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SRSF1 (serine/arginine-rich splicing factor 1)

Written2011-11Ruben Pio
Department of Biochemistry, Division of Oncology (CIMA), University of Navarra, Pamplona, Spain

(Note : for Links provided by Atlas : click)

Identity

Alias_namesSFRS1
splicing factor, arginine/serine-rich 1
serine/arginine-rich splicing factor 1
Alias_symbol (synonym)ASF
SF2
SRp30a
SF2p33
MGC5228
Other aliasFLJ53078
HGNC (Hugo) SRSF1
LocusID (NCBI) 6426
Atlas_Id 47631
Location 17q22  [Link to chromosome band 17q22]
Location_base_pair Starts at 58000919 and ends at 58007346 bp from pter ( according to hg19-Feb_2009)  [Mapping SRSF1.png]
Fusion genes
(updated 2016)
SH3BP4 (2q37.2) / SRSF1 (17q22)SRSF1 (17q22) / LMO4 (1p22.3)SRSF1 (17q22) / PCNX1 (14q24.2)
SRSF1 (17q22) / SRSF1 (17q22)

DNA/RNA

 
  Genomic structure of the SRSF1 gene. The black area indicates the coding sequence.
Description The SRSF1 locus spans 6424 bp on the minus (-) strand of the long arm of chromosome 17 and is composed of 4 exons.
Transcription ASF-1 (SF2) contains 4 exons (248 aa). Two additional cDNAs generated by alternative 3' splice-site use or by intron retention have been described and are designated ASF-2 (292 aa) and ASF-3 (201 aa), respectively. However, ASF/SF2 is the only isoform expressed at detectable levels.
Pseudogene No known pseudogenes.

Protein

 
  Schematic diagram of SF2/ASF protein. SF2/ASF has a modular structure with two RNA recognition motifs (RRM) that provide RNA-binding specificity and one arginine/serine-rich domain (RS), involved in protein-protein interactions that facilitate recruitment of the spliceosome. The RS domain acts also as a nuclear localization signal, controlling the subcellular localization of SF2/ASF. The protein can be phosphorilated in Ser residues in the C-terminal RS domain.
Description 248 amino acids, 28 kDa.
Expression SF2/ASF is constitutively expressed in all cell types. However, there are differences in expression levels between cell types and organs. Moreover, in some pathological conditions the expression levels are altered.
Localisation SF2/ASF is a shuttling protein with a high mobility between the nucleus and the cytoplasm. In the nucleus, SF2/ASF is concentrated in speckles and when transcription is activated it accumulates at the sites of transcription.
Function SF2/ASF modulates both constitutive and alternative pre-mRNA splicing. The function of SF2/ASF in splicing depends on the pre-mRNA sequence and the cellular context. Cis-acting sequences and trans-acting factors modulate SF2/ASF activity. For example, SF2/ASF antagonizes the activity of hnRNP A/B proteins in splice site selection. An excess of hnRNP A1 favors distal 5' splice sites, whereas SF2/ASF promotes the use of proximal 5' splice sites.
SF2/ASF is also involved in transcription, mRNA export, nonsense-mediated mRNA decay, and translation.
Homology SF2/ASF shares a high homology with other members of the SR family. SR proteins are conserved across vertebrates and invertebrates. They contain one or two copies of an RNA recognition motif (RRM) at the amino-terminus, spaced by a series of glycine residues that may form a flexible hinge, and a carboxy-terminal highly charged SR domain.

Mutations

Note No mutations have been reported. Gene amplification has been found in some tumor types.

Implicated in

Note
  
Entity Various cancers
Note SF2/ASF acts as an oncogene.
SF2/ASF is upregulated in various human tumors, including lung, colon, kidney, liver, pancreas, ovary, cervix, and breast. Upregulation is sometimes associated with gene amplification. Overexpression of SF2/ASF is sufficient to transform immortal rodent fibroblasts.
mTORC1 activation may be essential for SF2/ASF-mediated transformation.
SF2/ASF-bound mRNAs recruit the mTOR kinase, resulting in the phosphorylation and release of 4E-BP, leading to translation initiation. Clinical tumors with SF2/ASF up-regulation may be especially sensitive to mTOR inhibitors.
  
