1114 ENFNS-QDILLAPLLSAGIFGAKPLQSLQVCVQTVRT---QVYIAV 1155
Cdd:cd21557   82 KAVNKeYGSVLTPLLSAGIFGVPPEQSLNALLDAVDTtdaDVTVYC 127
Nsp1 pfam11501
Non structural protein Nsp1; Nsp1 is the N-terminal cleavage product from the viral replicase ...
7-144 6.66e-46

Non structural protein Nsp1; Nsp1 is the N-terminal cleavage product from the viral replicase that mediates RNA replication and processing. The specific function of the protein is unknown however the structure has been determined. The protein has a novel alpha/beta fold formed by a 6 stranded beta barrel with an alpha helix covering one end of the barrel and another helix alongside the barrel. Nsp1 could be involved in the degradation of mRNA.


Pssm-ID: 431911  Cd Length: 138  Bit Score: 163.71  E-value: 6.66e-46
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621      7 GVNEKTHVQLSLPVLQVRDV-LVRGFGDSVEEALSEAREHLKN-GTCGLVELEKGVLPQLEQPYVFIKRSdalsTNHGHK 84
Cdd:pfam11501    1 NEKRKDHVSLTLPWCDPGDVpKLTPWFMDGEEALETVKEQLKKgGKLLFVPLYLGFIKQLPGPRVYLVES----LTGGWK 76
                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 30027621     85 -----VVELVAEMDGIQYGRSGITLGVLVPHVGETPIAYRNVLLRKNgnkGAGGHSYGIDLKSYD 144
Cdd:pfam11501   77 sdpfpVNELAYDDDGVRTGRSGKTVGVLFPFDPQLPTGTYTILLRKY---GLGGNSFRDVPWLWD 138
Corona_NSP4_C pfam16348
Coronavirus nonstructural protein 4 C-terminus; This is the C-terminal domain of the ...
3146-3238 6.12e-44

Coronavirus nonstructural protein 4 C-terminus; This is the C-terminal domain of the coronavirus nonstructural protein 4 (NSP4). NSP4 is a membrane-spanning protein which is thought to anchor the viral replication-transcription complex (RTC) to modified endoplasmic reticulum membranes. This predominantly alpha-helical domain may be involved in protein-protein interactions.


Pssm-ID: 406690  Cd Length: 92  Bit Score: 156.14  E-value: 6.12e-44
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621   3146 GVTF-STFEEAALCTFLLNKEMYLKLRSEtlLPLTQYNRYLALYNKYKYFSGALDTTSYREAACCHLAKALNDFSNSGAD 3224
Cdd:pfam16348    1 GDEFvGTFEEAALGTFVIDKESYEKLTNS--ISLDKFNRYLSLYNKYKYYSGTMDEADYREACCAHLAKALDDFSNSGND 78
                           90
                   ....*....|....
gi 30027621   3225 VLYQPPQTSITSAV 3238
Cdd:pfam16348   79 ILYTPPTVSIGSSL 92
CoV_NSP15_M pfam19216
Coronavirus replicase NSP15, middle domain; This entry represents the non-catalytic middle ...
6491-6613 1.73e-42

Coronavirus replicase NSP15, middle domain; This entry represents the non-catalytic middle domain from coronavirus non-structural protein 15 (NSP15). NSP15 is encoded by ORF1a/1ab and proteolytically released from the pp1a/1ab polyprotein. This domain is formed by ten beta strands organized into three beta hairpins.


Pssm-ID: 437053  Cd Length: 118  Bit Score: 153.21  E-value: 1.73e-42
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621   6491 NIKPVPEIKILNNLGVDIAANTVIWDYKREAPAHVSTIGVCTMTDIakkptesACSSLTVLFDGRVEGQVDLFRNARNGV 6570
Cdd:pfam19216    1 NVGLTPELKLLRNLGVDVTYNFVLWDYEREAPFTNSTIGVCKYTDI-------DNEDLNVLYDGRDKGSLERFTQAKNAV 73
                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....
gi 30027621   6571 LITEGSVKGLTPSKGPAQASVNGVTLIGESVK-TQFNYFKKVDG 6613
Cdd:pfam19216   74 LISTTKIKKLTAIKGPNYAYLNGVPVSTVEKKpVTFYIYVRKNG 117
betaCoV_Nsp7 cd21827
betacoronavirus non-structural protein 7; This model represents the non-structural protein 7 ...
3837-3919 2.89e-41

betacoronavirus non-structural protein 7; This model represents the non-structural protein 7 (Nsp7) of betacoronaviruses including the highly pathogenic Severe acute respiratory syndrome-related coronavirus (SARS-CoV), SARS-CoV2 (also called 2019 novel CoV or 2019-nCoV), and Middle East respiratory syndrome-related (MERS) CoV. CoVs utilize a multi-subunit replication/transcription machinery. A set of non-structural proteins (Nsps) generated as cleavage products of the ORF1a and ORF1ab viral polyproteins assemble to facilitate viral replication and transcription. Upon processing of the Nsp7-10 region by protease M (Mpro), the released four small proteins Nsp7, Nsp8, Nsp9 and Nsp10 form functional complexes with CoV core enzymes and stimulate replication. Most importantly, a complex of Nsp7 with Nsp8 has been shown to activate and confer processivity to the RNA-synthesizing activity of Nsp12, the RNA-dependent RNA-polymerase (RdRp); in SARS-CoV, point mutations in the NSP7- or NSP8-coding region have been shown to delay virus growth. Nsp7 and Nsp8 cooperate in activating the primer-dependent activity of the Nsp12 RdRp such that the level of their association may constitute a limiting factor for obtaining a high RNA polymerase activity. The subsequent Nsp7/Nsp8/Nsp12 polymerase complex is then able to associate with an active bifunctional Nsp14, which includes N-terminal 3' to 5' exoribonuclease (ExoN) and C-terminal N7-guanine cap methyltransferase (N7-MTase) activities, thus representing a unique coronavirus Nsp assembly that incorporates RdRp, exoribonuclease, and N7-MTase activities. Interaction of Nsp7 with Nsp8 appears to be conserved across the coronavirus family, making these proteins interesting drug targets. Nsp7 has a 4-helical bundle conformation which is strongly affected by its interaction with Nsp8, especially where it concerns alpha-helix 4. SARS-CoV Nsp7 forms a 8:8 hexadecameric supercomplex with Nsp8 that adopts a hollow cylinder-like structure with a large central channel and positive electrostatic properties in the cylinder; the Nsp7/Nsp8 complex functions as a noncanonical RNA polymerase capable of synthesizing RNA of up to template length.


Pssm-ID: 409253  Cd Length: 83  Bit Score: 148.36  E-value: 2.89e-41
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 3837 SKMSDVKCTSVVLLSVLQQLRVESSSKLWAQCVQLHNDILLAKDTTEAFEKMVSLLSVLLSMQGAVDINRLCEEMLDNRA 3916
Cdd:cd21827    1 SKLTDVKCTSVVLLSVLQQLHVESNSKLWAYCVKLHNDILAAKDPTEAFEKFVSLLSVLLSFPGAVDLDALCSELLDNPT 80

                 ...
gi 30027621 3917 TLQ 3919
Cdd:cd21827   81 VLQ 83
SUD_C_SARS-CoV_Nsp3 cd21525
C-terminal SARS-Unique Domain (SUD) of non-structural protein 3 (Nsp3) from Severe Acute ...
1472-1538 3.45e-41

C-terminal SARS-Unique Domain (SUD) of non-structural protein 3 (Nsp3) from Severe Acute Respiratory Syndrome coronavirus and related betacoronaviruses in the B lineage; This subfamily contains the SUD-C of Severe Acute Respiratory Syndrome (SARS) coronavirus (CoV) non-structural protein 3 (Nsp3) and other Nsp3s from betacoronaviruses in the sarbecovirus subgenera (B lineage), such as SARS-CoV-2 and related bat CoVs. Non-structural protein 3 (Nsp3) is a large multi-functional multi-domain protein that is an essential component of the replication/transcription complex (RTC), which carries out RNA synthesis, RNA processing, and interference with the host cell innate immune system. Nsp3 of the Severe Acute Respiratory Syndrome (SARS) coronavirus includes a SARS-unique domain (SUD) consisting of three globular domains separated by short linker peptide segments: SUD-N, SUD-M, and SUD-C. SUD-N and SUD-M are macro domains which bind G-quadruplexes (unusual nucleic-acid structures formed by consecutive guanosine nucleotides). The SUD-C domain adopts a frataxin-like fold and has structural similarity to DNA-binding domains of DNA-modifying enzymes. It binds to single-stranded RNA and recognizes purine bases more strongly than pyrimidine bases. SUD-C also regulates the RNA binding behavior of the SUD-M macrodomain.


Pssm-ID: 394841  Cd Length: 67  Bit Score: 147.31  E-value: 3.45e-41
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 30027621 1472 TSEEHFVETVSLAGSYRDWSYSGQRTELGVEFLKRGDKIVYHTLESPVEFHLDGEVLSLDKLKSLLS 1538
Cdd:cd21525    1 TPEEHFVETVSLAGSYRDWSYSGQRTELGVEFLKRGDKIVYHTLESPVEFHLDGEVLPLDKLKSLLS 67
Nsp3_PL2pro pfam12124
Coronavirus polyprotein cleavage domain; This domain is found in SARS coronaviruses, and is ...
1473-1538 1.67e-39

Coronavirus polyprotein cleavage domain; This domain is found in SARS coronaviruses, and is about 70 amino acids in length. It is found associated with various other coronavirus proteins due to the polyprotein nature of most viral translation. PL2pro is a domain of the non-structural protein nsp3. The domain performs three of the cleavages required to separate the translated polyprotein into its distinct proteins.


Pssm-ID: 288939  Cd Length: 66  Bit Score: 142.53  E-value: 1.67e-39
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 30027621   1473 SEEHFVETVSLAGSYRDWSYSGQRTELGVEFLKRGDKIVYHTLESPVEFHLDGEVLSLDKLKSLLS 1538
Cdd:pfam12124    1 SEEHFVETVSLAGSYRDWSYSGQRTELGVEFLKRGDKIVYHTLESPVEFHLDGEVLSLDKLKSLLS 66
nsp7 pfam08716
nsp7 replicase; nsp7 (non structural protein 7) has been implicated in viral RNA replication ...
3837-3919 6.86e-39

nsp7 replicase; nsp7 (non structural protein 7) has been implicated in viral RNA replication and is predominantly alpha helical in structure. It forms a hexadecameric supercomplex with nsp7 that adopts a hollow cylinder-like structure. The dimensions of the central channel and positive electrostatic properties of the cylinder imply that it confers processivity on RNA-dependent RNA polymerase.


Pssm-ID: 285878  Cd Length: 83  Bit Score: 141.43  E-value: 6.86e-39
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621   3837 SKMSDVKCTSVVLLSVLQQLRVESSSKLWAQCVQLHNDILLAKDTTEAFEKMVSLLSVLLSMQGAVDINRLCEEMLDNRA 3916
Cdd:pfam08716    1 SKLTDVKCTNVVLLGLLQKLHVESNSKLWAYCVELHNEILLCDDPTEAFEKLLALLAVLLSKHSAVDLSDLCDSYLENRT 80

                   ...
gi 30027621   3917 TLQ 3919
Cdd:pfam08716   81 ILQ 83
SARS-CoV-like_Nsp1_C cd22662
C-terminal domain of non-structural protein 1 from Severe acute respiratory syndrome-related ...
128-180 6.79e-34

C-terminal domain of non-structural protein 1 from Severe acute respiratory syndrome-related coronavirus and betacoronavirus in the B lineage; This model represents the C-terminal domain of non-structural protein 1 (Nsp1) from betacoronaviruses in the sarbecovirus subgenus (B lineage), including highly pathogenic coronaviruses such as Severe acute respiratory syndrome-related coronavirus (SARS-CoV) and SARS-CoV2 (also called 2019 novel CoV or 2019-nCoV). CoVs utilize a multi-subunit replication/transcription machinery assembled from a set of non-structural proteins (Nsps) generated as cleavage products of the ORF1a and ORF1ab viral polyproteins. Nsp1 is the N-terminal cleavage product released from the ORF1a polyprotein by the action of papain-like protease (PLpro). Though Nsp1s of alphaCoVs and betaCoVs share structural similarity, they show no significant sequence similarity and may be considered as genus-specific markers. Despite low sequence similarity, the Nsp1s of alphaCoVs and betaCoVs exhibit remarkably similar biological functions, and are involved in the regulation of both host and viral gene expression. CoV Nsp1 induces suppression of host gene expression and interferes with host immune response. It inhibits host gene expression in two ways: by targeting the translation and stability of cellular mRNAs, and by inhibiting mRNA translation and inducing an endonucleolytic RNA cleavage in the 5'-UTR of cellular mRNAs through its tight association with the 40S ribosomal subunit, a key component of the cellular translation machinery. Inhibition of host mRNA translation includes that of type I interferons, major components of the host innate immune response. Nsp1 is critical in regulating viral replication and gene expression. SARS-CoV Nsp1 enhances virus replication by binding to a stem-loop structure in the 5'-UTR of its genome. When the SARS-CoV-2 5' UTR is bound to the Nsp1 N-terminus, the covalently linked Nsp1 C-terminus cannot bind the 40S ribosome, suggesting a bipartite mechanism whereby SARS-CoV-2 Nsp1 suppresses host but not viral translation.


Pssm-ID: 439355  Cd Length: 53  Bit Score: 126.14  E-value: 6.79e-34
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 30027621  128 NKGAGGHSYGIDLKSYDLGDELGTDPIEDYEQNWNTKHGSGALRELTRELNGG 180
Cdd:cd22662    1 NKGAGGHSYGIDLKSYDLGDELGTDPIEDYEQNWNTKHGSGALRELTRELNGG 53
NTD_alpha_betaCoV_Nsp15-like cd21171
N-terminal domain of alpha- and beta-coronavirus Nonstructural protein 15 (Nsp15), and related ...
6430-6490 3.55e-33

N-terminal domain of alpha- and beta-coronavirus Nonstructural protein 15 (Nsp15), and related proteins; Coronavirus (CoV) Nsp15 is a nidovirus endoribonuclease (NendoU). NendoUs are uridylate-specific endoribonucleases, which release a cleavage product containing a 2',3'-cyclic phosphate at the 3' terminal end. NendoUs include CoV Nsp15 and arterivirus Nsp11, both of which may participate in the viral replication process and in the evasion of the host immune system. This small NTD structure, present in coronavirus Nsp15, is missing in Nsp11. CoV Nsp15 has an N-terminal domain, a middle (M) domain, and a C-terminal catalytic (NendoU) domain. Nsp15 from Severe Acute Respiratory Syndrome (SARS)-CoV, human CoV229E (HCoV229E), and Murine Hepatitis Virus (MHV) form a functional hexamer. Residues in this N-terminal domain are important for hexamer (dimer of trimers) formation.


Pssm-ID: 439163  Cd Length: 61  Bit Score: 124.22  E-value: 3.55e-33
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 30027621 6430 SLENVAYNVVNKGHFDGHAGEAPVSIINNAVYTKVDGIDVEIFENKTTLPVNVAFELWAKR 6490
Cdd:cd21171    1 SLENVAYNVVKKGHFVGVEGELPVAIVNDKVFVKDGGVDVLVFTNKTSLPTNVAFELYAKR 61
CoV_NSP15_N pfam19219
Coronavirus replicase NSP15, N-terminal oligomerisation; This is the N-terminal domain of the ...
6430-6490 1.86e-32

Coronavirus replicase NSP15, N-terminal oligomerisation; This is the N-terminal domain of the coronavirus nonstructural protein 15 (NSP15), which is encoded by ORF1a/1ab and proteolytically released from the pp1a/1ab polyprotein. NSP15, is a nidoviral RNA uridylate-specific endoribonuclease (NendoU) carrying C-terminal catalytic domain belonging to the EndoU family. The SARS-CoV-2 NendoU monomers assemble into a double-ring hexamer, generated by a dimer of trimers. The hexamer is stabilized by the interactions of N-terminal oligomerization domain.


Pssm-ID: 437056  Cd Length: 61  Bit Score: 122.38  E-value: 1.86e-32
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 30027621   6430 SLENVAYNVVNKGHFDGHAGEAPVSIINNAVYTKVDGIDVEIFENKTTLPVNVAFELWAKR 6490
Cdd:pfam19219    1 SLENVAYNVVKKGHFDGVDGELPVAIVNDKVFVKVGGVDVLVFENKTSLPTNVAFELYAKR 61
Ubl1_cv_Nsp3_N-like cd21467
first ubiquitin-like (Ubl) domain located at the N-terminus of coronavirus SARS-CoV ...
839-925 1.02e-29

first ubiquitin-like (Ubl) domain located at the N-terminus of coronavirus SARS-CoV non-structural protein 3 (Nsp3) and related proteins; This ubiquitin-like (Ubl) domain (Ubl1) is found at the N-terminus of coronavirus Nsp3, a large multi-functional multi-domain protein which is an essential component of the replication/transcription complex (RTC). The functions of Ubl1 in CoVs are related to single-stranded RNA (ssRNA) binding and to interacting with the nucleocapsid (N) protein. SARS-CoV Ubl1 has been shown to bind ssRNA having AUA patterns, and since the 5'-UTR of the SARS-CoV genome has a number of AUA repeats, it may bind there. In mouse hepatitis virus (MHV), this Ubl1 domain binds the cognate N protein. Adjacent to Ubl1 is a Glu-rich acidic region (also referred to as hypervariable region, HVR); Ubl1 together with HVR has been called Nsp3a. Currently, the function of HVR in CoVs is unknown. This model corresponds to one of two Ubl domains in Nsp3; the other is located N-terminal to the papain-like protease (PLpro) and is not represented by this model.


Pssm-ID: 394822  Cd Length: 89  Bit Score: 115.36  E-value: 1.02e-29
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621  839 NVRITFELDERVDKVLNEKCSVYTVESGTEVTEFACVVAEAVVKTLQPVSDLL--TNMGIDLDEWSVATFYLFDDAGEEN 916
Cdd:cd21467    1 TVKVTYELDEVLDTILNKACSPFEVEKDLTVEEFADVVQDAVEEKLSPLLELPlgDKVDADLDDFIDNPCYLFDEDGDEV 80

                 ....*....
gi 30027621  917 FSSRMYCSF 925
Cdd:cd21467   81 LASEMYCSF 89
stalk_CoV_Nsp13-like cd21689
stalk domain of coronavirus Nsp13 helicase and related proteins; This model represents the ...
5400-5447 6.70e-25

stalk domain of coronavirus Nsp13 helicase and related proteins; This model represents the stalk domain of coronavirus non-structural protein 13 (Nsp13) helicase, found in the Nsp3s of alpha-, beta-, gamma-, and deltacoronaviruses, including Severe Acute Respiratory Syndrome coronavirus (SARS-CoV), SARS-CoV-2 (also called 2019 novel CoV or 2019-nCoV), and Middle East respiratory syndrome coronavirus (MERS-CoV). Helicases are classified based on the arrangement of conserved motifs into six superfamilies; coronavirus helicases in this family belong to superfamily 1 (SF1). Helicases catalyze NTP-dependent unwinding of nucleic acid duplexes into single strands. Nsp13 is a component of the viral RNA synthesis replication and transcription complex (RTC). It consists of an N-terminal ZBD (Cys/His rich zinc-binding domain), a stalk domain, a 1B regulatory domain, and SF1 helicase core. The stalk domain lies between the ZBD domain and the 1B domain; a short loop connects the ZBD to the stalk domain. The stalk domain is comprised of three tightly-interacting alpha-helices connected to the 1B domain, transferring the effect from the ZBD domain onto the helicase core domains. The ZBD and stalk domains are critical for the helicase activity of SARS-CoV Nsp13.


Pssm-ID: 410205  Cd Length: 48  Bit Score: 100.38  E-value: 6.70e-25
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*...
gi 30027621 5400 GSDNVTDFNAIATCDWTNAGDYILANTCTERLKLFAAETLKATEETFK 5447
Cdd:cd21689    1 GSPDVDDFNRLATSDWSDVEDYKLANTCKDSLKLFAAETIKAKEESVK 48
Macro pfam01661
Macro domain; This domain is an ADP-ribose binding module. It is found in a number of ...
1036-1143 7.62e-24

Macro domain; This domain is an ADP-ribose binding module. It is found in a number of otherwise unrelated proteins. It is found at the C-terminus of the macro-H2A histone protein. This domain is found in the non-structural proteins of several types of ssRNA viruses such as NSP3 from alphaviruses. This domain is also found on its own in a family of proteins from bacteria, archaebacteria and eukaryotes.


Pssm-ID: 426372  Cd Length: 116  Bit Score: 99.94  E-value: 7.62e-24
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621   1036 VNAANIHLKHGGGVAGALNKATNGAMQKESDDYIKlnGPLTVGGSCLLSGHNL-AKKCLHVVGPNLNAG---EDIQLLKA 1111
Cdd:pfam01661    1 VNAANSRLLGGGGVAGAIHRAAGPELLEECRELKK--GGCPTGEAVVTPGGNLpAKYVIHTVGPTWRHGgghGEEELLES 78
                           90       100       110
                   ....*....|....*....|....*....|....*...
gi 30027621   1112 AYENF----NSQDI--LLAPLLSAGIFGAKPLQSLQVC 1143
Cdd:pfam01661   79 CYRNAlalaEELGIksIAFPAISTGIYGFPWEEAARIA 116
A1pp smart00506
Appr-1"-p processing enzyme; Function determined by Martzen et al. Extended family detected by ...
1018-1142 4.28e-15

Appr-1"-p processing enzyme; Function determined by Martzen et al. Extended family detected by reciprocal PSI-BLAST searches (unpublished results, and Pehrson _ Fuji).


Pssm-ID: 214701  Cd Length: 133  Bit Score: 75.42  E-value: 4.28e-15
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621    1018 IKCV--DIVKeaqsANPMVIVNAANIHLKHGGGVAGALNKATNGamQKESDDYIKLNGPLTVGGSCLLS--GHNLAKKCL 1093
Cdd:smart00506    2 LKVVkgDITK----PRADAIVNAANSDGAHGGGVAGAIARAAGK--ALSKEEVRKLAGGECPVGTAVVTegGNLPAKYVI 75
                            90       100       110       120       130
                    ....*....|....*....|....*....|....*....|....*....|....*..
gi 30027621    1094 HVVGPNLNAGEDI--QLLKAAYENF------NSQDILLAPLLSAGIFGAKPLQSLQV 1142
Cdd:smart00506   76 HAVGPRASGHSKEgfELLENAYRNClelaieLGITSVALPLIGTGIYGVPKDRSAQA 132
PRK00431 PRK00431
ADP-ribose-binding protein;
1034-1148 2.94e-14

ADP-ribose-binding protein;


Pssm-ID: 234759  Cd Length: 177  Bit Score: 74.49  E-value: 2.94e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621  1034 VIVNAANIHLKHGGGVAGALNKATNGAMQKESDDYIKLNGPLTVGGSCLLSGHNL-AKKCLHVVGPNLNAGED--IQLLK 1110
Cdd:PRK00431   19 AIVNAANSSLLGGGGVDGAIHRAAGPEILEECRELRQQQGPCPTGEAVITSAGRLpAKYVIHTVGPVWRGGEDneAELLA 98
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*...
gi 30027621  1111 AAYenFNSqdILLA----------PLLSAGIFGAKPLQSLQVCVQTVR 1148
Cdd:PRK00431   99 SAY--RNS--LRLAaelglrsiafPAISTGVYGYPLEDAARIAVKTVR 142
DNA2 COG1112
Superfamily I DNA and/or RNA helicase [Replication, recombination and repair];
5624-5893 7.62e-13

Superfamily I DNA and/or RNA helicase [Replication, recombination and repair];


Pssm-ID: 224037 [Multi-domain]  Cd Length: 767  Bit Score: 75.77  E-value: 7.62e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 5624 KYLPIDKCSRIIpaRARVECFDKFKVNSTLEQYVFCTVNALPETTADIVVFDEISMATNYD-LSVVNarlRAKHYVYIGD 5702
Cdd:COG1112  446 KQKKILKELRRL--KKKAVTKILEAADVVLSTLSIAGFSILKKYEFDYVIIDEASQATEPSaLIALS---RAKKVILVGD 520
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 5703 PAQLPapRTLLTKGT----LEPEYFNSVCRLMKtiGPDMFLGTCRRCPAEIVDTVSALVYDNKLKAHKDKSAQCFKMFYK 5778
Cdd:COG1112  521 HKQLP--PTVFFKESspegLSASLFERLIDNGP--EVVYLLRVQYRMHPDIIAFSSKVFYNGRLEVHTSFLAFTLLDGEI 596
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 5779 GVITH-------DVSSAINRPQIG-------------VVREFLTRNPAWRKAVFISPYNSQNA-----VASKILGLPTQT 5833
Cdd:COG1112  597 PEVVIsnplefyDTLGAEEFFESKsklneleaeivkvIVDELLKDGLEENDIGVISPYRAQVSlirrlLNEAGKGVEVGT 676
                        250       260       270       280       290       300
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 30027621 5834 VDSSQGSEYDYVIFTQT------TETAHSCNVNRFNVAITRAKIGiLCIMSDRDLYDKLQFTSLEI 5893
Cdd:COG1112  677 VDGFQGREKDVIILSLVrsnddkGEIGFLGDPRRLNVALTRAKRK-LIVVGSSSTLESDPLYKRLI 741
AAA_12 pfam13087
AAA domain; This family of domains contain a P-loop motif that is characteristic of the AAA ...
5744-5881 9.73e-12

AAA domain; This family of domains contain a P-loop motif that is characteristic of the AAA superfamily. Many of the proteins in this family are conjugative transfer proteins.


Pssm-ID: 432964 [Multi-domain]  Cd Length: 196  Bit Score: 67.57  E-value: 9.73e-12
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621   5744 RCPAEIVDTVSALVYDNKLKAHKDKSAQ-CFKMFYKG-----VITHDVS-----------SAINRPQIGVV----REFLT 5802
Cdd:pfam13087   25 RMHPEIMEFPSKLFYGGKLKDGPSVAERpLPDDFHLPdplgpLVFIDVDgseeeesdggtSYSNEAEAELVvqlvEKLIK 104
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621   5803 RNP-AWRKAVFISPYNSQ--------NAVASKILGLPTQTVDSSQGSEYDYVIFTqTTETAHSCNV------NRFNVAIT 5867
Cdd:pfam13087  105 SGPeEPSDIGVITPYRAQvrlirkllKRKLGGKLEIEVNTVDGFQGREKDVIIFS-CVRSNEKGGIgflsdpRRLNVALT 183
                          170
                   ....*....|....
gi 30027621   5868 RAKIGiLCIMSDRD 5881
Cdd:pfam13087  184 RAKRG-LIIVGNAK 196
YmdB COG2110
O-acetyl-ADP-ribose deacetylase (regulator of RNase III), contains Macro domain [Translation, ...
1034-1135 4.48e-06

O-acetyl-ADP-ribose deacetylase (regulator of RNase III), contains Macro domain [Translation, ribosomal structure and biogenesis];


Pssm-ID: 225021 [Multi-domain]  Cd Length: 179  Bit Score: 50.81  E-value: 4.48e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 1034 VIVNAANIHLKHGGGVAGALNKATNGAMQKESDDYIKLNGP--LTVGGSCLLSGHNL-AKKCLHVVGPNLNAGEDI--QL 1108
Cdd:COG2110   19 AIVNAANSQLLGGGGVAGAIHRAAGPQLEEECAEIAPKRGGgrIPVGEAVITEAGRLpAKYVIHTVGPSWRGGSKDeaEL 98
                         90       100
                 ....*....|....*....|....*..
gi 30027621 1109 LKAAYenfnsqdilLAPLLSAGIFGAK 1135
Cdd:COG2110   99 LAAAY---------RAALRLAKEAGVR 116
AAA smart00382
ATPases associated with a variety of cellular activities; AAA - ATPases associated with a ...
5581-5713 4.62e-03

ATPases associated with a variety of cellular activities; AAA - ATPases associated with a variety of cellular activities. This profile/alignment only detects a fraction of this vast family. The poorly conserved N-terminal helix is missing from the alignment.


Pssm-ID: 214640 [Multi-domain]  Cd Length: 148  Bit Score: 41.20  E-value: 4.62e-03
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621    5581 LQGPPGTGKSHFAIGLALYY--PSARIVYTACSHAAVDALCEKALKYLPIDKCSRIIPARARvecfdkfKVNSTLEQYVF 5658
Cdd:smart00382    7 IVGPPGSGKTTLARALARELgpPGGGVIYIDGEDILEEVLDQLLLIIVGGKKASGSGELRLR-------LALALARKLKP 79
                            90       100       110       120       130
                    ....*....|....*....|....*....|....*....|....*....|....*
gi 30027621    5659 ctvnalpettaDIVVFDEIsmaTNYDLSVVNARLRAKHYVYIGDPAQLPAPRTLL 5713
Cdd:smart00382   80 -----------DVLILDEI---TSLLDAEQEALLLLLEELRLLLLLKSEKNLTVI 120
 
Name Accession Description Interval E-value
SARS-CoV-like_RdRp cd21591
Severe acute respiratory syndrome coronavirus RNA-dependent RNA polymerase, also known as ...
4375-5301 0e+00

Severe acute respiratory syndrome coronavirus RNA-dependent RNA polymerase, also known as non-structural protein 12, and similar proteins from betacoronaviruses in the B lineage: responsible for replication and transcription of the viral RNA genome; This group contains the RNA-dependent RNA polymerase (RdRp) of Severe acute respiratory syndrome coronavirus (SARS-CoV), SARS-CoV-2 (also known as 2019 novel CoV (2019-nCoV) or COVID-19 virus), and similar proteins from betacoronaviruses in the sarbecovirus subgenera (B lineage). CoVs utilize a multi-subunit replication/transcription machinery. A set of non-structural proteins (Nsps) generated as cleavage products of the ORF1a and ORF1ab viral polyproteins assemble to facilitate viral replication and transcription. A key component, the RNA-dependent RNA polymerase (RdRp, also known as Nsp12), catalyzes the synthesis of viral RNA and thus plays a central role in the replication and transcription cycle of CoV, possibly interacting with its co-factors, Nsp7 and Nsp8. RdRp is therefore considered a primary target for nucleotide analog antiviral inhibitors such as remdesivir, which shows potential for the treatment of SARS-CoV-2 viral infections. The structure of SARS-CoV-2 Nsp12 contains a RdRp domain as well as a large N-terminal extension that adopts a nidovirus RdRp-associated nucleotidyltransferase (NiRAN) architecture. Recent studies have shown that the SARS-CoV-2 RdRp requires two iron-sulfur clusters to function optimally. Earlier studies had mistakenly identified these iron-sulfur cluster binding sites for zinc-binding sites, likely because iron-sulfur clusters degrade easily under standard experimental conditions.The RdRp domain displays a right hand with three functional subdomains, called fingers, palm, and thumb. All RdRps contain conserved polymerase motifs (A-G), located in the palm (A-E motifs) and finger (F-G) subdomains. All these motifs have been implicated in RdRp fidelity such as processes of correct incorporation and reorganization of nucleotides.


Pssm-ID: 394895  Cd Length: 928  Bit Score: 1903.66  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 4375 TFLNRVCGVSAARLTPCGTGTSTDVVYRAFDIYNEKVAGFAKFLKTNCCRFQEKDEEGNLLDSYFVVKRHTMSNYQHEET 4454
Cdd:cd21591    2 SFLNRVCGVSAARLTPCGTGTSTDVVYRAFDIYNDKVAGFAKFLKTNCCRFQEKDEDGNLIDSYFVVKRHTFSNYQHEET 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 4455 IYNLVKDCPAVAVHDFFKFRVDGDMVPHISRQRLTKYTMADLVYALRHFDEGNCDTLKEILVTYNCCDDDYFNKKDWYDF 4534
Cdd:cd21591   82 IYNLLKDCPAVAVHDFFKFRVDGDMVPHISRQRLTKYTMADLVYALRHFDEGNCDTLKEILVTYNCCDDDYFNKKDWYDF 161
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 4535 VENPDILRVYANLGERVRQSLLKTVQFCDAMRDAGIVGVLTLDNQDLNGNWYDFGDFVQVAPGCGVPIVDSYYSLLMPIL 4614
Cdd:cd21591  162 VENPDILRVYANLGERVRQALLKTVQFCDAMRDAGIVGVLTLDNQDLNGNWYDFGDFIQTTPGSGVPIVDSYYSLLMPIL 241
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 4615 TLTRALAAESHMDADLAKPLIKWDLLKYDFTEERLCLFDRYFKYWDQTYHPNCINCLDDRCILHCANFNVLFSTVFPPTS 4694
Cdd:cd21591  242 TLTRALTAESHVDTDLTKPYIKWDLLKYDFTEERLKLFDRYFKYWDQTYHPNCVNCLDDRCILHCANFNVLFSTVFPPTS 321
                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 4695 FGPLVRKIFVDGVPFVVSTGYHFRELGVVHNQDVNLHSSRLSFKELLVYAADPAMHAASGNLLLDKRTTCFSVAALTNNV 4774
Cdd:cd21591  322 FGPLVRKIFVDGVPFVVSTGYHFRELGVVHNQDVNLHSSRLSFKELLVYAADPAMHAASGNLLLDKRTTCFSVAALTNNV 401
                        410       420       430       440       450       460       470       480
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 4775 AFQTVKPGNFNKDFYDFAVSKGFFKEGSSVELKHFFFAQDGNAAISDYDYYRYNLPTMCDIRQLLFVVEVVDKYFDCYDG 4854
Cdd:cd21591  402 AFQTVKPGNFNKDFYDFAVSKGFFKEGSSVELKHFFFAQDGNAAISDYDYYRYNLPTMCDIRQLLFVVEVVDKYFDCYDG 481
                        490       500       510       520       530       540       550       560
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 4855 GCINANQVIVNNLDKSAGFPFNKWGKARLYYDSMSYEDQDALFAYTKRNVIPTITQMNLKYAISAKNRARTVAGVSICST 4934
Cdd:cd21591  482 GCINANQVIVNNLDKSAGFPFNKWGKARLYYDSMSYEDQDALFAYTKRNVIPTITQMNLKYAISAKNRARTVAGVSICST 561
                        570       580       590       600       610       620       630       640
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 4935 MTNRQFHQKLLKSIAATRGATVVIGTSKFYGGWHNMLKTVYSDVETPHLMGWDYPKCDRAMPNMLRIMASLVLARKHNTC 5014
Cdd:cd21591  562 MTNRQFHQKLLKSIAATRGATVVIGTSKFYGGWHNMLKTVYSDVENPHLMGWDYPKCDRAMPNMLRIMASLVLARKHTTC 641
                        650       660       670       680       690       700       710       720
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 5015 CNLSHRFYRLANECAQVLSEMVMCGGSLYVKPGGTSSGDATTAYANSVFNICQAVTANVNALLSTDGNKIADKYVRNLQH 5094
Cdd:cd21591  642 CSLSHRFYRLANECAQVLSEMVMCGGSLYVKPGGTSSGDATTAYANSVFNICQAVTANVNALLSTDGNKIADKYVRNLQH 721
                        730       740       750       760       770       780       790       800
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 5095 RLYECLYRNRDVDHEFVDEFYAYLRKHFSMMILSDDAVVCYNSNYAAQGLVASIKNFKAVLYYQNNVFMSEAKCWTETDL 5174
Cdd:cd21591  722 RLYECLYRNRDVDTDFVNEFYAYLRKHFSMMILSDDAVVCFNSTYASQGLVASIKNFKSVLYYQNNVFMSEAKCWTETDL 801
                        810       820       830       840       850       860       870       880
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 5175 TKGPHEFCSQHTMLVKQGDDYVYLPYPDPSRILGAGCFVDDIVKTDGTLMIERFVSLAIDAYPLTKHPNQEYADVFHLYL 5254
Cdd:cd21591  802 TKGPHEFCSQHTMLVKQGDDYVYLPYPDPSRILGAGCFVDDIVKTDGTLMIERFVSLAIDAYPLTKHPNQEYADVFHLYL 881
                        890       900       910       920
                 ....*....|....*....|....*....|....*....|....*..
gi 30027621 5255 QYIRKLHDELTGHMLDMYSVMLTNDNTSRYWEPEFYEAMYTPHTVLQ 5301
Cdd:cd21591  882 QYIRKLHDELTGHMLDMYSVMLTNDNTSRYWEPEFYEAMYTPHTVLQ 928
betaCoV_RdRp cd21589
betacoronavirus RNA-dependent RNA polymerase, also known as non-structural protein 12: ...
4374-5301 0e+00

betacoronavirus RNA-dependent RNA polymerase, also known as non-structural protein 12: responsible for replication and transcription of the viral RNA genome; This subfamily contains the RNA-dependent RNA polymerase (RdRp) of betacoronaviruses, including the RdRps from three highly pathogenic human coronaviruses (CoVs) such as Middle East respiratory syndrome (MERS)-related CoV, Severe acute respiratory syndrome (SARS) CoV, and SARS-CoV-2, also known as 2019 novel CoV (2019-nCoV) or COVID-19 virus. CoVs utilize a multi-subunit replication/transcription machinery. A set of non-structural proteins (Nsps) generated as cleavage products of the ORF1a and ORF1ab viral polyproteins assemble to facilitate viral replication and transcription. A key component, the RNA-dependent RNA polymerase (RdRp, also known as Nsp12), catalyzes the synthesis of viral RNA and thus plays a central role in the replication and transcription cycle of CoV, possibly interacting with its co-factors, Nsp7 and Nsp8. RdRp is therefore considered a primary target for nucleotide analog antiviral inhibitors such as remdesivir, which shows potential for the treatment of SARS-CoV-2 viral infections. The structure of SARS-CoV-2 Nsp12 contains a RdRp domain as well as a large N-terminal extension that adopts a nidovirus RdRp-associated nucleotidyltransferase (NiRAN) architecture. The RdRp domain displays a right hand with three functional subdomains, called fingers, palm, and thumb. All RdRps contain conserved polymerase motifs (A-G), located in the palm (A-E motifs) and finger (F-G) subdomains. All these motifs have been implicated in RdRp fidelity such as processes of correct incorporation and reorganization of nucleotides.


Pssm-ID: 438016  Cd Length: 925  Bit Score: 1860.21  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 4374 STFLNRVCGVSA-ARLTPCGTGTSTDVVYRAFDIYNEKVAGFAKFLKTNCCRFQEKDEEGNLLDSYFVVKRHTMSNYQHE 4452
Cdd:cd21589    1 TNFLNRVRGTSVnARLVPCASGLSTDVQLRAFDICNANVAGIGLYYKVNCCRFQRLDEDGNKLDKFFVVKRTNLEVYNKE 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 4453 ETIYNLVKDCPAVAVHDFFKFRVDGDMVPHISRQRLTKYTMADLVYALRHFDEGNCDTLKEILVTYNCCDDDYFNKKDWY 4532
Cdd:cd21589   81 KECYELLKDCGVVAEHDFFTFDVDGSRVPHIVRKDLTKYTMLDLCYALRHFDRNDCSTLKEILVTYAECDESYFTKKDWY 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 4533 DFVENPDILRVYANLGERVRQSLLKTVQFCDAMRDAGIVGVLTLDNQDLNGNWYDFGDFVQVAPGCGVPIVDSYYSLLMP 4612
Cdd:cd21589  161 DFVENPDIINVYKKLGPIFNRALLNTAKFADAMVEAGLVGVLTLDNQDLNGQWYDFGDFVKTVPGCGVAVADSYYSYMMP 240
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 4613 ILTLTRALAAEShmdaDLAKPLIKWDLLKYDFTEERLCLFDRYFKYWDQTYHPNCINCLDDRCILHCANFNVLFSTVFPP 4692
Cdd:cd21589  241 MLTMCHALDCEL----FVNKPYRQFDLVQYDFTDYKLELFNKYFKYWSMTYHPNTVECEDDRCIIHCANFNILFSMVLPN 316
                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 4693 TSFGPLVRKIFVDGVPFVVSTGYHFRELGVVHNQDVNLHSSRLSFKELLVYAADPAMHAASGNLLLDKRTTCFSVAALTN 4772
Cdd:cd21589  317 TCFGPLVRQIFVDGVPFVVSIGYHYKELGVVMNMDVDTHRYRLSLKDLLLYAADPALHVASASALLDLRTCCFSVAAITS 396
                        410       420       430       440       450       460       470       480
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 4773 NVAFQTVKPGNFNKDFYDFAVSKGFFKEGSSVELKHFFFAQDGNAAISDYDYYRYNLPTMCDIRQLLFVVEVVDKYFDCY 4852
Cdd:cd21589  397 GVKFQTVKPGNFNQDFYDFILSKGLLKEGSSVDLKHFFFTQDGNAAITDYNYYKYNLPTMVDIKQLLFVLEVVYKYFEIY 476
                        490       500       510       520       530       540       550       560
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 4853 DGGCINANQVIVNNLDKSAGFPFNKWGKARLYYDSMSYEDQDALFAYTKRNVIPTITQMNLKYAISAKNRARTVAGVSIC 4932
Cdd:cd21589  477 DGGCIPASQVIVNNYDKSAGYPFNKFGKARLYYEALSFEEQDEIYAYTKRNVLPTLTQMNLKYAISAKNRARTVAGVSIL 556
                        570       580       590       600       610       620       630       640
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 4933 STMTNRQFHQKLLKSIAATRGATVVIGTSKFYGGWHNMLKTVYSDVETPHLMGWDYPKCDRAMPNMLRIMASLVLARKHN 5012
Cdd:cd21589  557 STMTGRMFHQKCLKSIAATRGVPVVIGTTKFYGGWDDMLRRLIKDVDNPVLMGWDYPKCDRAMPNILRIVSSLVLARKHD 636
                        650       660       670       680       690       700       710       720
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 5013 TCCNLSHRFYRLANECAQVLSEMVMCGGSLYVKPGGTSSGDATTAYANSVFNICQAVTANVNALLSTDGNKIADKYVRNL 5092
Cdd:cd21589  637 TCCSHSDRFYRLANECAQVLSEIVMCGGCYYVKPGGTSSGDATTAFANSVFNICQAVTANVCSLMACNGNKIEDLSIREL 716
                        730       740       750       760       770       780       790       800
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 5093 QHRLYECLYRNRDVDHEFVDEFYAYLRKHFSMMILSDDAVVCYNSNYAAQGLVASIKNFKAVLYYQNNVFMSEAKCWTET 5172
Cdd:cd21589  717 QKRLYSNVYRSDYVDPTFVNEYYEFLNKHFSMMILSDDGVVCYNSDYASKGYIANISAFQQVLYYQNNVFMSESKCWVET 796
                        810       820       830       840       850       860       870       880
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 5173 DLTKGPHEFCSQHTMLVKQGDDYVYLPYPDPSRILGAGCFVDDIVKTDGTLMIERFVSLAIDAYPLTKHPNQEYADVFHL 5252
Cdd:cd21589  797 DINKGPHEFCSQHTMLVKMDGDYVYLPYPDPSRILGAGCFVDDLLKTDSVLLIERFVSLAIDAYPLVYHENPEYQNVFRV 876
                        890       900       910       920
                 ....*....|....*....|....*....|....*....|....*....
gi 30027621 5253 YLQYIRKLHDELTGHMLDMYSVMLTNDNTSRYWEPEFYEAMYTPHTVLQ 5301
Cdd:cd21589  877 YLEYIKKLYNDLGNQILDSYSVILSTCDGQKFTDESFYKNMYLRSAVMQ 925
CoV_RdRp cd21530
coronavirus RNA-dependent RNA polymerase, also known as non-structural protein 12: responsible ...
4374-5301 0e+00

coronavirus RNA-dependent RNA polymerase, also known as non-structural protein 12: responsible for replication and transcription of the viral RNA genome; This family contains the RNA-dependent RNA polymerase of alpha-, beta-, gamma-, delta-coronaviruses, including three highly pathogenic human coronaviruses (CoVs) such as Middle East respiratory syndrome (MERS)-related CoV, Severe acute respiratory syndrome (SARS) CoV, and SARS-CoV-2, also known as 2019 novel CoV (2019-nCoV) or COVID-19 virus. CoVs utilize a multi-subunit replication/transcription machinery. A set of non-structural proteins (Nsps) generated as cleavage products of the ORF1a and ORF1ab viral polyproteins assemble to facilitate viral replication and transcription. A key component, the RNA-dependent RNA polymerase (RdRp, also known as Nsp12), catalyzes the synthesis of viral RNA and thus plays a central role in the replication and transcription cycle of CoV, possibly interacting with its co-factors, Nsp7 and Nsp8. RdRp is therefore considered a primary target for nucleotide analog antiviral inhibitors such as remdesivir, which shows potential for the treatment of SARS-CoV-2 viral infections. The structure of SARS-CoV-2 Nsp12 contains a RdRp domain as well as a large N-terminal extension that adopts a nidovirus RdRp-associated nucleotidyltransferase (NiRAN) architecture. The RdRp domain displays a right hand with three functional subdomains, called fingers, palm, and thumb. All RdRps contain conserved polymerase motifs (A-G), located in the palm (A-E motifs) and finger (F-G) subdomains. All these motifs have been implicated in RdRp fidelity such as processes of correct incorporation and reorganization of nucleotides.


Pssm-ID: 438015  Cd Length: 928  Bit Score: 1812.12  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 4374 STFLNRVCGVSAARLTPCGTGTSTDVVYRAFDIYNEKVAGFAKFLKTNCCRFQEKDEEGNLLDSYFVVKRHTMSNYQHEE 4453
Cdd:cd21530    1 QSYLNRVRGSSAARLTPLGNGTDPDVVKRAFDIYNDKVAGFFKFLKTNCARFQEKRENDNLIDSYFVVKRCTFSNYEHEE 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 4454 TIYNLVKDCPAVAVHDFFKFRVDGDMVPHISRQRLTKYTMADLVYALRHFDEGNCDTLKEILVTYNCCDDDYFNKKDWYD 4533
Cdd:cd21530   81 TCYNLLKDCGALAKHDFFKFRKDGDMVPNISRQRLTKYTMMDLVYALRHFDEGNCDVLKEILVTYGCCDDDYFNKKDWYD 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 4534 FVENPDILRVYANLGERVRQSLLKTVQFCDAMRDAGIVGVLTLDNQDLNGNWYDFGDFVQVAPGCGVPIVDSYYSLLMPI 4613
Cdd:cd21530  161 PVENPDIYRVYAKLGEIVRRALLKAVQFCDAMVNAGIVGVLTLDNQDLNGNFYDFGDFIQTTPGSGVPVVDSYYSYLMPI 240
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 4614 LTLTRALAAESHMDADLAKPLIKWDLLKYDFTEERLCLFDRYFKYWDQTYHPNCINCLDDRCILHCANFNVLFSTVFPPT 4693
Cdd:cd21530  241 MTLTRALAAECHVDTDLTKPYKKYDLLKYDFTEEKLKLFDKYFKYWDQTYHPNCVDCLDDRCVLHCANFNVLFSTVIPPT 320
                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 4694 SFGPLVRKIFVDGVPFVVSTGYHFRELGVVHNQDVNLHSSRLSFKELLVYAADPAMHAASGNLLLDKRTTCFSVAALTNN 4773
Cdd:cd21530  321 SFGPLCRKVFVDGVPFVVTTGYHFKELGVVHNQDVNTHSSRLSLKELLVFVGDPALIAASSNLLLDLRTTCFSVAALSSG 400
                        410       420       430       440       450       460       470       480
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 4774 VAFQTVKPGNFNKDFYDFAVSKGFFKEGSSVELKHFFFAQDGNAAISDYDYYRYNLPTMCDIRQLLFVVEVVDKYFDCYD 4853
Cdd:cd21530  401 IAFQTVKPGHFNKDFYDFAVSKGFFKEGSSVELKHFFFAQDGNAAISDYDYYRYNLPTMLDIRQLLFCLEVVDKYFDCYE 480
                        490       500       510       520       530       540       550       560
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 4854 GGCINANQVIVNNLDKSAGFPFNKWGKARLYYDSMSYEDQDALFAYTKRNVIPTITQMNLKYAISAKNRARTVAGVSICS 4933
Cdd:cd21530  481 GGCINANQVVVTNLDKSAGFPFNKFGKARLYYDSMSYEEQDALFAYTKRNVLPTITQMNLKYAISAKNRARTVAGVSILS 560
                        570       580       590       600       610       620       630       640
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 4934 TMTNRQFHQKLLKSIAATRGATVVIGTSKFYGGWHNMLKTVYSDVETPHLMGWDYPKCDRAMPNMLRIMASLVLARKHNT 5013
Cdd:cd21530  561 TMTNRQFHQKLLKSIVNTRNATVVIGTTKFYGGWDNMLRTLYSGVENPMLMGWDYPKCDRAMPNMLRIAASLVLARKHTN 640
                        650       660       670       680       690       700       710       720
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 5014 CCNLSHRFYRLANECAQVLSEMVMCGGSLYVKPGGTSSGDATTAYANSVFNICQAVTANVNALLSTDGNKIADKYVRNLQ 5093
Cdd:cd21530  641 CCTLSHRFYRLANECAQVLSEVVMSGGGLYVKPGGTSSGDATTAYANSVFNICQAVSANVNRLLSTDTNSIANKYVRDLQ 720
                        730       740       750       760       770       780       790       800
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 5094 HRLYECLYRNRDVDHEFVDEFYAYLRKHFSMMILSDDAVVCYNSNYAAQGLVASIKNFKAVLYYQNNVFMSEAKCWTETD 5173
Cdd:cd21530  721 RRLYECLYRNRSVDTDFVNEFYAYLRKHFSMMILSDDGVVCYNSTYAKQGLVADISGFKSILYYQNNVFMSDSKCWTETD 800
                        810       820       830       840       850       860       870       880
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 5174 LTKGPHEFCSQHTMLVKQGDDYVYLPYPDPSRILGAGCFVDDIVKTDGTLMIERFVSLAIDAYPLTKHPNQEYADVFHLY 5253
Cdd:cd21530  801 LTKGPHEFCSQHTMLVEQDDDPYYLPYPDPSRILGAGVFVDDVVKTDPVLMLERYVSLAIDAYPLTKHPNQEYAKVFYLL 880
                        890       900       910       920
                 ....*....|....*....|....*....|....*....|....*...
gi 30027621 5254 LQYIRKLHDELTGHMLDMYSVMLTNDNTSRYWEPEFYEAMYTPHTVLQ 5301
Cdd:cd21530  881 LDYIRKLHQELTGGMLDMYSVMLDNDNTSKFWEEEFYEAMYEPSTTLQ 928
MERS-CoV-like_RdRp cd21592
Middle East respiratory syndrome-related coronavirus RNA-dependent RNA polymerase, also known ...
4374-5301 0e+00

Middle East respiratory syndrome-related coronavirus RNA-dependent RNA polymerase, also known as non-structural protein 12, and similar proteins from betacoronaviruses in the C lineage: responsible for replication and transcription of the viral RNA genome; This group contains the RNA-dependent RNA polymerase (RdRp) of Middle East respiratory syndrome (MERS)-related CoV, bat-CoV HKU5, and similar proteins from betacoronaviruses in the merbecovirus subgenera (C lineage). CoVs utilize a multi-subunit replication/transcription machinery. A set of non-structural proteins (Nsps) generated as cleavage products of the ORF1a and ORF1ab viral polyproteins assemble to facilitate viral replication and transcription. A key component, the RNA-dependent RNA polymerase (RdRp, also known as Nsp12), catalyzes the synthesis of viral RNA and thus plays a central role in the replication and transcription cycle of CoV, possibly interacting with its co-factors, Nsp7 and Nsp8. RdRp is therefore considered a primary target for nucleotide analog antiviral inhibitors such as remdesivir, which has been shown to potently inhibit MERS RdRp. Nsp12 contains a RdRp domain as well as a large N-terminal extension that adopts a nidovirus RdRp-associated nucleotidyltransferase (NiRAN) architecture. The RdRp domain displays a right hand with three functional subdomains, called fingers, palm, and thumb. All RdRps contain conserved polymerase motifs (A-G), located in the palm (A-E motifs) and finger (F-G) subdomains. All these motifs have been implicated in RdRp fidelity such as processes of correct incorporation and reorganization of nucleotides.


Pssm-ID: 394896  Cd Length: 931  Bit Score: 1621.66  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 4374 STFLNRVCGVSA-ARLTPCGTGTSTDVVYRAFDI--YNEKVAGFAKFLKTNCCRFQEKDEEGNLLDSYFVVKRHTMSNYQ 4450
Cdd:cd21592    1 SNFLNRVRGSIVnARIEPCASGLSTDVVFRAFDIcnYKAKVAGIGKYYKTNTCRFVELDDQGHKLDSYFVVKRHTMENYE 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 4451 HEETIYNLVKDCPAVAVHDFFKFRVDGDMVPHISRQRLTKYTMADLVYALRHFDEGNCDTLKEILVTYNCCDDDYFNKKD 4530
Cdd:cd21592   81 LEKHCYDLLKDCDAVARHDFFVFDVDKVKTPHIVRQRLTEYTMMDLVYALRHFDQNNCEVLKSILVKYGCCDASYFDNKL 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 4531 WYDFVENPDILRVYANLGERVRQSLLKTVQFCDAMRDAGIVGVLTLDNQDLNGNWYDFGDFVQVAPGCGVPIVDSYYSLL 4610
Cdd:cd21592  161 WFDFVENPSVIGVYHKLGERVRQAVLNTVKFCDHMVKAGLVGVLTLDNQDLNGKWYDFGDFVITQPGSGVAIVDSYYSYL 240
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 4611 MPILTLTRALAAESHMDADLAKPLIKWDLLKYDFTEERLCLFDRYFKYWDQTYHPNCINCLDDRCILHCANFNVLFSTVF 4690
Cdd:cd21592  241 MPVLSMTDCLAAETHRDCDFNKPLIEWPLTEYDFTDYKVQLFEKYFKHWDQTYHANCVNCADDRCVLHCANFNVLFSMTL 320
                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 4691 PPTSFGPLVRKIFVDGVPFVVSTGYHFRELGVVHNQDVNLHSSRLSFKELLVYAADPAMHAASGNLLLDKRTTCFSVAAL 4770
Cdd:cd21592  321 PKTCFGPIVRKIFVDGVPFVVSCGYHYKELGLVMNMDVSLHRHRLSLKELMMYAADPAMHIASSNALLDLRTSCFSVAAL 400
                        410       420       430       440       450       460       470       480
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 4771 TNNVAFQTVKPGNFNKDFYDFAVSKGFFKEGSSVELKHFFFAQDGNAAISDYDYYRYNLPTMCDIRQLLFVVEVVDKYFD 4850
Cdd:cd21592  401 TTGLTFQTVRPGNFNQDFYDFVVSKGFFKEGSSVTLKHFFFAQDGHAAITDYNYYSYNLPTMCDIKQMLFCMEVVNKYFE 480
                        490       500       510       520       530       540       550       560
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 4851 CYDGGCINANQVIVNNLDKSAGFPFNKWGKARLYYDSMSYEDQDALFAYTKRNVIPTITQMNLKYAISAKNRARTVAGVS 4930
Cdd:cd21592  481 IYDGGCLNASEVVVNNLDKSAGYPFNKFGKARVYYESMSYQEQDELFAMTKRNVIPTITQMNLKYAISAKNRARTVAGVS 560
                        570       580       590       600       610       620       630       640
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 4931 ICSTMTNRQFHQKLLKSIAATRGATVVIGTSKFYGGWHNMLKTVYSDVETPHLMGWDYPKCDRAMPNMLRIMASLVLARK 5010
Cdd:cd21592  561 ILSTMTNRQYHQKMLKSMAATRGATCVIGTTKFYGGWDFMLKTLYKDVDNPHLMGWDYPKCDRAMPNMCRIFASLILARK 640
                        650       660       670       680       690       700       710       720
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 5011 HNTCCNLSHRFYRLANECAQVLSEMVMCGGSLYVKPGGTSSGDATTAYANSVFNICQAVTANVNALLSTDGNKIADKYVR 5090
Cdd:cd21592  641 HGTCCTTRDRFYRLANECAQVLSEYVLCGGGYYVKPGGTSSGDATTAYANSVFNILQATTANVSALMGANGNKIVDKEVK 720
                        730       740       750       760       770       780       790       800
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 5091 NLQHRLYECLYRNRDVDHEFVDEFYAYLRKHFSMMILSDDAVVCYNSNYAAQGLVASIKNFKAVLYYQNNVFMSEAKCWT 5170
Cdd:cd21592  721 DMQFDLYVNVYRNSKPDPKFVDKYYAFLNKHFSMMILSDDGVVCYNSDYAAKGYIAGIQNFKETLYYQNNVFMSEAKCWV 800
                        810       820       830       840       850       860       870       880
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 5171 ETDLTKGPHEFCSQHTMLVKQGDDYVYLPYPDPSRILGAGCFVDDIVKTDGTLMIERFVSLAIDAYPLTKHPNQEYADVF 5250
Cdd:cd21592  801 EPDLKKGPHEFCSQHTLYIKDGDDGYFLPYPDPSRILSAGCFVDDIVKTDGTLMVERFVSLAIDAYPLTKHEDIEYQNVF 880
                        890       900       910       920       930
                 ....*....|....*....|....*....|....*....|....*....|.
gi 30027621 5251 HLYLQYIRKLHDELTGHMLDMYSVMLTNDNTSRYWEPEFYEAMYTPHTVLQ 5301
Cdd:cd21592  881 WVYLQYIEKLYKDLTGHMLDSYSVMLCGDNSAKFWEESFYRDLYSAPTTLQ 931
batCoV-HKU9-like_RdRp cd21596
Bat coronavirus HKU9 RNA-dependent RNA polymerase, also known as non-structural protein 12, ...
4376-5301 0e+00

Bat coronavirus HKU9 RNA-dependent RNA polymerase, also known as non-structural protein 12, and similar proteins from betacoronaviruses in the D lineage: responsible for replication and transcription of the viral RNA genome; This group contains the RNA-dependent RNA polymerase (RdRp) of bat coronavirus HKU9 and similar proteins from betacoronaviruses in the nobecovirus subgenera (D lineage). CoVs utilize a multi-subunit replication/transcription machinery. A set of non-structural proteins (Nsps) generated as cleavage products of the ORF1a and ORF1ab viral polyproteins assemble to facilitate viral replication and transcription. A key component, the RNA-dependent RNA polymerase (RdRp, also known as Nsp12), catalyzes the synthesis of viral RNA and thus plays a central role in the replication and transcription cycle of CoV, possibly interacting with its co-factors, Nsp7 and Nsp8. RdRp is therefore considered a primary target for nucleotide analog antiviral inhibitors such as remdesivir. Nsp12 contains a RdRp domain as well as a large N-terminal extension that adopts a nidovirus RdRp-associated nucleotidyltransferase (NiRAN) architecture. The RdRp domain displays a right hand with three functional subdomains, called fingers, palm, and thumb. All RdRps contain conserved polymerase motifs (A-G), located in the palm (A-E motifs) and finger (F-G) subdomains. All these motifs have been implicated in RdRp fidelity such as processes of correct incorporation and reorganization of nucleotides.


