hnRNP-L/PTB/hephaestus splicing factor family; Included in this family of heterogeneous ribonucleoproteins are PTB (polypyrimidine tract binding protein) and hnRNP-L. These proteins contain four RNA recognition motifs (rrm: pfam00067).

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 253723235    5 SSGKRITRPGNTD-DPSGGNKVLLLSIQNPLYPITVDVLYTVCNPVGKVQRIVIFKRNG-IQAMVEFESVLCAQKAKAAL 82
Cdd:TIGR01649  75 STSQEIKRDGNSDfDSAGPNKVLRVIVENPMYPITLDVLYQIFNPYGKVLRIVTFTKNNvFQALVEFESVNSAQHAKAAL 154

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 253723235   83 NGADIYAGCCTLKIEYARPTRLNVIRNDNDSWDYTKPYL-GRR 124
Cdd:TIGR01649 155 NGADIYNGCCTLKIEYAKPTRLNVKYNDDDSRDYTNPDLpGRR 197

hnRNP-L/PTB/hephaestus splicing factor family; Included in this family of heterogeneous ribonucleoproteins are PTB (polypyrimidine tract binding protein) and hnRNP-L. These proteins contain four RNA recognition motifs (rrm: pfam00067).

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 253723235    5 SSGKRITRPGNTD-DPSGGNKVLLLSIQNPLYPITVDVLYTVCNPVGKVQRIVIFKRNG-IQAMVEFESVLCAQKAKAAL 82
Cdd:TIGR01649  75 STSQEIKRDGNSDfDSAGPNKVLRVIVENPMYPITLDVLYQIFNPYGKVLRIVTFTKNNvFQALVEFESVNSAQHAKAAL 154

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 253723235   83 NGADIYAGCCTLKIEYARPTRLNVIRNDNDSWDYTKPYL-GRR 124
Cdd:TIGR01649 155 NGADIYNGCCTLKIEYAKPTRLNVKYNDDDSRDYTNPDLpGRR 197

RRM-like domain; This domain is related to the RRM domains suggesting it may have an RNA-binding function.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 253723235   25 VLLLSIQNPLYPITVDVLYTVCNPVGKVQ-RIVIFKRNGIQAMVEFESVLCAQKAKAALNGADIYAGCCTLKIEYARP 101
Cdd:pfam11835  12 VLRVTVSHILYPVTSEVLHQVYDTYGAVAvQVLAVSTWHVEALVSFMSSCDAERARSATHGRNIYDGGCLLDVQHAQP 89

hnRNP-L/PTB/hephaestus splicing factor family; Included in this family of heterogeneous ribonucleoproteins are PTB (polypyrimidine tract binding protein) and hnRNP-L. These proteins contain four RNA recognition motifs (rrm: pfam00067).

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 253723235    5 SSGKRITRPGNTD-DPSGGNKVLLLSIQNPLYPITVDVLYTVCNPVGKVQRIVIFKRNG-IQAMVEFESVLCAQKAKAAL 82
Cdd:TIGR01649  75 STSQEIKRDGNSDfDSAGPNKVLRVIVENPMYPITLDVLYQIFNPYGKVLRIVTFTKNNvFQALVEFESVNSAQHAKAAL 154

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 253723235   83 NGADIYAGCCTLKIEYARPTRLNVIRNDNDSWDYTKPYL-GRR 124
Cdd:TIGR01649 155 NGADIYNGCCTLKIEYAKPTRLNVKYNDDDSRDYTNPDLpGRR 197

RNA recognition motif 2 (RRM2) found in heterogeneous nuclear ribonucleoprotein L (hnRNP-L) and similar proteins; This subfamily corresponds to the RRM2 of heterogeneous nuclear ribonucleoprotein L (hnRNP-L), heterogeneous nuclear ribonucleoprotein L-like (hnRNP-LL), and similar proteins. 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 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. It is closely related in domain structure and sequence to hnRNP-L, which contains three RNA-recognition motifs (RRMs), also known as RBD (RNA binding domain) or RNP (ribonucleoprotein domain).

