RNA recognition motif 2 (RRM2) found in vertebrate serine/arginine-rich splicing factor 5 (SRSF5); This subgroup corresponds to the RRM2 of SRSF5, also termed delayed-early protein HRS, or pre-mRNA-splicing factor SRp40, or splicing factor, arginine/serine-rich 5 (SFRS5), is an essential splicing regulatory serine/arginine (SR) protein that regulates both alternative splicing and basal splicing. It is the only SR protein efficiently selected from nuclear extracts (NE) by the splicing enhancer (ESE) and it is necessary for enhancer activation. SRSF5 also functions as a factor required for insulin-regulated splice site selection for protein kinase C (PKC) betaII mRNA. It is involved in the regulation of PKCbetaII exon inclusion by insulin via its increased phosphorylation by a phosphatidylinositol 3-kinase (PI 3-kinase) signaling pathway. Moreover, SRSF5 can regulate alternative splicing in exon 9 of glucocorticoid receptor pre-mRNA in a dose-dependent manner. SRSF5 contains two N-terminal RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), followed by a C-terminal RS domains rich in serine-arginine dipeptides. The specific RNA binding by SRSF5 requires the phosphorylation of its SR domain.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958782078  99 RNAPPVRTENRLIVENLSSRVSWQDLKDFMRQAGEVTFADAHRPKLNEGVVEFASYGDLKNAIEKLSGKEINGRKIKLIE 178
Cdd:cd12765     1 RNAPPMRTENRLIVENLSSRVSWQDLKDFMRQAGEVTFADAHRPKLNEGVVEFASYSDLKNAIEKLSGKEINGRKIKLIE 80

                  .
gi 1958782078 179 G 179
Cdd:cd12765    81 G 81

RNA recognition motif 2 (RRM2) found in vertebrate serine/arginine-rich splicing factor 5 (SRSF5); This subgroup corresponds to the RRM2 of SRSF5, also termed delayed-early protein HRS, or pre-mRNA-splicing factor SRp40, or splicing factor, arginine/serine-rich 5 (SFRS5), is an essential splicing regulatory serine/arginine (SR) protein that regulates both alternative splicing and basal splicing. It is the only SR protein efficiently selected from nuclear extracts (NE) by the splicing enhancer (ESE) and it is necessary for enhancer activation. SRSF5 also functions as a factor required for insulin-regulated splice site selection for protein kinase C (PKC) betaII mRNA. It is involved in the regulation of PKCbetaII exon inclusion by insulin via its increased phosphorylation by a phosphatidylinositol 3-kinase (PI 3-kinase) signaling pathway. Moreover, SRSF5 can regulate alternative splicing in exon 9 of glucocorticoid receptor pre-mRNA in a dose-dependent manner. SRSF5 contains two N-terminal RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), followed by a C-terminal RS domains rich in serine-arginine dipeptides. The specific RNA binding by SRSF5 requires the phosphorylation of its SR domain.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958782078  99 RNAPPVRTENRLIVENLSSRVSWQDLKDFMRQAGEVTFADAHRPKLNEGVVEFASYGDLKNAIEKLSGKEINGRKIKLIE 178
Cdd:cd12765     1 RNAPPMRTENRLIVENLSSRVSWQDLKDFMRQAGEVTFADAHRPKLNEGVVEFASYSDLKNAIEKLSGKEINGRKIKLIE 80

                  .
gi 1958782078 179 G 179
Cdd:cd12765    81 G 81

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 1958782078   6 VFIGRLNPAAREKDVERFFKGYGRIRDIDLK-------RGFGFVEFEDPRDADDAVYELDGKELCSERVT 68
Cdd:pfam00076   1 LFVGNLPPDTTEEDLKDLFSKFGPIKSIRLVrdetgrsKGFAFVEFEDEEDAEKAIEALNGKELGGRELK 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 1958782078   6 VFIGRLNPAAREKDVERFFKGYGRIRDIDL-------KRGFGFVEFEDPRDADDAVYELDGKELCSERVTIEHARarsrg 78
Cdd:TIGR01628  91 IFVKNLDKSVDNKALFDTFSKFGNILSCKVatdengkSRGYGFVHFEKEESAKAAIQKVNGMLLNDKEVYVGRFI----- 165

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958782078  79 grgrgrysdrfssrrPRNDRRNAPPVRTENrLIVENLSSRVSWQDLKDFMRQAGEVTFADAHRPKLNE----GVVEFASY 154
Cdd:TIGR01628 166 ---------------KKHEREAAPLKKFTN-LYVKNLDPSVNEDKLRELFAKFGEITSAAVMKDGSGRsrgfAFVNFEKH 229

                         170
                  ....*....|....*....
gi 1958782078 155 GDLKNAIEKLSGKEINGRK 173
Cdd:TIGR01628 230 EDAAKAVEEMNGKKIGLAK 248

RNA recognition motif;

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1958782078  109 RLIVENLSSRVSWQDLKDFMRQAGEVTFADAHRPKLNE-----GVVEFASYGDLKNAIEKLSGKEINGRKIKL 176
Cdd:smart00360   1 TLFVGNLPPDTTEEELRELFSKFGKVESVRLVRDKETGkskgfAFVEFESEEDAEKALEALNGKELDGRPLKV 73

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

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1958782078 108 NRLIVENLSSRVSWQDLKDFMRQAGEVTFA------DAHRPKlNEGVVEFASYGDLKNAIEKLSGKEINGRKIK 175
Cdd:COG0724     2 MKIYVGNLPYSVTEEDLRELFSEYGEVTSVklitdrETGRSR-GFGFVEMPDDEEAQAAIEALNGAELMGRTLK 74

ELAV/HuD family splicing factor; This model describes the ELAV/HuD subfamily of splicing factors found in metazoa. HuD stands for the human paraneoplastic encephalomyelitis antigen D of which there are 4 variants in human. ELAV stnds for the Drosophila Embryonic lethal abnormal visual protein. ELAV-like splicing factors are also known in human as HuB (ELAV-like protein 2), HuC (ELAV-like protein 3, Paraneoplastic cerebellar degeneration-associated antigen) and HuR (ELAV-like protein 1). These genes are most closely related to the sex-lethal subfamily of splicing factors found in Dipteran insects (TIGR01659). These proteins contain 3 RNA-recognition motifs (rrm: pfam00076).