Pssm-ID: 394898  Cd Length: 929  Bit Score: 1548.08  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 4376 FLNRVCGVSA-ARLTPCGTGTSTDVVYRAFDIYNEKVAGFAKFLKTNCCRFQEKDEEGNLLDSYFVVKRHTMSNYQHEET 4454
Cdd:cd21596    3 FLNRVRGTSGvARLVPLGSGVQPDVVLRAFDICNTKVAGFGLHLKNNCCRYQELDADGNQLDSYFVVKRHTESNYLLEQR 82
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 4455 IYNLVKDCPAVAVHDFFKFRVDGDMVPHISRQRLTKYTMADLVYALRHFDEGNCDTLKEILVTYNCCDDDYFNKKDWYDF 4534
Cdd:cd21596   83 CYEKLKDCGVVARHDFFKFNIEGVMTPHVSRERLTKYTMADLVYSLRHFDNNNCDTLKEILVLRGCCTVDYFDKKDWYDP 162
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 4535 VENPDILRVYANLGERVRQSLLKTVQFCDAMRDAGIVGVLTLDNQDLNGNWYDFGDFVQVAPGCGVPIVDSYYSLLMPIL 4614
Cdd:cd21596  163 VENPDIIRVYHKLGETVRKAVLSAVKMADAMVEQGLIGVLTLDNQDLNGQWYDFGDFIEGPAGAGVAVMDTYYSLAMPVY 242
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 4615 TLTRALAAESHMDADLAKPLIKWDLLKYDFTEERLCLFDRYFKYWDQTYHPNCINCLDDRCILHCANFNVLFSTVFPPTS 4694
Cdd:cd21596  243 TMTNMLAAECHVDGDLSKPKRVWDICKYDYTQFKYSLFSKYFKYWDMQYHPNCVACADDRCILHCANFNILFSMVLPNTS 322
                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 4695 FGPLVRKIFVDGVPFVVSTGYHFRELGVVHNQDVNLHSSRLSFKELLVYAADPAMHAASGNLLLDKRTTCFSVAALTNNV 4774
Cdd:cd21596  323 FGPLVQKIYVDGVPFVVSTGYHYRELGVVMNQDVRQHAQRLSLRELLVYAADPAMHVAASNALADKRTVCMSVAAMTTGV 402
                        410       420       430       440       450       460       470       480
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 4775 AFQTVKPGNFNKDFYDFAVSKGFFKEGSSVELKHFFFAQDGNAAISDYDYYRYNLPTMCDIRQLLFVVEVVDKYFDCYDG 4854
Cdd:cd21596  403 TFQTVKPGQFNEDFYKFAIKCGFFKEGSSISFKHFFYAQDGNAAISDYDYYRYNLPTMCDIKQLLFSLEVVDKYFDCYDG 482
                        490       500       510       520       530       540       550       560
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 4855 GCINANQVIVNNLDKSAGFPFNKWGKARLYYDSMSYEDQDALFAYTKRNVIPTITQMNLKYAISAKNRARTVAGVSICST 4934
Cdd:cd21596  483 GCLQASQVVVANYDKSAGFPFNKFGKARLYYESLSYADQDELFAYTKRNVLPTITQMNLKYAISAKNRARTVAGVSIAST 562
                        570       580       590       600       610       620       630       640
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 4935 MTNRQFHQKLLKSIAATRGATVVIGTSKFYGGWHNMLKTVYSDVETPHLMGWDYPKCDRAMPNMLRIMASLVLARKHNTC 5014
Cdd:cd21596  563 MTNRQFHQKMLKSIAAARGASVVIGTTKFYGGWNRMLRTLCEGVENPHLMGWDYPKCDRAMPNLLRIFASLILARKHSTC 642
                        650       660       670       680       690       700       710       720
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 5015 CNLSHRFYRLANECAQVLSEMVMCGGSLYVKPGGTSSGDATTAYANSVFNICQAVTANVNALLSTDGNKIADKYVRNLQH 5094
Cdd:cd21596  643 CNASERFYRLANECAQVLSEMVLCGGGFYVKPGGTSSGDSTTAYANSVFNICQAVSANLNTFLSIDGNKIYTTYVQELQR 722
                        730       740       750       760       770       780       790       800
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 5095 RLYECLYRNRDVDHEFVDEFYAYLRKHFSMMILSDDAVVCYNSNYAAQGLVASIKNFKAVLYYQNNVFMSEAKCWTETDL 5174
Cdd:cd21596  723 RLYLGIYRSNTVDNELVLDYYNYLRKHFSMMILSDDGVVCYNADYAQKGYVADIQGFKELLYFQNNVFMSEAKCWVEPDI 802
                        810       820       830       840       850       860       870       880
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 5175 TKGPHEFCSQHTMLVKQGDDYVYLPYPDPSRILGAGCFVDDIVKTDGTLMIERFVSLAIDAYPLTKHPNQEYADVFHLYL 5254
Cdd:cd21596  803 TKGPHEFCSQHTMLVDMNGEQVYLPYPDPSRILGAGCFVDDLLKTDGTLMMERYVSLAIDAYPLTKHSDPEYQNVFWCYL 882
                        890       900       910       920
                 ....*....|....*....|....*....|....*....|....*..
gi 30027621 5255 QYIRKLHDELTGHMLDMYSVMLTNDNTSRYWEPEFYEAMYTPHTVLQ 5301
Cdd:cd21596  883 QYIKKLHEELTGHLLDTYSVMLASDNASKYWEVDFYENMYMESATLQ 929
alphaCoV_RdRp cd21588
alphacoronavirus RNA-dependent RNA polymerase, also known as non-structural protein 12: ...
4374-5301 0e+00

alphacoronavirus RNA-dependent RNA polymerase, also known as non-structural protein 12: responsible for replication and transcription of the viral RNA genome; This subfamily contains the RNA-dependent RNA polymerase (RdRp) of alphacoronaviruses, including human coronaviruses (HCoVs), HCoV-NL63, and HCoV-229E. CoVs utilize a multi-subunit replication/transcription machinery. A set of non-structural proteins (Nsps) generated as cleavage products of the ORF1a and ORF1ab viral polyproteins assemble to facilitate viral replication and transcription. A key component, the RNA-dependent RNA polymerase (RdRp, also known as Nsp12), catalyzes the synthesis of viral RNA and thus plays a central role in the replication and transcription cycle of CoV, possibly interacting with its co-factors, Nsp7 and Nsp8. RdRp is therefore considered a primary target for nucleotide analog antiviral inhibitors such as remdesivir. Nsp12 contains a RdRp domain as well as a large N-terminal extension that adopts a nidovirus RdRp-associated nucleotidyltransferase (NiRAN) architecture. The RdRp domain displays a right hand with three functional subdomains, called fingers, palm, and thumb. All RdRps contain conserved polymerase motifs (A-G), located in the palm (A-E motifs) and finger (F-G) subdomains. All these motifs have been implicated in RdRp fidelity such as processes of correct incorporation and reorganization of nucleotides.


Pssm-ID: 394892  Cd Length: 924  Bit Score: 1498.46  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 4374 STFLNRVCGVSAARLTPCgTGTSTDVVYRAFDIYNEKVAGFAKFLKTNCCRFQEKDEEgnllDSYFVVKRHTMSNYQHEE 4453
Cdd:cd21588    1 QSYLNRVRGSSAARLEPC-NGTDTDHVVRAFDIYNKDVACIGKFLKVNCVRFKNLDKH----DAFYVVKRCTKSVMEHEQ 75
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 4454 TIYNLVKDCPAVAVHDFFKFRvDGDMV-PHISRQRLTKYTMADLVYALRHFDEGNCDTLKEILVTYNCCDDDYFNKKDWY 4532
Cdd:cd21588   76 SIYNLLKDSGAVAEHDFFTWK-DGRSIyGNVCRQDLTKYTMMDLCYALRNFDEKNCEVLKEILVLTGACDESYFDNKNWF 154
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 4533 DFVENPDILRVYANLGERVRQSLLKTVQFCDAMRDAGIVGVLTLDNQDLNGNWYDFGDFVQVAPGCGVPIVDSYYSLLMP 4612
Cdd:cd21588  155 DPVENEDIHRVYAKLGKIVANAMLKCVALCDAMVEKGIVGVLTLDNQDLNGNFYDFGDFVKTIPGMGVPCCTSYYSYMMP 234
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 4613 ILTLTRALAAESHMDADLAKPLIK-WDLLKYDFTEERLCLFDRYFKYWDQTYHPNCINCLDDRCILHCANFNVLFSTVFP 4691
Cdd:cd21588  235 VMGMTNCLASECFVKSDIFGSDFKtYDLLEYDFTEHKEKLFNKYFKYWGQDYHPNCVDCYDDMCIVHCANFNTLFSTTIP 314
                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 4692 PTSFGPLVRKIFVDGVPFVVSTGYHFRELGVVHNQDVNLHSSRLSFKELLVYAADPAMHAASGNLLLDKRTTCFSVAALT 4771
Cdd:cd21588  315 NTAFGPLCRKVFIDGVPLVTTAGYHFKQLGIVWNKDLNTHSSRLSINELLRFVTDPALLVASSPALVDQRTVCFSVAALS 394
                        410       420       430       440       450       460       470       480
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 4772 NNVAFQTVKPGNFNKDFYDFAVSKGFFKEGSSVELKHFFFAQDGNAAISDYDYYRYNLPTMCDIRQLLFVVEVVDKYFDC 4851
Cdd:cd21588  395 TGMTYQTVKPGHFNKEFYDFLREQGFFEEGSELTLKHFFFAQKGDAAIKDFDYYRYNRPTVLDICQARVVYKVVQRYFDI 474
                        490       500       510       520       530       540       550       560
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 4852 YDGGCINANQVIVNNLDKSAGFPFNKWGKARLYYDSMSYEDQDALFAYTKRNVIPTITQMNLKYAISAKNRARTVAGVSI 4931
Cdd:cd21588  475 YEGGCITAREVVVTNLNKSAGYPLNKFGKAGLYYESLSYEEQDALYALTKRNVLPTMTQLNLKYAISGKERARTVGGVSL 554
                        570       580       590       600       610       620       630       640
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 4932 CSTMTNRQFHQKLLKSIAATRGATVVIGTSKFYGGWHNMLKTVYSDVETPHLMGWDYPKCDRAMPNMLRIMASLVLARKH 5011
Cdd:cd21588  555 LSTMTTRQYHQKHLKSIVNTRNATVVIGTTKFYGGWDNMLKNLIDGVDNPCLMGWDYPKCDRALPNMIRMISAMILGSKH 634
                        650       660       670       680       690       700       710       720
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 5012 NTCCNLSHRFYRLANECAQVLSEMVMCGGSLYVKPGGTSSGDATTAYANSVFNICQAVTANVNALLSTDGNKIADKYVRN 5091
Cdd:cd21588  635 VTCCTHSDRFYRLCNELAQVLTEVVYSNGGFYLKPGGTTSGDATTAYANSVFNIFQAVSANVNRLLSVDSNTCNNLTVKS 714
                        730       740       750       760       770       780       790       800
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 5092 LQHRLYECLYRNRDVDHEFVDEFYAYLRKHFSMMILSDDAVVCYNSNYAAQGLVASIKNFKAVLYYQNNVFMSEAKCWTE 5171
Cdd:cd21588  715 LQRKLYDNCYRSSSVDDSFVDEYYGYLRKHFSMMILSDDGVVCYNKDYASLGYVADISAFKATLYYQNNVFMSTSKCWVE 794
                        810       820       830       840       850       860       870       880
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 5172 TDLTKGPHEFCSQHTMLVKQGDDYVYLPYPDPSRILGAGCFVDDIVKTDGTLMIERFVSLAIDAYPLTKHPNQEYADVFH 5251
Cdd:cd21588  795 PDLNKGPHEFCSQHTMQIVDKDGTYYLPYPDPSRILSAGVFVDDIVKTDAVILLERYVSLAIDAYPLSKHPNPEYRKVFY 874
                        890       900       910       920       930
                 ....*....|....*....|....*....|....*....|....*....|
gi 30027621 5252 LYLQYIRKLHDELTGHMLDMYSVMLTNDNTSRYWEPEFYEAMYTPHTVLQ 5301
Cdd:cd21588  875 VLLDWVKHLYKTLNQGVLESFSVTLLEDSSSKFWDESFYASMYEKSTVLQ 924
HCoV_HKU1-like_RdRp cd21593
human coronavirus HKU1 RNA-dependent RNA polymerase, also known as non-structural protein 12, ...
4374-5301 0e+00

human coronavirus HKU1 RNA-dependent RNA polymerase, also known as non-structural protein 12, and similar proteins from betacoronaviruses in the A lineage: responsible for replication and transcription of the viral RNA genome; This group contains the RNA-dependent RNA polymerase (RdRp) of human coronavirus HKU1, murine hepatitis virus, and similar proteins from betacoronaviruses in the embecovirus subgenera (A lineage). CoVs utilize a multi-subunit replication/transcription machinery. A set of non-structural proteins (Nsps) generated as cleavage products of the ORF1a and ORF1ab viral polyproteins assemble to facilitate viral replication and transcription. A key component, the RNA-dependent RNA polymerase (RdRp, also known as Nsp12), catalyzes the synthesis of viral RNA and thus plays a central role in the replication and transcription cycle of CoV, possibly interacting with its co-factors, Nsp7 and Nsp8. RdRp is therefore considered a primary target for nucleotide analog antiviral inhibitors such as remdesivir. Nsp12 contains a RdRp domain as well as a large N-terminal extension that adopts a nidovirus RdRp-associated nucleotidyltransferase (NiRAN) architecture. The RdRp domain displays a right hand with three functional subdomains, called fingers, palm, and thumb. All RdRps contain conserved polymerase motifs (A-G), located in the palm (A-E motifs) and finger (F-G) subdomains. All these motifs have been implicated in RdRp fidelity such as processes of correct incorporation and reorganization of nucleotides.


Pssm-ID: 394897  Cd Length: 925  Bit Score: 1481.36  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 4374 STFLNRVCGVSA-ARLTPCGTGTSTDVVYRAFDIYNEKVAGFAKFLKTNCCRFQEKDEEGNLLDSYFVVKRHTMSNYQHE 4452
Cdd:cd21593    1 TNFLNRVRGTSVnARLVPCASGLSTDVQLRAFDICNANRAGIGLYYKVNCCRFQRLDEDGNKLDKFFVVKRTNLEVYNKE 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 4453 ETIYNLVKDCPAVAVHDFFKFRVDGDMVPHISRQRLTKYTMADLVYALRHFDEGNCDTLKEILVTYNCCDDDYFNKKDWY 4532
Cdd:cd21593   81 KECYELTKSCGVVAEHEFFTFDVDGSRVPHIVRKDLSKYTMLDLCYALRHFDRNDCSTLCEILSMYAECDESYFTKKDWY 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 4533 DFVENPDILRVYANLGERVRQSLLKTVQFCDAMRDAGIVGVLTLDNQDLNGNWYDFGDFVQVAPGCGVPIVDSYYSLLMP 4612
Cdd:cd21593  161 DFVENPDIINVYKKLGPIFNRALVNTAKFADTLVEAGLVGVLTLDNQDLYGQWYDFGDFVKTVPGCGVAVADSYYSYMMP 240
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 4613 ILTLTRALAAESHMDADLAKplikWDLLKYDFTEERLCLFDRYFKYWDQTYHPNCINCLDDRCILHCANFNVLFSTVFPP 4692
Cdd:cd21593  241 MLTMCHALDCELFVNDTYRQ----FDLVQYDFTDYKLELFNKYFKYWSMTYHPNTCECEDDRCIIHCANFNILFSMVLPN 316
                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 4693 TSFGPLVRKIFVDGVPFVVSTGYHFRELGVVHNQDVNLHSSRLSFKELLVYAADPAMHAASGNLLLDKRTTCFSVAALTN 4772
Cdd:cd21593  317 TCFGPLVRQIFVDGVPFVVSIGYHYKELGVVMNMDVDTHRYRLSLKDLLLYAADPALHVASASALLDLRTCCFSVAAITS 396
                        410       420       430       440       450       460       470       480
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 4773 NVAFQTVKPGNFNKDFYDFAVSKGFFKEGSSVELKHFFFAQDGNAAISDYDYYRYNLPTMCDIRQLLFVVEVVDKYFDCY 4852
Cdd:cd21593  397 GVKFQTVKPGNFNQDFYDFILSKGLLKEGSSVDLKHFFFTQDGNAAITDYNYYKYNLPTMVDIKQLLFVLEVVYKYFEIY 476
                        490       500       510       520       530       540       550       560
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 4853 DGGCINANQVIVNNLDKSAGFPFNKWGKARLYYDSMSYEDQDALFAYTKRNVIPTITQMNLKYAISAKNRARTVAGVSIC 4932
Cdd:cd21593  477 DGGCIPASQVIVNNYDKSAGYPFNKFGKARLYYEALSFEEQDDIYAYTKRNVLPTLTQMNLKYAISAKNRARTVAGVSIL 556
                        570       580       590       600       610       620       630       640
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 4933 STMTNRQFHQKLLKSIAATRGATVVIGTSKFYGGWHNMLKTVYSDVETPHLMGWDYPKCDRAMPNMLRIMASLVLARKHN 5012
Cdd:cd21593  557 STMTGRMFHQKCLKSIAATRGVPVVIGTTKFYGGWDDMLRRLIKDVDNPVLMGWDYPKCDRAMPNILRIVSSLVLARKHD 636
                        650       660       670       680       690       700       710       720
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 5013 TCCNLSHRFYRLANECAQVLSEMVMCGGSLYVKPGGTSSGDATTAYANSVFNICQAVTANVNALLSTDGNKIADKYVRNL 5092
Cdd:cd21593  637 SCCSHGDRFYRLANECAQVLSEIVMCGGCYYVKPGGTSSGDATTAFANSVFNICQAVSANVCSLMACNGHKIEDLSIREL 716
                        730       740       750       760       770       780       790       800
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 5093 QHRLYECLYRNRDVDHEFVDEFYAYLRKHFSMMILSDDAVVCYNSNYAAQGLVASIKNFKAVLYYQNNVFMSEAKCWTET 5172
Cdd:cd21593  717 QKRLYSNVYRSDYVDPTFVNEYYEFLNKHFSMMILSDDGVVCYNSDYASKGYIANISAFQQVLYYQNNVFMSESKCWVET 796
                        810       820       830       840       850       860       870       880
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 5173 DLTKGPHEFCSQHTMLVKQGDDYVYLPYPDPSRILGAGCFVDDIVKTDGTLMIERFVSLAIDAYPLTKHPNQEYADVFHL 5252
Cdd:cd21593  797 DINNGPHEFCSQHTMLVKMDGDYVYLPYPDPSRILGAGCFVDDLLKTDSVLLIERFVSLAIDAYPLVYHENEEYQNVFRV 876
                        890       900       910       920
                 ....*....|....*....|....*....|....*....|....*....
gi 30027621 5253 YLQYIRKLHDELTGHMLDMYSVMLTNDNTSRYWEPEFYEAMYTPHTVLQ 5301
Cdd:cd21593  877 YLEYIKKLYNDLGNQILDSYSVILSTCDGQKFTDESFYKNMYLRSAVMQ 925
gammaCoV_RdRp cd21587
gammacoronavirus RNA-dependent RNA polymerase, also known as non-structural protein 12: ...
4376-5301 0e+00

gammacoronavirus RNA-dependent RNA polymerase, also known as non-structural protein 12: responsible for replication and transcription of the viral RNA genome; This subfamily contains the RNA-dependent RNA polymerase (RdRp) of gammacoronaviruses, including the RdRp of avian infectious bronchitis virus (IBV) and similar proteins. CoVs utilize a multi-subunit replication/transcription machinery. A set of non-structural proteins (Nsps) generated as cleavage products of the ORF1a and ORF1ab viral polyproteins assemble to facilitate viral replication and transcription. A key component, the RNA-dependent RNA polymerase (RdRp, also known as Nsp12), catalyzes the synthesis of viral RNA and thus plays a central role in the replication and transcription cycle of CoV, possibly interacting with its co-factors, Nsp7 and Nsp8. RdRp is therefore considered a primary target for nucleotide analog antiviral inhibitors such as remdesivir. Nsp12 contains a RdRp domain as well as a large N-terminal extension that adopts a nidovirus RdRp-associated nucleotidyltransferase (NiRAN) architecture. The RdRp domain displays a right hand with three functional subdomains, called fingers, palm, and thumb. All RdRps contain conserved polymerase motifs (A-G), located in the palm (A-E motifs) and finger (F-G) subdomains. All these motifs have been implicated in RdRp fidelity such as processes of correct incorporation and reorganization of nucleotides.


Pssm-ID: 394891  Cd Length: 931  Bit Score: 1358.41  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 4376 FLNRVCGVSAARLTPCGTGTSTDVVYRAFDIYNEKVAGFAKFLKTNCCRFQE--KDEEGNL--LDSYFVVKRHTMSNYQH 4451
Cdd:cd21587    3 YLNRVRGSSEARLIPLANGCDPDVVKRAFDVCNKESAGMFQNLKRNCARFQEvrDTEDGNLeyCDSYFVVKQTTPSNYEH 82
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 4452 EETIY-NLVKDCpaVAVHDFFKFRvdgDMVPHISRQRLTKYTMADLVYALRHFDEGNCDTLKEILVTYNCCDDDY----F 4526
Cdd:cd21587   83 EKACYeDLKSEV--TADHDFFVFN---KNIYNISRQRLTKYTMMDFCYALRHFDPKDCEVLKEILVTYGCIEDYHpkwfE 157
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 4527 NKKDWYDFVENPDILRVYANLGERVRQSLLKTVQFCDAMRDAGIVGVLTLDNQDLNGNWYDFGDFVQVAPGCGVPIVDSY 4606
Cdd:cd21587  158 ENKDWYDPIENPKYYAMLAKMGPIVRRALLNAVEFGNLMVEKGYVGVVTLDNQDLNGKFYDFGDFQKTAPGAGVPVFDTY 237
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 4607 YSLLMPILTLTRALAAESHMDADLAKPLIKWDLLKYDFTEERLCLFDRYFKYWDQTYHPNCINCLDDRCILHCANFNVLF 4686
Cdd:cd21587  238 YSYMMPIIAMTDALAPERYFEYDVHKGYKSYDLLKYDYTEEKQELFQKYFKYWDQEYHPNCRDCSDDRCLIHCANFNILF 317
                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 4687 STVFPPTSFGPLVRKIFVDGVPFVVSTGYHFRELGVVHNQDVNLHSSRLSFKELLVYAADPAMHAASGNLLLDKRTTCFS 4766
Cdd:cd21587  318 STLIPQTSFGNLCRKVFVDGVPFIATCGYHSKELGVIMNQDNTMSFSKMGLSQLMQFVGDPALLVGTSNNLVDLRTSCFS 397
                        410       420       430       440       450       460       470       480
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 4767 VAALTNNVAFQTVKPGNFNKDFYDFAVSKGFFKEGSSVELKHFFFAQDGNAAISDYDYYRYNLPTMCDIRQLLFVVEVVD 4846
Cdd:cd21587  398 VCALASGITHQTVKPGHFNKDFYDFAEKAGMFKEGSSIPLKHFFYPQTGNAAINDYDYYRYNRPTMFDIRQLLFCLEVTS 477
                        490       500       510       520       530       540       550       560
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 4847 KYFDCYDGGCINANQVIVNNLDKSAGFPFNKWGKARLYYDsMSYEDQDALFAYTKRNVIPTITQMNLKYAISAKNRARTV 4926
Cdd:cd21587  478 KYFECYEGGCIPASQVVVNNLDKSAGYPFNKFGKARLYYE-MSLEEQDQLFESTKKNVLPTITQMNLKYAISAKNRARTV 556
                        570       580       590       600       610       620       630       640
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 4927 AGVSICSTMTNRQFHQKLLKSIAATRGATVVIGTSKFYGGWHNMLKTVYSDVETPHLMGWDYPKCDRAMPNMLRIMASLV 5006
Cdd:cd21587  557 AGVSILSTMTNRQFHQKVLKSIVNTRNAPVVIGTTKFYGGWDNMLRNLIQGVEDPILMGWDYPKCDRAMPNLLRIAASLV 636
                        650       660       670       680       690       700       710       720
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 5007 LARKHNTCCNLSHRFYRLANECAQVLSEMVMCGGSLYVKPGGTSSGDATTAYANSVFNICQAVTANVNALLSTDGNKIAD 5086
Cdd:cd21587  637 LARKHTNCCTWSERIYRLYNECAQVLSETVLATGGIYVKPGGTSSGDATTAYANSVFNIIQATSANVARLLSVITRDIVY 716
                        730       740       750       760       770       780       790       800
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 5087 KYVRNLQHRLYECLYRNRDVDHEFVDEFYAYLRKHFSMMILSDDAVVCYNSNYAAQGLVASIKNFKAVLYYQNNVFMSEA 5166
Cdd:cd21587  717 DDIKSLQYELYQQVYRRVNFDPAFVEKFYSYLCKNFSLMILSDDGVVCYNNTLAKQGLVADISGFREILYYQNNVYMADS 796
                        810       820       830       840       850       860       870       880
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 5167 KCWTETDLTKGPHEFCSQHTMLVKQGDDYVYLPYPDPSRILGAGCFVDDIVKTDGTLMIERFVSLAIDAYPLTKHPNQEY 5246
Cdd:cd21587  797 KCWVEPDLEKGPHEFCSQHTMLVEVDGEPKYLPYPDPSRILGACVFVDDVDKTEPVAVMERYIALAIDAYPLVHHENEEY 876
                        890       900       910       920       930
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 30027621 5247 ADVFHLYLQYIRKLHDELTGHMLDMYSVMLTNDNTSRYWEPEFYEAMYTPHTVLQ 5301
Cdd:cd21587  877 KKVFFVLLSYIRKLYQELSQNMLMDYSFVMDIDKGSKFWEQEFYENMYRAPTTLQ 931
betaCoV_Nsp2_SARS-like cd21516
betacoronavirus non-structural protein 2 (Nsp2) similar to SARS-CoV Nsp2, and related proteins ...
182-818 0e+00

betacoronavirus non-structural protein 2 (Nsp2) similar to SARS-CoV Nsp2, and related proteins from betacoronaviruses in the B lineage; Non-structural proteins (Nsps) from Severe acute respiratory syndrome coronavirus (SARS-CoV) and betacoronaviruses in the sarbecovirus subgenus (B lineage) are encoded in ORF1a and ORF1b. Post infection, the SARS-CoV genomic RNA is released into the cytoplasm of the cell and translated into two long polyproteins (pp), pp1a and pp1ab, which are then autoproteolytically cleaved by two viral proteases Nsp3 and Nsp5 into smaller subunits. Nsp2 is one of these subunits. The function of Nsp2 remains unknown. Deletion of Nsp2 from the SARS-CoV genome results in only a modest reduction in viral titers. Rather than playing a role in viral replication, SARS-CoV Nsp2 may be involved in altering the host cell environment; it has been shown to interact with two host proteins, prohibitin 1 (PHB1) and PHB2 which have been implicated in cellular functions, including cell-cycle progression, cell migration, cellular differentiation, apoptosis, and mitochondrial biogenesis.


Pssm-ID: 439199  Cd Length: 637  Bit Score: 1238.88  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621  182 VTRYVDNNFCGPDGYPLDCIKDFLARAGKSMCTLSEQLDYIESKRGVYCCRDHEHEIAWFTERSDKSYEHQTPFEIKSAK 261
Cdd:cd21516    1 YTRYVDNNFCGPDGYPLECIKDLLARAGKSSCPLSEQLDFIGLKRGVYCCREHEHEIAWYTERSEKSYELQTPFEIKSAK 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621  262 KFDTFKGECPKFVFPLNSKVKVIQPRVEKKKTEGFMGRIRSVYPVASPQECNNMHLSTLMKCNHCDEVSWQTCDFLKATC 341
Cdd:cd21516   81 KFDTFKGECPHFVFPLNSTVKVIQPRVEKKKTEGFMGRIRSVYPVASPGECNPMALSTLMKCNHCGETSWQTSDFLKATC 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621  342 EHCGTENLVIEGPTTCGYLPTNAVVKMPCPACQDPEIGPEHSVADYHNHSNIETRLRKGGRTRCFGGCVFAYVGCYNKRA 421
Cdd:cd21516  161 EFCGTENLTKEGPTTCGYLPQNAVVKMPCPACKNDEVGPEHSLADYHNHSGIETRLRKGGRTVCFGGCVFAYVGCYNKCA 240
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621  422 YWVPRASADIGSGHTGITGDNVETLNEDLLEILSRERVNINIVGDFHLNEEVAIILASFSASTSAFIDTIKSLDYKSFKT 501
Cdd:cd21516  241 YWVPRASANIGSNHTGVVGEDVETLNDDLLEILQREKVNINIVGDFKLNEEVAIILASFSASTSAFIETVKGLDYKTFKQ 320
                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621  502 IVESCGNYKVTKGKPVKGAWNIGQQRSVLTPLCGFPSQAAGVIRSIFARTLDAANHSIPDLQRAAVTILDGISEQSLRLV 581
Cdd:cd21516  321 IVESCGNFKVTKGKAKKGAWNIGTQKSVLTPLLAFPSQAAGVVRSIFSRTLDTAGHSLRALQRAAITILDGISPQSLRLL 400
                        410       420       430       440       450       460       470       480
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621  582 DAMVYTSDLLTNSVIIMAYVTGGLVQQTSQWLSNLLGTTVEKLRPIFEWIEAKLSAGVEFLKDAWEILKFLITGVFDIVK 661
Cdd:cd21516  401 DAMVFTSDLATNSVLVMAYDTGGLVQVTSQWLDNLFGTCADKLKPVLTWLEEKLKEGVDFLRDAWEILKFLVTGAYKIVK 480
                        490       500       510       520       530       540       550       560
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621  662 GQIQVASDNIKDCVKCFIDVVNKALEMCIDQVTIAGAKLRSLNLGEVFIAQSKGLYRQCIRGKEQLQLLMPLKAPKEVTF 741
Cdd:cd21516  481 GQIVLAAKNIKECVQSFVAVVNKVLSLCYDQIQIAGAKVGALNLGETFIAQSKGLYRVCVRAREIQQLLMPLKAPKELTF 560
                        570       580       590       600       610       620       630
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 30027621  742 LEGDSHDTVLTSEEVVLKNGELEALETPVDSFTNGAIVGTPVCVNGLMLLEIKDKEQYCALSPGLLATNNVFRLKGG 818
Cdd:cd21516  561 LEGDTLDTELTSEEVVLKTGTLEALDTPTSEVVNGPVEGTPVCVNGLMLLEIKDKEQYCALSPDCQATNNVFTLKGG 637
TM_Y_SARS-CoV-like_Nsp3_C cd21717
C-terminus of non-structural protein 3, including transmembrane and Y domains, from Severe ...
2209-2739 0e+00

C-terminus of non-structural protein 3, including transmembrane and Y domains, from Severe acute respiratory syndrome-related coronavirus and betacoronavirus in the B lineage; This model represents the C-terminus of non-structural protein 3 (Nsp3) from betacoronavirus in the sarbecovirus subgenus (B lineage), including highly pathogenic human coronaviruses such as Severe acute respiratory syndrome-related coronavirus (SARS-CoV) and SARS-CoV2 (also called 2019 novel CoV or 2019-nCoV). This conserved C-terminus includes two transmembrane (TM) regions TM1 and TM2, an ectodomain (3Ecto) between the TM1 and TM2 that is glycosylated and located on the lumenal side of the ER, an amphiphatic region (AH1) that is not membrane-spanning, and a large Y domain of approximately 370 residues. Nsp3 is a large multi-functional multi-domain protein that is an essential component of the replication/transcription complex (RTC), which carries out RNA synthesis, RNA processing, and interference with the host cell innate immune system. In SARS-CoV and the related murine hepatitis virus (MHV), the TM1, 3Ecto and TM2 domains are important for the papain-like protease (PL2pro) domain to process Nsp3-Nsp4 cleavage. It has also been shown that the interaction of 3Ecto with the lumenal loop of Nsp4 is essential for ER rearrangements in cells infected with SARS-CoV or MHV. The Y domain, located at the cytosolic side of the ER, consists of the Y1 and CoV-Y subdomains, which are conserved in nidovirus and coronavirus, respectively. Functional information about the Y domain is limited; it has been shown that Nsp3 binding to Nsp4 is less efficient without the Y domain.


Pssm-ID: 409665  Cd Length: 531  Bit Score: 1169.76  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 2209 WLLLLSICLGSLICVTAAFGVLLSNFGAPSYCNGVRELYLNSSNVTTMDFCEGSFPCSICLSGLDSLDSYPALETIQVTI 2288
Cdd:cd21717    1 WLLLLSICLGSLIYVTAALGVLLSNLGAPSYCDGVRESYLNSSNVTTMDFCEGSFPCSVCLSGLDSLDSYPALETIQVTI 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 2289 SSYKLDLTILGLAAEWVLAYMLFTKFFYLLGLSAIMQVFFGYFASHFISNSWLMWFIISIVQMAPVSAMVRMYIFFASFY 2368
Cdd:cd21717   81 SSYKLDLTILGLAAEWFLAYMLFTKFFYLLGLSAIMQVFFGYFASHFISNSWLMWFIISIVQMAPVSAMVRMYIFFASFY 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 2369 YIWKSYVHIMDGCTSSTCMMCYKRNRATRVECTTIVNGMKRSFYVYANGGRGFCKTHNWNCLNCDTFCTGSTFISDEVAR 2448
Cdd:cd21717  161 YIWKSYVHIMDGCTSSTCMMCYKRNRATRVECTTIVNGMKRSFYVYANGGRGFCKTHNWNCLNCDTFCAGSTFISDEVAR 240
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 2449 DLSLQFKRPINPTDQSSYIVDSVAVKNGALHLYFDKAGQKTYERHPLSHFVNLDNLRANNTKGSLPINVIVFDGKSKCDE 2528
Cdd:cd21717  241 DLSLQFKRPINPTDQSSYVVDSVAVKNGALHLYFDKAGQKTYERHPLSHFVNLDNLRANNTKGSLPINVIVFDGKSKCDE 320
                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 2529 SASKSASVYYSQLMCQPILLLDQVLVSDVGDSTEVSVKMFDAYVDTFSATFSVPMEKLKALVATAHSELAKGVALDGVLS 2608
Cdd:cd21717  321 SAAKSASVYYSQLMCQPILLLDQALVSDVGDSTEVSVKMFDAYVDTFSATFSVPMEKLKALVATAHSELAKGVALDGVLS 400
                        410       420       430       440       450       460       470       480
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 2609 TFVSAARQGVVDTDVDTKDVIECLKLSHHSDLEVTGDSCNNFMLTYNKVENMTPRDLGACIDCNARHINAQVAKSHNVSL 2688
Cdd:cd21717  401 TFVSAARQGVVDTDVDTKDVIECLKLSHHSDLEVTGDSCNNFMLTYNKVENMTPRDLGACIDCNARHINAQVAKSHNVSL 480
                        490       500       510       520       530
                 ....*....|....*....|....*....|....*....|....*....|.
gi 30027621 2689 IWNVKDYMSLSEQLRKQIRSAAKKNNIPFRLTCATTRQVVNVITTKISLKG 2739
Cdd:cd21717  481 IWNVKDYMSLSEQLRKQIRSAAKKNNIPFRLTCATTRQVVNVITTKISLKG 531
betaCoV_Nsp14 cd21659
nonstructural protein 14 of betacoronavirus; Nonstructural protein 14 (Nsp14) of coronavirus ...
5907-6427 0e+00

nonstructural protein 14 of betacoronavirus; Nonstructural protein 14 (Nsp14) of coronavirus (CoV) plays an important role in viral replication and transcription. It consists of 2 domains with different enzymatic activities: an N-terminal exoribonuclease (ExoN) domain and a C-terminal cap (guanine-N7) methyltransferase (N7-MTase) domain. ExoN is important for proofreading and therefore, the prevention of lethal mutations. The association of Nsp14 with Nsp10 stimulates its ExoN activity; the complex hydrolyzes double-stranded RNA in a 3' to 5' direction as well as a single mismatched nucleotide at the 3'-end mimicking an erroneous replication product. The Nsp10/Nsp14 complex may function in a replicative mismatch repair mechanism. N7-MTase functions in mRNA capping. Nsp14 can methylate GTP, dGTP as well as cap analogs GpppG, GpppA and m7GpppG. The accumulation of m7GTP or Nsp14 has been found to interfere with protein translation of cellular mRNAs.


Pssm-ID: 394958  Cd Length: 519  Bit Score: 1085.52  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 5907 TGLFKDCSKIITGLHPTQAPTHLSVDIKFKTEG-LCVDIPGIPKDMTYRRLISMMGFKMNYQVNGYPNMFITREEAIRHV 5985
Cdd:cd21659    1 TGLFKDCSKSYVGLHPAYAPTFLSVDDKYKTNGdLCVCLNIIDSVVTYSRLISLMGFKLDLTLPGYPKLFITREEAIKRV 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 5986 RAWIGFDVEGCHATRDAVGTNLPLQLGFSTGVNLVAVPTGYVDTENNTEFTRVNAKPPPGDQFKHLIPLMYKGLPWNVVR 6065
Cdd:cd21659   81 RAWIGFDVEGAHATRDAIGTNFPLQLGFSTGVNFVVEPTGLVDTEDGYMFTKIVAKAPPGEQFKHLIPLMSKGQPWDVVR 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 6066 IKIVQMLSDTLKGLSDRVVFVLWAHGFELTSMKYFVKIGPERTCCLCDKRATCFSTSSDTYACWNHSVGFDYVYNPFMID 6145
Cdd:cd21659  161 IRIVQMLSDTLDDLSDSVVFVTWAHGFELTSLRYFAKIGKERTCCMCTKRATCYSSRTGYYGCWRHSVGCDYVYNPFIVD 240
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 6146 VQQWGFTGNLQSNHDQHCQVHGNAHVASCDAIMTRCLAVHECFVKRVDWSVEYPIIGDELRVNSACRKVQHMVVKSALLA 6225
Cdd:cd21659  241 VQQWGYTGNLQSNHDRYCSVHKGAHVASSDAIMTRCLAVHDCFCKRVNWDVEYPIISNELSINSSCRLVQRVVLKAALLA 320
                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 6226 DKFPVLHDIGNPKAIKCVPQAEVEWKFYDAQPCsdkAYKIEELFYSYATHHDKFTDGVCLFWNCNVDRYPANAIVCRFDT 6305
Cdd:cd21659  321 NRFDLCYDIGNPKGIACVKDPVVDWKFYDAQPV---VKSVKQLFYTYEAHKDQFKDGLCMFWNCNVDKYPANAIVCRFDT 397
                        410       420       430       440       450       460       470       480
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 6306 RVLSNLNLPGCDGGSLYVNKHAFHTPAFDKSAFTNLKQLPFFYYSDSPCESHGKQVVSDIDYVPLKSATCITRCNLGGAV 6385
Cdd:cd21659  398 RVLSKLNLPGCNGGSLYVNKHAFHTPAFDKSAFENLKPLPFFYYSDTPCEYHGGNDVKDVDYVPLKSATCITRCNLGGAV 477
                        490       500       510       520
                 ....*....|....*....|....*....|....*....|..
gi 30027621 6386 CRHHANEYRQYLDAYNMMISAGFSLWIYKQFDTYNLWNTFTR 6427
Cdd:cd21659  478 CRKHAEEYREYLEAYNTATTAGFTLWVYKTFDFYNLWNTFTK 519
deltaCoV_RdRp cd21590
deltacoronavirus RNA-dependent RNA polymerase, also known as non-structural protein 12: ...
4374-5301 0e+00

deltacoronavirus RNA-dependent RNA polymerase, also known as non-structural protein 12: responsible for replication and transcription of the viral RNA genome; This subfamily contains the RNA-dependent RNA polymerase (RdRp) of deltacoronaviruses. CoVs utilize a multi-subunit replication/transcription machinery. A set of non-structural proteins (Nsps) generated as cleavage products of the ORF1a and ORF1ab viral polyproteins assemble to facilitate viral replication and transcription. A key component, the RNA-dependent RNA polymerase (RdRp, also known as Nsp12), catalyzes the synthesis of viral RNA and thus plays a central role in the replication and transcription cycle of CoV, possibly interacting with its co-factors, Nsp7 and Nsp8. RdRp is therefore considered a primary target for nucleotide analog antiviral inhibitors such as remdesivir, which has been shown to inhibit human endemic and zoonotic deltacoronaviruses with a highly divergent RdRp. Nsp12 contains a RdRp domain as well as a large N-terminal extension that adopts a nidovirus RdRp-associated nucleotidyltransferase (NiRAN) architecture. The RdRp domain displays a right hand with three functional subdomains, called fingers, palm, and thumb. All RdRps contain conserved polymerase motifs (A-G), located in the palm (A-E motifs) and finger (F-G) subdomains. All these motifs have been implicated in RdRp fidelity such as processes of correct incorporation and reorganization of nucleotides.


Pssm-ID: 394894  Cd Length: 928  Bit Score: 1072.17  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 4374 STFLNRVCGVSAARLTPCGTGTSTDVVYRAFDIYNEKVAGFAKFLKTNCCRFQEKDEEGNL-----LDSYFVVKRHTMSN 4448
Cdd:cd21590    1 SAYLNRVTGSSDARLEPLQPGTQPDAVKRAFHVHNNTTSGIFLSTKTNCARFKTTRSALPLpnkgeVDLYFVTKQCSAKV 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 4449 YQHEETIYNLVKDC--------PAVAVHDFFKFrvdgDMVPHISRQRLTKYTMADLVYALRHFDEGNcDTLKEILVTYNC 4520
Cdd:cd21590   81 FEIEEKCYNALSTElyttddtfGVLAKTEFFKF----DKIPNVNRQYLTKYTLLDLAYALRHLSTSK-DVIQEILITMCG 155
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 4521 CDDDYFNKKdWYDFVENPDILRVYANLGERVRQSLLKTVQFCDAMRDAGIVGVLTLDNQDLNGNWYDFGDFVQVAPGCGV 4600
Cdd:cd21590  156 TPEDWFGEN-WFDPIENPTFYKEFHKLGDILNRCVLNANKFASACIDAGLVGILTPDNQDLLGQIYDFGDFIITQPGNGC 234
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 4601 PIVDSYYSLLMPILTLTRALAAEShMDADlaKPLIKWDLLKYDFTEERLCLFDRYFKYWDQTYHPNCINCLDDRCILHCA 4680
Cdd:cd21590  235 VDLSSYYSYLMPIMSMTHMLKCEC-MDSD--GNPLEYDGFQYDFTDFKLELFEKYFKYWDRPYHPNTVDCPDDRCVLHCA 311
                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 4681 NFNVLFSTVFPPTSFGPLVRKIFVDGVPFVVSTGYHFRELGVVHNQDVNLHSSRLSFKELLVYAADPAMHAASGNLLLDK 4760
Cdd:cd21590  312 NFNVLFAMCIPNTAFGNLCSQATVDGHLVVQTVGVHLKELGIVLNQDVTTHMSNINLNTLLRLVGDPTTIASVSDKCLDL 391
                        410       420       430       440       450       460       470       480
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 4761 RTTCFSVAALTNNVAFQTVKPGNFNKDFYDFAVSKGFFKEgSSVELKHFFFAQDGNAAISDYDYYRYNLPTMCDIRQLLF 4840
Cdd:cd21590  392 RTPCQTLATMSSGITKQSVKPGHFNQHFYKHLLDSNLLDQ-LGIDIRHFYYMQDGEAAITDYSYYRYNTPTMVDIKMFLF 470
                        490       500       510       520       530       540       550       560
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 4841 VVEVVDKYFDCYDGGCINANQVIVNNLDKSAGFPFNKWGKARLYYDsMSYEDQDALFAYTKRNVIPTITQMNLKYAISAK 4920
Cdd:cd21590  471 CLEVADKYLEPYEGGCINAQSVVVSNLDKSAGYPFNKLGKARNYYD-MTYAEQNQLFEYTKRNVLPTLTQMNLKYAISAK 549
                        570       580       590       600       610       620       630       640
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 4921 NRARTVAGVSICSTMTNRQFHQKLLKSIAATRGATVVIGTSKFYGGWHNMLKTVYSDVETPHLMGWDYPKCDRAMPNMLR 5000
Cdd:cd21590  550 DRARTVAGVSIISTMTNRQYHQKMLKSISLARNQTIVIGTTKFYGGWDNMLRRLMCNINNPILVGWDYPKCDRSMPNMLR 629
                        650       660       670       680       690       700       710       720
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 5001 IMASLVLARKHnTCCNLSHRFYRLANECAQVLSEMVMCGGSLYVKPGGTSSGDATTAYANSVFNICQAVTANVNALLSTD 5080
Cdd:cd21590  630 IAASCLLARKH-TCCNQSQRFYRLANECCQVLSEVVVSGNNLYVKPGGTSSGDATTAYANSVFNILQVVSANVATFLSTS 708
                        730       740       750       760       770       780       790       800
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 5081 GNKIADKYVRNLQHRLYECLYRNRDVDHEFVDEFYAYLRKHFSMMILSDDAVVCYNSNYAAQGLVASIKNFKAVLYYQNN 5160
Cdd:cd21590  709 TTSHINKDIADLHRSLYEDIYRGDSNDITVINRFYQHLQSYFGLMILSDDGVACIDSDAAKSGAVADLDGFRDILFYQNN 788
                        810       820       830       840       850       860       870       880
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 5161 VFMSEAKCWTETDLTKGPHEFCSQHTMLVKQGDDYVYLPYPDPSRILGAGCFVDDIVKTDGTLMIERFVSLAIDAYPLTK 5240
Cdd:cd21590  789 VYMADSKCWTETDMTVGPHEFCSQHTVLAEHDGKPYYLPYPDVSRILGACIFVDDVNKADPVQNLERYISLAIDAYPLTK 868
                        890       900       910       920       930       940
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 30027621 5241 HPNQEyADVFHLYLQYIRKLHDELTGHMLDMYSVMLTNDNTSRYWEPEFYEAMYTPHTVLQ 5301
Cdd:cd21590  869 VDPIK-GKVFYLLLDYIRVLAQELQDGILDAFQSLTDMSYVNNFVQEAFYAQMYEQSPTLQ 928
NSP11 pfam06471
NSP11; This region of coronavirus polyproteins encodes the NSP11 protein.
5905-6427 0e+00

NSP11; This region of coronavirus polyproteins encodes the NSP11 protein.


Pssm-ID: 399465  Cd Length: 515  Bit Score: 990.04  E-value: 0e+00
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621   5905 NVTGLFKDCSKIITGLHPTQAPTHLSVDIKFKTEG---LCVDIPgiPKDMTYRRLISMMGFKMNYQVNGYPNMFITREEA 5981
Cdd:pfam06471    1 NTTGLFKDCSKEYSGLHPAHAPTYLSLDDKFKTSGdlaVCVGVS--DKDVTYKRLISLMGFKMSLNVEGYHNMFITRDEA 78
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621   5982 IRHVRAWIGFDVEGCHATRDAVGTNLPLQLGFSTGVNLVAVPTGYVDTENNTEFTRVNAKPPPGDQFKHLIPLMYKGLPW 6061
Cdd:pfam06471   79 IRHVRAWIGFDVEGAHATGDNVGTNLPLQLGFSTGVDFVVTPEGCVDTENGSVFEPVNAKAPPGEQFKHLIPLMRKGQPW 158
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621   6062 NVVRIKIVQMLSDTLKGLSDRVVFVLWAHGFELTSMKYFVKIGPERTCClCDKRATCFSTSSDTYACWNHSVGFDYVYNP 6141
Cdd:pfam06471  159 HVVRIRIVQMLADTLAGLSDRVVFVLWAHGLELTTMRYFVKIGREQVCS-CGKRATCFNSSTDTYACWKHSLGCDYVYNP 237
                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621   6142 FMIDVQQWGFTGNLQSNHDQHCQVHGNAHVASCDAIMTRCLAVHECFVKRVDWSVEYPIIGDELRVNSACRKVQHMVVKS 6221
Cdd:pfam06471  238 FLIDIQQWGYTGSLSSNHDEHCNVHGNAHVASGDAIMTRCLAVHDCFVKRVDWSLEYPIIANELRVNKACRLVQRMVLKA 317
                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621   6222 ALLADKFPVLHDIGNPKAIKCVPQAEVEWKFYDAQPCSDkayKIEELFYSYATHHDkFTDGVCLFWNCNVDRYPANAIVC 6301
Cdd:pfam06471  318 ALLADKPPVVHDIGNPKGIKCVRRAGVKWKFYDANPIVK---NVKQLEYDYETHKD-KMDGLCLFWNCNVDMYPANAIVC 393
                          410       420       430       440       450       460       470       480
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621   6302 RFDTRVLSNLNLPGCDGGSLYVNKHAFHTPAFDKSAFTNLKQLPFFYYSDSPCESHGKQVvsdiDYVPLKSATCITRCNL 6381
Cdd:pfam06471  394 RFDTRVLSKLNLPGCNGGSLYVNKHAFHTPAFDRRAFANLKPMPFFYYSDSPCESVGKQV----DYVPLKSATCITRCNI 469
                          490       500       510       520
                   ....*....|....*....|....*....|....*....|....*.
gi 30027621   6382 GGAVCRHHANEYRQYLDAYNMMISAGFSLWIYKQFDTYNLWNTFTR 6427
Cdd:pfam06471  470 GGAVCKKHANEYREYVESYNMMTTAGFTFWVPKNFDTYNLWNTFTR 515
CoV_Nsp14 cd21528
nonstructural protein 14 of coronavirus; Nonstructural protein 14 (Nsp14) of coronavirus (CoV) ...
5907-6427 0e+00

nonstructural protein 14 of coronavirus; Nonstructural protein 14 (Nsp14) of coronavirus (CoV) plays an important role in viral replication and transcription. It consists of 2 domains with different enzymatic activities: an N-terminal exoribonuclease (ExoN) domain and a C-terminal cap (guanine-N7) methyltransferase (N7-MTase) domain. ExoN is important for proofreading and therefore, the prevention of lethal mutations. The association of Nsp14 with Nsp10 stimulates its ExoN activity; the complex hydrolyzes double-stranded RNA in a 3' to 5' direction as well as a single mismatched nucleotide at the 3'-end mimicking an erroneous replication product. The Nsp10/Nsp14 complex may function in a replicative mismatch repair mechanism. N7-MTase functions in mRNA capping. Nsp14 can methylate GTP, dGTP as well as cap analogs GpppG, GpppA and m7GpppG. The accumulation of m7GTP or Nsp14 has been found to interfere with protein translation of cellular mRNAs.


Pssm-ID: 394955  Cd Length: 518  Bit Score: 985.42  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 5907 TGLFKDCSKIITGLHPTQAPTHLSVDIKFKTEGLCVDI--PGIPKDMTYRRLISMMGFKMNYQVNGYPNMFITREEAIRH 5984
Cdd:cd21528    1 TGLFKDCSKIFSGLHPAHAPTHLSLDSNFKTDELLADLvgPGVGKDITYRHLISLMGFKMNLDVEGYHNMFITREEAIRN 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 5985 VRAWIGFDVEGCHATRDAVGTNLPLQLGFSTGVNLVAVPTGYVDTENNTEFTRVNAKPPPGDQFKHLIPLMYKGLPWNVV 6064
Cdd:cd21528   81 VRGWIGFDVEGAHAVGDNVGTNLPLQLGFSTGVNFVVVPEGLVDTESGTEFEPVRAKPPPGEQFKHLIPLMRKALPWSVV 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 6065 RIKIVQMLSDTLKGLSDRVVFVLWAHGFELTSMKYFVKIGPERTCClCDKRATCFSTSSDTYACWNHSVGFDYVYNPFMI 6144
Cdd:cd21528  161 RKRIVQMLADTLKGLSDRVVFVLWAHGLELTTMRYFVKIGPEKKCC-CGKRATCYNSSSDTYACWNHSLGCDYVYNPYII 239
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 6145 DVQQWGFTGNLQSNHDQHCQVHGNAHVASCDAIMTRCLAVHECFVKRVDWSVEYPIIGDELRVNSACRKVQHMVVKSALL 6224
Cdd:cd21528  240 DVQQWGYSGNLQSNHDEHCNVHGNAHVASADAIMTRCLAIHECFVKRVDWSIEYPIIGNELRLNSACRLVQRNFLNSALL 319
                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 6225 ADKFPVLHDIGNPKAIKCVPQAEVEWKFYDAQPCSdkaYKIEELFYSYATHHDKFTDGVCLFWNCNVDRYPANAIVCRFD 6304
Cdd:cd21528  320 AYKPKVVYDIGNPKGIKCVRRAEVKWKFFDKQPIV---SNVKKLFYDYAEHHDKFTDGLCLFWNCNVDRYPANSLVCRFD 396
                        410       420       430       440       450       460       470       480
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 6305 TRVLSNLNLPGCDGGSLYVNKHAFHTPAFDKSAFTNLKQLPFFYYSDSPCESHGKQVVSdIDYVPLKSATCITRCNLGGA 6384
Cdd:cd21528  397 TRVLSNLNLPGCNGGSLYVNKHAFHTPAFDKSAFKNLKPLPFFFYDDSPCETHQKQVSS-IDYVPLSAADCITRCNIGGA 475
                        490       500       510       520
                 ....*....|....*....|....*....|....*....|...
gi 30027621 6385 VCRHHANEYRQYLDAYNMMISAGFSLWIYKQFDTYNLWNTFTR 6427
Cdd:cd21528  476 VCSKHANEYREYVNAYNLMVSAGFTFWVPKQFDTYNLWKTFTR 518
betaCoV_Nsp2_SARS_MHV-like cd21515
betacoronavirus non-structural protein 2 (Nsp2), similar to SARS-CoV Nsp2 and MHV Nsp2 (p65), ...
183-783 0e+00

betacoronavirus non-structural protein 2 (Nsp2), similar to SARS-CoV Nsp2 and MHV Nsp2 (p65), and related proteins; Coronavirus non-structural proteins (Nsps) are encoded in ORF1a and ORF1b. Post infection, the genomic RNA is released into the cytoplasm of the cell and translated into two long polyproteins (pp), pp1a and pp1ab, which are then autoproteolytically cleaved by two viral proteases Nsp3 and Nsp5 into smaller subunits. Nsp2 is one of these subunits. This family includes Severe acute respiratory syndrome coronavirus (SARS-CoV) Nsp2, SARS-CoV-2 Nsp2, and Murine hepatitis virus (MHV) Nsp2 (also known as p65). The function of Nsp2 remains unclear. SARS-CoV Nsp2 rather than playing a role in viral replication, may be involved in altering the host cell environment; deletion of Nsp2 from the SARS-CoV genome results in only a modest reduction in viral titers. It has been shown to interact with two host proteins, prohibitin 1 (PHB1) and PHB2 which have been implicated in cellular functions, including cell-cycle progression, cell migration, cellular differentiation, apoptosis, and mitochondrial biogenesis. MHV Nsp2/p65, different from SARS-CoV Nsp2, may play an important role in the viral life cycle.


Pssm-ID: 439198  Cd Length: 562  Bit Score: 863.70  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621  183 TRYVDNNFCGPDGYPLDCIKDFLARAGKSMCTLS-EQLDYIESKRGVYCCRDHEHEIAWFTERSDKSYEHQTPFEIKSAK 261
Cdd:cd21515    2 TRYVDQYFCGPDGYPLECIKDLLAKAGKSSCTLSdEQLDFKELKRGGYCCRDHEHEIAWYVERSDAPYELQTPFTIKSAK 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621  262 KfDTFKGECPKFVFPLNSKVKVIQPRVEKKKTEGFMGRIRSVYPVASPQECNNMHLSTLMKCNHCDEVSWQTCDFLKATC 341
Cdd:cd21515   82 K-DTFKGEVPAFVFPLNSKVKVLKPRVVKKKLEGFMGKIRTVYPVASPNECNPMTLSALMKCDHCDETSWQTGNFVGATC 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621  342 eHCGTEN-LVIEGPTTCGYLPTNAVVKMPCPACQDPEIGPEHSVADYHNHSNIETRLRKGGRTRCFGGCVFAYVGCYNKR 420
Cdd:cd21515  161 -LCGAEYtLTKEDATSAGYLPPGAVVKMPCPACKNDEVGPEHSFADYHNSSGIKTFLRKGGRTVPFGGCVFAYVGCYNGC 239
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621  421 AYWVPRASADIGSGHTGITGDNVETLNEDLLEILSRERVNINIVGDFHLNEEVAIILASFSASTSAFIDTIKSLDYKSFK 500
Cdd:cd21515  240 AYWVPRAWSNIGSNHTGVVGSGVEVLNDDLLEILLREKVNINIVGDFKLNEEVVIILASFSASVLAFVDTVKGLDFETFK 319
                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621  501 TIVESCGNYKVTKGKPVKGAWNIGQQRSVLTPLCGFPSQAAGVIRSIFARTLDAANHSIPDLQRAAVTILDGISEQSLRL 580
Cdd:cd21515  320 FIVESCGNFPVTKGKFVPGAWNLGKSKQVLTPLPAFPSQAAMVVRSIFARTVFTATHSVPALQEAAITIIDGISPQALRL 399
                        410       420       430       440       450       460       470       480
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621  581 VDAMVYTSDLLTNSVIIMAYVTGGLVQQTSQWLSNLLGTTVEKLRPIFEWIEAKLSAGVEFLKDAWEILKFLITGVFDIV 660
Cdd:cd21515  400 LDAMRFTADLVTNSVLAMAYVTGGLVQVTSQWLDNLFGTVVDLLKPVLEWLEEKISSGIEFLIDLWEILKLLVTGAYKIV 479
                        490       500       510       520       530       540       550       560
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621  661 KGQIQVASDNIKDCVKCFIDVVNKALEmcidqvtiagaklrslnlgevfiaqskglyrqcirgkeqlqLLMPLKAPKEVT 740
Cdd:cd21515  480 KGQIVLAGKNVSEVVQSFLSVLNKALG-----------------------------------------LLLPLKAPKEEL 518
                        570       580       590       600
                 ....*....|....*....|....*....|....*....|....
gi 30027621  741 FL-EGDSHDTVLTSEEVVLKNGELEALETPVDSFTNGAIVGTPV 783
Cdd:cd21515  519 FLtEGDTVDTSLTSEEVVVKTGVLEELDTPTSKVVDGPLVGTPV 562
TM_Y_betaCoV_Nsp3_C cd21713
C-terminus of betacoronavirus non-structural protein 3, including transmembrane and Y domains; ...
2209-2739 0e+00

C-terminus of betacoronavirus non-structural protein 3, including transmembrane and Y domains; This model represents the C-terminus of non-structural protein 3 (Nsp3) from betacoronavirus, including highly pathogenic betacoronaviruses such as Severe acute respiratory syndrome-related coronavirus (SARS-CoV), SARS-CoV2 (also called 2019 novel CoV or 2019-nCoV), and Middle East respiratory syndrome-related (MERS) CoV. This conserved C-terminus includes two transmembrane (TM) regions TM1 and TM2, an ectodomain (3Ecto) between the TM1 and TM2 that is glycosylated and located on the lumenal side of the ER, an amphiphatic region (AH1) that is not membrane-spanning, and a large Y domain of approximately 370 residues. Nsp3 is a large multi-functional multi-domain protein that is an essential component of the replication/transcription complex (RTC), which carries out RNA synthesis, RNA processing, and interference with the host cell innate immune system. In SARS-CoV and murine hepatitis virus (MHV), the TM1, 3Ecto and TM2 domains are important for the papain-like protease (PL2pro) domain to process Nsp3-Nsp4 cleavage. It has also been shown that the interaction of 3Ecto with the lumenal loop of Nsp4 is essential for ER rearrangements in cells infected with SARS-CoV or MHV. The Y domain, located at the cytosolic side of the ER, consists of the Y1 and CoV-Y subdomains, which are conserved in nidovirus and coronavirus, respectively. Functional information about the Y domain is limited; it has been shown that Nsp3 binding to Nsp4 is less efficient without the Y domain.


Pssm-ID: 409661  Cd Length: 545  Bit Score: 808.64  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 2209 WLLLLSICLGSLICVTAAFGVLL----------SNFGAPSYCNGVRELYLNSSNVTTMD---FCEGSFPCSICLSGLDSL 2275
Cdd:cd21713    1 VSLLLFLCLTVLLLWFNFLYANFilsdsptfvgSIVAWFKYTLGISTICDFYQVTYLGDiseFCTGSMLCSLCLSGMDSL 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 2276 DSYPALETIQVTISSYKLDLTILGLAAEWVLAYMLFTKFFYLLGLSAIMQVFFGYFASHFISNSWLMWFIISIVQMAPVS 2355
Cdd:cd21713   81 DNYDALNMVQHTVSSRLSDDYIFKLVLELFFAYLLYTVAFYVLGLLAILQLFFSYLPLFFMLNSWLVVLFVYVINMVPAS 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 2356 AMVRMYIFFASFYYIWKSYVHIMDGCTSSTCMMCYKRNRATRVECTTIVNGMKRSFYVYANGGRGFCKTHNWNCLNCDTF 2435
Cdd:cd21713  161 TLVRMYIVVASLYFVYKLYVHVVYGCNDTACLMCYKRNRATRVECSTVVNGSKRSFYVMANGGTGFCTKHNWNCVNCDTY 240
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 2436 CTGSTFISDEVARDLSLQFKRPINPTDQSSYIVDSVAVKNGALHLYFDKAGQKTYERHPLSHFVNLDNLRANNTKGSLPI 2515
Cdd:cd21713  241 GPGNTFICDEVAADLSTQFKRPINPTDSSYYSVTSVEVKNGSVHLYYERDGQRVYERFSLSLFVNLDKLKHSEVKGSPPF 320
                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 2516 NVIVFDGKSKCDESASKSASVYYSQLMCQPILLLDQVLVSDVGDSTEVSVKMFDAYVDTFSATFSVPMEKLKALVATAHS 2595
Cdd:cd21713  321 NVIVFDASNRAEENGAKSAAVYYSQLLCKPILLVDKKLVTTVGDSAEVARKMFDAYVNSFLSTYNVTMDKLKTLVSTAHN 400
                        410       420       430       440       450       460       470       480
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 2596 ELAKGVALDGVLSTFVSAARQG-VVDTDVDTKDVIECLKLSHHSDLEVTGDSCNNFMLTYNKVENMTPRDLGACIDCNAR 2674
Cdd:cd21713  401 SLKEGVQLEQVLKTFIGAARQKaAVESDVETKDIVKCVQLAHQADVDFTTDSCNNLVPTYVKVDTITTADLGVLIDNNAK 480
                        490       500       510       520       530       540
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 30027621 2675 HINAQVAKSHNVSLIWNVKDYMSLSEQLRKQIRSAAKKNNIPFRLTCATTRQVVNVITTKISLKG 2739
Cdd:cd21713  481 HVNANVAKAANVALIWNVAAFLKLSESLRRQLRSAARKTGLNFKLTTSKLRAVVPILTTPFSLKG 545
alphaCoV_Nsp14 cd21660
nonstructural protein 14 of alphacoronavirus; Nonstructural protein 14 (Nsp14) of coronavirus ...
5907-6426 0e+00

nonstructural protein 14 of alphacoronavirus; Nonstructural protein 14 (Nsp14) of coronavirus (CoV) plays an important role in viral replication and transcription. It consists of 2 domains with different enzymatic activities: an N-terminal exoribonuclease (ExoN) domain and a C-terminal cap (guanine-N7) methyltransferase (N7-MTase) domain. ExoN is important for proofreading and therefore, the prevention of lethal mutations. The association of Nsp14 with Nsp10 stimulates its ExoN activity; the complex hydrolyzes double-stranded RNA in a 3' to 5' direction as well as a single mismatched nucleotide at the 3'-end mimicking an erroneous replication product. The Nsp10/Nsp14 complex may function in a replicative mismatch repair mechanism. N7-MTase functions in mRNA capping. Nsp14 can methylate GTP, dGTP as well as cap analogs GpppG, GpppA and m7GpppG. The accumulation of m7GTP or Nsp14 has been found to interfere with protein translation of cellular mRNAs.


