CID (CTD-Interacting Domain) of SR-related and CTD-associated factor 8; SR-related and CTD-associated factor 8 (SCAF8) is also called CDC5L complex-associated protein 7 (CCAP7) or RNA-binding motif protein 16 (RBM16). It may play a role in mRNA processing. SCAF8 contains a CTD-interacting domain (CID) at the amino terminus and a Ser/Arg-rich domain followed by an RNA recognition motif. CID binds tightly to the carboxy-terminal domain (CTD) of RNA polymerase (Pol) II (RNAP II). During transcription, RNAP II synthesizes eukaryotic messenger RNA. Transcription is coupled to RNA processing through the CTD, which consists of up to 52 repeats of the sequence Tyr1-Ser2-Pro3-Thr4-Ser5-Pro6-Ser7. CID contains eight alpha-helices in a right-handed superhelical arrangement, which closely resembles that of the VHS domains and ARM (Armadillo) repeat proteins, except for its two amino-terminal helices.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 555290149   83 KTFNSELYSLNDYKPPISKAKMTQITKAAIKAIKFYKHVVQSVEKFIQKCKPEYKVPGLYVIDSIVRQSRHQFGQEKDVF 162
Cdd:cd17004     1 KTFNSELYSLNDYKPPISKAKMTQITKAAIKAIKFYKHVVQSVEKFIQKCKPEYKVPGLYVIDSIVRQSRHQFGQEKDVF 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|.
gi 555290149  163 APRFSNNIISTFQNLYRCPGDDKSKIVRVLNLWQKNNVFKSEIIQPLLDMA 213
Cdd:cd17004    81 APRFSNNIISTFQNLYRCPGDDKSKIVRVLNLWQKNNVFKSEIIQPLLDMA 131

large tegument protein UL36; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 555290149  796 PSLSMTPETVKDVGFGSLVIPGGSVASNLATSALPAgnvfnAPTKQAEPEEKVPHLIDHQISSGENTRSviPNDISSNAA 875
Cdd:PHA03247 2702 PPPPPTPEPAPHALVSATPLPPGPAAARQASPALPA-----APAPPAVPAGPATPGGPARPARPPTTAG--PPAPAPPAA 2774

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 555290149  876 ILGGQPPNVTsnsgilgvqRPNVSSNSEILGVRPSNVSSSSGIIAAQPPNILNNSGIL---GIQPPSVS---NSSGLLGV 949
Cdd:PHA03247 2775 PAAGPPRRLT---------RPAVASLSESRESLPSPWDPADPPAAVLAPAAALPPAASpagPLPPPTSAqptAPPPPPGP 2845

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 555290149  950 LPPNIPNNSGLV----------GVQPPNVPNTPGLL--------GTQPPAGPQNLPPLSIPNQRMPTMPMldiRPGLIPQ 1011
Cdd:PHA03247 2846 PPPSLPLGGSVApggdvrrrppSRSPAAKPAAPARPpvrrlarpAVSRSTESFALPPDQPERPPQPQAPP---PPQPQPQ 2922

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 555290149 1012 APGPRFPLIQPGIPPQRGIPPPSVLDSAlhppprGPFPPGDIFSQPERPFLAPGRQSVDNVTNPEKRIPLGNDNIQQEGD 1091
Cdd:PHA03247 2923 PPPPPQPQPPPPPPPRPQPPLAPTTDPA------GAGEPSGAVPQPWLGALVPGRVAVPRFRVPQPAPSREAPASSTPPL 2996

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 555290149 1092 RDYRFPPIETRESI------SRPPPVDVRDVV-------------------------------GRPIDPREGPGRPPL-- 1132
Cdd:PHA03247 2997 TGHSLSRVSSWASSlalheeTDPPPVSLKQTLwppddtedsdadslfdsdsersdlealdplpPEPHDPFAHEPDPATpe 3076

                         410       420       430
                  ....*....|....*....|....*....|..
gi 555290149 1133 -----DGRDHFGRPPVDIRENLVRPGIDHLGR 1159
Cdd:PHA03247 3077 agareSPSSQFGPPPLSANAALSRRYVRSTGR 3108

CID (CTD-Interacting Domain) of SR-related and CTD-associated factor 8; SR-related and CTD-associated factor 8 (SCAF8) is also called CDC5L complex-associated protein 7 (CCAP7) or RNA-binding motif protein 16 (RBM16). It may play a role in mRNA processing. SCAF8 contains a CTD-interacting domain (CID) at the amino terminus and a Ser/Arg-rich domain followed by an RNA recognition motif. CID binds tightly to the carboxy-terminal domain (CTD) of RNA polymerase (Pol) II (RNAP II). During transcription, RNAP II synthesizes eukaryotic messenger RNA. Transcription is coupled to RNA processing through the CTD, which consists of up to 52 repeats of the sequence Tyr1-Ser2-Pro3-Thr4-Ser5-Pro6-Ser7. CID contains eight alpha-helices in a right-handed superhelical arrangement, which closely resembles that of the VHS domains and ARM (Armadillo) repeat proteins, except for its two amino-terminal helices.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 555290149   83 KTFNSELYSLNDYKPPISKAKMTQITKAAIKAIKFYKHVVQSVEKFIQKCKPEYKVPGLYVIDSIVRQSRHQFGQEKDVF 162
Cdd:cd17004     1 KTFNSELYSLNDYKPPISKAKMTQITKAAIKAIKFYKHVVQSVEKFIQKCKPEYKVPGLYVIDSIVRQSRHQFGQEKDVF 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|.
gi 555290149  163 APRFSNNIISTFQNLYRCPGDDKSKIVRVLNLWQKNNVFKSEIIQPLLDMA 213
Cdd:cd17004    81 APRFSNNIISTFQNLYRCPGDDKSKIVRVLNLWQKNNVFKSEIIQPLLDMA 131

CID domain; This domain binds to the phosphorylated C-terminal domain (CTD) of RNA polymerase II. This domain is known as the CTD-interacting domain (CID).

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 555290149    83 KTFNSELYSLNDykppiSKAKMTQITKAAIKAIKFYKHVVQSVEKFIQKCKPEYKVPGLYVIDSIVRQSRHQFGQEkdvF 162
Cdd:pfam04818    1 EALEKKLSSLNN-----SQESIQTLSKWILFHRKHAKAIVEVWEKYLKKAKPEKKLHLLYLANDVLQNSRKKGKSE---F 72

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*
gi 555290149   163 APRFSNNIISTFQNLYR-CPGDDKSKIVRVLNLWQKNNVFKSEII 206
Cdd:pfam04818   73 ADAFEPVLPEAFASAYKkCDEKLKKKLERLLNIWEERNVFSPEVI 117

RNA recognition motif;

                            10        20        30        40        50        60        70
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 555290149    556 TLWVGQVDKKATQQDLTNLFEEFGQIESINMIP------PRGCAYVCMVHRQDAFRALQKLssGSYKIGSKVIKI 624
Cdd:smart00360    1 TLFVGNLPPDTTEEELRELFSKFGKVESVRLVRdketgkSKGFAFVEFESEEDAEKALEAL--NGKELDGRPLKV 73

RNA recognition motif. (a.k.a. RRM, RBD, or RNP domain); The RRM motif is probably diagnostic of an RNA binding protein. RRMs are found in a variety of RNA binding proteins, including various hnRNP proteins, proteins implicated in regulation of alternative splicing, and protein components of snRNPs. The motif also appears in a few single stranded DNA binding proteins. The RRM structure consists of four strands and two helices arranged in an alpha/beta sandwich, with a third helix present during RNA binding in some cases The C-terminal beta strand (4th strand) and final helix are hard to align and have been omitted in the SEED alignment The LA proteins have an N terminal rrm which is included in the seed. There is a second region towards the C terminus that has some features characteriztic of a rrm but does not appear to have the important structural core of a rrm. The LA proteins are one of the main autoantigens in Systemic lupus erythematosus (SLE), an autoimmune disease.

