RNA recognition motif 1 (RRM1) found in vertebrate U1 small nuclear ribonucleoprotein A (U1A); This subgroup corresponds to the RRM1 of U1A (also termed U1 snRNP A or U1-A), an RNA-binding protein associated with the U1 snRNP, a small RNA-protein complex involved in pre-mRNA splicing. U1A binds with high affinity and specificity to stem-loop II (SLII) of U1 snRNA. It is predominantly a nuclear protein and it also shuttles between the nucleus and the cytoplasm independently of interactions with U1 snRNA. U1A may be involved in RNA 3'-end processing, specifically cleavage, splicing and polyadenylation, through interacting with a large number of non-snRNP proteins, including polypyrimidine tract binding protein (PTB), polypyrimidine-tract binding protein-associated factor (PSF), and non-POU-domain-containing, octamer-binding (NONO), DEAD (Asp-Glu-Ala-Asp) box polypeptide 5 (DDX5). It also binds to a flavivirus NS5 protein and plays an important role in virus replication. U1A contains two RNA recognition motifs (RRMs); the N-terminal RRM (RRM1) binds tightly and specifically to the U1 snRNA SLII and its own 3'-UTR, while in contrast, the C-terminal RRM (RRM2) does not appear to associate with any RNA and may be free to bind other proteins. U1A also contains a proline-rich region, and a nuclear localization signal (NLS) in the central domain that is responsible for its nuclear import.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 383873129   7 RPNHTIYINNLNEKIKKDELKKSLYAIFSQFGQILDILVSRSLKMRGQAFVIFKEVSSATNALRSMQGFPFYDKPMRIQY 86
Cdd:cd12477    1 RPNHTIYINNLNEKIKKDELKKSLHAIFSRFGQILDILVSRSLKMRGQAFVIFKEVSSATNALRSMQGFPFYDKPMRIQY 80

                 ....*....
gi 383873129  87 AKTDSDIIA 95
Cdd:cd12477   81 AKTDSDIIA 89

RNA recognition motif 1 (RRM1) found in vertebrate U1 small nuclear ribonucleoprotein A (U1A); This subgroup corresponds to the RRM1 of U1A (also termed U1 snRNP A or U1-A), an RNA-binding protein associated with the U1 snRNP, a small RNA-protein complex involved in pre-mRNA splicing. U1A binds with high affinity and specificity to stem-loop II (SLII) of U1 snRNA. It is predominantly a nuclear protein and it also shuttles between the nucleus and the cytoplasm independently of interactions with U1 snRNA. U1A may be involved in RNA 3'-end processing, specifically cleavage, splicing and polyadenylation, through interacting with a large number of non-snRNP proteins, including polypyrimidine tract binding protein (PTB), polypyrimidine-tract binding protein-associated factor (PSF), and non-POU-domain-containing, octamer-binding (NONO), DEAD (Asp-Glu-Ala-Asp) box polypeptide 5 (DDX5). It also binds to a flavivirus NS5 protein and plays an important role in virus replication. U1A contains two RNA recognition motifs (RRMs); the N-terminal RRM (RRM1) binds tightly and specifically to the U1 snRNA SLII and its own 3'-UTR, while in contrast, the C-terminal RRM (RRM2) does not appear to associate with any RNA and may be free to bind other proteins. U1A also contains a proline-rich region, and a nuclear localization signal (NLS) in the central domain that is responsible for its nuclear import.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 383873129   7 RPNHTIYINNLNEKIKKDELKKSLYAIFSQFGQILDILVSRSLKMRGQAFVIFKEVSSATNALRSMQGFPFYDKPMRIQY 86
Cdd:cd12477    1 RPNHTIYINNLNEKIKKDELKKSLHAIFSRFGQILDILVSRSLKMRGQAFVIFKEVSSATNALRSMQGFPFYDKPMRIQY 80

                 ....*....
gi 383873129  87 AKTDSDIIA 95
Cdd:cd12477   81 AKTDSDIIA 89

RNA recognition motif;

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 383873129    11 TIYINNLNEKIKKDELKKslyaIFSQFGQILDILVSR---SLKMRGQAFVIFKEVSSATNALRSMQGFPFYDKPMRI 84
Cdd:smart00360   1 TLFVGNLPPDTTEEELRE----LFSKFGKVESVRLVRdkeTGKSKGFAFVEFESEEDAEKALEALNGKELDGRPLKV 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 383873129   12 IYINNLNEKIKKDELKKslyaIFSQFGQILDILVSRSL--KMRGQAFVIFKEVSSATNALRSMQGFPFYDKPMR 83
Cdd:pfam00076   1 LFVGNLPPDTTEEDLKD----LFSKFGPIKSIRLVRDEtgRSKGFAFVEFEDEEDAEKAIEALNGKELGGRELK 70

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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 383873129   12 IYINNLNEKIKKDELKKslyaIFSQFGQILD--ILVSRSLKMRGQAFVIFKEVSSATNALRSMQGFPFYDKPMRIQYAKT 89
Cdd:TIGR01628 288 LYVKNLDDTVTDEKLRE----LFSECGEITSakVMLDEKGVSRGFGFVCFSNPEEANRAVTEMHGRMLGGKPLYVALAQR 363

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 383873129   90 DSDIIAKMKGTFVE-RDRKREKRKPKSQETPATKKAVQGGGAAPVVGAVQGPVPGMPPM--TQAPRIMHHMPGQPPYMPP 166
Cdd:TIGR01628 364 KEQRRAHLQDQFMQlQPRMRQLPMGSPMGGAMGQPPYYGQGPQQQFNGQPLGWPRMSMMptPMGPGGPLRPNGLAPMNAV 443

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 383873129  167 PGMIPPPGLAPGQIPPGAMP-----PQQLMPGQMPPAQPLSENPPNHILFLTNLPEETNELMLSML 227
Cdd:TIGR01628 444 RAPSRNAQNAAQKPPMQPVMyppnyQSLPLSQDLPQPQSTASQGGQNKKLAQVLASATPQMQKQVL 509

heterogeneous nuclear ribonucleoprotein R, Q family; Sequences in this subfamily include the human heterogeneous nuclear ribonucleoproteins (hnRNP) R, Q, and APOBEC-1 complementation factor (aka APOBEC-1 stimulating protein). These proteins contain three RNA recognition domains (rrm: pfam00076) and a somewhat variable C-terminal domain.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 383873129  184 AMPPQQLMPGQMPP---------AQPLSENPPN-----HILFLTNLPEETNELMLSMLFNQF-PGfkEVRLVPGRHDIAF 248
Cdd:TIGR01648 196 AMARRKLMPGRIQLwghviavdwAEPEEEVDEDvmakvKILYVRNLMTTTTEEIIEKSFSEFkPG--KVERVKKIRDYAF 273