Pssm-ID: 394959  Cd Length: 510  Bit Score: 759.57  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 5907 TGLFKDCSKIITGLHPTQAPTHLSVDIKFKTEG-LCVDIpGIPKDMTYRRLISMMGFKMNYQVNGYPNMFITREEAIRHV 5985
Cdd:cd21660    1 CGLFKDCSRNPDYLPPSHATTYMSLSDNFKTSGdLAVQI-GVKGPVTYEHVISFMGFRFDVNVPGYHTLFCTRDFAMRNV 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 5986 RAWIGFDVEGCHATRDAVGTNLPLQLGFSTGVNLVAVPTGYVDTENNTEFTRVNAKPPPGDQFKHLIPLMYKGLPWNVVR 6065
Cdd:cd21660   80 RGWLGFDVEGAHVCGDNVGTNVPLQLGFSNGVDFVVQPEGCVVTENGNSIKPVKARAPPGEQFTHLIPLMRKGQPWSVVR 159
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 6066 IKIVQMLSDTLKGLSDRVVFVLWAHGFELTSMKYFVKIGPERTcCLCDKRATCFSTSSDTYACWNHSVGFDYVYNPFMID 6145
Cdd:cd21660  160 KRIVQMCCDYLKGLSDILIFVLWAGGLELTTMRYFVKIGPVKH-CHCGKEATCYNSVSHAYCCFKHALGCDYLYNPYVID 238
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 6146 VQQWGFTGNLQSNHDQHCQVHGNAHVASCDAIMTRCLAVHECFVKRVDWSVEYPIIGDELRVNSACRKVQHMVVKSALLA 6225
Cdd:cd21660  239 IQQWGYTGSLSLNHHEHCNVHRNEHVASGDAIMTRCLAIYDCFVKNVDWSITYPFIANEKAINKSGRVVQSHVMRAALKL 318
                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 6226 DKFPVLHDIGNPKAIKCVpQAEVEWKFYDAQPCSDKAYKIEelfYSYATHhdKFTDGVCLFWNCNVDRYPANAIVCRFDT 6305
Cdd:cd21660  319 YNPKAIHDIGNPKGIRCA-VTDASWYCYDKQPINSNVKTLE---YDYITH--GQMDGLCLFWNCNVDMYPEFSIVCRFDT 392
                        410       420       430       440       450       460       470       480
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 6306 RVLSNLNLPGCDGGSLYVNKHAFHTPAFDKSAFTNLKQLPFFYYSDSPCEshgkqVVSD-IDYVPLKSATCITRCNLGGA 6384
Cdd:cd21660  393 RCRSKLNLEGCNGGSLYVNNHAFHTPAFDKRAFAKLKPMPFFFYDDSECD-----KVQDqVNYVPLRANNCITRCNIGGA 467
                        490       500       510       520
                 ....*....|....*....|....*....|....*....|..
gi 30027621 6385 VCRHHANEYRQYLDAYNMMISAGFSLWIYKQFDTYNLWNTFT 6426
Cdd:cd21660  468 VCSKHAALYHAYVEAYNTFTQAGFTIWVPTSFDLYNLWQTFV 509
Corona_RPol_N pfam06478
Coronavirus RPol N-terminus; This family covers the N-terminal region of the coronavirus ...
4383-4735 0e+00

Coronavirus RPol N-terminus; This family covers the N-terminal region of the coronavirus RNA-directed RNA Polymerase.


Pssm-ID: 428967  Cd Length: 353  Bit Score: 715.78  E-value: 0e+00
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621   4383 VSAARLTPCGTGTSTDVVYRAFDIYNEKVAGFAKFLKTNCCRFQEKDEEGNLLDSYFVVKRHTMSNYQHEETIYNLVKDC 4462
Cdd:pfam06478    1 SSAARLEPCASGTDPDVVYRAFDIYNKDVAGIGKFLKTNCCRFQEVDKDGNLLDSYFVVKRCTKSVYEHEESCYNLLKDC 80
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621   4463 PAVAVHDFFKFRVDGDMVPHISRQRLTKYTMADLVYALRHFDEGNCDTLKEILVTYNCCDDDYFNKKDWYDFVENPDILR 4542
Cdd:pfam06478   81 GVVAEHDFFKFDKGGDMVPNISRQDLTKYTMMDLCYALRHFDEKDCEVLKEILVTYGCCEEDYFEKKDWYDPVENPDIYR 160
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621   4543 VYANLGERVRQSLLKTVQFCDAMRDAGIVGVLTLDNQDLNGNWYDFGDFVQVAPGCGVPIVDSYYSLLMPILTLTRALAA 4622
Cdd:pfam06478  161 VYAKLGPIVRRALLKTVAFCDAMVEAGLVGVLTLDNQDLNGNFYDFGDFVKTAPGCGVPVVDSYYSYMMPIMTMTHALAS 240
                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621   4623 ESHMDADLAKPLIKWDLLKYDFTEERLCLFDRYFKYWDQTYHPNCINCLDDRCILHCANFNVLFSTVFPPTSFGPLVRKI 4702
Cdd:pfam06478  241 ECFVDSDLGKDYKKYDLLKYDFTEEKLELFDKYFKYWDQTYHPNCVDCLDDRCILHCANFNVLFSTVIPNTAFGPLVRKV 320
                          330       340       350
                   ....*....|....*....|....*....|...
gi 30027621   4703 FVDGVPFVVSTGYHFRELGVVHNQDVNLHSSRL 4735
Cdd:pfam06478  321 FVDGVPFVVTAGYHFKELGVVMNQDVNTHSSRL 353
betaCoV_Nsp13-helicase cd21722
helicase domain of betacoronavirus non-structural protein 13; This model represents the ...
5552-5891 0e+00

helicase domain of betacoronavirus non-structural protein 13; This model represents the helicase domain of non-structural protein 13 (Nsp13) from betacoronavirus, including pathogenic human viruses such as Severe acute respiratory syndrome coronavirus (SARS-CoV), SARS-CoV2 (also called 2019 novel CoV or 2019-nCoV), and Middle East respiratory syndrome-related (MERS) CoV. Helicases catalyze NTP-dependent unwinding of nucleic acid duplexes into single strands and are classified based on the arrangement of conserved motifs into six superfamilies. CoV Nsp13 is a member of the helicase superfamily 1 (SF1); SF1 and SF2 helicases do not form toroidal structures, while SF3-6 helicases do. Nsp13 is a component of the viral RNA synthesis replication and transcription complex (RTC). It is a multidomain protein containing a Cys/His rich zinc-binding domain (CH/ZBD), a stalk domain, a 1B domain involved in nucleic acid substrate binding, and a SF1 helicase core.


Pssm-ID: 409655 [Multi-domain]  Cd Length: 340  Bit Score: 707.72  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 5552 GLYPTLNISDEFSSNVANYQKVGMQKYSTLQGPPGTGKSHFAIGLALYYPSARIVYTACSHAAVDALCEKALKYLPIDKC 5631
Cdd:cd21722    1 GLYPTYNVPEEFQNNVVNYQKIGMKRYCTVQGPPGTGKSHLAIGLAVYYPTARVVYTACSHAAVDALCEKAFKFLNINKC 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 5632 SRIIPARARVECFDKFKVNSTLEQYVFCTVNALPETTADIVVFDEISMATNYDLSVVNARLRAKHYVYIGDPAQLPAPRT 5711
Cdd:cd21722   81 SRIIPAKARVECYDKFKVNDTSRQYVFSTINALPETVTDILVVDEVSMCTNYDLSVINARVRAKHIVYIGDPAQLPAPRT 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 5712 LLTKGTLEPEYFNSVCRLMKTIGPDMFLGTCRRCPAEIVDTVSALVYDNKLKAHKDKSAQCFKMFYKGVITHDVSSAINR 5791
Cdd:cd21722  161 LLTKGTLEPEYFNSVTRLMCCLGPDIFLGTCYRCPKEIVDTVSALVYDNKLKAKKDNSGQCFKVYYKGSVTHDSSSAINR 240
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 5792 PQIGVVREFLTRNPAWRKAVFISPYNSQNAVASKILGLPTQTVDSSQGSEYDYVIFTQTTETAHSCNVNRFNVAITRAKI 5871
Cdd:cd21722  241 PQIYLVKKFLKANPAWSKAVFISPYNSQNAVARRVLGLQTQTVDSSQGSEYDYVIYCQTAETAHSVNVNRFNVAITRAKK 320
                        330       340
                 ....*....|....*....|
gi 30027621 5872 GILCIMSDRDLYDKLQFTSL 5891
Cdd:cd21722  321 GILCVMSSMQLFESLQFTEL 340
CoV_Nsp13-helicase cd21718
helicase domain of coronavirus non-structural protein 13; This model represents the helicase ...
5552-5891 0e+00

helicase domain of coronavirus non-structural protein 13; This model represents the helicase domain of non-structural protein 13 (Nsp13) from alpha-, beta-, gamma-, and deltacoronavirus, including pathogenic human viruses such as Severe acute respiratory syndrome coronavirus (SARS-CoV), SARS-CoV2 (also called 2019 novel CoV or 2019-nCoV), and Middle East respiratory syndrome-related (MERS) CoV. Helicases catalyze NTP-dependent unwinding of nucleic acid duplexes into single strands and are classified based on the arrangement of conserved motifs into six superfamilies. CoV Nsp13 is a member of the helicase superfamily 1 (SF1); SF1 and SF2 helicases do not form toroidal structures, while SF3-6 helicases do. Nsp13 is a component of the viral RNA synthesis replication and transcription complex (RTC). It is a multidomain protein containing a Cys/His rich zinc-binding domain (CH/ZBD), a stalk domain, a 1B domain involved in nucleic acid substrate binding, and a SF1 helicase core.


Pssm-ID: 409652 [Multi-domain]  Cd Length: 341  Bit Score: 673.86  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 5552 GLYPTLNISDEFSSNVANYQKVGMQKYSTLQGPPGTGKSHFAIGLALYYPSARIVYTACSHAAVDALCEKALKYLPIDKC 5631
Cdd:cd21718    1 GLWPGNVIPHDFSNHVPSYQKIGKQKYTTVQGPPGTGKSHFAIGLALYYPGARIVYTACSHAAVDALCEKASKWLPNDKC 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 5632 SRIIPARARVECFDKFKVNSTLEQYVFCTVNALPETTADIVVFDEISMATNYDLSVVNARLRAKHYVYIGDPAQLPAPRT 5711
Cdd:cd21718   81 SRIVPQRARVECFDGFKVNNTNAQYIFSTINALPECSADIVVVDEVSMCTNYDLSVVNARLKYKHIVYVGDPAQLPAPRT 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 5712 LLTKGTLEPEYFNSVCRLMKTIGPDMFLGTCRRCPAEIVDTVSALVYDNKLKAHKDKSAQCFKMFYKGVITHDVSSAINR 5791
Cdd:cd21718  161 LLTEGSLEPKDYNVVTRLMVGSGPDVFLSKCYRCPKEIVDTVSKLVYDNKLKAIKPKSRQCFKTFGKGDVRHDNGSAINR 240
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 5792 PQIGVVREFLTRNPAWRKAVFISPYNSQNAVASKILGLPTQTVDSSQGSEYDYVIFTQTTETAHSCNVNRFNVAITRAKI 5871
Cdd:cd21718  241 PQLEFVKRFLDRNPRWRKAVFISPYNAMNNRASRLLGLSTQTVDSSQGSEYDYVIFCQTTDTAHALNINRFNVAITRAKH 320
                        330       340
                 ....*....|....*....|.
gi 30027621 5872 GILCIMSD-RDLYDKLQFTSL 5891
Cdd:cd21718  321 GILVIMRDeNDLYNALQFKSL 341
gammaCoV_Nsp14 cd21658
nonstructural protein 14 of gammacoronavirus; Nonstructural protein 14 (Nsp14) of coronavirus ...
5907-6426 0e+00

nonstructural protein 14 of gammacoronavirus; Nonstructural protein 14 (Nsp14) of coronavirus (CoV) plays an important role in viral replication and transcription. It consists of 2 domains with different enzymatic activities: an N-terminal exoribonuclease (ExoN) domain and a C-terminal cap (guanine-N7) methyltransferase (N7-MTase) domain. ExoN is important for proofreading and therefore, the prevention of lethal mutations. The association of Nsp14 with Nsp10 stimulates its ExoN activity; the complex hydrolyzes double-stranded RNA in a 3' to 5' direction as well as a single mismatched nucleotide at the 3'-end mimicking an erroneous replication product. The Nsp10/Nsp14 complex may function in a replicative mismatch repair mechanism. N7-MTase functions in mRNA capping. Nsp14 can methylate GTP, dGTP as well as cap analogs GpppG, GpppA and m7GpppG. The accumulation of m7GTP or Nsp14 has been found to interfere with protein translation of cellular mRNAs.


Pssm-ID: 394957  Cd Length: 518  Bit Score: 673.50  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 5907 TGLFKDCSKIITGLHPTQAPTHLSVDIKFKT-EGLCVDIP-GIPKDMTYRRLISMMGFKMNYQVNGYPNMFITREEAIRH 5984
Cdd:cd21658    1 TGLFKICNKEFSGVHPAYAVTTKALAATYKVnDELAALVNvEAGSEITYKHLISLLGFKMSVNVEGCHNMFITRDEAIRN 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 5985 VRAWIGFDVEGCHATRDAVGTNLPLQLGFSTGVNLVAVPTGYVDTENNTEFTRVNAKPPPGDQFKHLIPLMYKGLPWNVV 6064
Cdd:cd21658   81 VRGWVGFDVEATHACGTNIGTNLPFQVGFSTGADFVVTPEGLVDTSIGNNFEPVNSKAPPGEQFNHLRALFKSAKPWHVI 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 6065 RIKIVQMLSDTLKGLSDRVVFVLWAHGFELTSMKYFVKIGPERTCClCDKRATCFSTSSDTYACWNHSVGFDYVYNPFMI 6144
Cdd:cd21658  161 RPRIVQMLADNLCNVSDCVVFVTWCHGLELTTLRYFVKIGKEQVCS-CGSRATTFNSHTQAYACWKHCLGFDFVYNPLLV 239
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 6145 DVQQWGFTGNLQSNHDQHCQVHGNAHVASCDAIMTRCLAVHECFVKRVDWSVEYPIIGDELRVNSACRKVQHMVVKSALL 6224
Cdd:cd21658  240 DIQQWGYSGNLQFNHDLHCNVHGHAHVASADAIMTRCLAINNAFCQDVNWDLTYPHIANEDEVNSSCRYLQRMYLNACVD 319
                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 6225 ADKFPVLHDIGNPKAIKCVPQAEVEWKFYDAQPCSDkayKIEELFYSYATHHDKFTDGVCLFWNCNVDRYPANAIVCRFD 6304
Cdd:cd21658  320 ALKVNVVYDIGNPKGIKCVRRGDVSFRFYDKNPIVP---NVKQFEYDYNQHKDKFADGLCMFWNCNVDCYPDNSLVCRYD 396
                        410       420       430       440       450       460       470       480
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 6305 TRVLSNLNLPGCDGGSLYVNKHAFHTPAFDKSAFTNLKQLPFFYYSDSPCESHGKQVVSDiDYVPLKSATCITRCNLGGA 6384
Cdd:cd21658  397 TRNLSVFNLPGCNGGSLYVNKHAFHTPKFDRISFRNLKAMPFFFYDSSPCDTIQVDGVAQ-DLVSLATKDCITKCNIGGA 475
                        490       500       510       520
                 ....*....|....*....|....*....|....*....|..
gi 30027621 6385 VCRHHANEYRQYLDAYNMMISAGFSLWIYKQFDTYNLWNTFT 6426
Cdd:cd21658  476 VCKKHAQMYAEFVTSYNAAVTAGFTFWVTNNFNPYNLWKSFS 517
NSP13 pfam06460
Coronavirus NSP13; This family covers the NSP13 region of the coronavirus polyprotein. This ...
6777-7072 0e+00

Coronavirus NSP13; This family covers the NSP13 region of the coronavirus polyprotein. This protein has the predicted function of an mRNA cap-1 methyltransferase function.


Pssm-ID: 399456  Cd Length: 297  Bit Score: 596.02  E-value: 0e+00
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621   6777 SQAWQPGVAMPNLYKMQRMLLEKCDLQNYGENAVIPKGIMMNVAKYTQLCQYLNTLTLAVPYNMRVIHFGAGSDKGVAPG 6856
Cdd:pfam06460    1 SAAWKPGYSMPNLYKMQRMCLEPCNLYNYGAGITLPSGIMMNVAKYTQLCQYLNTTTLCVPHNMRVLHLGAGSDKGVAPG 80
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621   6857 TAVLRQWLPTGTLLVDSDLNDFVSDADSTLIGDCATVHTANKWDLIISDMYDPRTKHVTKENDSKEGFFTYLCGFIKQKL 6936
Cdd:pfam06460   81 SAVLRQWLPTGTILVDNDLNDYVSDADFSVTGDCATVYTEDKFDLIISDMYDPRTKHIDGENVSKDGFFTYLCGFIKEKL 160
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621   6937 ALGGSIAVKITEHSWNADLYKLMGHFSWWTAFVTNVNASSSEAFLIGANYLGK-PKEQIDGYTMHANYIFWRNTNPIQLS 7015
Cdd:pfam06460  161 ALGGSIAIKITEFSWNADLYELMQRFSWWTMFCTNVNASSSEAFLIGINYLGKsPKEQIDGKTMHANYIFWRNSTPMQLS 240
                          250       260       270       280       290
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 30027621   7016 SYSLFDMSKFPLKLRGTAVMSLKENQINDMIYSLLEKGRLIIRENNRVVVSSDILVN 7072
Cdd:pfam06460  241 AYSLFDMSKFPLKLKGTAVVSLKENQINDMVLSLLEKGKLLVRDNGKVVFFSDSLVN 297
betaCoV_Nsp5_Mpro cd21666
betacoronavirus non-structural protein 5, also called Main protease (Mpro); This subfamily ...
3244-3540 0e+00

betacoronavirus non-structural protein 5, also called Main protease (Mpro); This subfamily contains the coronavirus (CoV) non-structural protein 5 (Nsp5) also called the Main protease (Mpro), or 3C-like protease (3CLpro), found in betacoronaviruses. CoVs utilize a multi-subunit replication/transcription machinery. A set of non-structural proteins (Nsps) generated as cleavage products of the ORF1a and ORF1ab viral polyproteins assemble to facilitate viral replication and transcription. Mpro/Nsp5 is a key enzyme in this process, making it a high value target for the development of anti-coronavirus therapeutics. These enzymes belong to the MEROPS peptidase C30 family, where the active site residues His and Cys form a catalytic dyad. The structures of Mpro/Nsp5 consist of three domains with the first two containing anti-parallel beta barrels and the third consisting of an arrangement of alpha-helices. The catalytic residues are found in a cleft between the first two domains. Mpro requires a Gln residue in the P1 position of the substrate and space for only small amino-acid residues such as Gly, Ala, or Ser in the P1' position; since there is no known human protease with a specificity for Gln at the cleavage site of the substrate, these viral proteases are suitable targets for the development of antiviral drugs.


Pssm-ID: 394887  Cd Length: 297  Bit Score: 577.43  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 3244 RKMAFPSGKVEGCMVQVTCGTTTLNGLWLDDTVYCPRHVICTAEDMLNPNYEDLLIRKSNHSFLVQAGNVQLRVIGHSMQ 3323
Cdd:cd21666    1 RKMAFPSGKVEGCMVQVTCGTMTLNGLWLDDTVYCPRHVICTAEDMLNPNYEDLLIRKTNHSFLVQAGNVQLRVIGHSMQ 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 3324 NCLLRLKVDTSNPKTPKYKFVRIQPGQTFSVLACYNGSPSGVYQCAMRPNHTIKGSFLNGSCGSVGFNIDYDCVSFCYMH 3403
Cdd:cd21666   81 GCLLRLTVDTSNPKTPKYKFVRVKPGQTFSVLACYNGSPSGVYQCAMRPNHTIKGSFLCGSCGSVGYNIDGDCVSFCYMH 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 3404 HMELPTGVHAGTDLEGKFYGPFVDRQTAQAAGTDTTITLNVLAWLYAAVINGDRWFLNRFTTTLNDFNLVAMKYNYEPLT 3483
Cdd:cd21666  161 QMELPTGVHTGTDLEGKFYGPFVDRQTAQAAGTDTTITLNVLAWLYAAVLNGDRWFVNRFTTTLNDFNLWAMKYNYEPLT 240
                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 30027621 3484 QDHVDILGPLSAQTGIAVLDMCAALKELLQNGMNGRTILGSTILEDEFTPFDVVRQC 3540
Cdd:cd21666  241 QDHVDILDPLAAQTGIAVEDMLAALKELLQGGMQGRTILGSTILEDEFTPFDVVRQC 297
alphaCoV_Nsp13-helicase cd21723
helicase domain of alphacoronavirus non-structural protein 13; This model represents the ...
5553-5891 0e+00

helicase domain of alphacoronavirus non-structural protein 13; This model represents the helicase domain of non-structural protein 13 (Nsp13) from alphacoronavirus, including Porcine epidemic diarrhea virus and Human coronavirus (CoV) NL63. Helicases catalyze NTP-dependent unwinding of nucleic acid duplexes into single strands and are classified based on the arrangement of conserved motifs into six superfamilies. CoV Nsp13 is a member of the helicase superfamily 1 (SF1); SF1 and SF2 helicases do not form toroidal structures, while SF3-6 helicases do. Nsp13 is a component of the viral RNA synthesis replication and transcription complex (RTC). It is a multidomain protein containing a Cys/His rich zinc-binding domain (CH/ZBD), a stalk domain, a 1B domain involved in nucleic acid substrate binding, and a SF1 helicase core.


Pssm-ID: 409656 [Multi-domain]  Cd Length: 340  Bit Score: 563.20  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 5553 LYPTLNISDEFSSNVANYQKVGMQKYSTLQGPPGTGKSHFAIGLALYYPSARIVYTACSHAAVDALCEKALKYLPIDKCS 5632
Cdd:cd21723    2 LHPAFNISEAYSNLVPYYQLIGKQKITTIQGPPGSGKSHCVIGLGLYYPGARIVFTACSHAAVDSLCVKAATAYSVDKCS 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 5633 RIIPARARVECFDKFKVNSTLEQYVFCTVNALPETTADIVVFDEISMATNYDLSVVNARLRAKHYVYIGDPAQLPAPRTL 5712
Cdd:cd21723   82 RIIPARARVECYDGFKPNNTSAQYIFSTVNALPECNADIVVVDEVSMCTNYDLSVINQRVSYKHIVYVGDPQQLPAPRTM 161
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 5713 LTKGTLEPEYFNSVCRLMKTIGPDMFLGTCRRCPAEIVDTVSALVYDNKLKAHKDKSAQCFKMFYKGVITHDVSSAINRP 5792
Cdd:cd21723  162 ITRGVLEPKDYNVVTQRMCALGPDVFLHKCYRCPAEIVNTVSELVYENKFKPVHPESKQCFKIFCKGNVQVDNGSSINRR 241
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 5793 QIGVVREFLTRNPAWRKAVFISPYNSQNAVASKILGLPTQTVDSSQGSEYDYVIFTQTTETAHSCNVNRFNVAITRAKIG 5872
Cdd:cd21723  242 QLDVVKMFLAKNPKWSKAVFISPYNSQNYVASRVLGLQIQTVDSSQGSEYDYVIYTQTSDTAHACNVNRFNVAITRAKKG 321
                        330
                 ....*....|....*....
gi 30027621 5873 ILCIMSDRDLYDKLQFTSL 5891
Cdd:cd21723  322 ILCVMCDKELFDALKFFEL 340
TM_Y_CoV_Nsp3_C cd21686
C-terminus of coronavirus non-structural protein 3, including transmembrane and Y domains; ...
2209-2739 9.94e-174

C-terminus of coronavirus non-structural protein 3, including transmembrane and Y domains; This model represents the C-terminus of non-structural protein 3 (Nsp3) from alpha-, beta-, gamma-, and deltacoronavirus, including highly pathogenic betacoronaviruses such as Severe acute respiratory syndrome-related coronavirus (SARS-CoV), SARS-CoV2 (also called 2019 novel CoV or 2019-nCoV), and Middle East respiratory syndrome-related (MERS) CoV. This conserved C-terminus includes two transmembrane (TM) regions TM1 and TM2, an ectodomain (3Ecto) between the TM1 and TM2 that is glycosylated and located on the lumenal side of the ER, an amphiphatic region (AH1) that is not membrane-spanning, and a large Y domain of approximately 370 residues. Nsp3 is a large multi-functional multi-domain protein that is an essential component of the replication/transcription complex (RTC), which carries out RNA synthesis, RNA processing, and interference with the host cell innate immune system. In SARS-CoV and murine hepatitis virus (MHV), the TM1, 3Ecto and TM2 domains are important for the papain-like protease (PL2pro) domain to process Nsp3-Nsp4 cleavage. It has also been shown that the interaction of 3Ecto with the lumenal loop of Nsp4 is essential for ER rearrangements in cells infected with SARS-CoV or MHV. The Y domain, located at the cytosolic side of the ER, consists of the Y1 and CoV-Y subdomains, which are conserved in nidovirus and coronavirus, respectively. Functional information about the Y domain is limited; it has been shown that Nsp3 binding to Nsp4 is less efficient without the Y domain.


Pssm-ID: 409657  Cd Length: 476  Bit Score: 544.86  E-value: 9.94e-174
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 2209 WLLLLSICLGSLICVTAAFGVL-----LSNFGAPSYCNGVRELYLNSSNVTTMDFCEGSFPCSICLSGLDSLDSYPALET 2283
Cdd:cd21686    1 LFYLASVLFKSLAPFLLLPAVLyllnsGYTLGTGSYCKTYWPGYYNSTQHDYNSYCAGDLVCQVCLDGQDSLHLYPHLRV 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 2284 IQVTISSykldltilglaaeWVLAYMLFTKFFYLLGLSAIMQVFFGYFASHFIS--NSWLMWFIISIvqmAPVSAMVRMY 2361
Cdd:cd21686   81 VQQPLQT-------------TDYTVYALSLILYLANMTLFMGTFIVTFFVNFYGvgIPFYGWLLIDV---PQSAFMMTFS 144
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 2362 IFFasFYYIWKSYVHIMDGCTSSTCMMCYKRNRATRVECTTIVNGMKRSFYVYANGGRGFCKTHNWNCLNCDTFCTGSTF 2441
Cdd:cd21686  145 VFF--FYYVLKFFVHVTHGCKIPTCMVCAKLARPPRVEVETVVQGRKYSFYVYTNGGFTFCKEHNFYCKNCDLYGPGCTF 222
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 2442 ISDEVARDLSLQFKRPINPTDQSSYIVDSVAVKNgalHLYFDKAGQKTYERHPLSHFVNL-DNLRANNTkgslpinvivf 2520
Cdd:cd21686  223 ISDEVAEELSRATKLSVKPTAPAFLLVDDVEVQN---DVVFARAKYNQNAHVSLSKFSDIpDFIIAANF----------- 288
                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 2521 dgKSKCDE-SASKSASVYYSQLMCQPILLLDQVLVSDVGDSTEVsvkmfdayvdTFSATFSVPMEKLKALVAtahselak 2599
Cdd:cd21686  289 --GSNCEQlSTAKNAAVYYSQDLCKPILILDQALSRPIDNYQEV----------ASRIEKYYPVAKIKPTGD-------- 348
                        410       420       430       440       450       460       470       480
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 2600 gvaldgvlstFVSAARQGvvdTDVDTKDVIECLK-LSHHSDLEVTGDSCNNFMLTYNKVENMTPRDLGAcIDCNARHINA 2678
Cdd:cd21686  349 ----------IFTDIKQG---TDGEASDSAINAAvLAHQRDVEFTGDSFNNILPSYAKDESKLTAEDQA-MSVIAESGNA 414
                        490       500       510       520       530       540
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 30027621 2679 QVAKSHNVSLIWNVKDYMSLSEQLRKQIRSAAKKNNIPFRLTCATTRQVVNVITTK-ISLKG 2739
Cdd:cd21686  415 NVNVKGTIPVVWLVADFIRLSEQARKYIISAAKKNGVTFALTPSTLRMRGNIATQPlIAIKK 476
CoV_Nsp5_Mpro cd21646
coronavirus non-structural protein 5, also called Main protease (Mpro); This family contains ...
3244-3539 2.86e-169

coronavirus non-structural protein 5, also called Main protease (Mpro); This family contains the coronavirus (CoV) non-structural protein 5 (Nsp5) also called the Main protease (Mpro), or 3C-like protease (3CLpro). CoVs utilize a multi-subunit replication/transcription machinery. A set of non-structural proteins (Nsps) generated as cleavage products of the ORF1a and ORF1ab viral polyproteins assemble to facilitate viral replication and transcription. Mpro/Nsp5 is a key enzyme in this process, making it a high value target for the development of anti-coronavirus therapeutics. These enzymes belong to the MEROPS peptidase C30 family, where the active site residues His and Cys form a catalytic dyad. The structures of Mpro/Nsp5 consist of three domains with the first two containing anti-parallel beta barrels and the third consisting of an arrangement of alpha-helices. The catalytic residues are found in a cleft between the first two domains. Mpro/Nsp5 requires a Gln residue in the P1 position of the substrate and space for only small amino-acid residues such as Gly, Ala, or Ser in the P1' position; since there is no known human protease with a specificity for Gln at the cleavage site of the substrate, these viral proteases are suitable targets for the development of antiviral drugs.


Pssm-ID: 394885  Cd Length: 292  Bit Score: 523.91  E-value: 2.86e-169
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 3244 RKMAFPSGKVEGCMVQVTCGTTTLNGLWLDDTVYCPRHVICTAEDmLNPNYEDLLIRKSNHSFLVQAGNVQLRVIGHSMQ 3323
Cdd:cd21646    1 KKMAQPSGKVERCMVSVTYGSTTLNGLWLDDTVYCPRHVICKSTT-SGPDYDDLLSRARNHNFSVQSGGVQLRVVGVTMQ 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 3324 NCLLRLKVDTSNPKTPKYKFVRIQPGQTFSVLACYNGSPSGVYQCAMRPNHTIKGSFLNGSCGSVGFNIDYDCVSFCYMH 3403
Cdd:cd21646   80 GALLRLKVDTSNPHTPKYKFVTVKPGDSFTILACYNGSPSGVYGVNMRSNYTIKGSFLNGACGSVGYNIDGGTVEFCYMH 159
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 3404 HMELPTGVHAGTDLEGKFYGPFVDRQTAQAAGTDTTITLNVLAWLYAAVINGDRWFLNRFTTTLNDFNLVAMKYNYEPLT 3483
Cdd:cd21646  160 HLELPNGCHTGTDLTGKFYGPYVDQQVAQVEGADTLITDNVVAWLYAAIINGDRWWLNSSRTTVNDFNEWAMANGFTPVS 239
                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 30027621 3484 QdhVDILGPLSAQTGIAVLDMCAALKELLQNGmNGRTILGSTILEDEFTPFDVVRQ 3539
Cdd:cd21646  240 Q--VDCLSILAAKTGVSVERLLAAIQQLHQNF-GGKQILGSTSLEDEFTPEDVVRQ 292
Peptidase_C30 pfam05409
Coronavirus endopeptidase C30; Corresponds to Merops family C30. These peptidases are involved ...
3269-3546 1.80e-164

Coronavirus endopeptidase C30; Corresponds to Merops family C30. These peptidases are involved in viral polyprotein processing in replication.


Pssm-ID: 398852  Cd Length: 274  Bit Score: 509.29  E-value: 1.80e-164
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621   3269 GLWLDDTVYCPRHVICTAEDMLnPNYEDLLIRKSNHSFLVQAGNVQLRVIGHSMQNCLLRLKVDTSNPKTPKYKFVRIQP 3348
Cdd:pfam05409    1 GLWLGDTVYCPRHVIGSFTGML-PQYEHLLSIARNHDFCVVSGGVQLTVVSAKMQGAILVLKVHTNNPNTPKYKFVRLKP 79
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621   3349 GQTFSVLACYNGSPSGVYQCAMRPNHTIKGSFLNGSCGSVGFNIDYDCVSFCYMHHMELPTGVHAGTDLEGKFYGPFVDR 3428
Cdd:pfam05409   80 GESFTILAAYDGCPQGVYHVTMRSNHTIKGSFLNGACGSVGYNLKGGTVCFVYMHHLELPNGSHTGTDLEGVFYGPYVDE 159
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621   3429 QTAQAAGTDTTITLNVLAWLYAAVINGDRWFLNRFTTTLNDFNLVAMKYNYEPLTQDHVdiLGPLSAQTGIAVLDMCAAL 3508
Cdd:pfam05409  160 EVAQLEGTDQTYTDNVVAWLYAAIINGPRWFLASTTVSLEDFNAWAMTNGFTPFPCEDA--ILGLAAKTGVSVERLLAAI 237
                          250       260       270
                   ....*....|....*....|....*....|....*...
gi 30027621   3509 KElLQNGMNGRTILGSTILEDEFTPFDVVRQCSGVTFQ 3546
Cdd:pfam05409  238 KV-LNNGFGGRTILGSPSLEDEFTPEDVYNQMAGVTLQ 274
deltaCoV_Nsp14 cd21657
nonstructural protein 14 of deltacoronavirus; Nonstructural protein 14 (Nsp14) of coronavirus ...
5907-6426 2.58e-160

nonstructural protein 14 of deltacoronavirus; Nonstructural protein 14 (Nsp14) of coronavirus (CoV) plays an important role in viral replication and transcription. It consists of 2 domains with different enzymatic activities: an N-terminal exoribonuclease (ExoN) domain and a C-terminal cap (guanine-N7) methyltransferase (N7-MTase) domain. ExoN is important for proofreading and therefore, the prevention of lethal mutations. The association of Nsp14 with Nsp10 stimulates its ExoN activity; the complex hydrolyzes double-stranded RNA in a 3' to 5' direction as well as a single mismatched nucleotide at the 3'-end mimicking an erroneous replication product. The Nsp10/Nsp14 complex may function in a replicative mismatch repair mechanism. N7-MTase functions in mRNA capping. Nsp14 can methylate GTP, dGTP as well as cap analogs GpppG, GpppA and m7GpppG. The accumulation of m7GTP or Nsp14 has been found to interfere with protein translation of cellular mRNAs.


Pssm-ID: 394956  Cd Length: 508  Bit Score: 507.86  E-value: 2.58e-160
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 5907 TGLFKDCSKIITGLHPTQAPTHLSVDIKFKTEGLCVDIPGIPKD--MTYRRLISMMGFKMNYQVNGYPNMFITREEAIRH 5984
Cdd:cd21657    1 TPLFKRCGYEYNGVHPAHALTWHDCGAEYRCEEPLAKLVGVADGtlISYKTLVSALGFLPSLKIDTYHNMFLTKDACRAY 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 5985 VRAWIGFDVEGCHATRDAVGTNLPLQLGFSTGVNLVAVPTGYVDTENNTEFTRVNAKPPPGDQFKHLIPLMYKGLPWNVV 6064
Cdd:cd21657   81 VQSWIGIDVEAAHAVKPNVGTNLPLQIGFSTGKNFSVTPEGIWVNEHGSCTEPVPAKIPPGEQFRHLKKDMRQARPWKVV 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 6065 RIKIVQMLSDTLKGlSDRVVFVLWAHGFELTSMKYFVKIGPERTcCLCDKRAtCFSTSSDtYACWNH----SVGFDYVYN 6140
Cdd:cd21657  161 RREIAAHLAEVAPH-TDYICFVTWAHQLELATMRYFVKIGMEEK-CFCGRRA-CFTNGTE-FACKAHhsltTPQCDYVYN 236
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 6141 PFMIDVQQWGFTGNLQSNHDQHCQVHGNAHVASCDAIMTRCLAVHECFvKRVDWSVEYPIIGDELRVNSACRKVQHMVVK 6220
Cdd:cd21657  237 PFLIDVATWGFSGRLSTNHDAVCTYHANAHVASADAIMTVCLAIHELF-STVDWDLEFPVTPEQSQLNKACRLVQANYLN 315
                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 6221 SALLADKFPVLHDIGNPKAIKCVPQAEVEWKFYDAQPCSDkayKIEELFYSyATHHDKFTDGVCLFWNCNVDRYPANAIV 6300
Cdd:cd21657  316 ILLTTTKATVVHDIGNPKGIPIVRKPGVKYHFYDQAPIVK---HVQKLKYK-PEMEARFTDGLTMFWNCNVDTYPANALV 391
                        410       420       430       440       450       460       470       480
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 6301 CRFDTRVLSNLNLPgcDGGSLYVNKHAFHTPAFDKSAFTNLKQLPFFYYSDSPCESHGKQVVSDIDyvplksatCITRCN 6380
Cdd:cd21657  392 CRYDTHRQKHLIGP--NGSALYVNKHAFLTPEMHTYATHKLTLAPLVYYSTTDCSSEQPIVVTYRD--------CVTRCN 461
                        490       500       510       520
                 ....*....|....*....|....*....|....*....|....*.
gi 30027621 6381 LGGAVCRHHANEYRQYLDAYNMMISAGFSLWIYKQFDTYNLWNTFT 6426
Cdd:cd21657  462 TGTTICPTHALEYQEFINAYNLMARHGFNVYIPRNVNVYNCWLTFT 507
betaCoV_PLPro cd21732
betacoronavirus papain-like protease; This model represents the papain-like protease (PLPro) ...
1543-1845 1.12e-159

betacoronavirus papain-like protease; This model represents the papain-like protease (PLPro) found in non-structural protein 3 (Nsp3) of betacoronavirus, including highly pathogenic betacoronaviruses such as Severe acute respiratory syndrome-related coronavirus (SARS-CoV), SARS-CoV2 (also called 2019 novel CoV or 2019-nCoV), and Middle East respiratory syndrome-related (MERS) CoV. CoVs utilize a multi-subunit replication/transcription machinery. A set of non-structural proteins (Nsps) generated as cleavage products of the ORF1a and ORF1ab viral polyproteins assemble to facilitate viral replication and transcription. PLPro is a key enzyme in this process, making it a high value target for the development of anti-coronavirus therapeutics. PLPro, which belongs to the MEROPS peptidase C16 family, participates in the proteolytic processing of the N-terminal region of the replicase polyprotein; it can cleave Nsp1|Nsp2, Nsp2|Nsp3, and Nsp3|Nsp4 sites and its activity is dependent on zinc. In SARS-CoV and murine hepatitis virus (MHV), the C-terminal non-structural protein 3 region spanning transmembrane regions TM1 and TM2 with 3Ecto domain in between, are important for the PL2pro domain to process Nsp3-Nsp4 cleavage. Besides cleaving the polyproteins, PLPro also possesses a related enzymatic activity to promote virus replication: deubiquitinating (DUB) and de-ISGylating activities. Both, ubiquitin (Ub) and Ub-like interferon-stimulated gene product 15 (ISG15), are involved in preventing viral infection; coronaviruses utilize Ubl-conjugating pathways to counter the pro-inflammatory properties of Ubl-conjugated host proteins via the action of PLPro, which processes both 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains from cellular substrates. The Nsp3 PLPro domain of many of these CoVs has also been shown to antagonize host innate immune induction of type I interferon by interacting with IRF3 and blocking its activation. Interactions of SARS-CoV and MERS-CoV with antiviral interferon (IFN) responses of human cells are remarkably different; high-dose IFN treatment (type I and type III) shows MERS-CoV was substantially more IFN sensitive than SARS-CoV. This may be due to differences in the architecture of the oxyanion hole and of the S3 as well as the S5 specificity sites, despite the overall structures of SARS-CoV and MERS-CoV PLPro being similar.


Pssm-ID: 409649  Cd Length: 304  Bit Score: 496.72  E-value: 1.12e-159
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 1543 KTIKVFTTVDNTNLHTQLVDMSMTYGQQFGPTYLDGADVTKIKPHVNHEGKTFFVLPSDDTLRSEAFEY-YHTLDESFLG 1621
Cdd:cd21732    1 KTIEVLTTVDGVNFRTVLVNNGETFGKQLGNVFCDGVDVTKTKPSAKYEGKVLFQADNLSAEELEAVEYyYGFDDPTFLL 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 1622 RYMSALNHTKKWKFPQVGGLTSIKWADNNCYLSSVLLALQQLEVKFNAPALQEAYYRARAGDAANFCALILAYSNKTVGE 1701
Cdd:cd21732   81 RYYSALAHVKKWKFVVVDGYFSLKQADNNCYLNAACLMLQQLDLKFNTPALQEAYYEFRAGDPLRFVALVLAYGNFTFGE 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 1702 LGDVRETMTHLLQHANLESAKRVLNVVCKHCGQKTTTLTGVEAVMYMGTLSYDNLKTGVSIPCVCGRDATQYLVQQESSF 1781
Cdd:cd21732  161 PDDARDFLRVVLSHADLVSARRVLEEVCKVCGVKQEQRTGVDAVMYFGTLSLDDLYKGYTIDCSCGRKAIRYLVEQVPPF 240
                        250       260       270       280       290       300
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 30027621 1782 VMMSAPPAEYKLQQGTFLCANEYTGNYQCGHYTHITAKETLYRIDGAHLTKMSEYKGPVTDVFY 1845
Cdd:cd21732  241 LLMSNTPTEVPLPTGDFVAANVFTGDESVGHYTHVKNKSLLYLYDAGNVKKTSDLKGPVTDVLY 304
Viral_protease pfam08715
Papain like viral protease; This family of viral proteases are similar to the papain protease ...
1541-1859 3.37e-156

Papain like viral protease; This family of viral proteases are similar to the papain protease and are required for proteolytic processing of the replicase polyprotein. The structure of this protein has shown it adopts a fold similar that of de-ubiquitinating enzymes.


Pssm-ID: 430171  Cd Length: 318  Bit Score: 487.57  E-value: 3.37e-156
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621   1541 EVKTIKVFTTVDNTNLHTQLVDMSMTYGQQFGPTYLDGADVTKIKPHVNHEGKTFFVLPSDDTLRSEAFE---YYHTLDE 1617
Cdd:pfam08715    1 ECKQITIYLTEDGVNYHSIVVKPGDSLGQQFGQVYAKNKDLSGVFPADDVEDKEILYVPTTDWVEFYGFKsilEYYTLDA 80
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621   1618 SFLGRYMSALnhtkKWKFPQVGGLTSIKWADNNCYLSSVLLALQQLEVKFNAPALQEAYYRARAGDAANFCALILAYSNK 1697
Cdd:pfam08715   81 SKYVIYLSAL----TKNVQYVDGFLILKWRDNNCWISSVIVALQAAKIRFKGQFLTEAWAKLLGGDPTDFVAWCYASCTA 156
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621   1698 TVGELGDVRETMTHLLQHANLESAKRVLN-VVCKHCGQKTTTLTGVEAVMYMGTLSYDNLKTGVSIPCVCGRDATQYLVQ 1776
Cdd:pfam08715  157 KVGDFGDANWTLTNLAEHFDAEYTNAFLKkRVCCNCGIKSYELRGLEACIQVRATNLDHFKTGYSNCCVCGANNTDEVIE 236
                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621   1777 QESSFVMMSA---PPAEYKLQQGTFLCAneYTGNYQCGHYTHITAKETLYriDGAHLTKMSEYKGPVTDVFYKETSYTTT 1853
Cdd:pfam08715  237 ASLPYLLLSAtdgPAAVDCLEDGVGTVA--FVGSTNSGHYTYQTAKQAFY--DGAKDRKFGKKSPYVTAVYTRFAFKNET 312

                   ....*.
gi 30027621   1854 IKPVSY 1859
Cdd:pfam08715  313 SLPVAK 318
CoV_NSP3_C pfam19218
Coronavirus replicase NSP3, C-terminal; This family represents the C-terminal region of ...
2240-2726 4.38e-155

Coronavirus replicase NSP3, C-terminal; This family represents the C-terminal region of non-structural protein NSP3 (also known as nsp3). NSP3 is the product of ORF1a. It is found in human SARS coronavirus polyprotein 1a and 1ab, and in related coronavirus polyproteins. It is a multifunctional protein comprising up to 16 different domains and regions. NSP3 binds to viral RNA, nucleocapsid protein, as well as other viral proteins and participates in polyprotein processing.


Pssm-ID: 437055  Cd Length: 463  Bit Score: 490.68  E-value: 4.38e-155
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621   2240 CNGVRELYLNSSNVTTmDFCEGSFPCSICLSGLDSLDSYPALETIQVTISSYKLD--LTILGLAAEWVLAYMLFTKFFYL 2317
Cdd:pfam19218    4 CDGYVDGYSNSSFDKS-DYCNGSLLCKACLSGYDSLHDYPHLKVVQQHVKDPLFFdyTPLAYFAFELFVALALFGGTFVR 82
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621   2318 LGLSAIMQVFFGYFaSHFISNSWLMWFiisiVQMAPVSAMVRMYIFFASFYYIWKSYVHIMDGCTSSTCMMCYKRNRATR 2397
Cdd:pfam19218   83 LFLLYFLQQFVNFF-GVYLGLQDLSWF----LTLIPFDVFLREYVVVFYVIKLYRFFKHVVFGCKKPSCLACSKRARLTR 157
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621   2398 VECTTIVNGMKRSFYVYANGGRGFCKTHNWNCLNCDTFCTGSTFISDEVARDLSLQFKRPINPTDQSSYIVDSVAVKNGA 2477
Cdd:pfam19218  158 VPVSTVVNGSKKSFYVNANGGTKFCKKHNFFCVNCDSYGPGNTFINDEVAEDLSNVTKRSVKPTDPAYYEVDKVEFQDGF 237
                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621   2478 LHLYFDKAGQKTYERHPLSHFVNLDNLRANNTKGSLPINVIVFDgKSKCDESASKSASVYYSQLMCQPILLLDQVLVSDV 2557
Cdd:pfam19218  238 YYLYYGREFWRYYFDVTVSKFSDKEVLKNCNVTGYPLDNFIVYD-NNGSNLANAKNACVYYSQLLCKPIKLVDSNLLSTL 316
                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621   2558 GDSTEVSVKMFDAYVDTFSATFSVPMEKLKALVATAHSelakgvaldgvlstfvsaarqgvVDTDVDTKDVIECLKLSHH 2637
Cdd:pfam19218  317 GDSVDVNGALFDAFVDVLLNSFNVDLSKCKTLIECAKD-----------------------LGSDVDTDSFVNAVQNAHR 373
                          410       420       430       440       450       460       470       480
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621   2638 SDLEVTGDSCNNFMLTYNKV-ENMTPRDLGACIDCNARHINAQVAKSHNVSLIWNVKDYMSLSEQLRKQIRSAAKKNNIP 2716
Cdd:pfam19218  374 YDLLLTDDSFNNFVPTYAKPeDSLSTHDLAVCIRFGAKIVNHNVLKKENVSVVWSADDFNKLSEEARRYIVKAAKKKGVT 453
                          490
                   ....*....|
gi 30027621   2717 FRLTCATTRQ 2726
Cdd:pfam19218  454 FKLTFNKLRA 463
cv_Nsp4_TM cd21473
coronavirus non-structural protein 4 (Nsp4) transmembrane domain; Nsp4 may be involved in ...
2754-3134 1.99e-149

coronavirus non-structural protein 4 (Nsp4) transmembrane domain; Nsp4 may be involved in coronavirus-induced membrane remodeling. In order to assemble the replication-transcription complex (RTC), coronavirus induces the rearrangement of host endoplasmic reticulum (ER) membrane into double membrane vesicles (DMVs), zippered ER, or ER spherules. DMV formation has been observed in SARS-CoV cells overexpressing the three transmembrane-containing non-structural proteins of viral replicase polyprotein 1ab: Nsp3, Nsp4 and Nsp6. Together, Nsp3, Nsp4, and Nsp6 have the ability to induce the formation of DMVs that are similar to those seen in SARS-CoV-infected cells.


Pssm-ID: 394836  Cd Length: 376  Bit Score: 470.92  E-value: 1.99e-149
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 2754 TLLCVLAALVCYIVMPVHTLSIHDGYTNEIIGYKAIQDGVTRDIISTDDCFANKHAGFDAWFSQRGGS-YKNDKSCPVVA 2832
Cdd:cd21473    1 FLWLLLAAILLYAFLPSYSVFTVTVSSFPGYDFKVIENGVLRDIRSTDTCFANKFVNFDSWYQAKYGSvPTNSKSCPIVV 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 2833 AIITREIGFiVPGLPGTVLRaINGDFLHFLPRVFSAVGNICYTPSKLIEYSDFATSACVLAAECTIFKDaMGKPVPYCYD 2912
Cdd:cd21473   81 GVIDDVRGS-VPGVPAGVLL-VGKTLVHFVQTVFFGDTVVCYTPDGVITYDSFYTSACVFNSACTYLTG-LGGRQLYCYD 157
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 2913 TNLLEGSISYSELRPDTRYVLMDGSIIQFPNTYLEGSVRVVTTFDAEYCRHGTCERSEVGICLSTSGRWVLNNEHYRalS 2992
Cdd:cd21473  158 TGLVEGAKLYSDLLPHVRYKLVDGNYIKFPEVILEGGPRIVRTLATTYCRVGECEDSKAGVCVSFDGFWVYNNDYYG--P 235
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 2993 GVFCGVDAMNLIANIFTPLVQPVGALDVSASVVAGGIIAILVTCAAYYFMKFRRVFGEyNHVVAANALLFLMSFTILCLV 3072
Cdd:cd21473  236 GVYCGDGLFDLLTNLLSGFFQPVSVFALSGQLLFNTIVAILAVLACYYVQKFKRAFGD-MSVVVVTVVAAALVNNVLYVV 314
                        330       340       350       360       370       380
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 30027621 3073 PAYSFLPGVYSVFYLYLTFYFTNDVSFLAHLQWFAMFSPIVPFWITAIYVFCISLKHCHWFF 3134
Cdd:cd21473  315 TQNPLLMIVYAVLYFYATLYLTYERAWIMHLGWVVAYGPIAPWWLLALYVVAVLYDYLPWFF 376
betaCoV-Nsp6 cd21560
betacoronavirus non-structural protein 6; Coronaviruses (CoV) redirect and rearrange host cell ...
3547-3836 8.03e-149

betacoronavirus non-structural protein 6; Coronaviruses (CoV) redirect and rearrange host cell membranes as part of the viral genome replication and transcription machinery; they induce the formation of double-membrane vesicles in infected cells. CoV non-structural protein 6 (Nsp6), a transmembrane-containing protein, together with Nsp3 and Nsp4, have the ability to induce double-membrane vesicles that are similar to those observed in severe acute respiratory syndrome (SARS) coronavirus-infected cells. By itself, Nsp6 can generate autophagosomes from the endoplasmic reticulum. Autophagosomes are normally generated as a cellular response to starvation to carry cellular organelles and long-lived proteins to lysosomes for degradation. Degradation through autophagy may provide an innate defense against virus infection, or conversely, autophagosomes can promote infection by facilitating the assembly of replicase proteins. In addition to initiating autophagosome formation, Nsp6 also limits autophagosome expansion regardless of how they were induced, i.e. whether they were induced directly by Nsp6, or indirectly by starvation or chemical inhibition of MTOR signaling. This may favor coronavirus infection by compromising the ability of autophagosomes to deliver viral components to lysosomes for degradation.


Pssm-ID: 394846  Cd Length: 290  Bit Score: 465.18  E-value: 8.03e-149
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 3547 GKFKKIVKGTHHWMLLTFLTSLLILVQSTQWSLFFFVYENAFLPFTLGIMAIAACAMLLVKHKHAFLCLFLLPSLATVAY 3626
Cdd:cd21560    1 SKVKRVVKGTLHWLLATFVLFYLIILQLTKWTMFMYLTETMLLPLTPALCCVSACVMLLVKHKHTFLTLFLLPVLLTLAY 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 3627 FNMVYMPA-SWVMRIMTWLELADTSlSGYRLKDCVMYASALVLLILMTARTVYDDAARRVWTLMNVITLVYKVYYGNALD 3705
Cdd:cd21560   81 YNYVYVPKsSFLGYVYNWLNYVNPY-VDYTYTDEVTYGSLLLVLMLVTMRLVNHDAFSRVWAVCRVITWVYMWYTGSLEE 159
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 3706 QAISMWALVISVTSNYSGVVTTIMFLARAIVFVCVEYYPLLFITGNTLQCIMLVYCFLGYCCCCYFGLFCLLNRYFRLTL 3785
Cdd:cd21560  160 SALSYLTFLFSVTTNYTGVVTVSLALAKFITALWLAYNPLLFLDIPEVKCVLLVYLFIGYICTCYFGVFSLLNRLFRCPL 239
                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|.
gi 30027621 3786 GVYDYLVSTQEFRYMNSQGLLPPKSSIDAFKLNIKLLGIGGKPCIKVATVQ 3836
Cdd:cd21560  240 GVYDYKVSTQEFRYMNANGLRPPRNSWEALMLNFKLLGIGGVPCIKVSTVQ 290
alpha_betaCoV_Nsp2 cd21511
alpha- and betacoronavirus non-structural protein 2; Coronavirus Nsps are encoded in ORF1a and ...
182-687 8.35e-143

alpha- and betacoronavirus non-structural protein 2; Coronavirus Nsps are encoded in ORF1a and ORF1b. Post infection, the genomic RNA is released into the cytoplasm of the cell and translated into two long polyproteins (pp), pp1a and pp1ab, which are then autoproteolytically cleaved by two viral proteases Nsp3 and Nsp5 into smaller subunits. Nsp2 is one of these subunits. This alpha- and betacoronavirus family includes alphacoronavirus human coronavirus 229E (HCoV-229E) Nsp2, betacoronavirus Severe acute respiratory syndrome coronavirus (SARS-CoV) Nsp2, SARS-CoV-2 Nsp2, and Murine hepatitis virus (MHV) Nsp2 (also known as p65). The function of Nsp2 remains unclear. SARS-CoV Nsp2, rather than playing a role in viral replication, may be involved in altering the host cell environment; deletion of Nsp2 from the SARS-CoV genome results in only a modest reduction in viral titers. It has been shown to interact with two host proteins, prohibitin 1 (PHB1) and PHB2, which have been implicated in cellular functions, including cell-cycle progression, cell migration, cellular differentiation, apoptosis, and mitochondrial biogenesis. MHV Nsp2/p65, different from SARS-CoV Nsp2, may play an important role in the viral life cycle. This family may be distantly related to the gammacoronavirus Avian infectious bronchitis virus (IBV) Nsp2; IBV Nsp2 is a weak protein kinase R (PKR) antagonist, which may suggest that it plays a role in interfering with intracellular immunity.


Pssm-ID: 439197  Cd Length: 399  Bit Score: 452.78  E-value: 8.35e-143
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621  182 VTRYVDNNFCGPDGYPLDCIKDFLARAGKSMCTLSEQLDYIESKRGVYCCRDHEHEIAWFTERSDKSYEHQTPFEIKSAk 261
Cdd:cd21511    1 NVTYVDQYGCGPDGKPVECIKDLLDVAKKGSCTLSEQLDGIELKNGVYDLRDHEVVIAWYVERKDVPYEKQTIFTIKSA- 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621  262 KFDTFKGECPKFVFPLNSKVKVIQPRVEKKKTEGFMGRIRSVYPVASPQECNNMHLSTLMKCNHCDEVSWQTCDFL-KAT 340
Cdd:cd21511   80 KFGTFVGEVPAHVFPLNSIVKEIQPRVKKKKKVTLSGVIRSFYSKASPNECNPITLSALVKCTHCDEKSWQTGDFVdGFT 159
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621  341 CEhCGTENLV-IEGPTTCGYLPTNAVVKMPCPACQDPeigpehsvadyhnhsniETRLRKGGRTRCFGGCVFAYVGCYNK 419
Cdd:cd21511  160 CE-CGAEYLNwKLDAQSSGVLPPGAVVKTQCPACVNR-----------------ETFLRGGGRIVYFGGAVYSYVGCING 221
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621  420 RAYWVPRASADIGSGHTGITgdnvetlnedlleilsrervninivgdfhlneevaiilasfsastsafidtiksldyksf 499
Cdd:cd21511  222 VAYWVPRASSSVGCFHTGVV------------------------------------------------------------ 241
                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621  500 ktivescgnykvtkGKPVKGAWNIGQQRSVLTPLCgfpSQAAGVIRSIFARTLDAANHSIPDLQRAAVTILDGISEQSLR 579
Cdd:cd21511  242 --------------GKIVPGAWGLGASAQKLTPLT---TGAAVVFVLIFARTLFAAVGSVPQLQASAPTILDGIVNASDR 304
                        410       420       430       440       450       460       470       480
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621  580 LVDAMVYTSDLL---TNSVIIMAYVTGGLVQQtsqwlsnllgttvekLRPIFEWIEAKLsagveflkdaweilkflitgv 656
Cdd:cd21511  305 LVDAMQFSADLVvatTTSAGAAGYVVAGLVDL---------------LKPILEWVLSKI--------------------- 348
                        490       500       510
                 ....*....|....*....|....*....|.
gi 30027621  657 fdivkGQIQVASDNIKDCVKCFIDVVNKALE 687
Cdd:cd21511  349 -----GQVCYAGCDVYERVMAFLNVVVKAAG 374
gammaCoV_Nsp13-helicase cd21720
helicase domain of gammacoronavirus non-structural protein 13; This model represents the ...
5553-5891 5.18e-139

helicase domain of gammacoronavirus non-structural protein 13; This model represents the helicase domain of non-structural protein 13 (Nsp13) from gammacoronavirus, including Avian infectious bronchitis virus. Helicases catalyze NTP-dependent unwinding of nucleic acid duplexes into single strands and are classified based on the arrangement of conserved motifs into six superfamilies. Coronavirus (CoV) Nsp13 is a member of the helicase superfamily 1 (SF1); SF1 and SF2 helicases do not form toroidal structures, while SF3-6 helicases do. Nsp13 is a component of the viral RNA synthesis replication and transcription complex (RTC). It is a multidomain protein containing a Cys/His rich zinc-binding domain (CH/ZBD), a stalk domain, a 1B domain involved in nucleic acid substrate binding, and a SF1 helicase core.


Pssm-ID: 409653 [Multi-domain]  Cd Length: 343  Bit Score: 439.35  E-value: 5.18e-139
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 5553 LYPTLNISDEFSSNVANYQKVGMQKYSTLQGPPGTGKSHFAIGLALYYPSARIVYTACSHAAVDALCEKALKYLPIDKCS 5632
Cdd:cd21720    2 LRPNVMVPECFVNNIPLYHLVGKQKRTTVQGPPGSGKSHFAIGLAAYFSNARVVFTACSHAAVDALCEKAFKFLKVDDCT 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 5633 RIIPARARVECFDKFKVNSTLEQYVFCTVNALPETTADIVVFDEISMATNYDLSVVNARLRAKHYVYIGDPAQLPAPRTL 5712
Cdd:cd21720   82 RIVPQRTTVDCFSKFKANDTGKKYIFSTINALPEVSCDILLVDEVSMLTNYELSFINGKINYQYVVYVGDPAQLPAPRTL 161
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 5713 LTkGTLEPEYFNSVCRLMKTIGPDMFLGTCRRCPAEIVDTVSALVYDNKLKAHKDKSAQCFKMFY-KGV--ITHDVSSAI 5789
Cdd:cd21720  162 LN-GSLSPKDYNVVTNLMVCVKPDIFLAKCYRCPKEIVDTVSTLVYDGKFIANNPESRQCFKVIVnNGNsdVGHESGSAY 240
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 5790 NRPQIGVVREFLTRNPAWRKAVFISPYNSQNAVASKILGLPTQTVDSSQGSEYDYVIFTQTTETAHSCNVNRFNVAITRA 5869
Cdd:cd21720  241 NTTQLEFVKDFVCRNKEWREATFISPYNAMNQRAYRMLGLNVQTVDSSQGSEYDYVIFCVTADSQHALNINRFNVALTRA 320
                        330       340
                 ....*....|....*....|...
gi 30027621 5870 KIGILCIMSDRD-LYDKLQFTSL 5891
Cdd:cd21720  321 KRGILVVMRQRDeLYSALKFTEL 343
TM_Y_HKU9-like_Nsp3_C cd21715
C-terminus of non-structural protein 3, including transmembrane and Y domains, from Rousettus ...
2228-2739 4.48e-138

C-terminus of non-structural protein 3, including transmembrane and Y domains, from Rousettus bat coronavirus HKU9 and betacoronavirus in the D lineage; This model represents the C-terminus of non-structural protein 3 (Nsp3) from betacoronavirus in the nobecovirus subgenus (D lineage), including Rousettus bat coronavirus HKU9. This conserved C-terminus includes two transmembrane (TM) regions TM1 and TM2, an ectodomain (3Ecto) between the TM1 and TM2 that is glycosylated and located on the lumenal side of the ER, an amphiphatic region (AH1) that is not membrane-spanning, and a large Y domain of approximately 370 residues. Nsp3 is a large multi-functional multi-domain protein that is an essential component of the replication/transcription complex (RTC), which carries out RNA synthesis, RNA processing, and interference with the host cell innate immune system. In the related betacoronaviruses, Severe acute respiratory syndrome-related coronavirus (SARS-CoV) and murine hepatitis virus (MHV), the TM1, 3Ecto and TM2 domains are important for the papain-like protease (PL2pro) domain to process Nsp3-Nsp4 cleavage. It has also been shown that the interaction of 3Ecto with the lumenal loop of Nsp4 is essential for ER rearrangements in cells infected with SARS-CoV or MHV. The Y domain, located at the cytosolic side of the ER, consists of the Y1 and CoV-Y subdomains, which are conserved in nidovirus and coronavirus, respectively. Functional information about the Y domain is limited; it has been shown that Nsp3 binding to Nsp4 is less efficient without the Y domain.