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 555290149   557 LWVGQVDKKATQQDLTNLFEEFGQIESINMIP-----PRGCAYVCMVHRQDAFRALQKLSsgSYKIGSKVIK 623
Cdd:pfam00076    1 LFVGNLPPDTTEEDLKDLFSKFGPIKSIRLVRdetgrSKGFAFVEFEDEEDAEKAIEALN--GKELGGRELK 70

large tegument protein UL36; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 555290149  796 PSLSMTPETVKDVGFGSLVIPGGSVASNLATSALPAgnvfnAPTKQAEPEEKVPHLIDHQISSGENTRSviPNDISSNAA 875
Cdd:PHA03247 2702 PPPPPTPEPAPHALVSATPLPPGPAAARQASPALPA-----APAPPAVPAGPATPGGPARPARPPTTAG--PPAPAPPAA 2774

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 555290149  876 ILGGQPPNVTsnsgilgvqRPNVSSNSEILGVRPSNVSSSSGIIAAQPPNILNNSGIL---GIQPPSVS---NSSGLLGV 949
Cdd:PHA03247 2775 PAAGPPRRLT---------RPAVASLSESRESLPSPWDPADPPAAVLAPAAALPPAASpagPLPPPTSAqptAPPPPPGP 2845

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 555290149  950 LPPNIPNNSGLV----------GVQPPNVPNTPGLL--------GTQPPAGPQNLPPLSIPNQRMPTMPMldiRPGLIPQ 1011
Cdd:PHA03247 2846 PPPSLPLGGSVApggdvrrrppSRSPAAKPAAPARPpvrrlarpAVSRSTESFALPPDQPERPPQPQAPP---PPQPQPQ 2922

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 555290149 1012 APGPRFPLIQPGIPPQRGIPPPSVLDSAlhppprGPFPPGDIFSQPERPFLAPGRQSVDNVTNPEKRIPLGNDNIQQEGD 1091
Cdd:PHA03247 2923 PPPPPQPQPPPPPPPRPQPPLAPTTDPA------GAGEPSGAVPQPWLGALVPGRVAVPRFRVPQPAPSREAPASSTPPL 2996

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 555290149 1092 RDYRFPPIETRESI------SRPPPVDVRDVV-------------------------------GRPIDPREGPGRPPL-- 1132
Cdd:PHA03247 2997 TGHSLSRVSSWASSlalheeTDPPPVSLKQTLwppddtedsdadslfdsdsersdlealdplpPEPHDPFAHEPDPATpe 3076

                         410       420       430
                  ....*....|....*....|....*....|..
gi 555290149 1133 -----DGRDHFGRPPVDIRENLVRPGIDHLGR 1159
Cdd:PHA03247 3077 agareSPSSQFGPPPLSANAALSRRYVRSTGR 3108

CID (CTD-Interacting Domain) of SR-related and CTD-associated factor 8; SR-related and CTD-associated factor 8 (SCAF8) is also called CDC5L complex-associated protein 7 (CCAP7) or RNA-binding motif protein 16 (RBM16). It may play a role in mRNA processing. SCAF8 contains a CTD-interacting domain (CID) at the amino terminus and a Ser/Arg-rich domain followed by an RNA recognition motif. CID binds tightly to the carboxy-terminal domain (CTD) of RNA polymerase (Pol) II (RNAP II). During transcription, RNAP II synthesizes eukaryotic messenger RNA. Transcription is coupled to RNA processing through the CTD, which consists of up to 52 repeats of the sequence Tyr1-Ser2-Pro3-Thr4-Ser5-Pro6-Ser7. CID contains eight alpha-helices in a right-handed superhelical arrangement, which closely resembles that of the VHS domains and ARM (Armadillo) repeat proteins, except for its two amino-terminal helices.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 555290149   83 KTFNSELYSLNDYKPPISKAKMTQITKAAIKAIKFYKHVVQSVEKFIQKCKPEYKVPGLYVIDSIVRQSRHQFGQEKDVF 162
Cdd:cd17004     1 KTFNSELYSLNDYKPPISKAKMTQITKAAIKAIKFYKHVVQSVEKFIQKCKPEYKVPGLYVIDSIVRQSRHQFGQEKDVF 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|.
gi 555290149  163 APRFSNNIISTFQNLYRCPGDDKSKIVRVLNLWQKNNVFKSEIIQPLLDMA 213
Cdd:cd17004    81 APRFSNNIISTFQNLYRCPGDDKSKIVRVLNLWQKNNVFKSEIIQPLLDMA 131

CID (CTD-Interacting Domain) of Splicing factor arginine serine rich 15; Splicing factor arginine serine rich 15 (SFRS15) is also called CTD-binding SR-like protein RA4 or SR-related and CTD-associated factor 4 (SCAF4). It may act to physically and functionally link transcription and pre-mRNA processing. SFRS15/SCAF4 contains a CTD-interacting domain (CID) at the amino terminus and a Ser/Arg-rich domain followed by an RNA recognition motif. CID binds tightly to the carboxy-terminal domain (CTD) of RNA polymerase (Pol) II (RNAP II). During transcription, RNAP II synthesizes eukaryotic messenger RNA. Transcription is coupled to RNA processing through the CTD, which consists of up to 52 repeats of the sequence Tyr1-Ser2-Pro3-Thr4-Ser5-Pro6-Ser7. CID contains eight alpha-helices in a right-handed superhelical arrangement, which closely resembles that of the VHS domains and ARM (Armadillo) repeat proteins, except for its two amino-terminal helices.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 555290149   85 FNSELYSLNDYKPPISKAKMTQITKAAIKAIKFYKHVVQSVEKFIQKCKPEYKVPGLYVIDSIVRQSRHQFGQEKDVFAP 164
Cdd:cd17005     3 FNQELFSLMDMKPPISRAKMILITKAAIKAIKLYKHVVQIVEKFIKKCKPEYKVPGLYVIDSIVRQSRHQFGADKDVFGP 82

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*....
gi 555290149  165 RFSNNIISTFQNLYRCPGDDKSKIVRVLNLWQKNNVFKSEIIQPLLDMA 213
Cdd:cd17005    83 RFSKNITATFQYLYLCPSEDKSKIVRVLNLWQKNGVFKIEIIQPLLDMA 131

