RNA recognition motif 2 (RRM2) found in HIV Tat-specific factor 1 (Tat-SF1) and similar proteins; This subfamily corresponds to the RRM2 of Tat-SF1 and CUS2. Tat-SF1 is the cofactor for stimulation of transcriptional elongation by human immunodeficiency virus-type 1 (HIV-1) Tat. It is a substrate of an associated cellular kinase. Tat-SF1 contains two RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), and a highly acidic carboxyl-terminal half. The family also includes CUS2, a yeast homolog of human Tat-SF1. CUS2 interacts with U2 RNA in splicing extracts and functions as a splicing factor that aids assembly of the splicing-competent U2 snRNP in vivo. CUS2 also associates with PRP11 that is a subunit of the conserved splicing factor SF3a. Like Tat-SF1, CUS2 contains two RRMs as well.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 543266696 257 ERIVIIRNMFHPKDFEEDPLVLNEIREDLRTECEKFGQVKKVLIFDRHPDGVASVSFKEATEADLCKLTLNGRWFGGRQL 336
Cdd:cd12282    1 EKVVILKNMFHPKEFEEDPELINEIKEDLREECEKFGQVKKVVVFDRHPDGVASVKFKEPEEADKCIQALNGRWFAGRKL 80

                         90
                 ....*....|.
gi 543266696 337 SAETWDGVTDY 347
Cdd:cd12282   81 EAETWDGKTDY 91

RNA recognition motif 2 (RRM2) found in HIV Tat-specific factor 1 (Tat-SF1) and similar proteins; This subfamily corresponds to the RRM2 of Tat-SF1 and CUS2. Tat-SF1 is the cofactor for stimulation of transcriptional elongation by human immunodeficiency virus-type 1 (HIV-1) Tat. It is a substrate of an associated cellular kinase. Tat-SF1 contains two RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), and a highly acidic carboxyl-terminal half. The family also includes CUS2, a yeast homolog of human Tat-SF1. CUS2 interacts with U2 RNA in splicing extracts and functions as a splicing factor that aids assembly of the splicing-competent U2 snRNP in vivo. CUS2 also associates with PRP11 that is a subunit of the conserved splicing factor SF3a. Like Tat-SF1, CUS2 contains two RRMs as well.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 543266696 257 ERIVIIRNMFHPKDFEEDPLVLNEIREDLRTECEKFGQVKKVLIFDRHPDGVASVSFKEATEADLCKLTLNGRWFGGRQL 336
Cdd:cd12282    1 EKVVILKNMFHPKEFEEDPELINEIKEDLREECEKFGQVKKVVVFDRHPDGVASVKFKEPEEADKCIQALNGRWFAGRKL 80

                         90
                 ....*....|.
gi 543266696 337 SAETWDGVTDY 347
Cdd:cd12282   81 EAETWDGKTDY 91

RNA recognition motif;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 543266696   128 NVYVTGLPPDITKDEFVQVMSKCGIIMRdpqteehkIKLYKDKE-GNLKGDGLCCYLKRESVQLALRLLDEAEIRGYKLH 206
Cdd:smart00360   1 TLFVGNLPPDTTEEELRELFSKFGKVES--------VRLVRDKEtGKSKGFAFVEFESEEDAEKALEALNGKELDGRPLK 72

                   .
gi 543266696   207 V 207
Cdd:smart00360  73 V 73

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 543266696  127 TNVYVTGLPPDITKDEFVQVMSKCGIIMrdpqteehKIKLYKDKEGNLKGDGLCCYLKRESVQLALRLLDEAEI----RG 202
Cdd:TIGR01628 179 TNLYVKNLDPSVNEDKLRELFAKFGEIT--------SAAVMKDGSGRSRGFAFVNFEKHEDAAKAVEEMNGKKIglakEG 250

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 543266696  203 YKLHveVAKFQLKGEYDASKKKKKCKDYKKklsqqqkqldwRPEKKDGATrmrheriVIIRNMfhpkdfeeDPLVLNeir 282
Cdd:TIGR01628 251 KKLY--VGRAQKRAEREAELRRKFEELQQE-----------RKMKAQGVN-------LYVKNL--------DDTVTD--- 299

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 543266696  283 EDLRTECEKFGQVK--KVLIFD-RHPDGVASVSFKEATEADLCKLTLNGRWFGGRQL 336
Cdd:TIGR01628 300 EKLRELFSECGEITsaKVMLDEkGVSRGFGFVCFSNPEEANRAVTEMHGRMLGGKPL 356

RNA recognition motif;

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 543266696   283 EDLRTECEKFGQVKKV-LIFDRH---PDGVASVSFKEATEADLCKLTLNGRWFGGRQL 336
Cdd:smart00360  14 EELRELFSKFGKVESVrLVRDKEtgkSKGFAFVEFESEEDAEKALEALNGKELDGRPL 71