  
Entity Non-small cell lung cancer (NSCLC)
Note SF2/ASF and survivin expression are involved in non-small cell lung cancer progression.
SF2/ASF is overexpressed in lung cancer cell lines and human NSCLC specimens. SF2/ASF controls the expression of survivin through the activation of the mTOR pathway.
  
  
Entity Prostate cancer
Note Cyclin D1b oncogene is induced by SF2/ASF.
SF2/ASF associates with cyclin D1b mRNA, an alternative splicing of the CCND1 transcript with enhanced oncogenic functions. SF2/ASF expression correlates with cyclin D1b in human prostate cancer.
  
  
Entity Cystic fibrosis
Note Aberrant regulation of CFTR exon 9 alternative splicing by splicing factors may be associated with cystic fibrosis.
SF2/ASF binds to an intronic splicing silencer of exon 9 of CFTR and promotes exon exclusion.
  
  
Entity Cardiac remodeling
Note SF2/ASF has a role in cardiac remodeling.
ASF/SF2 is a key regulator of alternative splicing events during postnatal heart remodeling.
  
  
Entity Retroviral splicing
Note SF2/ASF regulates retroviral splicing.
SF2/ASF has been implicated in the regulation of retroviral splicing in Rous sarcoma virus, HIV-1 and HPV-16.
  
  
Entity Cell motility
Note SF2/ASF activates epithelial to mesenchymal transition.
DeltaRon, a splicing isoform of the tyrosine kinase receptor Ron, increases motility. DeltaRon is generated by the skipping of exon 11. SF2/ASF, by controlling the production of DeltaRon, activates epithelial to mesenchymal transition, leading to cell locomotion.
  

Bibliography

Processive phosphorylation of alternative splicing factor/splicing factor 2.
Aubol BE, Chakrabarti S, Ngo J, Shaffer J, Nolen B, Fu XD, Ghosh G, Adams JA.
Proc Natl Acad Sci U S A. 2003 Oct 28;100(22):12601-6. Epub 2003 Oct 10.
PMID 14555757
 
SR protein-mediated inhibition of CFTR exon 9 inclusion: molecular characterization of the intronic splicing silencer.
Buratti E, Stuani C, De Prato G, Baralle FE.
Nucleic Acids Res. 2007;35(13):4359-68. Epub 2007 Jun 18.
PMID 17576688
 
A specific subset of SR proteins shuttles continuously between the nucleus and the cytoplasm.
Caceres JF, Screaton GR, Krainer AR.
Genes Dev. 1998 Jan 1;12(1):55-66.
PMID 9420331
 
The oncoprotein SF2/ASF promotes non-small cell lung cancer survival by enhancing survivin expression.
Ezponda T, Pajares MJ, Agorreta J, Echeveste JI, Lopez-Picazo JM, Torre W, Pio R, Montuenga LM.
Clin Cancer Res. 2010 Aug 15;16(16):4113-25. Epub 2010 Aug 3.
PMID 20682707
 
Increased expression of cellular RNA-binding proteins in HPV-induced neoplasia and cervical cancer.
Fay J, Kelehan P, Lambkin H, Schwartz S.
J Med Virol. 2009 May;81(5):897-907.
PMID 19319956
 
Expression of splicing factors in human ovarian cancer.
Fischer DC, Noack K, Runnebaum IB, Watermann DO, Kieback DG, Stamm S, Stickeler E.
Oncol Rep. 2004 May;11(5):1085-90.
PMID 15069551
 
A protein factor, ASF, controls cell-specific alternative splicing of SV40 early pre-mRNA in vitro.
Ge H, Manley JL.
Cell. 1990 Jul 13;62(1):25-34.
PMID 2163768
 
Primary structure of the human splicing factor ASF reveals similarities with Drosophila regulators.
Ge H, Zuo P, Manley JL.
Cell. 1991 Jul 26;66(2):373-82.
PMID 1855257
 
Cell motility is controlled by SF2/ASF through alternative splicing of the Ron protooncogene.
Ghigna C, Giordano S, Shen H, Benvenuto F, Castiglioni F, Comoglio PM, Green MR, Riva S, Biamonti G.
Mol Cell. 2005 Dec 22;20(6):881-90.
PMID 16364913
 