RNA recognition motif (RRM) found in SR-related and CTD-associated factor 8 (SCAF8) and similar proteins; This subgroup corresponds to the RRM of SCAF8 (also termed CDC5L complex-associated protein 7, or RNA-binding motif protein 16, or CTD-binding SR-like protein RA8), a nuclear matrix protein that interacts specifically with a highly serine-phosphorylated form of the carboxy-terminal domain (CTD) of the largest subunit of RNA polymerase II (pol II). The pol II CTD plays a role in coupling transcription and pre-mRNA processing. SCAF8 co-localizes primarily with transcription sites that are enriched in nuclear matrix fraction, which is known to contain proteins involved in pre-mRNA processing. Thus, SCAF8 may play a direct role in coupling with both, transcription and pre-mRNA processing, processes. SCAF8, together with SCAF4, represents a new class of SCAFs (SR-like CTD-associated factors). They contain a conserved N-terminal CTD-interacting domain (CID), an atypical RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain), and serine/arginine-rich motifs.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 555290149  553 CSTTLWVGQVDKKATQQDLTNLFEEFGQIESINMIPPRGCAYVCMVHRQDAFRALQKLSSGSYKIGSKVIKIAWALNKG 631
Cdd:cd12462     1 CSTTLWVGQVDKKATQQDLTNLFEEFGQIESINMIPPRGCAYVCMVHRQDAYRALQKLSTGSFKIGSKIIKIAWALNKG 79

RNA recognition motif (RRM) found in SR-related and CTD-associated factor 4 (SCAF4), SR-related and CTD-associated factor 8 (SCAF8) and similar proteins; This subfamily corresponds to the RRM in a new class of SCAFs (SR-like CTD-associated factors), including SCAF4, SCAF8 and similar proteins. The biological role of SCAF4 remains unclear, but it shows high sequence similarity to SCAF8 (also termed CDC5L complex-associated protein 7, or RNA-binding motif protein 16, or CTD-binding SR-like protein RA8). SCAF8 is a nuclear matrix protein that interacts specifically with a highly serine-phosphorylated form of the carboxy-terminal domain (CTD) of the largest subunit of RNA polymerase II (pol II). The pol II CTD plays a role in coupling transcription and pre-mRNA processing. In addition, SCAF8 co-localizes primarily with transcription sites that are enriched in nuclear matrix fraction, which is known to contain proteins involved in pre-mRNA processing. Thus, SCAF8 may play a direct role in coupling with both, transcription and pre-mRNA processing, processes. SCAF8 and SCAF4 both contain a conserved N-terminal CTD-interacting domain (CID), an atypical RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNPs (ribonucleoprotein domain), and serine/arginine-rich motifs.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 555290149  553 CSTTLWVGQVDKKATQQDLTNLFEEFGQIESINMIPPRGCAYVCMVHRQDAFRALQKLSsgSYKIGSKVIKIAWALNKG 631
Cdd:cd12227     1 CSTTLWVGHLSKKVTQEELKNLFEEYGEIQSIDMIPPRGCAYVCMKTRQDAHRALQKLK--NHKLRGKSIKIAWAPNKG 77

domain present in proteins, which are involved in regulation of nuclear pre-mRNA;

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 555290149     84 TFNSELYSLNdykppISKAKMTQITKAAIKAIKFYKHVVQSVEKFIQKCKPEYKVPGLYVIDSIVRQSRHQFG-QEKDVF 162
Cdd:smart00582    1 AFEQKLESLN-----NSQESIQTLTKWAIEHASHAKEIVELWEKYIKKAPVPRKLPLLYLLDSIVQNSKRKYGsEFGDEL 75

                            90       100       110       120       130
                    ....*....|....*....|....*....|....*....|....*....|
gi 555290149    163 APRFSNNIISTFQNLYRcpgDDKSKIVRVLNLWQKNNVFKSEIIQPLLDM 212
Cdd:smart00582   76 GPVFQDALRRVLGAAPE---ELKKKIRRLLNIWEERGIFPPEVLRPLREK 122

CID (CTD-Interacting Domain) of Pcf11; Pcf11 is conserved across eukaryotes. The best studied protein is Saccharomyces cerevisiae Pcf11, also called protein 1 of CF I, an essential subunit of the cleavage factor IA (CFIA) complex which is required for polyadenylation-dependent pre-mRNA 3'-end processing and RNA polymerase (Pol) II (RNAP II) transcription termination. Human Pcf11, also referred to as pre-mRNA cleavage complex 2 protein Pcf11, has been shown to enhance degradation of RNAP II-associated nascent RNA and transcriptional termination. The family also includes plant PCFS4 (Pcf11-similar-4 protein or Polyadenylation and cleavage factor homolog 4) and Caenorhabditis elegans Polyadenylation and cleavage factor homolog 11. CID binds tightly to the carboxy-terminal domain (CTD) of RNAP II. Pcf11 CID preferentially interacts with CTD phosphorylated at Ser2. During transcription, RNAP II synthesizes eukaryotic messenger RNA. Transcription is coupled to RNA processing through the CTD, which consists of up to 52 repeats of the sequence Tyr1-Ser2-Pro3-Thr4-Ser5-Pro6-Ser7. CID contains eight alpha-helices in a right-handed superhelical arrangement, which closely resembles that of the VHS domains and ARM (Armadillo) repeat proteins, except for its two amino-terminal helices.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 555290149   82 VKTFNSELYSLNDYkppiSKAKMTQITKAAIKAIKFYKHVVQSVEKFIQKCKPEYKVPGLYVIDSIVrqsrhqfgqeKDV 161
Cdd:cd16982     1 VEEYRSALAELTFN----SKPIINNLTMLAEENIQAAQAIVEAIEERIRKVPPEQKLPALYLLDSIV----------KNV 66

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 555290149  162 ---FAPRFSNNIISTFQNLYR-CPGDDKSKIVRVLNLW 195
Cdd:cd16982    67 ggpYTSLFSPNLVDLFLDAYRlVDEKTRKKLEKLLNTW 104

RNA recognition motif;

                            10        20        30        40        50        60        70
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 555290149    556 TLWVGQVDKKATQQDLTNLFEEFGQIESINMIP------PRGCAYVCMVHRQDAFRALQKLssGSYKIGSKVIKI 624
Cdd:smart00360    1 TLFVGNLPPDTTEEELRELFSKFGKVESVRLVRdketgkSKGFAFVEFESEEDAEKALEAL--NGKELDGRPLKV 73

RNA recognition motif 3 (RRM3) found in yeast negative growth regulatory protein NGR1 (RBP1), yeast protein NAM8 and similar proteins; This subfamily corresponds to the RRM3 of NGR1 and NAM8. NGR1, also termed RNA-binding protein RBP1, is a putative glucose-repressible protein that binds both RNA and single-stranded DNA (ssDNA) in yeast. It may function in regulating cell growth in early log phase, possibly through its participation in RNA metabolism. NGR1 contains two RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), followed by a glutamine-rich stretch that may be involved in transcriptional activity. In addition, NGR1 has an asparagine-rich region near the carboxyl terminus which also harbors a methionine-rich region. The family also includes protein NAM8, which is a putative RNA-binding protein that acts as a suppressor of mitochondrial splicing deficiencies when overexpressed in yeast. It may be a non-essential component of the mitochondrial splicing machinery. Like NGR1, NAM8 contains two RRMs.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 555290149  555 TTLWVGQVDKKATQQDLTNLFEEFGQIESINMIPPRGCAYVCMVHRQDAFRALQKLSsgSYKIGSKVIKIAW 626
Cdd:cd12346     2 TTVFVGGLDPNVTEEDLRVLFGPFGEIVYVKIPPGKGCGFVQFVNRASAEAAIQKLQ--GTPIGGSRIRLSW 71