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1958782078   3 GCRVFIGRLNPAAREKDVERFFKGYGRI--------RDIDLKRGFGFVEFEDPRDADDAVYELDGK--ELCSERVTIE 70
Cdd:TIGR01661  89 GANLYVSGLPKTMTQHELESIFSPFGQIitsrilsdNVTGLSKGVGFIRFDKRDEADRAIKTLNGTtpSGCTEPITVK 166

RNA recognition motif 2 (RRM2) found in vertebrate serine/arginine-rich splicing factor 5 (SRSF5); This subgroup corresponds to the RRM2 of SRSF5, also termed delayed-early protein HRS, or pre-mRNA-splicing factor SRp40, or splicing factor, arginine/serine-rich 5 (SFRS5), is an essential splicing regulatory serine/arginine (SR) protein that regulates both alternative splicing and basal splicing. It is the only SR protein efficiently selected from nuclear extracts (NE) by the splicing enhancer (ESE) and it is necessary for enhancer activation. SRSF5 also functions as a factor required for insulin-regulated splice site selection for protein kinase C (PKC) betaII mRNA. It is involved in the regulation of PKCbetaII exon inclusion by insulin via its increased phosphorylation by a phosphatidylinositol 3-kinase (PI 3-kinase) signaling pathway. Moreover, SRSF5 can regulate alternative splicing in exon 9 of glucocorticoid receptor pre-mRNA in a dose-dependent manner. SRSF5 contains two N-terminal RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), followed by a C-terminal RS domains rich in serine-arginine dipeptides. The specific RNA binding by SRSF5 requires the phosphorylation of its SR domain.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958782078  99 RNAPPVRTENRLIVENLSSRVSWQDLKDFMRQAGEVTFADAHRPKLNEGVVEFASYGDLKNAIEKLSGKEINGRKIKLIE 178
Cdd:cd12765     1 RNAPPMRTENRLIVENLSSRVSWQDLKDFMRQAGEVTFADAHRPKLNEGVVEFASYSDLKNAIEKLSGKEINGRKIKLIE 80

                  .
gi 1958782078 179 G 179
Cdd:cd12765    81 G 81

RNA recognition motif 2 (RRM2) found in serine/arginine-rich splicing factor 4 (SRSF4) and similar proteins; This subfamily corresponds to the RRM2 of three serine/arginine (SR) proteins: serine/arginine-rich splicing factor 4 (SRSF4 or SRp75 or SFRS4), serine/arginine-rich splicing factor 5 (SRSF5 or SRp40 or SFRS5 or HRS), serine/arginine-rich splicing factor 6 (SRSF6 or SRp55). SRSF4 plays an important role in both, constitutive and alternative, splicing of many pre-mRNAs. It can shuttle between the nucleus and cytoplasm. SRSF5 regulates both alternative splicing and basal splicing. It is the only SR protein efficiently selected from nuclear extracts (NE) by the splicing enhancer (ESE) and is essential for enhancer activation. SRSF6 preferentially interacts with a number of purine-rich splicing enhancers (ESEs) to activate splicing of the ESE-containing exon. It is the only protein from HeLa nuclear extract or purified SR proteins that specifically binds B element RNA after UV irradiation. SRSF6 may also recognize different types of RNA sites. Members in this family contain two N-terminal RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), followed by a C-terminal RS domains rich in serine-arginine dipeptides.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1958782078 108 NRLIVENLSSRVSWQDLKDFMRQAGEVTFADAHRPKLNEGVVEFASYGDLKNAIEKLSGKEINGRKIKLIEG 179
Cdd:cd12600     1 YRLIVENLSSRVSWQDLKDYMRQAGEVTYADAHKQRKNEGVVEFASYSDMKNAIEKLDGTELNGRKIRLVED 72

RNA recognition motif 2 (RRM2) found found in vertebrate serine/arginine-rich splicing factor 6 (SRSF6); This subgroup corresponds to the RRM2 of SRSF6, also termed pre-mRNA-splicing factor SRp55, an essential splicing regulatory serine/arginine (SR) protein that preferentially interacts with a number of purine-rich splicing enhancers (ESEs) to activate splicing of the ESE-containing exon. It is the only protein from HeLa nuclear extract or purified SR proteins that specifically binds B element RNA after UV irradiation. SRSF6 may also recognize different types of RNA sites. For instance, it does not bind to the purine-rich sequence in the calcitonin-specific ESE, but binds to a region adjacent to the purine tract. Moreover, cellular levels of SRSF6 may control tissue-specific alternative splicing of the calcitonin/ calcitonin gene-related peptide (CGRP) pre-mRNA. SRSF6 contains two N-terminal RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), followed by a C-terminal RS domains rich in serine-arginine dipeptides.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1958782078 109 RLIVENLSSRVSWQDLKDFMRQAGEVTFADAHRPKLNEGVVEFASYGDLKNAIEKLSGKEINGRKIKLIEG 179
Cdd:cd12766     2 RLIVENLSSRCSWQDLKDFMRQAGEVTYADAHKERTNEGVIEFRSYSDMKRALEKLDGTEINGRKIRLVED 72

