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SOCS3 (suppressor of cytokine signaling 3)

Written2012-02Zoran Culig
Experimental Urology, Department of Urology, Innsbruck Medical University, Anichstrasse 35, A-6020 Innsbruck, Austria

(Note : for Links provided by Atlas : click)

Identity

Alias_symbol (synonym)SSI-3
CIS3
SOCS-3
Cish3
Other aliasATOD4
MGC71791
SSI3
HGNC (Hugo) SOCS3
LocusID (NCBI) 9021
Atlas_Id 44124
Location 17q25.3  [Link to chromosome band 17q25]
Location_base_pair Starts at 78356777 and ends at 78360079 bp from pter ( according to hg19-Feb_2009)  [Mapping SOCS3.png]
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
NSUN2 (5p15.31) / SOCS3 (17q25.3)

DNA/RNA

Description Size: 3300 bases.
Transcription 2 introns. Transcription generates 3 different mRNAs, 2 spliced variants and 1 unspliced form.

Protein

 
  KIR = kinase inhibitory region.
Description 225 amino acids, 24770 Da.
Expression Widely expressed in normal and tumor tissues. Expression in tumors is variable due to its different functions.
Localisation Cytoplasm.
Function SOCS is a negative regulator of cytokines that signal through the JAK/STAT pathway. It binds to tyrosine kinase receptors such as gp130 subunit of receptors. It interacts with cytokine receptors or JAK kinases and interaction with growth factor receptors (insulin-like growth factor-I, insulin, fibroblast growth factor). It inhibits JAK2 kinase activity. Part of the ubiquitin-protein ligase complex which contains elongin, RNF7, and CUL5. Binding to leptin. Tumor promoting or tumor suppressive functions. Antagonizing cAMP-antiproliferative effects. SOCS3 suppresses erythropoietin in fetal liver and IL-6 signaling in vivo.

Mutations

Note Mutations not detected.

Implicated in

Note
  
Entity Lung cancer
Note SOCS-3 acts as a tumor suppressor and is frequently lost in the disease. Its transient transfection in lung cancer cell lines leads to a decrease in proliferation.
  
  
Entity Liver cancer
Note SOCS-3 is silenced by methylation. SOCS-3 is a tumor suppressor in this malignancy. It is implicated in regulation of migration of cancer cells. SOCS-3 deletion enhances JAK/STAT and FAK signaling.
  
  
Entity Barret's adenocarcinoma
Note SOCS-3 is methylated. It is considered as a tumor suppressor.
  
  
Entity Glioblastoma multiforme
Note SOCS-3 expression is lost through promoter methylation.
  
  
Entity Head and neck squamous cell cancer
Note SOCS-3 is frequently down-regulated as a result of promoter methylation. It causes a growth inhibition.
  
  
Entity Hematological malignancies
Note SOCS-3 inhibits megakaryocytic growth, overexpression of SOCS-3 is associated with a decreased survival of patients with follicular lymphoma.
  
  
Entity Melanoma
Note SOCS-3 is a tumor promoter in melanoma and is constitutively expressed in several cell lines.
  
  
Entity Prostate cancer
Note SOCS-3 stimulates proliferation and inhibits apoptosis in prostate cancer cells which do not express the androgen receptor. It may also antagonize the effects of fibroblasts growth factor and mitogen-activated protein kinases. In androgen-sensitive prostate cancer cells, SOCS-3 is induced by androgen and may inhibit androgen-stimulated proliferation and secretion.
  
  
Entity Diabetes
Note SOCS-3 may antagonize function of insulin-like growth factors.
  
  
Entity Various cancers
Prognosis Loss of protein expression and promoter hypermethylation occur in lung, liver cancer, head and neck squamous cell cancer. Overexpression occurs in melanoma and prostate cancer.
  

Bibliography

Suppressor of cytokine signaling-3 antagonizes cAMP effects on proliferation and apoptosis and is expressed in human prostate cancer.
Bellezza I, Neuwirt H, Nemes C, Cavarretta IT, Puhr M, Steiner H, Minelli A, Bartsch G, Offner F, Hobisch A, Doppler W, Culig Z.
Am J Pathol. 2006 Dec;169(6):2199-208.
PMID 17148681
 
STAT3-mediated constitutive expression of SOCS-3 in cutaneous T-cell lymphoma.
Brender C, Nielsen M, Kaltoft K, Mikkelsen G, Zhang Q, Wasik M, Billestrup N, Odum N.
Blood. 2001 Feb 15;97(4):1056-62.
PMID 11159537
 
Epigenetic inactivation of suppressors of cytokine signalling in Philadelphia-negative chronic myeloproliferative disorders.
Capello D, Deambrogi C, Rossi D, Lischetti T, Piranda D, Cerri M, Spina V, Rasi S, Gaidano G, Lunghi M.
Br J Haematol. 2008 May;141(4):504-11. Epub 2008 Mar 3.
PMID 18318760
 