Pssm-ID: 409663  Cd Length: 526  Bit Score: 444.69  E-value: 4.48e-138
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 2228 GVLLSNFGAPSYCNGVRE---LYLNSSNVTTMDFCEGSFPcSICLSGLDSLDsYPALETIQVTISSyKLDLTILGLAAEW 2304
Cdd:cd21715   13 GVWLSEPYAPSLLTRFKHflgIVMPCDYVLVNETGTGWLH-HLCMAGMDGLD-YPALRMQQHRYGS-PYDYTYILMLLEA 89
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 2305 VLAYMLFTKFFYLLGLSAIMQVFFGYFASHfISNSWLMWFIISIVQMAPVSAMVRMYIFFASFYYIWKSYVHIMDGCTSS 2384
Cdd:cd21715   90 FCAYLLYTPALPIVGILAVLHLLVLYLPIP-LGNSWLVVFLYYIIRLVPFTSMLRMYIVIAFLWLCYKGFVHVRYGCNNV 168
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 2385 TCMMCYKRNRATRVECTTIVNGMKRSFYVYANGGRGFCKTHNWNCLNCDTFCTGSTFISDEVARDLSLQFKRPINPTDQS 2464
Cdd:cd21715  169 ACLMCYKKNVAKRIECSTVVNGVKRMFYVNANGGTYFCTKHNWNCVSCDTYTVDSTFISRQVALDLSAQFKRPINHTDEA 248
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 2465 SYIVDSVAVKNGALHLYFDKAGQKTYERHPLSHFVNLDNLRANNTKGSLP-INVIVFDGKSKCDESASKSASVYYSQLMC 2543
Cdd:cd21715  249 YYEVTSVEVRNGYVYCYFDSDGQRSYERFPMDAFTNVSKLHYSELKGAAPaFNVLVFDATNRIEENAVKTAAIYYAQLAC 328
                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 2544 QPILLLDQVLVSDVGDSTEVSVKMFDAYVDTFSATFSVPMEKLKALVATAHSELAKGVALDGVLSTFVSAARQGVVD--T 2621
Cdd:cd21715  329 KPILLVDKRMVGVVGDDATIAKAMFEAYAQNYLLKYSIAMDKVKHLYSTALQQIASGMTVESVLKVFVGSTRAEAKDleS 408
                        410       420       430       440       450       460       470       480
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 2622 DVDTKDVIECLKLSHHSDLEVTGDSCNNFMLTYNKVENMTPRDLGACIDCNARHINAQVAKSHNVSLIWNVKDYMSLSEQ 2701
Cdd:cd21715  409 DVDTNDLVSCIRLCHQEGWDWTTDSWNNLVPTYIKQDTLSTLEVGQFMTANARYVNANVAKGAAVNLVWRYADFIKLSES 488
                        490       500       510
                 ....*....|....*....|....*....|....*...
gi 30027621 2702 LRKQIRSAAKKNNIPFRLTCATTRQVVNVITTKISLKG 2739
Cdd:cd21715  489 MRRQLRVAARKTGLNLLVTTSSLKADVPCVVTPFKIVG 526
TM_Y_MERS-CoV-like_Nsp3_C cd21716
C-terminus of non-structural protein 3, including transmembrane and Y domains, from Middle ...
2223-2736 6.57e-138

C-terminus of non-structural protein 3, including transmembrane and Y domains, from Middle East respiratory syndrome-related coronavirus and betacoronavirus in the C lineage; This model represents the C-terminus of non-structural protein 3 (Nsp3) from betacoronavirus in the merbecovirus subgenus (C lineage), including Middle East respiratory syndrome-related coronavirus (MERS-CoV) and Tylonycteris bat coronavirus HKU4. This conserved C-terminus includes two transmembrane (TM) regions TM1 and TM2, an ectodomain (3Ecto) between the TM1 and TM2 that is glycosylated and located on the lumenal side of the ER, an amphiphatic region (AH1) that is not membrane-spanning, and a large Y domain of approximately 370 residues. Nsp3 is a large multi-functional multi-domain protein that is an essential component of the replication/transcription complex (RTC), which carries out RNA synthesis, RNA processing, and interference with the host cell innate immune system. In the related betacoronaviruses, Severe acute respiratory syndrome-related coronavirus (SARS-CoV) and murine hepatitis virus (MHV), the TM1, 3Ecto and TM2 domains are important for the papain-like protease (PL2pro) domain to process Nsp3-Nsp4 cleavage. It has also been shown that the interaction of 3Ecto with the lumenal loop of Nsp4 is essential for ER rearrangements in cells infected with SARS-CoV or MHV. The Y domain, located at the cytosolic side of the ER, consists of the Y1 and CoV-Y subdomains, which are conserved in nidovirus and coronavirus, respectively. Functional information about the Y domain is limited; it has been shown that Nsp3 binding to Nsp4 is less efficient without the Y domain.


Pssm-ID: 409664  Cd Length: 566  Bit Score: 445.79  E-value: 6.57e-138
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 2223 VTAAFGVLLSNFGAPSYCNGVRELYLNSS-NVTtmDFCEG-SFPCSICLSGLDSLDSYPALETIQVTISSYKLDLTILGL 2300
Cdd:cd21716   39 LKAFYKEVRSYLGISSACDGLASAYRANSfDVP--DFCANrSALCNWCLIGQDSITHYSALKMVQTHLSHYVLNIDWLWF 116
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 2301 AAEWVLAYMLFTKFFYLLGLSAIMQVFFGYfASHFI---SNSWLMWFIISIVQMAPVSAMVRMYIFFASFYYIWKSYVHI 2377
Cdd:cd21716  117 ALELLLAYVLYTSAFNWLLLACTLQYFFAQ-TSAFVdwrSYNYVVSGIFLLFTHIPLDGLVRIYNVLACLWFLRKFYNHV 195
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 2378 MDGCTSSTCMMCYKRNRATRVECTTIVNGMKRSFYVYANGGRGFCKTHNWNCLNCDTFCTGSTFISDEVARDLSLQFKRP 2457
Cdd:cd21716  196 INGCKDTACLLCYKRNRLTRVEASTVVCGGKRTFYITANGGTSFCRRHNWNCVDCDTAGVGNTFICEEVANDLTTSLRRL 275
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 2458 INPTDQSSYIVDSVAVKNGALHLYFDKAGQKTYERHPLSHFVNLDNLR----ANNTKGSLPINVIVFDGKSKCDESASKS 2533
Cdd:cd21716  276 VKPTDRSHYYVDSVEVKDTVVQLNYRRDGQSCYERFPLCYFTNLDKLKfkevCKTTTGIPEHNFIIYDSSDRGQENLARS 355
                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 2534 ASVYYSQLMCQPILLLDQVLVSDVGDSTEVSVKMFDAYVDTFSATFSVPMEKLKALVATAHSELAKGVALDGVLSTFVSA 2613
Cdd:cd21716  356 ACVYYSQVLCKPILLVDSNLVTSVGDSSEIAIKMFDSFVNSFVSLYNVTRDKLEKLISTARDGVKRGDNFQSVLKTFIDA 435
                        410       420       430       440       450       460       470       480
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 2614 AR-QGVVDTDVDTKDVIECLKLSHHSDLEVTGDSCNNFMLTYNKVENMTPRDLGACIDCNARHINAQVAKSHNVSLIWNV 2692
Cdd:cd21716  436 ARgPAGVESDVETNEIVDAVQYAHKHDIQLTTESYNNYVPSYVKPDSVATSDLGSLIDCNAASVNQTSMRNANGACIWNA 515
                        490       500       510       520
                 ....*....|....*....|....*....|....*....|....
gi 30027621 2693 KDYMSLSEQLRKQIRSAAKKNNIPFRLTCATTRQVVNVITTKIS 2736
Cdd:cd21716  516 AAYMKLSDSLKRQIRIACRKCNLNFRLTTSKLRANDNILSVKFS 559
CoV_PLPro cd21688
Coronavirus (CoV) papain-like protease (PLPro); This model represents the papain-like protease ...
1543-1845 3.61e-136

Coronavirus (CoV) papain-like protease (PLPro); This model represents the papain-like protease (PLPro) found in non-structural protein 3 (Nsp3) of alpha-, beta-, gamma-, and deltacoronavirus, including highly pathogenic betacoronaviruses such as Severe acute respiratory syndrome-related coronavirus (SARS-CoV), SARS-CoV2 (also called 2019 novel CoV or 2019-nCoV), and Middle East respiratory syndrome-related (MERS) CoV. CoVs utilize a multi-subunit replication/transcription machinery. A set of non-structural proteins (Nsps) generated as cleavage products of the ORF1a and ORF1ab viral polyproteins assemble to facilitate viral replication and transcription. PLPro is a key enzyme in this process, making it a high value target for the development of anti-coronavirus therapeutics. PLPro, which belongs to the MEROPS peptidase C16 family, participates in the proteolytic processing of the N-terminal region of the replicase polyprotein; it can cleave Nsp1|Nsp2, Nsp2|Nsp3, and Nsp3|Nsp4 sites and its activity is dependent on zinc. Besides cleaving the polyproteins, PLPro also possesses a related enzymatic activity to promote virus replication: deubiquitinating (DUB) and de-ISGylating activities. Both, ubiquitin (Ub) and Ub-like interferon-stimulated gene product 15 (ISG15), are involved in preventing viral infection; coronaviruses utilize Ubl-conjugating pathways to counter the pro-inflammatory properties of Ubl-conjugated host proteins via the action of PLPro, which processes both 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains from cellular substrates. The Nsp3 PLPro domain in many of these CoVs has also been shown to antagonize host innate immune induction of type I interferon by interacting with IRF3 and blocking its activation.


Pssm-ID: 409647  Cd Length: 299  Bit Score: 429.21  E-value: 3.61e-136
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 1543 KTIKVFTTVDNTNLHTQLVDMSMTYGQQFGPTYLDGADVTKIKPHvNHEGKTFFVLPSDDtlRSEAFEYYHTLDESFLGR 1622
Cdd:cd21688    1 KTKKVLVTVDGVNFRTIVVTTGDTYGQQLGPVYLDGADVTKGKPD-NHEGETFFVLPSTP--DKAALEYYGFLDPSFLGR 77
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 1623 YMSALNHTKKWKFpqVGGLTSIKWADNNCYLSSVLLALQQLEVKFNAPALQEAYYRARAGDAANFCALILAYSNKTVGEL 1702
Cdd:cd21688   78 YLSTLAHKWKVKV--VDGLRSLKWSDNNCYVSAVILALQQLKIKFKAPALQEAWNKFLGGDPARFVALIYASGNKTVGEP 155
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 1703 GDVRETMTHLLQHANLESAKRVLNVVCKHCGQKTTTLTGVEAVMYMGTLSYDNLKTGVSIPCVCGRDATQYLVQQESSFV 1782
Cdd:cd21688  156 GDVRETLTHLLQHADLSSATRVLRVVCKHCGIKTTTLTGVEAVMYVGALSYDDLKTGVSIPCPCGGEWTVQVIQQESPFL 235
                        250       260       270       280       290       300
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 30027621 1783 MMSA-PPAEYKLQQGTFLCANEYTGNYQCGHYTHITAKETLYRIDGAHLTKMSEYKGPVTDVFY 1845
Cdd:cd21688  236 LLSAaPPAEYKLQQDTFVAANVFTGNTNVGHYTHVTAKELLQKFDGAKVTKTSEDKGPVTDVLY 299
DEXSMc_CoV_Nsp13 cd22649
DEXSM-box helicase domain of coronavirus Nsp13 helicase; Helicases catalyze the NTP-dependent ...
5543-5744 5.98e-135

DEXSM-box helicase domain of coronavirus Nsp13 helicase; Helicases catalyze the NTP-dependent unwinding of nucleic acid duplexes into single strands and are classified into six superfamilies based on the arrangement of conserved motifs. This family contains coronavirus (CoV) non-structural protein 13 (Nsp13) helicase, including those from highly pathogenic human betaCoVs such as Severe Acute Respiratory Syndrome coronavirus (SARS) and SARS-CoV-2 (also known as 2019 novel CoV (2019-nCoV) or COVID-19 virus). Nsp13 helicase is a component of the viral RNA synthesis replication and transcription complex (RTC). SARS-Nsp13 is strongly inhibited by natural flavonoids, myricetin and scutellarein, and is emerging as a target for development of anti-SARS medications. It contains an N-terminal Cys/His rich zinc-binding domain (CH/ZBD), a stalk domain, a 1B regulatory domain, and an SF1 helicase core that carries a DEAD-box helicase domain. Nsp13 belongs to the DEAD-like helicase superfamily, a diverse family of proteins involved in ATP-dependent RNA or DNA unwinding. This domain contains the ATP-binding region.


Pssm-ID: 438713 [Multi-domain]  Cd Length: 202  Bit Score: 421.42  E-value: 5.98e-135
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 5543 PQEHYVRITGLYPTLNISDEFSSNVANYQKVGMQKYSTLQGPPGTGKSHFAIGLALYYPSARIVYTACSHAAVDALCEKA 5622
Cdd:cd22649    1 PQENYVRITGLYPTLNVPEEFSNNVPNYQKIGMQKYTTVQGPPGTGKSHFAIGLALYYPSARVVYTACSHAAVDALCEKA 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 5623 LKYLPIDKCSRIIPARARVECFDKFKVNSTLEQYVFCTVNALPETTADIVVFDEISMATNYDLSVVNARLRAKHYVYIGD 5702
Cdd:cd22649   81 FKFLNIDKCTRIIPARARVECYDKFKVNDTNAQYVFSTINALPETSADIVVVDEVSMCTNYDLSVINARIRAKHIVYIGD 160
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|..
gi 30027621 5703 PAQLPAPRTLLTKGTLEPEYFNSVCRLMKTIGPDMFLGTCRR 5744
Cdd:cd22649  161 PAQLPAPRTLLTKGTLEPEYFNSVTRLMCCLGPDIFLGTCYR 202
deltaCoV_Nsp13-helicase cd21721
helicase domain of deltacoronavirus non-structural protein 13; This model represents the ...
5569-5891 4.59e-131

helicase domain of deltacoronavirus non-structural protein 13; This model represents the helicase domain of non-structural protein 13 (Nsp13) from deltacoronavirus, including Bulbul coronavirus (CoV) HKU11 and Common moorhen CoV HKU21. Helicases catalyze NTP-dependent unwinding of nucleic acid duplexes into single strands and are classified based on the arrangement of conserved motifs into six superfamilies. CoV Nsp13 is a member of the helicase superfamily 1 (SF1); SF1 and SF2 helicases do not form toroidal structures, while SF3-6 helicases do. Nsp13 is a component of the viral RNA synthesis replication and transcription complex (RTC). It is a multidomain protein containing a Cys/His rich zinc-binding domain (CH/ZBD), a stalk domain, a 1B domain involved in nucleic acid substrate binding, and a SF1 helicase core.


Pssm-ID: 409654 [Multi-domain]  Cd Length: 342  Bit Score: 416.63  E-value: 4.59e-131
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 5569 NYQKVGMQKYSTLQGPPGTGKSHFAIGLALYYPSARIVYTACSHAAVDALCEKALKYLPIDKCSRIIPARARVECFDKFK 5648
Cdd:cd21721   18 SYNEIAMQKVTTVLGPPGTGKSTFAIGLAKYYPNARICYTASSHAAIDALCEKAFKTLPVGQCSRIVPTRTTVECFQDFV 97
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 5649 VNSTLEQYVFCTVNALPETTADIVVFDEISMATNYDLSVVNARLRAKHYVYIGDPAQLPAPRTLLTKGTLEPEYFNSVCR 5728
Cdd:cd21721   98 VNNTTAQYIFSTINALPDIKCDIVVVDEVSMLTNYELSSVNARLVYNHIVYVGDPYQLPSPRTMLTTGQLSPADYNVVTD 177
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 5729 LMKTIGPDMFLGTCRRCPAEIVDTVSALVYDNKLKAHKDKSAQCFKM---FYKGVITHDVSSAINRPQIGVVREFlTRNP 5805
Cdd:cd21721  178 IMVHAGADVMLDMCYRCPREIVDTVSKLVYDNKLKAAKPNSRQCYKTiinNGNNDIAHEGQSAYNEPQLRFALAF-RQYK 256
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 5806 AWRKAVFISPYNSQNAVASkILGLPTQTVDSSQGSEYDYVIFTQTTETAHSCNVNRFNVAITRAKIGILCIMSDRD-LYD 5884
Cdd:cd21721  257 RWDNVTFISPYNAMNVKAA-MAGFSTQTVDSSQGSEYDYVIFCVTTDSAHALNMSRLNVALTRAKIGILVVFRQANeLYN 335

                 ....*..
gi 30027621 5885 KLQFTSL 5891
Cdd:cd21721  336 SLQFESI 342
ps-ssRNAv_Nidovirales_RdRp cd23168
catalytic core domain of RNA-dependent RNA polymerase (RdRp) in the order Nidovirales of ...
4907-5261 4.34e-127

catalytic core domain of RNA-dependent RNA polymerase (RdRp) in the order Nidovirales of positive-sense single-stranded RNA [(+)ssRNA] viruses; This family contains the catalytic core domain of RdRP of Nidovirales, an order of enveloped, (+)ssRNA viruses which infect vertebrates and invertebrates. Host organisms include mammals, birds, reptiles, amphibians, fish, arthropods, mollusks, and helminths. The order Nidovirales currently comprises 88 formally recognized virus species of (+)ssRNA viruses which are classified into nine virus families: Abyssoviridae, Arteriviridae, Coronaviridae, Euroniviridae, Medioniviridae, Mesoniviridae, Mononiviridae, Roniviridae, and Tobaniviridae. Based on the genome size, the members of the order Nidovirales can be divided into two groups, large and small nidoviruses. The genomes of the large nidoviruses are well over 25 kb in length with size differences in the 5 kb range. Planarian secretory cell nidovirus (PSCNV), only member of the Mononiviridae family, has the largest known non-segmented RNA genome of 41.1 kb; its host is the planarian flatworm. The RdRp domain displays a right hand with three functional subdomains, called fingers, palm, and thumb. All RdRps contain conserved polymerase motifs (A-G), located in the palm (A-E motifs) and finger (F-G) subdomains. All these motifs have been implicated in RdRp fidelity such as processes of correct incorporation and reorganization of nucleotides.


Pssm-ID: 438018 [Multi-domain]  Cd Length: 310  Bit Score: 403.67  E-value: 4.34e-127
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 4907 TITQMNLKYAISAKNRARTVAGVSICSTMTNRQFHQKLLKSIAATRGATVVIGTSKFYGGWHNMLKTVYSDV-ETPHLMG 4985
Cdd:cd23168    1 TLTQVNPKYAIQKKKRARTILGVSIISTDVGRQLHQAVLAAIVNTRSANIVIIGTKFYGGWHKMLRYLYPGViEDPVLMG 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 4986 WDYPKCDRAMPNMLRIMASLVLARKHNTCCNLSHRFYRLANECAQVLSEMVMCGGSLYVKPGGTSSGDATTAYANSVFNI 5065
Cdd:cd23168   81 WDYPKCDRSVPNMLRYLANLLLASLYDNCCNLSEIVHLLINECAQVLYDYVVYGGNLYRKPGGVSSGDSTTAISNSIYNY 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 5066 CQAVTANvnallstdgnkiadkyvrnlqhrlyeclyrnrdvdhefvdefyaylrkhFSMMILSDDAVVCYNSNYAAQGLV 5145
Cdd:cd23168  161 FQTFIAN-------------------------------------------------VRLAILSDDGVACINPDLIDLGDV 191
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 5146 ASIKNFKAVLYYQNNVFMSEAKCWTETDLTKGPHEFCSQHTMLVKqgDDYVYLPYPDPSRILGAGCFVDDIVKTDGTLMI 5225
Cdd:cd23168  192 ASVSFFLASYYYTNNKKKYSSTCWVEPHEFCSPHEFKSDDKYQDR--VERVYLPIPDPSRMLSACLLVDTRTKTDILLMI 269
                        330       340       350       360
                 ....*....|....*....|....*....|....*....|.
gi 30027621 5226 ERFVSLAIDAYPLTKHP-----NQEYADVFHLYLQYIRKLH 5261
Cdd:cd23168  270 ERLISILIDAYPLTFHTktlpvNIEYAPLILLLLDYIKKLS 310
CoV_NSP4_N pfam19217
Coronavirus replicase NSP4, N-terminal; This is the N-terminal domain of the coronavirus ...
2765-3119 3.79e-116

Coronavirus replicase NSP4, N-terminal; This is the N-terminal domain of the coronavirus nonstructural protein 4 (NSP4). NSP4 is encoded by ORF1a/1ab and proteolytically released from the pp1a/1ab polyprotein. NSP4 is a membrane-spanning protein which is thought to anchor the viral replication-transcription complex to modified endoplasmic reticulum membranes. This N-terminal region represents the membrane spanning region, covering four transmembrane regions.


Pssm-ID: 437054  Cd Length: 351  Bit Score: 374.29  E-value: 3.79e-116
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621   2765 YIVMPVHTLSIHDGYTNEIIGYKAIQDGVTRDIISTDDCFANKHAGFDAWFSQRGGSYKNDKSCPVVAAIITREIGFIVP 2844
Cdd:pfam19217    1 YALSPSFFNTKVYFVSDPVYDFKVIENGVLRDFDSTDTCFHNKFDNFDQWHQAKFGTPTNSRSCPIVVGVVDGVVGRTVP 80
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621   2845 GLPGTVLRAiNGDFLHFLPRVFSAVGNICYTPSKLIEYSDFATSACVLAAECTIFKDAMGKPVPYCYDTNLLEGSISYSE 2924
Cdd:pfam19217   81 GVPAGVALV-GGTILHFVTRVFFGAGNVCYTPSGVISYEDFSASACVFNSACTTLTGLGGTRVLYCYDDGLVPGAKLYSD 159
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621   2925 LRPDTRYVLMDGSIIQFPNTYLEGSVRVVTTFDAEYCRHGTCERSEVGICLSTSGRWVLNNEHYralSGVFCGVDAMNLI 3004
Cdd:pfam19217  160 LKPHVRYKLVDGNYVKFPEVLFRGGFRIVRTLATTYCRVGECEDSKAGVCVGFDGSFVYNNDFG---PGVYCGDDFLDLV 236
                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621   3005 ANIFTPLVQPVGALDVSASVVAGGIIAILVTCAAYYFMKFRRVFGEYNHVVAANALLFLMSFTILCLVPAYSFLPGVYSV 3084
Cdd:pfam19217  237 RNVFSGFNTPISVFALTGQLMFNCVLALIAVCVCYYVLKFKRAFGDYTTGVLTVVLAALVNNLSYFVTQVNPVLMIVYAV 316
                          330       340       350
                   ....*....|....*....|....*....|....*
gi 30027621   3085 FYLYLTFYFTNDVSFLAHLQWFAMFSPIVPFWITA 3119
Cdd:pfam19217  317 LYFYATLYVTPEYAWIMHLSFLVAYVPVAPWWVLL 351
nsp8 pfam08717
nsp8 replicase; Viral nsp8 (non structural protein 8) forms a hexadecameric supercomplex with ...
3920-4116 4.68e-115

nsp8 replicase; Viral nsp8 (non structural protein 8) forms a hexadecameric supercomplex with nsp7 that adopts a hollow cylinder-like structure. The dimensions of the central channel and positive electrostatic properties of the cylinder imply that it confers processivity on RNA-dependent RNA polymerase.


Pssm-ID: 400866  Cd Length: 197  Bit Score: 364.17  E-value: 4.68e-115
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621   3920 AIASEFSSLPSYAAYATAQEAYEQAVANGDSEVVLKKLKKSLNVAKSEFDRDAAMQRKLEKMADQAMTQMYKQARSEDKR 3999
Cdd:pfam08717    1 SVASEFSSLPSYAAYETAKEAYEEAVANGSSQQVLKQLKKACNIAKSEFDRDAAVQKKLEKMAEQAMTQMYKEARAVDRK 80
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621   4000 AKVTSAMQTMLFTMLRKLDNDALNNIINNARDGCVPLNIIPLTTAAKLMVVVPDYGTYKNTCDGNTFTYASALWEIQQVV 4079
Cdd:pfam08717   81 SKVVSAMHTLLFSMLRKLDNSALNTIINNARNGVVPLNIIPATTAAKLTVVVPDYETFVKVVDGNTVTYAGAVWEIQEVK 160
                          170       180       190
                   ....*....|....*....|....*....|....*..
gi 30027621   4080 DADSKIVQLSEINMDNSPNLAWPLIVTALRANSAVKL 4116
Cdd:pfam08717  161 DADGKIVHLKEITMDNSPNLAWPLIVTAERANSAVKL 197
TM_Y_MHV-like_Nsp3_C cd21714
C-terminus of non-structural protein 3, including transmembrane and Y domains, from murine ...
2232-2739 1.16e-114

C-terminus of non-structural protein 3, including transmembrane and Y domains, from murine hepatitis virus and betacoronavirus in the A lineage; This model represents the C-terminus of non-structural protein 3 (Nsp3) from betacoronavirus in the embecovirus subgenus (A lineage), including murine hepatitis virus (MHV) and Human coronavirus HKU1. This conserved C-terminus includes two transmembrane (TM) regions TM1 and TM2, an ectodomain (3Ecto) between the TM1 and TM2 that is glycosylated and located on the lumenal side of the ER, an amphiphatic region (AH1) that is not membrane-spanning, and a large Y domain of approximately 370 residues. Nsp3 is a large multi-functional multi-domain protein that is an essential component of the replication/transcription complex (RTC), which carries out RNA synthesis, RNA processing, and interference with the host cell innate immune system. In MHV and the related Severe acute respiratory syndrome-related coronavirus (SARS-CoV), the TM1, 3Ecto and TM2 domains are important for the papain-like protease (PL2pro) domain to process Nsp3-Nsp4 cleavage. It has also been shown that the interaction of 3Ecto with the lumenal loop of Nsp4 is essential for ER rearrangements in cells infected with SARS-CoV or MHV. The Y domain, located at the cytosolic side of the ER, consists of the Y1 and CoV-Y subdomains, which are conserved in nidovirus and coronavirus, respectively. Functional information about the Y domain is limited; it has been shown that Nsp3 binding to Nsp4 is less efficient without the Y domain.


Pssm-ID: 409662  Cd Length: 555  Bit Score: 378.33  E-value: 1.16e-114
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 2232 SNFGAPSYCngvrELYLNSSNVTTMDFCEGSFPCSICLSGLDSLDSYPALETIQVTISSYKLD--LTILGLAAEWVLAYM 2309
Cdd:cd21714   49 NTFGLVTIC----DLYSVSDVGFKSQFCNGSMACQLCLSGFDMLDNYKAIDVVQYEVDRRVFFdyTSVLKLVVELVVSYA 124
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 2310 LFTKFFYLLGLSAIMQVFFGYFASHFISNS--WLMWFIISIVQMAPVSAMVRMYIFFASFYYIWKSYVHIMDGCTSSTCM 2387
Cdd:cd21714  125 LYTVWFYPLFCLIGLQLLTTWLPEFFMLETlhWSVRLFVFLANMLPAHVFLRFYIVVTAMYKIFCLFRHVVYGCSKPGCL 204
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 2388 MCYKRNRATRVECTTIVNGMKRSFYVYANGGRGFCKTHNWNCLNCDTFCTGSTFISDEVARDLSLQFKRPINPTDQSSYI 2467
Cdd:cd21714  205 FCYKRNRSVRVKCSTIVGGMLRYYDVMANGGTGFCSKHQWNCINCDSYKPGNTFITVEAAAELSKELKRPVNPTDVAYYT 284
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 2468 VDSVAVKNGALHLYFDKAGQKTYERHPLSHFVNLDNLRANNTKGSLPINVIVFDGKSkcDESASKSASVYYSQLMCQPIL 2547
Cdd:cd21714  285 VTDVKQVGCSMRLFYERDGQRVYDDVNASLFVDMNGLLHSKVKGVPNTHVVVVENDA--DKANFLNAAVFYAQSLFRPML 362
                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 2548 LLDQVLVSDVGDSTEVSVKMFDAYVDTFSATFSVPMEKLKALVATAHSELAKGVALDGVLSTFVSAARQGV-VDTDVDTK 2626
Cdd:cd21714  363 MVDKKLITTANTGTSVSQTMFDVYVDTFLSMFDVDRKSLNSFINTAHSSLKEGVQLEKVLDTFIGCARKSCsIDSDVDTK 442
                        410       420       430       440       450       460       470       480
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 2627 DVIECLKLSHHSDLEVTGDSCNNFMLTYNKVENMTPRDLGACIDCNARHINAQVAKSHNVSLIWNVKDYMSLSEQLRKQI 2706
Cdd:cd21714  443 CIAKSVMSAVAAGLEFTDESCNNLVPTYIKSDNIVAADLGVLIQNSAKHVQGNVAKAANVACIWSVDAFNQLSSDFQHKL 522
                        490       500       510
                 ....*....|....*....|....*....|...
gi 30027621 2707 RSAAKKNNIPFRLTCATTRQVVNVITTKISLKG 2739
Cdd:cd21714  523 KKACVKTGLKLKLTYNKQEANVSILTTPFSLKG 555
betaCoV_Nsp8 cd21831
betacoronavirus non-structural protein 8; This model represents the non-structural protein 8 ...
3923-4117 2.01e-110

betacoronavirus non-structural protein 8; This model represents the non-structural protein 8 (Nsp8) the highly pathogenic betacoronaviruses that include Severe acute respiratory syndrome-related coronavirus (SARS-CoV), SARS-CoV2 (also called 2019 novel CoV or 2019-nCoV), and Middle East respiratory syndrome-related (MERS) CoV. CoVs utilize a multi-subunit replication/transcription machinery. A set of non-structural proteins (Nsps) generated as cleavage products of the ORF1a and ORF1ab viral polyproteins assemble to facilitate viral replication and transcription. Upon processing of the Nsp7-10 region by protease M (Mpro), the released four small proteins Nsp7, Nsp8, Nsp9, and Nsp10 form functional complexes with CoV core enzymes and thereby stimulate replication. Most importantly, a complex of Nsp8 with Nsp7 has been shown to activate and confer processivity to the RNA-synthesizing activity of Nsp12, the RNA-dependent RNA-polymerase (RdRp); in SARS-CoV, point mutations in the genes encoding Nsp8 and Nsp7 have been shown to delay virus growth. Nsp8 and Nsp7 cooperate in activating the primer-dependent activity of the Nsp12 RdRp such that the level of their association may constitute a limiting factor for obtaining a high RNA polymerase activity. The subsequent Nsp7/Nsp8/Nsp12 polymerase complex is then able to associate with an active bifunctional Nsp14, which includes N-terminal 3' to 5' exoribonuclease (ExoN) and C-terminal N7-guanine cap methyltransferase (N7-MTase) activities, thus representing a unique coronavirus Nsp assembly that incorporates RdRp, exoribonuclease, and N7-MTase activities. Interaction of Nsp8 with Nsp7 appears to be conserved across the coronavirus family, making these proteins interesting drug targets. Nsp8 has a novel 'golf-club' fold composed of an N-terminal 'shaft' domain and a C-terminal 'head' domain. The shaft domain contains three helices, one of which is very long, while the head domain contains another three helices and seven beta-strands, forming an alpha/beta fold. SARS-CoV Nsp8 forms a 8:8 hexadecameric supercomplex with Nsp7 that adopts a hollow cylinder-like structure with a large central channel and positive electrostatic properties in the cylinder; the Nsp7/Nsp8 complex functions as a noncanonical RNA polymerase capable of synthesizing RNA of up to the template length.


Pssm-ID: 409258  Cd Length: 196  Bit Score: 351.01  E-value: 2.01e-110
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 3923 SEFSSLPSYAAYATAQEAYEQAVANGD-SEVVLKKLKKSLNVAKSEFDRDAAMQRKLEKMADQAMTQMYKQARSEDKRAK 4001
Cdd:cd21831    1 SEFSNLASYAEYETAQKAYDEAVASGDaSPQVLKALKKAVNVAKSAYEKDKAVARKLERMADQAMTSMYKQARAEDKKSK 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 4002 VTSAMQTMLFTMLRKLDNDALNNIINNARDGCVPLNIIPLTTAAKLMVVVPDYGTYKNTCDGNTFTYASALWEIQQVVDA 4081
Cdd:cd21831   81 VVSAMQTMLFGMIRKLDNDALNNIINNARNGCVPLSIIPLTAANKLRVVVPDYSVYKQVVDGPTLTYAGALWDIQQINDA 160
                        170       180       190
                 ....*....|....*....|....*....|....*..
gi 30027621 4082 DSKIVQLSEINMDNsPNLAWPLIVTALRAN-SAVKLQ 4117
Cdd:cd21831  161 DGKIVQLSDITEDS-ENLAWPLVVTATRANsSAVKLQ 196
alphaCoV_Nsp5_Mpro cd21665
alphacoronavirus non-structural protein 5, also called Main protease (Mpro); This subfamily ...
3243-3542 4.29e-110

alphacoronavirus non-structural protein 5, also called Main protease (Mpro); This subfamily contains the coronavirus (CoV) non-structural protein 5 (Nsp5) also called the Main protease (Mpro), or 3C-like protease (3CLpro), found in alphacoronaviruses. CoVs utilize a multi-subunit replication/transcription machinery. A set of non-structural proteins (Nsps) generated as cleavage products of the ORF1a and ORF1ab viral polyproteins assemble to facilitate viral replication and transcription. Mpro/Nsp5 is a key enzyme in this process, making it a high value target for the development of anti-coronavirus therapeutics. These enzymes belong to the MEROPS peptidase C30 family, where the active site residues His and Cys form a catalytic dyad. The structures of Mpro/Nsp5 consist of three domains with the first two containing anti-parallel beta barrels and the third consisting of an arrangement of alpha-helices. The catalytic residues are found in a cleft between the first two domains. Mpro/Nsp5 requires a Gln residue in the P1 position of the substrate and space for only small amino-acid residues such as Gly, Ala, or Ser in the P1' position; since there is no known human protease with a specificity for Gln at the cleavage site of the substrate, these viral proteases are suitable targets for the development of antiviral drugs.


Pssm-ID: 394886  Cd Length: 296  Bit Score: 354.29  E-value: 4.29e-110
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 3243 FRKMAFPSGKVEGCMVQVTCGTTTLNGLWLDDTVYCPRHVIctAED---MLNPNYEDLLIRKsnHSFLVQAGNVQLRVIG 3319
Cdd:cd21665    1 LRKMAQPSGVVEKCVVRVSYGNMVLNGLWLGDTVYCPRHVI--ASDttsTIDYDHEYSLMRL--HNFSISVGNVFLGVVG 76
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 3320 HSMQNCLLRLKVDTSNPKTPKYKFVRIQPGQTFSVLACYNGSPSGVYQCAMRPNHTIKGSFLNGSCGSVGFNIDYDCVSF 3399
Cdd:cd21665   77 VTMRGALLVIKVNQNNVNTPKYTFRTLKPGDSFNILACYDGVPSGVYGVNMRTNYTIKGSFINGACGSPGYNLNNGTVEF 156
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 3400 CYMHHMELPTGVHAGTDLEGKFYGPFVDRQTAQAAGTDTTITLNVLAWLYAAVINGDRWFLNRFTTTLNDFNLVAMKYNY 3479
Cdd:cd21665  157 CYMHQLELGSGCHVGSDLDGVMYGGYEDQPTLQVEGANVLVTENVVAFLYAALLNGCNWWLSSDRVTVEAFNEWAVANGF 236
                        250       260       270       280       290       300
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 30027621 3480 EPLTQdhVDILGPLSAQTGIAVLDMCAALKElLQNGMNGRTILGSTILEDEFTPFDVVRQCSG 3542
Cdd:cd21665  237 TTVSS--TDCFSILAAKTGVDVERLLAAIQR-LSKGFGGKTILGYTSLTDEFTLSEVIKQMYG 296
DUF3655 pfam12379
Protein of unknown function (DUF3655); This domain family is found in viruses, and is ...
881-1029 4.67e-108

Protein of unknown function (DUF3655); This domain family is found in viruses, and is approximately 70 amino acids in length. The family is found in association with pfam08716, pfam01661, pfam05409, pfam06471, pfam08717, pfam06478, pfam09401, pfam06460, pfam08715, pfam08710.


Pssm-ID: 432517  Cd Length: 149  Bit Score: 342.16  E-value: 4.67e-108
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621    881 VKTLQPVSDLLTNMGIDLDEWSVATFYLFDDAGEENFSSRMYCSFYPPDEEEEDDAECEEEEIDETCEHEYGTEDDYQGL 960
Cdd:pfam12379    1 VKTLQPVSDLLTNMGIDLDEWSVATFYLFDDAGEENFSSRMYCSFYPPDEEEEDDAECEEEEIDETCEHEYGTEDDYQGL 80
                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 30027621    961 PLEFGASAETVRVEEEEEEDWLDDTTEQSEIEPEPEPTPEEPVNQFTGYLKLTDNVAIKCVDIVKEAQS 1029
Cdd:pfam12379   81 PLEFGASAETVRVEEEEEEDWLDDTTEQSEIEPEPEPTPEEPVNQFTGYLKLTDNVAIKCVDIVKEAQS 149
CoV_Nsp8 cd21816
Coronavirus non-structural protein 8; This model represents the non-structural protein 8 (Nsp8) ...
3923-4117 1.03e-104

Coronavirus non-structural protein 8; This model represents the non-structural protein 8 (Nsp8) of alpha-, beta-, gamma- and deltacoronaviruses, including highly pathogenic betacoronaviruses such as Severe acute respiratory syndrome-related coronavirus (SARS-CoV), SARS-CoV2 (also called 2019 novel CoV or 2019-nCoV), and Middle East respiratory syndrome-related (MERS) CoV. CoVs utilize a multi-subunit replication/transcription machinery. A set of non-structural proteins (Nsps) generated as cleavage products of the ORF1a and ORF1ab viral polyproteins assemble to facilitate viral replication and transcription. Upon processing of the Nsp7-10 region by protease M (Mpro), the released four small proteins Nsp7, Nsp8, Nsp9, and Nsp10 form functional complexes with CoV core enzymes and thereby stimulate replication. Most importantly, a complex of Nsp8 with Nsp7 has been shown to activate and confer processivity to the RNA-synthesizing activity of Nsp12, the RNA-dependent RNA-polymerase (RdRp); in SARS-CoV, point mutations in the genes encoding Nsp8 and Nsp7 have been shown to delay virus growth. Nsp8 and Nsp7 cooperate in activating the primer-dependent activity of the Nsp12 RdRp such that the level of their association may constitute a limiting factor for obtaining a high RNA polymerase activity. The subsequent Nsp7/Nsp8/Nsp12 polymerase complex is then able to associate with an active bifunctional Nsp14, which includes N-terminal 3' to 5' exoribonuclease (ExoN) and C-terminal N7-guanine cap methyltransferase (N7-MTase) activities, thus representing a unique coronavirus Nsp assembly that incorporates RdRp, exoribonuclease, and N7-MTase activities. Interaction of Nsp8 with Nsp7 appears to be conserved across the coronavirus family, making these proteins interesting drug targets. Nsp8 has a novel 'golf-club' fold composed of an N-terminal 'shaft' domain and a C-terminal 'head' domain. The shaft domain contains three helices, one of which is very long, while the head domain contains another three helices and seven beta-strands, forming an alpha/beta fold. SARS-CoV Nsp8 forms a 8:8 hexadecameric supercomplex with Nsp7 that adopts a hollow cylinder-like structure with a large central channel and positive electrostatic properties in the cylinder, while Feline infectious peritonitis virus Nsp8 forms a 1:2 heterotrimer with Nsp7. Regardless of their oligomeric structure, the Nsp7/Nsp8 complex functions as a noncanonical RNA polymerase capable of synthesizing RNA of up to the template length.


Pssm-ID: 409256  Cd Length: 194  Bit Score: 334.49  E-value: 1.03e-104
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 3923 SEFSSLPSYAAYATAQEAYEQAVANGDSEVVLKKLKKSLNVAKSEFDRDAAMQRKLEKMADQAMTQMYKQARSEDKRAKV 4002
Cdd:cd21816    1 SEFSHLPSYAAYATAQAAYEQAVKNGDSPQELKKLTKALNIAKSEFDRDAAVQKKLEKMADQAMTSMYKEARAEDRRAKI 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 4003 TSAMQTMLFTMLRKLDNDALNNIINNARDGCVPLNIIPLTTAAKLMVVVPDYGTYKNTCDGNTFTYASALWEIQQVVDAD 4082
Cdd:cd21816   81 TSAMHALLFSMLKKLDSDAVNNIFEQARDGVVPLNIIPLTTANKLMVVIPDYETYKKTVDGNTFTYAGALWSIVTVVDAD 160
                        170       180       190
                 ....*....|....*....|....*....|....*
gi 30027621 4083 SKIVQLSEINMDNSPNLAWPLIVTALRANsAVKLQ 4117
Cdd:cd21816  161 GKIVHLSEINMDNSPNIAWPLIVTCLRAG-AVKLQ 194
CoV_Nsp6 cd21526
coronavirus non-structural protein 6; Coronaviruses (CoV) redirect and rearrange host cell ...
3552-3836 5.36e-103

coronavirus non-structural protein 6; Coronaviruses (CoV) redirect and rearrange host cell membranes as part of the viral genome replication and transcription machinery; they induce the formation of double-membrane vesicles in infected cells. CoV non-structural protein 6 (Nsp6), a transmembrane-containing protein, together with Nsp3 and Nsp4, have the ability to induce double-membrane vesicles that are similar to those observed in severe acute respiratory syndrome (SARS) coronavirus-infected cells. By itself, Nsp6 can generate autophagosomes from the endoplasmic reticulum. Autophagosomes are normally generated as a cellular response to starvation to carry cellular organelles and long-lived proteins to lysosomes for degradation. Degradation through autophagy may provide an innate defense against virus infection, or conversely, autophagosomes can promote infection by facilitating the assembly of replicase proteins. In addition to initiating autophagosome formation, Nsp6 also limits autophagosome expansion regardless of how they were induced, i.e. whether they were induced directly by Nsp6, or indirectly by starvation or chemical inhibition of MTOR signaling. This may favor coronavirus infection by compromising the ability of autophagosomes to deliver viral components to lysosomes for degradation.


Pssm-ID: 394843  Cd Length: 287  Bit Score: 333.73  E-value: 5.36e-103
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 3552 IVKGTHHWMLLTfltSLLILVQSTQWSLFFFVYENAFL--PFTLGIMAIAACAM------LLVKHKHAFLCLFLLPSLAT 3623
Cdd:cd21526    1 VYNQAPGVLLQS---VFVVKKTSTFWSHFLFAAFTMLLaaPLVFPVHAYVILLMcftvvtFTVKHKVAFLTTFLLPSLIT 77
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 3624 -VAYFNMVYMPasWVMRIMTWLelaDTSLSGYRLKDCVMYASALVLLILMTA------RTVYDDAARRVWTLM-NVITLV 3695
Cdd:cd21526   78 mVAIANTFWIQ--VVTFLRTWY---DTVFVSPIAQDLYGYTVALYMLIYAGLatnytlKTLRYRATSFLSFLMqNFLTLY 152
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 3696 YKVYYGNALDQAISMWALVISVTSNYSGVVTTIMFLARAIVFVCveyYPLLFitgNTLQCIMLVYCFLGYCCCCYFGLFC 3775
Cdd:cd21526  153 TAHYAYKLLPWTESLLFTALTMLSSHSLIGAIVFWLARWMLRVE---YPIIF---PDLAIRVLAYNVIGYVCTCYFGLMW 226
                        250       260       270       280       290       300
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 30027621 3776 LLNRYFRLTLGVYDYLVSTQEFRYMNSQGLLPPKSSIDAFKLNIKLLGIGGKPCIKVATVQ 3836
Cdd:cd21526  227 LANRFFTLTLGVYDYMVSVEQFRYMMAVKLNPPKNAFEVFILNIKLLGIGGNRNIKVATVQ 287
NendoU_cv_Nsp15-like cd21161
Nidoviral uridylate-specific endoribonuclease (NendoU) domain of coronavirus Nonstructural ...
6623-6773 2.52e-90

Nidoviral uridylate-specific endoribonuclease (NendoU) domain of coronavirus Nonstructural Protein 15 (Nsp15) and related proteins; Nidovirus endoribonucleases (NendoUs) are uridylate-specific endoribonucleases, which release a cleavage product containing a 2',3'-cyclic phosphate at the 3' terminal end. NendoUs include Nsp15 from coronaviruses and Nsp11 from arteriviruses, both of which may participate in the viral replication process and in the evasion of the host immune system. Except for turkey coronavirus (TCoV) Nsp15, Mn2+ is generally essential for the catalytic activity of coronavirus Nsp15. Coronavirus Nsp15 from Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV), human Coronavirus 229E (HCoV229E), and murine hepatitis virus (MHV) form a functional hexamer while Porcine DeltaCoronavirus (PDCoV) Nsp15 has been shown to exist as a dimer and a monomer in solution. NendoUs are distantly related to Xenopus laevis Mn(2+)-dependent uridylate-specific endoribonuclease (XendoU) which is involved in the processing of intron-encoded box C/D U16 small, nucleolar RNA.


Pssm-ID: 439158  Cd Length: 151  Bit Score: 291.47  E-value: 2.52e-90
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 6623 FTQSRDLEDFKPRSQMETDFLELAMDEFIQRYKLEGYAFEHIVYGDFSHGQLGGLHLMIGLAKRSQDSPLKLEDFIPMDS 6702
Cdd:cd21161    1 FTQGRSLEDFKPRSQMERDFLSMDQDVFIQKYGLEDLGFEHIVYGDFSKPTIGGLHLLIGLVRLKKEGKLYVEEFHNSDS 80
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 30027621 6703 TVKNYFITDAQTGSSKCVCSVIDLLLDDFVEIIKSQDLSVISKVVKVTIDYAEISFMLWCKDGHVETFYPK 6773
Cdd:cd21161   81 TVQNYFVTDANNGSSKQVCTVVDLLLDDFVDILKSQDLSVVSKVVTVSIDYKPIRFMLWCKDGKVKTFYPQ 151
gammaCoV_Nsp5_Mpro cd21667
gammacoronavirus non-structural protein 5, also called Main protease (Mpro); This subfamily ...
3242-3546 3.13e-85

gammacoronavirus non-structural protein 5, also called Main protease (Mpro); This subfamily contains the coronavirus (CoV) non-structural protein 5 (Nsp5) also called the Main protease (Mpro), or 3C-like protease (3CLpro), found in gammacoronaviruses. CoVs utilize a multi-subunit replication/transcription machinery. A set of non-structural proteins (Nsps) generated as cleavage products of the ORF1a and ORF1ab viral polyproteins assemble to facilitate viral replication and transcription. Mpro/Nsp5 is a key enzyme in this process, making it a high value target for the development of anti-coronavirus therapeutics. These enzymes belong to the MEROPS peptidase C30 family, where the active site residues His and Cys form a catalytic dyad. The structures of Mpro/Nsp5 consist of three domains with the first two containing anti-parallel beta barrels and the third consisting of an arrangement of alpha-helices. The catalytic residues are found in a cleft between the first two domains. Mpro/Nsp5 requires a Gln residue in the P1 position of the substrate and space for only small amino-acid residues such as Gly, Ala, or Ser in the P1' position; since there is no known human protease with a specificity for Gln at the cleavage site of the substrate, these viral proteases are suitable targets for the development of antiviral drugs.


Pssm-ID: 394888  Cd Length: 306  Bit Score: 283.60  E-value: 3.13e-85
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 3242 GFRKMAFPSGKVEGCMVQVTCGTTTLNGLWLDDTVYCPRHVI--CTAEDmlnpnYEDLLIRKSNHSFLVQAGN-VQLRVI 3318
Cdd:cd21667    1 GFKKLVSPSSAVEKCIVSVSYRGNNLNGLWLGDSIYCPRHVLgkFSGDQ-----WQDVLNLANNHEFEVVTQNgVTLNVV 75
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 3319 GHSMQNCLLRLKVDTSNPKTPKYKFVRIQPGQTFSVLACYNGSPSGVYQCAMRPNHTIKGSFLNGSCGSVGFNIDYDCVS 3398
Cdd:cd21667   76 SRRLKGAVLILQTAVANANTPKYKFVKANCGDSFTIACSYGGTVVGLYPVTMRSNGTIRASFLAGACGSVGFNIEKGVVN 155
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 3399 FCYMHHMELPTGVHAGTDLEGKFYGPFVDRQTAQAAGTDTTITLNVLAWLYAAVIN---GDRWF---LNRFTTTLNDFNL 3472
Cdd:cd21667  156 FFYMHHLELPNALHTGTDLMGEFYGGYVDEEVAQRVPPDNLVTNNIVAWLYAAIISvkeSSFSLpkwLESTTVSVEDYNK 235
                        250       260       270       280       290       300       310
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 30027621 3473 VAMKYNYEPL-TQDHVDIlgpLSAQTGIAVLDMCAALKElLQNGMNGRTILGSTILEDEFTPFDVVRQCSGVTFQ 3546
Cdd:cd21667  236 WASDNGFTPFsTSTAITK---LSAITGVDVCKLLRTIMV-KSAQWGSDPILGQYNFEDELTPESVFNQVGGVRLQ 306
alphaCoV_Nsp8 cd21830
alphacoronavirus non-structural protein 8; This model represents the non-structural protein 8 ...
3920-4117 4.83e-84

alphacoronavirus non-structural protein 8; This model represents the non-structural protein 8 (Nsp8) region of alphacoronaviruses that include Feline infectious peritonitis virus (FCoV), Human coronavirus NL63 (HCoV-NL63), and Porcine epidemic diarrhea coronavirus (PEDV), among others. CoVs utilize a multi-subunit replication/transcription machinery. A set of non-structural proteins (Nsps) generated as cleavage products of the ORF1a and ORF1ab viral polyproteins assemble to facilitate viral replication and transcription. Upon processing of the Nsp7-10 region by protease M (Mpro), the released four small proteins Nsp7, Nsp8, Nsp9, and Nsp10 form functional complexes with CoV core enzymes and thereby stimulate replication. Most importantly, a complex of Nsp8 with Nsp7 has been shown to activate and confer processivity to the RNA-synthesizing activity of Nsp12, the RNA-dependent RNA-polymerase (RdRp); in SARS-CoV, point mutations in the genes encoding Nsp8 and Nsp7 have been shown to delay virus growth. Nsp8 and Nsp7 cooperate in activating the primer-dependent activity of the Nsp12 RdRp such that the level of their association may constitute a limiting factor for obtaining a high RNA polymerase activity. The subsequent Nsp7/Nsp8/Nsp12 polymerase complex is then able to associate with an active bifunctional Nsp14, which includes N-terminal 3' to 5' exoribonuclease (ExoN) and C-terminal N7-guanine cap methyltransferase (N7-MTase) activities, thus representing a unique coronavirus Nsp assembly that incorporates RdRp, exoribonuclease, and N7-MTase activities. Interaction of Nsp8 with Nsp7 appears to be conserved across the coronavirus family, making these proteins interesting drug targets. Nsp8 has a novel 'golf-club' fold composed of an N-terminal 'shaft' domain and a C-terminal 'head' domain. The shaft domain contains three helices, one of which is very long, while the head domain contains another three helices and seven beta-strands, forming an alpha/beta fold. FCoV Nsp8 forms a 1:2 heterotrimer with Nsp7; the Nsp7/Nsp8 complex functions as a noncanonical RNA polymerase capable of synthesizing RNA of up to the template length.


Pssm-ID: 409257  Cd Length: 195  Bit Score: 275.38  E-value: 4.83e-84
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 3920 AIASEFSSLPSYAAYATAQEAYEQAVANGDSEVVLKKLKKSLNVAKSEFDRDAAMQRKLEKMADQAMTQMYKQARSEDKR 3999
Cdd:cd21830    1 SVASTFANMPSFIAYETARQDYEDAVKNGSSPQLIKQLKKAMNIAKSEFDREASVQRKLDRMAEQAAAQMYKEARAVNRK 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 4000 AKVTSAMQTMLFTMLRKLDNDALNNIINNARDGCVPLNIIPLTTAAKLMVVVPDYGTYKNTCDGNTFTYASALWEIQQVV 4079
Cdd:cd21830   81 SKVISAMHSLLFGMLRRLDMSSVDTILNLAKDGVVPLSIIPAASATRLVVVVPDLESFSKIRRDGCVHYAGVVWTIVDIK 160
                        170       180       190
                 ....*....|....*....|....*....|....*...
gi 30027621 4080 DADSKIVQLSEINMDNSPNLAWPLIVTALRansAVKLQ 4117
Cdd:cd21830  161 DNDGKVVHLKEVTAANEESLAWPLHLNCER---IVKLQ 195
CoV_NSP15_C pfam19215
Coronavirus replicase NSP15, uridylate-specific endoribonuclease; This entry represents the ...
6620-6773 4.99e-84

Coronavirus replicase NSP15, uridylate-specific endoribonuclease; This entry represents the C-terminal domain of coronavirus non-structural protein 15 (NSP15 or nsp15). NSP15 is encoded by ORF1a/1ab and proteolytically released from the pp1a/1ab polyprotein. This domain exhibits endoribonuclease activity designated EndoU, highly conserved in all known CoVs and is part of the replicase-transcriptase complex that plays important roles in virus replication and transcription. NSP15 is a Uridylate-specific endoribonuclease that cleaves the 5'-polyuridines from negative-sense viral RNA, termed PUN RNA either upstream or downstream of uridylates, at GUU or GU to produce molecules with 2',3'-cyclic phosphate ends. PUN RNA is a CoV MDA5-dependent pathogen-associated molecular pattern (PAMP).


Pssm-ID: 437052  Cd Length: 154  Bit Score: 273.42  E-value: 4.99e-84
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621   6620 ETYFTQSRDLEDFKPRSQMETDFLELAMDEFIQRYKLEGYAFEHIVYGDFSHGQLGGLHLMIGLAKRSQDSPLKLEDFIP 6699
Cdd:pfam19215    1 DTLFTQGRTLEDFVPRSTMEKDFLNMDQDVFIQKYGLEDYGFEHIVYGDFSKTTIGGLHLLISLVRLSQEGILKVEEFVP 80
                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 30027621   6700 MDSTVKNYFITDAQTGSSKCVCSVIDLLLDDFVEIIKSQDLSVISKVVKVTIDYAEISFMLWCKDGHVETFYPK 6773
Cdd:pfam19215   81 NDSTVKNCFVTYANDGSSKAVCTVIDLLLDDFVDIIKSLDLSVVSKVVTVNIDFQPIRFMLWCKDGKVQTFYPQ 154
CoV_Nsp10 cd21872
coronavirus non-structural protein 10; This model represents the non-structural protein 10 ...
4231-4361 1.32e-82

coronavirus non-structural protein 10; This model represents the non-structural protein 10 (Nsp10) of alpha-, beta-, gamma- and deltacoronaviruses, including highly pathogenic betacoronaviruses such as Severe acute respiratory syndrome-related coronavirus (SARS-CoV), SARS-CoV2 (also called 2019 novel CoV or 2019-nCoV), and Middle East respiratory syndrome-related (MERS) CoV. CoVs utilize a multi-subunit replication/transcription machinery. A set of non-structural proteins (Nsps) generated as cleavage products of the ORF1a and ORF1ab viral polyproteins assemble to facilitate viral replication and transcription. Upon processing of the Nsp7-10 region by protease M (Mpro), the released four small proteins Nsp7, Nsp8, Nsp9, and Nsp10 form functional complexes with CoV core enzymes and thereby stimulate replication. Coronaviruses cap their mRNAs; RNA cap methylation may involve at least three proteins: Nsp10, Nsp14, and Nsp16. Nsp10 serves as a cofactor for both Nsp14 and Nsp16. Nsp14 consists of 2 domains with different enzymatic activities: an N-terminal ExoN domain and a C-terminal cap (guanine-N7) methyltransferase (N7-MTase) domain. The association of Nsp10 with Nsp14 enhances Nsp14's exoribonuclease (ExoN) activity, and not its N7-Mtase activity. ExoN is important for proofreading and therefore, the prevention of lethal mutations. The Nsp10/Nsp14 complex hydrolyzes double-stranded RNA in a 3' to 5' direction as well as a single mismatched nucleotide at the 3'-end, mimicking an erroneous replication product, and may function in a replicative mismatch repair mechanism. Nsp16 Cap-0 specific (nucleoside-2'-O-)-methyltransferase (2'OMTase) acts sequentially to Nsp14 MTase in RNA capping methylation, and methylates the RNA cap at the ribose 2'-O position; it catalyzes the conversion of the cap-0 structure on m7GpppA-RNA to a cap-1 structure. The association of Nsp10 with Nsp16 enhances Nsp16's 2'OMTase activity, possibly through enhanced RNA binding affinity. Additionally, transmissible gastroenteritis virus (TGEV) Nsp10, Nsp16, and their complex can interact with DII4, which normally binds to Notch receptors; this interaction may disturb Notch signaling. Nsp10 also binds 2 zinc ions with high affinity.


Pssm-ID: 409325  Cd Length: 131  Bit Score: 268.57  E-value: 1.32e-82
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 4231 AGNATEVPANSTVLSFCAFAVDPAKAYKDYLASGGQPITNCVKMLCTHTGTGQAITVTPEANMDQESFGGASCCLYCRCH 4310
Cdd:cd21872    1 AGNATEVPANSTVLSFCAFAVDPAKAYKDYLASGGQPITNCVKMLCTHTGTGQAITVKPEANMDQESFGGASVCLYCRAH 80
                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|.
gi 30027621 4311 IDHPNPKGFCDLKGKYVQIPTTCANDPVGFTLRNTVCTVCGMWKGYGCSCD 4361
Cdd:cd21872   81 IDHPNPDGFCDYKGKFVQIPTTCANDPVGFTLRNTVCTVCQMWKGYGCSCD 131
SUD-M pfam11633
Single-stranded poly(A) binding domain; This family of proteins represents Nsp3c, the product ...
1344-1469 1.78e-82

Single-stranded poly(A) binding domain; This family of proteins represents Nsp3c, the product of ORF1a in group 2 coronavirus. The domain exhibits a macrodomain fold containing the nsp3 residues 528 to 648, with a flexibly extended N-terminal tail from residues 513 to 527 and a C-terminal flexible tail of residues 649 to 651. SUD-M(527-651) binds single-stranded poly(A); the contact area with this RNA on the protein surface, and the electrophoretic mobility shift assays confirm that SUD-M has higher affinity for purine bases than for pyrimidine bases.


Pssm-ID: 431970  Cd Length: 126  Bit Score: 267.77  E-value: 1.78e-82
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621   1344 LGTVSWNLREMLAHAEETRKLMPICMDVRAIMATIQRKYKGIKIQEGIVDYGVRFFFYTSKEPVASIITKLNSLNEPLVT 1423
Cdd:pfam11633    1 LGTVSWNLREMLAHAEETRKLMPICMDVRAIMATIQRKYKGIKIQEGIVDYGVRFFFYTSKEPVASIITKLNSLNEPLVT 80
                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*.
gi 30027621   1424 MPIGYVTHGFNLEEAARCMRSLKAPAVVSVSSPDAVTTYNGYLTSS 1469
Cdd:pfam11633   81 MPIGYVTHGFNLEEAARCMRSLKAPAVVSVSSPDAVTTYNGYLTSS 126
alpha_betaCoV_Nsp10 cd21901
alphacoronavirus and betacoronavirus non-structural protein 10; This model represents the ...
4231-4361 2.34e-82

alphacoronavirus and betacoronavirus non-structural protein 10; This model represents the non-structural protein 10 (Nsp10) of alpha- and betacoronaviruses, including highly pathogenic betacoronaviruses such as Severe acute respiratory syndrome-related coronavirus (SARS-CoV), SARS-CoV2 (also called 2019 novel CoV or 2019-nCoV), Middle East respiratory syndrome-related (MERS) CoV, and alphacoronaviruses such as Human coronavirus 229E. CoVs utilize a multi-subunit replication/transcription machinery. A set of non-structural proteins (Nsps) generated as cleavage products of the ORF1a and ORF1ab viral polyproteins assemble to facilitate viral replication and transcription. Upon processing of the Nsp7-10 region by protease M (Mpro), the released four small proteins Nsp7, Nsp8, Nsp9, and Nsp10 form functional complexes with CoV core enzymes and thereby stimulate replication. Coronaviruses cap their mRNAs; RNA cap methylation may involve at least three proteins: Nsp10, Nsp14, and Nsp16. Nsp10 serves as a cofactor for both Nsp14 and Nsp16. Nsp14 consists of 2 domains with different enzymatic activities: an N-terminal ExoN domain and a C-terminal cap (guanine-N7) methyltransferase (N7-MTase) domain. The association of Nsp10 with Nsp14 enhances Nsp14's exoribonuclease (ExoN) activity, and not its N7-Mtase activity. ExoN is important for proofreading and therefore, the prevention of lethal mutations. The Nsp10/Nsp14 complex hydrolyzes double-stranded RNA in a 3' to 5' direction as well as a single mismatched nucleotide at the 3'-end, mimicking an erroneous replication product, and may function in a replicative mismatch repair mechanism. Nsp16 Cap-0 specific (nucleoside-2'-O-)-methyltransferase (2'OMTase) acts sequentially to Nsp14 MTase in RNA capping methylation, and methylates the RNA cap at the ribose 2'-O position; it catalyzes the conversion of the cap-0 structure on m7GpppA-RNA to a cap-1 structure. The association of Nsp10 with Nsp16 enhances Nsp16's 2'OMTase activity, possibly through enhanced RNA binding affinity. Additionally, transmissible gastroenteritis virus (TGEV) Nsp10, Nsp16 and their complex can interact with DII4, which normally binds to Notch receptors; this interaction may disturb Notch signaling. Nsp10 also binds 2 zinc ions with high affinity.


