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Conserved domains on  [gi|1370483517|ref|XP_016861432|]
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probable guanine nucleotide exchange factor MCF2L2 isoform X1 [Homo sapiens]

Protein Classification

SEC14 and RhoGEF domain-containing protein( domain architecture ID 11271356)

protein containing domains SEC14, SPEC, RhoGEF, and PH-like

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
RhoGEF smart00325
Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Guanine nucleotide exchange ...
 623-820 1.44e-33

Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called Dbl-homologous (DH) domain. It appears that PH domains invariably occur C-terminal to RhoGEF/DH domains. Improved coverage.


:

Pssm-ID: 214619 [Multi-domain]  Cd Length: 180  Bit Score: 127.42  E-value: 1.44e-33
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370483517  623 IIRDLLETEEIYIKEIKSIIDGYITPMDFIWLKhlipdVLQNNKDFLFGNIRELYEFHnRTFLKELEKCAEN----PELL 698
Cdd:smart00325   1 VLKELLQTERNYVRDLKLLVEVFLKPLKKELKL-----LSPNELETLFGNIEEIYEFH-RDFLDELEERIEEwddsVERI 74

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370483517  699 AHCFLKRKEDLQIYFKYHKNLPRARAIWQEC-QDCAYFGVCQRQLDHN----LPLFKYLKGPSQRLIKYQMLLKGLLDFE 773
Cdd:smart00325  75 GDVFLKLEEFFKIYSEYCSNHPDALELLKKLkKNPRFQKFLKEIESSPqcrrLTLESLLLKPVQRLTKYPLLLKELLKHT 154

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....*..
gi 1370483517  774 SPEDMEidpgelggsakdgpkrtkdsafSTELQQALAVIEDLIKSCE 820
Cdd:smart00325 155 PEDHED----------------------REDLKKALKAIKELANQVN 179
PH-like super family cl17171
Pleckstrin homology-like domain; The PH-like family includes the PH domain, both the Shc-like ...
 827-956 1.64e-30

Pleckstrin homology-like domain; The PH-like family includes the PH domain, both the Shc-like and IRS-like PTB domains, the ran-binding domain, the EVH1 domain, a domain in neurobeachin and the third domain of FERM. All of these domains have a PH fold, but lack significant sequence similarity. They are generally involved in targeting to protein to the appropriate cellular location or interacting with a binding partner. This domain family possesses multiple functions including the ability to bind inositol phosphates and to other proteins.


The actual alignment was detected with superfamily member cd01227:

Pssm-ID: 473070 [Multi-domain]  Cd Length: 126  Bit Score: 116.91  E-value: 1.64e-30
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370483517 827 AVTECPDDIGKLGKLLLHGPFSVWTIHKDRYKMKDlIRFKPSQRQIYLFERGIVFCKIRmepGDQGLSPHYSFKKTMKLM 906
Cdd:cd01227     1 AITGYDGNLGDLGKLLMQGSFNVWTEHKKGHTKKL-ARFKPMQRHIFLYEKAVLFCKKR---GENGEAPSYSYKNSLNTT 76

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|
gi 1370483517 907 TLSIRQLGRGSHRKFEIASRNGLEKYILQAASKEIRDCWFSEISKLLMEQ 956
Cdd:cd01227    77 AVGLTENVKGDTKKFEIWLNGREEVFIIQAPTPEIKAAWVKAIRQVLLSQ 126
SEC14 smart00516
Domain in homologues of a S. cerevisiae phosphatidylinositol transfer protein (Sec14p); Domain ...
 52-190 1.45e-18

Domain in homologues of a S. cerevisiae phosphatidylinositol transfer protein (Sec14p); Domain in homologues of a S. cerevisiae phosphatidylinositol transfer protein (Sec14p) and in RhoGAPs, RhoGEFs and the RasGAP, neurofibromin (NF1). Lipid-binding domain. The SEC14 domain of Dbl is known to associate with G protein beta/gamma subunits.


:

Pssm-ID: 214706 [Multi-domain]  Cd Length: 158  Bit Score: 83.50  E-value: 1.45e-18
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370483517   52 LSGGRGED--GAPIITFP--EFSGFKHIPDEDFLNVMTYLTSIPSVEAASI---GFIVVIDRRRDKWSSVKASLTRIAV- 123
Cdd:smart00516   9 IPGGRGYDkdGRPVLIERagRFDLKSVTLEELLRYLVYVLEKILQEEKKTGgieGFTVIFDLKGLSMSNPDLSVLRKILk 88

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1370483517  124 ----AFPGNLQLIFILRPSRFIqRTFTDIGIKYYRNEFKTKVPIIMVNSVSDLHGYIDKSQLTRELGGTLE 190
Cdd:smart00516  89 ilqdHYPERLGKVYIINPPWFF-RVLWKIIKPFLDEKTREKIRFVGNDSKEELLEYIDKEQLPEELGGTLD 158
SPEC cd00176
Spectrin repeats, found in several proteins involved in cytoskeletal structure; family members ...
 321-523 1.94e-14

Spectrin repeats, found in several proteins involved in cytoskeletal structure; family members include spectrin, alpha-actinin and dystrophin; the spectrin repeat forms a three helix bundle with the second helix interrupted by proline in some sequences; the repeats are independent folding units; tandem repeats are found in differing numbers and arrange in an antiparallel manner to form dimers; the repeats are defined by a characteristic tryptophan (W) residue in helix A and a leucine (L) at the carboxyl end of helix C and separated by a linker of 5 residues; two copies of the repeat are present here


:

Pssm-ID: 238103 [Multi-domain]  Cd Length: 213  Bit Score: 73.25  E-value: 1.94e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370483517 321 QLQHFEHDFCKAKLALDNLlEEQAEFTGIGDSVMHVEQILKEHKKLEEKSQEPLEKAQLLALVGDQLIQSHHYAADAIRP 400
Cdd:cd00176     1 KLQQFLRDADELEAWLSEK-EELLSSTDYGDDLESVEALLKKHEALEAELAAHEERVEALNELGEQLIEEGHPDAEEIQE 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370483517 401 RCVELRHLCDDFingnKKKWDILGKSLE-------FHRQLDKVSQWCEAGIYLLASQavDKCQSREGVDIALNDIATFLG 473
Cdd:cd00176    80 RLEELNQRWEEL----RELAEERRQRLEealdlqqFFRDADDLEQWLEEKEAALASE--DLGKDLESVEELLKKHKELEE 153