                          90       100       110
                  ....*....|....*....|....*....|...
gi 383873129  249 VEFDNEVQAGAARDALQGfKITQNNAMKISFAK 281
Cdd:TIGR01648 274 VHFEDREDAVKAMDELNG-KELEGSEIEVTLAK 305

RNA recognition motif 1 (RRM1) found in vertebrate U1 small nuclear ribonucleoprotein A (U1A); This subgroup corresponds to the RRM1 of U1A (also termed U1 snRNP A or U1-A), an RNA-binding protein associated with the U1 snRNP, a small RNA-protein complex involved in pre-mRNA splicing. U1A binds with high affinity and specificity to stem-loop II (SLII) of U1 snRNA. It is predominantly a nuclear protein and it also shuttles between the nucleus and the cytoplasm independently of interactions with U1 snRNA. U1A may be involved in RNA 3'-end processing, specifically cleavage, splicing and polyadenylation, through interacting with a large number of non-snRNP proteins, including polypyrimidine tract binding protein (PTB), polypyrimidine-tract binding protein-associated factor (PSF), and non-POU-domain-containing, octamer-binding (NONO), DEAD (Asp-Glu-Ala-Asp) box polypeptide 5 (DDX5). It also binds to a flavivirus NS5 protein and plays an important role in virus replication. U1A contains two RNA recognition motifs (RRMs); the N-terminal RRM (RRM1) binds tightly and specifically to the U1 snRNA SLII and its own 3'-UTR, while in contrast, the C-terminal RRM (RRM2) does not appear to associate with any RNA and may be free to bind other proteins. U1A also contains a proline-rich region, and a nuclear localization signal (NLS) in the central domain that is responsible for its nuclear import.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 383873129   7 RPNHTIYINNLNEKIKKDELKKSLYAIFSQFGQILDILVSRSLKMRGQAFVIFKEVSSATNALRSMQGFPFYDKPMRIQY 86
Cdd:cd12477    1 RPNHTIYINNLNEKIKKDELKKSLHAIFSRFGQILDILVSRSLKMRGQAFVIFKEVSSATNALRSMQGFPFYDKPMRIQY 80

                 ....*....
gi 383873129  87 AKTDSDIIA 95
Cdd:cd12477   81 AKTDSDIIA 89

RNA recognition motif 2 (RRM2) found in vertebrate U1 small nuclear ribonucleoprotein A (U1 snRNP A or U1-A or U1A); This subgroup corresponds to the RRM2 of U1A (also termed U1 snRNP A or U1-A), an RNA-binding protein associated with the U1 snRNP, a small RNA-protein complex involved in pre-mRNA splicing. U1A binds with high affinity and specificity to stem-loop II (SLII) of U1 snRNA. It is predominantly a nuclear protein that shuttles between the nucleus and the cytoplasm independently of interactions with U1 snRNA. U1A may be involved in RNA 3'-end processing, specifically cleavage, splicing and polyadenylation, through interacting with a large number of non-snRNP proteins, including polypyrimidine tract binding protein (PTB), polypyrimidine-tract binding protein-associated factor (PSF), and non-POU-domain-containing, octamer-binding (NONO), DEAD (Asp-Glu-Ala-Asp) box polypeptide 5 (DDX5). U1A also binds to a flavivirus NS5 protein and plays an important role in virus replication. It contains two RNA recognition motifs (RRMs); the N-terminal RRM (RRM1) binds tightly and specifically to the U1 snRNA SLII and its own 3'-UTR, while in contrast, the C-terminal RRM (RRM2) does not appear to associate with any RNA and it may be free for binding other proteins. U1A also contains a proline-rich region, and a nuclear localization signal (NLS) in the central domain that is responsible for its nuclear import.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 383873129 197 PAQPLSENPPNHILFLTNLPEETNELMLSMLFNQFPGFKEVRLVPGRHDIAFVEFDNEVQAGAARDALQGFKITQNNAMK 276
Cdd:cd12480    1 PPQPVSENPPNHILFLTNLPEETNELMLSMLFNQFPGFKEVRLVPGRHDIAFVEFDNEVQAGAAREALQGFKITQSNAMK 80

                 ....*.
gi 383873129 277 ISFAKK 282
Cdd:cd12480   81 ISFAKK 86

RNA recognition motif 1 (RRM1) found in Drosophila melanogaster sex determination protein SNF and similar proteins; This subgroup corresponds to the RRM1 of SNF (Sans fille), also termed U1 small nuclear ribonucleoprotein A (U1 snRNP A or U1-A or U1A), an RNA-binding protein found in the U1 and U2 snRNPs of Drosophila. It is essential in Drosophila sex determination and possesses a novel dual RNA binding specificity. SNF binds with high affinity to both Drosophila U1 snRNA stem-loop II (SLII) and U2 snRNA stem-loop IV (SLIV). It can also bind to poly(U) RNA tracts flanking the alternatively spliced Sex-lethal (Sxl) exon, as does Drosophila Sex-lethal protein (SXL). SNF contains two RNA recognition motifs (RRMs); it can self-associate through RRM1, and each RRM can recognize poly(U) RNA binding independently.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 383873129   5 ETRPNHTIYINNLNEKIKKDELKKSLYAIFSQFGQILDILVSRSLKMRGQAFVIFKEVSSATNALRSMQGFPFYDKPMRI 84
Cdd:cd12476    2 DIRPNQTIYINNLNEKVKKEELKKSLYAIFSQFGQILDIVALKTLKMRGQAFVIFKDISSATNALRSMQGFPFYDKPMRI 81

                 ....
gi 383873129  85 QYAK 88
Cdd:cd12476   82 AYSK 85

RNA recognition motif 2 (RRM2) found in Drosophila melanogaster sex determination protein SNF and similar proteins; This subgroup corresponds to the RRM2 of SNF (Sans fille), also termed U1 small nuclear ribonucleoprotein A (U1 snRNP A or U1-A or U1A), an RNA-binding protein found in the U1 and U2 snRNPs of Drosophila. It is essential in Drosophila sex determination and possesses a novel dual RNA binding specificity. SNF binds with high affinity to both Drosophila U1 snRNA stem-loop II (SLII) and U2 snRNA stem-loop IV (SLIV). It can also bind to poly(U) RNA tracts flanking the alternatively spliced Sex-lethal (Sxl) exon, as does Drosophila Sex-lethal protein (SXL). SNF contains two RNA recognition motifs (RRMs); it can self-associate through RRM1, and each RRM can recognize poly(U) RNA binding independently.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 383873129 203 ENPPNHILFLTNLPEETNELMLSMLFNQFPGFKEVRLVPGRHDIAFVEFDNEVQAGAARDALQGFKITQNNAMKISFAKK 282
Cdd:cd12479    1 EQPPNQILFLTNLPEETNEMMLSMLFNQFPGFKEVRLVPGRHDIAFVEFENEVQSAAAKEALQGFKITPTHAMKITFAKK 80

