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 1446042969 464 RDCVRLRGLPYTATIEDILSFLGEAAADIRPHGVHMVLNQQGRPSGDAFIQMTSAERALAAAQRCHKKVMKERYVEVVPC 543
Cdd:cd12742     1 RDCIRLRGLPYAATIEDILEFLGEFAADIRPHGVHMVLNHQGRPSGDAFIQMKSADRAFLAAQKCHKKTMKDRYVEVFQC 80

                  .
gi 1446042969 544 S 544
Cdd:cd12742    81 S 81

DnaQ-like (or DEDD) 3'-5' exonuclease domain superfamily; The DnaQ-like exonuclease superfamily is a structurally conserved group of 3'-5' exonucleases, which catalyze the excision of nucleoside monophosphates at the DNA or RNA termini in the 3'-5' direction. It is also called the DEDD superfamily, after the four invariant acidic residues present in the catalytic site of its members. The superfamily consists of DNA- and RNA-processing enzymes such as the proofreading domains of DNA polymerases, other DNA exonucleases, RNase D, RNase T, Oligoribonuclease and RNA exonucleases (REX). The DnaQ-like exonuclease domain contains three conserved sequence motifs termed ExoI, ExoII and ExoIII, which are clustered around the active site and contain four conserved acidic residues that serve as ligands for the two metal ions required for catalysis. The conservation patterns of the three motifs may vary among different subfamilies. DnaQ-like exonucleases are classified as DEDDy or DEDDh exonucleases depending on the variation of motif III as YX(3)D or HX(4)D, respectively. The significance of the motif differences is still unclear. Almost all RNase families in this superfamily are present only in eukaryotes and bacteria, but not in archaea, suggesting a later origin, which in some cases are accompanied by horizontal gene transfer.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1446042969  86 CREASGLSADSLARAEPLDKVLQQFSQLVNGDvallggGPYMLCTDGQQLLRQVLHPEASRKNLVLPDMFFSFYDLRREF 165
Cdd:cd06133    58 CTELTGITQEDVDNAPSFPEVLKEFLEWLGKN------GKYAFVTWGDWDLKDLLQNQCKYKIINLPPFFRQWIDLKKEF 131

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1446042969 166 --HMQHPstcpaRDLTVATMAQGLGLETDATEDDfGVWEVKTMVAVILHLL 214
Cdd:cd06133   132 akFYGLK-----KRTGLSKALEYLGLEFEGRHHR-GLDDARNIARILKRLL 176

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 1446042969 464 RDCVRLRGLPYTATIEDILSFLGEAAADIRPHGVHMVLNQQGRPSGDAFIQMTSAERALAAAQRCHKKVMKERYVEVVPC 543
Cdd:cd12742     1 RDCIRLRGLPYAATIEDILEFLGEFAADIRPHGVHMVLNHQGRPSGDAFIQMKSADRAFLAAQKCHKKTMKDRYVEVFQC 80

                  .
gi 1446042969 544 S 544
Cdd:cd12742    81 S 81

DEDDh 3'-5' exonuclease domain of Caenorhabditis elegans ERI-1, human 3' exonuclease, and similar proteins; This subfamily is composed of Caenorhabditis elegans ERI-1, human 3' exonuclease (3'hExo), Drosophila exonuclease snipper (snp), and similar proteins from eukaryotes and bacteria. These are DEDDh-type DnaQ-like 3'-5' exonucleases containing three conserved sequence motifs termed ExoI, ExoII and ExoIII, with a specific Hx(4)D conserved pattern at ExoIII. These motifs are clustered around the active site and contain four conserved acidic residues that serve as ligands for the two metal ions required for catalysis. ERI-1 has been implicated in the degradation of small interfering RNAs (RNAi). 3'hExo participates in the degradation of histone mRNAs. Snp is a non-essential exonuclease that efficiently degrades structured RNA and DNA substrates as long as there is a minimum of 2 nucleotides in the 3' overhang to initiate degradation. Snp is not a functional homolog of either ERI-1 or 3'hExo.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1446042969  86 CREASGLSADSLARAEPLDKVLQQFSQLVNGDvallggGPYMLCTDGQQLLRQVLHPEASRKNLVLPDMFFSFYDLRREF 165
Cdd:cd06133    58 CTELTGITQEDVDNAPSFPEVLKEFLEWLGKN------GKYAFVTWGDWDLKDLLQNQCKYKIINLPPFFRQWIDLKKEF 131

