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SOCS1 (Suppressor of cytokine signaling 1)

Identity

Other namesJAB (JAK binding protein)
CIS1 (cytokine-inducible SH2 protein 1)
SSI1 (STAT-induced STAT inhibitor)
TIP3 (Tec-interacting protein 3)
CISH1
SSI-1
HGNC (Hugo) SOCS1
LocusID (NCBI) 8651
Location 16p13.13
Location_base_pair Starts at 11348274 and ends at 11350039 bp from pter ( according to hg19-Feb_2009)  [Mapping]

DNA/RNA

 
  The sequence numbering shown under the central diagram are according to Genebank accession no. NC000016 for SOCS1 DNA.
Description The SOCS1 gene is divided in 2 exons. The exon 1 contains the 5'untranslated region. The exon 2 contains part of 5'untranslated region, the translation initiation ATG, the stop codon, and the 3'untranslated region.
Transcription The 1216 bases of human SOCS1 mRNA contains an open reading frame of 633 bases, resulting in a protein of 211 amino acid residues.

Protein

Description The SOCS1 is a member of the STAT-induced STAT inhibitor (SSI), also known as suppressor of cytokine signaling (SOCS), family. The SSI family members are cytokine-inducible negative regulators of cytokine signaling. The SOCS1 possesses tumor suppressor function.
Localisation Cytoplasmic.
Function The SOCS1 functions downstream of cytokine receptors, and takes part in a negative feedback loop to attenuate cytokine signaling. The SOCS1 is rapidly induced following stimulation by several type I and type II cytokines, and it attenuates their signaling by its ability to bind and inhibit all four of the Janus family of intracellular tyrosine kinases (JAKs). The SOCS1 functions as a negative regulator in TNF-induced inflammation and activation of c-jun N-terminal kinase by mediating ASK1 degradation in endothelial cells. The SOCS-1 is found to colocalize and biochemically copurify with the microtubule organizing complex (MTOC) and its associated 20S proteasome. The SOCS-1 SH2 domain is required for the localization of SOCS-1 to the MTOC and targets Jak1 to a perinuclear distribution resembling the MTOC-associated 20S proteasome.

Mutations

Note Mutations of the tumor suppressor gene SOCS-1 in classical Hodgkin lymphoma and primary mediastinal B-cell lymphoma are frequent.
Somatic 191-218del (V64S, out-of-frame), 349-359del (V117, out-of-frame), 393-417del (Q131H, delA132-H136), 431-512del (F144C, out-of-frame), 435-446del (D145E, delC146-E149), 448C>G (L150V)
The sequence numberings are according to the Genebank accession number NM_003745 for SOCS1 mRNA.

Implicated in

Entity Various cancers and diseases
Note Aberrant methylation in the CpG island of SOCS1.
Disease Hepatocellular carcinoma, hepatoblastoma, hepatitis C virus-associated chronic hepatitis and liver cirrhosis, brain tumor, head and neck squamous cell carcinoma, gastric carcinoma, pancreatic cancer, colorectal cancer, acute myeloid leukemia, multiple myeloma, myelodysplastic syndrome, chronic myeloid leukemia.
Oncogenesis Loss-of-expression by aberrant DNA methylation.
  
Entity Hodgkin lymphoma, primary mediastinal B-cell lymphoma
Note Somatic origin.
Oncogenesis Loss-of-function mutations.
  