RNA recognition motif;

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 383873129    11 TIYINNLNEKIKKDELKKslyaIFSQFGQILDILVSR---SLKMRGQAFVIFKEVSSATNALRSMQGFPFYDKPMRI 84
Cdd:smart00360   1 TLFVGNLPPDTTEEELRE----LFSKFGKVESVRLVRdkeTGKSKGFAFVEFESEEDAEKALEALNGKELDGRPLKV 73

RNA recognition motif (RRM) superfamily; RRM, also known as RBD (RNA binding domain) or RNP (ribonucleoprotein domain), is a highly abundant domain in eukaryotes found in proteins involved in post-transcriptional gene expression processes including mRNA and rRNA processing, RNA export, and RNA stability. This domain is 90 amino acids in length and consists of a four-stranded beta-sheet packed against two alpha-helices. RRM usually interacts with ssRNA, but is also known to interact with ssDNA as well as proteins. RRM binds a variable number of nucleotides, ranging from two to eight. The active site includes three aromatic side-chains located within the conserved RNP1 and RNP2 motifs of the domain. The RRM domain is found in a variety heterogeneous nuclear ribonucleoproteins (hnRNPs), proteins implicated in regulation of alternative splicing, and protein components of small nuclear ribonucleoproteins (snRNPs).

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 383873129  12 IYINNLNEKIKKDELKKslyaIFSQFGQILDILV--SRSLKMRGQAFVIFKEVSSATNALRSMQGFPFYDKPMRIQ 85
Cdd:cd00590    1 LFVGNLPPDTTEEDLRE----LFSKFGEVVSVRIvrDRDGKSKGFAFVEFESPEDAEKALEALNGTELGGRPLKVS 72

RNA recognition motif 2 (RRM2) found in RNA-binding protein 40 (RBM40) and similar proteins; This subfamily corresponds to the RRM2 of RBM40 and the RRM of RBM41. RBM40, also known as RNA-binding region-containing protein 3 (RNPC3) or U11/U12 small nuclear ribonucleoprotein 65 kDa protein (U11/U12-65K protein). It serves as a bridging factor between the U11 and U12 snRNPs. It contains two RNA recognition motifs (RRMs), also known as RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), connected by a linker that includes a proline-rich region. It binds to the U11-associated 59K protein via its RRM1 and employs the RRM2 to bind hairpin III of the U12 small nuclear RNA (snRNA). The proline-rich region might be involved in protein-protein interactions. RBM41 contains only one RRM. Its biological function remains unclear.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 383873129   9 NHTIYINNLNEKIKKDELKkSLYAIFSQFGQI----LDILVSRSLKMRGQAFVIFKEVSSATNALRSMQGFPFYDKPMRI 84
Cdd:cd12239    1 SNRLYVKNLSKRVSEKDLK-YIFGRFVDSSSEeknmFDIRLMTEGRMKGQAFITFPSEELAEKALNLTNGYVLHGKPMVV 79

                 ...
gi 383873129  85 QYA 87
Cdd:cd12239   80 QFA 82

RNA recognition motif (RRM) found in yeast cell wall integrity protein scw1 and similar proteins; This subfamily corresponds to the RRM of the family including yeast cell wall integrity protein scw1, yeast Whi3 protein, yeast Whi4 protein and similar proteins. The strong cell wall protein 1, scw1, is a nonessential cytoplasmic RNA-binding protein that regulates septation and cell-wall structure in fission yeast. It may function as an inhibitor of septum formation, such that its loss of function allows weak SIN signaling to promote septum formation. It's RRM domain shows high homology to two budding yeast proteins, Whi3 and Whi4. Whi3 is a dose-dependent modulator of cell size and has been implicated in cell cycle control in the yeast Saccharomyces cerevisiae. It functions as a negative regulator of ceroid-lipofuscinosis, neuronal 3 (Cln3), a G1 cyclin that promotes transcription of many genes to trigger the G1/S transition in budding yeast. It specifically binds the CLN3 mRNA and localizes it into discrete cytoplasmic loci that may locally restrict Cln3 synthesis to modulate cell cycle progression. Moreover, Whi3 plays a key role in cell fate determination in budding yeast. The RRM domain is essential for Whi3 function. Whi4 is a partially redundant homolog of Whi3, also containing one RRM. Some uncharacterized family members of this subfamily contain two RRMs; their RRM1 shows high sequence homology to the RRM of RNA-binding protein with multiple splicing (RBP-MS)-like proteins.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 383873129 210 LFLTNLPEETNELMLSMLFNQFPGFKEVRLV-PGRHDIAFVEFDNEVQAGAARDALQGFKITQNN--AMKISFAK 281
Cdd:cd12245    5 LFVANLGPNVSEQELRQLFSRQPGFRRLRMHnKGGGPVCFVEFEDVPFATQALNHLQGAILSSSDrgGIRIEYAK 79

RNA recognition motif;

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 383873129   210 LFLTNLPEETNELMLSMLFNQFPGFKEVRLVPGRHD-----IAFVEFDNEVQAGAARDALQGFKI 269
Cdd:smart00360   2 LFVGNLPPDTTEEELRELFSKFGKVESVRLVRDKETgkskgFAFVEFESEEDAEKALEALNGKEL 66

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 383873129  11 TIYINNLNEKIKKDELKKSlyaiFSQFGQILDIlvsRSLKMRGQAFVIFKEVSSATNALRSMQGFPFYDKPMR 83
Cdd:cd12354    2 TVYVGNITKGLTEALLQQT----FSPFGQILEV---RVFPDKGYAFIRFDSHEAATHAIVSVNGTIINGQAVK 67

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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 383873129   12 IYINNLNEKIKKDELKKslyaIFSQFGQILD--ILVSRSLKMRGQAFVIFKEVSSATNALRSMQGFPFYDKPMRIQYAKT 89
Cdd:TIGR01628 288 LYVKNLDDTVTDEKLRE----LFSECGEITSakVMLDEKGVSRGFGFVCFSNPEEANRAVTEMHGRMLGGKPLYVALAQR 363

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 383873129   90 DSDIIAKMKGTFVE-RDRKREKRKPKSQETPATKKAVQGGGAAPVVGAVQGPVPGMPPM--TQAPRIMHHMPGQPPYMPP 166
Cdd:TIGR01628 364 KEQRRAHLQDQFMQlQPRMRQLPMGSPMGGAMGQPPYYGQGPQQQFNGQPLGWPRMSMMptPMGPGGPLRPNGLAPMNAV 443

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 383873129  167 PGMIPPPGLAPGQIPPGAMP-----PQQLMPGQMPPAQPLSENPPNHILFLTNLPEETNELMLSML 227
Cdd:TIGR01628 444 RAPSRNAQNAAQKPPMQPVMyppnyQSLPLSQDLPQPQSTASQGGQNKKLAQVLASATPQMQKQVL 509

