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| 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. |
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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. |
Note | |
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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. |
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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 |
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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 |
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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 |
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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 |
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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 |
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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 |
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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 |
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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 |
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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 |
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| Nomenclature |
HGNC (Hugo) | SRSF3 10785 |
| Cards |
Atlas | SRSF3ID42279ch6p21 |
Entrez_Gene (NCBI) | SRSF3 serine and arginine rich splicing factor 3 |
Aliases | SFRS3; SRp20 |
GeneCards (Weizmann) | SRSF3 |
Ensembl hg19 (Hinxton) | ENSG00000112081 [Gene_View] |
Ensembl hg38 (Hinxton) | ENSG00000112081 [Gene_View]  ENSG00000112081 [Sequence] chr6:36594362-36605600 [Contig_View] SRSF3 [Vega] |
ICGC DataPortal | ENSG00000112081 |
TCGA cBioPortal | SRSF3 |
AceView (NCBI) | SRSF3 |
Genatlas (Paris) | SRSF3 |
SOURCE (Princeton) | SRSF3 |
Genetics Home Reference (NIH) | SRSF3 |
| Genomic and cartography |
GoldenPath hg38 (UCSC) | SRSF3 - chr6:36594362-36605600 + 6p21.31-p21.2 [Description] (hg38-Dec_2013) |
GoldenPath hg19 (UCSC) | SRSF3 - 6p21.31-p21.2 [Description] (hg19-Feb_2009) |
GoldenPath | SRSF3 - 6p21.31-p21.2 [CytoView hg19] SRSF3 - 6p21.31-p21.2 [CytoView hg38] |
ImmunoBase | ENSG00000112081 |
genome Data Viewer NCBI | SRSF3 [Mapview hg19] |
OMIM | 603364 |
| Gene and transcription |
Genbank (Entrez) | AB451229 AB451352 AF107405 AK091927 AK095580 |
RefSeq transcript (Entrez) | NM_003017 |
RefSeq genomic (Entrez) | |
Consensus coding sequences : CCDS (NCBI) | SRSF3 |
Alternative Splicing Gallery | ENSG00000112081 |
Gene Expression | SRSF3 [ NCBI-GEO ] SRSF3 [ EBI - ARRAY_EXPRESS ]
SRSF3 [ SEEK ] SRSF3 [ MEM ] |
Gene Expression Viewer (FireBrowse) | SRSF3 [ Firebrowse - Broad ] |
Genevisible | Expression of SRSF3 in : [tissues]  [cell-lines]  [cancer]  [perturbations]   |
BioGPS (Tissue expression) | 6428 |
GTEX Portal (Tissue expression) | SRSF3 |
Human Protein Atlas | ENSG00000112081-SRSF3 [pathology] [cell] [tissue] |
| Protein : pattern, domain, 3D structure |
UniProt/SwissProt | P84103 [function] [subcellular_location] [family_and_domains] [pathology_and_biotech] [ptm_processing] [expression] [interaction] |
NextProt | P84103 [Sequence] [Exons] [Medical] [Publications] |
With graphics : InterPro | P84103 |
Splice isoforms : SwissVar | P84103 |
PhosPhoSitePlus | P84103 |
Domaine pattern : Prosite (Expaxy) | RRM (PS50102) |
Domains : Interpro (EBI) | Nucleotide-bd_a/b_plait_sf RBD_domain_sf RRM_dom |
Domain families : Pfam (Sanger) | RRM_1 (PF00076) |
Domain families : Pfam (NCBI) | pfam00076 |
Domain families : Smart (EMBL) | RRM (SM00360) |
Conserved Domain (NCBI) | SRSF3 |
Blocks (Seattle) | SRSF3 |
PDB (RSDB) | 2I2Y 2I38 |
PDB Europe | 2I2Y 2I38 |
PDB (PDBSum) | 2I2Y 2I38 |
PDB (IMB) | 2I2Y 2I38 |
Structural Biology KnowledgeBase | 2I2Y 2I38 |
SCOP (Structural Classification of Proteins) | 2I2Y 2I38 |
CATH (Classification of proteins structures) | 2I2Y 2I38 |
Superfamily | P84103 |
Human Protein Atlas [tissue] | ENSG00000112081-SRSF3 [tissue] |
Peptide Atlas | P84103 |
HPRD | 04530 |
IPI | IPI00010204 IPI00843996 |
| Protein Interaction databases |
DIP (DOE-UCLA) | P84103 |
IntAct (EBI) | P84103 |
BioGRID | SRSF3 |