Regulated tissue-specific expression of antagonistic pre-mRNA splicing factors.
Hanamura A, Caceres JF, Mayeda A, Franza BR Jr, Krainer AR.
RNA. 1998 Apr;4(4):430-44.
PMID 9630249
 
Dual effect of the SR proteins ASF/SF2, SC35 and 9G8 on HIV-1 RNA splicing and virion production.
Jacquenet S, Decimo D, Muriaux D, Darlix JL.
Retrovirology. 2005 May 22;2:33.
PMID 15907217
 
The splicing-factor oncoprotein SF2/ASF activates mTORC1.
Karni R, Hippo Y, Lowe SW, Krainer AR.
Proc Natl Acad Sci U S A. 2008 Oct 7;105(40):15323-7. Epub 2008 Oct 1.
PMID 18832178
 
The gene encoding the splicing factor SF2/ASF is a proto-oncogene.
Karni R, de Stanchina E, Lowe SW, Sinha R, Mu D, Krainer AR.
Nat Struct Mol Biol. 2007 Mar;14(3):185-93. Epub 2007 Feb 18.
PMID 17310252
 
The essential pre-mRNA splicing factor SF2 influences 5' splice site selection by activating proximal sites.
Krainer AR, Conway GC, Kozak D.
Cell. 1990b Jul 13;62(1):35-42.
PMID 2364434
 
Reduced mobility of the alternate splicing factor (ASF) through the nucleoplasm and steady state speckle compartments.
Kruhlak MJ, Lever MA, Fischle W, Verdin E, Bazett-Jones DP, Hendzel MJ.
J Cell Biol. 2000 Jul 10;150(1):41-51.
PMID 10893255
 
The SR protein family of splicing factors: master regulators of gene expression.
Long JC, Caceres JF.
Biochem J. 2009 Jan 1;417(1):15-27. (REVIEW)
PMID 19061484
 
Regulation of alternative pre-mRNA splicing by hnRNP A1 and splicing factor SF2.
Mayeda A, Krainer AR.
Cell. 1992 Jan 24;68(2):365-75.
PMID 1531115
 
An RNA splicing enhancer-like sequence is a component of a splicing inhibitor element from Rous sarcoma virus.
McNally LM, McNally MT.
Mol Cell Biol. 1998 Jun;18(6):3103-11.
PMID 9584151
 
The dynamics of a pre-mRNA splicing factor in living cells.
Misteli T, Caceres JF, Spector DL.
Nature. 1997 May 29;387(6632):523-7.
PMID 9168118
 
Identification of ASF/SF2 as a critical, allele-specific effector of the cyclin D1b oncogene.
Olshavsky NA, Comstock CE, Schiewer MJ, Augello MA, Hyslop T, Sette C, Zhang J, Parysek LM, Knudsen KE.
Cancer Res. 2010 May 15;70(10):3975-84. Epub 2010 May 11.
PMID 20460515
 
Splicing factors induce cystic fibrosis transmembrane regulator exon 9 skipping through a nonevolutionary conserved intronic element.
Pagani F, Buratti E, Stuani C, Romano M, Zuccato E, Niksic M, Giglio L, Faraguna D, Baralle FE.
J Biol Chem. 2000 Jul 14;275(28):21041-7.
PMID 10766763
 
Multiple ASF/SF2 sites in the human papillomavirus type 16 (HPV-16) E4-coding region promote splicing to the most commonly used 3'-splice site on the HPV-16 genome.
Somberg M, Schwartz S.
J Virol. 2010 Aug;84(16):8219-30. Epub 2010 Jun 2.
PMID 20519389
 
ASF/SF2-regulated CaMKIIdelta alternative splicing temporally reprograms excitation-contraction coupling in cardiac muscle.
Xu X, Yang D, Ding JH, Wang W, Chu PH, Dalton ND, Wang HY, Bermingham JR Jr, Ye Z, Liu F, Rosenfeld MG, Manley JL, Ross J Jr, Chen J, Xiao RP, Cheng H, Fu XD.
Cell. 2005 Jan 14;120(1):59-72.
PMID 15652482
 