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 383873129  14 INNLNEKIKKDELKKslyaIFSQFGQILDILVSRSL--KMRGQAFVIFKEVSSATNALRSMQGFPFYDKPMRIQYA 87
Cdd:cd12414    4 VRNLPFKCTEDDLKK----LFSKFGKVLEVTIPKKPdgKLRGFAFVQFTNVADAAKAIKGMNGKKIKGRPVAVDWA 75

RNA recognition motif (RRM) found in cyclophilin-33 (Cyp33) and similar proteins; This subfamily corresponds to the RRM of Cyp33, also termed peptidyl-prolyl cis-trans isomerase E (PPIase E), or cyclophilin E, or rotamase E. Cyp33 is a nuclear RNA-binding cyclophilin with an N-terminal RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain), and a C-terminal PPIase domain. Cyp33 possesses RNA-binding activity and preferentially binds to polyribonucleotide polyA and polyU, but hardly to polyG and polyC. It binds specifically to mRNA, which can stimulate its PPIase activity. Moreover, Cyp33 interacts with the third plant homeodomain (PHD3) zinc finger cassette of the mixed lineage leukemia (MLL) proto-oncoprotein and a poly-A RNA sequence through its RRM domain. It further mediates downregulation of the expression of MLL target genes HOXC8, HOXA9, CDKN1B, and C-MYC, in a proline isomerase-dependent manner. Cyp33 also possesses a PPIase activity that catalyzes cis-trans isomerization of the peptide bond preceding a proline, which has been implicated in the stimulation of folding and conformational changes in folded and unfolded proteins. The PPIase activity can be inhibited by the immunosuppressive drug cyclosporin A.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 383873129  12 IYINNLNEKIkkDElkKSLYAIFSQFGQILDILV---SRSLKMRGQAFVIFKEVSSATNALRSMQGFPFYDKPMRIQYA 87
Cdd:cd12347    1 LYVGGLAEEV--DE--KVLHAAFIPFGDIVDIQIpldYETEKHRGFAFVEFEEAEDAAAAIDNMNESELFGRTIRVNLA 75

RNA recognition motif (RRM) domain [Translation, ribosomal structure and biogenesis];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 383873129  11 TIYINNLNEKIKKDELKkslyAIFSQFGQILDILVSR---SLKMRGQAFVIFKEVSSATNALRSMQGFPFYDKPMRIQYA 87
Cdd:COG0724    3 KIYVGNLPYSVTEEDLR----ELFSEYGEVTSVKLITdreTGRSRGFGFVEMPDDEEAQAAIEALNGAELMGRTLKVNEA 78

                 .
gi 383873129  88 K 88
Cdd:COG0724   79 R 79

RNA recognition motif (RRM) found in yeast cell wall integrity protein scw1 and similar proteins; This subfamily corresponds to the RRM of the family including yeast cell wall integrity protein scw1, yeast Whi3 protein, yeast Whi4 protein and similar proteins. The strong cell wall protein 1, scw1, is a nonessential cytoplasmic RNA-binding protein that regulates septation and cell-wall structure in fission yeast. It may function as an inhibitor of septum formation, such that its loss of function allows weak SIN signaling to promote septum formation. It's RRM domain shows high homology to two budding yeast proteins, Whi3 and Whi4. Whi3 is a dose-dependent modulator of cell size and has been implicated in cell cycle control in the yeast Saccharomyces cerevisiae. It functions as a negative regulator of ceroid-lipofuscinosis, neuronal 3 (Cln3), a G1 cyclin that promotes transcription of many genes to trigger the G1/S transition in budding yeast. It specifically binds the CLN3 mRNA and localizes it into discrete cytoplasmic loci that may locally restrict Cln3 synthesis to modulate cell cycle progression. Moreover, Whi3 plays a key role in cell fate determination in budding yeast. The RRM domain is essential for Whi3 function. Whi4 is a partially redundant homolog of Whi3, also containing one RRM. Some uncharacterized family members of this subfamily contain two RRMs; their RRM1 shows high sequence homology to the RRM of RNA-binding protein with multiple splicing (RBP-MS)-like proteins.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 383873129   8 PNHTIYINNLNEKIKKDELKKsLYAIFSQFgqildilvsRSLKMRGQ-----AFVIFKEVSSATNALRSMQGF--PFYDK 80
Cdd:cd12245    1 PCNTLFVANLGPNVSEQELRQ-LFSRQPGF---------RRLRMHNKgggpvCFVEFEDVPFATQALNHLQGAilSSSDR 70

                 ....*....
gi 383873129  81 -PMRIQYAK 88
Cdd:cd12245   71 gGIRIEYAK 79

RNA recognition motif (RRM) found in polypyrimidine tract-binding protein 1 (PTB or hnRNP I), heterogeneous nuclear ribonucleoprotein L (hnRNP-L), and similar proteins; This subfamily corresponds to the RRM2 of polypyrimidine tract-binding protein 1 (PTB or hnRNP I), polypyrimidine tract-binding protein 2 (PTBP2 or nPTB), regulator of differentiation 1 (Rod1), heterogeneous nuclear ribonucleoprotein L (hnRNP-L), heterogeneous nuclear ribonucleoprotein L-like (hnRNP-LL), polypyrimidine tract-binding protein homolog 3 (PTBPH3), polypyrimidine tract-binding protein homolog 1 and 2 (PTBPH1 and PTBPH2), and similar proteins, and RRM3 of PTBPH1 and PTBPH2. PTB is an important negative regulator of alternative splicing in mammalian cells and also functions at several other aspects of mRNA metabolism, including mRNA localization, stabilization, polyadenylation, and translation. PTBP2 is highly homologous to PTB and is perhaps specific to the vertebrates. Unlike PTB, PTBP2 is enriched in the brain and in some neural cell lines. It binds more stably to the downstream control sequence (DCS) RNA than PTB does but is a weaker repressor of splicing in vitro. PTBP2 also greatly enhances the binding of two other proteins, heterogeneous nuclear ribonucleoprotein (hnRNP) H and KH-type splicing-regulatory protein (KSRP), to the DCS RNA. The binding properties of PTBP2 and its reduced inhibitory activity on splicing imply roles in controlling the assembly of other splicing-regulatory proteins. Rod1 is a mammalian polypyrimidine tract binding protein (PTB) homolog of a regulator of differentiation in the fission yeast Schizosaccharomyces pombe, where the nrd1 gene encodes an RNA binding protein negatively regulates the onset of differentiation. ROD1 is predominantly expressed in hematopoietic cells or organs. It might play a role controlling differentiation in mammals. hnRNP-L is a higher eukaryotic specific subunit of human KMT3a (also known as HYPB or hSet2) complex required for histone H3 Lys-36 trimethylation activity. It plays both, nuclear and cytoplasmic, roles in mRNA export of intronless genes, IRES-mediated translation, mRNA stability, and splicing. hnRNP-LL protein plays a critical and unique role in the signal-induced regulation of CD45 and acts as a global regulator of alternative splicing in activated T cells. This family also includes polypyrimidine tract binding protein homolog 3 (PTBPH3) found in plant. Although its biological roles remain unclear, PTBPH3 shows significant sequence similarity to other family members, all of which contain four RNA recognition motifs (RRM), also known as RBD (RNA binding domain) or RNP (ribonucleoprotein domain). Although their biological roles remain unclear, both PTBPH1 and PTBPH2 show significant sequence similarity to PTB. However, in contrast to PTB, they have three RRMs.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 383873129  14 INNLNEKIKKDelkkSLYAIFSQFGQILDILVSRSLKmRGQAFVIFKEVSSATNALRSMQGFPFYDK--PMRIQYAK 88
Cdd:cd12422    6 VTNLLYPVTVD----VLHQVFSPYGAVEKIVIFEKGT-GVQALVQFDSVESAEAAKKALNGRNIYDGccTLDIQFSR 77

