RNA recognition motif 1 (RRM1) found in epithelial splicing regulatory protein ESRP1, ESRP2, Drosophila RNA-binding protein Fusilli and similar proteins; This subfamily corresponds to the RRM1 of ESRPs and Fusilli. ESRP1 (also termed RBM35A) and ESRP2 (also termed RBM35B). These are epithelial-specific RNA binding proteins that promote splicing of the epithelial variant of the fibroblast growth factor receptor 2 (FGFR2), ENAH (also termed hMena), CD44 and CTNND1 (also termed p120-Catenin) transcripts. They are highly conserved paralogs and specifically bind to GU-rich binding site. ESRP1 and ESRP2 contain three RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains). The family also includes Drosophila fusilli (fus) gene encoding RNA-binding protein Fusilli. Loss of fusilli activity causes lethality during embryogenesis in flies. Drosophila Fusilli can regulate endogenous fibroblast growth factor receptor 2 (FGFR2) splicing and functions as a splicing factor. It shows high sequence homology to ESRPs and contains three RRMs as well. It also has an N-terminal domain with unknown function and a C-terminal domain particularly rich in alanine, glutamine, and serine.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 71998567 182 VCRARGLPWQASDHHVAQFFAGLDIVPGGIALCLSSEGRRNGEVLVQFSSQESRDLALKRHRNFLLSRYIEVYKA 256
Cdd:cd12507   1 VVRARGLPWQSSDQDIAQFFRGLNIAKGGVALCLSAQGRRNGEALIRFVDQEHRDLALQRHKHHMGTRYIEVYKA 75

RNA recognition motif 1 (RRM1) found in epithelial splicing regulatory protein ESRP1, ESRP2, Drosophila RNA-binding protein Fusilli and similar proteins; This subfamily corresponds to the RRM1 of ESRPs and Fusilli. ESRP1 (also termed RBM35A) and ESRP2 (also termed RBM35B). These are epithelial-specific RNA binding proteins that promote splicing of the epithelial variant of the fibroblast growth factor receptor 2 (FGFR2), ENAH (also termed hMena), CD44 and CTNND1 (also termed p120-Catenin) transcripts. They are highly conserved paralogs and specifically bind to GU-rich binding site. ESRP1 and ESRP2 contain three RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains). The family also includes Drosophila fusilli (fus) gene encoding RNA-binding protein Fusilli. Loss of fusilli activity causes lethality during embryogenesis in flies. Drosophila Fusilli can regulate endogenous fibroblast growth factor receptor 2 (FGFR2) splicing and functions as a splicing factor. It shows high sequence homology to ESRPs and contains three RRMs as well. It also has an N-terminal domain with unknown function and a C-terminal domain particularly rich in alanine, glutamine, and serine.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 71998567 182 VCRARGLPWQASDHHVAQFFAGLDIVPGGIALCLSSEGRRNGEVLVQFSSQESRDLALKRHRNFLLSRYIEVYKA 256
Cdd:cd12507   1 VVRARGLPWQSSDQDIAQFFRGLNIAKGGVALCLSAQGRRNGEALIRFVDQEHRDLALQRHKHHMGTRYIEVYKA 75

RNA recognition motif;

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 71998567    283 VRMRGLPYDCTDAQIRTFFEPL-KLTDKILFITRTDGRPTGDAFVQFETEEDAQQGLLK-HRQVIGQRYIEL 352
Cdd:smart00360   2 LFVGNLPPDTTEEELRELFSKFgKVESVRLVRDKETGKSKGFAFVEFESEEDAEKALEAlNGKELDGRPLKV 73

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

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*...
gi 71998567 286 RGLPYDCTDAQIRTFFEP------LKL-TDKilfitRTdGRPTGDAFVQFETEEDAQQ 336
Cdd:COG0724   7 GNLPYSVTEEDLRELFSEygevtsVKLiTDR-----ET-GRSRGFGFVEMPDDEEAQA 58

RNA recognition motif 1 (RRM1) found in epithelial splicing regulatory protein ESRP1, ESRP2, Drosophila RNA-binding protein Fusilli and similar proteins; This subfamily corresponds to the RRM1 of ESRPs and Fusilli. ESRP1 (also termed RBM35A) and ESRP2 (also termed RBM35B). These are epithelial-specific RNA binding proteins that promote splicing of the epithelial variant of the fibroblast growth factor receptor 2 (FGFR2), ENAH (also termed hMena), CD44 and CTNND1 (also termed p120-Catenin) transcripts. They are highly conserved paralogs and specifically bind to GU-rich binding site. ESRP1 and ESRP2 contain three RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains). The family also includes Drosophila fusilli (fus) gene encoding RNA-binding protein Fusilli. Loss of fusilli activity causes lethality during embryogenesis in flies. Drosophila Fusilli can regulate endogenous fibroblast growth factor receptor 2 (FGFR2) splicing and functions as a splicing factor. It shows high sequence homology to ESRPs and contains three RRMs as well. It also has an N-terminal domain with unknown function and a C-terminal domain particularly rich in alanine, glutamine, and serine.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 71998567 182 VCRARGLPWQASDHHVAQFFAGLDIVPGGIALCLSSEGRRNGEVLVQFSSQESRDLALKRHRNFLLSRYIEVYKA 256
Cdd:cd12507   1 VVRARGLPWQSSDQDIAQFFRGLNIAKGGVALCLSAQGRRNGEALIRFVDQEHRDLALQRHKHHMGTRYIEVYKA 75

RNA recognition motif 3 (RRM3) found in epithelial splicing regulatory protein ESRP1, ESRP2, Drosophila RNA-binding protein Fusilli and similar proteins; This subfamily corresponds to the RRM3 of ESRPs and Fusilli. ESRP1 (also termed RBM35A) and ESRP2 (also termed RBM35B) are epithelial-specific RNA binding proteins that promote splicing of the epithelial variant of the fibroblast growth factor receptor 2 (FGFR2), ENAH (also termed hMena), CD44 and CTNND1 (also termed p120-Catenin) transcripts. They are highly conserved paralogs and specifically bind to GU-rich binding site. ESRP1 and ESRP2 contain three RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains). The family also includes Drosophila fusilli (fus) gene encoding RNA-binding protein Fusilli. Loss of fusilli activity causes lethality during embryogenesis in flies. Drosophila Fusilli can regulate endogenous FGFR2 splicing and functions as a splicing factor. Fusilli shows high sequence homology to ESRPs and contains three RRMs as well. It also has an N-terminal domain with unknown function and a C-terminal domain particularly rich in alanine, glutamine, and serine.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998567 388 KDCVRLRGLPYEATVQHIVTFLGDFATMVKFQGVHMVYNNQGHPSGEAFIQMINEQAASACAAGVHNNfmsvGKKKRYIE 467
Cdd:cd12509   1 RDCIRLRGLPYSATVEDILNFLGEFAKHIAPQGVHMVINAQGRPSGDAFIQMLSAEFARLAAQKRHKH----HMGERYIE 76

                ....*
gi 71998567 468 VFQAS 472
Cdd:cd12509  77 VFQCS 81

RNA recognition motif 1 (RRM1) found in epithelial splicing regulatory protein 1 (ESRP1) and similar proteins; This subgroup corresponds to the RRM1 of ESRP1, also termed RNA-binding motif protein 35A (RBM35A), which has been identified as an epithelial cell type-specific regulator of fibroblast growth factor receptor 2 (FGFR2) splicing. It is required for expression of epithelial FGFR2-IIIb and the regulation of CD44, CTNND1 (p120-Catenin) and ENAH (hMena) splicing. It enhances epithelial-specific exons of CD44 and ENAH, silences mesenchymal exons of CTNND1, or both within FGFR2. Additional research indicated that ESRP1 functions as a tumor suppressor in colon cancer cells. It may be involved in posttranscriptional regulation of various genes by exerting a differential effect on protein translation via 5' untranslated regions (UTRs) of mRNAs. ESRP1 contains three RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains).