RNA recognition motif 2 (RRM2) found in HIV Tat-specific factor 1 (Tat-SF1) and similar proteins; This subfamily corresponds to the RRM2 of Tat-SF1 and CUS2. Tat-SF1 is the cofactor for stimulation of transcriptional elongation by human immunodeficiency virus-type 1 (HIV-1) Tat. It is a substrate of an associated cellular kinase. Tat-SF1 contains two RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), and a highly acidic carboxyl-terminal half. The family also includes CUS2, a yeast homolog of human Tat-SF1. CUS2 interacts with U2 RNA in splicing extracts and functions as a splicing factor that aids assembly of the splicing-competent U2 snRNP in vivo. CUS2 also associates with PRP11 that is a subunit of the conserved splicing factor SF3a. Like Tat-SF1, CUS2 contains two RRMs as well.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 543266696 257 ERIVIIRNMFHPKDFEEDPLVLNEIREDLRTECEKFGQVKKVLIFDRHPDGVASVSFKEATEADLCKLTLNGRWFGGRQL 336
Cdd:cd12282    1 EKVVILKNMFHPKEFEEDPELINEIKEDLREECEKFGQVKKVVVFDRHPDGVASVKFKEPEEADKCIQALNGRWFAGRKL 80

                         90
                 ....*....|.
gi 543266696 337 SAETWDGVTDY 347
Cdd:cd12282   81 EAETWDGKTDY 91

RNA recognition motif 3 (RRM3) found in UHM domain of poly(U)-binding-splicing factor PUF60 and similar proteins; This subgroup corresponds to the RRM3 of PUF60, also termed FUSE-binding protein-interacting repressor (FBP-interacting repressor or FIR), or Ro-binding protein 1 (RoBP1), or Siah-binding protein 1 (Siah-BP1), an essential splicing factor that functions as a poly-U RNA-binding protein required to reconstitute splicing in depleted nuclear extracts. Its function is enhanced through interaction with U2 auxiliary factor U2AF65. PUF60 also controls human c-myc gene expression by binding and inhibiting the transcription factor far upstream sequence element (FUSE)-binding-protein (FBP), an activator of c-myc promoters. PUF60 contains two central RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), and a C-terminal U2AF (U2 auxiliary factor) homology motifs (UHM) that harbors another RRM and binds to tryptophan-containing linear peptide motifs (UHM ligand motifs, ULMs) in several nuclear proteins. The research indicates that PUF60 binds FUSE as a dimer, and only the first two RRM domains participate in the single-stranded DNA recognition.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 543266696 258 RIVIIRNMFHPKDFEEDplvlneIREDLRTECEKFGQVKKVLIF------DRHPDGVAS--VSFKEATEADLCKLTLNGR 329
Cdd:cd12648    2 RVMVLRNMVGPEDIDDD------LEGEVTEECGKFGAVNRVIIYqekqgeEEDAEIIVKifVEFSMPSEAEKAIQALNGR 75

                         90
                 ....*....|...
gi 543266696 330 WFGGRQLSAETWD 342
Cdd:cd12648   76 WFGGRKVVAELYD 88

RNA recognition motif (RRM) found in UHM domain of 45 kDa-splicing factor (SPF45) and similar proteins; This subfamily corresponds to the RRM found in UHM domain of 45 kDa-splicing factor (SPF45 or RBM17), poly(U)-binding-splicing factor PUF60 (FIR or Hfp or RoBP1 or Siah-BP1), and similar proteins. SPF45 is an RNA-binding protein consisting of an unstructured N-terminal region, followed by a G-patch motif and a C-terminal U2AF (U2 auxiliary factor) homology motifs (UHM) that harbors a RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain) and an Arg-Xaa-Phe sequence motif. SPF45 regulates alternative splicing of the apoptosis regulatory gene FAS (also known as CD95). It induces exon 6 skipping in FAS pre-mRNA through the UHM domain that binds to tryptophan-containing linear peptide motifs (UHM ligand motifs, ULMs) present in the 3' splice site-recognizing factors U2AF65, SF1 and SF3b155. PUF60 is an essential splicing factor that functions as a poly-U RNA-binding protein required to reconstitute splicing in depleted nuclear extracts. Its function is enhanced through interaction with U2 auxiliary factor U2AF65. PUF60 also controls human c-myc gene expression by binding and inhibiting the transcription factor far upstream sequence element (FUSE)-binding-protein (FBP), an activator of c-myc promoters. PUF60 contains two central RRMs and a C-terminal UHM domain.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 543266696 258 RIVIIRNMFHPKDFEEDplvlneIREDLRTECEKFGQVKKVLIfdrHPDGVAS--------VSFKEATEADLCKLTLNGR 329
Cdd:cd12374    2 KILVLRNMVGPGEIDED------LKDEIKEECSKYGKVLNVII---HEVASSEaddavrvfVEFEDADEAIKAFRALNGR 72

                         90
                 ....*....|
gi 543266696 330 WFGGRQLSAE 339
Cdd:cd12374   73 FFGGRKVKAR 82