SR proteins: a conserved family of pre-mRNA splicing factors.
Zahler AM, Lane WS, Stolk JA, Roth MB.
Genes Dev. 1992 May;6(5):837-47.
PMID 1577277
 
The human splicing factor ASF/SF2 can specifically recognize pre-mRNA 5' splice sites.
Zuo P, Manley JL.
Proc Natl Acad Sci U S A. 1994 Apr 12;91(8):3363-7.
PMID 7512732
 

Citation

This paper should be referenced as such :
Pio, R
SRSF1 (serine/arginine-rich splicing factor 1)
Atlas Genet Cytogenet Oncol Haematol. 2012;16(4):286-288.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/SRSF1ID47631ch17q22.html


External links

Nomenclature
HGNC (Hugo)SRSF1   10780
Cards
AtlasSRSF1ID47631ch17q22
Entrez_Gene (NCBI)SRSF1  6426  serine and arginine rich splicing factor 1
AliasesASF; SF2; SF2p33; SFRS1; 
SRp30a
GeneCards (Weizmann)SRSF1
Ensembl hg19 (Hinxton)ENSG00000136450 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000136450 [Gene_View]  chr17:58000919-58007346 [Contig_View]  SRSF1 [Vega]
ICGC DataPortalENSG00000136450
TCGA cBioPortalSRSF1
AceView (NCBI)SRSF1
Genatlas (Paris)SRSF1
WikiGenes6426
SOURCE (Princeton)SRSF1
Genetics Home Reference (NIH)SRSF1
Genomic and cartography
GoldenPath hg38 (UCSC)SRSF1  -     chr17:58000919-58007346 -  17q22   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)SRSF1  -     17q22   [Description]    (hg19-Feb_2009)
EnsemblSRSF1 - 17q22 [CytoView hg19]  SRSF1 - 17q22 [CytoView hg38]
Mapping of homologs : NCBISRSF1 [Mapview hg19]  SRSF1 [Mapview hg38]
OMIM600812   
Gene and transcription
Genbank (Entrez)AB062124 AB209558 AK054610 AK095112 AK126318
RefSeq transcript (Entrez)NM_001078166 NM_006924
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)SRSF1
Cluster EST : UnigeneHs.744140 [ NCBI ]
CGAP (NCI)Hs.744140
Alternative Splicing GalleryENSG00000136450
Gene ExpressionSRSF1 [ NCBI-GEO ]   SRSF1 [ EBI - ARRAY_EXPRESS ]   SRSF1 [ SEEK ]   SRSF1 [ MEM ]
Gene Expression Viewer (FireBrowse)SRSF1 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)6426
GTEX Portal (Tissue expression)SRSF1
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ07955   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtQ07955  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProQ07955
Splice isoforms : SwissVarQ07955
PhosPhoSitePlusQ07955
Domaine pattern : Prosite (Expaxy)RRM (PS50102)   
Domains : Interpro (EBI)Nucleotide-bd_a/b_plait    RRM_dom   
Domain families : Pfam (Sanger)RRM_1 (PF00076)   
Domain families : Pfam (NCBI)pfam00076   
Domain families : Smart (EMBL)RRM (SM00360)  
Conserved Domain (NCBI)SRSF1
DMDM Disease mutations6426
Blocks (Seattle)SRSF1
PDB (SRS)1X4A    2M7S    2M8D    2O3D    3BEG    4C0O   
PDB (PDBSum)1X4A    2M7S    2M8D    2O3D    3BEG    4C0O   
PDB (IMB)1X4A    2M7S    2M8D    2O3D    3BEG    4C0O   
PDB (RSDB)1X4A    2M7S    2M8D    2O3D    3BEG    4C0O   
Structural Biology KnowledgeBase1X4A    2M7S    2M8D    2O3D    3BEG    4C0O   
SCOP (Structural Classification of Proteins)1X4A    2M7S    2M8D    2O3D    3BEG    4C0O   
CATH (Classification of proteins structures)1X4A    2M7S    2M8D    2O3D    3BEG    4C0O   
SuperfamilyQ07955
Human Protein AtlasENSG00000136450
Peptide AtlasQ07955
HPRD02887
IPIIPI00215884   IPI00218591   IPI00218592   
Protein Interaction databases
DIP (DOE-UCLA)Q07955
IntAct (EBI)Q07955
FunCoupENSG00000136450
BioGRIDSRSF1
STRING (EMBL)SRSF1
ZODIACSRSF1
Ontologies - Pathways
QuickGOQ07955