RNA recognition motif 2 (RRM2) found in vertebrate serine/arginine-rich splicing factor 4 (SRSF4); This subgroup corresponds to the RRM2 of SRSF4, also termed pre-mRNA-splicing factor SRp75, or SRP001LB, or splicing factor, arginine/serine-rich 4 (SFRS4), a splicing regulatory serine/arginine (SR) protein that plays an important role in both constitutive splicing and alternative splicing of many pre-mRNAs. For instance, it interacts with heterogeneous nuclear ribonucleoproteins, hnRNP G and hnRNP E2, and further regulates the 5' splice site of tau exon 10, whose misregulation causes frontotemporal dementia. SFRS4 also induces production of HIV-1 vpr mRNA through the inhibition of the 5'-splice site of exon 3. In addition, SRSF4 activates splicing of the cardiac troponin T (cTNT) alternative exon by direct interactions with the cTNT exon 5 enhancer RNA. SRSF4 can shuttle between the nucleus and cytoplasm. It contains an N-terminal RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain), a glycine-rich region, an internal region homologous to the RRM, and a very long, highly phosphorylated C-terminal RS domains rich in serine-arginine dipeptides.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958782078  99 RNAPPVRTENRLIVENLSSRVSWQDLKDFMRQAGEVTFADAHRPKLNEGVVEFASYGDLKNAIEKLSGKEINGRKIKLIE 178
Cdd:cd12764     4 KYGPPTRTEYRLIVENLSSRCSWQDLKDYMRQAGEVTYADAHKGRKNEGVIEFVSYSDMKRALEKLDGTEVNGRKIRLVE 83

RNA recognition motif 1 (RRM1) found in vertebrate serine/arginine-rich splicing factor 4 (SRSF4); This subgroup corresponds to the RRM1 of SRSF4, also termed pre-mRNA-splicing factor SRp75, or SRP001LB, or splicing factor, arginine/serine-rich 4 (SFRS4). SRSF4 is a splicing regulatory serine/arginine (SR) protein that plays an important role in both constitutive splicing and alternative splicing of many pre-mRNAs. For instance, it interacts with heterogeneous nuclear ribonucleoproteins, hnRNP G and hnRNP E2, and further regulates the 5' splice site of tau exon 10, whose misregulation causes frontotemporal dementia. SFSF4 also induces production of HIV-1 vpr mRNA through the inhibition of the 5'-splice site of exon 3. In addition, it activates splicing of the cardiac troponin T (cTNT) alternative exon by direct interactions with the cTNT exon 5 enhancer RNA. SRSF4 can shuttle between the nucleus and cytoplasm. It contains an N-terminal RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain), a glycine-rich region, an internal region homologous to the RRM, and a very long, highly phosphorylated C-terminal SR domains rich in serine-arginine dipeptides.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1958782078   5 RVFIGRLNPAAREKDVERFFKGYGRIRDIDLKRGFGFVEFEDPRDADDAVYELDGKELCSERVTIEH 71
Cdd:cd12594     3 RVYIGRLSYQARERDVERFFKGYGKILEVDLKNGYGFVEFDDLRDADDAVYELNGKDLCGERVIVEH 69

RNA recognition motif 1 (RRM1) found in serine/arginine-rich splicing factor 1 (SRSF1) and similar proteins; This subgroup corresponds to the RRM1 in three serine/arginine (SR) proteins: serine/arginine-rich splicing factor 1 (SRSF1 or ASF-1), serine/arginine-rich splicing factor 9 (SRSF9 or SRp30C), and plant pre-mRNA-splicing factor SF2 (SR1). SRSF1 is a shuttling SR protein involved in constitutive and alternative splicing, nonsense-mediated mRNA decay (NMD), mRNA export and translation. It also functions as a splicing-factor oncoprotein that regulates apoptosis and proliferation to promote mammary epithelial cell transformation. SRSF9 has been implicated in the activity of many elements that control splice site selection, the alternative splicing of the glucocorticoid receptor beta in neutrophils and in the gonadotropin-releasing hormone pre-mRNA. It can also interact with other proteins implicated in alternative splicing, including YB-1, rSLM-1, rSLM-2, E4-ORF4, Nop30, and p32. Both, SRSF1 and SRSF9, contain two N-terminal RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), and a C-terminal RS domains rich in serine-arginine dipeptides. In contrast, SF2 contains two N-terminal RRMs and a C-terminal PSK domain rich in proline, serine and lysine residues.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1958782078   5 RVFIGRLNPAAREKDVERFFKGYGRIRDIDLKRG-----FGFVEFEDPRDADDAVYELDGKELCSERVTIE 70
Cdd:cd12338     1 RIYVGNLPGDIRERDIEDLFYKYGPILAIDLKNRrrgppFAFVEFEDPRDAEDAIRGRDGYDFDGYRLRVE 71

RNA recognition motif (RRM) found in vertebrate serine/arginine-rich splicing factor 7 (SRSF7); This subgroup corresponds to the RRM of SRSF7, also termed splicing factor 9G8, is a splicing regulatory serine/arginine (SR) protein that plays a crucial role in both constitutive splicing and alternative splicing of many pre-mRNAs. Its localization and functions are tightly regulated by phosphorylation. SRSF7 is predominantly present in the nuclear and can shuttle between nucleus and cytoplasm. It cooperates with the export protein, Tap/NXF1, helps mRNA export to the cytoplasm, and enhances the expression of unspliced mRNA. SRSF7 inhibits tau E10 inclusion through directly interacting with the proximal downstream intron of E10, a clustering region for frontotemporal dementia with Parkinsonism (FTDP) mutations. SRSF7 contains a single N-terminal RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain), followed by a CCHC-type zinc knuckle motif in its median region, and a C-terminal RS domain rich in serine-arginine dipeptides. The RRM domain is involved in RNA binding, and the RS domain has been implicated in protein shuttling and protein-protein interactions.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1958782078   5 RVFIGRLNPAAREKDVERFFKGYGRIRDIDLKR---GFGFVEFEDPRDADDAVYELDGKELCSERVTIE 70
Cdd:cd12646     1 KVYVGNLGTGAGKGELERAFSYYGPLRTVWIARnppGFAFVEFEDPRDAEDAVRGLDGKVICGSRVRVE 69