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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 543266696 129 VYVTGLPPDITKDEFVQVMSKCGIIMRdpqteehkIKLYKDKEGNLKGDGLCCYLKRESVQLALRLLDEAEIRGYKLHVE 208
Cdd:cd00590    1 LFVGNLPPDTTEEDLRELFSKFGEVVS--------VRIVRDRDGKSKGFAFVEFESPEDAEKALEALNGTELGGRPLKVS 72

RNA recognition motif;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 543266696   128 NVYVTGLPPDITKDEFVQVMSKCGIIMRdpqteehkIKLYKDKE-GNLKGDGLCCYLKRESVQLALRLLDEAEIRGYKLH 206
Cdd:smart00360   1 TLFVGNLPPDTTEEELRELFSKFGKVES--------VRLVRDKEtGKSKGFAFVEFESEEDAEKALEALNGKELDGRPLK 72

                   .
gi 543266696   207 V 207
Cdd:smart00360  73 V 73

splicing factor, CC1-like family; This model represents a subfamily of RNA splicing factors including the Pad-1 protein (N. crassa), CAPER (M. musculus) and CC1.3 (H.sapiens). These proteins are characterized by an N-terminal arginine-rich, low complexity domain followed by three (or in the case of 4 H. sapiens paralogs, two) RNA recognition domains (rrm: pfam00706). These splicing factors are closely related to the U2AF splicing factor family (TIGR01642). A homologous gene from Plasmodium falciparum was identified in the course of the analysis of that genome at TIGR and was included in the seed.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 543266696  258 RIVIIRNMFHPKDfEEDPLVLNEIREDLRTECEKFGQVKKVLIFDRHPDGVASVSFKEATEADLCKLTLNGRWFGGRQLS 337
Cdd:TIGR01622 400 RCLVLSNMFDPAT-EEEPNWDKEIEDDVREECSKYGGVVHIYVDDKNSAGDIYLKFDSVQAAEAAIKALNGRYFGGKMIT 478

                  .
gi 543266696  338 A 338
Cdd:TIGR01622 479 A 479

RNA recognition motif (RRM) found in Drosophila melanogaster RNA-binding protein cabeza and similar proteins; This subgroup corresponds to the RRM in cabeza, also termed P19, or sarcoma-associated RNA-binding fly homolog (SARFH). It is a putative homolog of human RNA-binding proteins FUS (also termed TLS or Pigpen or hnRNP P2), EWS (also termed EWSR1), TAF15 (also termed hTAFII68 or TAF2N or RPB56), and belongs to the of the FET (previously TET) (FUS/TLS, EWS, TAF15) family of RNA- and DNA-binding proteins whose expression is altered in cancer. It is a nuclear RNA binding protein that may play an important role in the regulation of RNA metabolism during fly development. Cabeza contains one RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain).

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 543266696 129 VYVTGLPPDITKDEFVQVMSKCGIIMRDPQTEEHKIKLYKDKE-GNLKGDGLCCYLKRESVQLALRLLDEAEIRGYKLHV 207
Cdd:cd12534    1 VFVSNLPPNTTEQDLAEHFGSIGIIKIDKKTGKPKIWLYKDKDtGEPKGEATVTYDDPHAASAAIEWFNNKDFMGNTIKV 80

                 ...
gi 543266696 208 EVA 210
Cdd:cd12534   81 SLA 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 543266696  127 TNVYVTGLPPDITKDEFVQVMSKCGIIMrdpqteehKIKLYKDKEGNLKGDGLCCYLKRESVQLALRLLDEAEI----RG 202
Cdd:TIGR01628 179 TNLYVKNLDPSVNEDKLRELFAKFGEIT--------SAAVMKDGSGRSRGFAFVNFEKHEDAAKAVEEMNGKKIglakEG 250

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 543266696  203 YKLHveVAKFQLKGEYDASKKKKKCKDYKKklsqqqkqldwRPEKKDGATrmrheriVIIRNMfhpkdfeeDPLVLNeir 282
Cdd:TIGR01628 251 KKLY--VGRAQKRAEREAELRRKFEELQQE-----------RKMKAQGVN-------LYVKNL--------DDTVTD--- 299

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 543266696  283 EDLRTECEKFGQVK--KVLIFD-RHPDGVASVSFKEATEADLCKLTLNGRWFGGRQL 336
Cdd:TIGR01628 300 EKLRELFSECGEITsaKVMLDEkGVSRGFGFVCFSNPEEANRAVTEMHGRMLGGKPL 356

RNA recognition motif 3 (RRM3) found found in type I polyadenylate-binding proteins; This subfamily corresponds to the RRM3 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 an 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. 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 mammalian, 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 the 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        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 543266696 127 TNVYVTGLPPDITKDEFVQVMSKCGIIMrdpqteehKIKLYKDKEGNLKGDGLCCYLKRESVQLALRLLDEAEIRGYKLH 206
Cdd:cd12380    2 TNVYVKNFGEDVDDDELKELFEKYGKIT--------SAKVMKDDSGKSKGFGFVNFENHEAAQKAVEELNGKELNGKKLY 73