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 253723235  23 NKVLLLSIQNPLYPITVDVLYTVCNPVGKVQRIVIFKRNGIQAMVEFESVLCAQKAKAALNGADIYAGCCTLKIEYARPT 102
Cdd:cd12694    1 NHVLLFTILNPLYPITVDVIHTICSPYGKVLRIVIFRKNGVQAMVEFDSVESAQRAKAALNGADIYSGCCTLKIEYAKPT 80

                 ....*.
gi 253723235 103 RLNVIR 108
Cdd:cd12694   81 RLNVYK 86

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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 253723235  25 VLLLSIQNPLYPITVDVLYTVCNPVGKVQRIVIFKRN-GIQAMVEFESVLCAQKAKAALNGADIYAGCCTLKIEYARPTR 103
Cdd:cd12422    1 VLLVTVTNLLYPVTVDVLHQVFSPYGAVEKIVIFEKGtGVQALVQFDSVESAEAAKKALNGRNIYDGCCTLDIQFSRLKE 80

                 ....*
gi 253723235 104 LNVIR 108
Cdd:cd12422   81 LTVKY 85

RNA recognition motif 2 (RRM2) found in plant polypyrimidine tract-binding protein homolog 3 (PTBPH3); This subfamily corresponds to the RRM2 of PTBPH3. Although its biological roles remain unclear, PTBPH3 shows significant sequence similarity to polypyrimidine tract binding protein (PTB) that 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. Like PTB, PTBPH3 contains four RNA recognition motifs (RRM), also known as RBD (RNA binding domain) or RNP (ribonucleoprotein domain).

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 253723235  23 NKVLLLSIQNPLYPITVDVLYTVCNPVGKVQRIVIFKRN-GIQAMVEFESVLCAQKAKAALNGADIYAGCCTLKIEYARP 101
Cdd:cd12692    2 NRILLVTIHHPLYPITVDVLHQVFSPHGFVEKIVTFQKSaGLQALIQYQSQQSAVQARSALQGRNIYDGCCQLDIQFSNL 81

                 ....*
gi 253723235 102 TRLNV 106
Cdd:cd12692   82 QELQV 86

RNA recognition motif 2 (RRM2) found in vertebrate polypyrimidine tract-binding protein 1 (PTB); This subgroup corresponds to the RRM2 of PTB, also known as 58 kDa RNA-binding protein PPTB-1 or heterogeneous nuclear ribonucleoprotein I (hnRNP I), an important negative regulator of alternative splicing in mammalian cells. PTB also functions at several other aspects of mRNA metabolism, including mRNA localization, stabilization, polyadenylation, and translation. PTB contains four RNA recognition motifs (RRM), also known as RBD (RNA binding domain) or RNP (ribonucleoprotein domain). RRM1 and RRM2 are independent from each other and separated by flexible linkers. By contrast, there is an unusual and conserved interdomain interaction between RRM3 and RRM4. It is widely held that only RRMs 3 and 4 are involved in RNA binding and RRM2 mediates PTB homodimer formation. However, new evidence shows that the RRMs 1 and 2 also contribute substantially to RNA binding. Moreover, PTB may not always dimerize to repress splicing. It is a monomer in solution.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 253723235  20 SGGNKVLLLSIQNPLYPITVDVLYTVCNPVGKVQRIVIF-KRNGIQAMVEFESVLCAQKAKAALNGADIYAGCCTLKIEY 98
Cdd:cd12782    2 AGQSPVLRIIVENLFYPVTLDVLHQIFSKFGTVLKIITFtKNNQFQALLQYADPVSAQHAKLSLDGQNIYNACCTLRIDF 81

                         90       100
                 ....*....|....*....|...
gi 253723235  99 ARPTRLNVIRNDNDSWDYTKPYL 121
Cdd:cd12782   82 SKLTSLNVKYNNDKSRDYTRPDL 104

RNA recognition motif 2 (RRM2) found in vertebrate regulator of differentiation 1 (Rod1); This subgroup corresponds to the RRM2 of ROD1 coding protein Rod1, 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 and negatively regulates the onset of differentiation. ROD1 is predominantly expressed in hematopoietic cells or organs. It might play a role controlling differentiation in mammals. Rod1 contains four repeats of RNA recognition motifs (RRM), also known as RBD (RNA binding domain) or RNP (ribonucleoprotein domain) and does have RNA binding activities.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 253723235  21 GGNKVLLLSIQNPLYPITVDVLYTVCNPVGKVQRIVIF-KRNGIQAMVEFESVLCAQKAKAALNGADIYAGCCTLKIEYA 99
Cdd:cd12784    1 GQSPVLRIIVENLFYPVTLEVLHQIFSKFGTVLKIITFtKNNQFQALLQYADPMNAHHAKVALDGQNIYNACCTLRIEFS 80

                         90
                 ....*....|....*....
gi 253723235 100 RPTRLNVIRNDNDSWDYTK 118
Cdd:cd12784   81 KLTSLNVKYNNDKSRDFTR 99

RNA recognition motif 2 (RRM2) found in plant polypyrimidine tract-binding protein homolog 1 and 2 (PTBPH1 and PTBPH2); This subfamily corresponds to the RRM2 of PTBPH1 and PTBPH2. Although their biological roles remain unclear, PTBPH1 and PTBPH2 show significant sequence similarity to polypyrimidine tract binding protein (PTB) that 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. Both, PTBPH1 and PTBPH2, contain three RNA recognition motifs (RRM), also known as RBD (RNA binding domain) or RNP (ribonucleoprotein domain).

