ID:SRSF1_HUMAN DESCRIPTION: RecName: Full=Serine/arginine-rich splicing factor 1; AltName: Full=Alternative-splicing factor 1; Short=ASF-1; AltName: Full=Splicing factor, arginine/serine-rich 1; AltName: Full=pre-mRNA-splicing factor SF2, P33 subunit; FUNCTION: Plays 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. SUBUNIT: Consists 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. INTERACTION: Q86X95: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=2; 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; SUBCELLULAR LOCATION: Cytoplasm. Nucleus speckle. Note=In nuclear speckles. Shuttles between the nucleus and the cytoplasm. DOMAIN: The 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. PTM: Phosphorylated 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. PTM: Arg-97 is dimethylated, probably to asymmetric dimethylarginine. SIMILARITY: Belongs to the splicing factor SR family. SIMILARITY: Contains 2 RRM (RNA recognition motif) domains.
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on Q07955
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MF436148 - Homo sapiens serine and arginine rich splicing factor 1 transcript variant 4 (SRSF1) mRNA, 3' UTR; alternatively spliced. MF436149 - Homo sapiens serine and arginine rich splicing factor 1 transcript variant 5 (SRSF1) mRNA, partial cds and 3' UTR; alternatively spliced. JD560739 - Sequence 541763 from Patent EP1572962. JD560740 - Sequence 541764 from Patent EP1572962. JD441830 - Sequence 422854 from Patent EP1572962. AK225711 - Homo sapiens mRNA for Splice isoform ASF-2 of Q07955 variant, clone: TMS07306. AB062124 - Homo sapiens mRNA, complete cds, similar to splicing factor SF2p33. AB209558 - Homo sapiens mRNA for splicing factor, arginine/serine-rich 1 (splicing factor 2, alternate splicing factor) variant protein. BC010264 - Homo sapiens splicing factor, arginine/serine-rich 1, mRNA (cDNA clone MGC:5228 IMAGE:2900101), complete cds. BC033785 - Homo sapiens splicing factor, arginine/serine-rich 1, mRNA (cDNA clone MGC:45185 IMAGE:5166554), complete cds. JD138706 - Sequence 119730 from Patent EP1572962. M72709 - Human alternative splicing factor mRNA, complete cds. JD488932 - Sequence 469956 from Patent EP1572962. JD374741 - Sequence 355765 from Patent EP1572962. JD318655 - Sequence 299679 from Patent EP1572962. JD450541 - Sequence 431565 from Patent EP1572962. JD236328 - Sequence 217352 from Patent EP1572962. AK298527 - Homo sapiens cDNA FLJ53078 complete cds, highly similar to Splicing factor, arginine/serine-rich 1. JD241198 - Sequence 222222 from Patent EP1572962. JD264808 - Sequence 245832 from Patent EP1572962. JD467833 - Sequence 448857 from Patent EP1572962. JD428780 - Sequence 409804 from Patent EP1572962. JD058528 - Sequence 39552 from Patent EP1572962. M69040 - Human SF2p33 mRNA, complete cds. AK289933 - Homo sapiens cDNA FLJ77645 complete cds, highly similar to Homo sapiens splicing factor, arginine/serine-rich 1 (splicing factor 2, alternate splicing factor) (SFRS1), mRNA. JD281235 - Sequence 262259 from Patent EP1572962. JD348418 - Sequence 329442 from Patent EP1572962. JD278657 - Sequence 259681 from Patent EP1572962. DQ571955 - Homo sapiens piRNA piR-40067, complete sequence. AK312781 - Homo sapiens cDNA, FLJ93198, Homo sapiens splicing factor, arginine/serine-rich 1 (splicing factor 2, alternate splicing factor) (SFRS1), mRNA. KJ892127 - Synthetic construct Homo sapiens clone ccsbBroadEn_01521 SRSF1 gene, encodes complete protein. CU679661 - Synthetic construct Homo sapiens gateway clone IMAGE:100018607 5' read SFRS1 mRNA. AB384975 - Synthetic construct DNA, clone: pF1KB4679, Homo sapiens SFRS1 gene for splicing factor, arginine/serine-rich 1, complete cds, without stop codon, in Flexi system. JD230819 - Sequence 211843 from Patent EP1572962. JD140556 - Sequence 121580 from Patent EP1572962.
Biochemical and Signaling Pathways
Reactome (by CSHL, EBI, and GO)
Protein Q07955 (Reactome details) participates in the following event(s):
R-HSA-72107 Formation of the Spliceosomal E complex R-HSA-75080 Formation of AT-AC A complex R-HSA-75096 Docking of the TAP:EJC Complex with the NPC R-HSA-72143 Lariat Formation and 5'-Splice Site Cleavage R-HSA-72139 Formation of the active Spliceosomal C (B*) complex R-HSA-72124 Formation of the Spliceosomal A Complex R-HSA-72127 Formation of the Spliceosomal B Complex R-HSA-72130 Formation of an intermediate Spliceosomal C (Bact) complex R-HSA-8849157 TREX complex binds spliced, capped mRNA:CBC:EJC cotranscriptionally R-HSA-72185 mRNA polyadenylation R-HSA-72180 Cleavage of mRNA at the 3'-end R-HSA-75081 Formation of AT-AC B Complex R-HSA-75082 ATAC spliceosome mediated Lariat formation,5' splice site cleavage R-HSA-75079 Formation of AT-AC C complex R-HSA-75083 ATAC spliceosome mediated 3' splice site cleavage, exon ligation R-HSA-156661 Formation of Exon Junction Complex R-HSA-159101 NXF1:NXT1 (TAP:p15) binds capped mRNA:CBC:EJC:TREX (minus DDX39B) R-HSA-72163 mRNA Splicing - Major Pathway R-HSA-72165 mRNA Splicing - Minor Pathway R-HSA-159236 Transport of Mature mRNA derived from an Intron-Containing Transcript R-HSA-72187 mRNA 3'-end processing R-HSA-109688 Cleavage of Growing Transcript in the Termination Region R-HSA-72172 mRNA Splicing R-HSA-72202 Transport of Mature Transcript to Cytoplasm R-HSA-72203 Processing of Capped Intron-Containing Pre-mRNA R-HSA-73856 RNA Polymerase II Transcription Termination R-HSA-8953854 Metabolism of RNA R-HSA-73857 RNA Polymerase II Transcription R-HSA-74160 Gene expression (Transcription)
US Server
Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
