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SRSF3 (serine/arginine-rich splicing factor 3)

Identity

Other namesSFRS3
SRp20
HGNC (Hugo) SRSF3
LocusID (NCBI) 6428
Location 6p21.31
Location_base_pair Starts at 36562090 and ends at 36572244 bp from pter ( according to hg19-Feb_2009)

DNA/RNA

 
  Diagram of genomic structure of SRSF3 gene. The numbers above the diagram are the nucleotide positions in SRSF3 gene. The open boxes and broken lines represent exons and introns, respectively.
Description SRSF3 gene contains 6 exons and spans 10155 bp on the plus (+) strand of the short arm of chromosome 6.
Transcription SRSF3 mRNA is in size of 3144 nts and encodes a protein with 164 amino acid residues. By including an alternative exon between exon 3 and exon 4, SRSF3 pre-mRNA could generate additional isoform of SRSF3 transcript.
Pseudogene No.

Protein

 
  Diagram of protein structure of SRSF3. The numbers below the diagram are the amino acid positions in SRSF3 protein. SRSF3 has an RNA recognition motifs (RRM) in the N-terminus and an arginine/serine-rich domain (RS) at the C-terminus. RRM motif identifies and binds specific RNA sequences. RS domain interacts with other proteins and facilitates recruitment of the spliceosomal components. The serine residues of the RS domain can be phosphorylated.
Description 164 amino acid residues, 20 kDa.
Expression Expression of SRSF3 varies significantly in different cell types. For example, the expression of SRSF3 is abundant in the undifferentiated or intermediately differentiated keratinocytes in the basal and parabasal layers, but drops significantly in terminally differentiated keratinocytes in the superficial layers of the cervix or skin. In general, normal cells like muscle or nerve cells have no or little expression of SRSF3. In contrast, malignant tumor cells express remarkable amount of SRSF3 when compared to their normal counterparts.
Localisation SRSF3 is a shuttling protein between nucleus and cytoplasm.
Function SRSF3 is a splicing factor and involved in the regulation of RNA splicing. It affects alternative splicing by interacting with RNA cis-elements in a concentration and cell differentiation-dependent manner. Moreover, SRSF3 plays important roles in RNA export from nuclear to cytoplasm, termination of transcription, alternative RNA polyadenylation, and protein translation. SRSF3 is required for embryonic development and cell cycle progression. SRSF3 at increased expression is tumorigenic and is required for tumor initiation, progression, and maintenance.

Alternative splicing of pre-mRNA
SRSF3 controls viral early to late switch by regulation of gene expression of bovine papillomavirus type 1 and human papillomavirus through interaction with A/C-rich RNA elements (Jia et al., 2009). SRSF3 promotes the inclusion of exon 4 of its own mRNA and reduces the expression of full length SRSF3 protein (Juma and Nielsen, 1997). SRSF3 activates the inclusion of exon 10 of PK-M gene to promote the expression of oncogenic M2 isoform (Wang et al., 2012). SRSF3 inhibits the inclusion of a fibronectin cassette exon in the mature mRNA by interacting with RNA polymerase II C-terminal domain (de la Mata and Kornblihtt, 2006).

Termination of transcription
SRSF3 plays a role in termination of transcription by binding to RNA downstream of the cleavage site, facilitating its degradation, and the release of Pol II from template DNA (Cui et al., 2008).

Alternative polyadenylation
The 3'-terminal exon 4 of calcitonin pre-mRNA contains an alternative polyadenylation site. SRSF3 affects the inclusion of exon 4 and alternative polyadenylation by the interaction with CstF (Lou et al., 1998).

RNA export
SRSF3 associates with TAP promoting the export of intronless mRNA of histone H2a gene by interacting with a 22-nt RNA element (Huang et al., 2003; Huang and Steitz, 2001).

Protein translation
SRSF3 is required for poliovirus translation initiation. SRSF3 binds to internal ribosome entry site (IRES) of a viral RNA by interaction with PCBP2 (Bedard et al., 2007).

Homology Human SRSF3 protein is highly conserved in chimpanzee, dog, sheep, cow, mouse, rat, chicken, zebrafish and so on. SRSF3 is the smallest member of SR (serine/arginine-rich) family and shares a high homology with other members. All of SR proteins contain at least one RRM and one downstream RS domain enriched in repeating arginine-serine dipeptides.

Mutations

Note There is one mutation which causes amino acid residue change according to NCBI dbSNP database.