RNA recognition motif 1 (RRM1) and 2 (RRM2) found in CELF/Bruno-like family of RNA binding proteins and plant flowering time control protein FCA; This subfamily corresponds to the RRM1 and RRM2 domains of the CUGBP1 and ETR-3-like factors (CELF) as well as plant flowering time control protein FCA. CELF, also termed BRUNOL (Bruno-like) proteins, is a family of structurally related RNA-binding proteins involved in regulation of pre-mRNA splicing in the nucleus, and control of mRNA translation and deadenylation in the cytoplasm. The family contains six members: CELF-1 (also known as BRUNOL-2, CUG-BP1, NAPOR, EDEN-BP), CELF-2 (also known as BRUNOL-3, ETR-3, CUG-BP2, NAPOR-2), CELF-3 (also known as BRUNOL-1, TNRC4, ETR-1, CAGH4, ER DA4), CELF-4 (BRUNOL-4), CELF-5 (BRUNOL-5) and CELF-6 (BRUNOL-6). They all contain three highly conserved RNA recognition motifs (RRMs), also known as RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains): two consecutive RRMs (RRM1 and RRM2) situated in the N-terminal region followed by a linker region and the third RRM (RRM3) close to the C-terminus of the protein. The low sequence conservation of the linker region is highly suggestive of a large variety in the co-factors that associate with the various CELF family members. Based on both, sequence similarity and function, the CELF family can be divided into two subfamilies, the first containing CELFs 1 and 2, and the second containing CELFs 3, 4, 5, and 6. The different CELF proteins may act through different sites on at least some substrates. Furthermore, CELF proteins may interact with each other in varying combinations to influence alternative splicing in different contexts. This subfamily also includes plant flowering time control protein FCA that functions in the posttranscriptional regulation of transcripts involved in the flowering process. FCA contains two RRMs, and a WW protein interaction domain.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 555290149  557 LWVGQVDKKATQQDLTNLFEEFGQIESINMI------PPRGCAYVCMVHRQDAFRALQKL 610
Cdd:cd12361     2 LFVGMIPKTASEEDVRPLFEQFGNIEEVQILrdkqtgQSKGCAFVTFSTREEALRAIEAL 61

RNA recognition motif (RRM) found in U2-associated protein SR140 and similar proteins; This subgroup corresponds to the RRM of SR140 (also termed U2 snRNP-associated SURP motif-containing protein orU2SURP, or 140 kDa Ser/Arg-rich domain protein) which is a putative splicing factor mainly found in higher eukaryotes. Although it is initially identified as one of the 17S U2 snRNP-associated proteins, the molecular and physiological function of SR140 remains unclear. SR140 contains an N-terminal RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain), a SWAP/SURP domain that is found in a number of pre-mRNA splicing factors in the middle region, and a C-terminal arginine/serine-rich domain (RS domain).

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 555290149  554 STTLWVGQVDKKATQQDLTNLFEEFGQIESINMIPPRG---------CAYVCMVHRQDAFRALQKLSsgSYKIGSKVIKI 624
Cdd:cd12223     1 TTNLYVGNLPPSVTEEVLLREFGRFGPLASVKIMWPRTeeerrrnrnCGFVAFMSRADAERAMRELN--GKDVMGYELKL 78

                  ...
gi 555290149  625 AWA 627
Cdd:cd12223    79 GWG 81

RNA recognition motif 2 (RRM2) and 4 (RRM4) found in RNA-binding protein MRN1 and similar proteins; This subgroup corresponds to the RRM2 and RRM4 of MRN1, also termed multicopy suppressor of RSC-NHP6 synthetic lethality protein 1, or post-transcriptional regulator of 69 kDa, and is an RNA-binding protein found in yeast. Although its specific biological role remains unclear, MRN1 might be involved in translational regulation. Members in this family contain four copies of conserved RNA recognition motif (RRM), also known as RBD (RNA binding domain) or RNP (ribonucleoprotein domain).

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 555290149  554 STTLWVGQVDKKATQQDLTNLFEEFGQIESINMIPPRGCAYVCMVHRQDAFRALQKLSSGsyKIGSKVIKIAWA 627
Cdd:cd12262     3 SRNVYVGNLDDSLTEEEIRGILEKYGEIESIKILKEKNCAFVNYLNIANAIKAVQELPIK--NPKFKKVRINYG 74

RNA recognition motif. (a.k.a. RRM, RBD, or RNP domain); The RRM motif is probably diagnostic of an RNA binding protein. RRMs are found in a variety of RNA binding proteins, including various hnRNP proteins, proteins implicated in regulation of alternative splicing, and protein components of snRNPs. The motif also appears in a few single stranded DNA binding proteins. The RRM structure consists of four strands and two helices arranged in an alpha/beta sandwich, with a third helix present during RNA binding in some cases The C-terminal beta strand (4th strand) and final helix are hard to align and have been omitted in the SEED alignment The LA proteins have an N terminal rrm which is included in the seed. There is a second region towards the C terminus that has some features characteriztic of a rrm but does not appear to have the important structural core of a rrm. The LA proteins are one of the main autoantigens in Systemic lupus erythematosus (SLE), an autoimmune disease.

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 555290149   557 LWVGQVDKKATQQDLTNLFEEFGQIESINMIP-----PRGCAYVCMVHRQDAFRALQKLSsgSYKIGSKVIK 623
Cdd:pfam00076    1 LFVGNLPPDTTEEDLKDLFSKFGPIKSIRLVRdetgrSKGFAFVEFEDEEDAEKAIEALN--GKELGGRELK 70