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1446042969 166 --HMQHPstcpaRDLTVATMAQGLGLETDATEDDfGVWEVKTMVAVILHLL 214
Cdd:cd06133   132 akFYGLK-----KRTGLSKALEYLGLEFEGRHHR-GLDDARNIARILKRLL 176

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 1446042969 467 VRLRGLPYTATIEDILSFLGEaAADIRphGVHMVLNQQGRPSGDAFIQMTSAERALAAAQRCHKKVMKERYVE 539
Cdd:pfam00076   1 LFVGNLPPDTTEEDLKDLFSK-FGPIK--SIRLVRDETGRSKGFAFVEFEDEEDAEKAIEALNGKELGGRELK 70

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 1446042969 464 RDCVRLRGLPYTATIEDILSFLGEAAADIRPHGVHMVLNQQGRPSGDAFIQMTSAERALAAAQRCHKKVMKERYVEVVPC 543
Cdd:cd12742     1 RDCIRLRGLPYAATIEDILEFLGEFAADIRPHGVHMVLNHQGRPSGDAFIQMKSADRAFLAAQKCHKKTMKDRYVEVFQC 80

                  .
gi 1446042969 544 S 544
Cdd:cd12742    81 S 81

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 1446042969 248 VVRARGLPWQSSDQDVARFFKGLNVARGGVALCLNAQGRRNGEALIRFVDSEQRDLALQRHKHHMGVRYIEVYKATGEEF 327
Cdd:cd12737     1 VIRARGLPWQSSDQDIARFFKGLNIAKGGVALCLNAQGRRNGEALVRFVNSEQRDLALERHKHHMGSRYIEVYKATGEEF 80

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 1446042969 248 VVRARGLPWQSSDQDVARFFKGLNVARGGVALCLNAQGRRNGEALIRFVDSEQRDLALQRHKHHMGVRYIEVYKA 322
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 1446042969 464 RDCVRLRGLPYTATIEDILSFLGEAAADIRPHGVHMVLNQQGRPSGDAFIQMTSAERALAAAQRCHKKVMKERYVEVVPC 543
Cdd:cd12509     1 RDCIRLRGLPYSATVEDILNFLGEFAKHIAPQGVHMVINAQGRPSGDAFIQMLSAEFARLAAQKRHKHHMGERYIEVFQC 80

                  .
gi 1446042969 544 S 544
Cdd:cd12509    81 S 81

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 1446042969 331 AGGTSLEVARFLSREDQVILRLRGLPFSAGPTDVLGFL---GPECPVTGGTEGLLFVRHPDGRPTGDAFALFACEELAQA 407
Cdd:cd12741     1 AGGESNEAQNFLSKGGQVIIRMRGLPYDCTPKQVVEFFctgDKIPHVLDGAEGVLFVKKPDGRATGDAFVLFETEEVAEK 80

                          90
                  ....*....|....*....
gi 1446042969 408 ALRRHKGMLGKRYIELFRS 426
Cdd:cd12741    81 ALEKHRQHIGSRYIELFRS 99

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 1446042969 248 VVRARGLPWQSSDQDVARFFKGLNVARGGVALCLNAQGRRNGEALIRFVDSEQRDLALQRHKHHMGVRYIEVY 320
Cdd:cd12254     1 VVRLRGLPFSATEEDIRDFFSGLDIPPDGIHIVYDDDGRPTGEAYVEFASEEDAQRALRRHKGKMGGRYIEVF 73

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 1446042969 349 ILRLRGLPFSAGPTDVLGFLGPecpVTGGTEGLLFVRHPDGRPTGDAFALFACEELAQAALRRHKGMLGKRYIELF 424
Cdd:cd12254     1 VVRLRGLPFSATEEDIRDFFSG---LDIPPDGIHIVYDDDGRPTGEAYVEFASEEDAQRALRRHKGKMGGRYIEVF 73