RNA recognition motif 1 (RRM1) found in yeast nucleolar protein 3 (Npl3p) and similar proteins; This subfamily corresponds to the RRM1 of Npl3p, also termed mitochondrial targeting suppressor 1 protein, or nuclear polyadenylated RNA-binding protein 1. Npl3p is a major yeast RNA-binding protein that competes with 3'-end processing factors, such as Rna15, for binding to the nascent RNA, protecting the transcript from premature termination and coordinating transcription termination and the packaging of the fully processed transcript for export. It specifically recognizes a class of G/U-rich RNAs. Npl3p is a multi-domain protein containing two central RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), separated by a short linker and a C-terminal domain rich in glycine, arginine and serine residues.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 383873129 210 LFLTNLPEETNELMLSMLFNQFPGFKEVRLVPGRhDIAFVEFDNEVQAGAARDALQGF 267
Cdd:cd12340    2 LFVRPFPPDTSESAIREIFSPYGPVKEVKMLSDS-NFAFVEFEELEDAIRAKDSVHGR 58

RNA recognition motif 1 (RRM1) found in yeast meiotic activator RIM4 and similar proteins; This subfamily corresponds to the RRM1 of RIM4, also termed regulator of IME2 protein 4, a putative RNA binding protein that is expressed at elevated levels early in meiosis. It functions as a meiotic activator required for both the IME1- and IME2-dependent pathways of meiotic gene expression, as well as early events of meiosis, such as meiotic division and recombination, in Saccharomyces cerevisiae. RIM4 contains two RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains). The family also includes a putative RNA-binding protein termed multicopy suppressor of sporulation protein Msa1. It is a putative RNA-binding protein encoded by a novel gene, msa1, from the fission yeast Schizosaccharomyces pombe. Msa1 may be involved in the inhibition of sexual differentiation by controlling the expression of Ste11-regulated genes, possibly through the pheromone-signaling pathway. Like RIM4, Msa1 also contains two RRMs, both of which are essential for the function of Msa1.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 383873129   8 PNHTIYINNLNEKIKKDELKKSLYAIFSQFGQILDILVSRSLKMRGQAFVIFKEVSSATNALRSMQGFPFYDKPMRIQYA 87
Cdd:cd12453    1 PSACLFVASLSSARSDEELCAAVTNHFSKWGELLNVKVLKDWSNRPYAFVQYTNTEDAKNALVNGHNTLLDGRHLRVEKA 80

                 .
gi 383873129  88 K 88
Cdd:cd12453   81 K 81

RNA recognition motif 2 (RRM2) found in the U1A/U2B"/SNF protein family; This subfamily corresponds to the RRM2 of U1A/U2B"/SNF protein family, containing Drosophila sex determination protein SNF and its two mammalian counterparts, U1 small nuclear ribonucleoprotein A (U1 snRNP A or U1-A or U1A) and U2 small nuclear ribonucleoprotein B" (U2 snRNP B" or U2B"), all of which consist of two RNA recognition motifs (RRMs) connected by a variable, flexible linker. SNF is an RNA-binding protein found in the U1 and U2 snRNPs of Drosophila where it is essential in sex determination and possesses a novel dual RNA binding specificity. SNF binds with high affinity to both Drosophila U1 snRNA stem-loop II (SLII) and U2 snRNA stem-loop IV (SLIV). It can also bind to poly(U) RNA tracts flanking the alternatively spliced Sex-lethal (Sxl) exon, as does Drosophila Sex-lethal protein (SXL). U1A is an RNA-binding protein associated with the U1 snRNP, a small RNA-protein complex involved in pre-mRNA splicing. U1A binds with high affinity and specificity to stem-loop II (SLII) of U1 snRNA. It is predominantly a nuclear protein that shuttles between the nucleus and the cytoplasm independently of interactions with U1 snRNA. Moreover, U1A may be involved in RNA 3'-end processing, specifically cleavage, splicing and polyadenylation, through interacting with a large number of non-snRNP proteins. U2B", initially identified to bind to stem-loop IV (SLIV) at the 3' end of U2 snRNA, is a unique protein that comprises of the U2 snRNP. Additional research indicates U2B" binds to U1 snRNA stem-loop II (SLII) as well and shows no preference for SLIV or SLII on the basis of binding affinity. U2B" does not require an auxiliary protein for binding to RNA and its nuclear transport is independent on U2 snRNA binding.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 383873129   8 PNHTIYINNLNEKIKKDELKkslyAIFSQFGQILDIlvsRSLKMRGQAFVIFKEVSSATNALRSMQGF 75
Cdd:cd12247    1 PNKILFLQNLPEETTKEMLE----MLFNQFPGFKEV---RLVPRRGIAFVEFETEEQATVALQALQGF 61

