Conserved Protein Domain Family

cd12503: RRM1_hnRNPH_GRSF1_like 
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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.
PSSM-Id: 409926
Aligned: 10 rows
Threshold Bit Score: 121.727
Created: 13-Sep-2011
Updated: 25-Oct-2021
Aligned Rows:
PubMed ReferencesClick to see Conserved Features Help

Sequence Alignment
Format: Row Display: Color Bits: Type Selection:
XP_002115274   8 VVRIRGLPWSaTVEDVQKFFTgcr--vkeGRQGIHFTYASDGRAsGEAYIEFGSlEDFNRALERNr-------------- 71  Trichoplax adha...
XP_002612455   3 VVRMRGLPWSaTCEEVKNFLTsegckvkgGDGGIHFTFSKEGRPsGEAFVEVETsEDFEKALAKHn-------------- 68  Florida lancelet
XP_001629886   6 VVRARGLPWSaTPEDIQNFFKdcni-vggPQNGVHFTFGIDGRPsGECFVQFVSeKDVEKALEMNn-------------- 70  starlet sea ane...
EFX77658       8 VVRLRGLPWAvTDDDILKFFEdsn--ivgGAAGIHMTYTREGRPtGEGYLELSSeEDVERALTKHn-------------- 71  common water flea
XP_002741419  96 VIRARGLPWSaTADEVRSFFKgck--iaeTENGIKFTYTREGRPsGECFIELETeEDVKVALERHn-------------- 159 Saccoglossus ko...
CCD80290       4 VVRIRGLPFSaNADDIISFFHdcr--irgGKRGIYFPQGSNGRSnGEAFIELESkDDKQKAMAHHn-------------- 67  Schistosoma man...
AEO36606      11 VLRIRGLPWStTKEEILNFFTskecnikgGINGVHMTLSREGRPsGEAYIELESeQDVEVGLQRHn-------------- 76  Amblyomma macul...
XP_003374467   9 VVRVRGLPWSsKEEDIRKFFHdc-----sDIIGIHFTYSKEGRPsGEAYLEFGSaDDVDKALRHHhisdsiddirfgqdn 83  Trichinella spi...
2HGL_A       110 --------------------------eSMGHRYIEVFKS 122 human
2LMI_A        77 --------------------------mYMGQRYVEVYEI 89  human
XP_002115274  72 --------------------------cHMGKRYVEVFKS 84  Trichoplax adhaerens
XP_002612455  69 --------------------------qHMGHRYIEVFRS 81  Florida lancelet
XP_001629886  71 --------------------------eHMGKRYIEVFRS 83  starlet sea anemone
EFX77658      72 --------------------------eHLGPRYIEVFRS 84  common water flea
XP_002741419 160 --------------------------dHMGHRYVEVFRS 172 Saccoglossus kowalevskii
CCD80290      68 --------------------------qHLGRRYIEVFDS 80  Schistosoma mansoni
AEO36606      77 --------------------------eHIGHRYIEVFKS 89  Amblyomma maculatum
XP_003374467  84 sgrasgegfvrfsnkeateraldrhmeKIGHRYIEVFRS 122 Trichinella spiralis
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