RNA recognition motif 2 (RRM2) found in granule-associated RNA binding proteins (p40-TIA-1 and TIAR), and yeast nuclear and cytoplasmic polyadenylated RNA-binding protein PUB1; This subfamily corresponds to the RRM3 of TIA-1, TIAR, and PUB1. Nucleolysin TIA-1 isoform p40 (p40-TIA-1 or TIA-1) and nucleolysin TIA-1-related protein (TIAR) are granule-associated RNA binding proteins involved in inducing apoptosis in cytotoxic lymphocyte (CTL) target cells. They share high sequence similarity and are expressed in a wide variety of cell types. TIA-1 can be phosphorylated by a serine/threonine kinase that is activated during Fas-mediated apoptosis.TIAR is mainly localized in the nucleus of hematopoietic and nonhematopoietic cells. It is translocated from the nucleus to the cytoplasm in response to exogenous triggers of apoptosis. Both TIA-1 and TIAR bind specifically to poly(A) but not to poly(C) homopolymers. They are composed of three N-terminal highly homologous RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), and a glutamine-rich C-terminal auxiliary domain containing a lysosome-targeting motif. TIA-1 and TIAR interact with RNAs containing short stretches of uridylates and their RRM2 can mediate the specific binding to uridylate-rich RNAs. The C-terminal auxiliary domain may be responsible for interacting with other proteins. In addition, TIA-1 and TIAR share a potential serine protease-cleavage site (Phe-Val-Arg) localized at the junction between their RNA binding domains and their C-terminal auxiliary domains. This subfamily also includes a yeast nuclear and cytoplasmic polyadenylated RNA-binding protein PUB1, termed ARS consensus-binding protein ACBP-60, or poly uridylate-binding protein, or poly(U)-binding protein, which has been identified as both a heterogeneous nuclear RNA-binding protein (hnRNP) and a cytoplasmic mRNA-binding protein (mRNP). It may be stably bound to a translationally inactive subpopulation of mRNAs within the cytoplasm. PUB1 is distributed in both, the nucleus and the cytoplasm, and binds to poly(A)+ RNA (mRNA or pre-mRNA). Although it is one of the major cellular proteins cross-linked by UV light to polyadenylated RNAs in vivo, PUB1 is nonessential for cell growth in yeast. PUB1 also binds to T-rich single stranded DNA (ssDNA); however, there is no strong evidence implicating PUB1 in the mechanism of DNA replication. PUB1 contains three RRMs, and a GAR motif (glycine and arginine rich stretch) that is located between RRM2 and RRM3.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 555290149  555 TTLWVGQVDKKATQQDLTNLFEEFGQIESINMIPPRGCAYVCMVHRQDAFRALQKLSSGSykIGSKVIKIAW 626
Cdd:cd12354     1 TTVYVGNITKGLTEALLQQTFSPFGQILEVRVFPDKGYAFIRFDSHEAATHAIVSVNGTI--INGQAVKCSW 70

RNA recognition motif 1 (RRM1) found in granule-associated RNA binding proteins p40-TIA-1 and TIAR; This subfamily corresponds to the RRM1 of nucleolysin TIA-1 isoform p40 (p40-TIA-1 or TIA-1) and nucleolysin TIA-1-related protein (TIAR), both of which are granule-associated RNA binding proteins involved in inducing apoptosis in cytotoxic lymphocyte (CTL) target cells. TIA-1 and TIAR share high sequence similarity. They are expressed in a wide variety of cell types. TIA-1 can be phosphorylated by a serine/threonine kinase that is activated during Fas-mediated apoptosis.TIAR is mainly localized in the nucleus of hematopoietic and nonhematopoietic cells. It is translocated from the nucleus to the cytoplasm in response to exogenous triggers of apoptosis. Both, TIA-1 and TIAR, bind specifically to poly(A) but not to poly(C) homopolymers. They are composed of three N-terminal highly homologous RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), and a glutamine-rich C-terminal auxiliary domain containing a lysosome-targeting motif. TIA-1 and TIAR interact with RNAs containing short stretches of uridylates and their RRM2 can mediate the specific binding to uridylate-rich RNAs. The C-terminal auxiliary domain may be responsible for interacting with other proteins. In addition, TIA-1 and TIAR share a potential serine protease-cleavage site (Phe-Val-Arg) localized at the junction between their RNA binding domains and their C-terminal auxiliary domains.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 555290149  557 LWVGQVDKKATQQDLTNLFEEFGQIESINMIPPRGC----AYVCMVHRQDAFRALQKLSsgSYKIGSKVIKIAWA 627
Cdd:cd12352     1 LYVGNLDRQVTEDLILQLFSQIGPCKSCKMITEHGGndpyCFVEFYEHNHAAAALQAMN--GRKILGKEVKVNWA 73

CID (CTD-Interacting Domain) of Regulation of nuclear pre-mRNA domain-containing protein 1B; Regulation of nuclear pre-mRNA domain-containing protein 1B (RPRD1B) is also called Cell cycle-related and expression-elevated protein in tumor (CREPT). RPRD1B is a CID (CTD-Interacting Domain) containing protein that co-purifies with RNA polymerase (Pol) II (RNAP II) and three other RNAP II-associated proteins, RPAP2, GRINL1A and RECQL5, but not with the Mediator complex. CID binds tightly to the carboxy-terminal domain (CTD) of RNAP II. During transcription, RNAP II synthesizes eukaryotic messenger RNA. Transcription is coupled to RNA processing through the CTD, which consists of up to 52 repeats of the sequence Tyr1-Ser2-Pro3-Thr4-Ser5-Pro6-Ser7. RPRD1B form homodimers and heterodimers with RPRD1A through their coiled-coil domains. Both RPRD1A and RPRD1B associate directly with RPAP2 phosphatase and serve as CTD scaffolds to coordinate the dephosphorylation of phospho-S5 by RPAP2. RPRD1B is highly expressed during tumorigenesis and in endometrial cancer, has been shown to promote tumor growth by accelerating the cell cycle. CID contains eight alpha-helices in a right-handed superhelical arrangement, which closely resembles that of the VHS domains and ARM (Armadillo) repeat proteins, except for its two amino-terminal helices.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 555290149  115 IKFYKH---VVQSVEKFIQKCKPEYKVPGLYVIDSIVRQSRHQfGQEkdvFAPRFSNNIISTFQNLYRcPGDD--KSKIV 189
Cdd:cd17012    29 IHHRKHagpIVSVWHRELRKAKSSRKLTFLYLANDVIQNSKRK-GPE---FTREFESVLVDAFSHVAR-EADEgcKKPLE 103

                          90       100
                  ....*....|....*....|
gi 555290149  190 RVLNLWQKNNVFKSEIIQPL 209
Cdd:cd17012   104 RLLNIWQERSVYGGDFIQQL 123

polyadenylate binding protein, human types 1, 2, 3, 4 family; These eukaryotic proteins recognize the poly-A of mRNA and consists of four tandem RNA recognition domains at the N-terminus (rrm: pfam00076) followed by a PABP-specific domain (pfam00658) at the C-terminus. The protein is involved in the transport of mRNA's from the nucleus to the cytoplasm. There are four paralogs in Homo sapiens which are expressed in testis, platelets, broadly expressed and of unknown tissue range.

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 555290149   556 TLWVGQVDKKATQQDLTNLFEEFGQIESI----NMIPPR--GCAYVCMVHRQDAFRALQKLssgSYK-IGSKVIKIAW 626
Cdd:TIGR01628    2 SLYVGDLDPDVTEAKLYDLFKPFGPVLSVrvcrDSVTRRslGYGYVNFQNPADAERALETM---NFKrLGGKPIRIMW 76

