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).

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                  ....*....|....*....|....*....|....*....|....*....|..
gi 1720409418   1 MRQAGEVTYADAHKGRKNEGVIEFVSYSDMKRALEKLDGTEVNGRKIRLVED 52
Cdd:cd12600    21 MRQAGEVTYADAHKQRKNEGVVEFASYSDMKNAIEKLDGTELNGRKIRLVED 72

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.

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                  ....*....|....*....|....*....|....*....|....*....|..
gi 1720409418   1 MRQAGEVTYADAHKGRKNEGVIEFVSYSDMKRALEKLDGTEVNGRKIRLVED 52
Cdd:cd12600    21 MRQAGEVTYADAHKQRKNEGVVEFASYSDMKNAIEKLDGTELNGRKIRLVED 72

RNA recognition motif;

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                   ....*....|....*....|....*....|....*....|....*....|....
gi 1720409418    1 MRQAGEVTYA----DAHKGR-KNEGVIEFVSYSDMKRALEKLDGTEVNGRKIRL 49
Cdd:smart00360  20 FSKFGKVESVrlvrDKETGKsKGFAFVEFESEEDAEKALEALNGKELDGRPLKV 73

U2 snRNP auxilliary factor, large subunit, splicing factor; These splicing factors consist of an N-terminal arginine-rich low complexity domain followed by three tandem RNA recognition motifs (pfam00076). The well-characterized members of this family are auxilliary components of the U2 small nuclear ribonuclearprotein splicing factor (U2AF). These proteins are closely related to the CC1-like subfamily of splicing factors (TIGR01622). Members of this subfamily are found in plants, metazoa and fungi.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720409418 122 EKSRSPSKD-NKSRSRSRSPDKSRSKSKDHaedklqnndSAGKAKSHSPSRHDSKSRSRSQERRAEEERRRSVSRARSQE 200
Cdd:TIGR01642  10 EKSRGRDRDrSSERPRRRSRDRSRFRDRHR---------RSRERSYREDSRPRDRRRYDSRSPRSLRYSSVRRSRDRPRR 80

                          90       100       110
                  ....*....|....*....|....*....|....
gi 1720409418 201 KSRSQeKSLLKSRSRSRSKVGSRSRSRSKDKRKG 234
Cdd:TIGR01642  81 RSRSV-RSIEQHRRRLRDRSPSNQWRKDDKKRSL 113

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.

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                  ....*....|....*....|....*....|....*....|....*....|..
gi 1720409418   1 MRQAGEVTYADAHKGRKNEGVIEFVSYSDMKRALEKLDGTEVNGRKIRLVED 52
Cdd:cd12600    21 MRQAGEVTYADAHKQRKNEGVVEFASYSDMKNAIEKLDGTELNGRKIRLVED 72

RNA recognition motif 2 (RRM2) found in serine/arginine-rich splicing factor SRSF1, SRSF4 and similar proteins; This subfamily corresponds to the RRM2 of several serine/arginine (SR) proteins that have been classified into two subgroups. The first subgroup consists of serine/arginine-rich splicing factor 4 (SRSF4 or SRp75 or SFRS4), serine/arginine-rich splicing factor 5 (SRSF5 or SRp40 or SFRS5 or HRS) and serine/arginine-rich splicing factor 6 (SRSF6 or SRp55). The second subgroup is composed of 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). These SR proteins are mainly involved in regulating constitutive and alternative pre-mRNA splicing. They also have been implicated in transcription, genomic stability, mRNA export and translation. All SR proteins in this family, except SRSF5, undergo nucleocytoplasmic shuttling, suggesting their widespread roles in gene expression. These SR proteins share a common domain architecture comprising 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. Both domains can directly contact with RNA. The RRMs appear to determine the binding specificity and the SR domain also mediates protein-protein interactions. In addition, this subfamily includes the yeast nucleolar protein 3 (Npl3p), also termed mitochondrial targeting suppressor 1 protein, or nuclear polyadenylated RNA-binding protein 1. It is a major yeast RNA-binding protein that competes with 3'-end processing factors, such as Rna15, for binding to the nascent RNA, protecting the transcript from premature termination and coordinating transcription termination and the packaging of the fully processed transcript for export. It specifically recognizes a class of G/U-rich RNAs. Npl3p is a multi-domain protein with two RRMs, separated by a short linker and a C-terminal domain rich in glycine, arginine and serine residues.

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                  ....*....|....*....|....*....|....*....|....*....|
gi 1720409418   1 MRQAGEVTYADAHKGRKNEGVIEFVSYSDMKRALEKLDGTEVNGRKIRLV 50
Cdd:cd12339    21 MRKAGEVTYADVHRDREGEGVVEFTSEEDMKRAIEKLDGTEFNGRRIRVE 70

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.

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                  ....*....|....*....|....*....|....*....|....*....|.
gi 1720409418   1 MRQAGEVTYADAHKGRKNEGVIEFVSYSDMKRALEKLDGTEVNGRKIRLVE 51
Cdd:cd12765    30 MRQAGEVTFADAHRPKLNEGVVEFASYSDLKNAIEKLSGKEINGRKIKLIE 80

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.

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                  ....*....|....*....|....*....|....*....|.
gi 1720409418   1 MRQAGEVTYADAHkgRKNEGVIEFVSYSDMKRALEKLDGTE 41
Cdd:cd12601    21 MREAGDVCYADVY--RDGTGVVEFLRYEDMKYAVRKLDDSK 59

RNA recognition motif;

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                   ....*....|....*....|....*....|....*....|....*....|....
gi 1720409418    1 MRQAGEVTYA----DAHKGR-KNEGVIEFVSYSDMKRALEKLDGTEVNGRKIRL 49
Cdd:smart00360  20 FSKFGKVESVrlvrDKETGKsKGFAFVEFESEEDAEKALEALNGKELDGRPLKV 73

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.

