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SOCS2 (suppressor of cytokine signaling 2)

Identity

Other namesCIS-2, Cytokine-inducible SH2 protein 2
CIS2, STAT induced STAT inhibitor-2
Cish2, STAT-induced STAT inhibitor 2
SOCS-2, suppressor of cytokine signaling 2
SSI-2, suppressor of cytokine signaling-2
SSI2
STATI2
HGNC (Hugo) SOCS2
LocusID (NCBI) 8835
Location 12q22
Location_base_pair Starts at 93964175 and ends at 93970521 bp from pter ( according to hg19-Feb_2009)  [Mapping]
Local_order By cytogenetic and radiation hybrid mapping, SOCS-2 has been mapped to chromosome 12q21.3-q23 (Yandava et al., 1999).

DNA/RNA

Description 6,38 kb ; 3 Exons. Mouse SOCS2 gene is composed of 3 exons and 2 introns (Metcalf et al., 2000). Human SOCS-2 is a functioning gene that comprises 3 exons spanning roughly 6,38 kb of genomic DNA.
Transcription 2210 bp mRNA. 1 protein (22.2 kDa; 198 aa). Although constitutively expressed SOCS2 mRNA has been detected in several tissues and cell types, its expression is, in general, induced by stimulation with different cytokines and hormones (Rico-Bautista et al., 2006). SOCS2 promoter analysis indicates the presence of AhR and STAT5 binding sites that confer responsiveness to dioxin (Boverhof et al., 2004) and GH (Vidal et al., 2006), respectively.

Protein

 
  Diagram representing the structure of SOCS proteins. At least eight proteins belonging to the SOCS family of proteins are shown (upper panel). They are characterized by the presence of an SH2 central domain and the SOCS box domain at the C-terminus. A small domain called kinase inhibitory region (KIR), only found in SOCS1 and SOCS3, is shown as a small box at the N-terminal region. SOCS proteins can interact with phosphotyrosine phosphorylated proteins through their SH2 domain and with Elongin BC through their SOCS box domain. Other proteins containing a SOCS box domain but lacking a SH2 domain are also shown (lower panel). Adapted from Elliot and Johnston (Elliott and Johnston, 2004) with modifications.
Description 22.2 kDa; 198 aa.
Expression SOCS mRNA and protein levels are constitutively low in unstimulated cells, but their expression is rapidly induced upon cytokine stimulation, thereby creating a negative feedback loop. Its expression is, in general, induced by stimulation with different cytokines and hormones (Rico-Bautista et al., 2006).
Localisation Intracellular, cytoplasm.
Function SOCS mechanisms of action rely on their ability to bind tyrosine phosphorylated proteins through their SH2 domains, but also to bind Elongin BC through their SOCS box domains. SOCS family proteins form part of a classical negative feedback system that regulates cytokine signal transduction (Rico-Bautista et al., 2006). SOCS2 appears to be a negative regulator in the growth hormone/IGF1 signaling pathway (Metcalf et al., 2000). SOCS2 appear to be involved in regulating protein turnover, targeting proteins for proteasome-mediated degradation (Rico-Bautista et al., 2004).

Mutations

Note SNP: increasing the risk of type 2 diabetes.

Implicated in

Entity Diabete
Note Susceptibility: to type 2 diabetes (Kato et al., 2006).
  
Entity Metabolism
Note SOCS2 null mice are giants but not obese (Metcalf et al., 2000). SOCS2 deficient mice have some metabolic characteristics that can be related to the enhanced GH actions (Rico-Bautista et al., 2005).
  
Entity Bone
Note Analysis of SOCS2 null mice have revealed that the absence of SOCS2 induces a reduction in the trabecular and cortical volumetric bone mineral density (Lorentzon et al., 2005). SOCS2 induces the differentiation of C2C12 mesenchymal cells into myoblasts or osteoblasts (Ouyang et al., 2006).
  
Entity Neural development
Note SOCS2 plays a critical role in neuronal development, growth, and stem cell differentiation (Turnley et al., 2002).
  