Pssm-ID: 409326  Cd Length: 130  Bit Score: 267.61  E-value: 2.34e-82
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 4231 AGNATEVPANSTVLSFCAFAVDPAKAYKDYLASGGQPITNCVKMLCTHTGTGQAITVTPEANMDQESFGGASCCLYCRCH 4310
Cdd:cd21901    1 AGKQTEVASNSSLLTLCAFAVDPAKTYLDAVKSGGKPVGNCVKMLTNGTGTGQAITVKPEANTNQDSYGGASVCLYCRAH 80
                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|.
gi 30027621 4311 IDHPNPKGFCDLKGKYVQIPTTCaNDPVGFTLRNTVCTVCGMWKGYGCSCD 4361
Cdd:cd21901   81 VEHPDMDGVCKLKGKYVQVPLGT-NDPVRFCLENDVCKVCGCWLGNGCSCD 130
SARS-CoV-like_Nsp1_N cd21796
N-terminal domain of non-structural protein 1 from Severe acute respiratory syndrome-related ...
13-127 1.96e-79

N-terminal domain of non-structural protein 1 from Severe acute respiratory syndrome-related coronavirus and betacoronavirus in the B lineage; This model represents the N-terminal domain of non-structural protein 1 (Nsp1) from betacoronaviruses in the sarbecovirus subgenus (B lineage), including highly pathogenic coronaviruses such as Severe acute respiratory syndrome-related coronavirus (SARS-CoV) and SARS-CoV2 (also called 2019 novel CoV or 2019-nCoV). CoVs utilize a multi-subunit replication/transcription machinery assembled from a set of non-structural proteins (Nsps) generated as cleavage products of the ORF1a and ORF1ab viral polyproteins. Nsp1 is the N-terminal cleavage product released from the ORF1a polyprotein by the action of papain-like protease (PLpro). Though Nsp1s of alphaCoVs and betaCoVs share structural similarity, they show no significant sequence similarity and may be considered as genus-specific markers. Despite low sequence similarity, the Nsp1s of alphaCoVs and betaCoVs exhibit remarkably similar biological functions, and are involved in the regulation of both host and viral gene expression. CoV Nsp1 induces suppression of host gene expression and interferes with host immune response. It inhibits host gene expression in two ways: by targeting the translation and stability of cellular mRNAs, and by inhibiting mRNA translation and inducing an endonucleolytic RNA cleavage in the 5'-UTR of cellular mRNAs through its tight association with the 40S ribosomal subunit, a key component of the cellular translation machinery. Inhibition of host mRNA translation includes that of type I interferons, major components of the host innate immune response. Nsp1 is critical in regulating viral replication and gene expression, as shown by multiple evidences, including: mutations in the Nsp1 coding region of the transmissible gastroenteritis virus (TGEV) and murine hepatitis virus (MHV) genomes cause drastic reduction or elimination of infectious virus; bovine coronavirus (BCoV) Nsp1 is an RNA-binding protein that interacts with cis-acting replication elements in the 5'-UTR of the BCoV genome, implying its potential role in the regulation of viral translation or replication; and SARS-CoV Nsp1 enhances virus replication by binding to a stem-loop structure in the 5'-UTR of its genome.


Pssm-ID: 439285  Cd Length: 115  Bit Score: 258.67  E-value: 1.96e-79
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621   13 HVQLSLPVLQVRDVLVRGFGDSVEEALSEAREHLKNGTCGLVELEKGVLPQLEQPYVFIKRSDALSTNHGHKVVELVAEM 92
Cdd:cd21796    1 HVQLSLPVLQVRDVLVRGFGDSVEEALSEAREHLKNGTCGLVELEKGVLPQLEQPYVFIKRSDALSTNHGHKVVELVAEL 80
                         90       100       110
                 ....*....|....*....|....*....|....*
gi 30027621   93 DGIQYGRSGITLGVLVPHVGETPIAYRNVLLRKNG 127
Cdd:cd21796   81 DGIQYGRSGITLGVLVPHVGETPIAYRNVLLRKNG 115
SARS-CoV-like_Nsp3_betaSM cd21814
betacoronavirus-specific marker of non-structural protein 3 from Severe acute respiratory ...
2021-2136 2.40e-78

betacoronavirus-specific marker of non-structural protein 3 from Severe acute respiratory syndrome-related coronavirus and betacoronavirus in the B lineage; This model represents the betacoronavirus-specific marker (betaSM), also called group 2-specific marker (G2M), of non-structural protein 3 (Nsp3) from betacoronavirus in the sarbecovirus subgenus (B lineage), including highly pathogenic human coronaviruses such as Severe acute respiratory syndrome-related coronavirus (SARS-CoV) and SARS-CoV2 (also called 2019 novel CoV or 2019-nCoV). The betaSM/G2M is located C-terminal to the nucleic acid-binding (NAB) domain. This region is absent in alpha- and deltacoronavirus Nsp3; there is a gammacoronavirus-specific marker (gammaSM) at this position in gammacoronavirus Nsp3. Nsp3 is a large multi-functional multi-domain protein that is an essential component of the replication/transcription complex (RTC), which carries out RNA synthesis, RNA processing, and interference with the host cell innate immune system. Little is known about the betaSM/G2M domain; it is predicted to be non-enzymatic and may be an intrinsically disordered region. The betaSM/G2M domain is part of the predicted PLnc domain (made up of 385 amino acids) of SARS-CoV Nsp3 that may function as a replication/transcription scaffold, with interactions to Nsp5, Nsp12, Nsp13, Nsp14, and Nsp16.


Pssm-ID: 409629  Cd Length: 116  Bit Score: 255.57  E-value: 2.40e-78
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 2021 QQPTSEEVVENPTIQKEVIECDVKTTEVVGNVILKPSDEGVKVTQELGHEDLMAAYVENTSITIKKPNELSLALGLKTIA 2100
Cdd:cd21814    1 QQPTSEEVVENPTIQKEVIECDVKTTEVVGNVILKPSDEGVKVTQELGHEDLMAAYVENTSITIKKPNELSLALGLKTLA 80
                         90       100       110
                 ....*....|....*....|....*....|....*.
gi 30027621 2101 THGIAAINSVPWSKILAYVKPFLGQAAITTSNCAKR 2136
Cdd:cd21814   81 THGAAAINSVPWSKILAYVKPFLGQAAVTTSNCAKR 116
NendoU_nv cd21158
Nidoviral uridylate-specific endoribonuclease (NendoU) domain of coronavirus Nonstructural ...
6623-6773 1.29e-76

Nidoviral uridylate-specific endoribonuclease (NendoU) domain of coronavirus Nonstructural protein 15 (Nsp15), arterivirus Nsp11, torovirus endoribonuclease, and related proteins; Nidovirus endoribonucleases (NendoUs) are uridylate-specific endoribonucleases which release a cleavage product containing a 2',3'-cyclic phosphate at the 3' terminal end. NendoUs include Nsp15 from coronaviruses and Nsp11 from arteriviruses, both of which may participate in the viral replication process and in the evasion of the host immune system. This family also includes torovirus NendoUs. Except for turkey coronavirus (TCoV) Nsp15, Mn2+ is generally essential for the catalytic activity of coronavirus Nsp15. Mn2+ is dispensable, and to some extent inhibits the activity of arterivirus (Porcine Reproductive and Respiratory Syndrome virus) PRRSV Nsp11. Coronavirus Nsp15 from Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV), human Coronavirus 229E (HCoV229E), and murine hepatitis virus (MHV) form a functional hexamer while Porcine DeltaCoronavirus (PDCoV) Nsp15 has been shown to exist as a dimer and monomer in solution. Nsp11 from the arterivirus PRRSV is a dimer. NendoUs are distantly related to Xenopus laevis Mn(2+)-dependent uridylate-specific endoribonuclease (XendoU) which is involved in the processing of intron-encoded box C/D U16 small, nucleolar RNA.


Pssm-ID: 439157  Cd Length: 151  Bit Score: 252.18  E-value: 1.29e-76
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 6623 FTQSRDLEDFKPRSQMETDFLELAMDEFIQRYKLEGYAFEHIVYGDFSHGQLGGLHLMIGLAKRSQDSPLKLEDFIPMDS 6702
Cdd:cd21158    1 FTQGRNLQEFLPRSDMERDFLPVDMDVFIEKYGLEIYAFEHVVYGDFSHTTLGGLHLVISLYKRFKEGPLPREEFIPNDS 80
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 30027621 6703 TVKNYFITDAQTGSSKCVCSVIDLLLDDFVEIIKSQDLSVISKVVKVTIDYAEISFMLWCKDGHVETFYPK 6773
Cdd:cd21158   81 TVKNYGVTSPGTKASKAVCTLIDLLLDDFVEILKSQDLEVVSKVVKVMIDFKEVRFMLWCKDGDVQTFYPQ 151
Macro_cv_SUD-N_Nsp3-like cd21562
SUD-N macrodomain (or Mac2 domain) of the SARS Unique Domain (SUD) of SARS-CoV non-structural ...
1209-1334 7.87e-76

SUD-N macrodomain (or Mac2 domain) of the SARS Unique Domain (SUD) of SARS-CoV non-structural protein 3 and related macrodomains; This subfamily includes the macrodomain referred to as SUD-N (N-terminal subdomain) of the SARS-unique domain (SUD) which binds G-quadruplexes (unusual nucleic-acid structures formed by consecutive guanosine nucleotides). It is found in the non-structural protein 3 (Nsp3) of Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) and highly related coronaviruses. SUD consists of three globular domains separated by short linker peptide segments: SUD-N, SUD-M, and SUD-C. Among these, SUD-N and SUD-M are macrodomains: the SUD-M domain (not represented in this subfamily) is a related macrodomain which also binds G-quadruplexes. SUD-N (also called Mac2) is specific to the Nsp3 of SARS and betacoronaviruses of the sarbecovirus subgenera (B lineage), while SUD-M (also called Mac3) is present in most Nsp3 proteins except the Nsp3 from betacoronaviruses of the embecovirus subgenera (A lineage). SUD-C adopts a frataxin-like fold, has structural similarity to DNA-binding domains of DNA-modifying enzymes, binds single-stranded RNA, and regulates the RNA binding behavior of the SUD-M macrodomain. SARS-CoV Nsp3 contains a third macrodomain (the X-domain or Mac1) which is also not represented in this subfamily. The X-domain may function as a module binding poly(ADP-ribose); however, SUD-N and SUD-M do not bind ADP-ribose, as the triple glycine sequence involved in its binding is not conserved in these.


Pssm-ID: 394883  Cd Length: 126  Bit Score: 248.98  E-value: 7.87e-76
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 1209 KACIDEVTTTLEETKFLTNKLLLFADINGKLYHDSQNMLRGEDMSFLEKDAPYMVGDVITSGDITCVVIPSKKAGGTTEM 1288
Cdd:cd21562    1 KACIEEVTTTLEETKFLTNKLLLYADINGNLHEDSKNLLRGEDMSFLKKDAPYIVGDVITEGDITCVVIPSKKAGGTTEM 80
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*.
gi 30027621 1289 LSRALKKVPVDEYITTYPGQGCAGYTLEEAKTALKKCKSAFYVLPS 1334
Cdd:cd21562   81 LTRALKKVPTDEYITTYPGQGCAGYTLEEAKTALKKCKSAFYVLPS 126
NSP10 pfam09401
RNA synthesis protein NSP10; Non-structural protein 10 (NSP10) is involved in RNA synthesis. ...
4242-4361 2.63e-73

RNA synthesis protein NSP10; Non-structural protein 10 (NSP10) is involved in RNA synthesis. it is synthesized as a polyprotein whose cleavage generates many non-structural proteins. NSP10 contains two zinc binding motifs and forms two anti-parallel helices which are stacked against an irregular beta sheet. A cluster of basic residues on the protein surface suggests a nucleic acid-binding function.


Pssm-ID: 286486  Cd Length: 119  Bit Score: 241.20  E-value: 2.63e-73
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621   4242 TVLSFCAFAVDPAKAYKDYLASGGQPITNCVKMLCTHTGTGQAITVTPEANMDQESFGGASCCLYCRCHIDHPNPKGFCD 4321
Cdd:pfam09401    1 GLLSLCAFAVDPAKAYLDYLAQGGQPVTNCVKMLCNHAGTGQAITVKPEANTDQDSYGGASVCLYCRAHIEHPNPDGFCQ 80
                           90       100       110       120
                   ....*....|....*....|....*....|....*....|
gi 30027621   4322 LKGKYVQIPTTcANDPVGFTLRNTVCTVCGMWKGYGCSCD 4361
Cdd:pfam09401   81 LKGKFVQIPTG-TKDPVGFCLRNTVCTVCGCWLGYGCSCD 119
capping_2-OMTase_Nidovirales cd20762
Cap-0 specific (nucleoside-2'-O-)-methyltransferase of nidovirales; Cap-0 specific ...
6818-7008 4.66e-72

Cap-0 specific (nucleoside-2'-O-)-methyltransferase of nidovirales; Cap-0 specific (nucleoside-2'-O-)-methyltransferase (2'OMTase) catalyzes the methylation of Cap-0 (m7GpppNp) at the 2'-hydroxyl of the ribose of the first nucleotide, using S-adenosyl-L-methionine (AdoMet) as the methyl donor. This reaction is the fourth and last step in mRNA capping, the creation of the stabilizing five-prime cap (5' cap) on mRNA. Nidovirales, a family of ss(+)RNA viruses, cap their mRNAs. For one member, Coronavirus, the 2'OMTase activity is located in the nonstructural protein 16 (NSP16). For others, the 2'OMTase activity may be located in replicase polyprotein 1ab.


Pssm-ID: 394921  Cd Length: 176  Bit Score: 240.30  E-value: 4.66e-72
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 6818 NVAKYTQLCQYLNTLTLaVPYNMRVIHFGAGSDKGVAPGTAVLRQWLptGTLLVDSDLNDFVSDADSTLIGDCATVHTaN 6897
Cdd:cd20762    1 NISKYVQLCQYINDHLK-LPINPRVLHLGAASDKGYSPGDEVLRQPF--GGIVLDYDLNDFVSHSDIRHINDCNNVFS-G 76
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 6898 KWDLIISDMYDPRTkhvtkenDSKEGFFTYLCGFIKqklaLGGSIAVKITEHSWNADLYKLMGHFSWWTAFVTNVNASSS 6977
Cdd:cd20762   77 KYDLIISDIYAPDT-------DNTELLFDYLNNHLK----LGGSIIWKTTERSTSDNLYQIAKYFGSWTFFTTRVNASSS 145
                        170       180       190
                 ....*....|....*....|....*....|.
gi 30027621 6978 EAFLIGANYLGKPKEQIDGYTMHANYIFWRN 7008
Cdd:cd20762  146 EVFLVFKYYLGTYKEQIDYNDIHALLIAYRN 176
SARS-CoV-like_Nsp3_NAB cd21822
nucleic acid binding domain of non-structural protein 3 from Severe acute respiratory ...
1890-1996 4.77e-71

nucleic acid binding domain of non-structural protein 3 from Severe acute respiratory syndrome-related coronavirus and betacoronavirus in the B lineage; This model represents the nucleic acid binding (NAB) domain of non-structural protein 3 (Nsp3) from betacoronavirus in the sarbecovirus subgenus (B lineage) and hibecovirus subgenus, including highly pathogenic human coronaviruses (CoVs) such as Severe acute respiratory syndrome-related coronavirus (SARS-CoV) and SARS-CoV2 (also called 2019 novel CoV or 2019-nCoV). The NAB domain represents a new fold, with a parallel four-strand beta-sheet holding two alpha-helices of three and four turns that are oriented antiparallel to the beta-strands. NAB is a cytoplasmic domain located between the papain-like protease (PLPro) and betacoronavirus-specific marker (betaSM) domains of CoV Nsp3. Nsp3 is a large multi-functional multi-domain protein that is an essential component of the replication/transcription complex (RTC), which carries out RNA synthesis, RNA processing, and interference with the host cell innate immune system. The NAB domain both binds ssRNA and unwinds dsDNA. It prefers to bind ssRNA containing repeats of three consecutive guanines. A group of residues that form a positively charged patch on the protein surface of SARS-CoV Nsp3 NAB serves as the binding site of nucleic acids. This site is conserved in the NAB of Nsp3 from betacoronavirus in the B lineage.


Pssm-ID: 409348  Cd Length: 107  Bit Score: 234.35  E-value: 4.77e-71
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 1890 DLVPTQPLPNASFDNFKLTCSNTKFADDLNQMTGFTKPASRELSVTFFPDLNGDVVAIDYRHYSASFKKGAKLLHKPIVW 1969
Cdd:cd21822    1 DLVPTQPLPNASFDNFKLTCSNTKFADDLNQMTGFTKPASRELSVTFFPDLNGDVVAIDYRHYSPSFKKGAKLLHKPIVW 80
                         90       100
                 ....*....|....*....|....*..
gi 30027621 1970 HINQATTKTTFKPNTWCLRCLWSTKPV 1996
Cdd:cd21822   81 HINQATTKTTYKPNTWCLRCLWSTKPV 107
TM_Y_alphaCoV_Nsp3_C cd21712
C-terminus of alphacoronavirus non-structural protein 3, including transmembrane and Y domains; ...
2196-2739 1.69e-70

C-terminus of alphacoronavirus non-structural protein 3, including transmembrane and Y domains; This model represents the C-terminus of non-structural protein 3 (Nsp3) from alphacoronavirus, including Porcine epidemic diarrhea virus and Human coronavirus 229E, among others. This conserved C-terminus includes two transmembrane (TM) regions TM1 and TM2, an ectodomain (3Ecto) between the TM1 and TM2 that is glycosylated and located on the lumenal side of the ER, an amphiphatic region (AH1) that is not membrane-spanning, and a large Y domain of approximately 370 residues. Nsp3 is a large multi-functional multi-domain protein that is an essential component of the replication/transcription complex (RTC), which carries out RNA synthesis, RNA processing, and interference with the host cell innate immune system. In the related betacoronaviruses, Severe acute respiratory syndrome-related coronavirus (SARS-CoV) and murine hepatitis virus (MHV), the TM1, 3Ecto and TM2 domains are important for the papain-like protease (PL2pro) domain to process Nsp3-Nsp4 cleavage. It has also been shown that the interaction of 3Ecto with the lumenal loop of Nsp4 is essential for ER rearrangements in cells infected with SARS-CoV or MHV. The Y domain, located at the cytosolic side of the ER, consists of the Y1 and CoV-Y subdomains, which are conserved in nidovirus and coronavirus, respectively. Functional information about the Y domain is limited; it has been shown that Nsp3 binding to Nsp4 is less efficient without the Y domain.


Pssm-ID: 409660  Cd Length: 501  Bit Score: 248.31  E-value: 1.69e-70
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 2196 KSPKFSKLFTiamwLLLLSICLGSLICVTAAFGVLLSNFgapsyCNGVRELYLNSSNVTTmDFCEGSFPCSICLSGLDSL 2275
Cdd:cd21712    5 KKKKVWFFAK----LLLLLYALYALLFMFVRFPPLNSSL-----CSGYVDGYANSSFVKS-EVCGNSLLCKACLAGYDEL 74
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 2276 DSYPALetiQVTISSYKLDLtilglaaeWVLAYMLFTKFFYLLGLSAIMQVFFGYFASHFIsNSWLMWFI----ISIVQM 2351
Cdd:cd21712   75 SDFPHL---QVVWDHVSDPL--------FSNVLPLFYFAFLLIFGNNYVRCFLLYFVAQYI-NNWGVYFGyqdySWFLHF 142
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 2352 APVSAMVRMYIFFASFYYIWKSYVHIMDGCTSSTCMMCYKRNRATRVECTTIVNGMKRSFYVYANGGRGFCKTHNWNCLN 2431
Cdd:cd21712  143 VPFDSFSDEIVVIFIVVKVLLFLKHVIFGCDKPSCKACSKSARLTRIPVQTIVNGSMKSFYVHANGGGKFCKKHNFFCVN 222
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 2432 CDTFCTGSTFISDEVARDLSLQFKRPINPTDQSSYIVDSVAVKNGALHLYfdkaGQKTYERHPL----SHFVNLDNLRAN 2507
Cdd:cd21712  223 CDSYGVGNTFINDEVARELSNVVKTTVQPTGPAYIEVDKVEFSNGFYYLY----SGDTFWRYNFditeKKYSCKEVLKNC 298
                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 2508 NTKGslpiNVIVFDgKSKCDESASKSASVYYSQLMCQPILLLDQVLVSDVgdSTEVSVKMFDAYVDTFSATFSVPMEKLK 2587
Cdd:cd21712  299 NLLD----DFIVYN-NNGSNVAQVKNACVYFSQLLCKPIKLVDSALLSSL--SVDFNGALHKAFVKVLKNSFNKDLSNCK 371
                        410       420       430       440       450       460       470       480
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 2588 ALvatahSELAKGVALDGVLSTFVSAArqgvvdtdvdtkdvieclKLSHHSDLEVTGDSCNNFMLTYNKVEN-MTPRDLG 2666
Cdd:cd21712  372 TL-----EECKKALGLDVSDDEFESAV------------------SNAHRYDVLLTDRSFNNFVTSYAKPEEkLSTHDIA 428
                        490       500       510       520       530       540       550
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 30027621 2667 ACIDCNARHINAQVAKSHNVSLIWNVKDYMSLSEQLRKQIRSAAKKNNIPFRLTCATTRQVVNVITTKISLKG 2739
Cdd:cd21712  429 VCMRAGAKVVNHNVLTKENVPIVWLAKDFSALSEEARKYIVKTTKAKGVNFLLTFNDNRMTTTLPAVSIVSKK 501
deltaCoV_Nsp5_Mpro cd21668
deltacoronavirus non-structural protein 5, also called Main protease (Mpro); This subfamily ...
3240-3539 1.58e-64

deltacoronavirus non-structural protein 5, also called Main protease (Mpro); This subfamily contains the coronavirus (CoV) non-structural protein 5 (Nsp5) also called the Main protease (Mpro), or 3C-like protease (3CLpro), found in deltacoronaviruses. CoVs utilize a multi-subunit replication/transcription machinery. A set of non-structural proteins (Nsps) generated as cleavage products of the ORF1a and ORF1ab viral polyproteins assemble to facilitate viral replication and transcription. Mpro/Nsp5 is a key enzyme in this process, making it a high value target for the development of anti-coronavirus therapeutics. These enzymes belong to the MEROPS peptidase C30 family, where the active site residues His and Cys form a catalytic dyad. The structures of Mpro/Nsp5 consist of three domains with the first two containing anti-parallel beta barrels and the third consisting of an arrangement of alpha-helices. The catalytic residues are found in a cleft between the first two domains. Mpro/Nsp5 requires a Gln residue in the P1 position of the substrate and space for only small amino-acid residues such as Gly, Ala, or Ser in the P1' position; since there is no known human protease with a specificity for Gln at the cleavage site of the substrate, these viral proteases are suitable targets for the development of antiviral drugs.


Pssm-ID: 394889  Cd Length: 302  Bit Score: 223.54  E-value: 1.58e-64
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 3240 QSGFRKMAFPSGKVEGCMVQVTCGTTTLNGLWLDDTVYCPRHVI--CTAEdmlnpNYEDLLIRKSNHSFLV--QAGNVQL 3315
Cdd:cd21668    1 QAGIKILLHPSGVVERCMVSVTYNGSTLNGIWLHNVVYCPRHVIgkYTGS-----QWQDMVSIADCRDFVIfcPTQGIQL 75
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 3316 RVIGHSMQNCLLRLKVDTSNPKTPKYKFVRIQPGQTFSVLACYNGSPSGVYQCAMRPNHTIKGSFLNGSCGSVGFNIDYD 3395
Cdd:cd21668   76 TVQSVKMVGAVLQLTVHTKNLHTPDYEFERATPGSSMTIACAYDGIVRNVYHVVLQTNNLIYASFLNGACGSVGYTLKGK 155
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 3396 CVSFCYMHHMELPTGVHAGTDLEGKFYGPFVDRQTAQAAGTDTTITLNVLAWLYAAVINGDR---WfLNRFTTTLNDFNL 3472
Cdd:cd21668  156 TLLLHYMHHLEFNNKTHGGTDLHGHFYGPYVDEEVAQHQTAFQYYTDNVVAQIYAHLLTIDAkpkW-LASQEISVEDFNE 234
                        250       260       270       280       290       300
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 30027621 3473 VAMKYNYE--PLTQDHVDILGPLSAQTGIAVLDMCAALKELLQNgMNGRTILGSTILEDEFTPFDVVRQ 3539
Cdd:cd21668  235 WAANNSFAnfPCESSNMAYLEGLAQTTKVSVGRVLNTIIQLTLN-RGGALIMGKPDFECDWTPEMVYNQ 302
NAR pfam16251
Nucleic acid-binding domain (NAR); This domain, approximately 100 residues in length, is ...
1884-1996 4.84e-63

Nucleic acid-binding domain (NAR); This domain, approximately 100 residues in length, is mainly found in Orf1a polyproteins in severe acute respiratory syndrome coronavirus. The global domain of the NAR represents a new fold, with a parallel four-strand beta-sheet holding two alpha-helices of three and four turns that are oriented antiparallel to the beta-strands and a group of residues form a positively charged patch on the protein surface as the binding site responsible for binding affinity for nucleic acids.


Pssm-ID: 406621  Cd Length: 129  Bit Score: 212.41  E-value: 4.84e-63
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621   1884 YTEQPIDLVPTQPLPNASF----------DNFKLTCSNTKFADDLNQMTGF--TKPASRELSVTFFPDLNGDVVAIDYRH 1951
Cdd:pfam16251    1 YTEQPIDLVPTKPIIKAQFrtfekvdgvyDNFKLTCSGHKFADDLNAKLGFdcNKPASRELKITEFPDANGDVVAADDDH 80
                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*....
gi 30027621   1952 YSASFKKGAKLLHKPIVW--HINQATTKTTF--KPNTWCLRCLWSTKPV 1996
Cdd:pfam16251   81 YSARFKKGAILFGKPIVWlgHEEAALKKLTFfnKPNTVCLECKFNTKPV 129
CoV_NSP6 pfam19213
Coronavirus replicase NSP6; This entry represents proteins found in Coronaviruses and includes ...
3575-3836 3.13e-62

Coronavirus replicase NSP6; This entry represents proteins found in Coronaviruses and includes the Non-structural Protein 6 (NSP6). Coronaviruses encode large replicase polyproteins which are proteolytically processed by viral proteases to generate mature Nonstructural Proteins (NSPs). NSP6 is a membrane protein containing 6 transmembrane domains with a large C-terminal tail. NSP6 from the avian coronavirus, infectious bronchitis virus (IBV) and the mouse hepatitis virus (MHV) have been shown to localize to the ER and to generate autophagosomes. Coronavirus NSP6 proteins have also been shown to limit autophagosome expansion. This may favour coronavirus infection by reducing the ability of autophagosomes to deliver viral components to lysosomes for degradation. NSP6 from IBV, MHV and severe acute respiratory syndrome coronavirus (SARS-CoV) have also been found to activate autophagy.


Pssm-ID: 437050  Cd Length: 260  Bit Score: 215.57  E-value: 3.13e-62
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621   3575 TQWSLFFFVYENAFLPFTLGIMAIAACAMLLVKHKHAFLCLFLLPSLATVAYFNM--VYMPASWVMRIMTWlelaDTSLS 3652
Cdd:pfam19213    2 LMYTAFYWLPPNLITPVLPVLLCVSAILMLFIKHKHLFLTTFLLPSVVVLAYYNFtwDYYVNSFLRYVYDY----HMSLT 77
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621   3653 GYRLKDCVMYASALVLLILMTARTVYDDAARrVWTLMNVITLVYKVYYGNALDQA---ISMWALVISVTSNYSGVVTTIM 3729
Cdd:pfam19213   78 SFDLQGYFNIASCVFVNVLHTYRFVRSKSSI-ATYLVSLVVVVYMYVYGYALGTAsdpLSLLMMVLSLLTSYWYTGAIAY 156
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621   3730 FLARAIVFVCVEYYPLLFitgNTLQCIMLVYCFLGYCCCCYFGLFCLLNRYFRLTLGVYDYLVSTQEFRYMNSQGLLPPK 3809
Cdd:pfam19213  157 KLAKYIALYYPPSLIAVF---GDVKVVLLVYLCLGYVCCVYFGVLYWINRFTRLPLGVYDFKVSAAEFKYMVANGLSAPR 233
                          250       260
                   ....*....|....*....|....*..
gi 30027621   3810 SSIDAFKLNIKLLGIGGKPCIKVATVQ 3836
Cdd:pfam19213  234 NVFEALILNFKLLGIGGNRTIKISTVQ 260
ZBD_cv_Nsp13-like cd21401
Cys/His rich zinc-binding domain (CH/ZBD) of coronavirus SARS NSP13 helicase and related ...
5302-5396 1.22e-60

Cys/His rich zinc-binding domain (CH/ZBD) of coronavirus SARS NSP13 helicase and related proteins; Helicases catalyze NTP-dependent unwinding of nucleic acid duplexes into single strands and are classified based on the arrangement of conserved motifs into six superfamilies. This coronavirus family includes Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) non-structural protein 13 (SARS-Nsp13) and belongs to helicase superfamily 1 (SF1) and to a family of nindoviral replication helicases. SARS-Nsp13 has an N-terminal CH/ZBD, a stalk domain, a 1B regulatory domain, and SF1 helicase core. The CH/ZBD has 3 zinc-finger (ZnF1-3) motifs. SARS-Nsp13 is a component of the viral RNA synthesis replication and transcription complex (RTC). The SARS-Nsp13 CH/ZBD is indispensable for helicase activity and interacts with SARS-Nsp12, the RNA-dependent RNA polymerase (RdRp). Structural studies of a stable SARS-CoV-2 RTC which included two molecules of Nsp13, the RdRp holoenzyme (Nsp7, two molecules of Nsp8, Nsp12), and an RNA template product, show that one Nsp13 CH/ZBD domain interacts with Nsp12, and both Nsp13-CH/ZBD domains interact with the Nsp8. This stable SARS-CoV-2 RTC suggests that the Nsp13 helicase may drive RTC backtracking, affecting proofreading and template switching.


Pssm-ID: 439168  Cd Length: 95  Bit Score: 204.16  E-value: 1.22e-60
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 5302 AVGACVLCNSQTSLRCGACIRRPFLCCKCCYDHVISTSHKLVLSVNPYVCNAPGCDVTDVTQLYLGGMSYYCKSHKPPIS 5381
Cdd:cd21401    1 AVGLCVVCNSQTVLRCGDCIRRPFLCCKCCYDHVMSTSHKFILSINPYVCNAPGCGVSDVTKLYLGGMSYYCEDHKPSLS 80
                         90
                 ....*....|....*
gi 30027621 5382 FPLCANGQVFGLYKN 5396
Cdd:cd21401   81 FPLCANGFVFGLYKN 95
betaCoV_Nsp9 cd21898
betacoronavirus non-structural protein 9; This model represents the non-structural protein 9 ...
4118-4230 2.58e-59

betacoronavirus non-structural protein 9; This model represents the non-structural protein 9 (Nsp9) from betacoronaviruses including highly pathogenic Severe acute respiratory syndrome-related coronavirus (SARS-CoV), SARS-CoV2 (also called 2019 novel CoV or 2019-nCoV), and Middle East respiratory syndrome-related (MERS) CoV. CoVs utilize a multi-subunit replication/transcription machinery assembled from a set of non-structural proteins (Nsps) generated as cleavage products of the ORF1a and ORF1ab viral polyproteins. All of these Nsps, except for Nsp1 and Nsp2, are considered essential for transcription, replication, and translation of the viral RNA. Nsp9, with Nsp7, Nsp8, and Nsp10, localizes within the replication complex. Nsp9 is an essential single-stranded RNA-binding protein for coronavirus replication; it shares structural similarity to the oligosaccharide-binding (OB) fold, which is characteristic of proteins that bind to ssDNA or ssRNA. Nsp9 requires dimerization for binding and orienting RNA for subsequent use by the replicase machinery. CoV Nsp9s have diverse forms of dimerization that promote their biological function, which may help elucidate the mechanism underlying CoVs replication and contribute to the development of antiviral drugs. Generally, dimers are formed via interaction of the parallel alpha-helices containing the protein-protein interaction motif GXXXG; additionally, the N-finger region may also play a critical role in dimerization as seen in porcine delta coronavirus (PDCoV) Nsp9. As a member of the replication complex, Nsp9 may not have a specific RNA-binding sequence but may act in conjunction with other Nsps as a processivity factor, as shown by mutation studies indicating that Nsp9 is a key ingredient that intimately engages other proteins in the replicase complex to mediate efficient virus transcription and replication.


Pssm-ID: 409331  Cd Length: 111  Bit Score: 201.09  E-value: 2.58e-59
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 4118 NNELSPVALRQMSCAAGTTQTACtDDNALAYYNNSKGGRFVLALLSDHQDLKWARFPKSDGtGTIYTELEPPCRFVTDTP 4197
Cdd:cd21898    1 NNELMPQGLKTMVVTAGPDQTAC-NTPALAYYNNVQGGRMVMAILSDVDGLKYAKVEKSDG-GFVVLELDPPCKFLVQTP 78
                         90       100       110
                 ....*....|....*....|....*....|...
gi 30027621 4198 KGPKVKYLYFIKGLNNLNRGMVLGSLAATVRLQ 4230
Cdd:cd21898   79 KGPKVKYLYFVKGLNNLHRGQVLGTIAATVRLQ 111
CoV_Nsp9 cd21881
coronavirus non-structural protein 9; This model represents the non-structural protein 9 (Nsp9) ...
4118-4230 1.82e-57

coronavirus non-structural protein 9; This model represents the non-structural protein 9 (Nsp9) from coronaviruses, including highly pathogenic betacoronaviruses such as Severe acute respiratory syndrome-related coronavirus (SARS-CoV), SARS-CoV2 (also called 2019 novel CoV or 2019-nCoV), and Middle East respiratory syndrome-related (MERS) CoV. CoVs utilize a multi-subunit replication/transcription machinery assembled from a set of non-structural proteins (Nsps) generated as cleavage products of the ORF1a and ORF1ab viral polyproteins. All of these Nsps, except for Nsp1 and Nsp2, are considered essential for transcription, replication, and translation of the viral RNA. Nsp9, with Nsp7, Nsp8, and Nsp10, localizes within the replication complex. Nsp9 is an essential single-stranded RNA-binding protein for CoV replication; it shares structural similarity to the oligosaccharide-binding (OB) fold, which is characteristic of proteins that bind to ssDNA or ssRNA. Nsp9 requires dimerization for binding and orienting RNA for subsequent use by the replicase machinery. CoV Nsp9s have diverse forms of dimerization that promote their biological function, which may help elucidate the mechanism underlying CoVs replication and contribute to the development of antiviral drugs. Generally, dimers are formed via interaction of the parallel alpha-helices containing the protein-protein interaction motif GXXXG at the C-terminus; additionally, the N-finger region may also play a critical role in dimerization as seen in porcine delta coronavirus (PDCoV) Nsp9. As a member of the replication complex, Nsp9 may not have a specific RNA-binding sequence but may act in conjunction with other Nsps as a processivity factor, as shown by mutation studies indicating that Nsp9 is a key ingredient that intimately engages other proteins in the replicase complex to mediate efficient virus transcription and replication.


Pssm-ID: 409329  Cd Length: 111  Bit Score: 195.81  E-value: 1.82e-57
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 4118 NNELSPVALRQMSCAAGTTQTaCTDDNALAYYNNSKGGRFVLALLSDHQDLKWARFPKSDGtGTIYTELEPPCRFVTDTP 4197
Cdd:cd21881    1 NNELSPVALKQMSCAAGTDQT-CTDDEAKAYYNNSKGGRFVLAITSDKPDLKVARFLKEDG-GTIYTELEPPCRFVTDVP 78
                         90       100       110
                 ....*....|....*....|....*....|...
gi 30027621 4198 KGPKVKYLYFIKGLNNLNRGMVLGSLAATVRLQ 4230
Cdd:cd21881   79 KGPKVKYLYFIKNLNSLNRGMVLGSISATVRLQ 111
nsp9 pfam08710
nsp9 replicase; nsp9 is a single-stranded RNA-binding viral protein likely to be involved in ...
4118-4230 1.23e-56

nsp9 replicase; nsp9 is a single-stranded RNA-binding viral protein likely to be involved in RNA synthesis. Its structure comprises of a single beta barrel.


Pssm-ID: 285872  Cd Length: 111  Bit Score: 193.46  E-value: 1.23e-56
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621   4118 NNELSPVALRQMSCAAGTTQtACTDDNALAYYNNSKGGRFVLALLSDHQDLKWARFPKSDGTgTIYTELEPPCRFVTDTP 4197
Cdd:pfam08710    1 NNELMPGKLKTKACKAGVTD-AHCSVEGKAYYNNEGGGSFVYAILSSNPNLKYAKFEKEDGN-VIYVELEPPCRFVVDTP 78
                           90       100       110
                   ....*....|....*....|....*....|...
gi 30027621   4198 KGPKVKYLYFIKGLNNLNRGMVLGSLAATVRLQ 4230
Cdd:pfam08710   79 KGPEVKYLYFVKNLNNLRRGMVLGYISATVRLQ 111
NendoU_XendoU-like cd21144
Nidoviral uridylate-specific endoribonuclease (NendoU) domain of coronavirus Nonstructural ...
6660-6772 1.47e-55

Nidoviral uridylate-specific endoribonuclease (NendoU) domain of coronavirus Nonstructural protein 15 (Nsp15), arterivirus Nsp11, torovirus endoribonuclease, Xenopus laevis endoribonuclease XendoU, and related proteins; Nidovirus endoribonucleases (NendoUs) and eukaryotic Xenopus laevis-like endoribonucleases (XendoUs) are uridylate-specific endoribonucleases which release a cleavage product containing a 2',3'-cyclic phosphate at the 3' terminal end. NendoUs include Nsp15 from coronaviruses and Nsp11 from arteriviruses, both of which may participate in the viral replication process and in the evasion of the host immune system. XendoU is involved in the processing of intron-encoded box C/D U16 small, nucleolar RNA. Except for turkey coronavirus (TCoV) Nsp15, Mn2+ is generally essential for the catalytic activity of coronavirus Nsp15. Mn2+ is dispensable, and to some extent inhibits the activity of arterivirus (Porcine Reproductive and Respiratory Syndrome virus) PRRSV Nsp11. XendoU also requires Mn2+. Coronavirus Nsp15 from Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV), human Coronavirus 229E (HCoV229E), and murine hepatitis virus (MHV) forms a functional hexamer while Porcine DeltaCoronavirus (PDCoV) Nsp15 has been shown to exist as a dimer and a monomer in solution. Nsp11 from the arterivirus PRRSV is a dimer.


Pssm-ID: 439156  Cd Length: 113  Bit Score: 190.13  E-value: 1.47e-55
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 6660 AFEHIVYGDFSHGQLGGLHLMIGLAKRSQDSPLKLEDFIPMDSTVKNYFITDAQTGSSKCVCSVIDLLLDDFVEIIKSQD 6739
Cdd:cd21144    1 AFEHVVYGDFSHQELGGLHLLIGLYKREKEKNIDNESRPDEDSTVLNYFITWKQTEMVKPVCSVIDLSLDDFVAIYKSQD 80
                         90       100       110
                 ....*....|....*....|....*....|...
gi 30027621 6740 LSVISKVVKVTIDYAEISFMLWCKDGHVETFYP 6772
Cdd:cd21144   81 LQVVSKVVKVRIDETEIQFMLWCKDGYVGTFYP 113
M_alpha_beta_cv_Nsp15-like cd21167
middle domain of alpha- and beta-coronavirus Nonstructural protein 15 (Nsp15), and related ...
6494-6625 1.98e-55

middle domain of alpha- and beta-coronavirus Nonstructural protein 15 (Nsp15), and related proteins; Nidovirus endoribonucleases (NendoUs) are uridylate-specific endoribonucleases, which release a cleavage product containing a 2',3'-cyclic phosphate at the 3' terminal end. NendoUs include Nsp15 from coronaviruses and Nsp11 from arteriviruses, both of which may participate in the viral replication process and in the evasion of the host immune system. Coronavirus Nsp15 NendoUs have an N-terminal domain, a middle (M) domain and a C-terminal catalytic (NendoU) domain. Coronavirus Nsp15 from Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV), human Coronavirus 229E (HCoV229E), and Murine Hepatitis Virus (MHV) form a functional hexamer. This middle domain harbors residues involved in hexamer formation and in trimer stability. Oligomerization of Porcine DeltaCoronavirus (PDCoV) Nsp15 differs from that of the other coronaviruses; it has been shown to exist as a dimer and a monomer in solution.


Pssm-ID: 439161  Cd Length: 127  Bit Score: 190.62  E-value: 1.98e-55
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 6494 PVPEIKILNNLGVDIAANTVIWDYKREAPAHVSTIGVCTMTDIAKKptesacSSLTVLFDGRVEGQVDLFRNARNGVLIT 6573
Cdd:cd21167    1 PVPELKLLRNLGVDICYKFVLWDYEREAPFTSSTIGVCKYTDIDKK------SDLNVLFDGRDPGSLERFRSARNAVLIS 74
                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|...
gi 30027621 6574 EGSVKGLTPSKGPAQASVNGVTLIGES-VKTQFNYFKKVDGIIQQLPETYFTQ 6625
Cdd:cd21167   75 TTKVKGLKPIKGPNYASLNGVVVESVDkKKVKFYYYVRKDGEFVDLTDTYFTQ 127
Macro_cv_SUD-M_Nsp3-like cd21563
SUD-M macrodomain (or Mac3 domain) of the SARS Unique Domain (SUD) of SARS-CoV non-structural ...
1345-1465 1.06e-54

SUD-M macrodomain (or Mac3 domain) of the SARS Unique Domain (SUD) of SARS-CoV non-structural protein 3 and related macrodomains; This subfamily includes the macrodomain referred to as SUD-M (middle SUD subdomain) of the SARS-unique domain (SUD) which binds G-quadruplexes (unusual nucleic-acid structures formed by consecutive guanosine nucleotides). It is found in non-structural protein 3 (Nsp3) of Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) and related coronaviruses. SUD consists of three globular domains separated by short linker peptide segments: SUD-N, SUD-M, and SUD-C. Among these, SUD-N and SUD-M are macrodomains: The SUD-N domain (not represented in this subfamily) is a related macrodomain which also binds G-quadruplexes. While SUD-N (also called Mac2) is specific to the Nsp3 of SARS and betacoronaviruses of the sarbecovirus subgenera (B lineage), SUD-M (also called Mac3) is present in most Nsp3 proteins except the Nsp3 from betacoronaviruses of the embecovirus subgenera (A lineage). SUD-M, despite its name, is not specific to SARS. SUD-C adopts a frataxin-like fold, has structural similarity to DNA-binding domains of DNA-modifying enzymes, binds single-stranded RNA, and regulates the RNA binding behavior of the SUD-M macrodomain. SARS-CoV Nsp3 contains a third macrodomain (the X-domain or Mac1) which is also not represented in this subfamily. The X-domain may function as a module binding poly(ADP-ribose); however, SUD-N and SUD-M do not bind ADP-ribose, as the triple glycine sequence involved in its binding is not conserved in these.


Pssm-ID: 394884  Cd Length: 120  Bit Score: 188.27  E-value: 1.06e-54
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 1345 GTVSWNLREMLAHAEETRKLMPICMDVRAIMATIQRKYKGIKIQEGIVDyGVRFFFYTSKEPVASIITKLNSLNEPLVTM 1424
Cdd:cd21563    1 LTVSFNLRQMLAHAKEYGLLMPVCIDYKAFTKVLRRKGVDPKKGFQTVD-GVRFYFYSSKDPLADVIAALNSLGKPIITM 79
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|.
gi 30027621 1425 PIGYVTHGFNLEEAARCMRSLKAPAVVSVSSPDAVTTYNGY 1465
Cdd:cd21563   80 PLGYITHGLDLAEAAAIMRMLTVPYVVVLASPDAVPLYNGY 120
alphaCoV-Nsp6 cd21558
alphacoronavirus non-structural protein 6; Coronaviruses (CoV) redirect and rearrange host ...
3531-3836 3.51e-54

alphacoronavirus non-structural protein 6; Coronaviruses (CoV) redirect and rearrange host cell membranes as part of the viral genome replication and transcription machinery; they induce the formation of double-membrane vesicles in infected cells. CoV non-structural protein 6 (Nsp6), a transmembrane-containing protein, together with Nsp3 and Nsp4, have the ability to induce double-membrane vesicles that are similar to those observed in severe acute respiratory syndrome (SARS) coronavirus-infected cells. By itself, Nsp6 can generate autophagosomes from the endoplasmic reticulum. Autophagosomes are normally generated as a cellular response to starvation to carry cellular organelles and long-lived proteins to lysosomes for degradation. Degradation through autophagy may provide an innate defense against virus infection, or conversely, autophagosomes can promote infection by facilitating the assembly of replicase proteins. In addition to initiating autophagosome formation, Nsp6 also limits autophagosome expansion regardless of how they were induced, i.e. whether they were induced directly by Nsp6, or indirectly by starvation or chemical inhibition of MTOR signaling. This may favor coronavirus infection by compromising the ability of autophagosomes to deliver viral components to lysosomes for degradation.


Pssm-ID: 394844  Cd Length: 293  Bit Score: 193.57  E-value: 3.51e-54
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 3531 FTPFDVVRQCSGVTFQ-GKFKKIVKGthhwMLLTFLTSLLILVQSTQWSLFFFVYENAFLPFTLGIMAIAACAMLLVKHK 3609
Cdd:cd21558    1 FTTSEVIKQMYGVNLQsGKVKSAFKN----VLLVGVFLFMFWSELLMYTSFFWINPGLVTPVFLVLVLVSLLLTLFLKHK 76
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 3610 HAFLCLFLLPSLATVAYFNMVympasWVMRIMTWL-ELAD--TSLSGYRLKDCVMYASALVLLILMTARTVyddAARRVW 3686
Cdd:cd21558   77 MLFLQTFLLPSVIVTAFYNLA-----WDYYVTAVLaEYFDyhVSLMSFDIQGVLNIFVCLFVFFLHTYRFV---TSGTSW 148
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 3687 T--LMNVITLVYKVYYGNaldQAISMWALVISVTSNYSGVVTTIMFLARAIVFVCVeYYPLLFitgNTLQCIMLVYCFLG 3764
Cdd:cd21558  149 FtyVVSLVFVLYNYFYGN---DYLSLLMMVLSSITNNWYVGAIAYKLAYYIVYVPP-SLVADF---GTVKAVMLVYVALG 221
                        250       260       270       280       290       300       310
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 30027621 3765 YCCCCYFGLFCLLNRYFRLTLGVYDYLVSTQEFRYMNSQGLLPPKSSIDAFKLNIKLLGIGGKPCIKVATVQ 3836
Cdd:cd21558  222 YLCCVYYGILYWINRFTKLTLGVYDFKVSAAEFKYMVANGLKAPTGVFDALLLSFKLIGIGGERTIKISTVQ 293
CoV_NSP2_N pfam19211
Coronavirus replicase NSP2, N-terminal; This entry corresponds to the N-terminal region of ...
182-423 1.06e-52

Coronavirus replicase NSP2, N-terminal; This entry corresponds to the N-terminal region of coronavirus non-structural protein 2. NSP2 is encoded by ORF1a/1ab and proteolytically released from the pp1a/1ab polyprotein. The function of this protein is uncertain. This region contains numerous conserved and semi-conserved cysteine residues.


Pssm-ID: 437048 [Multi-domain]  Cd Length: 199  Bit Score: 185.59  E-value: 1.06e-52
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621    182 VTRYVDNNFCGPDGYPLD-----CIKDFLARAGKsmctlseqldyIESKRGVYCCrdheheiAWFTERSDKSYEHQTPFE 256
Cdd:pfam19211    1 DVIPVDQYMCGADGKPVLpedtwCFKDYFGDDGE-----------IVLNGGTYRK-------AWNVERKDVPYEKQSLFT 62
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621    257 IKSAKKFdtfkGECPKFVfpLNSKVKVIQPRVEKKKTEGFMGRIRSVYPVASPQECNN---MHLSTLMKCNHCDEVSWQT 333
Cdd:pfam19211   63 INSIEYL----GDVPHVL--PNGAVLVVAPRVKKSKKVVLSEKYKSLYDTYGSPFVTNpkpIFLHALVKCSSCGKESWTV 136
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621    334 CDFLKATCEHCGTENLVIeGPTTCGYLPTNAVVkmpcpacqdpeigpehsvadyhnhsnIETRLRKGGRTRCFGGCVFAY 413
Cdd:pfam19211  137 GDWSGFKCLCCGVYGNPV-CVQSAGLVKPGAVM--------------------------LITKAPVGAGTKFFGGAVLKY 189
                          250
                   ....*....|
gi 30027621    414 VGCYNKRAYW 423
Cdd:pfam19211  190 VGCVEGVAVW 199
capping_2-OMTase_viral cd20754
viral Cap-0 specific (nucleoside-2'-O-)-methyltransferase; Cap-0 specific (nucleoside-2'-O-) ...
6822-7007 4.52e-52

viral Cap-0 specific (nucleoside-2'-O-)-methyltransferase; Cap-0 specific (nucleoside-2'-O-)-methyltransferase (2'OMTase) catalyzes the methylation of Cap-0 (m7GpppNp) at the 2'-hydroxyl of the ribose of the first nucleotide, using S-adenosyl-L-methionine (AdoMet) as the methyl donor. This reaction is the fourth and last step in mRNA capping, the creation of the stabilizing five-prime cap (5' cap) on mRNA. Some dsDNA and dsRNA viruses, like the bluetongue virus (BTV), a member of the Reoviridae family, and Vaccinia virus, a member of the Poxviridae family, as well as some ss(+)RNA viruses, like Flaviviridae and Nidovirales, also cap their mRNAs and encode their own 2'OMTase. In BTV, all four reactions are catalyzed by a single protein, VP4. In Vaccinia, the activity is located in the processing factor of the poly(A) polymerase, VP39.


Pssm-ID: 394914  Cd Length: 179  Bit Score: 183.04  E-value: 4.52e-52
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 6822 YTQLCQYLNTLTLAVPYNMRVIHFGAGSdkgvAPGTAVLRQWlPTGTLLVDSDLNDFV---SDADSTLIGDCATVHT--- 6895
Cdd:cd20754    1 QLKLLLYLLTFLYKYPSAMRVIYIGAGP----GYHIYYLRDW-FTDSLWKLFDPRDFDhlgSNNIITKNKFFDHKLEklk 75
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 6896 --ANKWDLIISDMYDPRTKHVTKENDSKEGFFTYLCGFIKQKlaLGGSIAVKITEHSWNADlyklmGHFSWWTAFVTNVN 6973
Cdd:cd20754   76 flPNKKDLLISDIRSDRSSNVTKEEESTENNLDLQEEWIKII--NVGSACVKWRAPSWKDE-----GHFISGTLFPQPYA 148
                        170       180       190
                 ....*....|....*....|....*....|....
gi 30027621 6974 ASSSEAFLIGANYlGKPKEQIDGYtmHANYIFWR 7007
Cdd:cd20754  149 ASSSEMRLFFILY-LDTASLINVR--HADVEKLR 179
gammaCoV_Nsp10 cd21902
gammacoronavirus non-structural protein 10; This model represents the non-structural protein ...
4232-4361 4.09e-51

gammacoronavirus non-structural protein 10; This model represents the non-structural protein 10 (Nsp10) of gammacoronaviruses, including Infectious bronchitis virus (IBV)and Bottlenose dolphin coronavirus HKU22(BdCoV HKU22). CoVs utilize a multi-subunit replication/transcription machinery. A set of non-structural proteins (Nsps) generated as cleavage products of the ORF1a and ORF1ab viral polyproteins assemble to facilitate viral replication and transcription. Upon processing of the Nsp7-10 region by protease M (Mpro), the released four small proteins Nsp7, Nsp8, Nsp9, and Nsp10 form functional complexes with CoV core enzymes and thereby stimulate replication. Coronaviruses cap their mRNAs; RNA cap methylation may involve at least three proteins: Nsp10, Nsp14, and Nsp16. Nsp10 serves as a cofactor for both Nsp14 and Nsp16. Nsp14 consists of 2 domains with different enzymatic activities: an N-terminal ExoN domain and a C-terminal cap (guanine-N7) methyltransferase (N7-MTase) domain. The association of Nsp10 with Nsp14 enhances Nsp14's exoribonuclease (ExoN) activity, and not its N7-Mtase activity. ExoN is important for proofreading and therefore, the prevention of lethal mutations. The Nsp10/Nsp14 complex hydrolyzes double-stranded RNA in a 3' to 5' direction as well as a single mismatched nucleotide at the 3'-end, mimicking an erroneous replication product, and may function in a replicative mismatch repair mechanism. Nsp16 Cap-0 specific (nucleoside-2'-O-)-methyltransferase (2'OMTase) acts sequentially to Nsp14 MTase in RNA capping methylation and methylates the RNA cap at the ribose 2'-O position; it catalyzes the conversion of the cap-0 structure on m7GpppA-RNA to a cap-1 structure. The association of Nsp10 with Nsp16 enhances Nsp16's 2'OMTase activity, possibly through enhanced RNA binding affinity. Additionally, transmissible gastroenteritis virus (TGEV) Nsp10, Nsp16 and their complex can interact with DII4, which normally binds to Notch receptors; this interaction may disturb Notch signaling. Nsp10 also binds 2 zinc ions with high affinity.


Pssm-ID: 409327  Cd Length: 134  Bit Score: 178.55  E-value: 4.09e-51
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 4232 GNATEVPANSTVLSFCAFAVDPAKAYKDYLASGGQPITNCVKMLCTHTGTGQAITVTPEANMDQESFGGASCCLYCRCHI 4311
Cdd:cd21902    2 GHETEEVDAVGILSLCSFAVDPADTYCKYVAAGNQPLGNCVKMLTVHNGSGFAITSKPSPTPDQDSYGGASVCLYCRAHI 81
                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....
gi 30027621 4312 DHP----NPKGFCDLKGKYVQIPTTcANDPVGFTLRNTVCTVCGMWKGYGCSCD 4361
Cdd:cd21902   82 AHPggagNLDGRCQFKGSFVQIPTT-EKDPVGFCLRNKVCTVCQCWIGYGCQCD 134
gammaCoV_Nsp8 cd21832
gammacoronavirus non-structural protein 8; This model represents the non-structural protein 8 ...
3920-4109 1.38e-50

gammacoronavirus non-structural protein 8; This model represents the non-structural protein 8 (Nsp8) region of gammacoronaviruses that include Avian infectious bronchitis virus (IBV) and Canada goose coronavirus (CGCoV), among others. CoVs utilize a multi-subunit replication/transcription machinery. A set of non-structural proteins (Nsps) generated as cleavage products of the ORF1a and ORF1ab viral polyproteins assemble to facilitate viral replication and transcription. Upon processing of the Nsp7-10 region by protease M (Mpro), the released four small proteins Nsp7, Nsp8, Nsp9, and Nsp10 form functional complexes with CoV core enzymes and thereby stimulate replication. Most importantly, a complex of Nsp8 with Nsp7 has been shown to activate and confer processivity to the RNA-synthesizing activity of Nsp12, the RNA-dependent RNA-polymerase (RdRp); in SARS-CoV, point mutations in the genes encoding Nsp8 and Nsp7 have been shown to delay virus growth. Nsp8 and Nsp7 cooperate in activating the primer-dependent activity of the Nsp12 RdRp such that the level of their association may constitute a limiting factor for obtaining a high RNA polymerase activity. The subsequent Nsp7/Nsp8/Nsp12 polymerase complex is then able to associate with an active bifunctional Nsp14, which includes N-terminal 3' to 5' exoribonuclease (ExoN) and C-terminal N7-guanine cap methyltransferase (N7-MTase) activities, thus representing a unique coronavirus Nsp assembly that incorporates RdRp, exoribonuclease, and N7-MTase activities. Interaction of Nsp8 with Nsp7 appears to be conserved across the coronavirus family, making these proteins interesting drug targets. Nsp8 has a novel 'golf-club' fold composed of an N-terminal 'shaft' domain and a C-terminal 'head' domain. The shaft domain contains three helices, one of which is very long, while the head domain contains another three helices and seven beta-strands, forming an alpha/beta fold. SARS-CoV Nsp8 forms a 8:8 hexadecameric supercomplex with Nsp7 that adopts a hollow cylinder-like structure with a large central channel and positive electrostatic properties in the cylinder, while Feline infectious peritonitis virus Nsp8 forms a 1:2 heterotrimer with Nsp7. Regardless of their oligomeric structure, the Nsp7/Nsp8 complex functions as a noncanonical RNA polymerase capable of synthesizing RNA of up to the template length.


Pssm-ID: 409259  Cd Length: 210  Bit Score: 180.15  E-value: 1.38e-50
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 3920 AIASEFSSLPSYAAYATAQEAYEQAVANGDSEVV----LKKLKKSLNVAKSEFDRDAAMQRKLEKMADQAMTQMYKQARS 3995
Cdd:cd21832    1 SVTQEFSHIPSYAEYERAKDLYEKVLADSKNGGVtqqeLAAYRKAANIAKSVFDRDLAVQKKLDSMAERAMTTMYKEARV 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 3996 EDKRAKVTSAMQTMLFTMLRKLDNDALNNIINNARDGCVPLNIIPLTTAAKLMVVVPDYGTYKNTCDGNTFTYASALWEI 4075
Cdd:cd21832   81 TDRRAKLVSSLHALLFSMLKKIDSEKLNVLFDQASSGVVPLATVPIVCSNKLTLVIPDPETWVKCVEGMHVTYSTVVWNI 160
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|.
gi 30027621 4076 QQVVDADSkiVQLSEINMDNSP-------NLAWPLIVTALR 4109
Cdd:cd21832  161 DTVIDADG--TELHPTSTGSGLtycisgdNIAWPLKVNLTR 199
M_cv-Nsp15-like cd21165
middle domain of coronavirus Nonstructural protein 15 (Nsp15), and related proteins; Nidovirus ...
6494-6625 3.60e-48

middle domain of coronavirus Nonstructural protein 15 (Nsp15), and related proteins; Nidovirus endoribonucleases (NendoUs) are uridylate-specific endoribonucleases, which release a cleavage product containing a 2',3'-cyclic phosphate at the 3' terminal end. NendoUs include Nsp15 from coronaviruses and Nsp11 from arteriviruses, both of which may participate in the viral replication process and in the evasion of the host immune system. Coronavirus Nsp15 NendoUs have an N-terminal domain, a middle (M) domain and a C-terminal catalytic (NendoU) domain. Coronavirus Nsp15 from Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV), human Coronavirus 229E (HCoV229E), and Murine Hepatitis Virus (MHV) form a functional hexamer. Oligomerization of Porcine DeltaCoronavirus (PDCoV) Nsp15 differs from that of the other coronavirus members; it has been shown to exist as a dimer and a monomer in solution.


Pssm-ID: 439160  Cd Length: 126  Bit Score: 169.76  E-value: 3.60e-48
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 6494 PVPEIKILNNLGVDIAANTVIWDYKREAPAHVSTIGVCTMTDIAKKptesacSSLTVLFDGRVEGQVDLFRNARNGVLIT 6573
Cdd:cd21165    1 STPTLKLLKNLGVDATYNFVLWDYERDTPFFNSTNGVCTYTDIDPN------SGLTVLYDDRYGGSLERFLQADNAVLIS 74
                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|..
gi 30027621 6574 EGSVKGLTPSKGPAQASVNGVTLIGESVKTQFNYFKKVDGIIQQLPETYFTQ 6625
Cdd:cd21165   75 TTKVKGLSPPKGPNYASLNGVPVEGVDKGVQLYVYVRKDGQFVTLTDTYFTQ 126
1B_cv_Nsp13-like cd21409
1B domain of coronavirus SARS NSP13 helicase and related proteins; Helicases catalyze ...
5451-5529 8.33e-48

1B domain of coronavirus SARS NSP13 helicase and related proteins; Helicases catalyze NTP-dependent unwinding of nucleic acid duplexes into single strands and are classified based on the arrangement of conserved motifs into six superfamilies. Members of this subfamily belong to helicase superfamily 1 (SF1) and include coronavirus helicases such as Severe Acute Respiratory Syndrome coronavirus (SARS) non-structural protein 13 (SARS-Nsp13). SARS-Nsp13 is a component of the viral RNA synthesis replication and transcription complex (RTC). Structural studies of a stable RTC which included the RNA-dependent RNA polymerase holoenzyme (Nsp7, two molecules of Nsp82, Nsp12), two molecules of Nsp13 helicase accessory factor and an RNA template product suggests that the Nsp13 helicase may drive RTC backtracking, affecting proofreading and template switching. SARS-Nsp13 is a multidomain protein; its other domains include an N-terminal Cys/His rich zinc-binding domain (CH/ZBD) and a SF1 helicase core. The 1B domain is involved in nucleic acid substrate binding; the 1B domain of the related Equine arteritis virus (EAV) Nsp10 undergoes large conformational change upon substrate binding, and together with the 1A and 2A domains of the helicase core form a channel that accommodates the single stranded nucleic acids.


Pssm-ID: 394817  Cd Length: 79  Bit Score: 166.75  E-value: 8.33e-48
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 30027621 5451 GIATVREVLSDRELHLSWEVGKPRPPLNRNYVFTGYRVTKNSKVQIGEYTFEKGDYGDAVVYRGTTTYKLNVGDYFVLT 5529
Cdd:cd21409    1 ASATVKEVVGPRELVLSWEAGKTKPPLNRNYVFTGYHITKNSKTQLGEYTFEKSDYSDSVYYKSTTTYKLQPGDIFVLT 79
Macro_X_Nsp3-like cd21557
X-domain (or Mac1 domain) of viral non-structural protein 3 and related macrodomains; The ...
1034-1155 9.84e-48

X-domain (or Mac1 domain) of viral non-structural protein 3 and related macrodomains; The X-domain, also called Mac1, is the macrodomain found in riboviral non-structural protein 3 (Nsp3), including the Nsp3 of Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) as well as SARS-CoV-2, and other coronaviruses (alpha-, beta-, gamma-, and deltacoronavirus), among others. The SARS-CoV-2 Nsp3 Mac1 is highly conserved among all CoVs, and binds to and hydrolyzes mono-ADP-ribose (MAR) from target proteins. It appears to counter host-mediated antiviral ADP-ribosylation, a post-translational modification that is part of the host response to viral infections. Mac1 is essential for pathogenesis in multiple animal models of CoV infection, implicating it as a virulence factor and potential therapeutic target. Assays show that the de-MARylating activity leads to a rapid loss of substrate, and that Mac1 could not hydrolyze poly-ADP-ribose; thus, Mac1 is a MAR-hydrolase (mono-ADP ribosylhydrolase). Mac1 was originally named ADP-ribose-1"-phosphatase (ADRP) based on data demonstrating that it could remove the phosphate group from ADP-ribose-1"-phosphate; however, activity was modest and was unclear why this would impact a virus infection. This family also includes the X-domain of Avian infectious bronchitis virus (IBV) strain Beaudette coronavirus that does not bind ADP-ribose; the triple glycine sequence found in the X-domains of SARS-CoV and human coronavirus 229E (HCoV229E), which are involved in ADP-ribose binding, is not conserved in the IBV X-domain. SARS-CoVs have two other macrodomains referred to as the SUD-N (N-terminal subdomain, or Mac2) and SUD-M (middle SUD subdomain, or Mac3) of the SARS-unique domain (SUD), which also do not bind ADP-ribose; these bind G-quadruplexes (unusual nucleic-acid structures formed by consecutive guanosine nucleotides). SARS-CoV SUD-N and SUD-M are not included in this group.