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 1958782078   6 VFIGRLNPAAREKDVERFFKGYGRIRDIDLK-------RGFGFVEFEDPRDADDAVYELDGKELCSERVTIE 70
Cdd:cd00590     1 LFVGNLPPDTTEEDLRELFSKFGEVVSVRIVrdrdgksKGFAFVEFESPEDAEKALEALNGTELGGRPLKVS 72

RNA recognition motif 1 (RRM1) found in serine/arginine-rich splicing factor 1 (SRSF1) and similar proteins; This subgroup corresponds to the RRM1 of SRSF1, also termed alternative-splicing factor 1 (ASF-1), or pre-mRNA-splicing factor SF2, P33 subunit. SRSF1 is a splicing regulatory serine/arginine (SR) protein involved in constitutive and alternative splicing, nonsense-mediated mRNA decay (NMD), mRNA export and translation. It also functions as a splicing-factor oncoprotein that regulates apoptosis and proliferation to promote mammary epithelial cell transformation. SRSF1 is a shuttling SR protein and contains two N-terminal RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), separated by a long glycine-rich spacer, and a C-terminal RS domains rich in serine-arginine dipeptides.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1958782078   4 CRVFIGRLNPAAREKDVERFFKGYGRIRDIDLK--RG---FGFVEFEDPRDADDAVYELDGKELCSERVTIE 70
Cdd:cd12597     5 CRIYVGNLPPDIRTKDIEDVFYKYGAIRDIDLKnrRGgppFAFVEFEDPRDAEDAVYGRDGYDYDGYRLRVE 76

RNA recognition motif 1 (RRM1) found in vertebrate serine/arginine-rich splicing factor 9 (SRSF9); This subgroup corresponds to the RRM1 of SRSF9, also termed pre-mRNA-splicing factor SRp30C. SRSF9 is an essential splicing regulatory serine/arginine (SR) protein that has been implicated in the activity of many elements that control splice site selection, the alternative splicing of the glucocorticoid receptor beta in neutrophils and in the gonadotropin-releasing hormone pre-mRNA. SRSF9 can also interact with other proteins implicated in alternative splicing, including YB-1, rSLM-1, rSLM-2, E4-ORF4, Nop30, and p32. SRSF9 contains two N-terminal RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), followed by an unusually short C-terminal RS domains rich in serine-arginine dipeptides.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1958782078   5 RVFIGRLNPAAREKDVERFFKGYGRIRDIDLK--RG---FGFVEFEDPRDADDAVYELDGKELCSERVTIE 70
Cdd:cd12598     1 RIYVGNLPSDVREKDLEDLFYKYGRIRDIELKnrRGlvpFAFVRFEDPRDAEDAVFGRNGYDFGQCRLRVE 71

RNA recognition motif 2 (RRM2) found in serine/arginine-rich splicing factor SRSF1, SRSF9 and similar proteins; This subfamily corresponds to the RRM2 of serine/arginine-rich splicing factor SRSF1, SRSF9 and similar proteins. SRSF1, also termed ASF-1, is a shuttling SR protein involved in constitutive and alternative splicing, nonsense-mediated mRNA decay (NMD), mRNA export and translation. It also functions as a splicing-factor oncoprotein that regulates apoptosis and proliferation to promote mammary epithelial cell transformation. SRSF9, also termed SRp30C, has been implicated in the activity of many elements that control splice site selection, the alternative splicing of the glucocorticoid receptor beta in neutrophils and in the gonadotropin-releasing hormone pre-mRNA. SRSF9 can also interact with other proteins implicated in alternative splicing, including YB-1, rSLM-1, rSLM-2, E4-ORF4, Nop30, and p32. Both, SRSF1 and SRSF9, contain two N-terminal RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), and a C-terminal RS domains rich in serine-arginine dipeptides.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1958782078 108 NRLIVENLSSRVSWQDLKDFMRQAGEVTFADAHRPklNEGVVEFASYGDLKNAIEKL 164
Cdd:cd12601     1 YRVIVSGLPPTGSWQDLKDHMREAGDVCYADVYRD--GTGVVEFLRYEDMKYAVRKL 55

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1958782078   5 RVFIGRLNPAAREKDVERFFKGYGRIRDIDL--------KRGFGFVEFEDPRDADDAVYELDGKELCSERVTIEH 71
Cdd:cd12382     3 KLFIGGLNTETNEKALEAVFGKYGRIVEVLLmkdretnkSRGFAFVTFESPADAKDAARDMNGKELDGKAIKVEQ 77

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

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1958782078   5 RVFIGRLNPAAREKDVERFFKGYGRIRDIDL--------KRGFGFVEFEDPRDADDAVYELDGKEL 62
Cdd:COG0724     3 KIYVGNLPYSVTEEDLRELFSEYGEVTSVKLitdretgrSRGFGFVEMPDDEEAQAAIEALNGAEL 68

RNA recognition motif (RRM) found in Arabidopsis thaliana arginine/serine-rich-splicing factor RSp31 and similar proteins from plants; This subfamily corresponds to the RRM1in a family that represents a novel group of arginine/serine (RS) or serine/arginine (SR) splicing factors existing in plants, such as A. thaliana RSp31, RSp35, RSp41 and similar proteins. Like vertebrate RS splicing factors, these proteins function as plant splicing factors and play crucial roles in constitutive and alternative splicing in plants. They all contain two RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), at their N-terminus, and an RS domain at their C-terminus.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1958782078   6 VFIGRLNPAAREKDVERFFKGYGRIRDIDLKRGFGFVEFEDPRDADDAVYELDGKELCSER 66
Cdd:cd12234     3 VFCGNFEYDARQSEIERLFGKYGRVDRVDMKSGYAFVYMEDERDAEDAIRGLDNFEFGRQR 63