Entity Cancer
Note SOCS2 has been associated with cancer such as myeloid leukaemia, pulmonary adenocarcinoma, and ovarian cancer, breast cancer, and anal cancer.
  

External links

Nomenclature
HGNC (Hugo)SOCS2   19382
Cards
AtlasSOCS2ID44123ch12q21
Entrez_Gene (NCBI)SOCS2  8835  suppressor of cytokine signaling 2
GeneCards (Weizmann)SOCS2
Ensembl (Hinxton)ENSG00000120833 [Gene_View]  chr12:93964175-93970521 [Contig_View]  SOCS2 [Vega]
ICGC DataPortalENSG00000120833
cBioPortalSOCS2
AceView (NCBI)SOCS2
Genatlas (Paris)SOCS2
WikiGenes8835
SOURCE (Princeton)NM_001270467 NM_001270468 NM_001270469 NM_001270470 NM_001270471 NM_003877
Genomic and cartography
GoldenPath (UCSC)SOCS2  -  12q22   chr12:93964175-93970521 +  12q   [Description]    (hg19-Feb_2009)
EnsemblSOCS2 - 12q [CytoView]
Mapping of homologs : NCBISOCS2 [Mapview]
OMIM605117   
Gene and transcription
Genbank (Entrez)AB004903 AB006966 AB451318 AF020590 AF037989
RefSeq transcript (Entrez)NM_001270467 NM_001270468 NM_001270469 NM_001270470 NM_001270471 NM_003877
RefSeq genomic (Entrez)AC_000144 NC_000012 NC_018923 NT_029419 NW_001838061 NW_004929384
Consensus coding sequences : CCDS (NCBI)SOCS2
Cluster EST : UnigeneHs.737206 [ NCBI ]
CGAP (NCI)Hs.737206
Alternative Splicing : Fast-db (Paris)GSHG0006901
Alternative Splicing GalleryENSG00000120833
Gene ExpressionSOCS2 [ NCBI-GEO ]     SOCS2 [ SEEK ]   SOCS2 [ MEM ]
Protein : pattern, domain, 3D structure
UniProt/SwissProtO14508 (Uniprot)
NextProtO14508  [Medical]
With graphics : InterProO14508
Splice isoforms : SwissVarO14508 (Swissvar)
Domaine pattern : Prosite (Expaxy)SH2 (PS50001)    SOCS (PS50225)   
Domains : Interpro (EBI)SH2 [organisation]   SOCS [organisation]   SOCS2 [organisation]   SOCS_C [organisation]  
Related proteins : CluSTrO14508
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)  
DMDM Disease mutations8835
Blocks (Seattle)O14508
PDB (SRS)2C9W    4JGH   
PDB (PDBSum)2C9W    4JGH   
PDB (IMB)2C9W    4JGH   
PDB (RSDB)2C9W    4JGH   
Human Protein AtlasENSG00000120833 [gene] [tissue] [antibody] [cell] [cancer]
Peptide AtlasO14508
HPRD05490
IPIIPI00033944   IPI01010199   IPI01020907   IPI01022880   IPI01021714   IPI00978442   
Protein Interaction databases
DIP (DOE-UCLA)O14508
IntAct (EBI)O14508
FunCoupENSG00000120833
BioGRIDSOCS2
InParanoidO14508
Interologous Interaction database O14508
IntegromeDBSOCS2
STRING (EMBL)SOCS2
Ontologies - Pathways