Pssm-ID: 438957  Cd Length: 127  Bit Score: 168.50  E-value: 9.84e-48
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 1034 VIVNAANIHLKHGGGVAGALNKATNGAMQKESDdYIKLNGPLTVGGSCLLSGHNLAKKCLHVVGPNLNAGEDIQLLKAAY 1113
Cdd:cd21557    3 VVVNAANENLKHGGGVAGAIYKATGGAFQKESD-YIKKNGPLKVGTAVLLPGHGLAKNIIHVVGPRKRKGQDDQLLAAAY 81
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*.
gi 30027621 1114 ENFNS-QDILLAPLLSAGIFGAKPLQSLQVCVQTVRT---QVYIAV 1155
Cdd:cd21557   82 KAVNKeYGSVLTPLLSAGIFGVPPEQSLNALLDAVDTtdaDVTVYC 127
betaCoV_Nsp3_NAB cd21795
nucleic acid binding domain of betacoronavirus non-structural protein 3; This model represents ...
1890-1996 2.30e-46

nucleic acid binding domain of betacoronavirus non-structural protein 3; This model represents the nucleic acid binding (NAB) domain of non-structural protein 3 (Nsp3) from betacoronavirus including highly pathogenic human coronaviruses (CoVs) such as Severe acute respiratory syndrome-related coronavirus (SARS-CoV) and SARS-CoV2 (also called 2019 novel CoV or 2019-nCoV). The NAB domain represents a new fold, with a parallel four-strand beta-sheet holding two alpha-helices of three and four turns that are oriented antiparallel to the beta-strands. NAB is a cytoplasmic domain located between the papain-like protease (PLPro) and betacoronavirus-specific marker (betaSM) domains of CoV Nsp3. Nsp3 is a large multi-functional multi-domain protein that is an essential component of the replication/transcription complex (RTC), which carries out RNA synthesis, RNA processing, and interference with the host cell innate immune system. The NAB domain both binds ssRNA and unwinds dsDNA. It prefers to bind ssRNA containing repeats of three consecutive guanines. A group of residues that form a positively charged patch on the protein surface of SARS-CoV Nsp3 NAB serves as the binding site of nucleic acids. This site is conserved in the NAB of Nsp3 from betacoronavirus in the sarbecovirus subgenus (B lineage), but may not be conserved in the Nsp3 NAB from betacoronaviruses in other lineages.


Pssm-ID: 409347  Cd Length: 110  Bit Score: 163.90  E-value: 2.30e-46
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 1890 DLVPTQPLPNASFDNFKLT-CSNTKFADDLNQMTGFTKPASrELSVTFFPDLNGDVVAIDYRHYSASFKKGAKLLHKPIV 1968
Cdd:cd21795    1 LDVPAAPKPVTVYDNFKLVsCQNQSIADDFNRTLGFTKPGS-ELLLTVYPNTSGDVVAVSDDNYTVVYKKGSLLMGKPVL 79
                         90       100       110
                 ....*....|....*....|....*....|.
gi 30027621 1969 W-HINQATTK--TTFKPNTWCLRCLWSTKPV 1996
Cdd:cd21795   80 WvHKNNTWKKlvPLNKPNVVCLRNLFSVLPI 110
Nsp1 pfam11501
Non structural protein Nsp1; Nsp1 is the N-terminal cleavage product from the viral replicase ...
7-144 6.66e-46

Non structural protein Nsp1; Nsp1 is the N-terminal cleavage product from the viral replicase that mediates RNA replication and processing. The specific function of the protein is unknown however the structure has been determined. The protein has a novel alpha/beta fold formed by a 6 stranded beta barrel with an alpha helix covering one end of the barrel and another helix alongside the barrel. Nsp1 could be involved in the degradation of mRNA.


Pssm-ID: 431911  Cd Length: 138  Bit Score: 163.71  E-value: 6.66e-46
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621      7 GVNEKTHVQLSLPVLQVRDV-LVRGFGDSVEEALSEAREHLKN-GTCGLVELEKGVLPQLEQPYVFIKRSdalsTNHGHK 84
Cdd:pfam11501    1 NEKRKDHVSLTLPWCDPGDVpKLTPWFMDGEEALETVKEQLKKgGKLLFVPLYLGFIKQLPGPRVYLVES----LTGGWK 76
                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 30027621     85 -----VVELVAEMDGIQYGRSGITLGVLVPHVGETPIAYRNVLLRKNgnkGAGGHSYGIDLKSYD 144
Cdd:pfam11501   77 sdpfpVNELAYDDDGVRTGRSGKTVGVLFPFDPQLPTGTYTILLRKY---GLGGNSFRDVPWLWD 138
betaCoV_Nsp1 cd21876
non-structural protein 1 from betacoronavirus; This model represents the non-structural ...
13-127 1.59e-45

non-structural protein 1 from betacoronavirus; This model represents the non-structural protein 1 (Nsp1) from betacoronaviruses, including highly pathogenic coronaviruses such as Severe acute respiratory syndrome-related coronavirus (SARS-CoV), SARS-CoV2 (also called 2019 novel CoV or 2019-nCoV), and Middle East respiratory syndrome-related (MERS) CoV. CoVs utilize a multi-subunit replication/transcription machinery assembled from a set of non-structural proteins (Nsps) generated as cleavage products of the ORF1a and ORF1ab viral polyproteins. Nsp1 is the N-terminal cleavage product released from the ORF1a polyprotein by the action of papain-like protease (PLpro). Though Nsp1s of alphaCoVs and betaCoVs share structural similarity, they show no significant sequence similarity and may be considered as genus-specific markers. Despite low sequence similarity, the Nsp1s of alphaCoVs and betaCoVs exhibit remarkably similar biological functions, and are involved in the regulation of both host and viral gene expression. CoV Nsp1 induces suppression of host gene expression and interferes with host immune response. It inhibits host gene expression in two ways: by targeting the translation and stability of cellular mRNAs, and by inhibiting mRNA translation and inducing an endonucleolytic RNA cleavage in the 5'-UTR of cellular mRNAs through its tight association with the 40S ribosomal subunit, a key component of the cellular translation machinery. Inhibition of host mRNA translation includes that of type I interferons, major components of the host innate immune response. Nsp1 is critical in regulating viral replication and gene expression, as shown by multiple evidences, including: mutations in the Nsp1 coding region of the transmissible gastroenteritis virus (TGEV) and murine hepatitis virus (MHV) genomes cause drastic reduction or elimination of infectious virus; bovine coronavirus (BCoV) Nsp1 is an RNA-binding protein that interacts with cis-acting replication elements in the 5'-UTR of the BCoV genome, implying its potential role in the regulation of viral translation or replication; and SARS-CoV Nsp1 enhances virus replication by binding to a stem-loop structure in the 5'-UTR of its genome.


Pssm-ID: 409338  Cd Length: 114  Bit Score: 161.81  E-value: 1.59e-45
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621   13 HVQLSLPVLQVRDVLVRGFGDSVEEALSEAREHLKNGTCGLVELEKGVLPQLEQPYVFIKRSDALSTnHGHKVVELVAEM 92
Cdd:cd21876    1 HVSLTLPWLQALENPVQPWIDRPEEALESAKAALAEGKLVFVPPYKGLHPLLPGPRVFLVRRHGNPT-RPFDVRELAADA 79
                         90       100       110
                 ....*....|....*....|....*....|....*
gi 30027621   93 DGIQYGRSGITLGVLVPHVGETPIAYRNVLLRKNG 127
Cdd:cd21876   80 DGVNYGRSGRTIGVLVPLDGEQPYGYINILLRKYG 114
Corona_NSP4_C pfam16348
Coronavirus nonstructural protein 4 C-terminus; This is the C-terminal domain of the ...
3146-3238 6.12e-44

Coronavirus nonstructural protein 4 C-terminus; This is the C-terminal domain of the coronavirus nonstructural protein 4 (NSP4). NSP4 is a membrane-spanning protein which is thought to anchor the viral replication-transcription complex (RTC) to modified endoplasmic reticulum membranes. This predominantly alpha-helical domain may be involved in protein-protein interactions.


Pssm-ID: 406690  Cd Length: 92  Bit Score: 156.14  E-value: 6.12e-44
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621   3146 GVTF-STFEEAALCTFLLNKEMYLKLRSEtlLPLTQYNRYLALYNKYKYFSGALDTTSYREAACCHLAKALNDFSNSGAD 3224
Cdd:pfam16348    1 GDEFvGTFEEAALGTFVIDKESYEKLTNS--ISLDKFNRYLSLYNKYKYYSGTMDEADYREACCAHLAKALDDFSNSGND 78
                           90
                   ....*....|....
gi 30027621   3225 VLYQPPQTSITSAV 3238
Cdd:pfam16348   79 ILYTPPTVSIGSSL 92
CoV_NSP15_M pfam19216
Coronavirus replicase NSP15, middle domain; This entry represents the non-catalytic middle ...
6491-6613 1.73e-42

Coronavirus replicase NSP15, middle domain; This entry represents the non-catalytic middle domain from coronavirus non-structural protein 15 (NSP15). NSP15 is encoded by ORF1a/1ab and proteolytically released from the pp1a/1ab polyprotein. This domain is formed by ten beta strands organized into three beta hairpins.


Pssm-ID: 437053  Cd Length: 118  Bit Score: 153.21  E-value: 1.73e-42
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621   6491 NIKPVPEIKILNNLGVDIAANTVIWDYKREAPAHVSTIGVCTMTDIakkptesACSSLTVLFDGRVEGQVDLFRNARNGV 6570
Cdd:pfam19216    1 NVGLTPELKLLRNLGVDVTYNFVLWDYEREAPFTNSTIGVCKYTDI-------DNEDLNVLYDGRDKGSLERFTQAKNAV 73
                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....
gi 30027621   6571 LITEGSVKGLTPSKGPAQASVNGVTLIGESVK-TQFNYFKKVDG 6613
Cdd:pfam19216   74 LISTTKIKKLTAIKGPNYAYLNGVPVSTVEKKpVTFYIYVRKNG 117
betaCoV_Nsp7 cd21827
betacoronavirus non-structural protein 7; This model represents the non-structural protein 7 ...
3837-3919 2.89e-41

betacoronavirus non-structural protein 7; This model represents the non-structural protein 7 (Nsp7) of betacoronaviruses including the highly pathogenic Severe acute respiratory syndrome-related coronavirus (SARS-CoV), SARS-CoV2 (also called 2019 novel CoV or 2019-nCoV), and Middle East respiratory syndrome-related (MERS) CoV. CoVs utilize a multi-subunit replication/transcription machinery. A set of non-structural proteins (Nsps) generated as cleavage products of the ORF1a and ORF1ab viral polyproteins assemble to facilitate viral replication and transcription. Upon processing of the Nsp7-10 region by protease M (Mpro), the released four small proteins Nsp7, Nsp8, Nsp9 and Nsp10 form functional complexes with CoV core enzymes and stimulate replication. Most importantly, a complex of Nsp7 with Nsp8 has been shown to activate and confer processivity to the RNA-synthesizing activity of Nsp12, the RNA-dependent RNA-polymerase (RdRp); in SARS-CoV, point mutations in the NSP7- or NSP8-coding region have been shown to delay virus growth. Nsp7 and Nsp8 cooperate in activating the primer-dependent activity of the Nsp12 RdRp such that the level of their association may constitute a limiting factor for obtaining a high RNA polymerase activity. The subsequent Nsp7/Nsp8/Nsp12 polymerase complex is then able to associate with an active bifunctional Nsp14, which includes N-terminal 3' to 5' exoribonuclease (ExoN) and C-terminal N7-guanine cap methyltransferase (N7-MTase) activities, thus representing a unique coronavirus Nsp assembly that incorporates RdRp, exoribonuclease, and N7-MTase activities. Interaction of Nsp7 with Nsp8 appears to be conserved across the coronavirus family, making these proteins interesting drug targets. Nsp7 has a 4-helical bundle conformation which is strongly affected by its interaction with Nsp8, especially where it concerns alpha-helix 4. SARS-CoV Nsp7 forms a 8:8 hexadecameric supercomplex with Nsp8 that adopts a hollow cylinder-like structure with a large central channel and positive electrostatic properties in the cylinder; the Nsp7/Nsp8 complex functions as a noncanonical RNA polymerase capable of synthesizing RNA of up to template length.


Pssm-ID: 409253  Cd Length: 83  Bit Score: 148.36  E-value: 2.89e-41
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 3837 SKMSDVKCTSVVLLSVLQQLRVESSSKLWAQCVQLHNDILLAKDTTEAFEKMVSLLSVLLSMQGAVDINRLCEEMLDNRA 3916
Cdd:cd21827    1 SKLTDVKCTSVVLLSVLQQLHVESNSKLWAYCVKLHNDILAAKDPTEAFEKFVSLLSVLLSFPGAVDLDALCSELLDNPT 80

                 ...
gi 30027621 3917 TLQ 3919
Cdd:cd21827   81 VLQ 83
TM_Y_gammaCoV_Nsp3_C cd21710
C-terminus of gammacoronavirus non-structural protein 3, including transmembrane and Y domains; ...
2258-2735 3.19e-41

C-terminus of gammacoronavirus non-structural protein 3, including transmembrane and Y domains; This model represents the C-terminus of non-structural protein 3 (Nsp3) from gammacoronavirus, including Infectious bronchitis virus. This conserved C-terminus includes two transmembrane (TM) regions TM1 and TM2, an ectodomain (3Ecto) between the TM1 and TM2 that is glycosylated and located on the lumenal side of the ER, an amphiphatic region (AH1) that is not membrane-spanning, and a large Y domain of approximately 370 residues. Nsp3 is a large multi-functional multi-domain protein that is an essential component of the replication/transcription complex (RTC), which carries out RNA synthesis, RNA processing, and interference with the host cell innate immune system. In the related betacoronaviruses, Severe acute respiratory syndrome-related coronavirus (SARS-CoV) and murine hepatitis virus (MHV), the TM1, 3Ecto and TM2 domains are important for the papain-like protease (PL2pro) domain to process Nsp3-Nsp4 cleavage. It has also been shown that the interaction of 3Ecto with the lumenal loop of Nsp4 is essential for ER rearrangements in cells infected with SARS-CoV or MHV. The Y domain, located at the cytosolic side of the ER, consists of the Y1 and CoV-Y subdomains, which are conserved in nidovirus and coronavirus, respectively. Functional information about the Y domain is limited; it has been shown that Nsp3 binding to Nsp4 is less efficient without the Y domain.


Pssm-ID: 409658  Cd Length: 525  Bit Score: 162.61  E-value: 3.19e-41
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 2258 FCEGSFPCSICLSGLDSLDSYP-ALETIQVtissYKLdlTILGLAAEWVLAYMLFTKFF---------------YLLGLS 2321
Cdd:cd21710   61 YCGDDFTCRVCLHDKDSLHLYKhAYSVEQF----YKD--AVSGISFNWNWLYLVFLILFvkpvagfviicycvkYLVLSS 134
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 2322 AIMQVFFGYfashfisnswLMWFIISIvqmapvsaMVRMYIFFASFYY--IWKSYV---HIMdGCTSSTCMMCYKRNRAT 2396
Cdd:cd21710  135 TVLQTGVGF----------LDWFIQTV--------FTHFNFMGAGFYFwlFYKIYIqvhHIL-YCKDITCEVCKRVARSN 195
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 2397 RVECTTIVNGMKRSFYVYANGGRGFCKTHNWNCLNCDTFCTGSTFISDEVARDLSLQFKRPINPTDQSSYIVDSVAVKNG 2476
Cdd:cd21710  196 RHEVSVVVGGRKQLVHVYTNSGYNFCKRHNWYCRNCDKYGHQNTFMSPEVAGELSEKLKRHVKPTAHAYHVVDDACLVDD 275
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 2477 ALHLYFDKAGQKTYERHP-LSHFVNLDNLR-ANNTKGSLPINVIVFDGKSKCD-ESA-----SKSASVYYSQLMCQPILL 2548
Cdd:cd21710  276 FVNLKYKAATPGKDGAHSaVKCFSVSDFLKkAVFLKDALKCEQISNDSFIVCNtQSAhaleeAKNAAIYYAQYLCKPILI 355
                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 2549 LDQVLVsDVGDSTEVSVKMFDAYVDTFSATFSVPmeklkalvaTAHSELAKGVALDGVLSTfvsaarqgvvdtdvdTKD- 2627
Cdd:cd21710  356 LDQALY-EQLVVEPVSKSVVDKVCSILSNIISVD---------TAALNYKAGTLRDALLSV---------------TKDe 410
                        410       420       430       440       450       460       470       480
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 2628 -VIECLKLSHHSDLEVTGDSCNNFMLTYN-KVENMTPRDLGACIDCNARHINAQVAKSHNVslIWNVKDYMSLSEQLRKQ 2705
Cdd:cd21710  411 eAVDMAIFCHNNDVEYTSDGFTNVVPSYGiDTDKLTPRDRGFLINADASIANLRVKNAPPV--VWKFSDLIKLSDSCLKY 488
                        490       500       510
                 ....*....|....*....|....*....|
gi 30027621 2706 IRSAAKKNNIPFRLTCATTRQVVNVITTKI 2735
Cdd:cd21710  489 LISATVKSGGRFFITRSGAKQVISCHTQKL 518
SUD_C_SARS-CoV_Nsp3 cd21525
C-terminal SARS-Unique Domain (SUD) of non-structural protein 3 (Nsp3) from Severe Acute ...
1472-1538 3.45e-41

C-terminal SARS-Unique Domain (SUD) of non-structural protein 3 (Nsp3) from Severe Acute Respiratory Syndrome coronavirus and related betacoronaviruses in the B lineage; This subfamily contains the SUD-C of Severe Acute Respiratory Syndrome (SARS) coronavirus (CoV) non-structural protein 3 (Nsp3) and other Nsp3s from betacoronaviruses in the sarbecovirus subgenera (B lineage), such as SARS-CoV-2 and related bat CoVs. Non-structural protein 3 (Nsp3) is a large multi-functional multi-domain protein that is an essential component of the replication/transcription complex (RTC), which carries out RNA synthesis, RNA processing, and interference with the host cell innate immune system. Nsp3 of the Severe Acute Respiratory Syndrome (SARS) coronavirus includes a SARS-unique domain (SUD) consisting of three globular domains separated by short linker peptide segments: SUD-N, SUD-M, and SUD-C. SUD-N and SUD-M are macro domains which bind G-quadruplexes (unusual nucleic-acid structures formed by consecutive guanosine nucleotides). The SUD-C domain adopts a frataxin-like fold and has structural similarity to DNA-binding domains of DNA-modifying enzymes. It binds to single-stranded RNA and recognizes purine bases more strongly than pyrimidine bases. SUD-C also regulates the RNA binding behavior of the SUD-M macrodomain.


Pssm-ID: 394841  Cd Length: 67  Bit Score: 147.31  E-value: 3.45e-41
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 30027621 1472 TSEEHFVETVSLAGSYRDWSYSGQRTELGVEFLKRGDKIVYHTLESPVEFHLDGEVLSLDKLKSLLS 1538
Cdd:cd21525    1 TPEEHFVETVSLAGSYRDWSYSGQRTELGVEFLKRGDKIVYHTLESPVEFHLDGEVLPLDKLKSLLS 67
Macro_cv_SUD-N-M_Nsp3-like cd21556
SUD-N and SUD-M macrodomains of the SARS-Unique Domain (SUD) of SARS-CoV non-structural ...
1345-1453 1.04e-40

SUD-N and SUD-M macrodomains of the SARS-Unique Domain (SUD) of SARS-CoV non-structural protein 3 and related macrodomains; This family includes two macrodomains referred to as the SUD-N (N-terminal subdomain) and SUD-M (middle SUD subdomain) of the SARS-unique domain (SUD) which bind G-quadruplexes (unusual nucleic-acid structures formed by consecutive guanosine nucleotides). It is found in non-structural protein 3 (Nsp3) of Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) and highly related coronaviruses. SUD consists of three globular domains separated by short linker peptide segments: SUD-N, SUD-M, and SUD-C. Among these, SUD-N and SUD-M are macrodomains. SUD-N (also called Mac2) is specific to the Nsp3 of SARS and betacoronaviruses of the sarbecovirus subgenera (B lineage), while SUD-M (also called Mac3) is present in most Nsp3 proteins except the Nsp3 from betacoronaviruses of the embecovirus subgenera (A lineage). SUD-C adopts a frataxin-like fold, has structural similarity to DNA-binding domains of DNA-modifying enzymes, binds single-stranded RNA, and regulates the RNA binding behavior of the SUD-M macrodomain. SARS-CoV Nsp3 contains a third macrodomain (the X-domain or Mac1) which is not included in this family. The X-domain may function as a module binding poly(ADP-ribose); however, SUD-N and SUD-M do not bind ADP-ribose, as the triple glycine sequence involved in its binding is not conserved in these.


Pssm-ID: 438956  Cd Length: 108  Bit Score: 147.81  E-value: 1.04e-40
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 1345 GTVSWNLREMLAHAEETRKLMPICMDVRAIMATIQRKYKGIKIQEGIVDyGVRFFFYTSKEPVASIITKLNSLNEPLVTM 1424
Cdd:cd21556    1 LTVSENLRGMLREAKELGLLLPVCIDLSAFSKVLRRKGVAPKIGGDTVD-GVTFYFYSSKDPLEDLIKALNKLGDPIITT 79
                         90       100
                 ....*....|....*....|....*....
gi 30027621 1425 PIGYVTHGFNLEEAARCMRSLKAPAVVSV 1453
Cdd:cd21556   80 PLGYITHGLDLAQAAEEMRMLTVPFVVLL 108
Nsp3_PL2pro pfam12124
Coronavirus polyprotein cleavage domain; This domain is found in SARS coronaviruses, and is ...
1473-1538 1.67e-39

Coronavirus polyprotein cleavage domain; This domain is found in SARS coronaviruses, and is about 70 amino acids in length. It is found associated with various other coronavirus proteins due to the polyprotein nature of most viral translation. PL2pro is a domain of the non-structural protein nsp3. The domain performs three of the cleavages required to separate the translated polyprotein into its distinct proteins.


Pssm-ID: 288939  Cd Length: 66  Bit Score: 142.53  E-value: 1.67e-39
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 30027621   1473 SEEHFVETVSLAGSYRDWSYSGQRTELGVEFLKRGDKIVYHTLESPVEFHLDGEVLSLDKLKSLLS 1538
Cdd:pfam12124    1 SEEHFVETVSLAGSYRDWSYSGQRTELGVEFLKRGDKIVYHTLESPVEFHLDGEVLSLDKLKSLLS 66
nsp7 pfam08716
nsp7 replicase; nsp7 (non structural protein 7) has been implicated in viral RNA replication ...
3837-3919 6.86e-39

nsp7 replicase; nsp7 (non structural protein 7) has been implicated in viral RNA replication and is predominantly alpha helical in structure. It forms a hexadecameric supercomplex with nsp7 that adopts a hollow cylinder-like structure. The dimensions of the central channel and positive electrostatic properties of the cylinder imply that it confers processivity on RNA-dependent RNA polymerase.


Pssm-ID: 285878  Cd Length: 83  Bit Score: 141.43  E-value: 6.86e-39
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621   3837 SKMSDVKCTSVVLLSVLQQLRVESSSKLWAQCVQLHNDILLAKDTTEAFEKMVSLLSVLLSMQGAVDINRLCEEMLDNRA 3916
Cdd:pfam08716    1 SKLTDVKCTNVVLLGLLQKLHVESNSKLWAYCVELHNEILLCDDPTEAFEKLLALLAVLLSKHSAVDLSDLCDSYLENRT 80

                   ...
gi 30027621   3917 TLQ 3919
Cdd:pfam08716   81 ILQ 83
M_cv_Nsp15-NTD_av_Nsp11-like cd21163
middle (M) domain of coronavirus Nonstructural protein 15 (Nsp15) and the N-terminal domain ...
6494-6625 7.10e-38

middle (M) domain of coronavirus Nonstructural protein 15 (Nsp15) and the N-terminal domain (NTD) of arterivirus Nsp11 and related proteins; Nidovirus endoribonucleases (NendoUs) are uridylate-specific endoribonucleases, which release a cleavage product containing a 2',3'-cyclic phosphate at the 3' terminal end. NendoUs include Nsp15 from coronaviruses and Nsp11 from arteriviruses, both of which may participate in the viral replication process and in the evasion of the host immune system. Coronavirus Nsp15 NendoUs have an N-terminal domain, a middle (M) domain, and a C-terminal catalytic (NendoU) domain. Arterivirus Nsp11 has an N-terminal domain (NTD) and a C-terminal catalytic (NendoU) domain. The NTD of Nsp11 superimposes onto the M-domain of coronavirus Nsp15. Coronavirus Nsp15 from Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV), human Coronavirus 229E (HCoV229E), and Murine Hepatitis Virus (MHV) form a functional hexamer. Oligomerization of Porcine DeltaCoronavirus (PDCoV) Nsp15 differs from that of other coronavirus members; it has been shown to exist as a dimer and a monomer in solution. Nsp11 from the arterivirus PRRSV functions as a dimer.


Pssm-ID: 439159  Cd Length: 123  Bit Score: 140.16  E-value: 7.10e-38
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 6494 PVPEIKILNNLGVDIAANTVIWDYKREAPAHVstigvctmTDIAKKPTESACSSLTVLFDGRVEGQVDLFRNARNGVLIT 6573
Cdd:cd21163    1 STPLPKVLRNLGVDFTPNFVLWDYEDTAPFFN--------TTVCKYTPEELCEHLPVLYDDRYGGSLERFLSAPNAVLIS 72
                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|..
gi 30027621 6574 EGSVKgLTPSKGPAQASVNGVTLIGESVKTQFNYFKKVDGIIQQLPETYFTQ 6625
Cdd:cd21163   73 LTKVK-KYSIPPPAGAYLNGSVVVGTPKVVSFYLYKRKDGKFVTLPDTLFTQ 123
CoV_Nsp7 cd21811
coronavirus non-structural protein 7; This model represents the non-structural protein 7 (Nsp7) ...
3837-3919 7.52e-38

coronavirus non-structural protein 7; This model represents the non-structural protein 7 (Nsp7) of alpha-, beta-, gamma- and deltacoronaviruses, including highly pathogenic betacoronaviruses such as Severe acute respiratory syndrome-related coronavirus (SARS-CoV), SARS-CoV2 (also called 2019 novel CoV or 2019-nCoV), and Middle East respiratory syndrome-related (MERS) CoV. CoVs utilize a multi-subunit replication/transcription machinery. A set of non-structural proteins (Nsps) generated as cleavage products of the ORF1a and ORF1ab viral polyproteins assemble to facilitate viral replication and transcription. Upon processing of the Nsp7-10 region by protease M (Mpro), the released four small proteins Nsp7, Nsp8, Nsp9 and Nsp10 form functional complexes with CoV core enzymes and stimulate replication. Most importantly, a complex of Nsp7 with Nsp8 has been shown to activate and confer processivity to the RNA-synthesizing activity of Nsp12, the RNA-dependent RNA-polymerase (RdRp); in SARS-CoV, point mutations in the NSP7- or NSP8-coding region have been shown to delay virus growth. Nsp7 and Nsp8 cooperate in activating the primer-dependent activity of the Nsp12 RdRp such that the level of their association may constitute a limiting factor for obtaining a high RNA polymerase activity. The subsequent Nsp7/Nsp8/Nsp12 polymerase complex is then able to associate with an active bifunctional Nsp14, which includes N-terminal 3' to 5' exoribonuclease (ExoN) and C-terminal N7-guanine cap methyltransferase (N7-MTase) activities, thus representing a unique coronavirus Nsp assembly that incorporates RdRp, exoribonuclease, and N7-MTase activities. Interaction of Nsp7 with Nsp8 appears to be conserved across the coronavirus family, making these proteins interesting drug targets. Nsp7 has a 4-helical bundle conformation which is strongly affected by its interaction with Nsp8, especially where it concerns alpha-helix 4. SARS-CoV Nsp7 forms a 8:8 hexadecameric supercomplex with Nsp8 that adopts a hollow cylinder-like structure with a large central channel and positive electrostatic properties in the cylinder, while Feline infectious peritonitis virus Nsp7 forms a 2:1 heterotrimer with Nsp8. Regardless of their oligomeric structure, the Nsp7/Nsp8 complex functions as a noncanonical RNA polymerase capable of synthesizing RNA of up to template length.


Pssm-ID: 409251  Cd Length: 83  Bit Score: 138.39  E-value: 7.52e-38
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 3837 SKMSDVKCTSVVLLSVLQQLRVESSSKLWAQCVQLHNDILLAKDTTEAFEKMVSLLSVLLSMQGAVDINRLCEEMLDNRA 3916
Cdd:cd21811    1 SKLTDVKCTAVVLLSLLQKLRVESNSKLWKQCVQLHNDILLAKDTTEVFEKLVSLLSVLLSMQGAVDLNRLCEEMLENRA 80

                 ...
gi 30027621 3917 TLQ 3919
Cdd:cd21811   81 VLQ 83
deltaCoV_Nsp10 cd21903
deltacoronavirus non-structural protein 10; This model represents the non-structural protein ...
4232-4360 3.27e-37

deltacoronavirus non-structural protein 10; This model represents the non-structural protein 10 (Nsp10) of deltacoronaviruses, including Thrush coronavirus HKU12-600 and Wigeon coronavirus HKU20. CoVs utilize a multi-subunit replication/transcription machinery. A set of non-structural proteins (Nsps) generated as cleavage products of the ORF1a and ORF1ab viral polyproteins assemble to facilitate viral replication and transcription. Upon processing of the Nsp7-10 region by protease M (Mpro), the released four small proteins Nsp7, Nsp8, Nsp9, and Nsp10 form functional complexes with CoV core enzymes and thereby stimulate replication. Coronaviruses cap their mRNAs; RNA cap methylation may involve at least three proteins: Nsp10, Nsp14, and Nsp16. Nsp10 serves as a cofactor for both Nsp14 and Nsp16. Nsp14 consists of 2 domains with different enzymatic activities: an N-terminal ExoN domain and a C-terminal cap (guanine-N7) methyltransferase (N7-MTase) domain. The association of Nsp10 with Nsp14 enhances Nsp14's exoribonuclease (ExoN) activity, and not its N7-Mtase activity. ExoN is important for proofreading and therefore, the prevention of lethal mutations. The Nsp10/Nsp14 complex hydrolyzes double-stranded RNA in a 3' to 5' direction as well as a single mismatched nucleotide at the 3'-end, mimicking an erroneous replication product, and may function in a replicative mismatch repair mechanism. Nsp16 Cap-0 specific (nucleoside-2'-O-)-methyltransferase (2'OMTase) acts sequentially to Nsp14 MTase in RNA capping methylation and methylates the RNA cap at the ribose 2'-O position; it catalyzes the conversion of the cap-0 structure on m7GpppA-RNA to a cap-1 structure. The association of Nsp10 with Nsp16 enhances Nsp16's 2'OMTase activity, possibly through enhanced RNA binding affinity. Additionally, transmissible gastroenteritis virus (TGEV) Nsp10, Nsp16 and their complex can interact with DII4, which normally binds to Notch receptors; this interaction may disturb Notch signaling. Nsp10 also binds 2 zinc ions with high affinity.


Pssm-ID: 409328  Cd Length: 128  Bit Score: 138.46  E-value: 3.27e-37
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 4232 GNATEVPANSTVLSFCAFAVDPAKAYKDYLASGGQPITNCVKMLCThTGTGQAITVTPEANMDQESFGGASCCLYCRCHI 4311
Cdd:cd21903    2 GTQIEYQENASLLTYLAFAVDPKEAYLKHLADGGKPIQGCIQMIAP-LGPGFAVTTKPQPNEHQYSYGGASICLYCRAHI 80
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*....
gi 30027621 4312 DHPNPKGFCDLKGKYVQIPTTcaNDPVGFTLRNTVCTVCGMWKGYGCSC 4360
Cdd:cd21903   81 PHPGVDGRCPYKGRFVHIDKD--KEPVSFALTHEPCNSCQRWVNYDCTC 127
Tobaniviridae_RdRp cd23186
catalytic core domain of RNA-dependent RNA polymerase (RdRP) in the Tobaniviridae family of ...
4885-5293 3.97e-34

catalytic core domain of RNA-dependent RNA polymerase (RdRP) in the Tobaniviridae family of positive-sense single-stranded RNA [(+)ssRNA] viruses; This group contains the catalytic core domain of RdRp of RNA viruses belonging to the family Tobaniviridae, order Nidovirales. Tobaniviridae RNA viruses infect vertebrates; their host organisms include mammals, fish, and snakes. Member viruses have a viral envelope and (+)ssRNA genome. The genome size of Tobaniviruses ranges from 20 to 32 kilobases. The family is the only member of the suborder Tornidovirineae. The family Tobaniviridae has four subfamilies (Piscanivirinae, Remotovirinae, Remotovirinae, and Torovirinae) and eight genera (Bafinivirus, Oncotshavirus, Bostovirus, Infratovirus, Pregotovirus, Sectovirus, Tiruvirus, and Torovirus). The Tobaniviridae family belongs to the order Nidovirales, which currently comprises 88 formally recognized virus species of (+)ssRNA viruses, which are classified into nine virus families across seven different suborders. The structure of Tobaniviridae RdRp contains a RdRp domain as well as a large N-terminal extension that adopts a nidovirus RdRp-associated nucleotidyltransferase (NiRAN) architecture. The RdRp domain displays a right hand with three functional subdomains, called fingers, palm, and thumb. All RdRps contain conserved polymerase motifs (A-G), located in the palm (A-E motifs) and finger (F-G) subdomains. All these motifs have been implicated in RdRp fidelity such as processes of correct incorporation and reorganization of nucleotides.


Pssm-ID: 438036  Cd Length: 401  Bit Score: 138.68  E-value: 3.97e-34
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 4885 YDSMSYEDQDALFAYTKRNVIPTITQMNLKYAISAKNRARTVAGVSICSTMTNRQFHQKLLKSIAATRGATVV---IGTS 4961
Cdd:cd23186   61 YQALPEDFIDRLLELAKKTPLPFSTKIITKFALTKKARARTIAACSFIASTIFRFLHKPVTNNMVKQAQNNIGhclIGVS 140
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 4962 KFYGGWHNMLKTVYSDVETPHLMGWDYPKCDRAMPNMLRIMASLVLARkhntCCNLSHRFYRLANECAQVLSEMVMCGGS 5041
Cdd:cd23186  141 KFNLGFDKFLRSRYGGIEDYNVFGSDYTKCDRSFPLVFRALAAALLYE----LGGWDPKNHLFVNEIFAFMLDFVFIGGH 216
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 5042 LYVKPGGTSSGDATTAYANSVFNICQavtanvnallstdgnkiadKYVRNLQHrlyeclyrnrdvdhefvdeFYaylRKH 5121
Cdd:cd23186  217 IFNKPGGTSSGDATTAFSNTLYNYMV-------------------HLYVQFQT-------------------FY---FFN 255
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 5122 FsmmiLSDDAVVCynSNYAAQgLVASIKNFKAVLYYQNNVFMSEAKCWTETDLTkgpHEFCSQHTMLVkqgdDYVYLPYP 5201
Cdd:cd23186  256 F----LSDDSFIL--SKPEAF-PIFTTENFSRKLQTILHTTVDQTKAWSASGHI---HEFCSSHIEEV----NGVYQFIP 321
                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 5202 DPSRILGAGCFVDDIVKTDgtLMIERFVS----LAIDAYpltKHPNqeyadVFHLYLQYIRKLHDEltghMLDMYSVMLT 5277
Cdd:cd23186  322 DPNRLLAGLLITGKASDVD--LDIWRTVAilaeLAVYSR---VDPA-----FFNALFQLFQNKHAE----FVTKYGVNPL 387
                        410
                 ....*....|....*.
gi 30027621 5278 NDntsRYWEPEFYEAM 5293
Cdd:cd23186  388 PD---QLLEKDFYTNL 400
SARS-CoV-like_Nsp1_C cd22662
C-terminal domain of non-structural protein 1 from Severe acute respiratory syndrome-related ...
128-180 6.79e-34

C-terminal domain of non-structural protein 1 from Severe acute respiratory syndrome-related coronavirus and betacoronavirus in the B lineage; This model represents the C-terminal domain of non-structural protein 1 (Nsp1) from betacoronaviruses in the sarbecovirus subgenus (B lineage), including highly pathogenic coronaviruses such as Severe acute respiratory syndrome-related coronavirus (SARS-CoV) and SARS-CoV2 (also called 2019 novel CoV or 2019-nCoV). CoVs utilize a multi-subunit replication/transcription machinery assembled from a set of non-structural proteins (Nsps) generated as cleavage products of the ORF1a and ORF1ab viral polyproteins. Nsp1 is the N-terminal cleavage product released from the ORF1a polyprotein by the action of papain-like protease (PLpro). Though Nsp1s of alphaCoVs and betaCoVs share structural similarity, they show no significant sequence similarity and may be considered as genus-specific markers. Despite low sequence similarity, the Nsp1s of alphaCoVs and betaCoVs exhibit remarkably similar biological functions, and are involved in the regulation of both host and viral gene expression. CoV Nsp1 induces suppression of host gene expression and interferes with host immune response. It inhibits host gene expression in two ways: by targeting the translation and stability of cellular mRNAs, and by inhibiting mRNA translation and inducing an endonucleolytic RNA cleavage in the 5'-UTR of cellular mRNAs through its tight association with the 40S ribosomal subunit, a key component of the cellular translation machinery. Inhibition of host mRNA translation includes that of type I interferons, major components of the host innate immune response. Nsp1 is critical in regulating viral replication and gene expression. SARS-CoV Nsp1 enhances virus replication by binding to a stem-loop structure in the 5'-UTR of its genome. When the SARS-CoV-2 5' UTR is bound to the Nsp1 N-terminus, the covalently linked Nsp1 C-terminus cannot bind the 40S ribosome, suggesting a bipartite mechanism whereby SARS-CoV-2 Nsp1 suppresses host but not viral translation.


Pssm-ID: 439355  Cd Length: 53  Bit Score: 126.14  E-value: 6.79e-34
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 30027621  128 NKGAGGHSYGIDLKSYDLGDELGTDPIEDYEQNWNTKHGSGALRELTRELNGG 180
Cdd:cd22662    1 NKGAGGHSYGIDLKSYDLGDELGTDPIEDYEQNWNTKHGSGALRELTRELNGG 53
NTD_alpha_betaCoV_Nsp15-like cd21171
N-terminal domain of alpha- and beta-coronavirus Nonstructural protein 15 (Nsp15), and related ...
6430-6490 3.55e-33

N-terminal domain of alpha- and beta-coronavirus Nonstructural protein 15 (Nsp15), and related proteins; Coronavirus (CoV) Nsp15 is a nidovirus endoribonuclease (NendoU). NendoUs are uridylate-specific endoribonucleases, which release a cleavage product containing a 2',3'-cyclic phosphate at the 3' terminal end. NendoUs include CoV Nsp15 and arterivirus Nsp11, both of which may participate in the viral replication process and in the evasion of the host immune system. This small NTD structure, present in coronavirus Nsp15, is missing in Nsp11. CoV Nsp15 has an N-terminal domain, a middle (M) domain, and a C-terminal catalytic (NendoU) domain. Nsp15 from Severe Acute Respiratory Syndrome (SARS)-CoV, human CoV229E (HCoV229E), and Murine Hepatitis Virus (MHV) form a functional hexamer. Residues in this N-terminal domain are important for hexamer (dimer of trimers) formation.


Pssm-ID: 439163  Cd Length: 61  Bit Score: 124.22  E-value: 3.55e-33
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 30027621 6430 SLENVAYNVVNKGHFDGHAGEAPVSIINNAVYTKVDGIDVEIFENKTTLPVNVAFELWAKR 6490
Cdd:cd21171    1 SLENVAYNVVKKGHFVGVEGELPVAIVNDKVFVKDGGVDVLVFTNKTSLPTNVAFELYAKR 61
CoV_NSP15_N pfam19219
Coronavirus replicase NSP15, N-terminal oligomerisation; This is the N-terminal domain of the ...
6430-6490 1.86e-32

Coronavirus replicase NSP15, N-terminal oligomerisation; This is the N-terminal domain of the coronavirus nonstructural protein 15 (NSP15), which is encoded by ORF1a/1ab and proteolytically released from the pp1a/1ab polyprotein. NSP15, is a nidoviral RNA uridylate-specific endoribonuclease (NendoU) carrying C-terminal catalytic domain belonging to the EndoU family. The SARS-CoV-2 NendoU monomers assemble into a double-ring hexamer, generated by a dimer of trimers. The hexamer is stabilized by the interactions of N-terminal oligomerization domain.


Pssm-ID: 437056  Cd Length: 61  Bit Score: 122.38  E-value: 1.86e-32
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 30027621   6430 SLENVAYNVVNKGHFDGHAGEAPVSIINNAVYTKVDGIDVEIFENKTTLPVNVAFELWAKR 6490
Cdd:pfam19219    1 SLENVAYNVVKKGHFDGVDGELPVAIVNDKVFVKVGGVDVLVFENKTSLPTNVAFELYAKR 61
deltaCoV_Nsp8 cd21833
deltacoronavirus non-structural protein 8; This model represents the non-structural protein 8 ...
3920-4109 5.06e-32

deltacoronavirus non-structural protein 8; This model represents the non-structural protein 8 (Nsp8) region of deltacoronaviruses that include White-eye coronavirus HKU16 and Quail coronavirus UAE-HKU30, among others. CoVs utilize a multi-subunit replication/transcription machinery. A set of non-structural proteins (Nsps) generated as cleavage products of the ORF1a and ORF1ab viral polyproteins assemble to facilitate viral replication and transcription. Upon processing of the Nsp7-10 region by protease M (Mpro), the released four small proteins Nsp7, Nsp8, Nsp9, and Nsp10 form functional complexes with CoV core enzymes and thereby stimulate replication. Most importantly, a complex of Nsp8 with Nsp7 has been shown to activate and confer processivity to the RNA-synthesizing activity of Nsp12, the RNA-dependent RNA-polymerase (RdRp); in SARS-CoV, point mutations in the genes encoding Nsp8 and Nsp7 have been shown to delay virus growth. Nsp8 and Nsp7 cooperate in activating the primer-dependent activity of the Nsp12 RdRp such that the level of their association may constitute a limiting factor for obtaining a high RNA polymerase activity. The subsequent Nsp7/Nsp8/Nsp12 polymerase complex is then able to associate with an active bifunctional Nsp14, which includes N-terminal 3' to 5' exoribonuclease (ExoN) and C-terminal N7-guanine cap methyltransferase (N7-MTase) activities, thus representing a unique coronavirus Nsp assembly that incorporates RdRp, exoribonuclease, and N7-MTase activities. Interaction of Nsp8 with Nsp7 appears to be conserved across the coronavirus family, making these proteins interesting drug targets. Nsp8 has a novel 'golf-club' fold composed of an N-terminal 'shaft' domain and a C-terminal 'head' domain. The shaft domain contains three helices, one of which is very long, while the head domain contains another three helices and seven beta-strands, forming an alpha/beta fold. SARS-CoV Nsp8 forms a 8:8 hexadecameric supercomplex with Nsp7 that adopts a hollow cylinder-like structure with a large central channel and positive electrostatic properties in the cylinder, while Feline infectious peritonitis virus Nsp8 forms a 1:2 heterotrimer with Nsp7. Regardless of their oligomeric structure, the Nsp7/Nsp8 complex functions as a noncanonical RNA polymerase capable of synthesizing RNA of up to the template length.


Pssm-ID: 409260  Cd Length: 189  Bit Score: 125.89  E-value: 5.06e-32
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 3920 AIASEFSSLPSYAAYATAQEAYEQAVANGDSEVVLKKLKKSLNVAKSEFDRDAAMQRKLEKMADQAMTQMYKQARSEDKR 3999
Cdd:cd21833    1 AVVDANINLDSYRIYKEADAAYKKSVELNEPPQEQKKKLKAVNIAKAEWEREAASQRKLEKLADAAMKSMYLAERAEDRR 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 4000 AKVTSAMQTMLFTMLRKLDNDALNNIINNARDGCVPLNIIPLTTAAKLMVVVPDYGTYKNTCDGNTFTYASALWEIqqvv 4079
Cdd:cd21833   81 IKLTSGLTAMLYHMLRRLDSDRVKALFECAKQQILPIHAIVGVSNDNLKVIFNDKESYLQYVDGNTLIYKGVRYTI---- 156
                        170       180       190
                 ....*....|....*....|....*....|....
gi 30027621 4080 dadskivqLSEINMDNSP----NLAWPLIVTALR 4109
Cdd:cd21833  157 --------VKKLSLDNAPiegiPEEYPVVVETIR 182
alphaCoV_Nsp9 cd21897
alphacoronavirus non-structural protein 9; This model represents the non-structural protein 9 ...
4118-4230 5.06e-31

alphacoronavirus non-structural protein 9; This model represents the non-structural protein 9 (Nsp9) of alphacoronaviruses, including Porcine epidemic diarrhea virus (PEDV), Porcine transmissible gastroenteritis coronavirus (TGEV), and Human coronavirus 229E. CoVs utilize a multi-subunit replication/transcription machinery assembled from a set of non-structural proteins (Nsps) generated as cleavage products of the ORF1a and ORF1ab viral polyproteins. All of these Nsps, except for Nsp1 and Nsp2, are considered essential for transcription, replication, and translation of the viral RNA. Nsp9, with Nsp7, Nsp8, and Nsp10, localizes within the replication complex. Nsp9 is an essential single-stranded RNA-binding protein for coronavirus replication; it shares structural similarity to the oligosaccharide-binding (OB) fold, which is characteristic of proteins that bind to ssDNA or ssRNA. Nsp9 requires dimerization for binding and orienting RNA for subsequent use by the replicase machinery. CoV Nsp9s have diverse forms of dimerization that promote their biological function, which may help elucidate the mechanism underlying CoVs replication and contribute to the development of antiviral drugs. Generally, dimers are formed via interaction of the parallel alpha-helices containing the protein-protein interaction motif GXXXG; additionally, the N-finger region may also play a critical role in dimerization as seen in porcine delta coronavirus (PDCoV) Nsp9. As a member of the replication complex, Nsp9 may not have a specific RNA-binding sequence but may act in conjunction with other Nsps as a processivity factor, as shown by mutation studies indicating that Nsp9 is a key ingredient that intimately engages other proteins in the replicase complex to mediate efficient virus transcription and replication.


Pssm-ID: 409330  Cd Length: 108  Bit Score: 120.11  E-value: 5.06e-31
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 4118 NNELSPVALRQMSCAAGTTqTACTDDNALayYNNSKGGRFVLALLSDHQDLKWARFPKSDGTGTIytELEPPCRFVTDTP 4197
Cdd:cd21897    1 NNEIMPGKLKQRAVKAEGD-GFSGDGKAL--YNNEGGKTFMYAFIADKPDLKYVKWEFDGGCNTI--ELEPPCKFLVDTP 75
                         90       100       110
                 ....*....|....*....|....*....|...
gi 30027621 4198 KGPKVKYLYFIKGLNNLNRGMVLGSLAATVRLQ 4230
Cdd:cd21897   76 NGPQIKYLYFVKNLNTLRRGAVLGYIGATVRLQ 108
Ubl1_cv_Nsp3_N-like cd21467
first ubiquitin-like (Ubl) domain located at the N-terminus of coronavirus SARS-CoV ...
839-925 1.02e-29

first ubiquitin-like (Ubl) domain located at the N-terminus of coronavirus SARS-CoV non-structural protein 3 (Nsp3) and related proteins; This ubiquitin-like (Ubl) domain (Ubl1) is found at the N-terminus of coronavirus Nsp3, a large multi-functional multi-domain protein which is an essential component of the replication/transcription complex (RTC). The functions of Ubl1 in CoVs are related to single-stranded RNA (ssRNA) binding and to interacting with the nucleocapsid (N) protein. SARS-CoV Ubl1 has been shown to bind ssRNA having AUA patterns, and since the 5'-UTR of the SARS-CoV genome has a number of AUA repeats, it may bind there. In mouse hepatitis virus (MHV), this Ubl1 domain binds the cognate N protein. Adjacent to Ubl1 is a Glu-rich acidic region (also referred to as hypervariable region, HVR); Ubl1 together with HVR has been called Nsp3a. Currently, the function of HVR in CoVs is unknown. This model corresponds to one of two Ubl domains in Nsp3; the other is located N-terminal to the papain-like protease (PLpro) and is not represented by this model.


Pssm-ID: 394822  Cd Length: 89  Bit Score: 115.36  E-value: 1.02e-29
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621  839 NVRITFELDERVDKVLNEKCSVYTVESGTEVTEFACVVAEAVVKTLQPVSDLL--TNMGIDLDEWSVATFYLFDDAGEEN 916
Cdd:cd21467    1 TVKVTYELDEVLDTILNKACSPFEVEKDLTVEEFADVVQDAVEEKLSPLLELPlgDKVDADLDDFIDNPCYLFDEDGDEV 80

                 ....*....
gi 30027621  917 FSSRMYCSF 925
Cdd:cd21467   81 LASEMYCSF 89
ZBD_nv_SF1_Hel-like cd21399
Cys/His rich zinc-binding domain (CH/ZBD) of nidovirus helicases including coronavirus Nsp13 ...
5304-5376 5.65e-29

Cys/His rich zinc-binding domain (CH/ZBD) of nidovirus helicases including coronavirus Nsp13 and arterivirus Nsp10, and related proteins; Helicases catalyze NTP-dependent unwinding of nucleic acid duplexes into single strands and are classified based on the arrangement of conserved motifs into six superfamilies. This nidovirus family includes Severe Acute Respiratory Syndrome coronavirus (SARS) non-structural protein 13 (SARS-Nsp13) and equine arteritis virus (EAV) Nsp10 helicase, and belongs to helicase superfamily 1 (SF1). The CH/ZBD has 3 zinc-finger (ZnF1-3) motifs. SARS-Nsp13 is a component of the viral RNA synthesis replication and transcription complex (RTC). The SARS-Nsp13 CH/ZBD is indispensable for helicase activity and interacts with SARS-Nsp12, the RNA-dependent RNA polymerase. SARS-Nsp12 can enhance the helicase activity of SARS-Nsp13. SARS-Nsp13 and EAV Nsp10 are multidomain proteins; their other domains include a 1B regulatory domain and a SF1 helicase core.


Pssm-ID: 394806  Cd Length: 71  Bit Score: 112.67  E-value: 5.65e-29
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 30027621 5304 GACVLCNSQTSLRCGACIRRPFLCCKCCYDHVISTSHKLVLSVNPYVCNapGCDVTDVTQLYLGGMSYYCKSH 5376
Cdd:cd21399    1 GVCYVCGSQTSLRCGTCIRRPFFCCKCCYDHVIQTCHKTVLLASPYVCA--GCGESDITLLYTGGDSYRCVDH 71
alpha_betaCoV_Nsp1 cd21874
non-structural protein 1 from alpha- and betacoronavirus; This model represents the ...
13-125 1.67e-28

non-structural protein 1 from alpha- and betacoronavirus; This model represents the non-structural protein 1 (Nsp1) from alpha- and betacoronaviruses, including highly pathogenic betacoronaviruses such as Severe acute respiratory syndrome-related coronavirus (SARS-CoV), SARS-CoV2 (also called 2019 novel CoV or 2019-nCoV), and Middle East respiratory syndrome-related (MERS) CoV. Gamma- and deltaCoVs do not have Nsp1. CoVs utilize a multi-subunit replication/transcription machinery assembled from a set of non-structural proteins (Nsps) generated as cleavage products of the ORF1a and ORF1ab viral polyproteins. Nsp1 is the N-terminal cleavage product released from the ORF1a polyprotein by the action of papain-like protease (PLpro). Though Nsp1s of alphaCoVs and betaCoVs share structural similarity, they show no significant sequence similarity and may be considered as genus-specific markers. Despite low sequence similarity, the Nsp1s of alphaCoVs and betaCoVs exhibit remarkably similar biological functions, and are involved in the regulation of both host and viral gene expression. CoV Nsp1 induces suppression of host gene expression and interferes with host immune response. It inhibits host gene expression in two ways: by targeting the translation and stability of cellular mRNAs, and by inhibiting mRNA translation and inducing an endonucleolytic RNA cleavage in the 5'-UTR of cellular mRNAs through its tight association with the 40S ribosomal subunit, a key component of the cellular translation machinery. Inhibition of host mRNA translation includes that of type I interferons, major components of the host innate immune response. Nsp1 is critical in regulating viral replication and gene expression, as shown by multiple evidences, including: mutations in the Nsp1 coding region of the transmissible gastroenteritis virus (TGEV) and murine hepatitis virus (MHV) genomes cause drastic reduction or elimination of infectious virus; bovine coronavirus (BCoV) Nsp1 is an RNA-binding protein that interacts with cis-acting replication elements in the 5'-UTR of the BCoV genome, implying its potential role in the regulation of viral translation or replication; and SARS-CoV Nsp1 enhances virus replication by binding to a stem-loop structure in the 5'-UTR of its genome.


Pssm-ID: 409336  Cd Length: 103  Bit Score: 112.69  E-value: 1.67e-28
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621   13 HVQLSLPVLQVrDVLVRGFGDSVEEALSEAREHLKNG--TCGLVELEKGVL---PQLEQPYVFIKRSdalstnhghKVVE 87
Cdd:cd21874    1 SVQLSLPVLQV-DVLVRGFGDSVEEALSEAREHLKNGfgTCGFVELEKGDLvdcPQLEQYVVFVKGS---------KVVE 70
                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 30027621   88 LVAEMDGIqygRSGITLGVLVPHVGetPIAYRNVLLRK 125
Cdd:cd21874   71 LVAEMDGI---RSGITLGVLVPHNC--NIALENVLLRK 103
Macro_Af1521_BAL-like cd02907
macrodomain, Af1521-like family; Macrodomains are found in a variety of proteins with diverse ...
1015-1146 1.97e-28

macrodomain, Af1521-like family; Macrodomains are found in a variety of proteins with diverse cellular functions, as a stand-alone domain or in combination with other domains like in histone macroH2A and some PARPs (poly ADP-ribose polymerases). Macrodomains can recognize ADP-ribose (ADPr) in both its free and protein-linked forms, in related ligands, such as O-acyl-ADP-ribose (OAADPr), and even in ligands unrelated to ADPr. The macrodomains in this family show similarity to Af1521, a protein from Archaeoglobus fulgidus containing a stand-alone macrodomain. Af1521 binds ADP-ribose and exhibits phosphatase activity toward ADP-ribose-1"-monophosphate (Appr-1"-p). Also included in this family are the N-terminal (or first) macrodomains of BAL (B-aggressive lymphoma) proteins which contain multiple macrodomains, such as the first macrodomain of mono-ADP-ribosyltransferase PARP14 (PARP-14, also known as ADP-ribosyltransferase diphtheria toxin-like 8, ATRD8, B aggressive lymphoma protein 2, or BAL2). Most BAL proteins also contain a C-terminal PARP active site and are also named as PARPs. Human BAL1 (or PARP-9) was originally identified as a risk-related gene in diffuse large B-cell lymphoma that promotes malignant B-cell migration. Some BAL family proteins exhibit PARP activity. Poly (ADP-ribosyl)ation is an immediate DNA-damage-dependent post-translational modification of histones and other nuclear proteins. BAL proteins may also function as transcriptional repressors.


Pssm-ID: 394877 [Multi-domain]  Cd Length: 158  Bit Score: 114.51  E-value: 1.97e-28
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 1015 NVAIKCVDIVKEaqSANpmVIVNAANIHLKHGGGVAGALNKATNGAMQKESDDYIKLNGPLTVGGSCLLSGHNL-AKKCL 1093
Cdd:cd02907    3 KVSVYKGDITKE--KVD--AIVNAANERLKHGGGVAGAISKAGGPEIQEECDKYIKKNGKLRVGEVVVTSAGKLpCKYVI 78
                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 30027621 1094 HVVGPNLNAGEDIQ------------LLKAAYENFNSQDIllaPLLSAGIFGAKplqsLQVCVQT 1146
Cdd:cd02907   79 HAVGPRWSGGSKEEcedllykavlnsLEEAEELKATSIAI---PAISSGIFGFP----LDLCAEA 136
NTD_CoV_Nsp15-like cd21170
N-terminal domain of coronavirus Nonstructural protein 15 (Nsp15) and related proteins; ...
6431-6490 3.35e-28

N-terminal domain of coronavirus Nonstructural protein 15 (Nsp15) and related proteins; Coronavirus (CoV) Nsp15 is a nidovirus endoribonuclease (NendoU). NendoUs are uridylate-specific endoribonucleases, which release a cleavage product containing a 2',3'-cyclic phosphate at the 3' terminal end. NendoUs include CoV Nsp15 and arterivirus Nsp11, both of which may participate in the viral replication process and in the evasion of the host immune system. This NTD structure (approximately 60 residues) present in CoV Nsp15, is missing in Nsp11. CoV Nsp15 has an N-terminal domain, a middle (M) domain, and a C-terminal catalytic (NendoU) domain. Nsp15 from Severe Acute Respiratory Syndrome (SARS)-CoV, human CoV 229E (HCoV229E), and Murine Hepatitis Virus (MHV) form a functional hexamer. Oligomerization of Porcine DeltaCoronavirus (PDCoV) Nsp15 differs from the Nsp15 of these alpha- and beta-coronavirus; it has been shown to exist as dimers and monomers in solution, and to function as a dimer. Nsp15 from Turkey CoV (TCoV), a gammaCoV, has been reported to be a homohexamer.


Pssm-ID: 439162  Cd Length: 60  Bit Score: 110.17  E-value: 3.35e-28
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 6431 LENVAYNVVNKGHFDGHAGEAPVSIINNAVYTKVDGIDVEIFENKTTLPVNVAFELWAKR 6490
Cdd:cd21170    1 LENLAYNVVKKNHFDGVKGELPVVITGDKVFVKDDGVDVLLFENKTTLPTSVAFELYAKR 60
betaCoV_Nsp3_betaSM cd21727
betacoronavirus-specific marker of betacoronavirus non-structural protein 3; This model ...
2023-2136 1.86e-27

betacoronavirus-specific marker of betacoronavirus non-structural protein 3; This model represents the betacoronavirus-specific marker (betaSM), also called group 2-specific marker (G2M), of non-structural protein 3 (Nsp3) from betacoronavirus, including highly pathogenic human coronaviruses such as Severe acute respiratory syndrome-related coronavirus (SARS-CoV) and SARS-CoV2 (also called 2019 novel CoV or 2019-nCoV). The betaSM/G2M is located C-terminal to the nucleic acid-binding (NAB) domain. This region is absent in alpha- and deltacoronavirus Nsp3; there is a gammacoronavirus-specific marker (gammaSM) at this position in gammacoronavirus Nsp3. Nsp3 is a large multi-functional multi-domain protein that is an essential component of the replication/transcription complex (RTC), which carries out RNA synthesis, RNA processing, and interference with the host cell innate immune system. Little is known about the betaSM/G2M domain; it is predicted to be non-enzymatic and may be an intrinsically disordered region. The betaSM/G2M domain is part of the predicted PLnc domain (made up of 385 amino acids) of SARS-CoV Nsp3 that may function as a replication/transcription scaffold, with interactions to Nsp5, Nsp12, Nsp13, Nsp14, and Nsp16.


Pssm-ID: 409626  Cd Length: 125  Bit Score: 110.31  E-value: 1.86e-27
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 2023 PTSEEVVENPTIQKEVIECDVKTTEVV-GNVILKPSDEGVKVTQELGHEDLMAAYVENTSIT-IKKPNELSLALGLKTIA 2100
Cdd:cd21727    3 PVTVETSVSASQQKMVILKGLKKPFVVnGNVSVVDNDSGTKVVEELSKTDLYTMYVDGKYQVvVLKANELSRVLGLHTVE 82
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*
gi 30027621 2101 THgiAAINSVPWSKILAYVKPFL---------GQAAITTSNCAKR 2136
Cdd:cd21727   83 SH--AAVNVLASGSVTRYAKLLLrasfyfvefTKATFTATNAVSK 125
ZBD_UPF1_nv_SF1_Hel-like cd21343
Cys/His rich zinc-binding domain (CH/ZBD) of eukaryotic UPF1 helicase, nidovirus SF1 helicases ...
5305-5376 4.40e-26

Cys/His rich zinc-binding domain (CH/ZBD) of eukaryotic UPF1 helicase, nidovirus SF1 helicases including coronavirus Nsp13 and arterivirus Nsp10, and related proteins; Helicases catalyze NTP-dependent unwinding of nucleic acid duplexes into single strands, and are classified based on the arrangement of conserved motifs into six superfamilies. Members of this family belong to helicase superfamily 1 (SF1) and include nidoviral helicases such as Severe Acute Respiratory Syndrome coronavirus (SARS) non-structural protein 13 (SARS-Nsp13) and equine arteritis virus (EAV) Nsp10, as well as eukaryotic UPF1 helicase. The CH/ZBD has 3 zinc-finger (ZnF1-3) motifs. UPF1 participates in nonsense-mediated mRNA decay (NMD), a pathway which degrades transcripts with premature termination codons. The CH/ZBD of UPF1 interacts with UPF2, a factor also involved in NMD. SARS-Nsp13 is a component of the viral RNA synthesis replication and transcription complex (RTC). The SARS-Nsp13 CH/ZBD is indispensable for helicase activity and interacts with SARS-Nsp12, the RNA-dependent RNA polymerase. SARS-Nsp12 can enhance the helicase activity of SARS-Nsp13. UPF1, SARS-Nsp13 and EAV Nsp10 are multidomain proteins; their other domains include a 1B regulatory domain and a SF1 helicase core.


