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SRSF3 (serine/arginine-rich splicing factor 3)

Written2012-05Rong Jia, Zhi-Ming Zheng
School of Stomatology Wuhan University, PR. China (RJ); Tumor Virus RNA Biology Section, HIV, AIDS Malignancy Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USA (ZMZ)

(Note : for Links provided by Atlas : click)

Identity

Alias_namesSFRS3
splicing factor, arginine/serine-rich 3
serine/arginine-rich splicing factor 3
Alias_symbol (synonym)SRp20
HGNC (Hugo) SRSF3
LocusID (NCBI) 6428
Atlas_Id 42279
Location 6p21.31  [Link to chromosome band 6p21]
Location_base_pair Starts at 36562090 and ends at 36572244 bp from pter ( according to hg19-Feb_2009)  [Mapping SRSF3.png]
Fusion genes
(updated 2016)
BCL6 (3q27.3) / SRSF3 (6p21.31)PPIB (15q22.31) / SRSF3 (6p21.31)SRSF3 (6p21.31) / BCL6 (3q27.3)
SRSF3 (6p21.31) / SRSF3 (6p21.31)UBE2E2 (3p24.3) / SRSF3 (6p21.31)ZFAS1 (20q13.13) / SRSF3 (6p21.31)

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

Note
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.
  

Bibliography

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
 
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
 
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
 
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
 
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
 
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
 
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
 
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
 

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 journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/SRSF3ID42279ch6p21.html


Other Leukemias implicated (Data extracted from papers in the Atlas) [ 1 ]
  t(3;6)(q27;p21) SRSF3/BCL6