                 .
gi 543266696 207 V 207
Cdd:cd12380   74 V 74

RNA recognition motif (RRM) found in U2 small nuclear ribonucleoprotein auxiliary factor U2AF 35 kDa subunit (U2AF35) and similar proteins; This subfamily corresponds to the RRM in U2 small nuclear ribonucleoprotein (snRNP) auxiliary factor (U2AF) which has been implicated in the recruitment of U2 snRNP to pre-mRNAs. It is a highly conserved heterodimer composed of large and small subunits; this family includes the small subunit of U2AF (U2AF35 or U2AF1) and U2AF 35 kDa subunit B (U2AF35B or C3H60). U2AF35 directly binds to the 3' splice site of the conserved AG dinucleotide and performs multiple functions in the splicing process in a substrate-specific manner. It promotes U2 snRNP binding to the branch-point sequences of introns through association with the large subunit of U2AF (U2AF65 or U2AF2). Although the biological role of U2AF35B remains unclear, it shows high sequence homolgy to U2AF35, which contains two N-terminal zinc fingers, a central RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain), and a C-terminal arginine/serine (SR) -rich segment interrupted by glycines. In contrast to U2AF35, U2AF35B has a plant-specific conserved C-terminal region containing SERE motif(s), which may have an important function specific to higher plants.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 543266696 259 IVIIRNMF-HPKDFEE--DPLVL-----------NEIREDLRTECEKFGQVKKVLIFDR---HPDGVASVSFKEATEADL 321
Cdd:cd12287    1 TLLLKNMYpNPDNFISslDDGSLtlseeeiqehfDEFYEDVFLELSRFGEIEDLVVCSNlndHLLGNVYVKFESEEDAEA 80

                         90
                 ....*....|....*...
gi 543266696 322 CKLTLNGRWFGGRQLSAE 339
Cdd:cd12287   81 ALQALNGRYYAGRPLYPE 98

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
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 543266696  282 REDLRTECEKFGQVKKVLIF---DRHPDGVASVSFKEATEADLCKLTLNGRWFGGRQL 336
Cdd:pfam00076  12 EEDLKDLFSKFGPIKSIRLVrdeTGRSKGFAFVEFEDEEDAEKAIEALNGKELGGREL 69

RNA recognition motif (RRM) found in cleavage stimulation factor subunit 2 (CSTF2), yeast ortholog mRNA 3'-end-processing protein RNA15 and similar proteins; This subfamily corresponds to the RRM domain of CSTF2, its tau variant and eukaryotic homologs. CSTF2, also termed cleavage stimulation factor 64 kDa subunit (CstF64), is the vertebrate conterpart of yeast mRNA 3'-end-processing protein RNA15. It is expressed in all somatic tissues and is one of three cleavage stimulatory factor (CstF) subunits required for polyadenylation. CstF64 contains an N-terminal RNA recognition motif (RRM), also known as RBD (RNA binding domain) or RNP (ribonucleoprotein domain), a CstF77-binding domain, a repeated MEARA helical region and a conserved C-terminal domain reported to bind the transcription factor PC-4. During polyadenylation, CstF interacts with the pre-mRNA through the RRM of CstF64 at U- or GU-rich sequences within 10 to 30 nucleotides downstream of the cleavage site. CSTF2T, also termed tauCstF64, is a paralog of the X-linked cleavage stimulation factor CstF64 protein that supports polyadenylation in most somatic cells. It is expressed during meiosis and subsequent haploid differentiation in a more limited set of tissues and cell types, largely in meiotic and postmeiotic male germ cells, and to a lesser extent in brain. The loss of CSTF2T will cause male infertility, as it is necessary for spermatogenesis and fertilization. Moreover, CSTF2T is required for expression of genes involved in morphological differentiation of spermatids, as well as for genes having products that function during interaction of motile spermatozoa with eggs. It promotes germ cell-specific patterns of polyadenylation by using its RRM to bind to different sequence elements downstream of polyadenylation sites than does CstF64. The family also includes yeast ortholog mRNA 3'-end-processing protein RNA15 and similar proteins. RNA15 is a core subunit of cleavage factor IA (CFIA), an essential transcriptional 3'-end processing factor from Saccharomyces cerevisiae. RNA recognition by CFIA is mediated by an N-terminal RRM, which is contained in the RNA15 subunit of the complex. The RRM of RNA15 has a strong preference for GU-rich RNAs, mediated by a binding pocket that is entirely conserved in both yeast and vertebrate RNA15 orthologs.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 543266696 129 VYVTGLPPDITKDEFVQVMSKCGIIMrdpqteehKIKLYKDKE-GNLKGDGLCCYLKRESVQLALRLLDEAEIRGYKLHV 207
Cdd:cd12398    3 VFVGNIPYDATEEQLKEIFSEVGPVV--------SFRLVTDREtGKPKGYGFCEFRDAETALSAVRNLNGYELNGRPLRV 74