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 1446042969 247 TVVRARGLPWQSSDQDVARFFKGLNVARGGVALCLNAQGRRNGEALIRFVDSEQRDLALQRHKHHMGVRYIEVYKAT 323
Cdd:cd12504     1 GVVRLRGLPYGCTKEEIAQFFSGLEIVPNGITLPMDRRGRSTGEAFVQFASQEIAEQALGKHKEKIGHRYIEIFRSS 77

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 1446042969 234 TGPCSKADvvDSETVVRARGLPWQSSDQDVARFFKGLNVARGGVALCLNAQGRRNGEALIRFVDSEQRDLALQRHKHHMG 313
Cdd:cd12732     8 NGPTDTEN--SSDGTVRLRGLPFGCSKEEIVQFFSGLEIVPNGITLTMDYQGRSTGEAFVQFASKEIAENALGKHKERIG 85

                          90
                  ....*....|
gi 1446042969 314 VRYIEVYKAT 323
Cdd:cd12732    86 HRYIEIFKSS 95

RNA recognition motif 2 (RRM2) found in G-rich sequence factor 1 (GRSF-1) and similar proteins; This subfamily corresponds to the RRM2 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 1446042969 246 ETVVRARGLPWQSSDQDVARFFKGLNVarGGVALCLNAQG-RRNGEALIRFVDSEQRDLALQRHKHHMGVRYIEVY 320
Cdd:cd12505     1 DGVVRLRGLPYSCTEADIAHFFSGLDI--VDITFVMDLRGgRKTGEAFVQFASPEMAAQALLKHKEEIGNRYIEIF 74

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 1446042969 467 VRLRGLPYTATIEDILSFLGEAAADIRPHGVHMVLNQQGRPSGDAFIQMTSAERALAAAQRcHKKVMKERYVEV 540
Cdd:cd12503     2 VRARGLPWSATAEDVLNFFTDCRIKGGENGIHFTYTREGRPSGEAFIELESEEDVEKALEK-HNEHMGHRYIEV 74

RNA recognition motif 2 (RRM2) found in RNA-binding protein 12B (RBM12B) and similar proteins; This subgroup corresponds to the RRM2 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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1446042969 252 RGLPWQSSDQDVARFFKGLNVArgGVALCLNAQGRRNGEALIRFVDSEQRDLALQRHKHHMGVRYIEVYKATGEEFVKiA 331
Cdd:cd12746     8 RGMPYSATEDDVRNFFSGLKVD--GVIFLKHPNGRNNGNGLVKFATKEDASEGLKRHRQYMGSRFIEVTRTTEEQWIE-A 84

                  ..
gi 1446042969 332 GG 333
Cdd:cd12746    85 GG 86

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1446042969 249 VRARGLPWQSSDQDVARFFKGL--NVARGGVALCLNAQGRRNGEALIRFVDSEQ-RDLALQRHKHHMGVRYIEVYK 321
Cdd:cd12509     4 IRLRGLPYSATVEDILNFLGEFakHIAPQGVHMVINAQGRPSGDAFIQMLSAEFaRLAAQKRHKHHMGERYIEVFQ 79

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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1446042969 466 CVRLRGLPYTATIEDILSFLgeAAADIRPHGVHMVLNQQGRPSGDAFIQMTS---AERALAAaqrcHKKVMKERYVEVVP 542
Cdd:cd12504     2 VVRLRGLPYGCTKEEIAQFF--SGLEIVPNGITLPMDRRGRSTGEAFVQFASqeiAEQALGK----HKEKIGHRYIEIFR 75

                  ..
gi 1446042969 543 CS 544
Cdd:cd12504    76 SS 77

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 1446042969 349 ILRLRGLPFSAGPTDVLGFLGpECPVTGGTEGLLFVRHPDGRPTGDAFALFACEELAQAALRRHKGMLGKRYIELFRS 426
Cdd:cd12729     3 VVKVRGLPWSCSADEVQNFFS-DCKIANGASGIHFIYTREGRPSGEAFVELESEEDVKLALKKDRETMGHRYVEVFKS 79