External links

Nomenclature
HGNC (Hugo)SRSF3   10785
Cards
AtlasSRSF3ID42279ch6p21
Entrez_Gene (NCBI)SRSF3  6428  serine/arginine-rich splicing factor 3
AliasesSFRS3; SRp20
GeneCards (Weizmann)SRSF3
Ensembl hg19 (Hinxton)ENSG00000112081 [Gene_View]  chr6:36562090-36572244 [Contig_View]  SRSF3 [Vega]
Ensembl hg38 (Hinxton)ENSG00000112081 [Gene_View]  chr6:36562090-36572244 [Contig_View]  SRSF3 [Vega]
ICGC DataPortalENSG00000112081
TCGA cBioPortalSRSF3
AceView (NCBI)SRSF3
Genatlas (Paris)SRSF3
WikiGenes6428
SOURCE (Princeton)SRSF3
Genetics Home Reference (NIH)SRSF3
Genomic and cartography
GoldenPath hg19 (UCSC)SRSF3  -     chr6:36562090-36572244 +  6p21   [Description]    (hg19-Feb_2009)
GoldenPath hg38 (UCSC)SRSF3  -     6p21   [Description]    (hg38-Dec_2013)
EnsemblSRSF3 - 6p21 [CytoView hg19]  SRSF3 - 6p21 [CytoView hg38]
Mapping of homologs : NCBISRSF3 [Mapview hg19]  SRSF3 [Mapview hg38]
OMIM603364   
Gene and transcription
Genbank (Entrez)AB451229 AB451352 AF107405 AK091927 AK095580
RefSeq transcript (Entrez)NM_003017
RefSeq genomic (Entrez)NC_000006 NC_018917 NT_007592 NW_004929326
Consensus coding sequences : CCDS (NCBI)SRSF3
Cluster EST : UnigeneHs.405144 [ NCBI ]
CGAP (NCI)Hs.405144
Alternative Splicing GalleryENSG00000112081
Gene ExpressionSRSF3 [ NCBI-GEO ]   SRSF3 [ EBI - ARRAY_EXPRESS ]   SRSF3 [ SEEK ]   SRSF3 [ MEM ]
Gene Expression Viewer (FireBrowse)SRSF3 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)6428
GTEX Portal (Tissue expression)SRSF3
Protein : pattern, domain, 3D structure
UniProt/SwissProtP84103   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtP84103  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProP84103
Splice isoforms : SwissVarP84103
PhosPhoSitePlusP84103
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)SRSF3
DMDM Disease mutations6428
Blocks (Seattle)SRSF3
PDB (SRS)2I2Y    2I38   
PDB (PDBSum)2I2Y    2I38   
PDB (IMB)2I2Y    2I38   
PDB (RSDB)2I2Y    2I38   
Structural Biology KnowledgeBase2I2Y    2I38   
SCOP (Structural Classification of Proteins)2I2Y    2I38   
CATH (Classification of proteins structures)2I2Y    2I38   
SuperfamilyP84103
Human Protein AtlasENSG00000112081
Peptide AtlasP84103
HPRD04530
IPIIPI00010204   IPI00843996   
Protein Interaction databases
DIP (DOE-UCLA)P84103
IntAct (EBI)P84103
FunCoupENSG00000112081
BioGRIDSRSF3
STRING (EMBL)SRSF3
ZODIACSRSF3
Ontologies - Pathways
QuickGOP84103
Ontology : AmiGOnucleotide binding  mRNA splicing, via spliceosome  RNA binding  protein binding  nucleoplasm  cytoplasm  termination of RNA polymerase II transcription  RNA export from nucleus  mRNA export from nucleus  nuclear speck  mRNA 3'-end processing  phospholipase binding  poly(A) RNA binding  regulation of mRNA splicing, via spliceosome  sequence-specific mRNA binding  
Ontology : EGO-EBInucleotide binding  mRNA splicing, via spliceosome  RNA binding  protein binding  nucleoplasm  cytoplasm  termination of RNA polymerase II transcription  RNA export from nucleus  mRNA export from nucleus  nuclear speck  mRNA 3'-end processing  phospholipase binding  poly(A) RNA binding  regulation of mRNA splicing, via spliceosome  sequence-specific mRNA binding  
Pathways : KEGGSpliceosome    Herpes simplex infection   
REACTOMEP84103 [protein]
REACTOME PathwaysR-HSA-159236 Transport of Mature mRNA derived from an Intron-Containing Transcript [pathway]
REACTOME PathwaysR-HSA-72163 mRNA Splicing - Major Pathway [pathway]
REACTOME PathwaysR-HSA-109688 Cleavage of Growing Transcript in the Termination Region [pathway]
REACTOME PathwaysR-HSA-72187 mRNA 3'-end processing [pathway]
NDEx NetworkSRSF3
Atlas of Cancer Signalling NetworkSRSF3
Wikipedia pathwaysSRSF3
Orthology - Evolution
OrthoDB6428
GeneTree (enSembl)ENSG00000112081
Phylogenetic Trees/Animal Genes : TreeFamSRSF3
HOVERGENP84103
HOGENOMP84103
Homologs : HomoloGeneSRSF3
Homology/Alignments : Family Browser (UCSC)SRSF3
Gene fusions - Rearrangements
Fusion : MitelmanSRSF3/BCL6 [6p21.31/3q27.3]  
Fusion : TICdbSRSF3 [6p21.31]  -  BCL6 [3q27.3]
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerSRSF3 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)SRSF3
dbVarSRSF3
ClinVarSRSF3
1000_GenomesSRSF3 
Exome Variant ServerSRSF3
ExAC (Exome Aggregation Consortium)SRSF3 (select the gene name)
Genetic variants : HAPMAP6428
Genomic Variants (DGV)SRSF3 [DGVbeta]
DECIPHER (Syndromes)6:36562090-36572244  ENSG00000112081
CONAN: Copy Number AnalysisSRSF3 
Mutations
ICGC Data PortalSRSF3 
TCGA Data PortalSRSF3 
Broad Tumor PortalSRSF3
OASIS PortalSRSF3 [ Somatic mutations - Copy number]
Cancer Gene: CensusSRSF3 
Somatic Mutations in Cancer : COSMICSRSF3  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDSRSF3
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch SRSF3
DgiDB (Drug Gene Interaction Database)SRSF3
DoCM (Curated mutations)SRSF3 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)SRSF3 (select a term)
intoGenSRSF3
NCG5 (London)SRSF3
Cancer3DSRSF3(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM603364   
Orphanet
MedgenSRSF3
Genetic Testing Registry SRSF3
NextProtP84103 [Medical]
TSGene6428
GENETestsSRSF3
Huge Navigator SRSF3 [HugePedia]
snp3D : Map Gene to Disease6428
BioCentury BCIQSRSF3
ClinGenSRSF3
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD6428
Chemical/Pharm GKB GenePA35701
Clinical trialSRSF3
Miscellaneous
canSAR (ICR)SRSF3 (select the gene name)
Probes
Litterature
PubMed105 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineSRSF3
EVEXSRSF3
GoPubMedSRSF3
iHOPSRSF3
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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indexed on : Fri Nov 18 20:09:26 CET 2016

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