Ontology : AmiGOalternative mRNA splicing, via spliceosome  mRNA 5'-splice site recognition  mRNA splicing, via spliceosome  mRNA splicing, via spliceosome  in utero embryonic development  RNA binding  RNA binding  mRNA binding  protein binding  nucleus  nucleoplasm  nucleoplasm  cytoplasm  termination of RNA polymerase II transcription  mRNA splice site selection  mRNA processing  RNA export from nucleus  mRNA export from nucleus  nuclear speck  mRNA 3'-end processing  positive regulation of RNA splicing  exon-exon junction complex  protein kinase B binding  DNA topoisomerase binding  oligodendrocyte differentiation  RS domain binding  cardiac muscle contraction  extracellular exosome  catalytic step 2 spliceosome  liver regeneration  
Ontology : EGO-EBIalternative mRNA splicing, via spliceosome  mRNA 5'-splice site recognition  mRNA splicing, via spliceosome  mRNA splicing, via spliceosome  in utero embryonic development  RNA binding  RNA binding  mRNA binding  protein binding  nucleus  nucleoplasm  nucleoplasm  cytoplasm  termination of RNA polymerase II transcription  mRNA splice site selection  mRNA processing  RNA export from nucleus  mRNA export from nucleus  nuclear speck  mRNA 3'-end processing  positive regulation of RNA splicing  exon-exon junction complex  protein kinase B binding  DNA topoisomerase binding  oligodendrocyte differentiation  RS domain binding  cardiac muscle contraction  extracellular exosome  catalytic step 2 spliceosome  liver regeneration  
Pathways : KEGGSpliceosome    Herpes simplex infection   
REACTOMEQ07955 [protein]
REACTOME PathwaysR-HSA-72187 [pathway]   
NDEx NetworkSRSF1
Atlas of Cancer Signalling NetworkSRSF1
Wikipedia pathwaysSRSF1
Orthology - Evolution
OrthoDB6426
GeneTree (enSembl)ENSG00000136450
Phylogenetic Trees/Animal Genes : TreeFamSRSF1
HOVERGENQ07955
HOGENOMQ07955
Homologs : HomoloGeneSRSF1
Homology/Alignments : Family Browser (UCSC)SRSF1
Gene fusions - Rearrangements
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerSRSF1 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)SRSF1
dbVarSRSF1
ClinVarSRSF1
1000_GenomesSRSF1 
Exome Variant ServerSRSF1
ExAC (Exome Aggregation Consortium)SRSF1 (select the gene name)
Genetic variants : HAPMAP6426
Genomic Variants (DGV)SRSF1 [DGVbeta]
DECIPHERSRSF1 [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisSRSF1 
Mutations
ICGC Data PortalSRSF1 
TCGA Data PortalSRSF1 
Broad Tumor PortalSRSF1
OASIS PortalSRSF1 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICSRSF1  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDSRSF1
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch SRSF1
DgiDB (Drug Gene Interaction Database)SRSF1
DoCM (Curated mutations)SRSF1 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)SRSF1 (select a term)
intoGenSRSF1
NCG5 (London)SRSF1
Cancer3DSRSF1(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM600812   
Orphanet
MedgenSRSF1
Genetic Testing Registry SRSF1
NextProtQ07955 [Medical]
TSGene6426
GENETestsSRSF1
Target ValidationSRSF1
Huge Navigator SRSF1 [HugePedia]
snp3D : Map Gene to Disease6426
BioCentury BCIQSRSF1
ClinGenSRSF1
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD6426
Chemical/Pharm GKB GenePA35696
Clinical trialSRSF1
Miscellaneous
canSAR (ICR)SRSF1 (select the gene name)
Probes
Litterature
PubMed258 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineSRSF1
EVEXSRSF1
GoPubMedSRSF1
iHOPSRSF1
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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