Pssm-ID: 439166  Cd Length: 70  Bit Score: 104.50  E-value: 4.40e-26
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 30027621 5305 ACVLCNSQTSLRCGACIRRPFLCCKCCYDHVISTSHKLVLSVNPYVCNapGCDVTDVTQLYLGGMSYYCKSH 5376
Cdd:cd21343    1 ACYVCGSHTVVRCGTCIRRPWFCNSCIYDHLIRTKHKEVLLASPYVCA--GCGESDITLLYFGGVSYRCVDH 70
gammaCoV-Nsp6 cd21559
gammacoronavirus non-structural protein 6; Coronaviruses (CoV) redirect and rearrange host ...
3534-3836 8.93e-26

gammacoronavirus non-structural protein 6; Coronaviruses (CoV) redirect and rearrange host cell membranes as part of the viral genome replication and transcription machinery; they induce the formation of double-membrane vesicles in infected cells. CoV non-structural protein 6 (Nsp6), a transmembrane-containing protein, together with Nsp3 and Nsp4, have the ability to induce double-membrane vesicles that are similar to those observed in severe acute respiratory syndrome (SARS) coronavirus-infected cells. By itself, Nsp6 can generate autophagosomes from the endoplasmic reticulum. Autophagosomes are normally generated as a cellular response to starvation to carry cellular organelles and long-lived proteins to lysosomes for degradation. Degradation through autophagy may provide an innate defense against virus infection, or conversely, autophagosomes can promote infection by facilitating the assembly of replicase proteins. In addition to initiating autophagosome formation, Nsp6 also limits autophagosome expansion regardless of how they were induced, i.e. whether they were induced directly by Nsp6, or indirectly by starvation or chemical inhibition of MTOR signaling. This may favor coronavirus infection by compromising the ability of autophagosomes to deliver viral components to lysosomes for degradation.


Pssm-ID: 394845  Cd Length: 307  Bit Score: 111.78  E-value: 8.93e-26
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 3534 FDVVRQCSGVTFQGKFKKivKGTHHW----MLLTFLTSLLILVqstqwsLFFFVYENAFLPFTLGIMAIAACAMLLVKHK 3609
Cdd:cd21559    1 ESVFNQVGGVRLQSSFVK--KATSWFwsrcVLACFLFVLCAIV------LFTAVPLKYYVHAAVILLVAVLFISFTVKHV 72
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 3610 HAFLCLFLLPSLATVA---------YFNMVYmpASWVMRIMTWLE--LADTslsgyrlkdcvMYASALVLLILMTARTV- 3677
Cdd:cd21559   73 MAFMDTFLLPTLCTVIigvcaevpfIYNTLI--SQVVIFFSQWYDpvVFDT-----------VVPWMFLPLVLYTAFKCv 139
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 3678 -----YDDAARRVWTLMNVITLVYKVYYGNALDQAISM--WAL--------VISVTSNYSGVVTTIMFLARAIVFVCVEY 3742
Cdd:cd21559  140 qgcysINSFSTSLLVLYQFMKLGFVIYTSSNTLTAYTEgnWELffelvhttVLANFSSNSLIGLIVFKIAKWMLYYCNAT 219
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 3743 YPLLFITgntlqciMLVY-CFLGYCCCCYFGLFCLLNRYFRLTLGVYDYLVSTQEFRYMNSQGLLPPKSSIDAFKLNIKL 3821
Cdd:cd21559  220 YFNSYVL-------MAVMvNVIGWLFTCYFGLYWWLNKVFGLTLGKYNYKVSVEQYKYMCLHKIRPPKSVWDVFSTNMLI 292
                        330
                 ....*....|....*
gi 30027621 3822 LGIGGKPCIKVATVQ 3836
Cdd:cd21559  293 QGIGGERVLPIATVQ 307
stalk_CoV_Nsp13-like cd21689
stalk domain of coronavirus Nsp13 helicase and related proteins; This model represents the ...
5400-5447 6.70e-25

stalk domain of coronavirus Nsp13 helicase and related proteins; This model represents the stalk domain of coronavirus non-structural protein 13 (Nsp13) helicase, found in the Nsp3s of alpha-, beta-, gamma-, and deltacoronaviruses, including Severe Acute Respiratory Syndrome coronavirus (SARS-CoV), SARS-CoV-2 (also called 2019 novel CoV or 2019-nCoV), and Middle East respiratory syndrome coronavirus (MERS-CoV). Helicases are classified based on the arrangement of conserved motifs into six superfamilies; coronavirus helicases in this family belong to superfamily 1 (SF1). Helicases catalyze NTP-dependent unwinding of nucleic acid duplexes into single strands. Nsp13 is a component of the viral RNA synthesis replication and transcription complex (RTC). It consists of an N-terminal ZBD (Cys/His rich zinc-binding domain), a stalk domain, a 1B regulatory domain, and SF1 helicase core. The stalk domain lies between the ZBD domain and the 1B domain; a short loop connects the ZBD to the stalk domain. The stalk domain is comprised of three tightly-interacting alpha-helices connected to the 1B domain, transferring the effect from the ZBD domain onto the helicase core domains. The ZBD and stalk domains are critical for the helicase activity of SARS-CoV Nsp13.


Pssm-ID: 410205  Cd Length: 48  Bit Score: 100.38  E-value: 6.70e-25
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*...
gi 30027621 5400 GSDNVTDFNAIATCDWTNAGDYILANTCTERLKLFAAETLKATEETFK 5447
Cdd:cd21689    1 GSPDVDDFNRLATSDWSDVEDYKLANTCKDSLKLFAAETIKAKEESVK 48
Mesoniviridae_RdRp cd23187
catalytic core domain of RNA-dependent RNA polymerase (RdRp) in the Mesoniviridae family of ...
4870-5263 1.25e-24

catalytic core domain of RNA-dependent RNA polymerase (RdRp) in the Mesoniviridae family of positive-sense single-stranded RNA [(+)ssRNA] viruses; This group contains the catalytic core domain of RdRp of RNA viruses belonging to the family Mesoniviridae, order Nidovirales. Member viruses have a viral envelope and (+)ssRNA genome. The family is named after the size of the genomes relative to other nidoviruses, which is intermediate between that of the families Arteriviridae and Coronaviridae, with meso- coming from the Greek word mesos, which means medium, while -ni is an abbreviation of nido. The family Mesoniviridae comprises of mosquito-specific viruses with extensive geographic distribution and host range. The family has only one subfamily, Hexponivirinae, which contains only one genus, Alphamesonivirus. There are 8 subgenera (Casualivirus, Enselivirus, Hanalivirus, Kadilivirus, Karsalivirus, Menolivirus, Namcalivirus, and Ofalivirus) and 10 species in Alphamesonivirus. The structure of Mesoniviridae RdRp contains a RdRp domain as well as a large N-terminal extension that adopts a nidovirus RdRp-associated nucleotidyltransferase (NiRAN) architecture. The RdRp domain displays a right hand with three functional subdomains, called fingers, palm, and thumb. All RdRps contain conserved polymerase motifs (A-G), located in the palm (A-E motifs) and finger (F-G) subdomains. All these motifs have been implicated in RdRp fidelity such as processes of correct incorporation and reorganization of nucleotides.


Pssm-ID: 438037  Cd Length: 424  Bit Score: 110.76  E-value: 1.25e-24
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 4870 SAGFPFNKWGKARLYYDSMSyEDQDALFAYTKRNVIPTITQMNLKYAISAKNRARTVAGVSICSTMTNRQFHQKLLKSIA 4949
Cdd:cd23187    1 SAGTPYRKFGDSEFMRELYG-NYRDAIVYHKRHSADQQLTLTINKVAPSKNHRDRTILAISINKSEPGRSLYRWNLDKIK 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 4950 ATR--GATVVIGTSKFYGGWHNMLKTVYSDV------ETPH--LMGWDYPKCDRAMPNMLRIMASLVL-------ARKHN 5012
Cdd:cd23187   80 YTSslGGPILIGFTAQYGGWDKLYKYLYKNSpadnpdTAEHavLGGKDYPKWDRRISNMLQLTTTTVLyslidpnTQRKL 159
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 5013 TCCNLSHRFYRLANECAQVLSEMVMCGGSLYVKPGGTSSGDATTAYANSVFN-----------ICQAVTANV-------N 5074
Cdd:cd23187  160 NNATPAQTWHEYMAETTQVLYDYLVFGNELYQKPGGVTSGNSRTADGNSLLHllidfyaiisqLIQSTPENVhlevnlrN 239
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 5075 ALLSTDGNKIADKYVRNLQHRLyeclyRNRDVDHefvdefyaYLRKHFSM-MILSDDAVVCYNSNYAaqglvasiknfka 5153
Cdd:cd23187  240 ALCKTVFTRIPSDYIDSSCVTL-----RNTDTLH--------TIRRRVAKgAYLSDDGLIVIDPRII------------- 293
                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 5154 vlyyQNNVFMSEAKCWTETDLTKGPH------------EFCSQHTmlVKQGDdyVYLPYPDPSRILGAGCFVDDIVKTDG 5221
Cdd:cd23187  294 ----RYDDFMSVSHLISHYMIAQNKHkyhidaiqryarEFLSQDT--IKFGD--MVFPIPEFGRMYTAMLLSDNKNTLDP 365
                        410       420       430       440
                 ....*....|....*....|....*....|....*....|....*....
gi 30027621 5222 TLMIERFVSLAIDAYPL-------TKHPNQEYADVFHLYLQYIRKLHDE 5263
Cdd:cd23187  366 QINITRLLALFSYLYIYyfkyedqPTHPTLKFLDALRTYIENKLNTTDE 414
betaCoV_Nsp2_MERS-like cd21517
betacoronavirus non-structural protein 2 (Nsp2) similar to MERS-CoV Nsp2, and related proteins ...
186-818 1.79e-24

betacoronavirus non-structural protein 2 (Nsp2) similar to MERS-CoV Nsp2, and related proteins from betacoronaviruses in the C lineage; Coronavirus non-structural proteins (Nsps) are encoded in ORF1a and ORF1b. Post infection, the genomic RNA is released into the cytoplasm of the cell and translated into two long polyproteins (pp), pp1a and pp1ab, which are then autoproteolytically cleaved by two viral proteases Nsp3 and Nsp5 into smaller subunits. Nsp2 is one of these subunits. This subgroup includes Nsp2 from Middle East respiratory syndrome-related coronavirus (MERS-CoV) and betacoronaviruses in the merbecovirus subgenus (C lineage). It belongs to a family which includes Severe acute respiratory syndrome coronavirus (SARS-CoV) Nsp2, and Murine hepatitis virus (MHV) Nsp2 (also known as p65). The function of Nsp2 remains unclear. SARS-CoV Nsp2, rather than playing a role in viral replication, may be involved in altering the host cell environment; deletion of Nsp2 from the SARS-CoV genome results in only a modest reduction in viral titers. It has been shown to interact with two host proteins, prohibitin 1 (PHB1) and PHB2, which have been implicated in cellular functions, including cell-cycle progression, cell migration, cellular differentiation, apoptosis, and mitochondrial biogenesis. MHV Nsp2/p65, different from SARS-CoV Nsp2, may play an important role in the viral life cycle.


Pssm-ID: 394868  Cd Length: 660  Bit Score: 113.29  E-value: 1.79e-24
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621  186 VDNNFCGPDGYPldcIKDFLARAGK-SMCTLSEQLDYIES---KRGVYCCRDHEHEIAWFTERSDKSYEHQTPFEIKSAK 261
Cdd:cd21517    5 IDQYMCGKDGKP---IADYAALAAKeGLTKLADVEADVSSradSDGFITFKNKLYRIVWHVERKDVPYPKQTIFTINSVV 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621  262 KFDTFKgECPKFVFPLNSKVKVIQPRVEK--KKTEGFMGRI-RSVYPVASPQECNNMHLSTLMKCNHCDEVSWQTCDFLK 338
Cdd:cd21517   82 QKDGIE-DVPPHSFTLGGKVLVLVPRNKWggKSDLTLKQKLlYTFYGKDAVENPSYIYHSAFVDCTSCGNGSWLTGNAVQ 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621  339 ATCEHCG---TENLVIegPTTCGYLPTNAVVKMPCPACQDPEIGPE--HSVADYHNHSNIETRLRKGGR--TRCFGGCVF 411
Cdd:cd21517  161 GFACDCGasySANDVE--LQSSGLVKPNALFCATCPFAKGDSCSSSckHTVAQVVSYLSEKCVVEPDGKsfTLTFGGVVY 238
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621  412 AYVGCYNKRAYWVPRAS---ADIG-SGHTGITG--DNVETLNEDLLEILSRervNINIVGDFHLNEevaIILASFSASTS 485
Cdd:cd21517  239 AYMGCSEGTMYFVPRAKsvvSRIGdAIFTGCVGtwSKVTQIANLFLEQAQR---SLNFVGEFVLND---VVLAILSGTTS 312
                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621  486 AfIDTIKSL-DYKSFKTIVESCGNY--KVTKGKPVKGAWNIGQQR----------SVLTPLCGFPSQAAGV---IRSIFA 549
Cdd:cd21517  313 N-VDKLRDLlKNVTFEKLRDYLADYgiAVTMGPYVDGAINVGKQGlqfaaitapfVVLTGLGESFKKVAAIpykLCSSLK 391
                        410       420       430       440       450       460       470       480
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621  550 RTLDAANHSIpdLQRA-AVTILDGISEQSLRLVDAMVYTSdlltnsviIMAYVTGGLVQQTSQWLSNLLGTTVEKLRPIF 628
Cdd:cd21517  392 DTLDYYADSI--LYRVfPYDISSDVSDFSELLLDCVGLTA--------ASAYFVVRLLDEKVETLLSTIFSSCQTAVSSF 461
                        490       500       510       520       530       540       550       560
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621  629 ewIEAKLSAG---VEFLKDAWEILKFLITGVFDIVKGQIQVASDNIKDCVKCFIDVVNKALEMCIDQVTIAGAKLRSL-- 703
Cdd:cd21517  462 --LNTCFEATtatANFLLDLANLFKVFLRKAYVYTSAGFVAVGGKVSPLTKQLLDILSKAMQLLHTKVSWAGSKVSAViy 539
                        570       580       590       600       610       620       630       640
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621  704 NLGEVFIAQSkGLYrQCIRGK-----EQLQLLMPLK-APKEVTFLEGDSHDTVL------TSEEVVLknGELEaletPVD 771
Cdd:cd21517  540 NGRESLVFPS-GTY-YCVTTKassvqQQFDVVLPGElSKKQLGLLEPTNHSTTVdvrvqtNVVEVVV--GQLE----ETN 611
                        650       660       670       680       690
                 ....*....|....*....|....*....|....*....|....*....|..
gi 30027621  772 SFTNGAIVGTPVCVNGLMLLEIKDKEQYcALSPglLATN-----NVFRLKGG 818
Cdd:cd21517  612 MHSPDLVVGDYVIISDKLFVRSEEDGQT-VFYP--MCTNgkavpTLFRLKGG 660
CoV_NSP2_C pfam19212
Coronavirus replicase NSP2, C-terminal; This entry corresponds to a presumed domain found at ...
652-818 4.14e-24

Coronavirus replicase NSP2, C-terminal; This entry corresponds to a presumed domain found at the C-terminus of Coronavirus non-structural protein 2 (NSP2). NSP2 is encoded by ORF1a/1ab and proteolytically released from the pp1a/1ab polyprotein. The function of NSP2 is uncertain. This presumed domain is found in two copies in some viral NSP2 proteins. This domain is found in both alpha and betacoronaviruses.


Pssm-ID: 437049  Cd Length: 157  Bit Score: 101.95  E-value: 4.14e-24
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621    652 LITGVFDIVKGQIQV-ASDNIKDCVKCFIDVVNKALEMCIDQVTIAGAKLRSlnlGEVFIAQS-KGLYRQC---IRGKEQ 726
Cdd:pfam19212    1 LKNAKFTVVNGGIVFvVPDKFKSLVGTLLDLLNKAFDLVVDTVKIAGVKFKA---GGTYYLFSgNALVKVVsvkLKGKKQ 77
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621    727 LQLlmplKAPKEVTFLEGDSHDTVLTSEEVVlkNGELEaletPVDSFTNGAIVGTPVCVNGLMLLeiKDKEQYCALSPGL 806
Cdd:pfam19212   78 AGL----KGAKEATVFVGATVPVTSTRVEVV--TVELE----EVDYVPPPVVVGYVVVIDGYAFY--KSGDEYYPASTDG 145
                          170
                   ....*....|..
gi 30027621    807 LATNNVFRLKGG 818
Cdd:pfam19212  146 VVVPPVFKLKGG 157
Macro pfam01661
Macro domain; This domain is an ADP-ribose binding module. It is found in a number of ...
1036-1143 7.62e-24

Macro domain; This domain is an ADP-ribose binding module. It is found in a number of otherwise unrelated proteins. It is found at the C-terminus of the macro-H2A histone protein. This domain is found in the non-structural proteins of several types of ssRNA viruses such as NSP3 from alphaviruses. This domain is also found on its own in a family of proteins from bacteria, archaebacteria and eukaryotes.


Pssm-ID: 426372  Cd Length: 116  Bit Score: 99.94  E-value: 7.62e-24
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621   1036 VNAANIHLKHGGGVAGALNKATNGAMQKESDDYIKlnGPLTVGGSCLLSGHNL-AKKCLHVVGPNLNAG---EDIQLLKA 1111
Cdd:pfam01661    1 VNAANSRLLGGGGVAGAIHRAAGPELLEECRELKK--GGCPTGEAVVTPGGNLpAKYVIHTVGPTWRHGgghGEEELLES 78
                           90       100       110
                   ....*....|....*....|....*....|....*...
gi 30027621   1112 AYENF----NSQDI--LLAPLLSAGIFGAKPLQSLQVC 1143
Cdd:pfam01661   79 CYRNAlalaEELGIksIAFPAISTGIYGFPWEEAARIA 116
DEXXQc_Upf1-like cd17934
DEXXQ-box helicase domain of Upf1-like helicase; The Upf1-like helicase family includes UPF1, ...
5578-5744 1.03e-23

DEXXQ-box helicase domain of Upf1-like helicase; The Upf1-like helicase family includes UPF1, HELZ, Mov10L1, Aquarius, IGHMBP2 (SMUBP2), coronavirus Nsp13, and similar proteins. They belong to the DEAD-like helicase superfamily, a diverse family of proteins involved in ATP-dependent RNA or DNA unwinding. This domain contains the ATP-binding region.


Pssm-ID: 438708 [Multi-domain]  Cd Length: 121  Bit Score: 99.62  E-value: 1.03e-23
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 5578 YSTLQGPPGTGKSHFAIGLALYY----PSARIVYTACSHAAVDALcekalkylpidkcsriipararvecfdkfkvnstl 5653
Cdd:cd17934    1 ISLIQGPPGTGKTTTIAAIVLQLlkglRGKRVLVTAQSNVAVDNV----------------------------------- 45
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 5654 eqyvfctvnalpettaDIVVFDEISMATNYDLsvVNARLRAKHYVYIGDPAQLPAPRTLLTKGTLEP---EYFNSVCRLM 5730
Cdd:cd17934   46 ----------------DVVIIDEASQITEPEL--LIALIRAKKVVLVGDPKQLPPVVQEDHAALLGLsfiLSLLLLFRLL 107
                        170
                 ....*....|....
gi 30027621 5731 KTIGPDMFLGTCRR 5744
Cdd:cd17934  108 LPGSPKVMLDTQYR 121
gammaCoV_Nsp9 cd21899
gammacoronavirus non-structural protein 9; This model represents the non-structural protein 9 ...
4116-4230 1.13e-23

gammacoronavirus non-structural protein 9; This model represents the non-structural protein 9 (Nsp9) from gammacoronaviruses such as Avian infectious bronchitis virus (IBV). CoVs utilize a multi-subunit replication/transcription machinery assembled from a set of non-structural proteins (Nsps) generated as cleavage products of the ORF1a and ORF1ab viral polyproteins. All of these Nsps, except for Nsp1 and Nsp2, are considered essential for transcription, replication, and translation of the viral RNA. Nsp9, with Nsp7, Nsp8, and Nsp10, localizes within the replication complex. Nsp9 is an essential single-stranded RNA-binding protein for coronavirus replication; it shares structural similarity to the oligosaccharide-binding (OB) fold, which is characteristic of proteins that bind to ssDNA or ssRNA. Nsp9 requires dimerization for binding and orienting RNA for subsequent use by the replicase machinery. CoV Nsp9s have diverse forms of dimerization that promote their biological function, which may help elucidate the mechanism underlying CoVs replication and contribute to the development of antiviral drugs. Generally, dimers are formed via interaction of the parallel alpha-helices containing the protein-protein interaction motif GXXXG; additionally, the N-finger region may also play a critical role in dimerization as seen in porcine delta coronavirus (PDCoV) Nsp9. As a member of the replication complex, Nsp9 may not have a specific RNA-binding sequence but may act in conjunction with other Nsps as a processivity factor, as shown by mutation studies indicating that Nsp9 is a key ingredient that intimately engages other proteins in the replicase complex to mediate efficient virus transcription and replication.


Pssm-ID: 409332  Cd Length: 113  Bit Score: 99.16  E-value: 1.13e-23
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 4116 LQNNELSPVALRQMSCAAGTTQTACTDDnALAYYNNSKGGRFVLALLSDHQDLKWARFPKSDGTgTIYTELEPPCRFVTD 4195
Cdd:cd21899    1 LQNNELMPHGVKTKACVAGVDQAHCSVE-SKCYYTNISGNSVVAAITSSNPNLKVASFLNEAGN-QIYVDLDPPCKFGMK 78
                         90       100       110
                 ....*....|....*....|....*....|....*
gi 30027621 4196 TPKGPKVKYLYFIKGLNNLNRGMVLGSLAATVRLQ 4230
Cdd:cd21899   79 VGDKVEVVYLYFIKNTRSIVRGMVLGAISNVVVLQ 113
alphaCoV_Nsp7 cd21826
alphacoronavirus non-structural protein 7; This model represents the non-structural protein 7 ...
3837-3919 1.65e-21

alphacoronavirus non-structural protein 7; This model represents the non-structural protein 7 (Nsp7) of alphacoronaviruses that include Feline infectious peritonitis virus (FCoV), Human coronavirus NL63 (HCoV-NL63), and Porcine transmissible gastroenteritis coronavirus (TGEV), among others. CoVs utilize a multi-subunit replication/transcription machinery. A set of non-structural proteins (Nsps) generated as cleavage products of the ORF1a and ORF1ab viral polyproteins assemble to facilitate viral replication and transcription. Upon processing of the Nsp7-10 region by protease M (Mpro), the released four small proteins Nsp7, Nsp8, Nsp9 and Nsp10 form functional complexes with CoV core enzymes and stimulate replication. Most importantly, a complex of Nsp7 with Nsp8 has been shown to activate and confer processivity to the RNA-synthesizing activity of Nsp12, the RNA-dependent RNA-polymerase (RdRp); in SARS-CoV, point mutations in the NSP7- or NSP8-coding region have been shown to delay virus growth. Nsp7 and Nsp8 cooperate in activating the primer-dependent activity of the Nsp12 RdRp such that the level of their association may constitute a limiting factor for obtaining a high RNA polymerase activity. The subsequent Nsp7/Nsp8/Nsp12 polymerase complex is then able to associate with an active bifunctional Nsp14, which includes N-terminal 3' to 5' exoribonuclease (ExoN) and C-terminal N7-guanine cap methyltransferase (N7-MTase) activities, thus representing a unique coronavirus Nsp assembly that incorporates RdRp, exoribonuclease, and N7-MTase activities. Interaction of Nsp7 with Nsp8 appears to be conserved across the coronavirus family, making these proteins interesting drug targets. Nsp7 has a 4-helical bundle conformation which is strongly affected by its interaction with Nsp8, especially where it concerns alpha-helix 4. FCoV Nsp7 forms a 2:1 heterotrimer with Nsp8; the Nsp7/Nsp8 complex functions as a noncanonical RNA polymerase capable of synthesizing RNA of up to template length.


Pssm-ID: 409252  Cd Length: 83  Bit Score: 92.04  E-value: 1.65e-21
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 3837 SKMSDVKCTSVVLLSVLQQLRVESSSKLWAQCVQLHNDILLAKDTTEAFEKMVSLLSVLLSMQGAVDINRLCEEMLDNRA 3916
Cdd:cd21826    1 SKLTDIKCTNVVLLGCLSSMNVAANSKEWAYCVDLHNKINLCDDPEKAQEMLLALLAFFLSKQKDFGLDDLLDSYFDNNS 80

                 ...
gi 30027621 3917 TLQ 3919
Cdd:cd21826   81 ILQ 83
TM_Y_deltaCoV_Nsp3_C cd21711
C-terminus of deltacoronavirus non-structural protein 3, including transmembrane and Y domains; ...
2230-2724 1.73e-21

C-terminus of deltacoronavirus non-structural protein 3, including transmembrane and Y domains; This model represents the C-terminus of non-structural protein 3 (Nsp3) from deltacoronavirus, including Magpie-robin coronavirus HKU18 and Bulbul coronavirus HKU11, among others. This conserved C-terminus includes two transmembrane (TM) regions TM1 and TM2, an ectodomain (3Ecto) between the TM1 and TM2 that is glycosylated and located on the lumenal side of the ER, an amphiphatic region (AH1) that is not membrane-spanning, and a large Y domain of approximately 370 residues. Nsp3 is a large multi-functional multi-domain protein that is an essential component of the replication/transcription complex (RTC), which carries out RNA synthesis, RNA processing, and interference with the host cell innate immune system. In the related betacoronaviruses, Severe acute respiratory syndrome-related coronavirus (SARS-CoV) and murine hepatitis virus (MHV), the TM1, 3Ecto and TM2 domains are important for the papain-like protease (PL2pro) domain to process Nsp3-Nsp4 cleavage. It has also been shown that the interaction of 3Ecto with the lumenal loop of Nsp4 is essential for ER rearrangements in cells infected with SARS-CoV or MHV. The Y domain, located at the cytosolic side of the ER, consists of the Y1 and CoV-Y subdomains, which are conserved in nidovirus and coronavirus, respectively. Functional information about the Y domain is limited; it has been shown that Nsp3 binding to Nsp4 is less efficient without the Y domain.


Pssm-ID: 409659  Cd Length: 490  Bit Score: 102.48  E-value: 1.73e-21
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 2230 LLSNFGAPSYCNGVRELYLNSsnvttmdFCEGSFPCSICLSGLDSLDSYPALETIQVTI-----SSYKLDLTILGLAAEW 2304
Cdd:cd21711   35 LYAKTGLPCYYNATQHYDYNS-------FCAGDLTCQACFDGQDSLHLYKHLRVNQQPVqttdyTVYALSIVLLLANPTL 107
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 2305 VLAYMLFTKFFYLLGLSaIMqvFFGyfashfisnswlmwfiisIVQMAPVSAmvrmYIFFASFYYIWKSYV---HIMDGC 2381
Cdd:cd21711  108 VLGTLLVVFFVNFYGVQ-IP--FYG------------------TLQLDYQNT----LVMVFSVYYFYKVMKffrHLAKGC 162
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 2382 TSSTCMMCYKRNRATRVECTTIVNGMKRSFYVYANGGRGFCKTHNWNCLNCDTFCTGSTFISDEVARDLS---LQFKrPI 2458
Cdd:cd21711  163 KKPTCSICAKKRIPPTITVETVVQGRKYPSVIETNGGFNICKEHNFYCKNCDSQTPGTFIPTEAVESLSRktrLSVK-PT 241
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 2459 NP--------TDQSSYIVDSVAVkNGALHLYFDKAgqktyerhplSHFVNLDNLRANNTKGSLPINVIV---FDgkskcD 2527
Cdd:cd21711  242 APayllardvECQTDVVVARATH-NGNAHVCISKY----------SDIRTVDQLLKPTPLFSYTPDVIIaadFD-----N 305
                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 2528 ESASKSA---SVYYSQLMCQPILLLDQvlvsdvgdstevsvkMFDAYVDTFSATFSVpMEKLKALvatahselaKGVALD 2604
Cdd:cd21711  306 AGSLKTAkelAVVLSMDLKRTIIIIDQ---------------AYSRPIDNYQEVKSR-IEKYYPF---------QKITPT 360
                        410       420       430       440       450       460       470       480
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 2605 GVLSTFVSAARQGVVdtdvdTKDVIECLKLSHHSDLEVTGDSCNNFMLTYN-KVENMTPRDLGACIDCNarhINAQVAKS 2683
Cdd:cd21711  361 GDIFADIKQATNGQA-----SDSAINAAILAVQRGLDFTIDNPNNILPHYAfDFSTLSAEDQSTLIESG---CAKGNLKG 432
                        490       500       510       520
                 ....*....|....*....|....*....|....*....|.
gi 30027621 2684 HNVSLIWNVKDYMSLSEQLRKQIRSAAKKNNIpfrlTCATT 2724
Cdd:cd21711  433 TNVGVVLSANLVTRLSQKAIRVIANAASRNGV----TCAVT 469
deltaCoV-Nsp6 cd21561
deltacoronavirus non-structural protein 6; Coronaviruses (CoV) redirect and rearrange host ...
3552-3836 6.52e-21

deltacoronavirus non-structural protein 6; Coronaviruses (CoV) redirect and rearrange host cell membranes as part of the viral genome replication and transcription machinery; they induce the formation of double-membrane vesicles in infected cells. CoV non-structural protein 6 (Nsp6), a transmembrane-containing protein, together with Nsp3 and Nsp4, have the ability to induce double-membrane vesicles that are similar to those observed in severe acute respiratory syndrome (SARS) coronavirus-infected cells. By itself, Nsp6 can generate autophagosomes from the endoplasmic reticulum. Autophagosomes are normally generated as a cellular response to starvation to carry cellular organelles and long-lived proteins to lysosomes for degradation. Degradation through autophagy may provide an innate defense against virus infection, or conversely, autophagosomes can promote infection by facilitating the assembly of replicase proteins. In addition to initiating autophagosome formation, Nsp6 also limits autophagosome expansion regardless of how they were induced, i.e. whether they were induced directly by Nsp6, or indirectly by starvation or chemical inhibition of MTOR signaling. This may favor coronavirus infection by compromising the ability of autophagosomes to deliver viral components to lysosomes for degradation.


Pssm-ID: 394847  Cd Length: 296  Bit Score: 97.05  E-value: 6.52e-21
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 3552 IVKGTHHWmLLTFLTSLLILVQSTqWSLFFFVYENAFLPFTLGImaiAACAMLLVKHKHAFLCLFLLPSL-ATVAYFNMV 3630
Cdd:cd21561   22 VVKKTCMW-FFHFLFMAVIFLLAA-LHVFPVHLYPIVLPVFTIL---AFLLTLTIKHTVVFTTTYLLPSLlMMVVNANTF 96
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 3631 YMPASWVMRIMTWLELADTSLSGYRLKDCVMYASALVLLILMTARTVYDDAARRVWTLMNVIT---LVYKVYygNALDQA 3707
Cdd:cd21561   97 WIPNTYLRSIYEYVFGSFISERLYGYTVALYILVYAQLAINYTLRTRRYRATSFISFCMQALQygyVAHIVY--RLLTTP 174
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 3708 ISMWALVISVTsnysgvVTTIMFLARAIVFVCVEYYPLLFITGNtLQCIMLVYCFLGYCCCCYFGLFCLLNRYFRLTLGV 3787
Cdd:cd21561  175 WTEGLLFTAFS------LLTSHPLLAALSWWLAGRIPLPLILPD-LAIRVIVYYVIGYVMCMRFGLFWLINKFTTIPMGT 247
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|....*....
gi 30027621 3788 YDYLVSTQEFRYMNSQGLLPPKSSIDAFKLNIKLLGIGGKPCIKVATVQ 3836
Cdd:cd21561  248 YKYMVSIEQLKYMMAVKMSPPRNAFEVLWANIRLLGLGGNRNIAVSTVQ 296
Macro_cv_SUD-N-M_Nsp3-like cd21556
SUD-N and SUD-M macrodomains of the SARS-Unique Domain (SUD) of SARS-CoV non-structural ...
1214-1333 6.82e-21

SUD-N and SUD-M macrodomains of the SARS-Unique Domain (SUD) of SARS-CoV non-structural protein 3 and related macrodomains; This family includes two macrodomains referred to as the SUD-N (N-terminal subdomain) and SUD-M (middle SUD subdomain) of the SARS-unique domain (SUD) which bind G-quadruplexes (unusual nucleic-acid structures formed by consecutive guanosine nucleotides). It is found in non-structural protein 3 (Nsp3) of Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) and highly related coronaviruses. SUD consists of three globular domains separated by short linker peptide segments: SUD-N, SUD-M, and SUD-C. Among these, SUD-N and SUD-M are macrodomains. SUD-N (also called Mac2) is specific to the Nsp3 of SARS and betacoronaviruses of the sarbecovirus subgenera (B lineage), while SUD-M (also called Mac3) is present in most Nsp3 proteins except the Nsp3 from betacoronaviruses of the embecovirus subgenera (A lineage). SUD-C adopts a frataxin-like fold, has structural similarity to DNA-binding domains of DNA-modifying enzymes, binds single-stranded RNA, and regulates the RNA binding behavior of the SUD-M macrodomain. SARS-CoV Nsp3 contains a third macrodomain (the X-domain or Mac1) which is not included in this family. The X-domain may function as a module binding poly(ADP-ribose); however, SUD-N and SUD-M do not bind ADP-ribose, as the triple glycine sequence involved in its binding is not conserved in these.


Pssm-ID: 438956  Cd Length: 108  Bit Score: 91.19  E-value: 6.82e-21
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 1214 EVTTTLEETKFLtNKLLLFADingKLYHDSQNMLRGEDmsflekdAPYMVGDVITSgdITCVVIPSKKaggTTEMLSRAL 1293
Cdd:cd21556    6 NLRGMLREAKEL-GLLLPVCI---DLSAFSKVLRRKGV-------APKIGGDTVDG--VTFYFYSSKD---PLEDLIKAL 69
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|
gi 30027621 1294 KKVPvDEYITTYPGQGCAGYTLEEAKTALKKCKSAFYVLP 1333
Cdd:cd21556   70 NKLG-DPIITTPLGYITHGLDLAQAAEEMRMLTVPFVVLL 108
gammaCoV_PLPro cd21733
gammacoronavirus papain-like protease; This model represents the papain-like protease (PLPro) ...
1542-1813 1.72e-19

gammacoronavirus papain-like protease; This model represents the papain-like protease (PLPro) found in non-structural protein 3 (Nsp3) of gammacoronavirus, including Avian coronavirus, Canada goose coronavirus, and Beluga whale coronavirus SW1. CoVs utilize a multi-subunit replication/transcription machinery. A set of non-structural proteins (Nsps) generated as cleavage products of the ORF1a and ORF1ab viral polyproteins assemble to facilitate viral replication and transcription. PLPro is a key enzyme in this process, making it a high value target for the development of anti-coronavirus therapeutics. PLPro, which belongs to the MEROPS peptidase C16 family, participates in the proteolytic processing of the N-terminal region of the replicase polyprotein; it can cleave Nsp1|Nsp2, Nsp2|Nsp3, and Nsp3|Nsp4 sites and its activity is dependent on zinc. Besides cleaving the polyproteins, PLPro also possesses a related enzymatic activity to promote virus replication: deubiquitinating (DUB) and de-ISGylating activities. Both, ubiquitin (Ub) and Ub-like interferon-stimulated gene product 15 (ISG15), are involved in preventing viral infection; coronaviruses utilize Ubl-conjugating pathways to counter the pro-inflammatory properties of Ubl-conjugated host proteins via the action of PLPro, which processes both 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains from cellular substrates. The Nsp3 PLPro domain in several CoVs has also been shown to antagonize host innate immune induction of type I interferon by interacting with IRF3 and blocking its activation.


Pssm-ID: 409650  Cd Length: 304  Bit Score: 92.88  E-value: 1.72e-19
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 1542 VKTIKVFTTVDNTNLHTQLVDMSMTYGQqFGPTYLDGADVTKiKPHVnhEGKTFFVLPSDDtlrSEAFEYYHtLDESFLG 1621
Cdd:cd21733    2 CKQKTIYLTEDGVKYRSVVVKPGDSLSQ-FGQVFARNKTVFT-ADDV--EDKEILFIPTTD---KAVLEYYG-LDAQKYV 73
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 1622 RYMSALNHtkKWKFPQVGGLTSIKWADNNCYLSSVLLALQQLEVKFNApALQEAYYRARAGDAANFCALILAYSNKTVGE 1701
Cdd:cd21733   74 IYLQTLAQ--KWNVQYRDNFLILEWRDGNCWISSAIVLLQAAKIRFKG-FLAEAWAKFLGGDPTEFVAWCYASCNAKVGD 150
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 1702 LGDVRETMTHLLQH--ANLESAKRVLNVVCKhCGQKTTTLTGVEA----VMYMGTLsydNLKTGVSIPCVCGRDATQYLV 1775
Cdd:cd21733  151 FSDANWLLANLAEYfdADYTNAFLKRRVSCN-CGVKNYELRGLEAciqpVRAPNLL---HFKTQYSNCPTCGANSVDEVV 226
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|
gi 30027621 1776 QQESSFVMMSAP--PAEYKLqQGTFLCANEYTGNYQCGHY 1813
Cdd:cd21733  227 EASLPYLLLLATdgPATVDC-DENAVGNVVFIGSTNSGHC 265
Medioniviridae_RdRp cd23188
catalytic core domain of RNA-dependent RNA polymerase (RdRp) in the Medioniviridae family of ...
4870-5262 3.05e-18

catalytic core domain of RNA-dependent RNA polymerase (RdRp) in the Medioniviridae family of positive-sense single-stranded RNA [(+)ssRNA] viruses; This group contains the catalytic core domain of RdRp of RNA viruses belonging to the family Medioniviridae, order Nidovirales. Member viruses have a viral envelope and (+)ssRNA genome. The Medioniviridae subgenera includes Turrinivirus and Balbicanovirus. The structure of Medioniviridae RdRp contains a RdRp domain as well as a large N-terminal extension that adopts a nidovirus RdRp-associated nucleotidyltransferase (NiRAN) architecture. The RdRp domain displays a right hand with three functional subdomains, called fingers, palm, and thumb. All RdRps contain conserved polymerase motifs (A-G), located in the palm (A-E motifs) and finger (F-G) subdomains. All these motifs have been implicated in RdRp fidelity such as processes of correct incorporation and reorganization of nucleotides.


Pssm-ID: 438038  Cd Length: 391  Bit Score: 90.91  E-value: 3.05e-18
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 4870 SAGFPFNKWGKARLYyDSMSYEDQDALFAYTKRNVIPTITQMNLKYAISAKNRARTVAGVSICSTMTNRQFHQKLLKSIA 4949
Cdd:cd23188    1 SAGQPYVKVGDSDVV-RGVLGDDRDTMIKHRCHSHHQTLVTANAKLAVGGKFKCRPISGINVLESDVGRTLFTAILEAIK 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 4950 AT-RGATVVIGTSKFYggWHNMLKTVYSDVETPH----LMGWDYPKCDRAMPNMLRIMASLVLARK-----HNTCCNLSH 5019
Cdd:cd23188   80 HCcYENMIVIGWSKFT--GFDRLFRNFLNSRLDHidyrLSGKDFPQWDRSVESNMQLLTNFLIFCSydwalCREFCSLQE 157
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 5020 RFYRLANECAQVLSEMVMCGGSLYVKPGGTSSGDATTAYANSVFNICQAVTANVNALLSTDGNKIADKYVRNLQhRLYEC 5099
Cdd:cd23188  158 ALHLFCTEFTNTVYSYFICDNLVMRKSGGVCSGNSKTAPGNSIMHAIWEYAAIIEHLHYYRGEDPELIELRQFF-MLYES 236
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 5100 LYRNR-DVDHEFVDEFYAYLRKHFSMMILSDDAVvcynsNYAAQGLVASIK-NFKAVLYYQNNVFMSEAkcWTETDLTKG 5177
Cdd:cd23188  237 HSLSAlREHDHLLDTNLLRLQSHHLLRVLSDDGM-----VLHDKELLFDYSsLFPYFYLYSNYHFTNDK--HYSCAPLHG 309
                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 5178 PHEFCSQHTMLVkqgdDYVYLPYPDPSRILGAGCFVDDIVKTDGTLMIERFVSLAIDAYPL---TKHPNQEYAdvfhLYL 5254
Cdd:cd23188  310 PHEFCSAEAIIV----DDKYYLCPEPGRHLGALFYSSRTTRFDINVRIALLSSYILEGIPLlfnTLLPYHERI----LPL 381

                 ....*...
gi 30027621 5255 QYIRKLHD 5262
Cdd:cd23188  382 ILLDYIKK 389
gammaCoV_Nsp7 cd21828
gammacoronavirus non-structural protein 7; This model represents the non-structural protein 7 ...
3837-3919 3.42e-18

gammacoronavirus non-structural protein 7; This model represents the non-structural protein 7 (Nsp7) of gammacoronaviruses that include Avian infectious bronchitis virus (IBV) and Canada goose coronavirus (CGCoV), among others. CoVs utilize a multi-subunit replication/transcription machinery. A set of non-structural proteins (Nsps) generated as cleavage products of the ORF1a and ORF1ab viral polyproteins assemble to facilitate viral replication and transcription. Upon processing of the Nsp7-10 region by protease M (Mpro), the released four small proteins Nsp7, Nsp8, Nsp9 and Nsp10 form functional complexes with CoV core enzymes and stimulate replication. Most importantly, a complex of Nsp7 with Nsp8 has been shown to activate and confer processivity to the RNA-synthesizing activity of Nsp12, the RNA-dependent RNA-polymerase (RdRp); in SARS-CoV, point mutations in the NSP7- or NSP8-coding region have been shown to delay virus growth. Nsp7 and Nsp8 cooperate in activating the primer-dependent activity of the Nsp12 RdRp such that the level of their association may constitute a limiting factor for obtaining a high RNA polymerase activity. The subsequent Nsp7/Nsp8/Nsp12 polymerase complex is then able to associate with an active bifunctional Nsp14, which includes N-terminal 3' to 5' exoribonuclease (ExoN) and C-terminal N7-guanine cap methyltransferase (N7-MTase) activities, thus representing a unique coronavirus Nsp assembly that incorporates RdRp, exoribonuclease, and N7-MTase activities. Interaction of Nsp7 with Nsp8 appears to be conserved across the coronavirus family, making these proteins interesting drug targets. Nsp7 has a 4-helical bundle conformation which is strongly affected by its interaction with Nsp8, especially where it concerns alpha-helix 4. SARS-CoV Nsp7 forms a 8:8 hexadecameric supercomplex with Nsp8 that adopts a hollow cylinder-like structure with a large central channel and positive electrostatic properties in the cylinder, while Feline infectious peritonitis virus Nsp7 forms a 2:1 heterotrimer with Nsp8. Regardless of their oligomeric structure, the Nsp7/Nsp8 complex functions as a noncanonical RNA polymerase capable of synthesizing RNA of up to template length.


Pssm-ID: 409254  Cd Length: 83  Bit Score: 82.53  E-value: 3.42e-18
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 3837 SKMSDVKCTSVVLLSVLQQLRVESSSKLWAQCVQLHNDILLAKDTTEAFEKMVSLLSVLLSMQGAVDINRLCEEMLDNRA 3916
Cdd:cd21828    1 SKLTDVKCTTVVLMQLLTKLNVEANSKMHKYLVELHNKILASDDVVECMDNLLGMLVTLLCIDSTIDLSEYCDDILKRST 80

                 ...
gi 30027621 3917 TLQ 3919
Cdd:cd21828   81 VLQ 83
1B_UPF1_nv_SF1_Hel-like cd21344
1B domain of eukaryotic UPF1 helicase, nidovirus SF1 helicases including coronavirus Nsp13 and ...
5451-5529 1.40e-16

1B domain of eukaryotic UPF1 helicase, nidovirus SF1 helicases including coronavirus Nsp13 and arterivirus Nsp10, and related proteins; Helicases catalyze NTP-dependent unwinding of nucleic acid duplexes into single strands and are classified based on the arrangement of conserved motifs into six superfamilies. Members of this family belong to helicase superfamily 1 (SF1) and include nidoviral helicases such as Severe Acute Respiratory Syndrome coronavirus (SARS) non-structural protein 13 (SARS-Nsp13), Equine arteritis virus (EAV) Nsp10, and eukaryotic UPF1 RNA helicase. SARS-Nsp13 is a component of the viral RNA synthesis replication and transcription complex (RTC). UPF1 participates in nonsense-mediated mRNA decay (NMD), a pathway which degrades transcripts with premature termination codons. UPF1, EAV Nsp10 and SARS-Nsp13 are multidomain proteins with an N-terminal Cys/His rich zinc-binding domain (CH/ZBD), a 1B domain and a SF1 helicase core. The 1B domain is involved in nucleic acid substrate binding; the 1B domain of EAV Nsp10 undergoes large conformational change upon substrate binding, and together with the 1A and 2A domains of the helicase core form a channel that accommodates the single stranded nucleic acids.


Pssm-ID: 439170  Cd Length: 86  Bit Score: 78.12  E-value: 1.40e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 5451 GIATVREVL---SDRELHLSWEVGKP--RPPLNRNYVFTGYRVTknskVQIGEYTFEKGDY------GDAVVYRGTTTYK 5519
Cdd:cd21344    1 LIITVRWRLalnDFRGAYFSLEKGKSqcKPPLGDEIVLTYYGDT----VPLWEGIGEVIDLpntgndDDALELKGSTTYP 76
                         90
                 ....*....|
gi 30027621 5520 LNVGDYFVLT 5529
Cdd:cd21344   77 LTVTHIFVLT 86
Macro_SF cd02749
macrodomain superfamily; Macrodomains are found in a variety of proteins with diverse cellular ...
1034-1142 8.72e-16

macrodomain superfamily; Macrodomains are found in a variety of proteins with diverse cellular functions, as a stand-alone domain or in combination with other domains like in histone macroH2A and some PARPs (poly ADP-ribose polymerases). Macrodomains can recognize ADP-ribose (ADPr) in both its free and protein-linked forms, in related ligands, such as O-acyl-ADP-ribose (OAADPr), and even in ligands unrelated to ADPr. Macrodomains include the yeast macrodomain Poa1 which is a phosphatase of ADP-ribose-1"-phosphate, a by-product of tRNA splicing. Some macrodomains have ADPr-unrelated binding partners such as the coronavirus SUD-N (N-terminal subdomain) and SUD-M (middle subdomain) of the SARS-unique domain (SUD) which bind G-quadruplexes (unusual nucleic-acid structures formed by consecutive guanosine nucleotides). Macrodomains regulate a wide variety of cellular and organismal processes, including DNA damage repair, signal transduction, and immune response.


Pssm-ID: 394871  Cd Length: 121  Bit Score: 77.05  E-value: 8.72e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 1034 VIVNAANIHLKHGGGVAGALNKATNGAMQKESdDYIKLNGPLTVGGSCLLSGHNL-AKKCLHVVGPN-LNAGEDIQLLKA 1111
Cdd:cd02749    2 AIVNPANNDLYLGGGVAKAISKKAGGDLQEEC-EERKKNGYLKVGEVAVTKGGNLpARYIIHVVGPVaSSKKKTYEPLKK 80
                         90       100       110
                 ....*....|....*....|....*....|....*..
gi 30027621 1112 AYENFNSQDI------LLAPLLSAGIFGAKPLQSLQV 1142
Cdd:cd02749   81 CVKNCLSLADekglksVAFPAIGTGIAGFPPEEAARI 117
A1pp smart00506
Appr-1"-p processing enzyme; Function determined by Martzen et al. Extended family detected by ...
1018-1142 4.28e-15

Appr-1"-p processing enzyme; Function determined by Martzen et al. Extended family detected by reciprocal PSI-BLAST searches (unpublished results, and Pehrson _ Fuji).


Pssm-ID: 214701  Cd Length: 133  Bit Score: 75.42  E-value: 4.28e-15
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621    1018 IKCV--DIVKeaqsANPMVIVNAANIHLKHGGGVAGALNKATNGamQKESDDYIKLNGPLTVGGSCLLS--GHNLAKKCL 1093
Cdd:smart00506    2 LKVVkgDITK----PRADAIVNAANSDGAHGGGVAGAIARAAGK--ALSKEEVRKLAGGECPVGTAVVTegGNLPAKYVI 75
                            90       100       110       120       130
                    ....*....|....*....|....*....|....*....|....*....|....*..
gi 30027621    1094 HVVGPNLNAGEDI--QLLKAAYENF------NSQDILLAPLLSAGIFGAKPLQSLQV 1142
Cdd:smart00506   76 HAVGPRASGHSKEgfELLENAYRNClelaieLGITSVALPLIGTGIYGVPKDRSAQA 132
deltaCoV_Nsp9 cd21900
deltacoronavirus non-structural protein 9; This model represents the non-structural protein 9 ...
4118-4230 1.80e-14

deltacoronavirus non-structural protein 9; This model represents the non-structural protein 9 (Nsp9) from deltacoronaviruses such as the Porcine delta coronavirus (PDCoV) Porcine coronavirus HKU15. CoVs utilize a multi-subunit replication/transcription machinery assembled from a set of non-structural proteins (Nsps) generated as cleavage products of the ORF1a and ORF1ab viral polyproteins. All of these Nsps, except for Nsp1 and Nsp2, are considered essential for transcription, replication, and translation of the viral RNA. Nsp9, with Nsp7, Nsp8, and Nsp10, localizes within the replication complex. Nsp9 is an essential single-stranded RNA-binding protein for coronavirus replication; it shares structural similarity to the oligosaccharide-binding (OB) fold, which is characteristic of proteins that bind to ssDNA or ssRNA. Nsp9 requires dimerization for binding and orienting RNA for subsequent use by the replicase machinery. CoV Nsp9s have diverse forms of dimerization that promote their biological function, which may help elucidate the mechanism underlying CoVs replication and contribute to the development of antiviral drugs. Generally, dimers are formed via interaction of the parallel alpha-helices containing the protein-protein interaction motif GXXXG; additionally, the N-finger region may also play a critical role in dimerization as seen in porcine delta coronavirus (PDCoV) Nsp9. As a member of the replication complex, Nsp9 may not have a specific RNA-binding sequence but may act in conjunction with other Nsps as a processivity factor, as shown by mutation studies indicating that Nsp9 is a key ingredient that intimately engages other proteins in the replicase complex to mediate efficient virus transcription and replication.


Pssm-ID: 409333  Cd Length: 109  Bit Score: 72.85  E-value: 1.80e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 4118 NNELspvALRQMSCAagttQTACTDDN-----ALAYYNNSKGGRFVLALLSDHQDLKWArFPKSDgTGTIYTELEPPCRF 4192
Cdd:cd21900    1 NNEL---CLRNVFTA----QNTASDGNgnestAKSFYVSRTGKKILVAVTSTKDNLKTV-TCDTD-TGKVVLNLDPPMRF 71
                         90       100       110
                 ....*....|....*....|....*....|....*....
gi 30027621 4193 -VTDTPKgPKVKYLYFIKGLNNLNRGMVLGSLAATVRLQ 4230
Cdd:cd21900   72 sHVVGGK-QSVVYLYFIQNISSLNRGMVIGHISGTTILQ 109
PRK00431 PRK00431
ADP-ribose-binding protein;
1034-1148 2.94e-14

ADP-ribose-binding protein;


Pssm-ID: 234759  Cd Length: 177  Bit Score: 74.49  E-value: 2.94e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621  1034 VIVNAANIHLKHGGGVAGALNKATNGAMQKESDDYIKLNGPLTVGGSCLLSGHNL-AKKCLHVVGPNLNAGED--IQLLK 1110
Cdd:PRK00431   19 AIVNAANSSLLGGGGVDGAIHRAAGPEILEECRELRQQQGPCPTGEAVITSAGRLpAKYVIHTVGPVWRGGEDneAELLA 98
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*...
gi 30027621  1111 AAYenFNSqdILLA----------PLLSAGIFGAKPLQSLQVCVQTVR 1148
Cdd:PRK00431   99 SAY--RNS--LRLAaelglrsiafPAISTGVYGYPLEDAARIAVKTVR 142
alphaCoV_PLPro cd21731
alphacoronavirus papain-like protease; This model represents the papain-like protease (PLPro) ...
1543-1742 1.30e-13

alphacoronavirus papain-like protease; This model represents the papain-like protease (PLPro) found in non-structural protein 3 (Nsp3) of alphacoronavirus, including Swine acute diarrhea syndrome coronavirus (SADS-CoV) which causes severe diarrhea in piglets, and Human coronavirus 229E which infects humans and bats and causes the common cold. CoVs utilize a multi-subunit replication/transcription machinery. A set of non-structural proteins (Nsps) generated as cleavage products of the ORF1a and ORF1ab viral polyproteins assemble to facilitate viral replication and transcription. PLPro is a key enzyme in this process, making it a high value target for the development of anti-coronavirus therapeutics. PLPro, which belongs to the MEROPS peptidase C16 family, participates in the proteolytic processing of the N-terminal region of the replicase polyprotein; it can cleave Nsp1|Nsp2, Nsp2|Nsp3, and Nsp3|Nsp4 sites and its activity is dependent on zinc. Besides cleaving the polyproteins, PLPro also possesses a related enzymatic activity to promote virus replication: deubiquitinating (DUB) and de-ISGylating activities. Both, ubiquitin (Ub) and Ub-like interferon-stimulated gene product 15 (ISG15), are involved in preventing viral infection; coronaviruses utilize Ubl-conjugating pathways to counter the pro-inflammatory properties of Ubl-conjugated host proteins via the action of PLPro, which processes both 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains from cellular substrates. The Nsp3 PLPro domain in SADS-CoV and many others has also been shown to antagonize host innate immune induction of type I interferon by interacting with IRF3 and blocking its activation.


Pssm-ID: 409648  Cd Length: 289  Bit Score: 75.35  E-value: 1.30e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 1543 KTIKVFTTVDNTNLHTQLVDMSMTYGQQFGPTYLDGADVTKIKPhVNHEGKTFFVLPSDDTL------RSEAFeyyHTLD 1616
Cdd:cd21731    1 KSVVVKVTEDGRNVKDVVVDTDKTFGEQLGVCSVNDKDVTGVVP-PDDSDKVVSVAPDVDWDshygfpNAAVF---HTLD 76
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 1617 ESflgRYmsalnhtkKWKFPQVGGLTSIKWADNNCYLSSVLLALQQLEVKFNAPALQEAYYRARAGDAANFCALILAYSN 1696
Cdd:cd21731   77 HS---AY--------AFESDIVNGKRVLKQSDNNCWVNAVCLQLQFAKPTFKSEGLQALWNKFLTGDVAGFVHWLYWITG 145
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*...
gi 30027621 1697 KTVGELGDVrETMTHLLQHANLESAKRVLNVV--CKHCGQKTTTLTGV 1742
Cdd:cd21731  146 ANKGDPGDA-ENTLNKLSKYLVSSGSVTVERTtgCDSCNSKRTVTTPV 192
HKU9-like_Nsp3_NAB cd21825
nucleic acid binding domain of non-structural protein 3 from Rousettus bat coronavirus HKU9 ...
1883-2007 2.61e-13

nucleic acid binding domain of non-structural protein 3 from Rousettus bat coronavirus HKU9 and betacoronavirus in the D lineage; This model represents the nucleic acid binding (NAB) domain of non-structural protein 3 (Nsp3) from betacoronavirus in the nobecovirus subgenus (D lineage), including Rousettus bat coronavirus HKU9. The NAB domain represents a new fold, with a parallel four-strand beta-sheet holding two alpha-helices of three and four turns that are oriented antiparallel to the beta-strands. NAB is a cytoplasmic domain located between the papain-like protease (PLPro) and betacoronavirus-specific marker (betaSM) domains of CoV Nsp3. Nsp3 is a large multi-functional multi-domain protein that is an essential component of the replication/transcription complex (RTC), which carries out RNA synthesis, RNA processing, and interference with the host cell innate immune system. The NAB domain both binds ssRNA and unwinds dsDNA. It prefers to bind ssRNA containing repeats of three consecutive guanines. A group of residues that form a positively charged patch on the protein surface of SARS-CoV Nsp3 NAB serves as the binding site of nucleic acids. This site is conserved in the NAB of Nsp3 from betacoronavirus in the sarbecovirus subgenus (B lineage), but is not conserved in the Nsp3 NAB from betacoronaviruses in the D lineage.


Pssm-ID: 409351  Cd Length: 117  Bit Score: 69.86  E-value: 2.61e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 1883 YYTEQPIDLVPTqPLPNASFDNFKLT-CSNTKFADDLNQMTGFTKPASRELsVTFFPDLNGDVVAIDYRHYSAsFKKGAK 1961
Cdd:cd21825    3 YFTTAPLEVVAA-PKLVTPYDGFYLSsCQNLALAESFNKAINATKQGPKKL-LTVYPNCSGDVVAVSDDNVTA-HPYGSL 79
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*..
gi 30027621 1962 LLHKPIVWhinqattktTFKPNTW-CLRCLWSTKPVDTSNSFEVLAV 2007
Cdd:cd21825   80 IMGKPVLF---------VTKPNTWkKLVPLLSALVVETTNKYEVLPV 117
NTD_gammaCoV_Nsp15-like cd22650
N-terminal domain of gammacoronavirus Nonstructural protein 15 (Nsp15), and related proteins; ...
6431-6490 3.19e-13

N-terminal domain of gammacoronavirus Nonstructural protein 15 (Nsp15), and related proteins; Coronavirus (CoV) Nsp15 is a nidovirus endoribonuclease (NendoU). NendoUs are uridylate-specific endoribonucleases, which release a cleavage product containing a 2',3'-cyclic phosphate at the 3' terminal end. NendoUs include coronavirus Nsp15 and arterivirus Nsp11, both of which may participate in the viral replication process and in the evasion of the host immune system. This NTD structure (approximately 60 residues) present in coronavirus Nsp15, is missing in Nsp11. CoV Nsp15 has an N-terminal domain, a middle (M) domain, and a C-terminal catalytic (NendoU) domain. Nsp15 from alpha- and betaCoVs such as Severe Acute Respiratory Syndrome (SARS)-CoV, human Coronavirus 229E (HCoV229E), and Murine Hepatitis Virus (MHV) form a functional hexamer. The active form of the Nsp15 of Turkey CoV (TCoV), a gammaCoV, has been reported to be a homohexamer. Residues in this N-terminal domain may be important for hexamer formation.


Pssm-ID: 439165  Cd Length: 60  Bit Score: 67.58  E-value: 3.19e-13
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 6431 LENVAYNVVNKGHFDGHAGEAPVSIINNAVYTKVDGIDVEIFENKTTLPVNVAFELWAKR 6490
Cdd:cd22650    1 IDNIAYNMYKGGHYDAIAGEMPTVITGDKVFVIDQGVEKAVFVNQTTLPTSVAFELYAKR 60
DNA2 COG1112
Superfamily I DNA and/or RNA helicase [Replication, recombination and repair];
5624-5893 7.62e-13

Superfamily I DNA and/or RNA helicase [Replication, recombination and repair];


Pssm-ID: 224037 [Multi-domain]  Cd Length: 767  Bit Score: 75.77  E-value: 7.62e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 5624 KYLPIDKCSRIIpaRARVECFDKFKVNSTLEQYVFCTVNALPETTADIVVFDEISMATNYD-LSVVNarlRAKHYVYIGD 5702
Cdd:COG1112  446 KQKKILKELRRL--KKKAVTKILEAADVVLSTLSIAGFSILKKYEFDYVIIDEASQATEPSaLIALS---RAKKVILVGD 520
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 5703 PAQLPapRTLLTKGT----LEPEYFNSVCRLMKtiGPDMFLGTCRRCPAEIVDTVSALVYDNKLKAHKDKSAQCFKMFYK 5778
Cdd:COG1112  521 HKQLP--PTVFFKESspegLSASLFERLIDNGP--EVVYLLRVQYRMHPDIIAFSSKVFYNGRLEVHTSFLAFTLLDGEI 596
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 5779 GVITH-------DVSSAINRPQIG-------------VVREFLTRNPAWRKAVFISPYNSQNA-----VASKILGLPTQT 5833
Cdd:COG1112  597 PEVVIsnplefyDTLGAEEFFESKsklneleaeivkvIVDELLKDGLEENDIGVISPYRAQVSlirrlLNEAGKGVEVGT 676
                        250       260       270       280       290       300
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 30027621 5834 VDSSQGSEYDYVIFTQT------TETAHSCNVNRFNVAITRAKIGiLCIMSDRDLYDKLQFTSLEI 5893
Cdd:COG1112  677 VDGFQGREKDVIILSLVrsnddkGEIGFLGDPRRLNVALTRAKRK-LIVVGSSSTLESDPLYKRLI 741
MERS-CoV-like_Nsp3_NAB cd21823
nucleic acid binding domain of non-structural protein 3 from Middle East respiratory ...
1883-1996 8.21e-13

nucleic acid binding domain of non-structural protein 3 from Middle East respiratory syndrome-related coronavirus and betacoronavirus in the C lineage; This model represents the nucleic acid binding (NAB) domain of non-structural protein 3 (Nsp3) from betacoronavirus in the merbecovirus subgenus (C lineage), including Middle East respiratory syndrome-related coronavirus (MERS-CoV) and Tylonycteris bat coronavirus HKU4. The NAB domain represents a new fold, with a parallel four-strand beta-sheet holding two alpha-helices of three and four turns that are oriented antiparallel to the beta-strands. NAB is a cytoplasmic domain located between the papain-like protease (PLPro) and betacoronavirus-specific marker (betaSM) domains of CoV Nsp3. Nsp3 is a large multi-functional multi-domain protein that is an essential component of the replication/transcription complex (RTC), which carries out RNA synthesis, RNA processing, and interference with the host cell innate immune system. The NAB domain both binds ssRNA and unwinds dsDNA. It prefers to bind ssRNA containing repeats of three consecutive guanines. A group of residues that form a positively charged patch on the protein surface of SARS-CoV Nsp3 NAB serves as the binding site of nucleic acids. This site is conserved in the NAB of Nsp3 from betacoronavirus in the sarbecovirus subgenus (B lineage), and appears to be partially conserved in the Nsp3 NAB from betacoronaviruses in the C lineage.