Implicated in

Entity Cancer
Note SRSF3 is a protooncogene. Overexpression of SRSF3 has been found in various cancers, including cervix, lung, breast, stomach, skin, bladder, colon, liver, thyroid, and kidney; and in various soft tissue tumors, including B-cell lymphoma, rhabdomyosarcoma, hemangioendothelioma, hemangiopericytoma, neurofibroma, neurilemmoma, liposarcoma, leiomyosarcoma, histiocytoma, and synovial sarcoma. SRSF3 at overexpression has transformation activity for MEF/3T3 cells, a mouse embroynic fibroblast cell line. SRSF3 controls cell cycle progression and thereby cell proliferation presumably by regulating the expression of forkhead box transcription factor M1 (FoxM1), PLK1 and Cdc25B.
  

Other Leukemias implicated (Data extracted from papers in the Atlas)

Leukemias 11q23ChildAMLID1615

External links

Nomenclature
HGNC (Hugo)SRSF3   10785
Cards
AtlasSRSF3ID42279ch6p21
Entrez_Gene (NCBI)SRSF3  6428  serine/arginine-rich splicing factor 3
GeneCards (Weizmann)SRSF3
Ensembl (Hinxton) [Gene_View]  chr6:36562090-36572244 [Contig_View]  SRSF3 [Vega]
cBioPortalSRSF3
AceView (NCBI)SRSF3
Genatlas (Paris)SRSF3
WikiGenes6428
SOURCE (Princeton)NM_003017
Genomic and cartography
GoldenPath (UCSC)SRSF3  -  6p21.31   chr6:36562090-36572244 +  6p21   [Description]    (hg19-Feb_2009)
EnsemblSRSF3 - 6p21 [CytoView]
Mapping of homologs : NCBISRSF3 [Mapview]
OMIM603364   
Gene and transcription
Genbank (Entrez)AB451229 AB451352 AF107405 AK091927 AK095580
RefSeq transcript (Entrez)NM_003017
RefSeq genomic (Entrez)AC_000138 NC_000006 NC_018917 NT_007592 NW_001838980 NW_004929326
Consensus coding sequences : CCDS (NCBI)SRSF3
Cluster EST : UnigeneHs.405144 [ NCBI ]
CGAP (NCI)Hs.405144
Alternative Splicing : Fast-db (Paris)GSHG0025685
Gene ExpressionSRSF3 [ NCBI-GEO ]     SRSF3 [ SEEK ]   SRSF3 [ MEM ]
Protein : pattern, domain, 3D structure
UniProt/SwissProtP84103 (Uniprot)
NextProtP84103  [Medical]
With graphics : InterProP84103
Splice isoforms : SwissVarP84103 (Swissvar)
Domaine pattern : Prosite (Expaxy)RRM (PS50102)   
Domains : Interpro (EBI)Nucleotide-bd_a/b_plait [organisation]   RRM_dom [organisation]  
Related proteins : CluSTrP84103
Domain families : Pfam (Sanger)RRM_1 (PF00076)   
Domain families : Pfam (NCBI)pfam00076   
Domain families : Smart (EMBL)RRM (SM00360)  
DMDM Disease mutations6428
Blocks (Seattle)P84103
PDB (SRS)2I2Y    2I38   
PDB (PDBSum)2I2Y    2I38   
PDB (IMB)2I2Y    2I38   
PDB (RSDB)2I2Y    2I38   
Peptide AtlasP84103
HPRD04530
IPIIPI00010204   IPI00843996   
Protein Interaction databases
DIP (DOE-UCLA)P84103
IntAct (EBI)P84103
BioGRIDSRSF3
InParanoidP84103
Interologous Interaction database P84103
IntegromeDBSRSF3
STRING (EMBL)SRSF3
Ontologies - Pathways
Ontology : AmiGOnucleotide binding  mRNA splicing, via spliceosome  RNA binding  protein binding  nucleoplasm  cytoplasm  transcription from RNA polymerase II promoter  termination of RNA polymerase II transcription  mRNA export from nucleus  RNA splicing  gene expression  mRNA 3'-end processing  poly(A) RNA binding  
Ontology : EGO-EBInucleotide binding  mRNA splicing, via spliceosome  RNA binding  protein binding  nucleoplasm  cytoplasm  transcription from RNA polymerase II promoter  termination of RNA polymerase II transcription  mRNA export from nucleus  RNA splicing  gene expression  mRNA 3'-end processing  poly(A) RNA binding  
Pathways : KEGGSpliceosome    Herpes simplex infection   
Protein Interaction DatabaseSRSF3
Wikipedia pathwaysSRSF3
Gene fusion - rearrangments
Rearrangement : TICdbSRSF3 [6p21.31]  -  BCL6 [2p23.2]
Polymorphisms : SNP, mutations, diseases
SNP Single Nucleotide Polymorphism (NCBI)SRSF3
snp3D : Map Gene to Disease6428
SNP (GeneSNP Utah)SRSF3
SNP : HGBaseSRSF3
Genetic variants : HAPMAPSRSF3
Exome VariantSRSF3
1000_GenomesSRSF3 
Cancer Gene: CensusSRSF3 
Somatic Mutations in Cancer : COSMICSRSF3 
CONAN: Copy Number AnalysisSRSF3 
Mutations and Diseases : HGMDSRSF3
Genomic VariantsSRSF3  SRSF3 [DGVbeta]
dbVarSRSF3
ClinVarSRSF3
Pred. of missensesPolyPhen-2  SIFT(SG)  SIFT(JCVI)  Align-GVGD  MutAssessor  Mutanalyser  
Pred. splicesGeneSplicer  Human Splicing Finder  MaxEntScan  
Diseases
OMIM603364   
MedgenSRSF3
GENETestsSRSF3
Disease Genetic AssociationSRSF3
Huge Navigator SRSF3 [HugePedia]  SRSF3 [HugeCancerGEM]
General knowledge
Homologs : HomoloGeneSRSF3
Homology/Alignments : Family Browser (UCSC)SRSF3
Phylogenetic Trees/Animal Genes : TreeFamSRSF3
Chemical/Protein Interactions : CTD6428
Chemical/Pharm GKB GenePA35701
Clinical trialSRSF3
Other databases
Probes
Litterature
PubMed93 Pubmed reference(s) in Entrez
CoreMineSRSF3
iHOPSRSF3
OncoSearchSRSF3