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998567 179 DNVVCRARGLPWQASDHHVAQFFAGLDIVPGGIALCLSSEGRRNGEVLVQFSSQESRDLALKRHRNFLLSRYIEVYKAGL 258
Cdd:cd12736   8 DNTVIRARGLPWQSSDQDIARFFKGLNIAKGGAALCLNAQGRRNGEALVRFVNEEHRDLALQRHKHHMGNRYIEVYKATG 87

                ....*.
gi 71998567 259 DEFMHV 264
Cdd:cd12736  88 EDFLKI 93

RNA recognition motif 1 (RRM1) found in epithelial splicing regulatory protein 2 (ESRP2) and similar proteins; This subgroup corresponds to the RRM1 of ESRP2, also termed RNA-binding motif protein 35B (RBM35B), which has been identified as an epithelial cell type-specific regulator of fibroblast growth factor receptor 2 (FGFR2) splicing. It is required for expression of epithelial FGFR2-IIIb and the regulation of CD44, CTNND1 (also termed p120-Catenin) and ENAH (also termed hMena) splicing. It enhances epithelial-specific exons of CD44 and ENAH, silences mesenchymal exons of CTNND1, or both within FGFR2. ESRP2 contains three RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains).

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998567 182 VCRARGLPWQASDHHVAQFFAGLDIVPGGIALCLSSEGRRNGEVLVQFSSQESRDLALKRHRNFLLSRYIEVYKAGLDEF 261
Cdd:cd12737   1 VIRARGLPWQSSDQDIARFFKGLNIAKGGVALCLNAQGRRNGEALVRFVNSEQRDLALERHKHHMGSRYIEVYKATGEEF 80

RNA recognition motif 3 (RRM3) found in epithelial splicing regulatory protein ESRP1, ESRP2 and similar proteins; This subgroup corresponds to the RRM3 of ESRP1 (also termed RBM35A) and ESRP2 (also termed RBM35B). These are epithelial-specific RNA binding proteins that promote splicing of the epithelial variant of the fibroblast growth factor receptor 2 (FGFR2), ENAH (also termed hMena), CD44 and CTNND1 (also termed p120-Catenin) transcripts. They are highly conserved paralogs and specifically bind to GU-rich binding site. ESRP1 and ESRP2 contain three RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains).

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998567 388 KDCVRLRGLPYEATVQHIVTFLGDFATMVKFQGVHMVYNNQGHPSGEAFIQMINEQAASACAAGVHNNFMsvgkKKRYIE 467
Cdd:cd12742   1 RDCIRLRGLPYAATIEDILEFLGEFAADIRPHGVHMVLNHQGRPSGDAFIQMKSADRAFLAAQKCHKKTM----KDRYVE 76

                ....*
gi 71998567 468 VFQAS 472
Cdd:cd12742  77 VFQCS 81

RNA recognition motif 2 (RRM2) found in heterogeneous nuclear ribonucleoprotein (hnRNP) H protein family; This subfamily corresponds to the RRM2 of hnRNP H protein family which includes hnRNP H (also termed mcs94-1), hnRNP H2 (also termed FTP-3 or hnRNP H'), hnRNP F and hnRNP H3 (also termed hnRNP 2H9). They represent a group of nuclear RNA binding proteins that are involved in pre-mRNA processing, having similar RNA binding affinities and specifically recognizing the sequence GGGA. They can either stimulate or repress splicing upon binding to a GGG motif. hnRNP H binds to the RNA substrate in the presence or absence of these proteins, whereas hnRNP F binds to the nuclear mRNA only in the presence of cap-binding proteins. Furthermore, hnRNP H and hnRNP H2 are almost identical; both have been found to bind nuclear-matrix proteins. hnRNP H activates exon inclusion by binding G-rich intronic elements downstream of the 5' splice site in the transcripts of c-src, human immunodeficiency virus type 1 (HIV-1), Bcl-X, GRIN1, and myelin. It silences exons when bound to exonic elements in the transcripts of beta-tropomyosin, HIV-1, and alpha-tropomyosin. hnRNP H2 has been implicated in pre-mRNA 3' end formation. hnRNP H3 may be involved in the splicing arrest induced by heat shock. Most family members contain three RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), except for hnRNP H3, in which the RRM1 is absent. RRM1 and RRM2 are responsible for the binding to the RNA at DGGGD motifs, and they play an important role in efficiently silencing the exon. Members in this family can regulate the alternative splicing of the fibroblast growth factor receptor 2 (FGFR2) transcripts, and function as silencers of FGFR2 exon IIIc through an interaction with the exonic GGG motifs. The lack of RRM1 could account for the reduced silencing activity within hnRNP H3. In addition, the family members have an extensive glycine-rich region near the C-terminus, which may allow them to homo- or heterodimerize. The family also includes a cytoplasmic poly(A)+ mRNA binding protein, GRSF-1, which interacts with RNA in a G-rich element-dependent manner. It may function in RNA packaging, stabilization of RNA secondary structure, or other macromolecular interactions. GRSF-1 also contains three potential RRMs responsible for the RNA binding, and two auxiliary domains (an acidic alpha-helical domain and an N-terminal alanine-rich region) that may play a role in protein-protein interactions and provide binding specificity.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 71998567 282 IVRMRGLPYDCTDAQIRTFFEPLKLT-DKILFITRTDGRPTGDAFVQFETEEDAQQGLLKHRQVIGQRYIELFKST 356
Cdd:cd12504   2 VVRLRGLPYGCTKEEIAQFFSGLEIVpNGITLPMDRRGRSTGEAFVQFASQEIAEQALGKHKEKIGHRYIEIFRSS 77