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1370483517 474 TV--KEYPLLSPKEFYNEFELLLTLDA----KAKAQKVLQRLDDVQEIFHKRQVSL 523
Cdd:cd00176   154 ELeaHEPRLKSLNELAEELLEEGHPDAdeeiEEKLEELNERWEELLELAEERQKKL 209
 
Name Accession Description Interval E-value
RhoGEF smart00325
Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Guanine nucleotide exchange ...
 623-820 1.44e-33

Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called Dbl-homologous (DH) domain. It appears that PH domains invariably occur C-terminal to RhoGEF/DH domains. Improved coverage.


Pssm-ID: 214619 [Multi-domain]  Cd Length: 180  Bit Score: 127.42  E-value: 1.44e-33
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370483517  623 IIRDLLETEEIYIKEIKSIIDGYITPMDFIWLKhlipdVLQNNKDFLFGNIRELYEFHnRTFLKELEKCAEN----PELL 698
Cdd:smart00325   1 VLKELLQTERNYVRDLKLLVEVFLKPLKKELKL-----LSPNELETLFGNIEEIYEFH-RDFLDELEERIEEwddsVERI 74

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370483517  699 AHCFLKRKEDLQIYFKYHKNLPRARAIWQEC-QDCAYFGVCQRQLDHN----LPLFKYLKGPSQRLIKYQMLLKGLLDFE 773
Cdd:smart00325  75 GDVFLKLEEFFKIYSEYCSNHPDALELLKKLkKNPRFQKFLKEIESSPqcrrLTLESLLLKPVQRLTKYPLLLKELLKHT 154

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....*..
gi 1370483517  774 SPEDMEidpgelggsakdgpkrtkdsafSTELQQALAVIEDLIKSCE 820
Cdd:smart00325 155 PEDHED----------------------REDLKKALKAIKELANQVN 179
PH_Dbs cd01227
DBL's big sister protein pleckstrin homology (PH) domain; Dbs (also called MCF2-transforming ...
 827-956 1.64e-30

DBL's big sister protein pleckstrin homology (PH) domain; Dbs (also called MCF2-transforming sequence-like protein 2) is a guanine nucleotide exchange factor (GEF), which contains spectrin repeats, a rhoGEF (DH) domain and a PH domain. The Dbs PH domain participates in binding to both the Cdc42 and RhoA GTPases. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 269934 [Multi-domain]  Cd Length: 126  Bit Score: 116.91  E-value: 1.64e-30
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370483517 827 AVTECPDDIGKLGKLLLHGPFSVWTIHKDRYKMKDlIRFKPSQRQIYLFERGIVFCKIRmepGDQGLSPHYSFKKTMKLM 906
Cdd:cd01227     1 AITGYDGNLGDLGKLLMQGSFNVWTEHKKGHTKKL-ARFKPMQRHIFLYEKAVLFCKKR---GENGEAPSYSYKNSLNTT 76

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|
gi 1370483517 907 TLSIRQLGRGSHRKFEIASRNGLEKYILQAASKEIRDCWFSEISKLLMEQ 956
Cdd:cd01227    77 AVGLTENVKGDTKKFEIWLNGREEVFIIQAPTPEIKAAWVKAIRQVLLSQ 126
RhoGEF cd00160
Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Also called Dbl-homologous ...
 620-820 1.24e-27

Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Also called Dbl-homologous (DH) domain. It appears that PH domains invariably occur C-terminal to RhoGEF/DH domains.


Pssm-ID: 238091 [Multi-domain]  Cd Length: 181  Bit Score: 110.47  E-value: 1.24e-27
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370483517 620 RRRIIRDLLETEEIYIKEIKSIIDGYITPMDfiwlKHLIPDvLQNNKDFLFGNIRELYEFHNRtFLKELEKCAEN----P 695
Cdd:cd00160     1 RQEVIKELLQTERNYVRDLKLLVEVFLKPLD----KELLPL-SPEEVELLFGNIEEIYEFHRI-FLKSLEERVEEwdksG 74

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370483517 696 ELLAHCFLKRKEDLQIYFKYHKNLPRARAIWQECQD-CAYFGVCQRQLD---HNLPLFKYLKGPSQRLIKYQMLLKGLLD 771
Cdd:cd00160    75 PRIGDVFLKLAPFFKIYSEYCSNHPDALELLKKLKKfNKFFQEFLEKAEsecGRLKLESLLLKPVQRLTKYPLLLKELLK 154

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1370483517 772 F--ESPEDMEidpgelggsakdgpkrtkdsafstELQQALAVIEDLIKSCE 820
Cdd:cd00160   155 HtpDGHEDRE------------------------DLKKALEAIKEVASQVN 181
RhoGEF pfam00621
RhoGEF domain; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called ...
 623-819 2.90e-24

RhoGEF domain; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called Dbl-homologous (DH) domain. It appears that pfam00169 domains invariably occur C-terminal to RhoGEF/DH domains.