                 ...
gi 543266696 208 EVA 210
Cdd:cd12398   75 DFA 77

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 543266696 127 TNVYVTGLPPDITKDEFVQVMSKCGI-----IMRdPQTEEHKIKlykdkegnlkgDGLC---CYLKRESVQLALRLLDEA 198
Cdd:cd12223    2 TNLYVGNLPPSVTEEVLLREFGRFGPlasvkIMW-PRTEEERRR-----------NRNCgfvAFMSRADAERAMRELNGK 69

                         90
                 ....*....|...
gi 543266696 199 EIRGYKLHVEVAK 211
Cdd:cd12223   70 DVMGYELKLGWGK 82

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 543266696 125 RNTNVYVTGLPPDITKDEFVQVMSKCGIIMrdpqteehKIKLYKDK-EGNLKGDGLCCYLKRESVQLALRLLD 196
Cdd:cd12651    1 KDTNLYVTNLPRTITEDELDTIFGAYGNIV--------QKNLLRDKlTGRPRGVAFVRYDKREEAQAAISALN 65

RNA recognition motif 3 (RRM3) found in RNA-binding protein 28 (RBM28) and similar proteins; This subfamily corresponds to the RRM3 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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 543266696 258 RIVIIRNMfhPKDFEEdplvlneirEDLRTECEKFGQVKKVLI-FDR---HPDGVASVSFKEATEADLC------KLTLN 327
Cdd:cd12415    1 KTVFIRNL--SFDTTE---------EDLKEFFSKFGEVKYARIvLDKdtgHSKGTAFVQFKTKESADKCieaandESEDG 69

                         90
                 ....*....|
gi 543266696 328 GRWFGGRQLS 337
Cdd:cd12415   70 GLVLDGRKLI 79

RNA recognition motif 2 (RRM2) found in RNA-binding protein 34 (RBM34) and similar proteins; This subfamily corresponds to the RRM2 of RBM34, a putative RNA-binding protein containing two RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains). Although the function of RBM34 remains unclear currently, its RRM domains may participate in mRNA processing. RBM34 may act as an mRNA processing-related protein.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 543266696 129 VYVTGLPPDITKDEFVQVMSKCGIIMRdpqteehkIKLYKDKEGNL-KGDGLCCYLKRESVQLALRlLDEAEIRGYKLHV 207
Cdd:cd12395    2 VFVGNLPFDIEEEELRKHFEDCGDVEA--------VRIVRDRETGIgKGFGYVLFKDKDSVDLALK-LNGSKLRGRKLRV 72

                 .
gi 543266696 208 E 208
Cdd:cd12395   73 K 73

RNA recognition motif (RRM) found in serine/arginine-rich splicing factor SRSF10, SRSF12 and similar proteins; This subfamily corresponds to the RRM of SRSF10 and SRSF12. 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). It 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. SRSF12, also termed 35 kDa SR repressor protein (SRrp35), or splicing factor, arginine/serine-rich 13B (SFRS13B), or splicing factor, arginine/serine-rich 19 (SFRS19), is a serine/arginine (SR) protein-like alternative splicing regulator that antagonizes authentic SR proteins in the modulation of alternative 5' splice site choice. For instance, it activates distal alternative 5' splice site of the adenovirus E1A pre-mRNA in vivo. Both, SRSF10 and SRSF12, contain 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
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 543266696 283 EDLRTECEKFGQVKKVLI----FDRHPDGVASVSFKEATEADLCKLTLNGRWFGGRQLSAE 339
Cdd:cd12312   15 DDLRREFGRYGPIVDVYIpldfYTRRPRGFAYIQFEDVRDAEDALYYLDRTRFLGREIEIQ 75

RNA recognition motif in the Set1-like family of histone-lysine N-methyltransferases; This subfamily corresponds to the RRM of the Set1-like family of histone-lysine N-methyltransferases which includes Set1A and Set1B that are ubiquitously expressed vertebrates histone methyltransferases exhibiting high homology to yeast Set1. Set1A and Set1B proteins exhibit a largely non-overlapping subnuclear distribution in euchromatic nuclear speckles, strongly suggesting that they bind to a unique set of target genes and thus make non-redundant contributions to the epigenetic control of chromatin structure and gene expression. With the exception of the catalytic component, the subunit composition of the Set1A and Set1B histone methyltransferase complexes are identical. Each complex contains six human homologs of the yeast Set1/COMPASS complex, including Set1A or Set1B, Ash2 (homologous to yeast Bre2), CXXC finger protein 1 (CFP1; homologous to yeast Spp1), Rbbp5 (homologous to yeast Swd1), Wdr5 (homologous to yeast Swd3), and Wdr82 (homologous to yeast Swd2). The genomic targeting of these complexes is determined by the identity of the catalytic subunit present in each histone methyltransferase complex. Thus, the Set1A and Set1B complexes may exhibit both overlapping and non-redundant properties. Both Set1A and Set1B contain an N-terminal RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain), an N- SET domain, and a C-terminal catalytic SET domain followed by a post-SET domain. In contrast to Set1B, Set1A additionally contains an HCF-1 binding motif that interacts with HCF-1 in vivo.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 543266696 278 LNE-IRED-LRTECEKFGQVKKVLIFdRHPD-----GVASVSFKEATEADLCKLTLNGRWFGGRQLSAE 339
Cdd:cd12304   10 LNDnINEGfLKDMCKKYGEVEEVKIY-FHPKtgkhlGLARVVFDTTKGAKDCVEKLNQTSVMGNIIHVF 77