RNA recognition motif 1 (RRM1) found in CUGBP Elav-like family member CELF-3, CELF-4, CELF-5, CELF-6 and similar proteins; This subfamily corresponds to the RRM1 of CELF-3, CELF-4, CELF-5, CELF-6, all of which belong to the CUGBP1 and ETR-3-like factors (CELF) or BRUNOL (Bruno-like) family of RNA-binding proteins that display dual nuclear and cytoplasmic localizations and have been implicated in the regulation of pre-mRNA splicing and in the control of mRNA translation and deadenylation. CELF-3, expressed in brain and testis only, is also known as bruno-like protein 1 (BRUNOL-1), or CAG repeat protein 4, or CUG-BP- and ETR-3-like factor 3, or embryonic lethal abnormal vision (ELAV)-type RNA-binding protein 1 (ETR-1), or expanded repeat domain protein CAG/CTG 4, or trinucleotide repeat-containing gene 4 protein (TNRC4). It plays an important role in the pathogenesis of tauopathies. CELF-3 contains three highly conserved RNA recognition motifs (RRMs), also known as RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains): two consecutive RRMs (RRM1 and RRM2) situated in the N-terminal region followed by a linker region and the third RRM (RRM3) close to the C-terminus of the protein.The effect of CELF-3 on tau splicing is mediated mainly by the RNA-binding activity of RRM2. The divergent linker region might mediate the interaction of CELF-3 with other proteins regulating its activity or involved in target recognition. CELF-4, highly expressed throughout the brain and in glandular tissues, moderately expressed in heart, skeletal muscle, and liver, is also known as bruno-like protein 4 (BRUNOL-4), or CUG-BP- and ETR-3-like factor 4. Like CELF-3, CELF-4 also contain three highly conserved RRMs. The splicing activation or repression activity of CELF-4 on some specific substrates is mediated by its RRM1/RRM2. On the other hand, both RRM1 and RRM2 of CELF-4 can activate cardiac troponin T (cTNT) exon 5 inclusion. CELF-5, expressed in brain, is also known as bruno-like protein 5 (BRUNOL-5), or CUG-BP- and ETR-3-like factor 5. Although its biological role remains unclear, CELF-5 shares same domain architecture with CELF-3. CELF-6, strongly expressed in kidney, brain, and testis, is also known as bruno-like protein 6 (BRUNOL-6), or CUG-BP- and ETR-3-like factor 6. It activates exon inclusion of a cardiac troponin T minigene in transient transfection assays in an muscle-specific splicing enhancer (MSE)-dependent manner and can activate inclusion via multiple copies of a single element, MSE2. CELF-6 also promotes skipping of exon 11 of insulin receptor, a known target of CELF activity that is expressed in kidney. In additiona to three highly conserved RRMs, CELF-6 also possesses numerous potential phosphorylation sites, a potential nuclear localization signal (NLS) at the C terminus, and an alanine-rich region within the divergent linker region.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 555290149  554 STTLWVGQVDKKATQQDLTNLFEEFGQIESINMIPPR------GCAYVCMVHRQDAFRA 606
Cdd:cd12632     5 AIKLFIGQIPRNLEEKDLRPLFEQFGKIYELTVLKDKytgmhkGCAFLTYCARESALKA 63

RNA recognition motif 2 (RRM2) found in squamous cell carcinoma antigen recognized by T-cells 3 (SART3) and similar proteins; This subfamily corresponds to the RRM2 of SART3, also termed Tat-interacting protein of 110 kDa (Tip110), is an RNA-binding protein expressed in the nucleus of the majority of proliferating cells, including normal cells and malignant cells, but not in normal tissues except for the testes and fetal liver. It is involved in the regulation of mRNA splicing probably via its complex formation with RNA-binding protein with a serine-rich domain (RNPS1), a pre-mRNA-splicing factor. SART3 has also been identified as a nuclear Tat-interacting protein that regulates Tat transactivation activity through direct interaction and functions as an important cellular factor for HIV-1 gene expression and viral replication. In addition, SART3 is required for U6 snRNP targeting to Cajal bodies. It binds specifically and directly to the U6 snRNA, interacts transiently with the U6 and U4/U6 snRNPs, and promotes the reassembly of U4/U6 snRNPs after splicing in vitro. SART3 contains an N-terminal half-a-tetratricopeptide repeat (HAT)-rich domain, a nuclearlocalization signal (NLS) domain, and two C-terminal RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains).

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 555290149  556 TLWVGQVDKKATQQDLTNLFEEFGQIESINMIP-----PRGCAYVCMVHRQDAFRALQKLSsgSYKIGSKVIKIA 625
Cdd:cd12392     4 KLFVKGLPFSCTKEELEELFKQHGTVKDVRLVTyrngkPKGLAYVEYENEADASQAVLKTD--GTEIKDHTISVA 76

RNA recognition motif 1 (RRM1) found in CUGBP Elav-like family member CELF-1, CELF-2, Drosophila melanogaster Bruno protein and similar proteins; This subgroup corresponds to the RRM1 of CELF-1, CELF-2 and Bruno protein. CELF-1 (also termed BRUNOL-2, or CUG-BP1, or EDEN-BP) and CELF-2 (also termed BRUNOL-3, or ETR-3, or CUG-BP2, or NAPOR) belong to the CUGBP1 and ETR-3-like factors (CELF) or BRUNOL (Bruno-like) family of RNA-binding proteins that have been implicated in regulation of pre-mRNA splicing, and control of mRNA translation and deadenylation. CELF-1 is strongly expressed in all adult and fetal tissues tested. The human CELF-1 is a nuclear and cytoplasmic RNA-binding protein that regulates multiple aspects of nuclear and cytoplasmic mRNA processing, with implications for onset of type 1 myotonic dystrophy (DM1), a neuromuscular disease associated with an unstable CUG triplet expansion in the 3'-UTR (3'-untranslated region) of the DMPK (myotonic dystrophy protein kinase) gene; it preferentially targets UGU-rich mRNA elements. It has been shown to bind to a Bruno response element, a cis-element involved in translational control of oskar mRNA in Drosophila, and share sequence similarity to Bruno, the Drosophila protein that mediates this process. The Xenopus homolog embryo deadenylation element-binding protein (EDEN-BP) mediates sequence-specific deadenylation of Eg5 mRNA. It binds specifically to the EDEN motif in the 3'-untranslated regions of maternal mRNAs and targets these mRNAs for deadenylation and translational repression. CELF-1 contain three highly conserved RNA recognition motifs (RRMs), also known as RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains): two consecutive RRMs (RRM1 and RRM2) situated in the N-terminal region followed by a linker region and the third RRM (RRM3) close to the C-terminus of the protein. The two N-terminal RRMs of EDEN-BP are necessary for the interaction with EDEN as well as a part of the linker region (between RRM2 and RRM3). Oligomerization of EDEN-BP is required for specific mRNA deadenylation and binding. CELF-2 is expressed in all tissues at some level, but highest in brain, heart, and thymus. It has been implicated in the regulation of nuclear and cytoplasmic RNA processing events, including alternative splicing, RNA editing, stability and translation. CELF-2 shares high sequence identity with CELF-1, but shows different binding specificity; it binds preferentially to sequences with UG repeats and UGUU motifs. It has been shown to bind to a Bruno response element, a cis-element involved in translational control of oskar mRNA in Drosophila, and share sequence similarity to Bruno, the Drosophila protein that mediates this process. It also binds to the 3'-UTR of cyclooxygenase-2 messages, affecting both translation and mRNA stability, and binds to apoB mRNA, regulating its C to U editing. CELF-2 also contains three highly conserved RRMs. It binds to RNA via the first two RRMs, which are also important for localization in the cytoplasm. The splicing activation or repression activity of CELF-2 on some specific substrates is mediated by RRM1/RRM2. Both, RRM1 and RRM2 of CELF-2, can activate cardiac troponin T (cTNT) exon 5 inclusion. In addition, CELF-2 possesses a typical arginine and lysine-rich nuclear localization signal (NLS) in the C-terminus, within RRM3. This subgroup also includes Drosophila melanogaster Bruno protein, which plays a central role in regulation of Oskar (Osk) expression in flies. It mediates repression by binding to regulatory Bruno response elements (BREs) in the Osk mRNA 3' UTR. The full-length Bruno protein contains three RRMs, two located in the N-terminal half of the protein and the third near the C-terminus, separated by a linker region.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 555290149  557 LWVGQVDKKATQQDLTNLFEEFGQIESINMI------PP--RGCAYVCMVHRQDAFRA 606
Cdd:cd12631     4 MFVGQIPRSWSEKELRELFEQYGAVYQINVLrdrsqnPPqsKGCCFVTFYTRKAALEA 61