Pssm-ID: 409349  Cd Length: 123  Bit Score: 68.62  E-value: 8.21e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 1883 YYTEQP-IDLVPTQPLPNASFDNFKLTCSNTKFADD-----LNQMTGF--TKPASRELSVTFFPDLNGDVVAIDYRHYSA 1954
Cdd:cd21823    2 YFTSKPpIEYSPATVLAGSVYTNSCLVASDGTPGGDaislaFNNLLGFdeSKPVSKKLTYSLLPNEDGDVLLAEFSTYDP 81
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|..
gi 30027621 1955 SFKKGAKLLHKPIVWHINQATTKTTFKPNTWCLRCLWSTKPV 1996
Cdd:cd21823   82 IYKNGAMLKGKPILWVNNGLFDSALNKFNRASLRQIYDVAPV 123
M_gcv_Nsp15-like cd21168
middle domain of gammacoronavirus Nonstructural protein 15 (Nsp15), and related proteins; ...
6495-6625 9.07e-13

middle domain of gammacoronavirus Nonstructural protein 15 (Nsp15), and related proteins; Nidovirus endoribonucleases (NendoUs) are uridylate-specific endoribonucleases, which release a cleavage product containing a 2',3'-cyclic phosphate at the 3' terminal end. NendoUs include Nsp15 from coronaviruses and Nsp11 from arteriviruses, both of which may participate in the viral replication process and in the evasion of the host immune system. Coronavirus Nsp15 NendoUs have an N-terminal domain, a middle (M) domain and a C-terminal catalytic (NendoU) domain. Coronavirus Nsp15 from Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV), human Coronavirus 229E (HCoV229E), and Murine Hepatitis Virus (MHV) form a functional hexamer. This middle domain harbors residues involved in hexamer formation and in trimer stability. Oligomerization of Porcine DeltaCoronavirus (PDCoV) Nsp15 differs from that of the other coronaviruses; it has been shown to exist as a dimer and a monomer in solution.


Pssm-ID: 394906  Cd Length: 123  Bit Score: 68.34  E-value: 9.07e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 6495 VPEIKILNNLGVDIAANTVIWDYKREAPAHVSTIGVCTMTDIAKkptesacSSLTVLFDGRVEGQVDLFRNARNGVLITE 6574
Cdd:cd21168    2 IPNTAILYGLGVDVTAGFTIWDYENSQPVFRNTVKVCKYTDIEP-------NGLCVLYDDRYKGDYQRFLAADNAVLIST 74
                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|..
gi 30027621 6575 GSVKGLTPSKGPAQASV-NGVTLigESVKTQFNYfKKVDGIIQQLPETYFTQ 6625
Cdd:cd21168   75 QCYKVYSSVRIPSSCQIqNGSTL--KDGANLFVY-KRVNGKFVTLPSTLNTQ 123
SF1_C_Upf1 cd18808
C-terminal helicase domain of Upf1-like family helicases; The Upf1-like helicase family ...
5745-5882 3.81e-12

C-terminal helicase domain of Upf1-like family helicases; The Upf1-like helicase family includes UPF1, HELZ, Mov10L1, Aquarius, IGHMBP2 (SMUBP2), and similar proteins. They are DEAD-like helicases belonging to superfamily (SF)1, a diverse family of proteins involved in ATP-dependent RNA or DNA unwinding. Similar to SF2 helicases, SF1 helicases do not form toroidal structures like SF3-6 helicases. Their helicase core consists of two similar protein domains that resemble the fold of the recombination protein RecA. This model describes the C-terminal domain, also called HelicC.


Pssm-ID: 350195 [Multi-domain]  Cd Length: 184  Bit Score: 68.41  E-value: 3.81e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 5745 CPAEIVDTVSALVYDNKLKAHKDKSAQCFKMFYKG----VITHDVSSA----------INRPQIGVVRE---FLTRNPAW 5807
Cdd:cd18808    1 MHPEISEFPSKLFYEGKLKAGVSVAARLNPPPLPGpskpLVFVDVSGGeereesgtskSNEAEAELVVElvkYLLKSGVK 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 5808 RKAV-FISPYNSQ-----NAVASKILGLPT---QTVDSSQGSEYDYVIFTqtteTAHSC----------NVNRFNVAITR 5868
Cdd:cd18808   81 PSSIgVITPYRAQvalirELLRKRGGLLEDvevGTVDNFQGREKDVIILS----LVRSNesggsigflsDPRRLNVALTR 156
                        170
                 ....*....|....
gi 30027621 5869 AKIGiLCIMSDRDL 5882
Cdd:cd18808  157 AKRG-LIIVGNPDT 169
AAA_12 pfam13087
AAA domain; This family of domains contain a P-loop motif that is characteristic of the AAA ...
5744-5881 9.73e-12

AAA domain; This family of domains contain a P-loop motif that is characteristic of the AAA superfamily. Many of the proteins in this family are conjugative transfer proteins.


Pssm-ID: 432964 [Multi-domain]  Cd Length: 196  Bit Score: 67.57  E-value: 9.73e-12
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621   5744 RCPAEIVDTVSALVYDNKLKAHKDKSAQ-CFKMFYKG-----VITHDVS-----------SAINRPQIGVV----REFLT 5802
Cdd:pfam13087   25 RMHPEIMEFPSKLFYGGKLKDGPSVAERpLPDDFHLPdplgpLVFIDVDgseeeesdggtSYSNEAEAELVvqlvEKLIK 104
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621   5803 RNP-AWRKAVFISPYNSQ--------NAVASKILGLPTQTVDSSQGSEYDYVIFTqTTETAHSCNV------NRFNVAIT 5867
Cdd:pfam13087  105 SGPeEPSDIGVITPYRAQvrlirkllKRKLGGKLEIEVNTVDGFQGREKDVIIFS-CVRSNEKGGIgflsdpRRLNVALT 183
                          170
                   ....*....|....
gi 30027621   5868 RAKIGiLCIMSDRD 5881
Cdd:pfam13087  184 RAKRG-LIIVGNAK 196
betaCoV_Nsp2_HKU9-like cd21518
betacoronavirus non-structural protein 2 (Nsp2) similar to bat coronavirus HKU9 Nsp2, and ...
275-818 6.16e-11

betacoronavirus non-structural protein 2 (Nsp2) similar to bat coronavirus HKU9 Nsp2, and related proteins from betacoronaviruses in the D lineage; Coronavirus non-structural proteins (Nsps) are encoded in ORF1a and ORF1b. Post infection, the genomic RNA is released into the cytoplasm of the cell and translated into two long polyproteins (pp), pp1a and pp1ab, which are then autoproteolytically cleaved by two viral proteases Nsp3 and Nsp5 into smaller subunits. Nsp2 is one of these subunits. This subgroup includes Nsp2 from Rousettus bat coronavirus HKU9 and betacoronaviruses in the nobecovirus subgenus (D lineage). It belongs to a family which includes Severe acute respiratory syndrome coronavirus (SARS-CoV) Nsp2, and Murine hepatitis virus (MHV) Nsp2 (also known as p65). The function of Nsp2 remains unclear. SARS-CoV Nsp2, rather than playing a role in viral replication, may be involved in altering the host cell environment; deletion of Nsp2 from the SARS-CoV genome results in only a modest reduction in viral titers. It has been shown to interact with two host proteins, prohibitin 1 (PHB1) and PHB2, which have been implicated in cellular functions, including cell-cycle progression, cell migration, cellular differentiation, apoptosis, and mitochondrial biogenesis. MHV Nsp2/p65, different from SARS-CoV Nsp2, may play an important role in the viral life cycle.


Pssm-ID: 394869  Cd Length: 597  Bit Score: 69.41  E-value: 6.16e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621  275 FPLNSKVKVIQPRVEK---KKTEGFMGRI--RSVYPVASPqecnnmhlSTLMKCNHCDEVSWQTC-DFLKATCEhCGTEN 348
Cdd:cd21518   92 YSTGSVVKHTKPRRDSpvgKTVESIMLSLygTSGYNPATP--------VVRLRCSYCDFYGWVPLkDMGTVVCS-CGAEY 162
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621  349 LVIegpTTCGYLPTNAVVKMPCPACQDPEIGpehsvadyhnhsnieTRLRKGGRTR-CFGGCVFAYVGCYNKRAYWVPRA 427
Cdd:cd21518  163 QLT---SSCVDAESAGFIKPGCVMLLDKSPG---------------MRLIPGNRTYvAFGGAIWSPIGKVNDVTVWVPRA 224
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621  428 SADIGSGHTGITGD-NVETLNEDLLEIlsrervninIVGDFHLNEEV--AIILASFSASTSafIDTiKSLDYKSFKTIVE 504
Cdd:cd21518  225 YSVVAGDHSGAVGSgDVRAINKELMAL---------LIEGFKIDEETleKPSCAKFIANLQ--CDD-KLPVVHTVDTLNQ 292
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621  505 SCGNYKVTKGK---------PVKGAWNIGQQRSvltplCGFPSQAagvirsifARTLDAanhsIPDLQRAAVTILDGISE 575
Cdd:cd21518  293 LCLDNKVMLGDhplpsdefhPAIVGLSYHVQRA-----CWYAALA--------SKTFGA----MRTFVRKEEERLAVFCG 355
                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621  576 QSLRLVDAMVYTSDLLTNSVIIMAY-VTGGLVQQTSQWLSNLLGTTVEKLRPIFEWIEAKLSagveFLKDAW----EILK 650
Cdd:cd21518  356 KDYAPQLSCVQMAYTTGVVTLLSAYqVLDAAVSKTKDAFGGATSIVKDLLKPVLDWVLNKMT----LAKGAWldyaEALL 431
                        410       420       430       440       450       460       470       480
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621  651 FLITGVFDIVKGQIQVASDNIKDCVKCFIDVVNKALEMCIDQVTIAGAKLRSLNLGEVFIAQSKGLYRQC-IRGKEQLQL 729
Cdd:cd21518  432 ALFKAQFTFVKGKFQFLRDALNKSCGALRDLLTVVLSKLLTTAKWAGCKVEALYTGTYHYFSRCGVLTEVqVCAKSLGVL 511
                        490       500       510       520       530       540       550       560
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621  730 LMPLKAPKEVTFLEGDSHDTV-LTSEEVVLKNGELEAletpVDSFTNGAIV-GTPVCVNGLMLLEIKDKEQYCALSPG-- 805
Cdd:cd21518  512 LTPRQQKMEVEVLEGDFDAPVeLTSEELEEAAGTLEE----VFGASDLQLVkGSLVTLASKVFVRTEDGLFYRYVKSGgv 587
                        570
                 ....*....|...
gi 30027621  806 LLatnNVFRLKGG 818
Cdd:cd21518  588 LL---KAFRLRGG 597
SUD_C_DPUP_CoV_Nsp3 cd21513
C-terminal SARS-Unique Domain (SUD) of betacoronavirus non-structural protein 3 (Nsp3); This ...
1472-1524 1.56e-10

C-terminal SARS-Unique Domain (SUD) of betacoronavirus non-structural protein 3 (Nsp3); This family contains the SUD-C of Nsp3 from Severe Acute Respiratory Syndrome (SARS) coronavirus (CoV), Middle East respiratory syndrome-related (MERS) CoV, and Rousettus bat CoV HKU9, as well as the DPUP (domain preceding Ubl2 and PLP2) of murine hepatitis virus (MHV) Nsp3. Though structurally similar, there is little sequence similarity between these four domain subfamilies: SARS SUD-C, MERS SUD-C, HKU9 SUD-C, and MHV DPUP. Non-structural protein 3 (Nsp3) is a large multi-functional multi-domain protein that is an essential component of the replication/transcription complex (RTC), which carries out RNA synthesis, RNA processing, and interference with the host cell innate immune system. Nsp3 of SARS coronavirus includes a SARS-unique domain (SUD) consisting of three globular domains separated by short linker peptide segments: SUD-N, SUD-M, and SUD-C. SUD-N and SUD-M are macro domains which bind G-quadruplexes (unusual nucleic-acid structures formed by consecutive guanosine nucleotides). The SUD-C domain adopts a frataxin-like fold and has structural similarity to DNA-binding domains of DNA-modifying enzymes. It binds to single-stranded RNA and recognizes purine bases more strongly than pyrimidine bases. SUD-C also regulates the RNA binding behavior of the SUD-M macrodomain. SUD-C is not as specific to SARS CoV Nsp3 as originally thought, and is conserved in the Nsp3s of all four lineages (A-D) of betacoronavirus.


Pssm-ID: 394838  Cd Length: 71  Bit Score: 60.26  E-value: 1.56e-10
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 30027621 1472 TSEEHFVETVSLAGSyRDWSYSGQRTE----LGVEFLKRGDKIVYHTLespVEFHLD 1524
Cdd:cd21513    1 TDERVFVQAVMLNGP-RDWRLVNKFDSvdgvRYKKYLKRGGIFVCSQD---KKFYYV 53
Macro_OAADPr_deacetylase cd02908
macrodomain, O-acetyl-ADP-ribose (OAADPr) family; Macrodomains are found in a variety of ...
1034-1148 1.94e-10

macrodomain, O-acetyl-ADP-ribose (OAADPr) family; Macrodomains are found in a variety of proteins with diverse cellular functions, as a stand-alone domain or in combination with other domains like in histone macroH2A and some PARPs (poly ADP-ribose polymerases). Macrodomains can recognize ADP-ribose (ADPr) in both its free and protein-linked forms, in related ligands, such as O-acyl-ADP-ribose (OAADPr), and even in ligands unrelated to ADPr. This family includes eukaryotic macrodomain proteins such as human MacroD1 and MacroD2, and bacterial proteins such as Escherichia coli YmdB; these have been shown to be O-acetyl-ADP-ribose (OAADPr) deacetylases that efficiently catalyze the hydrolysis of OAADPr to produce ADP-ribose and free acetate. OAADPr is a sirtuin reaction product generated from the NAD+-dependent protein deacetylation reactions and has been implicated as a signaling molecule. By acting on mono-ADP-ribosylated substrates, OAADPr deacetylases may reverse cellular ADP-ribosylation.


Pssm-ID: 438955  Cd Length: 166  Bit Score: 62.92  E-value: 1.94e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 1034 VIVNAANIHLKHGGGVAGALNKATNGAMQKESDdyiKLNGPLTVGGSCLLSGHNL-AKKCLHVVGPNLNAGEDI--QLLK 1110
Cdd:cd02908   16 AIVNAANSSLLGGGGVDGAIHRAAGPELLEECR---KLGGVCPTGEAKITPGYNLpAKYVIHTVGPIGEGGVEEepELLA 92
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*.
gi 30027621 1111 AAYEnfNSQDILLA--------PLLSAGIFGAKPLQSLQVCVQTVR 1148
Cdd:cd02908   93 SCYR--SSLELALEnglksiafPCISTGIYGYPNEEAAEIALNTVR 136
Macro_SF cd02749
macrodomain superfamily; Macrodomains are found in a variety of proteins with diverse cellular ...
1363-1445 3.83e-10

macrodomain superfamily; Macrodomains are found in a variety of proteins with diverse cellular functions, as a stand-alone domain or in combination with other domains like in histone macroH2A and some PARPs (poly ADP-ribose polymerases). Macrodomains can recognize ADP-ribose (ADPr) in both its free and protein-linked forms, in related ligands, such as O-acyl-ADP-ribose (OAADPr), and even in ligands unrelated to ADPr. Macrodomains include the yeast macrodomain Poa1 which is a phosphatase of ADP-ribose-1"-phosphate, a by-product of tRNA splicing. Some macrodomains have ADPr-unrelated binding partners such as the coronavirus SUD-N (N-terminal subdomain) and SUD-M (middle subdomain) of the SARS-unique domain (SUD) which bind G-quadruplexes (unusual nucleic-acid structures formed by consecutive guanosine nucleotides). Macrodomains regulate a wide variety of cellular and organismal processes, including DNA damage repair, signal transduction, and immune response.


Pssm-ID: 394871  Cd Length: 121  Bit Score: 60.87  E-value: 3.83e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 1363 KLMPICMDV-----RAIMATIQRKYKG---------------IKIQEGIVDYG---VRFFFYT----------SKEPVAS 1409
Cdd:cd02749    1 DAIVNPANNdlylgGGVAKAISKKAGGdlqeeceerkkngylKVGEVAVTKGGnlpARYIIHVvgpvasskkkTYEPLKK 80
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|.
gi 30027621 1410 IITKLNSL-----NEPLVTMPIGYVTHGFNLEEAARCMRSL 1445
Cdd:cd02749   81 CVKNCLSLadekgLKSVAFPAIGTGIAGFPPEEAARIMLEA 121
NTD_deltaCoV_Nsp15-like cd21172
N-terminal domain of deltacoronavirus Nonstructural protein 15 (Nsp15), and related proteins; ...
6431-6490 9.48e-10

N-terminal domain of deltacoronavirus Nonstructural protein 15 (Nsp15), and related proteins; Coronavirus (CoV) Nsp15 is a nidovirus endoribonuclease (NendoU). NendoUs are uridylate-specific endoribonucleases, which release a cleavage product containing a 2',3'-cyclic phosphate at the 3' terminal end. NendoUs include coronavirus Nsp15 and arterivirus Nsp11, both of which may participate in the viral replication process and in the evasion of the host immune system. This small NTD structure, present in CoV Nsp15, is missing in Nsp11. CoV Nsp15 has an N-terminal domain, a middle (M) domain, and a C-terminal catalytic (NendoU) domain. Oligomerization of Porcine DeltaCoronavirus (PDCoV) Nsp15 differs from the Nsp15 of alpha- and beta-coronavirus, such as Severe Acute Respiratory Syndrome (SARS)-CoV and Murine Hepatitis Virus (MHV) which form functional hexamers; PDCoV Nsp15 has been shown to exist as dimers and monomers in solution, and to function as a dimer.


Pssm-ID: 439164  Cd Length: 60  Bit Score: 57.56  E-value: 9.48e-10
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 6431 LENVAYNVVNKGHFDGHAGEAPVSIINNAVYTKVDGIDVEIFENKTTLPVNVAFELWAKR 6490
Cdd:cd21172    1 LENLAYNCYYKNCNAHVDGQLDVVINNNAVYAKVDNNLVKLFDNRTNLPVSVAFEHYTNR 60
NendoU_tv_PToV-like cd21162
Nidoviral uridylate-specific endoribonuclease (NendoU) domain of Porcine torovirus (PToV) ...
6663-6773 1.80e-09

Nidoviral uridylate-specific endoribonuclease (NendoU) domain of Porcine torovirus (PToV) endoribonuclease and related proteins; Nidovirus endoribonucleases (NendoUs) are uridylate-specific endoribonucleases, which release a cleavage product containing a 2',3'-cyclic phosphate at the 3' terminal end. The Porcine torovirus (PToV) strain PToV-NPL/2013 NendoU domain is located at the N-terminus of the ORF1ab replicase polyprotein, between regions annotated as Nonstructural proteins 11 (Nsp11) and 13 (Nsp13). This subfamily belongs to a family which includes Nsp15 from coronaviruses and Nsp11 from arteriviruses, which may participate in the viral replication process and in the evasion of the host immune system. These vary in their requirement for Mn2+. Coronavirus Nsp15 generally form functional hexamers, with the exception of Porcine DeltaCoronavirus (PDCoV) Nsp15 which exists as a dimer and a monomer in solution. Arterivirus (Porcine Reproductive and Respiratory Syndrome virus) PRRSV Nsp11 is a dimer. NendoUs are distantly related to Xenopus laevis Mn(2+)-dependent uridylate-specific endoribonuclease (XendoU) which is involved in the processing of intron-encoded box C/D U16 small, nucleolar RNA.


Pssm-ID: 394913  Cd Length: 133  Bit Score: 59.14  E-value: 1.80e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 6663 HIVYGDFSH--GQLGGLHLMIGL--AKRSQdsplkledfIPMDSTvKNYFITDAQTGSSKCVCSVIDLLLDDFVEIIKSQ 6738
Cdd:cd21162   27 HVFLGEFTEvsTTIGGVHHVPALngTKGSI---------IPSYVK-PIHTGLINVGKGVKRCTTLVDVCANQLYELVKQQ 96
                         90       100       110
                 ....*....|....*....|....*....|....*.
gi 30027621 6739 DLSV-ISKVVKVTIDYAEISFMLWCKDGHVETFYPK 6773
Cdd:cd21162   97 INGVtVSKVIFINIDFQEVQFMVFASEGDIQTAYPQ 132
deltaCoV_PLPro cd21734
deltacoronavirus papain-like protease; This model represents the papain-like protease (PLPro) ...
1543-1745 1.07e-08

deltacoronavirus papain-like protease; This model represents the papain-like protease (PLPro) found in the non-structural protein 3 (Nsp3) region of deltacoronavirus, including Porcine deltacoronavirus, Bulbul coronavirus HKU11, and Common moorhen coronavirus HKU21. CoVs utilize a multi-subunit replication/transcription machinery. A set of non-structural proteins (Nsps) generated as cleavage products of the ORF1a and ORF1ab viral polyproteins assemble to facilitate viral replication and transcription. PLPro is a key enzyme in this process, making it a high value target for the development of anti-coronavirus therapeutics. PLPro, which belongs to the MEROPS peptidase C16 family, participates in the proteolytic processing of the N-terminal region of the replicase polyprotein; it can cleave Nsp1|Nsp2, Nsp2|Nsp3, and Nsp3|Nsp4 sites and its activity is dependent on zinc. Besides cleaving the polyproteins, PLPro also possesses a related enzymatic activity to promote virus replication: deubiquitinating (DUB) and de-ISGylating activities. Both, ubiquitin (Ub) and Ub-like interferon-stimulated gene product 15 (ISG15), are involved in preventing viral infection; coronaviruses utilize Ubl-conjugating pathways to counter the pro-inflammatory properties of Ubl-conjugated host proteins via the action of PLPro, which processes both 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains from cellular substrates. The Nsp3 PLPro domain in many of these CoVs has also been shown to antagonize host innate immune induction of type I interferon by interacting with IRF3 and blocking its activation.


Pssm-ID: 409651  Cd Length: 313  Bit Score: 60.90  E-value: 1.07e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 1543 KTIkVFTTVDNTNLHTQLvdmsMTYGQQFGPTYLDGAD-VTKIKPHVNHegktffvLPSDDTLRSEAFEYYHTLDESFlg 1621
Cdd:cd21734   14 RTV-VRTTKDFDQVTTKA----LTPQGVLDANLFDGEDfVQEPKPGQIY-------LAVTDEVQQQAKELDLTLSQYC-- 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 1622 RYMSALNHtkKWKFPQVGGLTSIKWADNNCYLSSVLLALQQLEVKFNaPALQEAYYRARAGDAANFCALILAYSNKTVGE 1701
Cdd:cd21734   80 VYLKYCHH--KWSVSRTNGLMHLKQKDNNCFVSAAINLFQNTHYQLR-PAIDALYQEYLNGNPSRFVAWIYASTNQEIGE 156
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....
gi 30027621 1702 LGDVRETMTHLLQHANlesAKRVLNVVCkhCGqKTTTLTGVEAV 1745
Cdd:cd21734  157 MGCPQQVLSLLVNNSN---AKFSGTTAC--CG-TYFTHDGVISV 194
DEXXQc_SETX cd18042
DEXXQ-box helicase domain of SETX; The RNA/DNA helicase senataxin (SETX) plays a role in ...
5574-5708 1.97e-08

DEXXQ-box helicase domain of SETX; The RNA/DNA helicase senataxin (SETX) plays a role in transcription, neurogenesis, and antiviral response. SEXT is an R-loop-associated protein that is thought to function as an RNA/DNA helicase. R-loops consist of RNA/DNA hybrids, formed during transcription when nascent RNA hybridizes to the DNA template strand, displacing the non-template DNA strand. Mutations in SETX are linked to two neurodegenerative disorders: ataxia with oculomotor apraxia type 2 (AOA2) and amyotrophic lateral sclerosis type 4 (ALS4). S. cerevisiae homolog splicing endonuclease 1 (Sen1) is an exclusively nuclear protein, important for nucleolar organization. S. cerevisiae Sen1 and its ortholog, the Schizosaccharomyces pombe Sen1, share conserved domains and belong to the family I class of helicases. Both proteins translocate 5' to 3' and unwind both DNA and RNA duplexes and also RNA/DNA hybrids in vitro. SETX is a member of the DEAD-like helicase superfamily, a diverse family of proteins involved in ATP-dependent RNA or DNA unwinding. This domain contains the ATP-binding region.


Pssm-ID: 438712 [Multi-domain]  Cd Length: 218  Bit Score: 58.38  E-value: 1.97e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 5574 GMQKYSTLQGPPGTGKSHFAIGL--ALYY-------------------------PSARIVYTACSHAAVDALCEKALKYL 5626
Cdd:cd18042   15 NSPGITLIQGPPGTGKTKTIVGIlsVLLAgkyrkyyekvkkklrklqrnlnnkkKKNRILVCAPSNAAVDEIVLRLLSEG 94
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 5627 PID--------KCSRIIPARARVECFDKFKVnstleqyVFCTVNA----LPETTA---DIVVFDEISMATnyDLSVVNA- 5690
Cdd:cd18042   95 FLDgdgrsykpNVVRVGRQELRASILNEADI-------VCTTLSSsgsdLLESLPrgfDTVIIDEAAQAV--ELSTLIPl 165
                        170
                 ....*....|....*...
gi 30027621 5691 RLRAKHYVYIGDPAQLPA 5708
Cdd:cd18042  166 RLGCKRLILVGDPKQLPA 183
Euroniviridae_RdRp cd23191
catalytic core domain of RNA-dependent RNA polymerase (RdRp) in the family Eunroniviridae of ...
4907-5238 2.22e-08

catalytic core domain of RNA-dependent RNA polymerase (RdRp) in the family Eunroniviridae of positive-sense single-stranded RNA [(+)ssRNA] viruses; This group contains the catalytic core domain of RdRp of RNA viruses belonging to the family Eunroniviridae, order Nidovirales. Member viruses have a viral envelope and (+)ssRNA genome. Eunroniviridae is a closely related family of crustacean nidoviruses, within the suborder Ronidovirineae, which also includes the family Roniviridae. Ronidovirineae, named "rod-shaped nidovirus", is 150-200 nm long and approximately 60 nm thick. There are 3 viral species in the Euroniviridae family, all of which have been detected in crustaceans. The structure of Euroniviridae RdRp contains a RdRp domain as well as a large N-terminal extension that adopts a nidovirus RdRp-associated nucleotidyltransferase (NiRAN) architecture. The RdRp domain displays a right hand with three functional subdomains, called fingers, palm, and thumb. All RdRps contain conserved polymerase motifs (A-G), located in the palm (A-E motifs) and finger (F-G) subdomains. All these motifs have been implicated in RdRp fidelity such as processes of correct incorporation and reorganization of nucleotides.


Pssm-ID: 438041  Cd Length: 345  Bit Score: 59.91  E-value: 2.22e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 4907 TITQMNLKYAISAKNRA-RTVAGVSICSTMTNRQFHQKLLKSIAATRgaTVVIGTSKFYGGWHNMLKTVYsdvETPH--L 4983
Cdd:cd23191    1 FITQVRPKIAVQPQEKPlRSIISGSPVITDCIRHVTQNMMRIMVSLR--HLFIGNRADPRGFTEMLQFLE---ESPAdyQ 75
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 4984 MGWDYPKCDRAMPNMLRI---MASLVLARKHNTCCNLSHRFY---RLANECAQVLSEmvmcgGSLYVKPGGTSSGDATTA 5057
Cdd:cd23191   76 VSLDHSKFDRRVDSLLSYaghLATMDLTDLCGHDPQLVHNIMashFMTYTYNLLLFD-----GMLYIKNGGVSSGNSITA 150
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 5058 YANSVfnICQAVTANVNALLSTDGNKIADKYvrnlQHRLYECLYRNRDVDHEFVDEFYAYLRkhfsMMILSDDAVVCYNS 5137
Cdd:cd23191  151 LNNSL--AAQQHTFICCMREALKGPKIQWEY----QKYQFDLFMDPMELIDIEPNKIWKYFR----IAGLSDDVVASVPS 220
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 5138 NYA-AQGLVASIKNFKAVLYYQNNVFMSEAKcwtetdltKGPHEFCSQHTMLVKQGDDyVYLPYPDPSRILGAGCFVDDI 5216
Cdd:cd23191  221 MLIdPDDLMAQFKSFGYIMVKDKKYFVSGKD--------EPPTELMSRWPERVPVGPE-IEMPHPTVDRVLSSMLLIEKR 291
                        330       340
                 ....*....|....*....|..
gi 30027621 5217 VKTDGTLMIERFVSLAIDAYPL 5238
Cdd:cd23191  292 SSLDPLVKRMRTISILLDGITL 313
ZBD_tv_SF1_Hel-like cd21403
Cys/His rich zinc-binding domain (CH/ZBD) of tornidovirus SF1 helicase and related proteins; ...
5302-5384 3.07e-07

Cys/His rich zinc-binding domain (CH/ZBD) of tornidovirus SF1 helicase and related proteins; Helicases catalyze NTP-dependent unwinding of nucleic acid duplexes into single strands and are classified based on the arrangement of conserved motifs into six superfamilies. This tornidovirus group includes White bream virus (WBV) SF1 helicase encoded on ORF1b and belongs to helicase superfamily 1 (SF1). The CH/ZBD has 3 zinc-finger (ZnF1-3) motifs. Members of this group belong to a family of nindoviral replication helicases which include includes Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) non-structural protein 13 (SARS-Nsp13), a component of the viral RNA synthesis replication and transcription complex (RTC). The SARS-Nsp13 CH/ZBD is indispensable for helicase activity and interacts with SARS-Nsp12, the RNA-dependent RNA polymerase.


Pssm-ID: 394810  Cd Length: 95  Bit Score: 51.58  E-value: 3.07e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 5302 AVGACVLCNSQTSLRCGACIRRPFLCCKCCYDHVISTSHKLvlsVNPYVCNAPGCDVTDVTQLYL----GGMSYYCKSHK 5377
Cdd:cd21403    1 SDQQCYCCPNPTVSTCTSCPVPYPLCAYCAYEHYVQTGHLV---THLPKCHHPGCGESDPRNLNFclvnGGFTTRCDEHV 77

                 ....*..
gi 30027621 5378 PPISFPL 5384
Cdd:cd21403   78 TGFSIPL 84
DEXXQc_SF1 cd18043
DEXXQ-box helicase domain of Superfamily 1 helicases; Superfamily 1 (SF1) helicases are ...
5581-5713 3.81e-07

DEXXQ-box helicase domain of Superfamily 1 helicases; Superfamily 1 (SF1) helicases are nucleic acid motor proteins that couple ATP hydrolysis to translocation along with the concomitant unwinding of DNA or RNA. This is central to many aspects of cellular DNA and RNA metabolism and accordingly, they are implicated in a wide range of nucleic acid processing events including DNA replication, recombination, and repair as well as many aspects of RNA metabolism. Superfamily 1 helicases are members of the DEAD-like helicase superfamily, a diverse family of proteins involved in ATP-dependent RNA or DNA unwinding. This domain contains the ATP-binding region.


Pssm-ID: 350801 [Multi-domain]  Cd Length: 127  Bit Score: 52.58  E-value: 3.81e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 5581 LQGPPGTGKSHF---AIGLALYYpSARIVYTACSHAAVDALcekalkYLPI-----DKCSRIIPARarvecFDKFkvnst 5652
Cdd:cd18043   19 IQGPPGTGKSQTianIIANALAR-GKRVLFVSEKKAALDVV------RFPCwimspLSVSQYLPLN-----RNLF----- 81
                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 30027621 5653 leqyvfctvnalpettaDIVVFDEISMAtnYDLSVVNARLRAKHYVYIGDPAQLPaPRTLL 5713
Cdd:cd18043   82 -----------------DLVIFDEASQI--PIEEALPALFRGKQVVVVGDDKQLP-PSILL 122
Macro_H2A-like cd02904
macrodomain, macroH2A-like family; Macrodomains are found in a variety of proteins with ...
1035-1115 4.13e-07

macrodomain, macroH2A-like family; Macrodomains are found in a variety of proteins with diverse cellular functions, as a stand-alone domain or in combination with other domains like in histone macroH2A and some PARPs (poly ADP-ribose polymerases). Macrodomains can recognize ADP-ribose (ADPr) in both its free and protein-linked forms, in related ligands, such as O-acyl-ADP-ribose (OAADPr), and even in ligands unrelated to ADPr. Members of this family are similar to macroH2A, a variant of the major-type core histone H2A, which contains an N-terminal H2A domain and a C-terminal nonhistone macrodomain. Histone macroH2A is enriched on the inactive X chromosome of mammalian female cells. It does not bind poly ADP-ribose, but does bind the monomeric SirT1 metabolite O-acetyl-ADP-ribose (OAADPR) with high affinity through its macrodomain. This family also includes the ADP-ribose binding macrodomain of the macroH2A variant, macroH2A1.1. The macroH2A1.1 isoform inhibits PARP1-dependent DNA-damage induced chromatin dynamics. The putative ADP-ribose binding pocket of the human macroH2A2 macrodomain exhibits marked structural differences compared with the macroH2A1.1 variant.


Pssm-ID: 394875  Cd Length: 188  Bit Score: 53.86  E-value: 4.13e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 1035 IVNAANIHLKHGGGVAGALNKATNGAMQKESDDYIKLNGPLTVGGSCLLSGHNL-AKKCLHVVGPNLNAGEDIQLLKAAY 1113
Cdd:cd02904   35 IVHPTNATFYLGGEVGSALEKAGGKEFVEEVKELRKSNGPLEVAGAAISPGHNLpAKFVIHCNSPSWGSDKCEELLEKTV 114

                 ..
gi 30027621 1114 EN 1115
Cdd:cd02904  115 KN 116
RdRP_1 pfam00680
RNA dependent RNA polymerase;
4866-5133 1.62e-06

RNA dependent RNA polymerase;


Pssm-ID: 425815  Cd Length: 450  Bit Score: 54.72  E-value: 1.62e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621   4866 NLDKSAGFPF--NKWGKARLYYD----SMSYEDQDALfaYTKRNVIPTITQMNLKYAISAKNRARTVAGVS--------I 4931
Cdd:pfam00680   97 NWDTSAGYPYvgLGGKKGDLIEHlkdgTEARELAERL--AADWEVLQNGTPLKLVYQTCLKDELRPLEKVEkgktrlvwG 174
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621   4932 CSTMTN---RQFHQKLLKSIAATRG-ATVVIGTSKFYGGWHNMLKTVYSdvETPHLMGWDYPKCDRAMPNMLRIMASLVL 5007
Cdd:pfam00680  175 EPVEYLlleRAFFDPFNQAFMLNNGfHPIQVGINPFDRGWPRLLRRLAR--FGDYVYELDYSGFDSSVPPWLIRFAFEIL 252
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621   5008 arKHNTCCNLSHRFYRLANECAqVLSEMVMCGGSLYVKPGGTSSGDATTAYANSVFNicqavtanvnallstdgnkiadk 5087
Cdd:pfam00680  253 --RELLGFPSNVKEWRAILELL-IYTPIALPNGTVFKKTGGLPSGSPFTSIINSIVN----------------------- 306
                          250       260       270       280
                   ....*....|....*....|....*....|....*....|....*.
gi 30027621   5088 YVRNLQHRLYECLyrNRDVDHEFVDefyaylrKHFSMMILSDDAVV 5133
Cdd:pfam00680  307 YLLILYALLKSLE--NDGPRVCNLD-------KYFDFFTYGDDSLV 343
DEXXQc_SMUBP2 cd18044
DEXXQ-box helicase domain of SMUBP2; SMUBP2 (also called immunoglobulin mu-binding protein 2, ...
5581-5707 3.07e-06

DEXXQ-box helicase domain of SMUBP2; SMUBP2 (also called immunoglobulin mu-binding protein 2, or IGHMBP2) is a 5' to 3' helicase that unwinds RNA and DNA duplexes in an ATP-dependent reaction. It is a DNA-binding protein specific to 5'-phosphorylated single-stranded guanine-rich sequence (5'-GGGCT-3') related to the immunoglobulin mu chain switch region. The IGHMBP2 gene is responsible for Charcot-Marie-Tooth disease (CMT) type 2S and spinal muscular atrophy with respiratory distress type 1 (SMARD1). It is also thought to play a role in frontotemporal dementia (FTD) with amyotrophic lateral sclerosis (ALS) and major depressive disorder (MDD). SMUBP2 is a member of the DEAD-like helicase superfamily, a diverse family of proteins involved in ATP-dependent RNA or DNA unwinding. This domain contains the ATP-binding region.


Pssm-ID: 350802 [Multi-domain]  Cd Length: 191  Bit Score: 51.46  E-value: 3.07e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 5581 LQGPPGTGKSH--FAIGLALYYPSARIVYTACSHAAVDALCEK----ALKYLPIDKCSRIIPARARVeCFDkFKVNStle 5654
Cdd:cd18044   22 IHGPPGTGKTTtvVEIILQAVKRGEKVLACAPSNIAVDNLVERlvalKVKVVRIGHPARLLESVLDH-SLD-ALVAA--- 96
                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 30027621 5655 QYVFCT-VNA-----LPETTADIVVFDEISMATnyDLSVVNARLRAKHYVYIGDPAQLP 5707
Cdd:cd18044   97 QVVLATnTGAgsrqlLPNELFDVVVIDEAAQAL--EASCWIPLLKARRCILAGDHKQLP 153
Macro_Ttha0132-like cd03330
Macrodomain, uncharacterized family similar to Thermus thermophilus hypothetical protein ...
1034-1133 3.37e-06

Macrodomain, uncharacterized family similar to Thermus thermophilus hypothetical protein Ttha0132; Macrodomains are found in a variety of proteins with diverse cellular functions, as a stand-alone domain or in combination with other domains like in histone macroH2A and some PARPs (poly ADP-ribose polymerases). Macrodomains can recognize ADP-ribose (ADPr) in both its free and protein-linked forms, in related ligands, such as O-acyl-ADP-ribose (OAADPr), and even in ligands unrelated to ADPr. Macrodomains include the yeast macrodomain Poa1 which is a phosphatase of ADP-ribose-1"-phosphate, a by-product of tRNA splicing. Some macrodomains have ADPr-unrelated binding partners such as the coronavirus SUD-N (N-terminal subdomain) and SUD-M (middle subdomain) of the SARS-unique domain (SUD) which bind G-quadruplexes (unusual nucleic-acid structures formed by consecutive guanosine nucleotides). Macrodomains regulate a wide variety of cellular and organismal processes, including DNA damage repair, signal transduction, and immune response. This family is composed of uncharacterized proteins containing a stand-alone macrodomain, similar to Thermus thermophilus hypothetical protein Ttha0132.


Pssm-ID: 394879  Cd Length: 147  Bit Score: 50.12  E-value: 3.37e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 1034 VIVNAANIHLKHGGGVAGALNKATNGAMQKESDDyiklNGPLTVGGSCLLSGHNL-AKKCLH--VVGPNLNAG-EDIQ-- 1107
Cdd:cd03330   16 AIVNAANRRLLMGSGVAGAIKRKGGEEIEREAMR----KGPIRVGEAVETGAGKLpAKYVIHaaVMGMPGRSSeESIRda 91
                         90       100       110
                 ....*....|....*....|....*....|
gi 30027621 1108 ----LLKAAYENFNSqdiLLAPLLSAGIFG 1133
Cdd:cd03330   92 trnaLAKAEELGLES---VAFPAIGTGVGG 118
YmdB COG2110
O-acetyl-ADP-ribose deacetylase (regulator of RNase III), contains Macro domain [Translation, ...
1034-1135 4.48e-06

O-acetyl-ADP-ribose deacetylase (regulator of RNase III), contains Macro domain [Translation, ribosomal structure and biogenesis];


Pssm-ID: 225021 [Multi-domain]  Cd Length: 179  Bit Score: 50.81  E-value: 4.48e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 1034 VIVNAANIHLKHGGGVAGALNKATNGAMQKESDDYIKLNGP--LTVGGSCLLSGHNL-AKKCLHVVGPNLNAGEDI--QL 1108
Cdd:COG2110   19 AIVNAANSQLLGGGGVAGAIHRAAGPQLEEECAEIAPKRGGgrIPVGEAVITEAGRLpAKYVIHTVGPSWRGGSKDeaEL 98
                         90       100
                 ....*....|....*....|....*..
gi 30027621 1109 LKAAYenfnsqdilLAPLLSAGIFGAK 1135
Cdd:COG2110   99 LAAAY---------RAALRLAKEAGVR 116
SF1_C cd18786
C-terminal helicase domain of superfamily 1 DEAD/H-box helicases; Superfamily (SF)1 family ...
5799-5873 3.33e-05

C-terminal helicase domain of superfamily 1 DEAD/H-box helicases; Superfamily (SF)1 family members include UvrD/Rep, Pif1-like, and Upf-1-like proteins. Similar to SF2 helicases, they do not form toroidal, predominantly hexameric structures like SF3-6. SF1 helicases are a diverse family of proteins involved in ATP-dependent RNA or DNA unwinding. Their helicase core is surrounded by C- and N-terminal domains with specific functions such as nucleases, RNA or DNA binding domains, or domains engaged in protein-protein interactions. The core consists of two similar protein domains that resemble the fold of the recombination protein RecA. This model describes the C-terminal domain, also called HelicC.


Pssm-ID: 350173 [Multi-domain]  Cd Length: 89  Bit Score: 45.89  E-value: 3.33e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 5799 EFLTRNPAWRKAVFISPYNSQNAVASKILGLPTQ-----------TVDSSQGSEYDYVIFtqTTETAHSCNVNRFNVAIT 5867
Cdd:cd18786    2 AIVNAANGLYKGVVLTPYHRDRAYLNQYLQGLSLdefdlqlvgaiTIDSSQGLTFDVVTL--YLPTANSLTPRRLYVALT 79

                 ....*.
gi 30027621 5868 RAKIGI 5873
Cdd:cd18786   80 RARKRL 85
NendoU_av_Nsp11-like cd21160
Nidoviral uridylate-specific endoribonuclease (NendoU) domain of arterivirus PRRSV ...
6694-6772 4.63e-05

Nidoviral uridylate-specific endoribonuclease (NendoU) domain of arterivirus PRRSV Nonstructural protein 11 (Nsp11), and related proteins; Nidovirus endoribonucleases (NendoUs) are uridylate-specific endoribonucleases, which release a cleavage product containing a 2',3'-cyclic phosphate at the 3' terminal end. NendoUs include Nsp15 from coronaviruses and Nsp11 from arteriviruses, both of which may participate in the viral replication process and in the evasion of the host immune system. Mn2+ is dispensable, and to some extent inhibits the activity of arterivirus (Porcine Reproductive and Respiratory Syndrome virus) PRRSV Nsp11. This Nsp11 exists as a dimer. NendoUs are distantly related to Xenopus laevis Mn(2+)-dependent uridylate-specific endoribonuclease (XendoU) which is involved in the processing of intron-encoded box C/D U16 small, nucleolar RNA.


Pssm-ID: 394911  Cd Length: 120  Bit Score: 46.16  E-value: 4.63e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 6694 LEDFIPMDSTVKnyfITDAQTG-SSKCVCSVIDLLLDDFVEIIKSqdlSVISKVVKVTIDYAEISFMLWcKDghvETFYP 6772
Cdd:cd21160   49 LPPVLPAGSVVK---VGVSSPGkAAKALCTVTDVYLPYLEPYLNP---PTQSKVYKVNIDFKPVRLMVW-KD---ATMYF 118
AAA_11 pfam13086
AAA domain; This family of domains contain a P-loop motif that is characteristic of the AAA ...
5581-5634 5.78e-05

AAA domain; This family of domains contain a P-loop motif that is characteristic of the AAA superfamily. Many of the proteins in this family are conjugative transfer proteins.


Pssm-ID: 404072 [Multi-domain]  Cd Length: 248  Bit Score: 48.49  E-value: 5.78e-05
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 30027621   5581 LQGPPGTGKSHFAIGLALY---------YPSARIVYTACSHAAVDALCEKALKY--LPIDKCSRI 5634
Cdd:pfam13086   18 IQGPPGTGKTTTIVELIRQllsypatsaAAGPRILVCAPSNAAVDNILERLLRKgqKYGPKIVRI 82
DEXXQc_DNA2 cd18041
DEXXQ-box helicase domain of DNA2; DNA2 (DNA Replication Helicase/Nuclease 2) possesses ...
5569-5707 1.73e-04

DEXXQ-box helicase domain of DNA2; DNA2 (DNA Replication Helicase/Nuclease 2) possesses different enzymatic activities, such as single-stranded DNA (ssDNA)-dependent ATPase, 5-3 helicase, and endonuclease activities, and is involved in DNA replication and DNA repair in the nucleus and mitochondrion. It is involved in Okazaki fragment processing by cleaving long flaps that escape FEN1: flaps that are longer than 27 nucleotides are coated by replication protein A complex (RPA), leading to recruit DNA2 which cleaves the flap until it is too short to bind RPA and becomes a substrate for FEN1. It is also involved in 5-end resection of DNA during double-strand break (DSB) repair; it is recruited by BLM and mediates the cleavage of 5-ssDNA, while the 3-ssDNA cleavage is prevented by the presence of RPA. DNA2 is a member of the DEAD-like helicase superfamily, a diverse family of proteins involved in ATP-dependent RNA or DNA unwinding. This domain contains the ATP-binding region.


Pssm-ID: 350799 [Multi-domain]  Cd Length: 203  Bit Score: 46.46  E-value: 1.73e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 5569 NYQKVGMQK------YSTLQGPPGTGKSHFAIGL--ALYYPSARIVYTACSHAAVDALCEKALK----YLPIDKCSRIIP 5636
Cdd:cd18041    4 KDQRQAIKKvlnakdYALILGMPGTGKTTTIAALvrILVALGKSVLLTSYTHSAVDNILLKLKKfgvnFLRLGRLKKIHP 83
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 5637 ARARVECFDKFKVNSTLEQY---------VFCTV-----NALPETTADIVVFDEISMATnyDLSVVNARLRAKHYVYIGD 5702
Cdd:cd18041   84 DVQEFTLEAILKSCKSVEELeskyesvsvVATTClginhPIFRRRTFDYCIVDEASQIT--LPICLGPLRLAKKFVLVGD 161

                 ....*
gi 30027621 5703 PAQLP 5707
Cdd:cd18041  162 HYQLP 166
UvrD_C_2 pfam13538
UvrD-like helicase C-terminal domain; This domain is found at the C-terminus of a wide variety ...
5833-5870 2.21e-04

UvrD-like helicase C-terminal domain; This domain is found at the C-terminus of a wide variety of helicase enzymes. This domain has a AAA-like structural fold.


Pssm-ID: 433290 [Multi-domain]  Cd Length: 51  Bit Score: 42.17  E-value: 2.21e-04
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|.
gi 30027621   5833 TVDSSQGSEYDYVIFTQTTETAHSCNVNRFN---VAITRAK 5870
Cdd:pfam13538    5 TVHKAQGSEFPAVFLVDPDLTAHYHFMLRRRllyTAVTRAR 45
AAA_30 pfam13604
AAA domain; This family of domains contain a P-loop motif that is characteristic of the AAA ...
5578-5708 5.16e-04

AAA domain; This family of domains contain a P-loop motif that is characteristic of the AAA superfamily. Many of the proteins in this family are conjugative transfer proteins. There is a Walker A and Walker B.


Pssm-ID: 433343 [Multi-domain]  Cd Length: 191  Bit Score: 44.86  E-value: 5.16e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621   5578 YSTLQGPPGTGKSHFAIGLALYYPSA--RIVYTACSHAAVDALcEKALKylpidkcsriIPARarvecfdkfkvnsTLEQ 5655
Cdd:pfam13604   20 VAVLVGPAGTGKTTALKALREAWEAAgyRVIGLAPTGRAAKVL-GEELG----------IPAD-------------TIAK 75
                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621   5656 YVFCTVNALPETTADIVVFDEISMATNYDL-------SVVNARLRAkhyvyIGDPAQLPA 5708
Cdd:pfam13604   76 LLHRLGGRAGLDPGTLLIVDEAGMVGTRQMarllklaEDAGARVIL-----VGDPRQLPS 130
Roniviridae_RdRp cd23190
catalytic core domain of RNA-dependent RNA polymerase (RdRp) in the family Roniviridae of ...
4955-5243 7.97e-04

catalytic core domain of RNA-dependent RNA polymerase (RdRp) in the family Roniviridae of positive-sense single-stranded RNA [(+)ssRNA] viruses; This group contains the catalytic core domain of RdRp of RNA viruses belonging to the family Roniviridae, order Nidovirales. Member viruses have a viral envelope and (+)ssRNA genome. The family Roniviridae includes a single genus (Okavirus) for three species of viruses (Yellow head virus, Gill-associated virus and Okavirus 1) with enveloped, rod-shaped virions. Roniviruses infect penaeid and palaemonid shrimp. Natural infections are usually without apparent clinical signs. One member of the family (yellow head virus) is highly pathogenic for shrimp. Roniviruses are most closely related to other nidoviruses infecting arthropods, including members of the families Mesoniviridae (from mosquitoes) and Euroniviridae (from crustaceans). The structure of Roniviridae RdRp contains a RdRp domain as well as a large N-terminal extension that adopts a nidovirus RdRp-associated nucleotidyltransferase (NiRAN) architecture. The RdRp domain displays a right hand with three functional subdomains, called fingers, palm, and thumb. All RdRps contain conserved polymerase motifs (A-G), located in the palm (A-E motifs) and finger (F-G) subdomains. All these motifs have been implicated in RdRp fidelity such as processes of correct incorporation and reorganization of nucleotides.


Pssm-ID: 438040  Cd Length: 379  Bit Score: 45.81  E-value: 7.97e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 4955 TVVIGTSKFYGGWHNMLKTVYSDVETPHLMGW---DYPKCDRAMPNMLRiMASLVLARKHNTCCNLSHRFYRLANECAQV 5031
Cdd:cd23190   77 TVLIGFKDTHCGINKLINGIKAGFNPKGKAKWisqDYPKFDTCVDTMAQ-YSYIMNHAYHYTHTNLSLIVRGLCQLIANS 155
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 5032 LSEMVMCGGSLYVKPGGTSSGDATTAYANSVfniCQAVTANVNALLSTDGNKIADKYvRNLQHRLYECLYRNRDVDHEFV 5111
Cdd:cd23190  156 TSPIIYYNSILIRKLHGVSSGDGATAIKNSH---CNSVITNIAFYRQIVDNQVPEEY-RGLQSTLYTTLINGIHSKDDAY 231
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 5112 DEFYAYLRKHFSMMILSDDAVVCYNSNyaAQGLVASIKNFKAVLYYQnnvFMSEAKCWTETDltkgPHEFCSQHTMlvkq 5191
Cdd:cd23190  232 STHRAFEWNISRCATLSDDTLAIINPD--VFDLDQYLSSYRTLGGYE---ITNEKKIFVRDE----PYEFTSRYFF---- 298
                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|..
gi 30027621 5192 GDDYVYLPYPDPSRILGAGCFVDDIVKTDGTLMIERFVSLAIDAYPLTKHPN 5243
Cdd:cd23190  299 KEDGFWYNAPLIERVFSSIVQCSKATSLCPEIMGGRLLSILINAWPLTRTDN 350
ps-ssRNAv_RdRp-like cd23167
conserved catalytic core domain of RNA-dependent RNA polymerase (RdRp) from the positive-sense ...
4982-5136 9.07e-04

conserved catalytic core domain of RNA-dependent RNA polymerase (RdRp) from the positive-sense single-stranded RNA [(+)ssRNA] viruses and closely related viruses; This family contains the catalytic core domain of RdRp of RNA viruses which belong to Group IV of the Baltimore classification system, and are a group of related viruses that have positive-sense (+), single-stranded (ss) genomes made of ribonucleic acid (RNA). RdRp (also known as RNA replicase) catalyzes the replication of RNA from an RNA template; specifically, it catalyzes the synthesis of the RNA strand complementary to a given RNA template. The Baltimore Classification is divided into 7 classes, 3 of which include RNA viruses: Group IV (+) RNA viruses, Group III double-stranded (ds) RNA viruses, and Group V negative-sense (-) RNA viruses. Baltimore groups of viruses differ with respect to the nature of their genome (i.e., the nucleic acid form that is packaged into virions) and correspond to distinct strategies of genome replication and expression. (+) viral RNA is similar to mRNA and thus can be immediately translated by the host cell. (+)ssRNA viruses can also produce (+) copies of the genome from (-) strands of an intermediate dsRNA genome. This acts as both a transcription and a replication process since the replicated RNA is also mRNA. RdRps belong to the expansive class of polymerases containing so-called palm catalytic domains along with the accessory fingers and thumb domains. All RdRps also have six conserved structural motifs (A-F), located in its majority in the palm subdomain (A-E motifs) and the F motif is located on the finger subdomain. All these motifs have been shown to be implicated in RdRp fidelity such as processes of correct incorporation and reorganization of nucleotides. In addition to Group IV viruses, this model also includes Picobirnaviruses (PBVs), members of the family Picobirnaviridae of dsRNA viruses (Baltimore classification Group III), which are bi-segmented dsRNA viruses. The phylogenetic tree of the RdRps of RNA viruses (realm Riboviria) showed that picobirnaviruses are embedded in the branch of diverse (+)RNA viruses; sometimes they are collectively referred to as the picornavirus supergroup. RdRps of members of the family Permutatetraviridae, a distinct group of RNA viruses that encompass a circular permutation within the RdRp palm domain, are not included in this model.


Pssm-ID: 438017 [Multi-domain]  Cd Length: 73  Bit Score: 41.17  E-value: 9.07e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 4982 HLMGWDYPKCDRAMPNMLRIMaslvlarkhntccnlshrfyrlanecaqvlsemvmcggslyvkpgGTSSGDATTAYANS 5061
Cdd:cd23167    1 HVVESDYSGFDSSISPDLLKA---------------------------------------------GQPSGSPNTSADNS 35
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 30027621 5062 VFNICQAVTANVNALLStdgnkiadkyvrnlqhrlyeclyrnrdvdhefvdefyAYLRKHFSMMILSDDAVVCYN 5136
Cdd:cd23167   36 LINLLLARLALRKACGR-------------------------------------AEFLNSVGILVYGDDSLVSVP 73
AAA smart00382
ATPases associated with a variety of cellular activities; AAA - ATPases associated with a ...
5581-5713 4.62e-03

ATPases associated with a variety of cellular activities; AAA - ATPases associated with a variety of cellular activities. This profile/alignment only detects a fraction of this vast family. The poorly conserved N-terminal helix is missing from the alignment.


Pssm-ID: 214640 [Multi-domain]  Cd Length: 148  Bit Score: 41.20  E-value: 4.62e-03
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621    5581 LQGPPGTGKSHFAIGLALYY--PSARIVYTACSHAAVDALCEKALKYLPIDKCSRIIPARARvecfdkfKVNSTLEQYVF 5658
Cdd:smart00382    7 IVGPPGSGKTTLARALARELgpPGGGVIYIDGEDILEEVLDQLLLIIVGGKKASGSGELRLR-------LALALARKLKP 79
                            90       100       110       120       130
                    ....*....|....*....|....*....|....*....|....*....|....*
gi 30027621    5659 ctvnalpettaDIVVFDEIsmaTNYDLSVVNARLRAKHYVYIGDPAQLPAPRTLL 5713
Cdd:smart00382   80 -----------DVLILDEI---TSLLDAEQEALLLLLEELRLLLLLKSEKNLTVI 120
DUF4175 pfam13779
Domain of unknown function (DUF4175);
3937-4021 6.18e-03

Domain of unknown function (DUF4175);


Pssm-ID: 433472 [Multi-domain]  Cd Length: 817  Bit Score: 43.41  E-value: 6.18e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621   3937 AQEAYEQAVANGDSEVVLKKLKKSLNvaksefdrdAAMQRKLEKMADQAMTQMYKQARSEDKRAKVTSamQTMLFTMLRK 4016
Cdd:pfam13779  476 AQERLSEALERGASDEEIARLMQELR---------AALDDYMQALAEQAQRNPQAQQARPGDNAQQMT--QQDLQRMMDR 544

                   ....*
gi 30027621   4017 LDNDA 4021
Cdd:pfam13779  545 IEELA 549
DEXXQc_Helz-like cd18038
DEXXQ/H-box helicase domain of Helz-like helicase; This subfamily contains HELZ, Mov10L1, and ...
5583-5630 7.35e-03

DEXXQ/H-box helicase domain of Helz-like helicase; This subfamily contains HELZ, Mov10L1, and similar proteins. Helicase with zinc finger (HELZ) acts as a helicase that plays a role in RNA metabolism during development. Moloney leukemia virus 10-like protein 1 (Mov10L1) binds Piwi-interacting RNA (piRNA) precursors to initiate piRNA processing. All are members of the DEAD-like helicase superfamily, a diverse family of proteins involved in ATP-dependent RNA or DNA unwinding. This domain contains the ATP-binding region.


Pssm-ID: 350796 [Multi-domain]  Cd Length: 229  Bit Score: 41.84  E-value: 7.35e-03
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 30027621 5583 GPPGTGKShFAIGLALY-----YPSARIVYTACSHAAVDALCEKALKYLPIDK 5630
Cdd:cd18038   27 GPPGTGKT-VTLVEAILqvlrqPPEARILVCAPSNSAADLLAERLLNALVTKR 78
deltaCoV_Nsp7 cd21829
deltacoronavirus non-structural protein 7; This model represents the non-structural protein 7 ...
3838-3928 9.79e-03

deltacoronavirus non-structural protein 7; This model represents the non-structural protein 7 (Nsp7) of deltacoronaviruses that include White-eye coronavirus HKU16 and Quail coronavirus UAE-HKU30, among others. CoVs utilize a multi-subunit replication/transcription machinery. A set of non-structural proteins (Nsps) generated as cleavage products of the ORF1a and ORF1ab viral polyproteins assemble to facilitate viral replication and transcription. Upon processing of the Nsp7-10 region by protease M (Mpro), the released four small proteins Nsp7, Nsp8, Nsp9 and Nsp10 form functional complexes with CoV core enzymes and stimulate replication. Most importantly, a complex of Nsp7 with Nsp8 has been shown to activate and confer processivity to the RNA-synthesizing activity of Nsp12, the RNA-dependent RNA-polymerase (RdRp); in SARS-CoV, point mutations in the NSP7- or NSP8-coding region have been shown to delay virus growth. Nsp7 and Nsp8 cooperate in activating the primer-dependent activity of the Nsp12 RdRp such that the level of their association may constitute a limiting factor for obtaining a high RNA polymerase activity. The subsequent Nsp7/Nsp8/Nsp12 polymerase complex is then able to associate with an active bifunctional Nsp14, which includes N-terminal 3' to 5' exoribonuclease (ExoN) and C-terminal N7-guanine cap methyltransferase (N7-MTase) activities, thus representing a unique coronavirus Nsp assembly that incorporates RdRp, exoribonuclease, and N7-MTase activities. Interaction of Nsp7 with Nsp8 appears to be conserved across the coronavirus family, making these proteins interesting drug targets. Nsp7 has a 4-helical bundle conformation which is strongly affected by its interaction with Nsp8, especially where it concerns alpha-helix 4. SARS-CoV Nsp7 forms a 8:8 hexadecameric supercomplex with Nsp8 that adopts a hollow cylinder-like structure with a large central channel and positive electrostatic properties in the cylinder, while Feline infectious peritonitis virus Nsp7 forms a 2:1 heterotrimer with Nsp8. Regardless of their oligomeric structure, the Nsp7/Nsp8 complex functions as a noncanonical RNA polymerase capable of synthesizing RNA of up to template length.


Pssm-ID: 409255  Cd Length: 96  Bit Score: 39.05  E-value: 9.79e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30027621 3838 KMSDVKCTSVVLLSVLQQLRVESSSKLWAQCVQLHNDILLAKDTTEAFEKMVSLLSVLLSMQGAVDInrlcEEMLDNRAT 3917
Cdd:cd21829    2 KTLDAKATAVVVANLLEKAGVTNKHEVCKKIVKLHNDTLKATTYEEAETSLVKLLAHIIEFLPTDQV----DAYLADAVK 77
                         90
                 ....*....|.
gi 30027621 3918 LQAIASEFSSL 3928
Cdd:cd21829   78 VQHLNTYFDSL 88
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.20
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

  • Wang J et al. (2023), "The conserved domain database in 2023", Nucleic Acids Res.51(D)384-8.
  • Lu S et al. (2020), "The conserved domain database in 2020", Nucleic Acids Res.48(D)265-8.
  • Marchler-Bauer A et al. (2017), "CDD/SPARCLE: functional classification of proteins via subfamily domain architectures.", Nucleic Acids Res.45(D)200-3.
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