Pssm-ID: 459876 [Multi-domain]  Cd Length: 176  Bit Score: 100.45  E-value: 2.90e-24
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370483517 623 IIRDLLETEEIYIKEIKSIIDGYITPmdfiwlKHLIPDVLQNNKDFLFGNIRELYEFHNRTFLKELEKCAENPELLAHCF 702
Cdd:pfam00621   1 VIKELLQTERSYVRDLEILVEVFLPP------NSKPLSESEEEIKTIFSNIEEIYELHRQLLLEELLKEWISIQRIGDIF 74

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370483517 703 LKRKEDLQIYFKYHKNLPRARAIWQECQD-----CAYFGVCQRQLD-HNLPLFKYLKGPSQRLIKYQMLLKGLLDFESPE 776
Cdd:pfam00621  75 LKFAPGFKVYSTYCSNYPKALKLLKKLLKknpkfRAFLEELEANPEcRGLDLNSFLIKPVQRIPRYPLLLKELLKHTPPD 154

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|...
gi 1370483517 777 DMEidpgelggsakdgpkrtkdsafSTELQQALAVIEDLIKSC 819
Cdd:pfam00621 155 HPD----------------------YEDLKKALEAIKEVAKQI 175
SEC14 smart00516
Domain in homologues of a S. cerevisiae phosphatidylinositol transfer protein (Sec14p); Domain ...
 52-190 1.45e-18

Domain in homologues of a S. cerevisiae phosphatidylinositol transfer protein (Sec14p); Domain in homologues of a S. cerevisiae phosphatidylinositol transfer protein (Sec14p) and in RhoGAPs, RhoGEFs and the RasGAP, neurofibromin (NF1). Lipid-binding domain. The SEC14 domain of Dbl is known to associate with G protein beta/gamma subunits.


Pssm-ID: 214706 [Multi-domain]  Cd Length: 158  Bit Score: 83.50  E-value: 1.45e-18
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370483517   52 LSGGRGED--GAPIITFP--EFSGFKHIPDEDFLNVMTYLTSIPSVEAASI---GFIVVIDRRRDKWSSVKASLTRIAV- 123
Cdd:smart00516   9 IPGGRGYDkdGRPVLIERagRFDLKSVTLEELLRYLVYVLEKILQEEKKTGgieGFTVIFDLKGLSMSNPDLSVLRKILk 88

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1370483517  124 ----AFPGNLQLIFILRPSRFIqRTFTDIGIKYYRNEFKTKVPIIMVNSVSDLHGYIDKSQLTRELGGTLE 190
Cdd:smart00516  89 ilqdHYPERLGKVYIINPPWFF-RVLWKIIKPFLDEKTREKIRFVGNDSKEELLEYIDKEQLPEELGGTLD 158
CRAL_TRIO_2 pfam13716
Divergent CRAL/TRIO domain; This family includes divergent members of the CRAL-TRIO domain ...
 60-191 5.75e-18

Divergent CRAL/TRIO domain; This family includes divergent members of the CRAL-TRIO domain family. This family includes ECM25 that contains a divergent CRAL-TRIO domain identified by Gallego and colleagues.


Pssm-ID: 463965 [Multi-domain]  Cd Length: 140  Bit Score: 81.22  E-value: 5.75e-18
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370483517  60 GAPIITFPE-FSGFKHIPDEDFLNVMTYLTSIPSVEAASIGFIVVIDRR------RDKWSSVKASLTRIAVAFPGNLQLI 132
Cdd:pfam13716   1 GRPVLVFISkLLPSRPASLDDLDRLLFYLLKTLSEKLKGKPFVVVVDHTgvtsenFPSLSFLKKAYDLLPRAFKKNLKAV 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1370483517 133 FILRPSRFIQRTFTDIGIKYYRNEFKTKVpiIMVNSVSDLHGYIDKSQLTRELGGTLEY 191
Cdd:pfam13716  81 YVVHPSTFLRTFLKTLGSLLGSKKLRKKV--HYVSSLSELWEGIDREQLPTELPGVLSY 137
SPEC cd00176
Spectrin repeats, found in several proteins involved in cytoskeletal structure; family members ...
 321-523 1.94e-14

Spectrin repeats, found in several proteins involved in cytoskeletal structure; family members include spectrin, alpha-actinin and dystrophin; the spectrin repeat forms a three helix bundle with the second helix interrupted by proline in some sequences; the repeats are independent folding units; tandem repeats are found in differing numbers and arrange in an antiparallel manner to form dimers; the repeats are defined by a characteristic tryptophan (W) residue in helix A and a leucine (L) at the carboxyl end of helix C and separated by a linker of 5 residues; two copies of the repeat are present here


Pssm-ID: 238103 [Multi-domain]  Cd Length: 213  Bit Score: 73.25  E-value: 1.94e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370483517 321 QLQHFEHDFCKAKLALDNLlEEQAEFTGIGDSVMHVEQILKEHKKLEEKSQEPLEKAQLLALVGDQLIQSHHYAADAIRP 400
Cdd:cd00176     1 KLQQFLRDADELEAWLSEK-EELLSSTDYGDDLESVEALLKKHEALEAELAAHEERVEALNELGEQLIEEGHPDAEEIQE 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370483517 401 RCVELRHLCDDFingnKKKWDILGKSLE-------FHRQLDKVSQWCEAGIYLLASQavDKCQSREGVDIALNDIATFLG 473
Cdd:cd00176    80 RLEELNQRWEEL----RELAEERRQRLEealdlqqFFRDADDLEQWLEEKEAALASE--DLGKDLESVEELLKKHKELEE 153

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1370483517 474 TV--KEYPLLSPKEFYNEFELLLTLDA----KAKAQKVLQRLDDVQEIFHKRQVSL 523
Cdd:cd00176   154 ELeaHEPRLKSLNELAEELLEEGHPDAdeeiEEKLEELNERWEELLELAEERQKKL 209
SEC14 cd00170
Sec14p-like lipid-binding domain; Sec14p-like lipid-binding domains are found in secretory ...
 39-188 4.54e-12

Sec14p-like lipid-binding domain; Sec14p-like lipid-binding domains are found in secretory proteins, such as S. cerevisiae phosphatidylinositol transfer protein (Sec14p), and in lipid regulated proteins such as RhoGAPs, RhoGEFs and neurofibromin (NF1). SEC14 domain of Dbl is known to associate with G protein beta/gamma subunits.