STRING (EMBL) | SRSF3 |
ZODIAC | SRSF3 |
| Ontologies - Pathways |
QuickGO | P84103 |
Ontology : AmiGO | "regulation of alternative mRNA splicing, via spliceosome mRNA splicing, via spliceosome RNA binding RNA binding RNA binding protein binding nucleus nucleoplasm cytoplasm RNA export from nucleus mRNA export from nucleus mRNA export from nucleus nuclear speck nuclear speck mRNA 3'-end processing phospholipase binding mRNA cis splicing, via spliceosome regulation of mRNA splicing, via spliceosome sequence-specific mRNA binding cellular response to leukemia inhibitory factor" |
Ontology : EGO-EBI | "regulation of alternative mRNA splicing, via spliceosome mRNA splicing, via spliceosome RNA binding RNA binding RNA binding protein binding nucleus nucleoplasm cytoplasm RNA export from nucleus mRNA export from nucleus mRNA export from nucleus nuclear speck nuclear speck mRNA 3'-end processing phospholipase binding mRNA cis splicing, via spliceosome regulation of mRNA splicing, via spliceosome sequence-specific mRNA binding cellular response to leukemia inhibitory factor" |
Pathways : KEGG | Spliceosome Herpes simplex infection |
REACTOME | P84103 [protein] |
REACTOME Pathways | R-HSA-73856 [pathway] |
NDEx Network | SRSF3 |
Atlas of Cancer Signalling Network | SRSF3 |
Wikipedia pathways | SRSF3 |
| Orthology - Evolution |
OrthoDB | 6428 |
GeneTree (enSembl) | ENSG00000112081 |
Phylogenetic Trees/Animal Genes : TreeFam | SRSF3 |
HOGENOM | P84103 |
Homologs : HomoloGene | SRSF3 |
Homology/Alignments : Family Browser (UCSC) | SRSF3 |
| Gene fusions - Rearrangements |
Fusion : Mitelman | SRSF3/BCL6 [6p21.31/3q27.3]   |
Fusion : TICdb | SRSF3 [6p21.31] - BCL6 [3q27.3] |
Fusion : Fusion_Hub | AKAP10--SRSF3 BCL6--SRSF3 FKBP5--SRSF3 GTF2IRD2--SRSF3 MAP4K4--SRSF3 MCM3--SRSF3 MSMB--SRSF3 PLOD2--SRSF3 PPIB--SRSF3 PSMB9--SRSF3 RP11-31K23.1--SRSF3 SAMM50--SRSF3 SRPK1--SRSF3 SRSF3--BCL6 SRSF3--DNAJC7 |
| SRSF3--FBXO18 SRSF3--MTHFD2L SRSF3--SRSF3 SRSF3--SUCO SRSF3--TCF25 SRSF3--U2AF1 SRSF3--USP6 SRSF3--ZMYND11 UBE2E2--SRSF3 ZBED4--SRSF3 ZCCHC10--SRSF3 ZNFX1-AS1--SRSF3 |
Fusion : Quiver | SRSF3 |
| Polymorphisms : SNP and Copy number variants |
NCBI Variation Viewer | SRSF3 [hg38] |
dbVar | SRSF3 |
ClinVar | SRSF3 |
Monarch | SRSF3 |
1000_Genomes | SRSF3 |
Exome Variant Server | SRSF3 |
GNOMAD Browser | ENSG00000112081 |
Varsome Browser | SRSF3 |
Genomic Variants (DGV) | SRSF3 [DGVbeta] |
DECIPHER | SRSF3 [patients] [syndromes] [variants] [genes] |
CONAN: Copy Number Analysis | SRSF3 |
| Mutations |
ICGC Data Portal | SRSF3 |
TCGA Data Portal | SRSF3 |
Broad Tumor Portal | SRSF3 |
OASIS Portal | SRSF3 [ Somatic mutations - Copy number] |
Cancer Gene: Census | SRSF3 |
Somatic Mutations in Cancer : COSMIC | SRSF3 [overview] [genome browser] [tissue] [distribution] |
Somatic Mutations in Cancer : COSMIC3D | SRSF3 |
Mutations and Diseases : HGMD | SRSF3 |
LOVD (Leiden Open Variation Database) | Whole genome datasets |
LOVD (Leiden Open Variation Database) | LOVD 3.0 shared installation |
BioMuta | search 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) |
intoGen | SRSF3 |
OncoKB | SRSF3 |
NCG6 (London) | select SRSF3 |
Cancer3D | SRSF3(select the gene name) |
Impact of mutations | [PolyPhen2] [Provean] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser] |
| Diseases |
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OMIM | 603364 |
Orphanet | |
DisGeNET | SRSF3 |
Medgen | SRSF3 |
Genetic Testing Registry | SRSF3
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NextProt | P84103 [Medical] |
GENETests | SRSF3 |
Target Validation | SRSF3 |
Huge Navigator |
SRSF3 [HugePedia] |
ClinGen | SRSF3 |
| Clinical trials, drugs, therapy |
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MyCancerGenome | SRSF3 |
Protein Interactions : CTD | |
Pharm GKB Gene | PA35701 |
Pharos | P84103 |
Clinical trial | SRSF3 |
| Miscellaneous |
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canSAR (ICR) | SRSF3 (select the gene name) |
Harmonizome | SRSF3 |
DataMed Index | SRSF3 |
| Probes |
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| Litterature |
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PubMed | 192 Pubmed reference(s) in Entrez |
GeneRIFs | Gene References Into Functions (Entrez) |
EVEX | SRSF3 |