RNA recognition motif (RRM) found in heterogeneous nuclear ribonucleoprotein (hnRNP) H protein family, epithelial splicing regulatory proteins (ESRPs), Drosophila RNA-binding protein Fusilli, RNA-binding protein 12 (RBM12) and similar proteins; The family includes RRM domains in the hnRNP H protein family, G-rich sequence factor 1 (GRSF-1), ESRPs (also termed RBM35), Drosophila Fusilli, RBM12 (also termed SWAN), RBM12B, RBM19 (also termed RBD-1) and similar proteins. The hnRNP H protein family includes hnRNP H (also termed mcs94-1), hnRNP H2 (also termed FTP-3 or hnRNP H'), hnRNP F and hnRNP H3 (also termed hnRNP 2H9), which represent a group of nuclear RNA binding proteins that are involved in pre-mRNA processing. GRSF-1 is a cytoplasmic poly(A)+ mRNA binding protein which interacts with RNA in a G-rich element-dependent manner. It may function in RNA packaging, stabilization of RNA secondary structure, or other macromolecular interactions. ESRP1 (also termed RBM35A) and ESRP2 (also termed RBM35B) are epithelial-specific RNA binding proteins that promote splicing of the epithelial variant of fibroblast growth factor receptor 2 (FGFR2), ENAH (also termed hMena), CD44 and CTNND1 (also termed p120-Catenin) transcripts. Fusilli shows high sequence homology to ESRPs. It can regulate endogenous FGFR2 splicing and functions as a splicing factor. The biological roles of both, RBM12 and RBM12B, remain unclear. RBM19 is a nucleolar protein conserved in eukaryotes. It is involved in ribosome biogenesis by processing rRNA. In addition, it is essential for preimplantation development. Members in this family contain 2~6 conserved RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains).

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 71998567 184 RARGLPWQASDHHVAQFFAGLDIVPGGIALCLSSEGRRNGEVLVQFSSQESRDLALKRHRNFLLSRYIEVY 254
Cdd:cd12254   3 RLRGLPFSATEEDIRDFFSGLDIPPDGIHIVYDDDGRPTGEAYVEFASEEDAQRALRRHKGKMGGRYIEVF 73

RNA recognition motif 1 (RRM1) found in heterogeneous nuclear ribonucleoprotein (hnRNP) H protein family, G-rich sequence factor 1 (GRSF-1) and similar proteins; This subfamily corresponds to the RRM1 of hnRNP H proteins and GRSF-1. The hnRNP H protein family includes hnRNP H (also termed mcs94-1), hnRNP H2 (also termed FTP-3 or hnRNP H'), hnRNP F and hnRNP H3 (also termed hnRNP 2H9), which represent a group of nuclear RNA binding proteins that are involved in pre-mRNA processing. These proteins have similar RNA binding affinities and specifically recognize the sequence GGGA. They can either stimulate or repress splicing upon binding to a GGG motif. hnRNP H binds to the RNA substrate in the presence or absence of these proteins, whereas hnRNP F binds to the nuclear mRNA only in the presence of cap-binding proteins. hnRNP H and hnRNP H2 are almost identical; both have been found to bind nuclear-matrix proteins. hnRNP H activates exon inclusion by binding G-rich intronic elements downstream of the 5' splice site in the transcripts of c-src, human immunodeficiency virus type 1 (HIV-1), Bcl-X, GRIN1, and myelin. It silences exons when bound to exonic elements in the transcripts of beta-tropomyosin, HIV-1, and alpha-tropomyosin. hnRNP H2 has been implicated in pre-mRNA 3' end formation. hnRNP H3 may be involved in splicing arrest induced by heat shock. Most family members contain three RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), except for hnRNP H3, in which the RRM1 is absent. RRM1 and RRM2 are responsible for the binding to the RNA at DGGGD motifs, and play an important role in efficiently silencing the exon. Members in this family can regulate the alternative splicing of fibroblast growth factor receptor 2 (FGFR2) transcripts, and function as silencers of FGFR2 exon IIIc through an interaction with the exonic GGG motifs. The lack of RRM1 could account for the reduced silencing activity within hnRNP H3. Members in this family have an extensive glycine-rich region near the C-terminus, which may allow them to homo- or heterodimerize. They also include a cytoplasmic poly(A)+ mRNA binding protein, GRSF-1, which interacts with RNA in a G-rich element-dependent manner. They may function in RNA packaging, stabilization of RNA secondary structure, or other macromolecular interactions. GRSF-1 contains three potential RRMs responsible for the RNA binding, and two auxiliary domains (an acidic alpha-helical domain and an N-terminal alanine-rich region) that may play a role in protein-protein interactions and provide binding specificity.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 71998567 282 IVRMRGLPYDCTDAQIRTFFEPLKLTDK---ILFITRTDGRPTGDAFVQFETEEDAQQGLLKHRQVIGQRYIELFKS 355
Cdd:cd12503   1 VVRARGLPWSATAEDVLNFFTDCRIKGGengIHFTYTREGRPSGEAFIELESEEDVEKALEKHNEHMGHRYIEVFRS 77

RNA recognition motif 2 (RRM2) found in heterogeneous nuclear ribonucleoprotein hnRNP H, hnRNP H2, hnRNP F and similar proteins; This subgroup corresponds to the RRM2 of hnRNP H (also termed mcs94-1), hnRNP H2 (also termed FTP-3 or hnRNP H') and hnRNP F. These represent a group of nuclear RNA binding proteins that play important roles in the regulation of alternative splicing decisions. hnRNP H and hnRNP F are two closely related proteins, both of which bind to the RNA sequence DGGGD. They are present in a complex with the tissue-specific splicing factor Fox2, and regulate the alternative splicing of the fibroblast growth factor receptor 2 (FGFR2) transcripts. The presence of Fox 2 can allows hnRNP H and hnRNP F to better compete with the SR protein ASF/SF2 for binding to FGFR2 exon IIIc. Thus, hnRNP H and hnRNP F can function as potent silencers of FGFR2 exon IIIc inclusion through an interaction with the exonic GGG motifs. Furthermore, hnRNP H and hnRNP H2 are almost identical; both have been found to bind nuclear-matrix proteins. hnRNP H activates exon inclusion by binding G-rich intronic elements downstream of the 5' splice site in the transcripts of c-src, human immunodeficiency virus type 1 (HIV-1), Bcl-X, GRIN1, and myelin. It silences exons when bound to exonic elements in the transcripts of beta-tropomyosin, HIV-1, and alpha-tropomyosin. hnRNP H2 has been implicated in pre-mRNA 3' end formation. Members in this family contain three RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains). RRM1 and RRM2 are responsible for the binding to the RNA at DGGGD motifs, and they play an important role in efficiently silencing the exon. In addition, the family members have an extensive glycine-rich region near the C-terminus, which may allow them to homo- or heterodimerize.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998567 277 SANAIIVRMRGLPYDCTDAQIRTFFEPLKLT-DKILFITRTDGRPTGDAFVQFETEEDAQQGLLKHRQVIGQRYIELFKS 355
Cdd:cd12731   5 TANDGFVRLRGLPFGCSKEEIVQFFSGLEIVpNGITLPVDFQGRSTGEAFVQFASQEIAEKALKKHKERIGHRYIEIFKS 84