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 253723235  25 VLLLSIQN-PLYPITVDVLYTVCNPVGKVQRIVIF-KRNGIQAMVEFESVLCAQKAKAALNGADI-------YAGCCTLK 95
Cdd:cd12691    3 VLLVTIEGvEAGDVSIDVLHLVFSAFGFVHKIATFeKTAGFQALVQFTDAETASAARSALDGRSIpryllpeHVGPCSLR 82

                         90
                 ....*....|.
gi 253723235  96 IEYARPTRLNV 106
Cdd:cd12691   83 ISYSAHTDLNV 93

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 253723235   35 YPITVDVLYTVCNPVGKVQRIVIFKRNGIQAM----VEFESVLCAQKAKAALNGADIY 88
Cdd:pfam00076   8 PDTTEEDLKDLFSKFGPIKSIRLVRDETGRSKgfafVEFEDEEDAEKAIEALNGKELG 65

RNA recognition motif 1 (RRM1) found in the U1A/U2B"/SNF protein family; This subfamily corresponds to the RRM1 of U1A/U2B"/SNF protein family which contains 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. Moreover, U2B" does not require an auxiliary protein for binding to RNA, and its nuclear transport is independent of U2 snRNA binding.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 253723235  42 LYTVCNPVGKVQRIVIFKRNGI--QAMVEFESVLCAQKAKAALNGADIYAGccTLKIEYAR 100
Cdd:cd12246   20 LYALFSQFGPVLDIVASKSLKMrgQAFVVFKDVESATNALRALQGFPFYGK--PMRIQYAK 78

RNA recognition motif 3 (RRM3) found in vertebrate RNA-binding protein 39 (RBM39) and similar proteins; This subfamily corresponds to the RRM3 of RBM39, also termed hepatocellular carcinoma protein 1, or RNA-binding region-containing protein 2, or splicing factor HCC1, ia nuclear autoantigen that contains an N-terminal arginine/serine rich (RS) motif and three RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains). An octapeptide sequence called the RS-ERK motif is repeated six times in the RS region of RBM39. Based on the specific domain composition, RBM39 has been classified into a family of non-snRNP (small nuclear ribonucleoprotein) splicing factors that are usually not complexed to snRNAs.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|.
gi 253723235  46 CNPVGKVQRIVIFKRN--GIqAMVEFESVLCAQKAKAALNG 84
Cdd:cd12285   32 CSKYGPVLHIYVDKNSpqGN-VYVKFKTIEAAQKCVQAMNG 71

RNA recognition motif 3 (RRM3) found in plant polypyrimidine tract-binding protein homolog 3 (PTBPH3); This subgroup corresponds to the RRM3 of PTBPH3. Although its biological roles remain unclear, PTBPH3 shows significant sequence similarity to polypyrimidine tract binding protein (PTB) that 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. Like PTB, PTBPH3 contains four RNA recognition motifs (RRM), also known as RBD (RNA binding domain) or RNP (ribonucleoprotein domain).

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 253723235  25 VLLLSIQNPLYpITVDVLYTVCNPVGKVQRIVIFKRNGIQAMVEFESVLCAQKAKAALNGADIY 88
Cdd:cd12698    3 VLLVSNLNPEK-VDVDKLFNLFSLYGNIVRIKILRNKPDHALIQMSDPFQAELAVNYLKGAMLF 65

RNA recognition motif 3 (RRM3) found in vertebrate polypyrimidine tract-binding protein 2 (PTBP2); This subgroup corresponds to the RRM3 of PTBP2, also known as neural polypyrimidine tract-binding protein or neurally-enriched homolog of PTB (nPTB), highly homologous to polypyrimidine tract binding protein (PTB) and 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. PTBP2 contains four RNA recognition motifs (RRMs), also known as RBD (RNA binding domain) or RNP (ribonucleoprotein domain).

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 253723235   9 RITRPGNTddpSGGNKVLLLSIQNPLYpITVDVLYTVCNPVGKVQRIVIFKRNGIQAMVEFESVLCAQKAKAALNGADIY 88
Cdd:cd12696    2 RVGMPGVS---AGGNTVLLVSNLNEEM-VTPQSLFTLFGVYGDVQRVKILYNKKDSALIQMADGNQSQLAMSHLNGQKMY 77

                 .
gi 253723235  89 A 89
Cdd:cd12696   78 G 78