Pssm-ID: 469559 [Multi-domain]  Cd Length: 156  Bit Score: 65.05  E-value: 4.54e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370483517  39 VEIIEQLHRQFAILsGGRGEDGAPIITF-PEFSGFKHIPDEDFLNVMTYL--TSIPSVEAASIGFIVVIDRRRDKWSS-- 113
Cdd:cd00170     1 LEELLELLGGIGYL-GGRDKEGRPVLVFrAGWDPPKLLDLEELLRYLVYLleKALRELEEQVEGFVVIIDLKGFSLSNls 79

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1370483517 114 ----VKASLTRIAVAFPGNLQLIFILRPSRFIqRTFTDIGIKYYRNEFKTKVpIIMVNSVSDLHGYIDKSQLTRELGGT 188
Cdd:cd00170    80 dlslLKKLLKILQDHYPERLKKIYIVNAPWIF-SALWKIVKPFLSEKTRKKI-VFLGSDLEELLEYIDPDQLPKELGGT 156
SPEC smart00150
Spectrin repeats;
323-428 2.79e-09

Spectrin repeats;


Pssm-ID: 197544 [Multi-domain]  Cd Length: 101  Bit Score: 55.41  E-value: 2.79e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370483517  323 QHFEHDFCKAKLALDNLlEEQAEFTGIGDSVMHVEQILKEHKKLEEKSQEPLEKAQLLALVGDQLIQSHHYAADAIRPRC 402
Cdd:smart00150   1 QQFLRDADELEAWLEEK-EQLLASEDLGKDLESVEALLKKHEAFEAELEAHEERVEALNELGEQLIEEGHPDAEEIEERL 79

                           90       100
                   ....*....|....*....|....*.
gi 1370483517  403 VELRHLCDDFingnKKKWDILGKSLE 428
Cdd:smart00150  80 EELNERWEEL----KELAEERRQKLE 101
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
 857-953 1.13e-05

Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The domain family possesses multiple functions including the abilities to bind inositol phosphates, and various proteins. PH domains have been found to possess inserted domains (such as in PLC gamma, syntrophins) and to be inserted within other domains. Mutations in Brutons tyrosine kinase (Btk) within its PH domain cause X-linked agammaglobulinaemia (XLA) in patients. Point mutations cluster into the positively charged end of the molecule around the predicted binding site for phosphatidylinositol lipids.


Pssm-ID: 214574 [Multi-domain]  Cd Length: 102  Bit Score: 45.23  E-value: 1.13e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370483517  857 YKMKDLIRFKPSQRQIYLFERGIVFCKIRMEPGDqglsphYSFKKTMKLMTLSIRQLGRGSHRK----FEIASRNGlEKY 932
Cdd:smart00233   8 YKKSGGGKKSWKKRYFVLFNSTLLYYKSKKDKKS------YKPKGSIDLSGCTVREAPDPDSSKkphcFEIKTSDR-KTL 80

                           90       100
                   ....*....|....*....|.
gi 1370483517  933 ILQAASKEIRDCWFSEISKLL 953
Cdd:smart00233  81 LLQAESEEEREKWVEALRKAI 101
PH pfam00169
PH domain; PH stands for pleckstrin homology.
 857-953 1.11e-03

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 459697 [Multi-domain]  Cd Length: 105  Bit Score: 39.47  E-value: 1.11e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370483517 857 YKMKDLIRFKPSQRQIYLFERGIVFCKirmepgDQGLSPHYSFKKTMKLMTLSIRQLGRGSHRK----FEI--ASRNGLE 930
Cdd:pfam00169   8 LKKGGGKKKSWKKRYFVLFDGSLLYYK------DDKSGKSKEPKGSISLSGCEVVEVVASDSPKrkfcFELrtGERTGKR 81

                          90       100
                  ....*....|....*....|...
gi 1370483517 931 KYILQAASKEIRDCWFSEISKLL 953
Cdd:pfam00169  82 TYLLQAESEEERKDWIKAIQSAI 104
 
Name Accession Description Interval E-value
RhoGEF smart00325
Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Guanine nucleotide exchange ...
 623-820 1.44e-33

Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called Dbl-homologous (DH) domain. It appears that PH domains invariably occur C-terminal to RhoGEF/DH domains. Improved coverage.


Pssm-ID: 214619 [Multi-domain]  Cd Length: 180  Bit Score: 127.42  E-value: 1.44e-33
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370483517  623 IIRDLLETEEIYIKEIKSIIDGYITPMDFIWLKhlipdVLQNNKDFLFGNIRELYEFHnRTFLKELEKCAEN----PELL 698
Cdd:smart00325   1 VLKELLQTERNYVRDLKLLVEVFLKPLKKELKL-----LSPNELETLFGNIEEIYEFH-RDFLDELEERIEEwddsVERI 74

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370483517  699 AHCFLKRKEDLQIYFKYHKNLPRARAIWQEC-QDCAYFGVCQRQLDHN----LPLFKYLKGPSQRLIKYQMLLKGLLDFE 773
Cdd:smart00325  75 GDVFLKLEEFFKIYSEYCSNHPDALELLKKLkKNPRFQKFLKEIESSPqcrrLTLESLLLKPVQRLTKYPLLLKELLKHT 154

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....*..
gi 1370483517  774 SPEDMEidpgelggsakdgpkrtkdsafSTELQQALAVIEDLIKSCE 820
Cdd:smart00325 155 PEDHED----------------------REDLKKALKAIKELANQVN 179
PH_Dbs cd01227
DBL's big sister protein pleckstrin homology (PH) domain; Dbs (also called MCF2-transforming ...
 827-956 1.64e-30

DBL's big sister protein pleckstrin homology (PH) domain; Dbs (also called MCF2-transforming sequence-like protein 2) is a guanine nucleotide exchange factor (GEF), which contains spectrin repeats, a rhoGEF (DH) domain and a PH domain. The Dbs PH domain participates in binding to both the Cdc42 and RhoA GTPases. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 269934 [Multi-domain]  Cd Length: 126  Bit Score: 116.91  E-value: 1.64e-30
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370483517 827 AVTECPDDIGKLGKLLLHGPFSVWTIHKDRYKMKDlIRFKPSQRQIYLFERGIVFCKIRmepGDQGLSPHYSFKKTMKLM 906
Cdd:cd01227     1 AITGYDGNLGDLGKLLMQGSFNVWTEHKKGHTKKL-ARFKPMQRHIFLYEKAVLFCKKR---GENGEAPSYSYKNSLNTT 76

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|
gi 1370483517 907 TLSIRQLGRGSHRKFEIASRNGLEKYILQAASKEIRDCWFSEISKLLMEQ 956
Cdd:cd01227    77 AVGLTENVKGDTKKFEIWLNGREEVFIIQAPTPEIKAAWVKAIRQVLLSQ 126
RhoGEF cd00160
Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Also called Dbl-homologous ...
 620-820 1.24e-27

Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Also called Dbl-homologous (DH) domain. It appears that PH domains invariably occur C-terminal to RhoGEF/DH domains.