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 1446042969 248 VVRARGLPWQSSDQDVARFFKGLNVARG--GVALCLNAQGRRNGEALIRFVDSEQRDLALQRHKHHMGVRYIEVYKA 322
Cdd:cd12729     3 VVKVRGLPWSCSADEVQNFFSDCKIANGasGIHFIYTREGRPSGEAFVELESEEDVKLALKKDRETMGHRYVEVFKS 79

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 1446042969 349 ILRLRGLPFSAGPTDVLGFLGpECPVTGGTEGLLFVRHPDGRPTGDAFALFACEELAQAALRRHKGMLGKRYIELF 424
Cdd:cd12730     3 IVRARGLPWSCTAEDVLSFFS-DCRIRNGEDGIHFLLNRDGKRRGDALIELESEEDVQKALEQHRKYMGQRYVEVF 77

RNA recognition motif 2 (RRM2) found in RNA-binding protein 12B (RBM12B) and similar proteins; This subgroup corresponds to the RRM2 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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1446042969 346 DQVILRLRGLPFSAGPTDVLGFLGPECpvtggTEGLLFVRHPDGRPTGDAFALFACEELAQAALRRHKGMLGKRYIELFR 425
Cdd:cd12746     1 DDVYLFLRGMPYSATEDDVRNFFSGLK-----VDGVIFLKHPNGRNNGNGLVKFATKEDASEGLKRHRQYMGSRFIEVTR 75

                  ..
gi 1446042969 426 ST 427
Cdd:cd12746    76 TT 77

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        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1446042969 248 VVRARGLPWQSSDQDVARFFKGLNVARggVALCLNAQGRRNGEALIRFVDSEQRDLALQRHKHHMGVRYIEVY 320
Cdd:cd12506     2 TVHMRGLPYRATENDIFEFFSPLNPVN--VRIRYNKDGRATGEADVEFATHEDAVAAMSKDRENMGHRYIELF 72

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 1446042969 465 DCVRLRGLPYTATIEDILSFLGeaAADIRPHGVHMVLNQQGRPSGDAFIQMTSAERALAAAQRCHKKVMKERYVEV 540
Cdd:cd12515     1 CVVKMRNLPFKATIEDILDFFY--GYRVIPDSVSIRYNDDGQPTGDARVAFPSPREARRAVRELNNRPLGGRKVKL 74

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 1446042969 349 ILRLRGLPFSAGPTDVLGF-LGPECPVTGGTEGLLFvrhpDGRPTGDAFALFACEELAQAALRRHKGMLGKRYIELFRST 427
Cdd:cd12732    20 TVRLRGLPFGCSKEEIVQFfSGLEIVPNGITLTMDY----QGRSTGEAFVQFASKEIAENALGKHKERIGHRYIEIFKSS 95

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        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1446042969 466 CVRLRGLPYTATIEDILSFLgeaaADIRPHGVHMVLNQQGRPSGDAFIQMTSAERALAAAQRcHKKVMKERYVE 539
Cdd:cd12506     2 TVHMRGLPYRATENDIFEFF----SPLNPVNVRIRYNKDGRATGEADVEFATHEDAVAAMSK-DRENMGHRYIE 70

RNA recognition motif 2 (RRM2) found in G-rich sequence factor 1 (GRSF-1) and similar proteins; This subfamily corresponds to the RRM2 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 1446042969 349 ILRLRGLPFSAGPTDVLGFLGPECPVtggteGLLFV-RHPDGRPTGDAFALFACEELAQAALRRHKGMLGKRYIELFRS 426
Cdd:cd12505     3 VVRLRGLPYSCTEADIAHFFSGLDIV-----DITFVmDLRGGRKTGEAFVQFASPEMAAQALLKHKEEIGNRYIEIFPS 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 1446042969 457 PLAPGTGRDC-VRLRGLPYTATIEDILSFLgeAAADIRPHGVHMVLNQQGRPSGDAFIQMTSAERALAAAQRcHKKVMKE 535
Cdd:cd12732    10 PTDTENSSDGtVRLRGLPFGCSKEEIVQFF--SGLEIVPNGITLTMDYQGRSTGEAFVQFASKEIAENALGK-HKERIGH 86