Bibliography

The splicing factor SRp20 modifies splicing of its own mRNA and ASF/SF2 antagonizes this regulation.
Jumaa H, Nielsen PJ.
EMBO J. 1997 Aug 15;16(16):5077-85.
PMID 9305649
 
Regulation of alternative polyadenylation by U1 snRNPs and SRp20.
Lou H, Neugebauer KM, Gagel RF, Berget SM.
Mol Cell Biol. 1998 Sep;18(9):4977-85.
PMID 9710581
 
Splicing factors SRp20 and 9G8 promote the nucleocytoplasmic export of mRNA.
Huang Y, Steitz JA.
Mol Cell. 2001 Apr;7(4):899-905.
PMID 11336712
 
SR splicing factors serve as adapter proteins for TAP-dependent mRNA export.
Huang Y, Gattoni R, Stevenin J, Steitz JA.
Mol Cell. 2003 Mar;11(3):837-43.
PMID 12667464
 
RNA polymerase II C-terminal domain mediates regulation of alternative splicing by SRp20.
de la Mata M, Kornblihtt AR.
Nat Struct Mol Biol. 2006 Nov;13(11):973-80. Epub 2006 Oct 8.
PMID 17028590
 
A nucleo-cytoplasmic SR protein functions in viral IRES-mediated translation initiation.
Bedard KM, Daijogo S, Semler BL.
EMBO J. 2007 Jan 24;26(2):459-67. Epub 2006 Dec 21.
PMID 17183366
 
Genes involved in pre-mRNA 3'-end formation and transcription termination revealed by a lin-15 operon Muv suppressor screen.
Cui M, Allen MA, Larsen A, Macmorris M, Han M, Blumenthal T.
Proc Natl Acad Sci U S A. 2008 Oct 28;105(43):16665-70. Epub 2008 Oct 22.
PMID 18946043
 
Control of the papillomavirus early-to-late switch by differentially expressed SRp20.
Jia R, Liu X, Tao M, Kruhlak M, Guo M, Meyers C, Baker CC, Zheng ZM.
J Virol. 2009 Jan;83(1):167-80. Epub 2008 Oct 22.
PMID 18945760
 
SRp20 is a proto-oncogene critical for cell proliferation and tumor induction and maintenance.
Jia R, Li C, McCoy JP, Deng CX, Zheng ZM.
Int J Biol Sci. 2010 Dec 15;6(7):806-26.
PMID 21179588
 
Exon-centric regulation of pyruvate kinase M alternative splicing via mutually exclusive exons.
Wang Z, Chatterjee D, Jeon HY, Akerman M, Vander Heiden MG, Cantley LC, Krainer AR.
J Mol Cell Biol. 2012 Apr;4(2):79-87. Epub 2011 Nov 1.
PMID 22044881
 
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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Contributor(s)

Written05-2012Rong Jia, Zhi-Ming Zheng
School of Stomatology Wuhan University, PR. China (RJ); Tumor Virus RNA Biology Section, HIV and AIDS Malignancy Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USA (ZMZ)

Citation

This paper should be referenced as such :
Jia, R ; Zheng, ZM
SRSF3 (serine/arginine-rich splicing factor 3)
Atlas Genet Cytogenet Oncol Haematol. 2012;16(11):838-840.
Free online version   Free pdf version   [Bibliographic record ]
URL : http://AtlasGeneticsOncology.org/Genes/SRSF3ID42279ch6p21.html

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indexed on : Wed Jul 30 16:58:10 CEST 2014

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