                ....*.
gi 71998567 356 TAAEVQ 361
Cdd:cd12731  85 SRAEVR 90

RNA recognition motif 1 (RRM1) found in heterogeneous nuclear ribonucleoprotein hnRNP H , hnRNP H2, hnRNP F and similar proteins; This subgroup corresponds to the RRM1 of hnRNP H (also termed mcs94-1), hnRNP H2 (also termed FTP-3 or hnRNP H') and hnRNP F. These represent a group of nuclear RNA binding proteins that play important roles in the regulation of alternative splicing decisions. hnRNP H and hnRNP F are two closely related proteins, both of which bind to the RNA sequence DGGGD. They are present in a complex with the tissue-specific splicing factor Fox2, and regulate the alternative splicing of the fibroblast growth factor receptor 2 (FGFR2) transcripts. The presence of Fox 2 can allows hnRNP H and hnRNP F to better compete with the SR protein ASF/SF2 for binding to FGFR2 exon IIIc. Thus, hnRNP H and hnRNP F can function as potent silencers of FGFR2 exon IIIc inclusion through an interaction with the exonic GGG motifs. Furthermore, hnRNP H and hnRNP H2 are almost identical. Both of them have been found to bind nuclear-matrix proteins. hnRNP H activates exon inclusion by binding G-rich intronic elements downstream of the 5' splice site in the transcripts of c-src, human immunodeficiency virus type 1 (HIV-1), Bcl-X, GRIN1, and myelin. It silences exons when bound to exonic elements in the transcripts of beta-tropomyosin, HIV-1, and alpha-tropomyosin. hnRNP H2 has been implicated in pre-mRNA 3' end formation. Members in this family contain three RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains). RRM1 and RRM2 are responsible for the binding to the RNA at DGGGD motifs, and they play an important role in efficiently silencing the exon. In addition, the family members have an extensive glycine-rich region near the C-terminus, which may allow them to homo- or heterodimerize.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 71998567 282 IVRMRGLPYDCTDAQIRTFFEPLKLTDK---ILFITRTDGRPTGDAFVQFETEEDAQQGLLKHRQVIGQRYIELFKS 355
Cdd:cd12729   3 VVKVRGLPWSCSADEVQNFFSDCKIANGasgIHFIYTREGRPSGEAFVELESEEDVKLALKKDRETMGHRYVEVFKS 79

RNA recognition motif 1 (RRM1) found in heterogeneous nuclear ribonucleoprotein (hnRNP) H protein family, G-rich sequence factor 1 (GRSF-1) and similar proteins; This subfamily corresponds to the RRM1 of hnRNP H proteins and GRSF-1. The hnRNP H protein family includes hnRNP H (also termed mcs94-1), hnRNP H2 (also termed FTP-3 or hnRNP H'), hnRNP F and hnRNP H3 (also termed hnRNP 2H9), which represent a group of nuclear RNA binding proteins that are involved in pre-mRNA processing. These proteins have similar RNA binding affinities and specifically recognize the sequence GGGA. They can either stimulate or repress splicing upon binding to a GGG motif. hnRNP H binds to the RNA substrate in the presence or absence of these proteins, whereas hnRNP F binds to the nuclear mRNA only in the presence of cap-binding proteins. hnRNP H and hnRNP H2 are almost identical; both have been found to bind nuclear-matrix proteins. hnRNP H activates exon inclusion by binding G-rich intronic elements downstream of the 5' splice site in the transcripts of c-src, human immunodeficiency virus type 1 (HIV-1), Bcl-X, GRIN1, and myelin. It silences exons when bound to exonic elements in the transcripts of beta-tropomyosin, HIV-1, and alpha-tropomyosin. hnRNP H2 has been implicated in pre-mRNA 3' end formation. hnRNP H3 may be involved in splicing arrest induced by heat shock. Most family members contain three RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), except for hnRNP H3, in which the RRM1 is absent. RRM1 and RRM2 are responsible for the binding to the RNA at DGGGD motifs, and play an important role in efficiently silencing the exon. Members in this family can regulate the alternative splicing of fibroblast growth factor receptor 2 (FGFR2) transcripts, and function as silencers of FGFR2 exon IIIc through an interaction with the exonic GGG motifs. The lack of RRM1 could account for the reduced silencing activity within hnRNP H3. Members in this family have an extensive glycine-rich region near the C-terminus, which may allow them to homo- or heterodimerize. They also include a cytoplasmic poly(A)+ mRNA binding protein, GRSF-1, which interacts with RNA in a G-rich element-dependent manner. They may function in RNA packaging, stabilization of RNA secondary structure, or other macromolecular interactions. GRSF-1 contains three potential RRMs responsible for the RNA binding, and two auxiliary domains (an acidic alpha-helical domain and an N-terminal alanine-rich region) that may play a role in protein-protein interactions and provide binding specificity.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 71998567 182 VCRARGLPWQASDHHVAQFFAGLDIVPG--GIALCLSSEGRRNGEVLVQFSSQESRDLALKRHRNFLLSRYIEVYK 255
Cdd:cd12503   1 VVRARGLPWSATAEDVLNFFTDCRIKGGenGIHFTYTREGRPSGEAFIELESEEDVEKALEKHNEHMGHRYIEVFR 76

RNA recognition motif 2 (RRM2) found in heterogeneous nuclear ribonucleoprotein H3 (hnRNP H3) and similar proteins; This subgroup corresponds to the RRM2 of hnRNP H3 (also termed hnRNP 2H9), a nuclear RNA binding protein that belongs to the hnRNP H protein family that also includes hnRNP H (also termed mcs94-1), hnRNP H2 (also termed FTP-3 or hnRNP H') and hnRNP F. This family is involved in mRNA processing and exhibit extensive sequence homology. Currently, little is known about the functions of hnRNP H3 except for its role in the splicing arrest induced by heat shock. In addition, the typical hnRNP H proteins contain contain three RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), except for hnRNP H3, in which the RRM1 is absent. RRM1 and RRM2 are responsible for the binding to the RNA at DGGGD motifs, and play an important role in efficiently silencing the exon. Members in this family can regulate the alternative splicing of the fibroblast growth factor receptor 2 (FGFR2) transcripts, and function as silencers of FGFR2 exon IIIc through an interaction with the exonic GGG motifs. The lack of RRM1 could account for the reduced silencing activity within hnRNP H3. In addition, like other hnRNP H protein family members, hnRNP H3 has an extensive glycine-rich region near the C-terminus, which may allow it to homo- or heterodimerize.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998567 177 DGDNVVCRARGLPWQASDHHVAQFFAGLDIVPGGIALCLSSEGRRNGEVLVQFSSQESRDLALKRHRNFLLSRYIEVYKA 256
Cdd:cd12732  15 NSSDGTVRLRGLPFGCSKEEIVQFFSGLEIVPNGITLTMDYQGRSTGEAFVQFASKEIAENALGKHKERIGHRYIEIFKS 94