Pssm-ID: 238091 [Multi-domain]  Cd Length: 181  Bit Score: 110.47  E-value: 1.24e-27
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370483517 620 RRRIIRDLLETEEIYIKEIKSIIDGYITPMDfiwlKHLIPDvLQNNKDFLFGNIRELYEFHNRtFLKELEKCAEN----P 695
Cdd:cd00160     1 RQEVIKELLQTERNYVRDLKLLVEVFLKPLD----KELLPL-SPEEVELLFGNIEEIYEFHRI-FLKSLEERVEEwdksG 74

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370483517 696 ELLAHCFLKRKEDLQIYFKYHKNLPRARAIWQECQD-CAYFGVCQRQLD---HNLPLFKYLKGPSQRLIKYQMLLKGLLD 771
Cdd:cd00160    75 PRIGDVFLKLAPFFKIYSEYCSNHPDALELLKKLKKfNKFFQEFLEKAEsecGRLKLESLLLKPVQRLTKYPLLLKELLK 154

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1370483517 772 F--ESPEDMEidpgelggsakdgpkrtkdsafstELQQALAVIEDLIKSCE 820
Cdd:cd00160   155 HtpDGHEDRE------------------------DLKKALEAIKEVASQVN 181
RhoGEF pfam00621
RhoGEF domain; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called ...
 623-819 2.90e-24

RhoGEF domain; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called Dbl-homologous (DH) domain. It appears that pfam00169 domains invariably occur C-terminal to RhoGEF/DH domains.


Pssm-ID: 459876 [Multi-domain]  Cd Length: 176  Bit Score: 100.45  E-value: 2.90e-24
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370483517 623 IIRDLLETEEIYIKEIKSIIDGYITPmdfiwlKHLIPDVLQNNKDFLFGNIRELYEFHNRTFLKELEKCAENPELLAHCF 702
Cdd:pfam00621   1 VIKELLQTERSYVRDLEILVEVFLPP------NSKPLSESEEEIKTIFSNIEEIYELHRQLLLEELLKEWISIQRIGDIF 74

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370483517 703 LKRKEDLQIYFKYHKNLPRARAIWQECQD-----CAYFGVCQRQLD-HNLPLFKYLKGPSQRLIKYQMLLKGLLDFESPE 776
Cdd:pfam00621  75 LKFAPGFKVYSTYCSNYPKALKLLKKLLKknpkfRAFLEELEANPEcRGLDLNSFLIKPVQRIPRYPLLLKELLKHTPPD 154

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|...
gi 1370483517 777 DMEidpgelggsakdgpkrtkdsafSTELQQALAVIEDLIKSC 819
Cdd:pfam00621 155 HPD----------------------YEDLKKALEAIKEVAKQI 175
PH2_Kalirin_Trio_p63RhoGEF cd13241
p63RhoGEF pleckstrin homology (PH) domain, repeat 2; The guanine nucleotide exchange factor ...
 835-959 1.28e-18

p63RhoGEF pleckstrin homology (PH) domain, repeat 2; The guanine nucleotide exchange factor p63RhoGEF is an effector of the heterotrimeric G protein, Galphaq and linking Galphaq-coupled receptors (GPCRs) to the activation of RhoA. The Dbl(DH) and PH domains of p63RhoGEF interact with the effector-binding site and the C-terminal region of Galphaq and appear to relieve autoinhibition of the catalytic DH domain by the PH domain. Trio, Duet, and p63RhoGEF are shown to constitute a family of Galphaq effectors that appear to activate RhoA both in vitro and in intact cells. Dbs is a guanine nucleotide exchange factor (GEF), which contains spectrin repeats, a rhoGEF (DH) domain and a PH domain. The Dbs PH domain participates in binding to both the Cdc42 and RhoA GTPases. Trio plays an essential role in regulating the actin cytoskeleton during axonal guidance and branching. Trio is a multidomain signaling protein that contains two RhoGEF(DH)-PH domains in tandem. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270061  Cd Length: 140  Bit Score: 83.08  E-value: 1.28e-18
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370483517 835 IGKLGKLLLHGPFSVwtihkdrYKMKDLIRFKPSQRQIYLFERGIVFCKIrMEPGDQGLSPHYSFKKTMKLMTLSIRQLG 914
Cdd:cd13241    11 ITAQGKLLLQGTLLV-------SEPSAGLLQKGKERRVFLFEQIIIFSEI-LGKKTQFSNPGYIYKNHIKVNKMSLEENV 82

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*...
gi 1370483517 915 RGSHRKFEIASR---NGLEKYILQAASKEIRDCWFSEISKLLmEQQNN 959
Cdd:cd13241    83 DGDPLRFALKSRdpnNPSETFILQAASPEVRQEWVDTINQIL-DTQRD 129
SEC14 smart00516
Domain in homologues of a S. cerevisiae phosphatidylinositol transfer protein (Sec14p); Domain ...
 52-190 1.45e-18

Domain in homologues of a S. cerevisiae phosphatidylinositol transfer protein (Sec14p); Domain in homologues of a S. cerevisiae phosphatidylinositol transfer protein (Sec14p) and in RhoGAPs, RhoGEFs and the RasGAP, neurofibromin (NF1). Lipid-binding domain. The SEC14 domain of Dbl is known to associate with G protein beta/gamma subunits.