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        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1958782078   6 VFIGRLNPAAREKDVERFFKGYGRIRDIDL--------KRGFGFVEFEDPRDADDAVYELDGKELCSERVTIE 70
Cdd:cd12312     3 LFVRNVADDTRPDDLRREFGRYGPIVDVYIpldfytrrPRGFAYIQFEDVRDAEDALYYLDRTRFLGREIEIQ 75

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 1958782078 110 LIVENLSSRVSWQDLKDFMRQAGEVT----FADAHRPKLNEGVVEFASYGDLKNAIEKLSGKEINGRKIK 175
Cdd:pfam00076   1 LFVGNLPPDTTEEDLKDLFSKFGPIKsirlVRDETGRSKGFAFVEFEDEEDAEKAIEALNGKELGGRELK 70

RNA recognition motif 1 (RRM1) and 2 (RRM2) found in RRM-containing coactivator activator/modulator (CoAA) and similar proteins; This subfamily corresponds to the RRM in CoAA (also known as RBM14 or PSP2) and RNA-binding protein 4 (RBM4). CoAA is a heterogeneous nuclear ribonucleoprotein (hnRNP)-like protein identified as a nuclear receptor coactivator. It mediates transcriptional coactivation and RNA splicing effects in a promoter-preferential manner, and is enhanced by thyroid hormone receptor-binding protein (TRBP). CoAA contains two N-terminal RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), and a TRBP-interacting domain. RBM4 is a ubiquitously expressed splicing factor with two isoforms, RBM4A (also known as Lark homolog) and RBM4B (also known as RBM30), which are very similar in structure and sequence. RBM4 may also function as a translational regulator of stress-associated mRNAs as well as play a role in micro-RNA-mediated gene regulation. RBM4 contains two N-terminal RRMs, a CCHC-type zinc finger, and three alanine-rich regions within their C-terminal regions. This family also includes Drosophila RNA-binding protein lark (Dlark), a homolog of human RBM4. It plays an important role in embryonic development and in the circadian regulation of adult eclosion. Dlark shares high sequence similarity with RBM4 at the N-terminal region. However, Dlark has three proline-rich segments instead of three alanine-rich segments within the C-terminal region.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1958782078   5 RVFIGRLNPAAREKDVERFFKGYGRIRDIDLKRGFGFVEFEDPRDADDAVYELDGKELCSERVTIE 70
Cdd:cd12343     1 KIFVGNLPDAATSEELRALFEKYGKVTECDIVKNYAFVHMEKEEDAEDAIKALNGYEFMGSRINVE 66

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 1958782078   6 VFIGRLNPAAREKDVERFFKGYGRI------RD-IDLKRGFGFVEFEDPRDADDAVYELDGKELcservtiehararSRG 78
Cdd:TIGR01628 181 LYVKNLDPSVNEDKLRELFAKFGEItsaavmKDgSGRSRGFAFVNFEKHEDAAKAVEEMNGKKI-------------GLA 247

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958782078  79 GRGRGRYSDRFSSR--RPRNDRRNAPPVRTENR-------LIVENLSSRVSWQDLKDFMRQAGEVTFA----DAHRPKLN 145
Cdd:TIGR01628 248 KEGKKLYVGRAQKRaeREAELRRKFEELQQERKmkaqgvnLYVKNLDDTVTDEKLRELFSECGEITSAkvmlDEKGVSRG 327

                         170       180
                  ....*....|....*....|....*..
gi 1958782078 146 EGVVEFASYGDLKNAIEKLSGKEINGR 172
Cdd:TIGR01628 328 FGFVCFSNPEEANRAVTEMHGRMLGGK 354

RNA recognition motif 1 (RRM1) found in Saccharomyces cerevisiae protein HRB1, G-strand-binding protein 2 (GBP2) and similar proteins; The family includes Saccharomyces cerevisiae protein HRB1 (also called protein TOM34) and GBP2, both of which are SR-like mRNA-binding proteins which shuttle from the nucleus to the cytoplasm when bound to the mature mRNA molecules. They act as quality control factors for spliced mRNAs. GBP2, also called RAP1 localization factor 6, is a single-strand telomeric DNA-binding protein that binds single-stranded telomeric sequences of the type (TG[1-3])n in vitro. It also binds to RNA. GBP2 influences the localization of RAP1 in the nuclei and plays a role in modulating telomere length. Members in this family contain three RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains). The model corresponds to the first RRM motif.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1958782078 107 ENRLIVENLSSRVSWQDLKDFMRQAGEVTFADA------HRpklNEGVVEFASYGDLKNAIEKLSGKEINGRKI 174
Cdd:cd21605     1 ENSIFVGNLPFDCTWEDLKDHFSQVGEVIRADIvtsrgrHR---GMGTVEFTNKEDVDRAISKFDHTMFMGREI 71