RNA recognition motif 2 (RRM2) found in the Hu proteins family, Drosophila sex-lethal (SXL), and similar proteins; This subfamily corresponds to the RRM2 of Hu proteins and SXL. The Hu proteins family represents a group of RNA-binding proteins involved in diverse biological processes. Since the Hu proteins share high homology with the Drosophila embryonic lethal abnormal vision (ELAV) protein, the Hu family is sometimes referred to as the ELAV family. Drosophila ELAV is exclusively expressed in neurons and is required for the correct differentiation and survival of neurons in flies. The neuronal members of the Hu family include Hu-antigen B (HuB or ELAV-2 or Hel-N1), Hu-antigen C (HuC or ELAV-3 or PLE21), and Hu-antigen D (HuD or ELAV-4), which play important roles in neuronal differentiation, plasticity and memory. HuB is also expressed in gonads. Hu-antigen R (HuR or ELAV-1 or HuA) is the ubiquitously expressed Hu family member. It has a variety of biological functions mostly related to the regulation of cellular response to DNA damage and other types of stress. Hu proteins perform their cytoplasmic and nuclear molecular functions by coordinately regulating functionally related mRNAs. In the cytoplasm, Hu proteins recognize and bind to AU-rich RNA elements (AREs) in the 3' untranslated regions (UTRs) of certain target mRNAs, such as GAP-43, vascular epithelial growth factor (VEGF), the glucose transporter GLUT1, eotaxin and c-fos, and stabilize those ARE-containing mRNAs. They also bind and regulate the translation of some target mRNAs, such as neurofilament M, GLUT1, and p27. In the nucleus, Hu proteins function as regulators of polyadenylation and alternative splicing. Each Hu protein contains three RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains). RRM1 and RRM2 may cooperate in binding to an ARE. RRM3 may help to maintain the stability of the RNA-protein complex, and might also bind to poly(A) tails or be involved in protein-protein interactions. Also included in this subfamily is the sex-lethal protein (SXL) from Drosophila melanogaster. SXL governs sexual differentiation and X chromosome dosage compensation in flies. 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 RRMs that show high preference to bind single-stranded, uridine-rich target RNA transcripts.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 543266696 127 TNVYVTGLPPDITKDEFVQVMSKCGIIMRDpqteehkiKLYKDK-EGNLKGDGLCCYLKRESVQLALRLLD 196
Cdd:cd12376    1 ANLYVSGLPKTMTQKELEQLFSQYGRIITS--------RILRDQlTGVSRGVGFIRFDKRIEAEEAIKGLN 63

RNA recognition motif (RRM) found in U2AF homology motif kinase 1 (UHMK1) and similar proteins; This subgroup corresponds to the RRM of UHMK1. UHMK1, also termed kinase interacting with stathmin (KIS) or P-CIP2, is a serine/threonine protein kinase functionally related to RNA metabolism and neurite outgrowth. It contains an N-terminal kinase domain and a C-terminal RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain), with high homology to the corresponding motif of the mammalian U2 small nuclear ribonucleoprotein auxiliary factor U2AF 65 kDa subunit (U2AF65 or U2AF2). UHMK1 targets two key regulators of cell proliferation and migration, the cyclin-dependent kinase (CDK) inhibitor p27Kip1 and the microtubule-destabilizing protein stathmin. It plays a critical role during vascular wound repair by preventing excessive vascular smooth muscle cell (VSMC) migration into the vascular lesion. Moreover, UHMK1 may control cell migration and neurite outgrowth by interacting with and phosphorylating the splicing factor SF1, thereby probably contributing to the control of protein expression. Furthermore, UHMK1 may be functionally related to microtubule dynamics and axon development. It localizes to RNA granules, interacts with three proteins found in RNA granules (KIF3A, NonO, and eEF1A), and further enhances the local translation. UHMK1 is highly expressed in regions of the brain implicated in schizophrenia and may play a role in susceptibility to schizophrenia.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 543266696 280 EIREDLRTECEKFGQVKKVLIFDRHP-DGVASVSFKEATEADLCKLTLNGRWFGGR 334
Cdd:cd12465   25 DIVEDVREECQKYGPVVSLLIPKENPgKGQVFVEYANAGDSKAAQKMLTGRMFDGK 80