                  ....*....
gi 1446042969 536 RYVEVVPCS 544
Cdd:cd12732    87 RYIEIFKSS 95

RNA recognition motif 2 (RRM2) found in G-rich sequence factor 1 (GRSF-1) and similar proteins; This subfamily corresponds to the RRM2 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 1446042969 467 VRLRGLPYTATIEDILSFLgeaaADIRPHGVHMVLNQQG-RPSGDAFIQMTSAERALAAAQRcHKKVMKERYVEVVP 542
Cdd:cd12505     4 VRLRGLPYSCTEADIAHFF----SGLDIVDITFVMDLRGgRKTGEAFVQFASPEMAAQALLK-HKEEIGNRYIEIFP 75

RNA recognition motif 3 (RRM3) found in heterogeneous nuclear ribonucleoprotein H3 (hnRNP H3) and similar proteins; This subgroup corresponds to the RRM3 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 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, 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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1446042969 249 VRARGLPWQSSDQDVARFFKGLNVARggVALCLNAQGRRNGEALIRFVDSEQRDLALQRHKHHMGVRYIEVY 320
Cdd:cd12735     3 VHMRGLPFRATESDIANFFSPLNPIR--VHIDIGADGRATGEADVEFATHEDAVAAMSKDKNHMQHRYIELF 72

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 1446042969 467 VRLRGLPYTATIEDILSFLgeAAADIRPHGVHMVLNQQGRPSGDAFIQMTSAERALAAAQRcHKKVMKERYVEVVPCSTE 546
Cdd:cd12737     2 IRARGLPWQSSDQDIARFF--KGLNIAKGGVALCLNAQGRRNGEALVRFVNSEQRDLALER-HKHHMGSRYIEVYKATGE 78

                  .
gi 1446042969 547 E 547
Cdd:cd12737    79 E 79

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 1446042969 350 LRLRGLPFSAGPTDVLGFLGPECpvtggTEGLLFVRHPDGRPTGDAFALFACEELAQAALRRHKGMLGKRYIELF 424
Cdd:cd12511     2 LSLHGMPYSAMENDVRDFFHGLR-----VDGVHLLKDHVGRNNGNALVKFASPQDASEGLKCHRMLMGQRFVEVS 71

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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1446042969 244 DSETVVRARGLPWQSSDQDVARFFKGLNVARGGVALCLNAQGRRNGEALIRFVDSEQRDLALQRHKHHMGVRYIEVYKAT 323
Cdd:cd12512     7 EKGFCVYLKGLPYEAENKHVIEFFKKLDIVEDSIYIAYGPNGRATGEGFVEFRNEIDYKAALCRHKQYMGNRFIQVHPIT 86

RNA recognition motif 1 (RRM1) found in RNA-binding protein 12B (RBM12B) and similar proteins; This subgroup corresponds to the RRM1 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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1446042969 348 VILRLRGLPFSAGPTDVLGF-LGPECPvTGGTegllfvrHPDGRPTGDAFALFACEELAQAALRRHKGMLGKRYIELFRS 426
Cdd:cd12744     2 VVIRLQGLPVVAGSTDIRHFfTGLTIP-DGGV-------HIIGGELGEAFIIFATDEDARRAMSRSGGFIKGSRVELFLS 73

                  ....*.
gi 1446042969 427 TAAEVQ 432
Cdd:cd12744    74 SKAEMQ 79

RNA recognition motif 3 (RRM3) found in Drosophila RNA-binding protein Fusilli and similar proteins; This subgroup corresponds to the RRM3 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 1446042969 249 VRARGLPWQSSDQDVARFFK--GLNVARGGVALCLNAQGRRNGEALIRfVDSEQ--RDLALQRHKHHMGV----RYIEVY 320
Cdd:cd12743     4 IRLRGLPYEAQVEHILEFLGdfAKMIVFQGVHMVYNAQGQPSGEAFIQ-MDSEQsaSACAQQRHNRYMVFgkkqRYIEVF 82