Pssm-ID: 214706 [Multi-domain]  Cd Length: 158  Bit Score: 83.50  E-value: 1.45e-18
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370483517   52 LSGGRGED--GAPIITFP--EFSGFKHIPDEDFLNVMTYLTSIPSVEAASI---GFIVVIDRRRDKWSSVKASLTRIAV- 123
Cdd:smart00516   9 IPGGRGYDkdGRPVLIERagRFDLKSVTLEELLRYLVYVLEKILQEEKKTGgieGFTVIFDLKGLSMSNPDLSVLRKILk 88

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1370483517  124 ----AFPGNLQLIFILRPSRFIqRTFTDIGIKYYRNEFKTKVPIIMVNSVSDLHGYIDKSQLTRELGGTLE 190
Cdd:smart00516  89 ilqdHYPERLGKVYIINPPWFF-RVLWKIIKPFLDEKTREKIRFVGNDSKEELLEYIDKEQLPEELGGTLD 158
CRAL_TRIO_2 pfam13716
Divergent CRAL/TRIO domain; This family includes divergent members of the CRAL-TRIO domain ...
 60-191 5.75e-18

Divergent CRAL/TRIO domain; This family includes divergent members of the CRAL-TRIO domain family. This family includes ECM25 that contains a divergent CRAL-TRIO domain identified by Gallego and colleagues.


Pssm-ID: 463965 [Multi-domain]  Cd Length: 140  Bit Score: 81.22  E-value: 5.75e-18
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370483517  60 GAPIITFPE-FSGFKHIPDEDFLNVMTYLTSIPSVEAASIGFIVVIDRR------RDKWSSVKASLTRIAVAFPGNLQLI 132
Cdd:pfam13716   1 GRPVLVFISkLLPSRPASLDDLDRLLFYLLKTLSEKLKGKPFVVVVDHTgvtsenFPSLSFLKKAYDLLPRAFKKNLKAV 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1370483517 133 FILRPSRFIQRTFTDIGIKYYRNEFKTKVpiIMVNSVSDLHGYIDKSQLTRELGGTLEY 191
Cdd:pfam13716  81 YVVHPSTFLRTFLKTLGSLLGSKKLRKKV--HYVSSLSELWEGIDREQLPTELPGVLSY 137
SPEC cd00176
Spectrin repeats, found in several proteins involved in cytoskeletal structure; family members ...
 321-523 1.94e-14

Spectrin repeats, found in several proteins involved in cytoskeletal structure; family members include spectrin, alpha-actinin and dystrophin; the spectrin repeat forms a three helix bundle with the second helix interrupted by proline in some sequences; the repeats are independent folding units; tandem repeats are found in differing numbers and arrange in an antiparallel manner to form dimers; the repeats are defined by a characteristic tryptophan (W) residue in helix A and a leucine (L) at the carboxyl end of helix C and separated by a linker of 5 residues; two copies of the repeat are present here


Pssm-ID: 238103 [Multi-domain]  Cd Length: 213  Bit Score: 73.25  E-value: 1.94e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370483517 321 QLQHFEHDFCKAKLALDNLlEEQAEFTGIGDSVMHVEQILKEHKKLEEKSQEPLEKAQLLALVGDQLIQSHHYAADAIRP 400
Cdd:cd00176     1 KLQQFLRDADELEAWLSEK-EELLSSTDYGDDLESVEALLKKHEALEAELAAHEERVEALNELGEQLIEEGHPDAEEIQE 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370483517 401 RCVELRHLCDDFingnKKKWDILGKSLE-------FHRQLDKVSQWCEAGIYLLASQavDKCQSREGVDIALNDIATFLG 473
Cdd:cd00176    80 RLEELNQRWEEL----RELAEERRQRLEealdlqqFFRDADDLEQWLEEKEAALASE--DLGKDLESVEELLKKHKELEE 153

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1370483517 474 TV--KEYPLLSPKEFYNEFELLLTLDA----KAKAQKVLQRLDDVQEIFHKRQVSL 523
Cdd:cd00176   154 ELeaHEPRLKSLNELAEELLEEGHPDAdeeiEEKLEELNERWEELLELAEERQKKL 209
PH_puratrophin-1 cd13242
Puratrophin-1 pleckstrin homology (PH) domain; Puratrophin-1 (also called Purkinje cell ...
 821-961 1.15e-13

Puratrophin-1 pleckstrin homology (PH) domain; Puratrophin-1 (also called Purkinje cell atrophy-associated protein 1 or PLEKHG4/Pleckstrin homology domain-containing family G member 4) contains a spectrin repeat, a RhoGEF (DH) domain, and a PH domain. It is thought to function in intracellular signaling and cytoskeleton dynamics at the Golgi. Puratrophin-1 is expressed in kidney, Leydig cells in the testis, epithelial cells in the prostate gland and Langerhans islet in the pancreas. A single nucleotide substitution in the puratrophin-1 gene were once thought to result in autosomal dominant cerebellar ataxia (ADCA), but now it has been demonstrated that this ataxia is a result of defects in the BEAN gene. Puratrophin contains a domain architecture similar to that of Dbl family members Dbs and Trio. Dbs is a guanine nucleotide exchange factor (GEF), which contains spectrin repeats, a RhoGEF (DH) domain and a PH domain. The Dbs PH domain participates in binding to both the Cdc42 and RhoA GTPases. Trio plays an essential role in regulating the actin cytoskeleton during axonal guidance and branching. Trio is a multidomain signaling protein that contains two RhoGEF(DH)-PH domains in tandem. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270062  Cd Length: 136  Bit Score: 68.86  E-value: 1.15e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370483517 821 LAVDlaAVTECPDDIGKLGKLLLHGPFSVWtihkdrykmkdlIRFKPSQRQIYLFERGIVFCKIRMEPGDQGLsphYSFK 900
Cdd:cd13242    11 LAMD--SIRGCDVNLKEQGQLLRQDEFLVW------------QGRKKCLRHVFLFEDLILFSKPKKTPGGKDV---YIYK 73