RNA recognition motif (RRM) found in RNA-binding protein with serine-rich domain 1 (RNPS1) and similar proteins; This subfamily corresponds to the RRM of RNPS1 and its eukaryotic homologs. RNPS1, also termed RNA-binding protein prevalent during the S phase, or SR-related protein LDC2, was originally characterized as a general pre-mRNA splicing activator, which activates both constitutive and alternative splicing of pre-mRNA in vitro.It has been identified as a protein component of the splicing-dependent mRNP complex, or exon-exon junction complex (EJC), and is directly involved in mRNA surveillance. Furthermore, RNPS1 is a splicing regulator whose activator function is controlled in part by CK2 (casein kinase II) protein kinase phosphorylation. It can also function as a squamous-cell carcinoma antigen recognized by T cells-3 (SART3)-binding protein, and is involved in the regulation of mRNA splicing. RNPS1 contains an N-terminal serine-rich (S) domain, a central RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain), and the C-terminal arginine/serine/proline-rich (RS/P) domain.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1958782078   6 VFIGRLNPAAREKDVERFFKGYGRIRDIDL--------KRGFGFVEFEDPRDADDAVYELDGKELCSERVTIE 70
Cdd:cd12365     1 LHVGKLTRNVTKDHLKEIFSVYGTVKNVDLpidrepnlPRGYAYVEFESPEDAEKAIKHMDGGQIDGQEVTVE 73

RNA recognition motif (RRM) found in U1 small nuclear ribonucleoprotein 70 kDa (U1-70K) and similar proteins; This subfamily corresponds to the RRM of U1-70K, also termed snRNP70, a key component of the U1 snRNP complex, which is one of the key factors facilitating the splicing of pre-mRNA via interaction at the 5' splice site, and is involved in regulation of polyadenylation of some viral and cellular genes, enhancing or inhibiting efficient poly(A) site usage. U1-70K plays an essential role in targeting the U1 snRNP to the 5' splice site through protein-protein interactions with regulatory RNA-binding splicing factors, such as the RS protein ASF/SF2. Moreover, U1-70K protein can specifically bind to stem-loop I of the U1 small nuclear RNA (U1 snRNA) contained in the U1 snRNP complex. It also mediates the binding of U1C, another U1-specific protein, to the U1 snRNP complex. U1-70K contains a conserved RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain), followed by an adjacent glycine-rich region at the N-terminal half, and two serine/arginine-rich (SR) domains at the C-terminal half. The RRM is responsible for the binding of stem-loop I of U1 snRNA molecule. Additionally, the most prominent immunodominant region that can be recognized by auto-antibodies from autoimmune patients may be located within the RRM. The SR domains are involved in protein-protein interaction with SR proteins that mediate 5' splice site recognition. For instance, the first SR domain is necessary and sufficient for ASF/SF2 Binding. The family also includes Drosophila U1-70K that is an essential splicing factor required for viability in flies, but its SR domain is dispensable. The yeast U1-70k doesn't contain easily recognizable SR domains and shows low sequence similarity in the RRM region with other U1-70k proteins and therefore not included in this family. The RRM domain is dispensable for yeast U1-70K function.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1958782078   7 FIGRLNPAAREKDVERFFKGYGRIRDI----DLK----RGFGFVEFEDPRDADDAVYELDGKELCSERV 67
Cdd:cd12236     5 FVARLSYDTTESKLRREFEKYGPIKRVrlvrDKKtgksRGYAFIEFEHERDMKAAYKHADGKKIDGRRV 73

RNA recognition motif (RRM) found in ist3 family; This subfamily corresponds to the RRM of the ist3 family that includes fungal U2 small nuclear ribonucleoprotein (snRNP) component increased sodium tolerance protein 3 (ist3), X-linked 2 RNA-binding motif proteins (RBMX2) found in Metazoa and plants, and similar proteins. Gene IST3 encoding ist3, also termed U2 snRNP protein SNU17 (Snu17p), is a novel yeast Saccharomyces cerevisiae protein required for the first catalytic step of splicing and for progression of spliceosome assembly. It binds specifically to the U2 snRNP and is an intrinsic component of prespliceosomes and spliceosomes. Yeast ist3 contains an atypical RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain). In the yeast pre-mRNA retention and splicing complex, the atypical RRM of ist3 functions as a scaffold that organizes the other two constituents, Bud13p (bud site selection 13) and Pml1p (pre-mRNA leakage 1). Fission yeast Schizosaccharomyces pombe gene cwf29 encoding ist3, also termed cell cycle control protein cwf29, is an RNA-binding protein complexed with cdc5 protein 29. It also contains one RRM. The biological function of RBMX2 remains unclear. It shows high sequence similarity to yeast ist3 protein and harbors one RRM as well.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1958782078   6 VFIGRLNPAAREKDVERFFKGYGRIRDIDLKR--------GFGFVEFEDPRDADDAVYELDGKELCSERVTIEH 71
Cdd:cd12411    12 IYIGGLPYELTEGDILCVFSQYGEIVDINLVRdkktgkskGFAFLAYEDQRSTILAVDNLNGIKLLGRTIRVDH 85

RNA recognition motif 2 (RRM2) found in Nicotiana sylvestris chloroplastic 33 kDa ribonucleoprotein (NsCP33) and similar proteins; The family includes NsCP33, Arabidopsis thaliana chloroplastic 31 kDa ribonucleoprotein (CP31A) and mitochondrial glycine-rich RNA-binding protein 2 (AtGR-RBP2). NsCP33 may be involved in splicing and/or processing of chloroplast RNA's. AtCP31A, also called RNA-binding protein 1/2/3 (AtRBP33), or RNA-binding protein CP31A, or RNA-binding protein RNP-T, or RNA-binding protein cp31, is required for specific RNA editing events in chloroplasts and stabilizes specific chloroplast mRNAs, as well as for normal chloroplast development under cold stress conditions by stabilizing transcripts of numerous mRNAs under these conditions. CP31A may modulate telomere replication through RNA binding domains. AtGR-RBP2, also called AtRBG2, or glycine-rich protein 2 (AtGRP2), or mitochondrial RNA-binding protein 1a (At-mRBP1a), plays a role in RNA transcription or processing during stress. It binds RNAs and DNAs sequence with a preference to single-stranded nucleic acids. AtGR-RBP2 displays strong affinity to poly(U) sequence. It exerts cold and freezing tolerance, probably by exhibiting an RNA chaperone activity during the cold and freezing adaptation process. Some members in this family contain two RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains). The model corresponds to the second RRM motif.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1958782078   5 RVFIGRLNPAAREKDVERFFKGYGRIRDIDLK--------RGFGFVEFEDPRDADDAVYELDGKEL 62
Cdd:cd21608     1 KLYVGNLSWDTTEDDLRDLFSEFGEVESAKVItdretgrsRGFGFVTFSTAEAAEAAIDALNGKEL 66