RNA recognition motif 2 (RRM2) found in CUGBP Elav-like family member CELF-1, CELF-2 and similar proteins; This subgroup corresponds to the RRM2 of CELF-1 (also termed BRUNOL-2, or CUG-BP1, or EDEN-BP), CELF-2 (also termed BRUNOL-3, or ETR-3, or CUG-BP2, or NAPOR), both of which belong to the CUGBP1 and ETR-3-like factors (CELF) or BRUNOL (Bruno-like) family of RNA-binding proteins that have been implicated in the regulation of pre-mRNA splicing and in the control of mRNA translation and deadenylation. CELF-1 is strongly expressed in all adult and fetal tissues tested. Human CELF-1 is a nuclear and cytoplasmic RNA-binding protein that regulates multiple aspects of nuclear and cytoplasmic mRNA processing, with implications for onset of type 1 myotonic dystrophy (DM1), a neuromuscular disease associated with an unstable CUG triplet expansion in the 3'-UTR (3'-untranslated region) of the DMPK (myotonic dystrophy protein kinase) gene; it preferentially targets UGU-rich mRNA elements. It has been shown to bind to a Bruno response element, a cis-element involved in translational control of oskar mRNA in Drosophila, and share sequence similarity to Bruno, the Drosophila protein that mediates this process. The Xenopus homolog embryo deadenylation element-binding protein (EDEN-BP) mediates sequence-specific deadenylation of Eg5 mRNA. It binds specifically to the EDEN motif in the 3'-untranslated regions of maternal mRNAs and targets these mRNAs for deadenylation and translational repression. CELF-1 contains three highly conserved RNA recognition motifs (RRMs), also known as RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains): two consecutive RRMs (RRM1 and RRM2) situated in the N-terminal region followed by a linker region and the third RRM (RRM3) close to the C-terminus of the protein. The two N-terminal RRMs of EDEN-BP are necessary for the interaction with EDEN as well as a part of the linker region (between RRM2 and RRM3). Oligomerization of EDEN-BP is required for specific mRNA deadenylation and binding. CELF-2 is expressed in all tissues at some level, but highest in brain, heart, and thymus. It has been implicated in the regulation of nuclear and cytoplasmic RNA processing events, including alternative splicing, RNA editing, stability and translation. CELF-2 shares high sequence identity with CELF-1, but shows different binding specificity; it preferentially binds to sequences with UG repeats and UGUU motifs. It has been shown to bind to a Bruno response element, a cis-element involved in translational control of oskar mRNA in Drosophila, and share sequence similarity to Bruno, the Drosophila protein that mediates this process. It also binds to the 3'-UTR of cyclooxygenase-2 messages, affecting both translation and mRNA stability, and binds to apoB mRNA, regulating its C to U editing. CELF-2 also contains three highly conserved RRMs. It binds to RNA via the first two RRMs, which are also important for localization in the cytoplasm. The splicing activation or repression activity of CELF-2 on some specific substrates is mediated by RRM1/RRM2. Both, RRM1 and RRM2 of CELF-2, can activate cardiac troponin T (cTNT) exon 5 inclusion. In addition, CELF-2 possesses a typical arginine and lysine-rich nuclear localization signal (NLS) in the C-terminus, within RRM3.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 555290149  557 LWVGQVDKKATQQDLTNLFEEFGQIESINMIP-----PRGCAYVCMVHR---QDAFRALQK 609
Cdd:cd12634     4 LFIGMVSKKCNENDIRVMFSPFGQIEECRILRgpdglSRGCAFVTFSTRamaQNAIKAMHQ 64

RNA recognition motif 2 (RRM2) found in RNA-binding protein 28 (RBM28) and similar proteins; This subfamily corresponds to the RRM2 of RBM28 and Nop4p. RBM28 is a specific nucleolar component of the spliceosomal small nuclear ribonucleoproteins (snRNPs), possibly coordinating their transition through the nucleolus. It specifically associates with U1, U2, U4, U5, and U6 small nuclear RNAs (snRNAs), and may play a role in the maturation of both small nuclear and ribosomal RNAs. RBM28 has four RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), and an extremely acidic region between RRM2 and RRM3. The family also includes nucleolar protein 4 (Nop4p or Nop77p) encoded by YPL043W from Saccharomyces cerevisiae. It is an essential nucleolar protein involved in processing and maturation of 27S pre-rRNA and biogenesis of 60S ribosomal subunits. Nop4p also contains four RRMs.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 555290149  565 KATQQDLTNLFEEFGQIESINmIP------PRGCAYVCMVHRQDAFRALQKLSsgSYKIGSKVIKIAWAL 628
Cdd:cd12414    10 KCTEDDLKKLFSKFGKVLEVT-IPkkpdgkLRGFAFVQFTNVADAAKAIKGMN--GKKIKGRPVAVDWAV 76

large tegument protein UL36; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 555290149  796 PSLSMTPETVKDVGFGSLVIPGGSVASNLATSALPAgnvfnAPTKQAEPEEKVPHLIDHQISSGENTRSviPNDISSNAA 875
Cdd:PHA03247 2702 PPPPPTPEPAPHALVSATPLPPGPAAARQASPALPA-----APAPPAVPAGPATPGGPARPARPPTTAG--PPAPAPPAA 2774

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 555290149  876 ILGGQPPNVTsnsgilgvqRPNVSSNSEILGVRPSNVSSSSGIIAAQPPNILNNSGIL---GIQPPSVS---NSSGLLGV 949
Cdd:PHA03247 2775 PAAGPPRRLT---------RPAVASLSESRESLPSPWDPADPPAAVLAPAAALPPAASpagPLPPPTSAqptAPPPPPGP 2845

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 555290149  950 LPPNIPNNSGLV----------GVQPPNVPNTPGLL--------GTQPPAGPQNLPPLSIPNQRMPTMPMldiRPGLIPQ 1011
Cdd:PHA03247 2846 PPPSLPLGGSVApggdvrrrppSRSPAAKPAAPARPpvrrlarpAVSRSTESFALPPDQPERPPQPQAPP---PPQPQPQ 2922

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 555290149 1012 APGPRFPLIQPGIPPQRGIPPPSVLDSAlhppprGPFPPGDIFSQPERPFLAPGRQSVDNVTNPEKRIPLGNDNIQQEGD 1091
Cdd:PHA03247 2923 PPPPPQPQPPPPPPPRPQPPLAPTTDPA------GAGEPSGAVPQPWLGALVPGRVAVPRFRVPQPAPSREAPASSTPPL 2996