SOCS-3 is frequently silenced by hypermethylation and suppresses cell growth in human lung cancer.
He B, You L, Uematsu K, Zang K, Xu Z, Lee AY, Costello JF, McCormick F, Jablons DM.
Proc Natl Acad Sci U S A. 2003 Nov 25;100(24):14133-8. Epub 2003 Nov 14.
PMID 14617776
 
Constitutive suppressor of cytokine signaling 3 expression confers a growth advantage to a human melanoma cell line.
Komyod W, Bohm M, Metze D, Heinrich PC, Behrmann I.
Mol Cancer Res. 2007 Mar;5(3):271-81.
PMID 17374732
 
Prognostic relevance of SOCS3 hypermethylation in patients with glioblastoma multiforme.
Martini M, Pallini R, Luongo G, Cenci T, Lucantoni C, Larocca LM.
Int J Cancer. 2008 Dec 15;123(12):2955-60.
PMID 18770864
 
Methylation silencing of SOCS-3 promotes cell growth and migration by enhancing JAK/STAT and FAK signalings in human hepatocellular carcinoma.
Niwa Y, Kanda H, Shikauchi Y, Saiura A, Matsubara K, Kitagawa T, Yamamoto J, Kubo T, Yoshikawa H.
Oncogene. 2005 Sep 22;24(42):6406-17.
PMID 16007195
 
Type 2 diabetes impairs insulin receptor substrate-2-mediated phosphatidylinositol 3-kinase activity in primary macrophages to induce a state of cytokine resistance to IL-4 in association with overexpression of suppressor of cytokine signaling-3.
O'Connor JC, Sherry CL, Guest CB, Freund GG.
J Immunol. 2007 Jun 1;178(11):6886-93.
PMID 17513737
 
Down-regulation of suppressor of cytokine signaling-3 causes prostate cancer cell death through activation of the extrinsic and intrinsic apoptosis pathways.
Puhr M, Santer FR, Neuwirt H, Susani M, Nemeth JA, Hobisch A, Kenner L, Culig Z.
Cancer Res. 2009 Sep 15;69(18):7375-84. Epub 2009 Sep 8.
PMID 19738059
 
SOCS-3 is frequently methylated in head and neck squamous cell carcinoma and its precursor lesions and causes growth inhibition.
Weber A, Hengge UR, Bardenheuer W, Tischoff I, Sommerer F, Markwarth A, Dietz A, Wittekind C, Tannapfel A.
Oncogene. 2005 Oct 6;24(44):6699-708.
PMID 16007169
 

Citation

This paper should be referenced as such :
Culig, Z
SOCS3 (suppressor of cytokine signaling 3)
Atlas Genet Cytogenet Oncol Haematol. 2012;16(7):496-497.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/SOCS3ID44124ch17q25.html