RNA recognition motif 1 (RRM1) found in vertebrate RRM-containing coactivator activator/modulator (CoAA); This subgroup corresponds to the RRM1 of CoAA, also termed RNA-binding protein 14 (RBM14), or paraspeckle protein 2 (PSP2), or synaptotagmin-interacting protein (SYT-interacting protein), a heterogeneous nuclear ribonucleoprotein (hnRNP)-like protein identified as a nuclear receptor coactivator. It mediates transcriptional coactivation and RNA splicing effects in a promoter-preferential manner and is enhanced by thyroid hormone receptor-binding protein (TRBP). CoAA contains two N-terminal RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), and a TRBP-interacting domain. It stimulates transcription through its interactions with coactivators, such as TRBP and CREB-binding protein CBP/p300, via the TRBP-interacting domain and interaction with an RNA-containing complex, such as DNA-dependent protein kinase-poly(ADP-ribose) polymerase complexes, via the RRMs.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1958782078   5 RVFIGRLNPAAREKDVERFFKGYGRIRDIDLKRGFGFVEFEDPRDADDAVYELDGKELCSERVTIEH 71
Cdd:cd12608     2 KIFVGNVDEDTSQEELSALFEPYGAVLSCAVMKQFAFVHMRGEAAADRAIRELNGRELHGRALVVEE 68

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 1958782078 109 RLIVENLSSRVSWQDLKDFMRQAGEVTfaDAHRPKLNEG------VVEFASYGDLKNAIEKLSGKEINGRKI 174
Cdd:cd12414     1 RLIVRNLPFKCTEDDLKKLFSKFGKVL--EVTIPKKPDGklrgfaFVQFTNVADAAKAIKGMNGKKIKGRPV 70

RNA recognition motif 2 (RRM2) found in yeast multiple RNA-binding domain-containing protein 1 (MRD1) and similar proteins; This subgroup corresponds to the RRM2 of MRD1 which 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 RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), which may play an important structural role in organizing specific rRNA processing events.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1958782078   5 RVFIGRLNPAAREKDVERFFKGYGRIRDIDL--------KRGFGFVEFEDPRDADDAVYELDGK 60
Cdd:cd12566     4 RLFLRNLPYSTKEDDLQKLFSKFGEVSEVHVpidkktkkSKGFAYVLFLDPEDAVQAYNELDGK 67

RNA recognition motif (RRM) found in eukaryotic RNA-binding protein 18 and similar proteins; This subfamily corresponds to the RRM of RBM18, a putative RNA-binding protein containing a well-conserved RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain). The biological role of RBM18 remains unclear.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1958782078   5 RVFIGRLNPAAREKDVERFFKGYGRIRDID-----------LKRGFGFVEFEDPRDADDAVYELDGK 60
Cdd:cd12355     1 RLWIGNLDPRLTEYHLLKLLSKYGKIKKFDflfhktgplkgQPRGYCFVTFETKEEAEKAIECLNGK 67

RNA recognition motif (RRM) found in RNA-binding protein RBM8A, RBM8B nd similar proteins; This subfamily corresponds to the RRM of RBM8, also termed binder of OVCA1-1 (BOV-1), or RNA-binding protein Y14, which is one of the components of the exon-exon junction complex (EJC). It has two isoforms, RBM8A and RBM8B, both of which are identical except that RBM8B is 16 amino acids shorter at its N-terminus. RBM8, together with other EJC components (such as Magoh, Aly/REF, RNPS1, Srm160, and Upf3), plays critical roles in postsplicing processing, including nuclear export and cytoplasmic localization of the mRNA, and the nonsense-mediated mRNA decay (NMD) surveillance process. RBM8 binds to mRNA 20-24 nucleotides upstream of a spliced exon-exon junction. It is also involved in spliced mRNA nuclear export, and the process of nonsense-mediated decay of mRNAs with premature stop codons. RBM8 forms a specific heterodimer complex with the EJC protein Magoh which then associates with Aly/REF, RNPS1, DEK, and SRm160 on the spliced mRNA, and inhibits ATP turnover by eIF4AIII, thereby trapping the EJC core onto RNA. RBM8 contains an N-terminal putative bipartite nuclear localization signal, one RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain), in the central region, and a C-terminal serine-arginine rich region (SR domain) and glycine-arginine rich region (RG domain).