RNA recognition motif 1 (RRM1) found in G-rich sequence factor 1 (GRSF-1) and similar proteins; This subgroup corresponds to the RRM1 of GRSF-1, a cytoplasmic poly(A)+ mRNA binding protein which interacts with RNA in a G-rich element-dependent manner. It may function in RNA packaging, stabilization of RNA secondary structure, or other macromolecular interactions. GRSF-1 contains three potential RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), which are responsible for the RNA binding. In addition, GRSF-1 has two auxiliary domains, an acidic alpha-helical domain and an N-terminal alanine-rich region, that may play a role in protein-protein interactions and provide binding specificity.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 71998567 282 IVRMRGLPYDCTDAQIRTFFEPLKL---TDKILFITRTDGRPTGDAFVQFETEEDAQQGLLKHRQVIGQRYIELFK 354
Cdd:cd12730   3 IVRARGLPWSCTAEDVLSFFSDCRIrngEDGIHFLLNRDGKRRGDALIELESEEDVQKALEQHRKYMGQRYVEVFE 78

RNA recognition motif 2 (RRM2) found in RNA-binding protein 19 (RBM19) and similar proteins; This subfamily corresponds to the RRM2 of RBM19, also termed RNA-binding domain-1 (RBD-1), a nucleolar protein conserved in eukaryotes. It is involved in ribosome biogenesis by processing rRNA and is also essential for preimplantation development. RBM19 has a unique domain organization containing 6 conserved RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains).

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 71998567 283 VRMRGLPYDCTDAQIRTFFEPLKLTdKILFITRTDGRPTGDAFVQFETEEDAQQGLLKHRQVIGQRYIELF 353
Cdd:cd12502   3 VKLRGAPFNVKEKQIREFFSPLKPV-AIRIVKNAHGNKTGYVFVDFKSEEDVEKALKRNKDYMGGRYIEVF 72

RNA recognition motif 2 (RRM2) found in epithelial splicing regulatory protein ESRP1, ESRP2, Drosophila RNA-binding protein Fusilli and similar proteins; This subfamily corresponds to the RRM2 of ESRPs and Fusilli. ESRP1 (also termed RBM35A) and ESRP2 (also termed RBM35B) are epithelial-specific RNA binding proteins that promote splicing of the epithelial variant of the fibroblast growth factor receptor 2 (FGFR2), ENAH (also termed hMena), CD44 and CTNND1 (also termed p120-Catenin) transcripts. They are highly conserved paralogs and specifically bind to GU-rich binding site. ESRP1 and ESRP2 contain three RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains). The family also includes Drosophila fusilli (fus) gene encoding RNA-binding protein Fusilli.Loss of fusilli activity causes lethality during embryogenesis in flies. Drosophila Fusilli can regulate endogenous FGFR2 splicing and functions as a splicing factor. It shows high sequence homology to ESRPs and contains three RRMs as well. It also has an N-terminal domain with unknown function and a C-terminal domain particularly rich in alanine, glutamine, and serine.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 71998567 181 VVCRARGLPWQASDHHVAQFFAGLDIV---PGGIALCLSSEGRRNGEVLVQFSSQESRDLALKRHRNFLLSRYIEVYK 255
Cdd:cd12508   2 VIVRMRGLPFSATAADILAFFGGECPVtggKDGILFVTYPDGRPTGDAFVLFATEEDAQQALGKHKELLGKRYIELFR 79

RNA recognition motif 1 (RRM1) found in heterogeneous nuclear ribonucleoprotein (hnRNP) H protein family, G-rich sequence factor 1 (GRSF-1) and similar proteins; This subfamily corresponds to the RRM1 of hnRNP H proteins and GRSF-1. The hnRNP H protein family includes hnRNP H (also termed mcs94-1), hnRNP H2 (also termed FTP-3 or hnRNP H'), hnRNP F and hnRNP H3 (also termed hnRNP 2H9), which represent a group of nuclear RNA binding proteins that are involved in pre-mRNA processing. These proteins have similar RNA binding affinities and specifically recognize the sequence GGGA. They can either stimulate or repress splicing upon binding to a GGG motif. hnRNP H binds to the RNA substrate in the presence or absence of these proteins, whereas hnRNP F binds to the nuclear mRNA only in the presence of cap-binding proteins. hnRNP H and hnRNP H2 are almost identical; both have been found to bind nuclear-matrix proteins. hnRNP H activates exon inclusion by binding G-rich intronic elements downstream of the 5' splice site in the transcripts of c-src, human immunodeficiency virus type 1 (HIV-1), Bcl-X, GRIN1, and myelin. It silences exons when bound to exonic elements in the transcripts of beta-tropomyosin, HIV-1, and alpha-tropomyosin. hnRNP H2 has been implicated in pre-mRNA 3' end formation. hnRNP H3 may be involved in splicing arrest induced by heat shock. Most family members contain three RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), except for hnRNP H3, in which the RRM1 is absent. RRM1 and RRM2 are responsible for the binding to the RNA at DGGGD motifs, and play an important role in efficiently silencing the exon. Members in this family can regulate the alternative splicing of fibroblast growth factor receptor 2 (FGFR2) transcripts, and function as silencers of FGFR2 exon IIIc through an interaction with the exonic GGG motifs. The lack of RRM1 could account for the reduced silencing activity within hnRNP H3. Members in this family have an extensive glycine-rich region near the C-terminus, which may allow them to homo- or heterodimerize. They also include a cytoplasmic poly(A)+ mRNA binding protein, GRSF-1, which interacts with RNA in a G-rich element-dependent manner. They may function in RNA packaging, stabilization of RNA secondary structure, or other macromolecular interactions. GRSF-1 contains three potential RRMs responsible for the RNA binding, and two auxiliary domains (an acidic alpha-helical domain and an N-terminal alanine-rich region) that may play a role in protein-protein interactions and provide binding specificity.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998567 391 VRLRGLPYEATVQHIVTFLGDFATMVKFQGVHMVYNNQGHPSGEAFIQMINEQAASAcAAGVHNNFMSvgkkKRYIEVFQ 470
Cdd:cd12503   2 VRARGLPWSATAEDVLNFFTDCRIKGGENGIHFTYTREGRPSGEAFIELESEEDVEK-ALEKHNEHMG----HRYIEVFR 76

RNA recognition motif 2 (RRM2) found in RNA-binding protein RBM12, RBM12B and similar proteins; This subfamily corresponds to the RRM2 of RBM12 and RBM12B. RBM12, also termed SH3/WW domain anchor protein in the nucleus (SWAN), is ubiquitously expressed. It contains five distinct RNA binding motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), two proline-rich regions, and several putative transmembrane domains. RBM12B shows high sequence semilarity with RBM12. It contains five distinct RRMs as well. The biological roles of both RBM12 and RBM12B remain unclear.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 71998567 283 VRMRGLPYDCTDAQIRTFFEPLKLtDKILFITRTDGRPTGDAFVQFETEEDAQQGLLKHRQVIGQRYIELF 353
Cdd:cd12511   2 LSLHGMPYSAMENDVRDFFHGLRV-DGVHLLKDHVGRNNGNALVKFASPQDASEGLKCHRMLMGQRFVEVS 71