External links

Nomenclature
HGNC (Hugo)SOCS3   19391
LRG (Locus Reference Genomic)LRG_619
Cards
AtlasSOCS3ID44124ch17q25
Entrez_Gene (NCBI)SOCS3  9021  suppressor of cytokine signaling 3
AliasesATOD4; CIS3; Cish3; SOCS-3; 
SSI-3; SSI3
GeneCards (Weizmann)SOCS3
Ensembl hg19 (Hinxton)ENSG00000184557 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000184557 [Gene_View]  chr17:78356777-78360079 [Contig_View]  SOCS3 [Vega]
ICGC DataPortalENSG00000184557
TCGA cBioPortalSOCS3
AceView (NCBI)SOCS3
Genatlas (Paris)SOCS3
WikiGenes9021
SOURCE (Princeton)SOCS3
Genetics Home Reference (NIH)SOCS3
Genomic and cartography
GoldenPath hg38 (UCSC)SOCS3  -     chr17:78356777-78360079 -  17q25.3   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)SOCS3  -     17q25.3   [Description]    (hg19-Feb_2009)
EnsemblSOCS3 - 17q25.3 [CytoView hg19]  SOCS3 - 17q25.3 [CytoView hg38]
Mapping of homologs : NCBISOCS3 [Mapview hg19]  SOCS3 [Mapview hg38]
OMIM604176   
Gene and transcription
Genbank (Entrez)AB004904 AB006967 AF159854 AK309756 AK314212
RefSeq transcript (Entrez)NM_003955
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)SOCS3
Cluster EST : UnigeneHs.703620 [ NCBI ]
CGAP (NCI)Hs.703620
Alternative Splicing GalleryENSG00000184557
Gene ExpressionSOCS3 [ NCBI-GEO ]   SOCS3 [ EBI - ARRAY_EXPRESS ]   SOCS3 [ SEEK ]   SOCS3 [ MEM ]
Gene Expression Viewer (FireBrowse)SOCS3 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)9021
GTEX Portal (Tissue expression)SOCS3
Human Protein AtlasENSG00000184557-SOCS3 [pathology]   [cell]   [tissue]
Protein : pattern, domain, 3D structure
UniProt/SwissProtO14543   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtO14543  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProO14543
Splice isoforms : SwissVarO14543
PhosPhoSitePlusO14543
Domaine pattern : Prosite (Expaxy)SH2 (PS50001)    SOCS (PS50225)   
Domains : Interpro (EBI)SH2    SOCS3    SOCS_box   
Domain families : Pfam (Sanger)SH2 (PF00017)    SOCS_box (PF07525)   
Domain families : Pfam (NCBI)pfam00017    pfam07525   
Domain families : Smart (EMBL)SH2 (SM00252)  SOCS (SM00253)  SOCS_box (SM00969)  
Conserved Domain (NCBI)SOCS3
DMDM Disease mutations9021
Blocks (Seattle)SOCS3
SuperfamilyO14543
Human Protein Atlas [tissue]ENSG00000184557-SOCS3 [tissue]
Peptide AtlasO14543
HPRD05006
IPIIPI00297349   
Protein Interaction databases
DIP (DOE-UCLA)O14543
IntAct (EBI)O14543
FunCoupENSG00000184557
BioGRIDSOCS3
STRING (EMBL)SOCS3
ZODIACSOCS3
Ontologies - Pathways
QuickGOO14543
Ontology : AmiGOphosphotyrosine binding  protein kinase inhibitor activity  protein binding  cytoplasm  cytosol  negative regulation of protein kinase activity  JAK-STAT cascade  protein ubiquitination  cytokine-mediated signaling pathway  regulation of growth  negative regulation of apoptotic process  positive regulation of cell differentiation  negative regulation of JAK-STAT cascade  negative regulation of insulin receptor signaling pathway  negative regulation of inflammatory response  regulation of interferon-gamma-mediated signaling pathway  branching involved in labyrinthine layer morphogenesis  placenta blood vessel development  trophoblast giant cell differentiation  spongiotrophoblast differentiation  
Ontology : EGO-EBIphosphotyrosine binding  protein kinase inhibitor activity  protein binding  cytoplasm  cytosol  negative regulation of protein kinase activity  JAK-STAT cascade  protein ubiquitination  cytokine-mediated signaling pathway  regulation of growth  negative regulation of apoptotic process  positive regulation of cell differentiation  negative regulation of JAK-STAT cascade  negative regulation of insulin receptor signaling pathway  negative regulation of inflammatory response  regulation of interferon-gamma-mediated signaling pathway  branching involved in labyrinthine layer morphogenesis  placenta blood vessel development  trophoblast giant cell differentiation  spongiotrophoblast differentiation  
Pathways : BIOCARTAIL22 Soluble Receptor Signaling [Genes]    IL-2 Receptor Beta Chain in T cell Activation [Genes]   
Pathways : KEGG   
REACTOMEO14543 [protein]
REACTOME PathwaysR-HSA-983168 [pathway]   
NDEx NetworkSOCS3
Atlas of Cancer Signalling NetworkSOCS3
Wikipedia pathwaysSOCS3
Orthology - Evolution
OrthoDB9021
GeneTree (enSembl)ENSG00000184557
Phylogenetic Trees/Animal Genes : TreeFamSOCS3
HOVERGENO14543
HOGENOMO14543
Homologs : HomoloGeneSOCS3
Homology/Alignments : Family Browser (UCSC)SOCS3
Gene fusions - Rearrangements
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerSOCS3 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)SOCS3
dbVarSOCS3
ClinVarSOCS3
1000_GenomesSOCS3 
Exome Variant ServerSOCS3
ExAC (Exome Aggregation Consortium)ENSG00000184557
GNOMAD BrowserENSG00000184557
Genetic variants : HAPMAP9021
Genomic Variants (DGV)SOCS3 [DGVbeta]
DECIPHERSOCS3 [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisSOCS3 
Mutations
ICGC Data PortalSOCS3 
TCGA Data PortalSOCS3 
Broad Tumor PortalSOCS3
OASIS PortalSOCS3 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICSOCS3  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDSOCS3
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch SOCS3
DgiDB (Drug Gene Interaction Database)SOCS3
DoCM (Curated mutations)SOCS3 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)SOCS3 (select a term)
intoGenSOCS3
NCG5 (London)SOCS3
Cancer3DSOCS3(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM604176   
Orphanet
MedgenSOCS3
Genetic Testing Registry SOCS3
NextProtO14543 [Medical]
TSGene9021
GENETestsSOCS3
Target ValidationSOCS3
Huge Navigator SOCS3 [HugePedia]
snp3D : Map Gene to Disease9021
BioCentury BCIQSOCS3
ClinGenSOCS3
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD9021
Chemical/Pharm GKB GenePA134885765
Clinical trialSOCS3
Miscellaneous
canSAR (ICR)SOCS3 (select the gene name)
Probes
Litterature
PubMed391 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineSOCS3
EVEXSOCS3
GoPubMedSOCS3
iHOPSOCS3
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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indexed on : Thu Oct 12 16:34:08 CEST 2017

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