RNA recognition motif (RRM) found in cleavage stimulation factor subunit 2 (CSTF2), cleavage stimulation factor subunit 2 tau variant (CSTF2T) and similar proteins; This subgroup corresponds to the RRM domain of CSTF2, its tau variant and eukaryotic homologs. CSTF2, also termed cleavage stimulation factor 64 kDa subunit (CstF64), is the vertebrate conterpart of yeast mRNA 3'-end-processing protein RNA15. It is expressed in all somatic tissues and is one of three cleavage stimulatory factor (CstF) subunits required for polyadenylation. CstF64 contains an N-terminal RNA recognition motif (RRM), also known as RBD (RNA binding domain) or RNP (ribonucleoprotein domain), a CstF77-binding domain, a repeated MEARA helical region and a conserved C-terminal domain reported to bind the transcription factor PC-4. During polyadenylation, CstF interacts with the pre-mRNA through the RRM of CstF64 at U- or GU-rich sequences within 10 to 30 nucleotides downstream of the cleavage site. CSTF2T, also termed tauCstF64, is a paralog of the X-linked cleavage stimulation factor CstF64 protein that supports polyadenylation in most somatic cells. It is expressed during meiosis and subsequent haploid differentiation in a more limited set of tissues and cell types, largely in meiotic and postmeiotic male germ cells, and to a lesser extent in brain. The loss of CSTF2T will cause male infertility, as it is necessary for spermatogenesis and fertilization. Moreover, CSTF2T is required for expression of genes involved in morphological differentiation of spermatids, as well as for genes having products that function during interaction of motile spermatozoa with eggs. It promotes germ cell-specific patterns of polyadenylation by using its RRM to bind to different sequence elements downstream of polyadenylation sites than does CstF64.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 543266696 128 NVYVTGLPPDITKDEFVQVMSKCGIIMrdpqteehKIKLYKDKE-GNLKGDGLCCYLKRESVQLALRLLDEAEIRGYKLH 206
Cdd:cd12671    8 SVFVGNIPYEATEEQLKDIFSEVGPVV--------SFRLVYDREtGKPKGYGFCEYQDQETALSAMRNLNGYELNGRALR 79

                 ....
gi 543266696 207 VEVA 210
Cdd:cd12671   80 VDNA 83

RNA recognition motif (RRM) found in serine/arginine-rich splicing factor 12 (SRSF12) and similar proteins; This subgroup corresponds to the RRM of SRSF12, also termed 35 kDa SR repressor protein (SRrp35), or splicing factor, arginine/serine-rich 13B (SFRS13B), or splicing factor, arginine/serine-rich 19 (SFRS19). SRSF12 is a serine/arginine (SR) protein-like alternative splicing regulator that antagonizes authentic SR proteins in the modulation of alternative 5' splice site choice. For instance, it activates distal alternative 5' splice site of the adenovirus E1A pre-mRNA in vivo. SRSF12 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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 543266696 283 EDLRTECEKFGQVKKVLI----FDRHPDGVASVSFKEATEADLCKLTLNGRWFGGRQLSAETWDG 343
Cdd:cd12560   15 EDLRREFGRYGPIVDVYIpldfYNRRPRGFAYIQFEDVRDAEDALYNLNRKWVCGRQIEIQFAQG 79

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
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 543266696 282 REDLRTECEKFGQVKKV-LIFDR--HPDGVASVSFKEATEADLCKLTLNGRWFGGRQLS 337
Cdd:cd12392   16 KEELEELFKQHGTVKDVrLVTYRngKPKGLAYVEYENEADASQAVLKTDGTEIKDHTIS 74

RNA recognition motif 3 (RRM3) found in RNA-binding protein 19 (RBM19) and RNA recognition motif 2 found in multiple RNA-binding domain-containing protein 1 (MRD1); This subfamily corresponds to the RRM3 of RBM19 and RRM2 of MRD1. RBM19, also termed RNA-binding domain-1 (RBD-1), is a nucleolar protein conserved in eukaryotes involved in ribosome biogenesis by processing rRNA and is essential for preimplantation development. It has a unique domain organization containing 6 conserved RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains). MRD1 is encoded by a novel yeast gene MRD1 (multiple RNA-binding domain). It is well conserved in yeast and its homologs exist in all eukaryotes. MRD1 is present in the nucleolus and the nucleoplasm. It interacts with the 35 S precursor rRNA (pre-rRNA) and U3 small nucleolar RNAs (snoRNAs). It is essential for the initial processing at the A0-A2 cleavage sites in the 35 S pre-rRNA. MRD1 contains 5 conserved RRMs, which may play an important structural role in organizing specific rRNA processing events.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 543266696 283 EDLRTECEKFGQVKKVLI-FDR---HPDGVASVSFKEATEADLCKLTLNGRWFGGRQL 336
Cdd:cd12316   14 DELRELFEAFGKISEVHIpLDKqtkRSKGFAFVLFVIPEDAVKAYQELDGSIFQGRLL 71