RNA recognition motif 2 (RRM2) found in epithelial splicing regulatory protein ESRP1, ESRP2, Drosophila RNA-binding protein Fusilli and similar proteins; This subfamily corresponds to the RRM2 of ESRPs and Fusilli. ESRP1 (also termed RBM35A) and ESRP2 (also termed RBM35B) are epithelial-specific RNA binding proteins that promote splicing of the epithelial variant of the fibroblast growth factor receptor 2 (FGFR2), ENAH (also termed hMena), CD44 and CTNND1 (also termed p120-Catenin) transcripts. They are highly conserved paralogs and specifically bind to GU-rich binding site. ESRP1 and ESRP2 contain three RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains). The family also includes Drosophila fusilli (fus) gene encoding RNA-binding protein Fusilli.Loss of fusilli activity causes lethality during embryogenesis in flies. Drosophila Fusilli can regulate endogenous FGFR2 splicing and functions as a splicing factor. It shows high sequence homology to ESRPs and contains three RRMs as well. It also has an N-terminal domain with unknown function and a C-terminal domain particularly rich in alanine, glutamine, and serine.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998567 391 VRLRGLPYEATVQHIVTFLGDFATMVKF-QGVHMVYNNQGHPSGEAFIQMINEQAASAcAAGVHNNFMSvgkkKRYIEVF 469
Cdd:cd12508   4 VRMRGLPFSATAADILAFFGGECPVTGGkDGILFVTYPDGRPTGDAFVLFATEEDAQQ-ALGKHKELLG----KRYIELF 78

RNA recognition motif 2 (RRM2) found in RNA-binding protein RBM12, RBM12B and similar proteins; This subfamily corresponds to the RRM2 of RBM12 and RBM12B. RBM12, also termed SH3/WW domain anchor protein in the nucleus (SWAN), is ubiquitously expressed. It contains five distinct RNA binding motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), two proline-rich regions, and several putative transmembrane domains. RBM12B shows high sequence semilarity with RBM12. It contains five distinct RRMs as well. The biological roles of both RBM12 and RBM12B remain unclear.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 71998567 184 RARGLPWQASDHHVAQFFAGLDIvpGGIALCLSSEGRRNGEVLVQFSSQESRDLALKRHRNFLLSRYIEVYKA 256
Cdd:cd12511   3 SLHGMPYSAMENDVRDFFHGLRV--DGVHLLKDHVGRNNGNALVKFASPQDASEGLKCHRMLMGQRFVEVSPA 73

RNA recognition motif 2 (RRM2) found in RNA-binding protein 19 (RBM19) and similar proteins; This subfamily corresponds to the RRM2 of RBM19, also termed RNA-binding domain-1 (RBD-1), a nucleolar protein conserved in eukaryotes. It is involved in ribosome biogenesis by processing rRNA and is also essential for preimplantation development. RBM19 has a unique domain organization containing 6 conserved RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains).

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 71998567 183 CRARGLPWQASDHHVAQFFAGLDivPGGIALCLSSEGRRNGEVLVQFSSQESRDLALKRHRNFLLSRYIEVY 254
Cdd:cd12502   3 VKLRGAPFNVKEKQIREFFSPLK--PVAIRIVKNAHGNKTGYVFVDFKSEEDVEKALKRNKDYMGGRYIEVF 72

RNA recognition motif 2 (RRM2) found in Drosophila RNA-binding protein Fusilli and similar proteins; This subgroup corresponds to the RRM2 of RNA-binding protein Fusilli which is encoded by Drosophila fusilli (fus) gene. Loss of Fusilli activity causes lethality during embryogenesis in flies. Drosophila Fusilli can regulate endogenous fibroblast growth factor receptor 2 (FGFR2) splicing and functions as a splicing factor. Fusilli contains three RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), an N-terminal domain with unknown function and a C-terminal domain particularly rich in alanine, glutamine, and serine.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998567 170 EDQEVGADGDNVVCRARGLPWQASDHHVAQFFAGLDIVPG------GIALCLSSEGRRNGEVLVQFSSQESRDLALKRHR 243
Cdd:cd12741   7 EAQNFLSKGGQVIIRMRGLPYDCTPKQVVEFFCTGDKIPHvldgaeGVLFVKKPDGRATGDAFVLFETEEVAEKALEKHR 86

                        90
                ....*....|...
gi 71998567 244 NFLLSRYIEVYKA 256
Cdd:cd12741  87 QHIGSRYIELFRS 99

RNA recognition motif 1 (RRM1) found in heterogeneous nuclear ribonucleoprotein hnRNP H , hnRNP H2, hnRNP F and similar proteins; This subgroup corresponds to the RRM1 of hnRNP H (also termed mcs94-1), hnRNP H2 (also termed FTP-3 or hnRNP H') and hnRNP F. These represent a group of nuclear RNA binding proteins that play important roles in the regulation of alternative splicing decisions. hnRNP H and hnRNP F are two closely related proteins, both of which bind to the RNA sequence DGGGD. They are present in a complex with the tissue-specific splicing factor Fox2, and regulate the alternative splicing of the fibroblast growth factor receptor 2 (FGFR2) transcripts. The presence of Fox 2 can allows hnRNP H and hnRNP F to better compete with the SR protein ASF/SF2 for binding to FGFR2 exon IIIc. Thus, hnRNP H and hnRNP F can function as potent silencers of FGFR2 exon IIIc inclusion through an interaction with the exonic GGG motifs. Furthermore, hnRNP H and hnRNP H2 are almost identical. Both of them have been found to bind nuclear-matrix proteins. hnRNP H activates exon inclusion by binding G-rich intronic elements downstream of the 5' splice site in the transcripts of c-src, human immunodeficiency virus type 1 (HIV-1), Bcl-X, GRIN1, and myelin. It silences exons when bound to exonic elements in the transcripts of beta-tropomyosin, HIV-1, and alpha-tropomyosin. hnRNP H2 has been implicated in pre-mRNA 3' end formation. Members in this family contain three RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains). RRM1 and RRM2 are responsible for the binding to the RNA at DGGGD motifs, and they play an important role in efficiently silencing the exon. In addition, the family members have an extensive glycine-rich region near the C-terminus, which may allow them to homo- or heterodimerize.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998567 391 VRLRGLPYEATVQHIVTFLGDFATMVKFQGVHMVYNNQGHPSGEAFIQMINEQAASacaAGVHNNFMSVGkkKRYIEVFQ 470
Cdd:cd12729   4 VKVRGLPWSCSADEVQNFFSDCKIANGASGIHFIYTREGRPSGEAFVELESEEDVK---LALKKDRETMG--HRYVEVFK 78