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1370483517 901 KTMKLMTLSIRQLGRGSHRKFEI--ASRNGLEKYILQAASKEIRDCWFSEISKLLMEQQNNIK 961
Cdd:cd13242    74 HSIKTSDIGLTENVGDSGLKFEIwfRRRKARDTYILQATSPEIKQAWTSDIAKLLWKQAIRNR 136
SEC14 cd00170
Sec14p-like lipid-binding domain; Sec14p-like lipid-binding domains are found in secretory ...
 39-188 4.54e-12

Sec14p-like lipid-binding domain; Sec14p-like lipid-binding domains are found in secretory proteins, such as S. cerevisiae phosphatidylinositol transfer protein (Sec14p), and in lipid regulated proteins such as RhoGAPs, RhoGEFs and neurofibromin (NF1). SEC14 domain of Dbl is known to associate with G protein beta/gamma subunits.


Pssm-ID: 469559 [Multi-domain]  Cd Length: 156  Bit Score: 65.05  E-value: 4.54e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370483517  39 VEIIEQLHRQFAILsGGRGEDGAPIITF-PEFSGFKHIPDEDFLNVMTYL--TSIPSVEAASIGFIVVIDRRRDKWSS-- 113
Cdd:cd00170     1 LEELLELLGGIGYL-GGRDKEGRPVLVFrAGWDPPKLLDLEELLRYLVYLleKALRELEEQVEGFVVIIDLKGFSLSNls 79

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1370483517 114 ----VKASLTRIAVAFPGNLQLIFILRPSRFIqRTFTDIGIKYYRNEFKTKVpIIMVNSVSDLHGYIDKSQLTRELGGT 188
Cdd:cd00170    80 dlslLKKLLKILQDHYPERLKKIYIVNAPWIF-SALWKIVKPFLSEKTRKKI-VFLGSDLEELLEYIDPDQLPKELGGT 156
PH_Obscurin cd13239
Obscurin pleckstrin homology (PH) domain; Obscurin (also called Obscurin-RhoGEF; ...
 832-959 1.67e-10

Obscurin pleckstrin homology (PH) domain; Obscurin (also called Obscurin-RhoGEF; Obscurin-myosin light chain kinase/Obscurin-MLCK) is a giant muscle protein that is concentrated at the peripheries of Z-disks and M-lines. It binds small ankyrin I, a component of the sarcoplasmic reticulum (SR) membrane. It is associated with the contractile apparatus through binding with titin and sarcomeric myosin. It plays important roles in the organization and assembly of the myofibril and the SR. Obscurin has been observed as alternatively-spliced isoforms. The major isoform in sleletal muscle, approximately 800 kDa in size, is composed of many adhesion modules and signaling domains. It harbors 49 Ig and 2 FNIII repeats at the N-terminues, a complex middle region with additional Ig domains, an IQ motif, and a conserved SH3 domain near RhoGEF and PH domains, and a non-modular C-terminus with phosphorylation motifs. The obscurin gene also encodes two kinase domains, which are not part of the 800 kDa form of the protein, but is part of smaller spliced products that present in heart muscle. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270059  Cd Length: 125  Bit Score: 59.48  E-value: 1.67e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370483517 832 PDDIGKLGKLLLHGPFSVWTiHKDRYKMKDlirfKPSQRQIYLFERGIVFCKIRMEPGDQGLSphYSFKKTMKLMTLSIR 911
Cdd:cd13239     6 PAPLQALGEPIRQGHFTVWE-EAPEVKTSS----RGHHRHVFLFKNCVVICKPKRDSRTDTVT--YVFKNKMKLSDIDVK 78

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|
gi 1370483517 912 QLGRGSHRKFEI--ASRNGLEKYILQAASKEIRDCWFSEISKLlmeQQNN 959
Cdd:cd13239    79 DTVEGDDRSFGLwhEHRGSVRKYTLQARSAIIKSSWLKDLRDL---QQRL 125
SPEC smart00150
Spectrin repeats;
323-428 2.79e-09

Spectrin repeats;


Pssm-ID: 197544 [Multi-domain]  Cd Length: 101  Bit Score: 55.41  E-value: 2.79e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370483517  323 QHFEHDFCKAKLALDNLlEEQAEFTGIGDSVMHVEQILKEHKKLEEKSQEPLEKAQLLALVGDQLIQSHHYAADAIRPRC 402
Cdd:smart00150   1 QQFLRDADELEAWLEEK-EQLLASEDLGKDLESVEALLKKHEAFEAELEAHEERVEALNELGEQLIEEGHPDAEEIEERL 79

                           90       100
                   ....*....|....*....|....*.
gi 1370483517  403 VELRHLCDDFingnKKKWDILGKSLE 428
Cdd:smart00150  80 EELNERWEEL----KELAEERRQKLE 101
PH1_Kalirin_Trio_like cd13240
Triple functional domain pleckstrin homology pleckstrin homology (PH) domain, repeat 1; ...
 831-955 3.33e-07

Triple functional domain pleckstrin homology pleckstrin homology (PH) domain, repeat 1; RhoGEFs, Kalirin and Trio, the mammalian homologs of Drosophila Trio and Caenorhabditis elegans UNC-73 regulate a novel step in secretory granule maturation. Their signaling modulates the extent to which regulated cargo enter and remain in the regulated secretory pathway. This allows for fine tuning of peptides released by a single secretory cell type with impaired signaling leading to pathological states. Trio plays an essential role in regulating the actin cytoskeleton during axonal guidance and branching. Kalirin and Trio are encoded by separate genes in mammals and by a single one in invertebrates. Kalirin and Trio share the same complex multidomain structure and display several splice variants. The longest Kalirin and Trio proteins have a Sec14 domain, a stretch of spectrin repeats, a RhoGEF(DH)/PH cassette (also called GEF1), an SH3 domain, a second RhoGEF(DH)/PH cassette (also called GEF2), a second SH3 domain, Ig/FNIII domains, and a kinase domain. The first RhoGEF(DH)/PH cassette catalyzes exchange on Rac1 and RhoG while the second RhoGEF(DH)/PH cassette is specific for RhoA. Kalirin and Trio are closely related to p63RhoGEF and have PH domains of similar function. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains.