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 555290149 1092 RDYRFPPIETRESI------SRPPPVDVRDVV-------------------------------GRPIDPREGPGRPPL-- 1132
Cdd:PHA03247 2997 TGHSLSRVSSWASSlalheeTDPPPVSLKQTLwppddtedsdadslfdsdsersdlealdplpPEPHDPFAHEPDPATpe 3076

                         410       420       430
                  ....*....|....*....|....*....|..
gi 555290149 1133 -----DGRDHFGRPPVDIRENLVRPGIDHLGR 1159
Cdd:PHA03247 3077 agareSPSSQFGPPPLSANAALSRRYVRSTGR 3108

RNA recognition motif (RRM) found in yeast pre-mRNA-splicing factor Cwc2 and similar proteins; This subfamily corresponds to the RRM of yeast protein Cwc2, also termed Complexed with CEF1 protein 2, or PRP19-associated complex protein 40 (Ntc40), or synthetic lethal with CLF1 protein 3, one of the components of the Prp19-associated complex [nineteen complex (NTC)] that can bind to RNA. NTC is composed of the scaffold protein Prp19 and a number of associated splicing factors, and plays a crucial role in intron removal during premature mRNA splicing in eukaryotes. Cwc2 functions as an RNA-binding protein that can bind both small nuclear RNAs (snRNAs) and pre-mRNA in vitro. It interacts directly with the U6 snRNA to link the NTC to the spliceosome during pre-mRNA splicing. In the N-terminal half, Cwc2 contains a CCCH-type zinc finger (ZnF domain), a RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain), and an intervening loop, also termed RNA-binding loop or RB loop, between ZnF and RRM, all of which are necessary and sufficient for RNA binding. The ZnF is also responsible for mediating protein-protein interaction. The C-terminal flexible region of Cwc2 interacts with the WD40 domain of Prp19.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 555290149  556 TLWVGQVD-KKATQQDLTNL----FEEFGQIESINMIPPRGCAYVCMVHRQDAFRALQKLSSGSYKiGSKVIKIAWA 627
Cdd:cd12360     3 TLYVGGIKaASNKLAQIEEIlrrhFGEWGEIERIRVLPSKGIAFVRYKNRANAEFAKEAMADQSLD-GGEVLNVRWA 78

RNA recognition motif 1 (RRM1) found in yeast nucleolar protein 4 (Nop4p) and similar proteins; This subgroup corresponds to the RRM1 of Nop4p (also known as Nop77p), encoded by YPL043W from Saccharomyces cerevisiae. It is an essential nucleolar protein involved in processing and maturation of 27S pre-rRNA and biogenesis of 60S ribosomal subunits. Nop4p has four RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains).

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 555290149  555 TTLWVGQVDKKATQQDLTNLFEEFGQIESINMI------PPRGCAYVCMVHRQDAFRALQKLSsgSYKIGSKVIKIAWA 627
Cdd:cd12674     1 TTLFVRNLPFDVTLESLTDFFSDIGPVKHAVVVtdpetkKSRGYGFVSFSTHDDAEEALAKLK--NRKLSGHILKLDFA 77

RNA recognition motif 3 in fungal pre-messenger RNA splicing protein 24 (Prp24) and similar proteins; This subfamily corresponds to the RRM3 of Prp24, also termed U4/U6 snRNA-associated-splicing factor PRP24 (U4/U6 snRNP), an RNA-binding protein with four well conserved RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains). It facilitates U6 RNA base-pairing with U4 RNA during spliceosome assembly. Prp24 specifically binds free U6 RNA primarily with RRMs 1 and 2 and facilitates pairing of U6 RNA bases with U4 RNA bases. Additionally, it may also be involved in dissociation of the U4/U6 complex during spliceosome activation.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 555290149  563 DKKATQQDLTNLFEEFGQIESINMiPP----------RGCAYVCMVHRQDAFRALQK 609
Cdd:cd12298     9 DFELDEEALRGIFEKFGEIESINI-PKkqknrkgrhnNGFAFVTFEDADSAESALQL 64

RNA recognition motif 2 (RRM2) found in Drosophila sex-lethal (SXL) and similar proteins; This subfamily corresponds to the RRM2 of the sex-lethal protein (SXL) which governs sexual differentiation and X chromosome dosage compensation in Drosophila melanogaster. It induces female-specific alternative splicing of the transformer (tra) pre-mRNA by binding to the tra uridine-rich polypyrimidine tract at the non-sex-specific 3' splice site during the sex-determination process. SXL binds also to its own pre-mRNA and promotes female-specific alternative splicing. SXL contains an N-terminal Gly/Asn-rich domain that may be responsible for the protein-protein interaction, and tandem RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), that show high preference to bind single-stranded, uridine-rich target RNA transcripts.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 555290149  555 TTLWVGQVDKKATQQDLTNLFEEFGQIESINMIP------PRGCAYVCMVHRQDAFRALQKLSSGSYKIGSKVIKIAWA 627
Cdd:cd12651     3 TNLYVTNLPRTITEDELDTIFGAYGNIVQKNLLRdkltgrPRGVAFVRYDKREEAQAAISALNGTIPEGGTQPLSVRLA 81

RNA recognition motif 3 (RRM3) found in Schizosaccharomyces pombe mRNA export factor Crp79, meiotically up-regulated gene 28 protein (Mug28) and similar proteins; Crp79, also called meiotic expression up-regulated protein 5 (Mug5), or polyadenylate-binding protein crp79, or PABP, or poly(A)-binding protein, is an auxiliary mRNA export factor that binds the poly(A) tail of mRNA and is involved in the export of mRNA from the nucleus to the cytoplasm. Mug28 is a meiosis-specific protein that regulates spore wall formation. Members in this family contain three RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains). The model corresponds to the three RRM motif.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 555290149  557 LWVGQVDKK--ATQQDLTNLFEEFGQIES--INMIP----PRGCAYVCMVHRQDAFRALQKLSsgSYKIGSKVIKIAWAL 628
Cdd:cd21622     6 LFVKNLDDTviTNKEDLEQLFSPFGQIVSsyLATYPgtgiSKGFGFVAFSKPEDAAKAKETLN--GVMVGRKRIFVSYAE 83

                  ..
gi 555290149  629 NK 630
Cdd:cd21622    84 RK 85

RNA recognition motif 2 (RRM2) found in RNA-binding protein MRN1 and similar proteins; This subgroup corresponds to the RRM2 of MRN1, also termed multicopy suppressor of RSC-NHP6 synthetic lethality protein 1, or post-transcriptional regulator of 69 kDa, which is a RNA-binding protein found in yeast. Although its specific biological role remains unclear, MRN1 might be involved in translational regulation. Members in this family contain four copies of conserved RNA recognition motif (RRM), also known as RBD (RNA binding domain) or RNP (ribonucleoprotein domain).

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 555290149  554 STTLWVGQVDKKATQQDLTNLFEEFGQIESINMIPPRGCAYVCMVHRQDAFRALQKLS 611
Cdd:cd12523     3 SRNVYLGNLPESITEEELREDLEKFGPIDQIKIVKEKNIAFVHFLSIANAIKVVTTLP 60