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
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 543266696 284 DLRTECEKFGQVKKVLIF----DRHPDGVASVSFKEATEADLCKLTLNGRWFGGRQLSA 338
Cdd:cd12393   17 DLHQIFSKYGKVVKVTILkdkeTRKSKGVAFVLFLDRESAHNAVRAMNNKELFGRTLKC 75

RNA recognition motif 1 (RRM1) found in vertebrate APOBEC-1 complementation factor (ACF); This subgroup corresponds to the RRM1 of ACF, also termed APOBEC-1-stimulating protein, 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. ACF shuttles between the cytoplasm and nucleus. It contains three RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), which display high affinity for an 11 nucleotide AU-rich mooring sequence 3' of the edited cytidine in apoB mRNA. All three RRMs may be required for complementation of editing activity in living cells. RRM2/3 are implicated in ACF interaction with APOBEC-1.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 543266696 129 VYVTGLPPDITKDEFVQVMSKCGIImrdpqteeHKIKLYKDKEGNLKGDGLCCYLKRESVQLALRLLDEAEIRGYKL 205
Cdd:cd12486    4 IFIGKLPRDLFEDELVPLCEKIGKI--------YEMRMMMDFNGNNRGYAFVTFSNKQEARNAIKQLNNYEIRNGRL 72

RNA recognition motif 2 (RRM2) found in ribonucleoprotein PTB-binding raver-1, raver-2 and similar proteins; This subfamily corresponds to the RRM2 of raver-1 and raver-2. Raver-1 is a ubiquitously expressed heterogeneous nuclear ribonucleoprotein (hnRNP) that serves as a co-repressor of the nucleoplasmic splicing repressor polypyrimidine tract-binding protein (PTB)-directed splicing of select mRNAs. It shuttles between the cytoplasm and the nucleus and can accumulate in the perinucleolar compartment, a dynamic nuclear substructure that harbors PTB. Raver-1 also modulates focal adhesion assembly by binding to the cytoskeletal proteins, including alpha-actinin, vinculin, and metavinculin (an alternatively spliced isoform of vinculin) at adhesion complexes, particularly in differentiated muscle tissue. Raver-2 is a novel member of the heterogeneous nuclear ribonucleoprotein (hnRNP) family. It shows high sequence homology to raver-1. Raver-2 exerts a spatio-temporal expression pattern during embryogenesis and is mainly limited to differentiated neurons and glia cells. Although it displays nucleo-cytoplasmic shuttling in heterokaryons, raver2 localizes to the nucleus in glia cells and neurons. Raver-2 can interact with PTB and may participate in PTB-mediated RNA-processing. However, there is no evidence indicating that raver-2 can bind to cytoplasmic proteins. Both, raver-1 and raver-2, contain three N-terminal RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), two putative nuclear localization signals (NLS) at the N- and C-termini, a central leucine-rich region, and a C-terminal region harboring two [SG][IL]LGxxP motifs. They binds to RNA through the RRMs. In addition, the two [SG][IL]LGxxP motifs serve as the PTB-binding motifs in raver1. However, raver-2 interacts with PTB through the SLLGEPP motif only.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 543266696 131 VTGLPPDITKDEFVQVMSKCGIImrdpqteEHKIKLYKDKEGNLKGDGLCCYLKRESVQLALRLLDEAEIRGYKLHV 207
Cdd:cd12389    4 VTNLPLSFTEEQFEELVRPYGNV-------ERCFLVYSEVTGESKGYGFVEYTSKESAIRAKNQLHGRQIGGRALQV 73

RNA recognition motif 1 (RRM1) found in vertebrate heterogeneous nuclear ribonucleoprotein R (hnRNP R); This subgroup corresponds to the RRM1 of hnRNP R, which is a ubiquitously expressed nuclear RNA-binding protein that specifically binds mRNAs with a preference for poly(U) stretches. Upon binding of RNA, hnRNP R forms oligomers, most probably dimers. hnRNP R has been implicated in mRNA processing and mRNA transport, and also acts as a regulator to modify binding to ribosomes and RNA translation. It is predominantly located in axons of motor neurons and to a much lower degree in sensory axons. In axons of motor neurons, it also functions as a cytosolic protein and interacts with wild type of survival motor neuron (SMN) proteins directly, further providing a molecular link between SMN and the spliceosome. Moreover, hnRNP R plays an important role in neural differentiation and development, and in retinal development and light-elicited cellular activities. hnRNP R contains an acidic auxiliary N-terminal region, followed by two well defined and one degenerated RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), and a C-terminal RGG motif; it binds RNA through its RRM domains.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 543266696 127 TNVYVTGLPPDITKDEFVQVMSKCGII-----MRDPQTeehkiklykdkeGNLKGDGLCCYLKRESVQLALRLLDEAEIR 201
Cdd:cd12482    2 TEVFVGKIPRDLYEDELVPLFEKAGPIwdlrlMMDPLS------------GQNRGYAFITFCNKEAAQEAVKLCDNYEIR 69