Pssm-ID: 270060  Cd Length: 123  Bit Score: 50.08  E-value: 3.33e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370483517 831 CPDDIGKLGKLLLHGPFSVWtihkdryKMKDLIRfKPSQRQIYLFERGIVFCKirmEPGDQGLSPHYSFKktMKLMTLSI 910
Cdd:cd13240     5 CDEDLDSLGEVILQDSFQVW-------DPKQLIR-KGRERHVFLFELCLVFSK---EVKDSNGKSKYIYK--SRLMTSEI 71

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|
gi 1370483517 911 RQLGR--GSHRKFEIASR---NGLEKYILQAASKEIRDCWFSEISKLLME 955
Cdd:cd13240    72 GVTEHieGDPCKFALWTGrvpTSDNKIVLKASSLEVKQTWVKKLREVIQE 121
PH_unc89 cd13325
unc89 pleckstrin homology (PH) domain; unc89 is a myofibrillar protein. unc89-B the largest ...
 834-951 4.44e-07

unc89 pleckstrin homology (PH) domain; unc89 is a myofibrillar protein. unc89-B the largest isoform is composed of 53 immunoglobulin (Ig) domains, 2 Fn3 domains, a triplet of SH3, DH and PH domains at its N-terminus, and 2 protein kinase domains (PK1 and PK2) at its C-terminus. unc-89 mutants display disorganization of muscle A-bands, and usually lack M-lines. The COOH-terminal region of obscurin, the human homolog of unc89, interacts via two specific Ig-like domains with the NH(2)-terminal Z-disk region of titin, a protein that connects the Z line to the M line in the sarcomere and contributes to the contraction of striated muscle. obscurin is also thought to be involved in Ca2+/calmodulin via its IQ domains, as well as G protein-coupled signal transduction in the sarcomere via its RhoGEF/DH domain. The DH-PH region of OBSCN and unc89, the C. elegans homolog, has exchange activity for RhoA and Rho-1 respectively, but not for the small GTPases homologous to Cdc42 or Rac. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270134  Cd Length: 114  Bit Score: 49.27  E-value: 4.44e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370483517 834 DIGKLGKLLLHGPFSVWTihkdrykmkdlIRFKPSQRQIYLFERGIVFCKIRMEPGDQGLsphYSFKKTMKLMTLSIRQL 913
Cdd:cd13325     2 NIHKLGRLLRHDWFTVTD-----------GEGKAKERYLFLFKSRILITKVRRISEDRSV---FILKDIIRLPEVNVKQH 67

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 1370483517 914 GrGSHRKFEI---ASRNGLEKYILQAASKEIRDCWFSEISK 951
Cdd:cd13325    68 P-DDERTFELqpkLPAFGILPIDFKAHKDEIKDYWLNEIEE 107
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
 857-953 1.13e-05

Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The domain family possesses multiple functions including the abilities to bind inositol phosphates, and various proteins. PH domains have been found to possess inserted domains (such as in PLC gamma, syntrophins) and to be inserted within other domains. Mutations in Brutons tyrosine kinase (Btk) within its PH domain cause X-linked agammaglobulinaemia (XLA) in patients. Point mutations cluster into the positively charged end of the molecule around the predicted binding site for phosphatidylinositol lipids.


Pssm-ID: 214574 [Multi-domain]  Cd Length: 102  Bit Score: 45.23  E-value: 1.13e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370483517  857 YKMKDLIRFKPSQRQIYLFERGIVFCKIRMEPGDqglsphYSFKKTMKLMTLSIRQLGRGSHRK----FEIASRNGlEKY 932
Cdd:smart00233   8 YKKSGGGKKSWKKRYFVLFNSTLLYYKSKKDKKS------YKPKGSIDLSGCTVREAPDPDSSKkphcFEIKTSDR-KTL 80

                           90       100
                   ....*....|....*....|.
gi 1370483517  933 ILQAASKEIRDCWFSEISKLL 953
Cdd:smart00233  81 LLQAESEEEREKWVEALRKAI 101
PH cd00821
Pleckstrin homology (PH) domain; PH domains have diverse functions, but in general are ...
 857-949 6.09e-05

Pleckstrin homology (PH) domain; PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 275388 [Multi-domain]  Cd Length: 92  Bit Score: 42.53  E-value: 6.09e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370483517 857 YKMKDLIRFKPSQRQIYLFERGIVFCKIRMEPgdqglspHYSFKKTMKL-MTLSIRQLGRGSHR-KFEIASRNGlEKYIL 934
Cdd:cd00821     6 LKRGGGGLKSWKKRWFVLFEGVLLYYKSKKDS-------SYKPKGSIPLsGILEVEEVSPKERPhCFELVTPDG-RTYYL 77

                          90
                  ....*....|....*
gi 1370483517 935 QAASKEIRDCWFSEI 949
Cdd:cd00821    78 QADSEEERQEWLKAL 92
PH pfam00169
PH domain; PH stands for pleckstrin homology.
 857-953 1.11e-03

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 459697 [Multi-domain]  Cd Length: 105  Bit Score: 39.47  E-value: 1.11e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370483517 857 YKMKDLIRFKPSQRQIYLFERGIVFCKirmepgDQGLSPHYSFKKTMKLMTLSIRQLGRGSHRK----FEI--ASRNGLE 930
Cdd:pfam00169   8 LKKGGGKKKSWKKRYFVLFDGSLLYYK------DDKSGKSKEPKGSISLSGCEVVEVVASDSPKrkfcFELrtGERTGKR 81

                          90       100
                  ....*....|....*....|...
gi 1370483517 931 KYILQAASKEIRDCWFSEISKLL 953
Cdd:pfam00169  82 TYLLQAESEEERKDWIKAIQSAI 104
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.21
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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