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MGP002812

UniProt Annotations

Entry Information
Gene Nameserine/arginine-rich splicing factor 1
Protein EntrySRSF1_HUMAN
UniProt IDQ07955
SpeciesHuman
Comments
Comment typeDescription
Alternative ProductsEvent=Alternative splicing; Named isoforms=3; Name=ASF-1; IsoId=Q07955-1; Sequence=Displayed; Name=ASF-2; IsoId=Q07955-2; Sequence=VSP_005856; Name=ASF-3; IsoId=Q07955-3; Sequence=VSP_005857, VSP_005858; Note=May be due to intron retention.;
DomainThe RRM 2 domain plays an important role in governing both the binding mode and the phosphorylation mechanism of the RS domain by SRPK1. RS domain and RRM 2 are uniquely positioned to initiate a highly directional (C-terminus to N-terminus) phosphorylation reaction in which the RS domain slides through an extended electronegative channel separating the docking groove of SRPK1 and the active site. RRM 2 binds toward the periphery of the active site and guides the directional phosphorylation mechanism. Both the RS domain and an RRM domain are required for nucleocytoplasmic shuttling. {ECO:0000269|PubMed:18342604}.
FunctionPlays a role in preventing exon skipping, ensuring the accuracy of splicing and regulating alternative splicing. Interacts with other spliceosomal components, via the RS domains, to form a bridge between the 5'- and 3'-splice site binding components, U1 snRNP and U2AF. Can stimulate binding of U1 snRNP to a 5'-splice site-containing pre-mRNA. Binds to purine-rich RNA sequences, either the octamer, 5'-RGAAGAAC-3' (r=A or G) or the decamers, AGGACAGAGC/AGGACGAAGC. Binds preferentially to the 5'- CGAGGCG-3' motif in vitro. Three copies of the octamer constitute a powerful splicing enhancer in vitro, the ASF/SF2 splicing enhancer (ASE) which can specifically activate ASE-dependent splicing. Isoform ASF-2 and isoform ASF-3 act as splicing repressors. May function as export adapter involved in mRNA nuclear export through the TAP/NXF1 pathway. {ECO:0000269|PubMed:8139654}.
InteractionQ86X95:CIR1; NbExp=3; IntAct=EBI-398920, EBI-627102; P23511:NFYA; NbExp=5; IntAct=EBI-398920, EBI-389739; Q9UBU9:NXF1; NbExp=5; IntAct=EBI-398920, EBI-398874; Q96SB4:SRPK1; NbExp=3; IntAct=EBI-398920, EBI-539478; O70551:Srpk1 (xeno); NbExp=5; IntAct=EBI-398920, EBI-593343; O54781:Srpk2 (xeno); NbExp=3; IntAct=EBI-398920, EBI-593325; O00463:TRAF5; NbExp=2; IntAct=EBI-398920, EBI-523498;
PtmAsymmetrically dimethylated at arginines, probably by PRMT1, methylation promotes localization to nuclear speckles. {ECO:0000269|PubMed:20308322}.
PtmPhosphorylated by CLK1, CLK2, CLK3 and CLK4. Phosphorylated by SRPK1 at multiple serines in its RS domain via a directional (C-terminal to N-terminal) and a dual-track mechanism incorporating both processive phosphorylation (in which the kinase stays attached to the substrate after each round of phosphorylation) and distributive phosphorylation steps (in which the kinase and substrate dissociate after each phosphorylation event). The RS domain of SRSF1 binds to a docking groove in the large lobe of the kinase domain of SRPK1 and this induces certain structural changes in SRPK1 and/or RRM 2 domain of SRSF1, allowing RRM 2 to bind the kinase and initiate phosphorylation. The cycles continue for several phosphorylation steps in a processive manner (steps 1-8) until the last few phosphorylation steps (approximately steps 9-12). During that time, a mechanical stress induces the unfolding of the beta-4 motif in RRM 2, which then docks at the docking groove of SRPK1. This also signals RRM 2 to begin to dissociate, which facilitates SRSF1 dissociation after phosphorylation is completed. {ECO:0000269|PubMed:14555757, ECO:0000269|PubMed:18155240, ECO:0000269|PubMed:18669648, ECO:0000269|PubMed:18687337, ECO:0000269|PubMed:19477182, ECO:0000269|PubMed:19886675, ECO:0000269|PubMed:20068231, ECO:0000269|PubMed:21406692}.
SimilarityBelongs to the splicing factor SR family. {ECO:0000305}.
SimilarityContains 2 RRM (RNA recognition motif) domains. {ECO:0000255|PROSITE-ProRule:PRU00176}.
Subcellular LocationCytoplasm. Nucleus speckle. Note=In nuclear speckles. Shuttles between the nucleus and the cytoplasm.
SubunitConsists of two polypeptides of p32 and p33. In vitro, self-associates and binds SRSF2, SNRNP70 and U2AF1 but not U2AF2. Binds SREK1/SFRS12. Interacts with SAFB/SAFB1. Interacts with PSIP1/LEDGF. Interacts with SRPK1. Identified in the spliceosome C complex. Interacts with RSRC1 (via Arg/Ser-rich domain). Interacts with ZRSR2/U2AF1-RS2. Interacts with CCDC55 (via C-terminus). Interacts with SRPK1 and a sliding docking interaction is essential for its sequential and processive phosphorylation by SRPK1. Interacts with NXF1. {ECO:0000269|PubMed:10757789, ECO:0000269|PubMed:11991638, ECO:0000269|PubMed:12667464, ECO:0000269|PubMed:14555757, ECO:0000269|PubMed:15798186, ECO:0000269|PubMed:18342604, ECO:0000269|PubMed:21296756, ECO:0000269|PubMed:8261509, ECO:0000269|PubMed:9237760, ECO:0000269|PubMed:9671816, ECO:0000269|PubMed:9885563}.
Web ResourceName=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/SRSF1ID47631ch17q22.html";
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