                .
gi 71998567 471 A 471
Cdd:cd12729  79 S 79

RNA recognition motif 1 (RRM1) found in RNA-binding protein RBM12, RBM12B and similar proteins; This subfamily corresponds to the RRM1 of RBM12 and RBM12B. RBM12, also termed SH3/WW domain anchor protein in the nucleus (SWAN), is ubiquitously expressed. It contains five distinct RNA binding motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), two proline-rich regions, and several putative transmembrane domains. RBM12B show high sequence semilarity with RBM12. It contains five distinct RRMs as well. The biological roles of both RBM12 and RBM12B remain unclear.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 71998567 280 AIIVRMRGLPYDCTDAQIRTFFEPLKLTDKILFITrtdGRPTGDAFVQFETEEDAQQGLLKHRQVIGQRYIELFKST 356
Cdd:cd12510   1 SVVIRLQGLPWEAGSLDIRRFFSGLTIPDGGVHII---GGEKGEAFIIFATDEDARLAMMRDGQTIKGSKVKLFLSS 74

RNA recognition motif 3 (RRM3) found in RNA-binding protein 12 (RBM12) and similar proteins; This subfamily corresponds to the RRM3 of RBM12. RBM12, also termed SH3/WW domain anchor protein in the nucleus (SWAN), is ubiquitously expressed. It contains five distinct RNA binding motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), two proline-rich regions, and several putative transmembrane domains. The biological role of RBM12 remains unclear.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 71998567 283 VRMRGLPYDCTDAQIRTFFEPLKLTDKILFITR-TDGRPTGDAFVQFETEEDAQQGLLKHRQVIGQRYIEL 352
Cdd:cd12512  12 VYLKGLPYEAENKHVIEFFKKLDIVEDSIYIAYgPNGRATGEGFVEFRNEIDYKAALCRHKQYMGNRFIQV 82

RNA recognition motif 1 (RRM1) found in G-rich sequence factor 1 (GRSF-1) and similar proteins; This subgroup corresponds to the RRM1 of GRSF-1, a cytoplasmic poly(A)+ mRNA binding protein which interacts with RNA in a G-rich element-dependent manner. It may function in RNA packaging, stabilization of RNA secondary structure, or other macromolecular interactions. GRSF-1 contains three potential RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), which are responsible for the RNA binding. In addition, GRSF-1 has two auxiliary domains, an acidic alpha-helical domain and an N-terminal alanine-rich region, that may play a role in protein-protein interactions and provide binding specificity.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998567 390 CVRLRGLPYEATVQHIVTFLGDFATMVKFQGVHMVYNNQGHPSGEAFIQMINEQAASAcAAGVHNNFMsvgkKKRYIEVF 469
Cdd:cd12730   3 IVRARGLPWSCTAEDVLSFFSDCRIRNGEDGIHFLLNRDGKRRGDALIELESEEDVQK-ALEQHRKYM----GQRYVEVF 77

                .
gi 71998567 470 Q 470
Cdd:cd12730  78 E 78

RNA recognition motif 5 (RRM5) found in RNA-binding protein RBM12, RBM12B and similar proteins; This subfamily corresponds to the RRM5 of RBM12 and RBM12B. RBM12, also termed SH3/WW domain anchor protein in the nucleus (SWAN), is ubiquitously expressed. It contains five distinct RNA binding motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), two proline-rich regions, and several putative transmembrane domains. RBM12B show high sequence semilarity with RBM12. It contains five distinct RRMs as well. The biological roles of both RBM12 and RBM12B remain unclear.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 71998567 282 IVRMRGLPYDCTDAQIRTFFEPLKLTDKILFITRTD-GRPTGDAFVQFETEEDAQQGLLK-HRQVIGQRYIELF 353
Cdd:cd12515   2 VVKMRNLPFKATIEDILDFFYGYRVIPDSVSIRYNDdGQPTGDARVAFPSPREARRAVRElNNRPLGGRKVKLF 75

RNA recognition motif 1 (RRM1) found in epithelial splicing regulatory protein ESRP1, ESRP2, Drosophila RNA-binding protein Fusilli and similar proteins; This subfamily corresponds to the RRM1 of ESRPs and Fusilli. ESRP1 (also termed RBM35A) and ESRP2 (also termed RBM35B). These are epithelial-specific RNA binding proteins that promote splicing of the epithelial variant of the fibroblast growth factor receptor 2 (FGFR2), ENAH (also termed hMena), CD44 and CTNND1 (also termed p120-Catenin) transcripts. They are highly conserved paralogs and specifically bind to GU-rich binding site. ESRP1 and ESRP2 contain three RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains). The family also includes Drosophila fusilli (fus) gene encoding RNA-binding protein Fusilli. Loss of fusilli activity causes lethality during embryogenesis in flies. Drosophila Fusilli can regulate endogenous fibroblast growth factor receptor 2 (FGFR2) splicing and functions as a splicing factor. It shows high sequence homology to ESRPs and contains three RRMs as well. It also has an N-terminal domain with unknown function and a C-terminal domain particularly rich in alanine, glutamine, and serine.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998567 390 CVRLRGLPYEATVQHIVTFlgdFATM-VKFQGVHMVYNNQGHPSGEAFIQMINEQAASaCAAGVHNNFMSvgkkKRYIEV 468
Cdd:cd12507   1 VVRARGLPWQSSDQDIAQF---FRGLnIAKGGVALCLSAQGRRNGEALIRFVDQEHRD-LALQRHKHHMG----TRYIEV 72

                ...
gi 71998567 469 FQA 471
Cdd:cd12507  73 YKA 75

RNA recognition motif 3 (RRM3) found in epithelial splicing regulatory protein ESRP1, ESRP2 and similar proteins; This subgroup corresponds to the RRM3 of ESRP1 (also termed RBM35A) and ESRP2 (also termed RBM35B). These are epithelial-specific RNA binding proteins that promote splicing of the epithelial variant of the fibroblast growth factor receptor 2 (FGFR2), ENAH (also termed hMena), CD44 and CTNND1 (also termed p120-Catenin) transcripts. They are highly conserved paralogs and specifically bind to GU-rich binding site. ESRP1 and ESRP2 contain three RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains).