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                  ....*....|....*....|....*....|....*....|....*....|...
gi 1720409418   3 QAGEVTYAD--AHKGR-KNEGVIEFVSYSDMKRALEKLDGTEVNGRKIRLVED 52
Cdd:cd21605    24 QVGEVIRADivTSRGRhRGMGTVEFTNKEDVDRAISKFDHTMFMGREIFVRQD 76

RNA recognition motif 2 (RRM2) found in vertebrate RNA-binding protein RBM23, RBM39 and similar proteins; This subfamily corresponds to the RRM2 of RBM39 (also termed HCC1), a 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. Although the cellular function of RBM23 remains unclear, it shows high sequence homology to RBM39 and contains two RRMs. It may possibly function as a pre-mRNA splicing factor.

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                  ....*....|....*....|....*....|....*....|....*....|
gi 1720409418   5 GEVTYADAHK----GR-KNEGVIEFVSYSDMKRALEKLDGTEVNGRKIRL 49
Cdd:cd12284    23 GKIEFVQLQKdpetGRsKGYGFIQFRDAEDAKKALEQLNGFELAGRPMKV 72

RNA recognition motif 1 (RRM1) found in heterogeneous nuclear ribonucleoprotein M (hnRNP M) and similar proteins; This subfamily corresponds to the RRM1 of heterogeneous nuclear ribonucleoprotein M (hnRNP M), myelin expression factor 2 (MEF-2 or MyEF-2 or MST156) and similar proteins. hnRNP M is pre-mRNA binding protein that may play an important role in the pre-mRNA processing. It also preferentially binds to poly(G) and poly(U) RNA homopolymers. Moreover, hnRNP M is able to interact with early spliceosomes, further influencing splicing patterns of specific pre-mRNAs. hnRNP M functions as the receptor of carcinoembryonic antigen (CEA) that contains the penta-peptide sequence PELPK signaling motif. In addition, hnRNP M and another splicing factor Nova-1 work together as dopamine D2 receptor (D2R) pre-mRNA-binding proteins. They regulate alternative splicing of D2R pre-mRNA in an antagonistic manner. hnRNP M contains three RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), and an unusual hexapeptide-repeat region rich in methionine and arginine residues (MR repeat motif). MEF-2 is a sequence-specific single-stranded DNA (ssDNA) binding protein that binds specifically to ssDNA derived from the proximal (MB1) element of the myelin basic protein (MBP) promoter and represses transcription of the MBP gene. MEF-2 shows high sequence homology with hnRNP M. It also contains three RRMs, which may be responsible for its ssDNA binding activity.

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                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1720409418   2 RQAGEVTYA----DAHKGRKNEGVIEFVSYSDMKRALEKLDGTEVNGRKIRLVED 52
Cdd:cd12385    22 EKVGEVTYVelfkDENGKSRGCGIVEFKDLESVQKALETMNRYELKGRKLVVKED 76

RNA recognition motif 1 (RRM1) found in vertebrate heterogeneous nuclear ribonucleoprotein M (hnRNP M); This subgroup corresponds to the RRM1 of hnRNP M, a pre-mRNA binding protein that may play an important role in the pre-mRNA processing. It also preferentially binds to poly(G) and poly(U) RNA homopolymers. Moreover, hnRNP M is able to interact with early spliceosomes, further influencing splicing patterns of specific pre-mRNAs. hnRNP M functions as the receptor of carcinoembryonic antigen (CEA) that contains the penta-peptide sequence PELPK signaling motif. In addition, hnRNP M and another splicing factor Nova-1 work together as dopamine D2 receptor (D2R) pre-mRNA-binding proteins. They regulate alternative splicing of D2R pre-mRNA in an antagonistic manner. hnRNP M contains three RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), and an unusual hexapeptide-repeat region rich in methionine and arginine residues (MR repeat motif).

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1720409418   3 QAGEVTYA----DAHKGRKNEGVIEFVSYSDMKRALEKLDGTEVNGRKIRLVED 52
Cdd:cd12657    23 KVGEVTYVellmDAEGKSRGCAVVEFKTEESMKKAVEVLNKHSFNGRPLKVKED 76

U2 snRNP auxilliary factor, large subunit, splicing factor; These splicing factors consist of an N-terminal arginine-rich low complexity domain followed by three tandem RNA recognition motifs (pfam00076). The well-characterized members of this family are auxilliary components of the U2 small nuclear ribonuclearprotein splicing factor (U2AF). These proteins are closely related to the CC1-like subfamily of splicing factors (TIGR01622). Members of this subfamily are found in plants, metazoa and fungi.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720409418 122 EKSRSPSKD-NKSRSRSRSPDKSRSKSKDHaedklqnndSAGKAKSHSPSRHDSKSRSRSQERRAEEERRRSVSRARSQE 200
Cdd:TIGR01642  10 EKSRGRDRDrSSERPRRRSRDRSRFRDRHR---------RSRERSYREDSRPRDRRRYDSRSPRSLRYSSVRRSRDRPRR 80

                          90       100       110
                  ....*....|....*....|....*....|....
gi 1720409418 201 KSRSQeKSLLKSRSRSRSKVGSRSRSRSKDKRKG 234
Cdd:TIGR01642  81 RSRSV-RSIEQHRRRLRDRSPSNQWRKDDKKRSL 113