RNA recognition motif (RRM) found in heterogeneous nuclear ribonucleoprotein G (hnRNP G), Y chromosome RNA recognition motif 1 (hRBMY), testis-specific heterogeneous nuclear ribonucleoprotein G-T (hnRNP G-T) and similar proteins; This subfamily corresponds to the RRM domain of hnRNP G, also termed glycoprotein p43 or RBMX, an RNA-binding motif protein located on the X chromosome. It is expressed ubiquitously and has been implicated in the splicing control of several pre-mRNAs. Moreover, hnRNP G may function as a regulator of transcription for SREBP-1c and GnRH1. Research has shown that hnRNP G may also act as a tumor-suppressor since it upregulates the Txnip gene and promotes the fidelity of DNA end-joining activity. In addition, hnRNP G appears to play a critical role in proper neural development of zebrafish and frog embryos. The family also includes several paralogs of hnRNP G, such as hRBMY and hnRNP G-T (also termed RNA-binding motif protein, X-linked-like-2). Both, hRBMY and hnRNP G-T, are exclusively expressed in testis and critical for male fertility. Like hnRNP G, hRBMY and hnRNP G-T interact with factors implicated in the regulation of pre-mRNA splicing, such as hTra2-beta1 and T-STAR. Although members in this family share a high conserved N-terminal RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain), they appear to recognize different RNA targets. For instance, hRBMY interacts specifically with a stem-loop structure in which the loop is formed by the sequence CA/UCAA. In contrast, hnRNP G associates with single stranded RNA sequences containing a CCA/C motif. In addition to the RRM, hnRNP G contains a nascent transcripts targeting domain (NTD) in the middle region and a novel auxiliary RNA-binding domain (RBD) in its C-terminal region. The C-terminal RBD exhibits distinct RNA binding specificity, and would play a critical role in the regulation of alternative splicing by hnRNP G.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 383873129  12 IYINNLNEKIkkDElkKSLYAIFSQFGQILDILVSR---SLKMRGQAFVIFKEVSSATNALRSMQGFPFYDKPMRIQYAK 88
Cdd:cd12382    4 LFIGGLNTET--NE--KALEAVFGKYGRIVEVLLMKdreTNKSRGFAFVTFESPADAKDAARDMNGKELDGKAIKVEQAT 79

RNA recognition motif (RRM) found in serine/arginine-rich splicing factor SRSF2, SRSF8 and similar proteins; This subfamily corresponds to the RRM of SRSF2 and SRSF8. SRSF2, also termed protein PR264, or splicing component, 35 kDa (splicing factor SC35 or SC-35), is a prototypical SR protein that plays important roles in the alternative splicing of pre-mRNA. It is also involved in transcription elongation by directly or indirectly mediating the recruitment of elongation factors to the C-terminal domain of polymerase II. SRSF2 is exclusively localized in the nucleus and is restricted to nuclear processes. It contains a single N-terminal RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain), followed by a C-terminal RS domain rich in serine-arginine dipeptides. The RRM is responsible for the specific recognition of 5'-SSNG-3' (S=C/G) RNA. In the regulation of alternative splicing events, it specifically binds to cis-regulatory elements on the pre-mRNA. The RS domain modulates SRSF2 activity through phosphorylation, directly contacts RNA, and promotes protein-protein interactions with the spliceosome. SRSF8, also termed SRP46 or SFRS2B, is a novel mammalian SR splicing factor encoded by a PR264/SC35 functional retropseudogene. SRSF8 is localized in the nucleus and does not display the same activity as PR264/SC35. It functions as an essential splicing factor in complementing a HeLa cell S100 extract deficient in SR proteins. Like SRSF2, SRSF8 contains a single N-terminal RRM and a C-terminal RS domain.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 383873129  14 INNLNEKIKKDELKKslyaIFSQFGQILDILVSR---SLKMRGQAFVIFKEVSSATNALRSMQGFPFYDKPMRIQ 85
Cdd:cd12311    3 VDNLTYRTTPDDLRR----VFEKYGEVGDVYIPRdryTRESRGFAFVRFYDKRDAEDAIDAMDGAELDGRELRVQ 73

RNA recognition motif 1 (RRM1) found in type I polyadenylate-binding proteins; This subfamily corresponds to the RRM1 of type I poly(A)-binding proteins (PABPs), highly conserved proteins that bind to the poly(A) tail present at the 3' ends of most eukaryotic mRNAs. They have been implicated in the regulation of poly(A) tail length during the polyadenylation reaction, translation initiation, mRNA stabilization by influencing the rate of deadenylation and inhibition of mRNA decapping. The family represents type I polyadenylate-binding proteins (PABPs), including polyadenylate-binding protein 1 (PABP-1 or PABPC1), polyadenylate-binding protein 3 (PABP-3 or PABPC3), polyadenylate-binding protein 4 (PABP-4 or APP-1 or iPABP), polyadenylate-binding protein 5 (PABP-5 or PABPC5), polyadenylate-binding protein 1-like (PABP-1-like or PABPC1L), polyadenylate-binding protein 1-like 2 (PABPC1L2 or RBM32), polyadenylate-binding protein 4-like (PABP-4-like or PABPC4L), yeast polyadenylate-binding protein, cytoplasmic and nuclear (PABP or ACBP-67), and similar proteins. PABP-1 is a ubiquitously expressed multifunctional protein that may play a role in 3' end formation of mRNA, translation initiation, mRNA stabilization, protection of poly(A) from nuclease activity, mRNA deadenylation, inhibition of mRNA decapping, and mRNP maturation. Although PABP-1 is thought to be a cytoplasmic protein, it is also found in the nucleus. PABP-1 may be involved in nucleocytoplasmic trafficking and utilization of mRNP particles. PABP-1 contains four copies of RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), a less well conserved linker region, and a proline-rich C-terminal conserved domain (CTD). PABP-3 is a testis-specific poly(A)-binding protein specifically expressed in round spermatids. It is mainly found in mammalian and may play an important role in the testis-specific regulation of mRNA homeostasis. PABP-3 shows significant sequence similarity to PABP-1. However, it binds to poly(A) with a lower affinity than PABP-1. Moreover, PABP-1 possesses an A-rich sequence in its 5'-UTR and allows binding of PABP and blockage of translation of its own mRNA. In contrast, PABP-3 lacks the A-rich sequence in its 5'-UTR. PABP-4 is an inducible poly(A)-binding protein (iPABP) that is primarily localized to the cytoplasm. It shows significant sequence similarity to PABP-1 as well. The RNA binding properties of PABP-1 and PABP-4 appear to be identical. PABP-5 is encoded by PABPC5 gene within the X-specific subinterval, and expressed in fetal brain and in a range of adult tissues in mammals, such as ovary and testis. It may play an important role in germ cell development. Moreover, unlike other PABPs, PABP-5 contains only four RRMs, but lacks both the linker region and the CTD. PABP-1-like and PABP-1-like 2 are the orthologs of PABP-1. PABP-4-like is the ortholog of PABP-5. Their cellular functions remain unclear. The family also includes yeast PABP, a conserved poly(A) binding protein containing poly(A) tails that can be attached to the 3'-ends of mRNAs. The yeast PABP and its homologs may play important roles in the initiation of translation and in mRNA decay. Like vertebrate PABP-1, the yeast PABP contains four RRMs, a linker region, and a proline-rich CTD as well. The first two RRMs are mainly responsible for specific binding to poly(A). The proline-rich region may be involved in protein-protein interactions.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 383873129  30 LYAIFSQFGQILDILVSRSLKMR---GQAFVIFKEVSSATNALRSMQGFPFYDKPMRIQYAKTD 90
Cdd:cd12378   16 LYEKFSPAGPVLSIRVCRDAVTRrslGYAYVNFQQPADAERALDTLNFDVIKGKPIRIMWSQRD 79