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1958782078   6 VFIGRLNPAAREKDVERFFKGYGRIRDIDLK--------RGFGFVEFEDPRDADDAVYELDGKELCSERVTI 69
Cdd:cd12324     9 IFVTGVHEEAQEEDIHDKFAEFGEIKNLHLNldrrtgfvKGYALVEYETKKEAQAAIEGLNGKELLGQTISV 80

RNA recognition motif 1 (RRM1) found in the p54nrb/PSF/PSP1 family; This subfamily corresponds to the RRM1 of the p54nrb/PSF/PSP1 family, including 54 kDa nuclear RNA- and DNA-binding protein (p54nrb or NonO or NMT55), polypyrimidine tract-binding protein (PTB)-associated-splicing factor (PSF or POMp100), paraspeckle protein 1 (PSP1 or PSPC1), which are ubiquitously expressed and are conserved in vertebrates. p54nrb is a multi-functional protein involved in numerous nuclear processes including transcriptional regulation, splicing, DNA unwinding, nuclear retention of hyperedited double-stranded RNA, viral RNA processing, control of cell proliferation, and circadian rhythm maintenance. PSF is also a multi-functional protein that binds RNA, single-stranded DNA (ssDNA), double-stranded DNA (dsDNA) and many factors, and mediates diverse activities in the cell. PSP1 is a novel nucleolar factor that accumulates within a new nucleoplasmic compartment, termed paraspeckles, and diffusely distributes in the nucleoplasm. The cellular function of PSP1 remains unknown currently. This subfamily also includes some p54nrb/PSF/PSP1 homologs from invertebrate species, such as the Drosophila melanogaster gene no-ontransient A (nonA) encoding puff-specific protein Bj6 (also termed NONA) and Chironomus tentans hrp65 gene encoding protein Hrp65. D. melanogaster NONA is involved in eye development and behavior, and may play a role in circadian rhythm maintenance, similar to vertebrate p54nrb. C. tentans Hrp65 is a component of nuclear fibers associated with ribonucleoprotein particles in transit from the gene to the nuclear pore. All family members contain a DBHS domain (for Drosophila behavior, human splicing), which comprises two conserved RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), and a charged protein-protein interaction module. PSF has an additional large N-terminal domain that differentiates it from other family members.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1958782078   4 CRVFIGRLNPAAREKDVERFFKGYGRIRD--IDLKRGFGFVEFEDPRDADDAVYELDGK 60
Cdd:cd12332     2 CRLFVGNLPNDITEEEFKELFQKYGEVSEvfLNKGKGFGFIRLDTRANAEAAKAELDGT 60

RNA recognition motif (RRM) found in yeast nuclear polyadenylated RNA-binding protein 3 (Nab3p) and similar proteins; This subfamily corresponds to the RRM of Nab3p, an acidic nuclear polyadenylated RNA-binding protein encoded by Saccharomyces cerevisiae NAB3 gene that is essential for cell viability. Nab3p is predominantly localized within the nucleoplasm and essential for growth in yeast. It may play an important role in packaging pre-mRNAs into ribonucleoprotein structures amenable to efficient nuclear RNA processing. Nab3p contains an N-terminal aspartic/glutamic acid-rich region, a central RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain), and a C-terminal region rich in glutamine and proline residues.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1958782078   5 RVFIGRL-NPAAREKDVERFFKGYGRIRDIDLKRGFGFVEFEDPRDADDAV 54
Cdd:cd12342     1 RLFIGNLpTKRVSKEDLFRIFSPYGHLMQIVIKNAFGFVQFDSPQSCRNAI 51

RNA recognition motif 2 (RRM2) found in Saccharomyces cerevisiae protein HRB1, G-strand-binding protein 2 (GBP2) and similar proteins; The family includes Saccharomyces cerevisiae protein HRB1 (also called protein TOM34) and GBP2, both of which are SR-like mRNA-binding proteins which shuttle from the nucleus to the cytoplasm when bound to the mature mRNA molecules. They act as quality control factors for spliced mRNAs. GBP2, also called RAP1 localization factor 6, is a single-strand telomeric DNA-binding protein that binds single-stranded telomeric sequences of the type (TG[1-3])n in vitro. It also binds to RNA. GBP2 influences the localization of RAP1 in the nuclei and plays a role in modulating telomere length. Members in this family contain three RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains). The model corresponds to the second RRM motif.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958782078 110 LIVENLSSRVSWQDLKDFMRQAGEVTFADAhrpKLNE-------GVVEFASYGDLKNAIEKLSGKEINGR 172
Cdd:cd21606     4 VFIANLPYSINWQALKDMFKECGDVLRADV---ELDYngrsrgfGTVIYATEEEMHRAIDTFNGYELEGR 70

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        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1958782078   5 RVFIGRLNPAAREKDVERFFKGYGRIRDIDL--------KRGFGFVEFEDPRDADDAVYELDGK 60
Cdd:cd12316     1 RLFVRNLPFTATEDELRELFEAFGKISEVHIpldkqtkrSKGFAFVLFVIPEDAVKAYQELDGS 64

RNA recognition motif 1 (RRM1) found in fission yeast pre-mRNA-splicing factor Srp1p and similar proteins; This subgroup corresponds to the RRM domain in Srp1p encoded by gene srp1 from fission yeast Schizosaccharomyces pombe. It plays a role in the pre-mRNA splicing process, but not essential for growth. Srp1p is closely related to the SR protein family found in metazoa. It contains an N-terminal RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain), a glycine hinge and a RS domain in the middle, and a C-terminal domain. Some family members also contain another RRM domain.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1958782078  16 REKDVERFFKGYGRIRDIDL-------KRGFGFVEFEDPRDADDAVYELDGKELCSERVTI 69
Cdd:cd12467    12 RARDLAYEFERYGRLVRCDIppprtfqSRPFAFVEYESHRDAEDAYEEMHGRRFPDTGDTL 72

RNA recognition motif 2 (RRM2) found in (U)-binding-splicing factor PUF60 and similar proteins; This subfamily corresponds to the RRM2 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). 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 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. Research indicates that PUF60 binds FUSE as a dimer, and only the first two RRM domains participate in the single-stranded DNA recognition.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1958782078   5 RVFIGRLNPAAREKDVERFFKGYGRIRDIDL--------KRGFGFVEFEDPRDADDAV-----YELDGKEL 62
Cdd:cd12371     2 RIYVASVHPDLSEDDIKSVFEAFGKIKSCSLapdpetgkHKGYGFIEYENPQSAQDAIasmnlFDLGGQYL 72