Ontology : AmiGOregulation of cell growth  SH3/SH2 adaptor activity  growth hormone receptor binding  insulin-like growth factor receptor binding  protein binding  cytoplasm  cytosol  JAK-STAT cascade  aging  JAK pathway signal transduction adaptor activity  regulation of signal transduction  positive regulation of signal transduction  protein ubiquitination  response to estradiol  cellular response to hormone stimulus  negative regulation of apoptotic process  negative regulation of JAK-STAT cascade  growth hormone receptor signaling pathway  JAK-STAT cascade involved in growth hormone signaling pathway  
Ontology : EGO-EBIregulation of cell growth  SH3/SH2 adaptor activity  growth hormone receptor binding  insulin-like growth factor receptor binding  protein binding  cytoplasm  cytosol  JAK-STAT cascade  aging  JAK pathway signal transduction adaptor activity  regulation of signal transduction  positive regulation of signal transduction  protein ubiquitination  response to estradiol  cellular response to hormone stimulus  negative regulation of apoptotic process  negative regulation of JAK-STAT cascade  growth hormone receptor signaling pathway  JAK-STAT cascade involved in growth hormone signaling pathway  
Pathways : KEGGJak-STAT signaling pathway    Insulin signaling pathway    Prolactin signaling pathway    Type II diabetes mellitus   
Protein Interaction DatabaseSOCS2
Wikipedia pathwaysSOCS2
Gene fusion - rearrangments
Polymorphisms : SNP, mutations, diseases
SNP Single Nucleotide Polymorphism (NCBI)SOCS2
snp3D : Map Gene to Disease8835
SNP (GeneSNP Utah)SOCS2
SNP : HGBaseSOCS2
Genetic variants : HAPMAPSOCS2
Exome VariantSOCS2
1000_GenomesSOCS2 
ICGC programENSG00000120833 
Somatic Mutations in Cancer : COSMICSOCS2 
CONAN: Copy Number AnalysisSOCS2 
Mutations and Diseases : HGMDSOCS2
Mutations and Diseases : intOGenSOCS2
Genomic VariantsSOCS2  SOCS2 [DGVbeta]
dbVarSOCS2
ClinVarSOCS2
Pred. of missensesPolyPhen-2  SIFT(SG)  SIFT(JCVI)  Align-GVGD  MutAssessor  Mutanalyser  
Pred. splicesGeneSplicer  Human Splicing Finder  MaxEntScan  
Diseases
OMIM605117   
MedgenSOCS2
GENETestsSOCS2
Disease Genetic AssociationSOCS2
Huge Navigator SOCS2 [HugePedia]  SOCS2 [HugeCancerGEM]
General knowledge
Homologs : HomoloGeneSOCS2
Homology/Alignments : Family Browser (UCSC)SOCS2
Phylogenetic Trees/Animal Genes : TreeFamSOCS2
Chemical/Protein Interactions : CTD8835
Chemical/Pharm GKB GenePA128394542
Clinical trialSOCS2
Cancer Resource (Charite)ENSG00000120833
Other databases
Probes
Litterature
PubMed79 Pubmed reference(s) in Entrez
CoreMineSOCS2
iHOPSOCS2
OncoSearchSOCS2