RNA recognition motif 3 (RRM3) found in heterogeneous nuclear ribonucleoprotein R (hnRNP R) and similar proteins; This subfamily corresponds to the RRM3 in hnRNP R, hnRNP Q, and APOBEC-1 complementation factor (ACF). hnRNP R is a ubiquitously expressed nuclear RNA-binding protein that specifically bind mRNAs with a preference for poly(U) stretches and has been implicated in mRNA processing and mRNA transport, and also acts as a regulator to modify binding to ribosomes and RNA translation. hnRNP Q is also a ubiquitously expressed nuclear RNA-binding protein. It has been identified as a component of the spliceosome complex, as well as a component of the apobec-1 editosome, and has been implicated in the regulation of specific mRNA transport. ACF is an RNA-binding subunit of a core complex that interacts with apoB mRNA to facilitate C to U RNA editing. It may also act as an apoB mRNA recognition factor and chaperone and play a key role in cell growth and differentiation. This family also includes two functionally unknown RNA-binding proteins, RBM46 and RBM47. All members contain three conserved RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains).

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 383873129 209 ILFLTNLPEETNELMLSMLFNQFPGFKEVRLVpgrHDIAFVEFDNEVQAGAARDALQGFKITQNNaMKISFAK 281
Cdd:cd12251    3 VLYVRNLMLSTTEEKLRELFSEYGKVERVKKI---KDYAFVHFEERDDAVKAMEEMNGKELEGSE-IEVSLAK 71

RNA recognition motif (RRM) found in RNA-binding protein 7 (RBM7) and similar proteins; This subfamily corresponds to the RRM of RBM7, RBM11 and their eukaryotic homologous. RBM7 is an ubiquitously expressed pre-mRNA splicing factor that enhances messenger RNA (mRNA) splicing in a cell-specific manner or in a certain developmental process, such as spermatogenesis. It interacts with splicing factors SAP145 (the spliceosomal splicing factor 3b subunit 2) and SRp20, and may play a more specific role in meiosis entry and progression. Together with additional testis-specific RNA-binding proteins, RBM7 may regulate the splicing of specific pre-mRNA species that are important in the meiotic cell cycle. RBM11 is a novel tissue-specific splicing regulator that is selectively expressed in brain, cerebellum and testis, and to a lower extent in kidney. It is localized in the nucleoplasm and enriched in SRSF2-containing splicing speckles. It may play a role in the modulation of alternative splicing during neuron and germ cell differentiation. Both, RBM7 and RBM11, contain an N-terminal RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain), and a region lacking known homology at the C-terminus. The RRM is responsible for RNA binding, whereas the C-terminal region permits nuclear localization and homodimerization.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 383873129   9 NHTIYINNLNEKIKkDELkksLYAIFSQFGQILDILV--SRSLKMRGQAFVIFKEVSSATNALRSMQGFPFYDKPMRIQ 85
Cdd:cd12336    1 DRTLFVGNLDPRVT-EEI---LYELFLQAGPLEGVKIpkDPNGKPKNFAFVTFKHEVSVPYAIQLLNGIRLFGREIRIK 75

RNA recognition motif (RRM) found in serine/arginine-rich splicing factor 10 (SRSF10) and similar proteins; This subgroup corresponds to the RRM of SRSF10, also termed 40 kDa SR-repressor protein (SRrp40), or FUS-interacting serine-arginine-rich protein 1 (FUSIP1), or splicing factor SRp38, or splicing factor, arginine/serine-rich 13A (SFRS13A), or TLS-associated protein with Ser-Arg repeats (TASR). SRSF10 is a serine-arginine (SR) protein that acts as a potent and general splicing repressor when dephosphorylated. It mediates global inhibition of splicing both in M phase of the cell cycle and in response to heat shock. SRSF10 emerges as a modulator of cholesterol homeostasis through the regulation of low-density lipoprotein receptor (LDLR) splicing efficiency. It also regulates cardiac-specific alternative splicing of triadin pre-mRNA and is required for proper Ca2+ handling during embryonic heart development. In contrast, the phosphorylated SRSF10 functions as a sequence-specific splicing activator in the presence of a nuclear cofactor. It activates distal alternative 5' splice site of adenovirus E1A pre-mRNA in vivo. Moreover, SRSF10 strengthens pre-mRNA recognition by U1 and U2 snRNPs. SRSF10 localizes to the nuclear speckles and can shuttle between nucleus and cytoplasm. It contains a single N-terminal RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain), followed by a C-terminal RS domain rich in serine-arginine dipeptides.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 383873129   8 PNHTIYINNLNEKIKKDELKKSlyaiFSQFGQILDILVS---RSLKMRGQAFVIFKEVSSATNALRSMQGFPFYDKPMRI 84
Cdd:cd12559    4 PNTSLFVRNVADDTRSEDLRRE----FGRYGPIVDVYVPldfYTRRPRGFAYVQFEDVRDAEDALHNLDRKWICGRQIEI 79

                         90
                 ....*....|....*
gi 383873129  85 QYAKTDSDIIAKMKG 99
Cdd:cd12559   80 QFAQGDRKTPNQMKA 94

RNA recognition motif (RRM) found in the DnaJ homolog subfamily C member 17; The CD corresponds to the RRM of some eukaryotic DnaJ homolog subfamily C member 17 and similar proteins. DnaJ/Hsp40 (heat shock protein 40) proteins are highly conserved and play crucial roles in protein translation, folding, unfolding, translocation, and degradation. They act primarily by stimulating the ATPase activity of Hsp70s, an important chaperonine family. Members in this family contains an N-terminal DnaJ domain or J-domain, which mediates the interaction with Hsp70. They also contains a RNA recognition motif (RRM), also known as RBD (RNA binding domain) or RNP (ribonucleoprotein domain), at the C-terminus, which may play an essential role in RNA binding.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 383873129  20 KIKKDEL---KKSLYAIFSQFGQILDILVSRslKMRGQAFVIFKEVSSATNALRSMQGFPfyDKPMRIQYA 87
Cdd:cd12429    8 KSKKGNGgysEEELRKIFSKYGPVSDVVISS--KKKGSAIVEFATVVAADAAVENEVGLP--DNPLLVSWL 74