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 71998567 283 VRMRGLPYDCTDAQIRTF---FEPLKLTDKILFITRTDGRPTGDAFVQFETEEDAQQGLLK-HRQVIGQRYIELFK 354
Cdd:cd12742   4 IRLRGLPYAATIEDILEFlgeFAADIRPHGVHMVLNHQGRPSGDAFIQMKSADRAFLAAQKcHKKTMKDRYVEVFQ 79

RNA recognition motif 2 (RRM2) found in heterogeneous nuclear ribonucleoprotein hnRNP H, hnRNP H2, hnRNP F and similar proteins; This subgroup corresponds to the RRM2 of hnRNP H (also termed mcs94-1), hnRNP H2 (also termed FTP-3 or hnRNP H') and hnRNP F. These represent a group of nuclear RNA binding proteins that play important roles in the regulation of alternative splicing decisions. hnRNP H and hnRNP F are two closely related proteins, both of which bind to the RNA sequence DGGGD. They are present in a complex with the tissue-specific splicing factor Fox2, and regulate the alternative splicing of the fibroblast growth factor receptor 2 (FGFR2) transcripts. The presence of Fox 2 can allows hnRNP H and hnRNP F to better compete with the SR protein ASF/SF2 for binding to FGFR2 exon IIIc. Thus, hnRNP H and hnRNP F can function as potent silencers of FGFR2 exon IIIc inclusion through an interaction with the exonic GGG motifs. Furthermore, hnRNP H and hnRNP H2 are almost identical; both have been found to bind nuclear-matrix proteins. hnRNP H activates exon inclusion by binding G-rich intronic elements downstream of the 5' splice site in the transcripts of c-src, human immunodeficiency virus type 1 (HIV-1), Bcl-X, GRIN1, and myelin. It silences exons when bound to exonic elements in the transcripts of beta-tropomyosin, HIV-1, and alpha-tropomyosin. hnRNP H2 has been implicated in pre-mRNA 3' end formation. Members in this family contain three RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains). RRM1 and RRM2 are responsible for the binding to the RNA at DGGGD motifs, and they play an important role in efficiently silencing the exon. In addition, the family members have an extensive glycine-rich region near the C-terminus, which may allow them to homo- or heterodimerize.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998567 382 APEEKKKDCVRLRGLPYEATVQHIVTFlgdfatmvkFQGVHMVYNN-------QGHPSGEAFIQMINEQAASAcAAGVHN 454
Cdd:cd12731   2 SPDTANDGFVRLRGLPFGCSKEEIVQF---------FSGLEIVPNGitlpvdfQGRSTGEAFVQFASQEIAEK-ALKKHK 71

                        90       100
                ....*....|....*....|..
gi 71998567 455 NFMSvgkkKRYIEVFQASAEEL 476
Cdd:cd12731  72 ERIG----HRYIEIFKSSRAEV 89

RNA recognition motif 3 (RRM3) found in RNA-binding protein 12B (RBM12B) and similar proteins; This subgroup corresponds to the RRM3 of RBM12B which contains five distinct RNA binding motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains). Its biological role remains unclear.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 71998567 283 VRMRGLPYDCTDAQIRTFFEPLKLTDK-ILFITRTDGRPTGDAFVQFETEEDAQQGLLKHRQVIGQRYIELF 353
Cdd:cd12513   3 VHLKNLSYSVDKRDIRNFFRDLDISDDqIKFLHDKYGKRTREAFVMFKNEKDYQTALSLHKGCLGNRTVYIY 74

RNA recognition motif 3 (RRM3) found in heterogeneous nuclear ribonucleoprotein hnRNP H protein family, G-rich sequence factor 1 (GRSF-1) and similar proteins; This subfamily corresponds to the RRM3 of hnRNP H proteins and GRSF-1. The hnRNP H protein family includes hnRNP H (also termed mcs94-1), hnRNP H2 (also termed FTP-3 or hnRNP H'), hnRNP F and hnRNP H3 (also termed hnRNP 2H9), which represent a group of nuclear RNA binding proteins that are involved in pre-mRNA processing. These proteins have similar RNA binding affinities and specifically recognize the sequence GGGA. They can either stimulate or repress splicing upon binding to a GGG motif. hnRNP H binds to the RNA substrate in the presence or absence of these proteins, whereas hnRNP F binds to the nuclear mRNA only in the presence of cap-binding proteins. hnRNP H and hnRNP H2 are almost identical; both have been found to bind nuclear-matrix proteins. hnRNP H activates exon inclusion by binding G-rich intronic elements downstream of the 5' splice site in the transcripts of c-src, human immunodeficiency virus type 1 (HIV-1), Bcl-X, GRIN1, and myelin. It silences exons when bound to exonic elements in the transcripts of beta-tropomyosin, HIV-1, and alpha-tropomyosin. hnRNP H2 has been implicated in pre-mRNA 3' end formation. hnRNP H3 may be involved in the splicing arrest induced by heat shock. Most family members contain three RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), except for hnRNP H3, in which the RRM1 is absent. RRM1 and RRM2 are responsible for the binding to the RNA at DGGGD motifs, and they play an important role in efficiently silencing the exon. For instance, members in this family can regulate the alternative splicing of the fibroblast growth factor receptor 2 (FGFR2) transcripts, and function as silencers of FGFR2 exon IIIc through an interaction with the exonic GGG motifs. The lack of RRM1 could account for the reduced silencing activity within hnRNP H3. In addition, the family members have an extensive glycine-rich region near the C-terminus, which may allow them to homo- or heterodimerize. The family also includes a cytoplasmic poly(A)+ mRNA binding protein, GRSF-1, which interacts with RNA in a G-rich element-dependent manner. It may function in RNA packaging, stabilization of RNA secondary structure, or other macromolecular interactions. GRSF-1 also contains three potential RRMs responsible for the RNA binding, and two auxiliary domains (an acidic alpha-helical domain and an N-terminal alanine-rich region) that may play a role in protein-protein interactions and provide binding specificity.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 71998567 186 RGLPWQASDHHVAQFFAGLDivPGGIALCLSSEGRRNGEVLVQFSSQESRDLALKRHRNFLLSRYIEVY 254
Cdd:cd12506   6 RGLPYRATENDIFEFFSPLN--PVNVRIRYNKDGRATGEADVEFATHEDAVAAMSKDRENMGHRYIELF 72

RNA recognition motif 2 (RRM2) found in epithelial splicing regulatory protein 1 (ESRP1) and similar proteins; This subgroup corresponds to the RRM2 of ESRP1, also termed RNA-binding motif protein 35A (RBM35A), which has been identified as an epithelial cell type-specific regulator of fibroblast growth factor receptor 2 (FGFR2) splicing. It is required for expression of epithelial FGFR2-IIIb and the regulation of CD44, CTNND1 (also termed p120-Catenin) and ENAH (also termed hMena) splicing. It enhances epithelial-specific exons of CD44 and ENAH, silences mesenchymal exons of CTNND1, or both within FGFR2. Additional research indicated that ESRP1 functions as a tumor suppressor in colon cancer cells. It may be involved in posttranscriptional regulation of various genes by exerting a differential effect on protein translation via 5' untranslated regions (UTRs) of mRNAs. ESRP1 contains three RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains).

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998567 179 DNVVCRARGLPWQASDHHVAQFFAGLDIVPGG---IALCLSSEGRRNGEVLVQFSSQESRDLALKRHRNFLLSRYIEVYK 255
Cdd:cd12739  15 NQVIVRMRGLPFTATAEEVLAFFGQHCPVTGGkegILFVTYPDSRPTGDAFVLFACEEYAQNALKKHKDLLGKRYIELFR 94

                ....*....
gi 71998567 256 AGLDEFMHV 264
Cdd:cd12739  95 STAAEVQQV 103