Bibliography

Radiation hybrid and cytogenetic mapping of SOCS1 and SOCS2 to chromosomes 16p13 and 12q, respectively.
Yandava CN, Pillari A, Drazen JM
Genomics. 1999 ; 61 (1) : 108-111.
PMID 10512686
 
Gigantism in mice lacking suppressor of cytokine signalling-2.
Metcalf D, Greenhalgh CJ, Viney E, Willson TA, Starr R, Nicola NA, Hilton DJ, Alexander WS
Nature. 2000 ; 405 (6790) : 1069-1073.
PMID 10890450
 
Suppressor of cytokine signaling 2 regulates neuronal differentiation by inhibiting growth hormone signaling.
Turnley AM, Faux CH, Rietze RL, Coonan JR, Bartlett PF
Nature neuroscience. 2002 ; 5 (11) : 1155-1162.
PMID 12368809
 
2,3,7,8-Tetrachlorodibenzo-p-dioxin induces suppressor of cytokine signaling 2 in murine B cells.
Boverhof DR, Tam E, Harney AS, Crawford RB, Kaminski NE, Zacharewski TR
Molecular pharmacology. 2004 ; 66 (6) : 1662-1670.
PMID 15371557
 
SOCS: role in inflammation, allergy and homeostasis.
Elliott J, Johnston JA
Trends in immunology. 2004 ; 25 (8) : 434-440.
PMID 15275643
 
Downregulation of the growth hormone-induced Janus kinase 2/signal transducer and activator of transcription 5 signaling pathway requires an intact actin cytoskeleton.
Rico-Bautista E, Negrˆ‚n-Martˆ‚nez C, Novoa-Mogollˆ„n J, Fernˆ°ndez-Perez L, Flores-Morales A
Experimental cell research. 2004 ; 294 (1) : 269-280.
PMID 14980520
 
Reduced bone mineral density in SOCS-2-deficient mice.
Lorentzon M, Greenhalgh CJ, Mohan S, Alexander WS, Ohlsson C
Pediatric research. 2005 ; 57 (2) : 223-226.
PMID 15585682
 
Suppressor of cytokine signaling-2 deficiency induces molecular and metabolic changes that partially overlap with growth hormone-dependent effects.
Rico-Bautista E, Greenhalgh CJ, Tollet-Egnell P, Hilton DJ, Alexander WS, Norstedt G, Flores-Morales A
Molecular endocrinology (Baltimore, Md.). 2005 ; 19 (3) : 781-793.
PMID 15563548
 
Association of single-nucleotide polymorphisms in the suppressor of cytokine signaling 2 (SOCS2) gene with type 2 diabetes in the Japanese.
Kato H, Nomura K, Osabe D, Shinohara S, Mizumori O, Katashima R, Iwasaki S, Nishimura K, Yoshino M, Kobori M, Ichiishi E, Nakamura N, Yoshikawa T, Tanahashi T, Keshavarz P, Kunika K, Moritani M, Kudo E, Tsugawa K, Takata Y, Hamada D, Yasui N, Miyamoto T, Shiota H, Inoue H, Itakura M
Genomics. 2006 ; 87 (4) : 446-458.
PMID 16406727
 
SOCS-2 interferes with myotube formation and potentiates osteoblast differentiation through upregulation of JunB in C2C12 cells.
Ouyang X, Fujimoto M, Nakagawa R, Serada S, Tanaka T, Nomura S, Kawase I, Kishimoto T, Naka T
Journal of cellular physiology. 2006 ; 207 (2) : 428-436.
PMID 16419040
 
Suppressor of cytokine signaling (SOCS) 2, a protein with multiple functions.
Rico-Bautista E, Flores-Morales A, Fernˆ°ndez-Pˆ©rez L
Cytokine & growth factor reviews. 2006 ; 17 (6) : 431-439.
PMID 17070092
 
In vivo transcript profiling and phylogenetic analysis identifies suppressor of cytokine signaling 2 as a direct signal transducer and activator of transcription 5b target in liver.
Vidal OM, Merino R, Rico-Bautista E, Fernandez-Perez L, Chia DJ, Woelfle J, Ono M, Lenhard B, Norstedt G, Rotwein P, Flores-Morales A
Molecular endocrinology (Baltimore, Md.). 2007 ; 21 (1) : 293-311.
PMID 17008382
 
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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Contributor(s)

Written10-2007Leandro Fernández-Pérez, Amilcar Flores-Morales
University of Las Palmas de GC, Faculty of Health Sciences, Molecular and Translational Endocrinology Group, c/ Dr. Pasteur s/n - Campus San Cristobal, 35016 - Las Palmas, Spain, (LFP); Department of Molecular Medicine and Surgery, Karolinska Institute, 17176 Stockholm, Sweden (AFM)

Citation

This paper should be referenced as such :
Fernandez-Pérez, L ; Flores-Morales, A
SOCS2 (suppressor of cytokine signaling 2)
Atlas Genet Cytogenet Oncol Haematol. 2008;12(3):240-242.
Free online version   Free pdf version   [Bibliographic record ]
URL : http://AtlasGeneticsOncology.org/Genes/SOCS2ID44123ch12q21.html

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indexed on : Tue Aug 26 15:26:43 CEST 2014

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