RNA recognition motif 1 (RRM1) found in splicing factor 3B subunit 4 (SF3B4) and similar proteins; This subfamily corresponds to the RRM1 of SF3B4, also termed pre-mRNA-splicing factor SF3b 49 kDa (SF3b50), or spliceosome-associated protein 49 (SAP 49). SF3B4 a component of the multiprotein complex splicing factor 3b (SF3B), an integral part of the U2 small nuclear ribonucleoprotein (snRNP) and the U11/U12 di-snRNP. SF3B is essential for the accurate excision of introns from pre-messenger RNA, and is involved in the recognition of the pre-mRNA's branch site within the major and minor spliceosomes. SF3B4 functions to tether U2 snRNP with pre-mRNA at the branch site during spliceosome assembly. It is an evolutionarily highly conserved protein with orthologs across diverse species. SF3B4 contains two closely adjacent N-terminal RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains). It binds directly to pre-mRNA and also interacts directly and highly specifically with another SF3B subunit called SAP 145.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 383873129  12 IYINNLNEKIKkDELkksLYAIFSQFGQILDILVSR---SLKMRGQAFVIFKEVSSATNALRSMQGFPFYDKPMRI 84
Cdd:cd12334    1 VYVGNLDEKVT-EEL---LWELFIQAGPVVNVHMPKdrvTQQHQGYGFVEFLSEEDADYAIKIMNMIKLYGKPIRV 72

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 383873129   9 NHTIYINNLNEKIKKDELKKslyaIFSQFGQILDILVSRSlkmRGQAFVIFKEVSSATNALRSMQGFPFYDKPMRI 84
Cdd:cd12346    1 NTTVFVGGLDPNVTEEDLRV----LFGPFGEIVYVKIPPG---KGCGFVQFVNRASAEAAIQKLQGTPIGGSRIRL 69

RNA recognition motif (RRM) found in Zinc finger CCHC-type and RNA-binding motif-containing protein 1 (ZCRB1) and similar proteins; This subfamily corresponds to the RRM of ZCRB1, also termed MADP-1, or U11/U12 small nuclear ribonucleoprotein 31 kDa protein (U11/U12 snRNP 31 or U11/U12-31K), a novel multi-functional nuclear factor, which may be involved in morphine dependence, cold/heat stress, and hepatocarcinoma. It is located in the nucleoplasm, but outside the nucleolus. ZCRB1 is one of the components of U11/U12 snRNPs that bind to U12-type pre-mRNAs and form a di-snRNP complex, simultaneously recognizing the 5' splice site and branchpoint sequence. ZCRB1 is characterized by an RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain), and a CCHC-type Zinc finger motif. In addition, it contains core nucleocapsid motifs, and Lys- and Glu-rich domains.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 383873129  11 TIYINNLNEKIKKDELKKslyaIFSQFGQILDILVSR---SLKMRGQAFVIFKEVSSATNALRSMQG 74
Cdd:cd12393    3 TVYVSNLPFSLTNNDLHQ----IFSKYGKVVKVTILKdkeTRKSKGVAFVLFLDRESAHNAVRAMNN 65

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 383873129  12 IYINNLNEKIKKDELKKslyaIFSQFGQI--LDILVSRSLKMRGQ----AFVIFKEVSSATNALRSMQGFPFYDKPMRIQ 85
Cdd:cd12223    4 LYVGNLPPSVTEEVLLR----EFGRFGPLasVKIMWPRTEEERRRnrncGFVAFMSRADAERAMRELNGKDVMGYELKLG 79

                 ....
gi 383873129  86 YAKT 89
Cdd:cd12223   80 WGKA 83

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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 383873129   12 IYINNLNEKIKKDELKKslyaIFSQFGQILDILVSR--SLKMRGQAFVIFKEVSSATNALRSMQG--FPFYDKPMRI--Q 85
Cdd:TIGR01628 181 LYVKNLDPSVNEDKLRE----LFAKFGEITSAAVMKdgSGRSRGFAFVNFEKHEDAAKAVEEMNGkkIGLAKEGKKLyvG 256

                          90       100       110
                  ....*....|....*....|....*....|.
gi 383873129   86 YAKTDSDIIAKMKGTFverDRKREKRKPKSQ 116
Cdd:TIGR01628 257 RAQKRAEREAELRRKF---EELQQERKMKAQ 284

RNA recognition motif 2 (RRM2) found in the Spen (split end) protein family; This subfamily corresponds to the RRM2 domain in the Spen (split end) protein family which includes RNA binding motif protein 15 (RBM15), putative RNA binding motif protein 15B (RBM15B), and similar proteins found in Metazoa. RBM15, also termed one-twenty two protein 1 (OTT1), conserved in eukaryotes, is a novel mRNA export factor and component of the NXF1 pathway. It binds to NXF1 and serves as receptor for the RNA export element RTE. It also possess mRNA export activity and can facilitate the access of DEAD-box protein DBP5 to mRNA at the nuclear pore complex (NPC). RNA-binding protein 15B (RBM15B), also termed one twenty-two 3 (OTT3), is a paralog of RBM15 and therefore has post-transcriptional regulatory activity. It is a nuclear protein sharing with RBM15 the association with the splicing factor compartment and the nuclear envelope as well as the binding to mRNA export factors NXF1 and Aly/REF. Members in this family belong to the Spen (split end) protein family, which share a domain architecture comprising of three N-terminal RNA recognition motifs (RRMs), also known as RBD (RNA binding domain) or RNP (ribonucleoprotein domain), and a C-terminal SPOC (Spen paralog and ortholog C-terminal) domain.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 383873129   9 NHTIYINNLNEKIKKDELkkslYAIFSQFGQILDILVSRSlkMRGQ----AFVIFKEVSSATNALRSMQGFPFYDKPMRI 84
Cdd:cd12309    2 TRTLFVGNLEITITEEEL----RRAFERYGVVEDVDIKRP--PRGQgnayAFVKFLNLDMAHRAKVAMSGQYIGRNQIKI 75

                 ....
gi 383873129  85 QYAK 88
Cdd:cd12309   76 GYGK 79

RNA recognition motif (RRM) found in RNA-binding protein with multiple splicing (RBP-MS)-like proteins; This subfamily corresponds to the RRM of RNA-binding proteins with multiple splicing (RBP-MS)-like proteins, including protein products of RBPMS genes (RBP-MS and its paralogue RBP-MS2), the Drosophila couch potato (cpo), and Caenorhabditis elegans Mec-8 genes. RBP-MS may be involved in regulation of mRNA translation and localization during Xenopus laevis development. It has also been shown to physically interact with Smad2, Smad3 and Smad4, and stimulates Smad-mediated transactivation. Cpo may play an important role in regulating normal function of the nervous system, whereas mutations in Mec-8 affect mechanosensory and chemosensory neuronal function. All members contain a well conserved RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain). Some uncharacterized family members contain two RRMs; this subfamily includes their RRM1. Their RRM2 shows high sequence homology to the RRM of yeast proteins scw1, Whi3, and Whi4.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 383873129 210 LFLTNLPEETNELMLSMLFNQFPGFKEVRLVP---GRHDIAFVEFDNEVQAGAARDALQGFK 268
Cdd:cd12420    3 LFVSGLPLDVKERELYNLFRPLPGYEASQLKFtgkNTQPVGFVTFESRAAAEAAKDALQGMR 64