External links

Nomenclature
HGNC (Hugo)SOCS1   19383
Cards
AtlasSOCS1ID42350ch16p13
Entrez_Gene (NCBI)SOCS1  8651  suppressor of cytokine signaling 1
GeneCards (Weizmann)SOCS1
Ensembl (Hinxton)ENSG00000185338 [Gene_View]  chr16:11348274-11350039 [Contig_View]  SOCS1 [Vega]
ICGC DataPortalENSG00000185338
cBioPortalSOCS1
AceView (NCBI)SOCS1
Genatlas (Paris)SOCS1
WikiGenes8651
SOURCE (Princeton)NM_003745
Genomic and cartography
GoldenPath (UCSC)SOCS1  -  16p13.13   chr16:11348274-11350039 -  16p13.13   [Description]    (hg19-Feb_2009)
EnsemblSOCS1 - 16p13.13 [CytoView]
Mapping of homologs : NCBISOCS1 [Mapview]
OMIM603597   
Gene and transcription
Genbank (Entrez)AB000676 AB000734 AB005043 AK127621 BC029307
RefSeq transcript (Entrez)NM_003745
RefSeq genomic (Entrez)AC_000148 NC_000016 NC_018927 NT_010393 NW_001838343 NW_004929400
Consensus coding sequences : CCDS (NCBI)SOCS1
Cluster EST : UnigeneHs.50640 [ NCBI ]
CGAP (NCI)Hs.50640
Alternative Splicing : Fast-db (Paris)GSHG0011626
Alternative Splicing GalleryENSG00000185338
Gene ExpressionSOCS1 [ NCBI-GEO ]     SOCS1 [ SEEK ]   SOCS1 [ MEM ]
Protein : pattern, domain, 3D structure
UniProt/SwissProtO15524 (Uniprot)
NextProtO15524  [Medical]
With graphics : InterProO15524
Splice isoforms : SwissVarO15524 (Swissvar)
Domaine pattern : Prosite (Expaxy)SH2 (PS50001)    SOCS (PS50225)   
Domains : Interpro (EBI)SH2 [organisation]   SOCS [organisation]   SOCS1 [organisation]   SOCS_C [organisation]  
Related proteins : CluSTrO15524
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 mutations8651
Blocks (Seattle)O15524
Human Protein AtlasENSG00000185338 [gene] [tissue] [antibody] [cell] [cancer]
Peptide AtlasO15524
HPRD04669
IPIIPI00021491   
Protein Interaction databases
DIP (DOE-UCLA)O15524
IntAct (EBI)O15524
FunCoupENSG00000185338
BioGRIDSOCS1
InParanoidO15524
Interologous Interaction database O15524
IntegromeDBSOCS1
STRING (EMBL)SOCS1
Ontologies - Pathways
Ontology : AmiGOregulation of protein phosphorylation  protein kinase inhibitor activity  insulin-like growth factor receptor binding  protein binding  nucleus  cytoplasm  cytosol  negative regulation of protein kinase activity  JAK-STAT cascade  cytoplasmic membrane-bounded vesicle  protein ubiquitination  kinase inhibitor activity  cytokine-mediated signaling pathway  cytokine-mediated signaling pathway  protein kinase binding  regulation of growth  negative regulation of tyrosine phosphorylation of Stat3 protein  fat cell differentiation  negative regulation of JAK-STAT cascade  negative regulation of JAK-STAT cascade  negative regulation of insulin receptor signaling pathway  interferon-gamma-mediated signaling pathway  regulation of interferon-gamma-mediated signaling pathway  type I interferon signaling pathway  regulation of type I interferon-mediated signaling pathway  JAK-STAT cascade involved in growth hormone signaling pathway  cellular response to amino acid stimulus  
Ontology : EGO-EBIregulation of protein phosphorylation  protein kinase inhibitor activity  insulin-like growth factor receptor binding  protein binding  nucleus  cytoplasm  cytosol  negative regulation of protein kinase activity  JAK-STAT cascade  cytoplasmic membrane-bounded vesicle  protein ubiquitination  kinase inhibitor activity  cytokine-mediated signaling pathway  cytokine-mediated signaling pathway  protein kinase binding  regulation of growth  negative regulation of tyrosine phosphorylation of Stat3 protein  fat cell differentiation  negative regulation of JAK-STAT cascade  negative regulation of JAK-STAT cascade  negative regulation of insulin receptor signaling pathway  interferon-gamma-mediated signaling pathway  regulation of interferon-gamma-mediated signaling pathway  type I interferon signaling pathway  regulation of type I interferon-mediated signaling pathway  JAK-STAT cascade involved in growth hormone signaling pathway  cellular response to amino acid stimulus  
Pathways : BIOCARTAGrowth Hormone Signaling Pathway [Genes]    IL-2 Receptor Beta Chain in T cell Activation [Genes]   
Pathways : KEGGUbiquitin mediated proteolysis    Osteoclast differentiation    Jak-STAT signaling pathway    Insulin signaling pathway    Prolactin signaling pathway    Type II diabetes mellitus    Toxoplasmosis    MicroRNAs in cancer   
Protein Interaction DatabaseSOCS1
Wikipedia pathwaysSOCS1
Gene fusion - rearrangments
Polymorphisms : SNP, mutations, diseases
SNP Single Nucleotide Polymorphism (NCBI)SOCS1
snp3D : Map Gene to Disease8651
SNP (GeneSNP Utah)SOCS1
SNP : HGBaseSOCS1
Genetic variants : HAPMAPSOCS1
Exome VariantSOCS1
1000_GenomesSOCS1 
ICGC programENSG00000185338 
Cancer Gene: CensusSOCS1 
Somatic Mutations in Cancer : COSMICSOCS1 
CONAN: Copy Number AnalysisSOCS1 
Mutations and Diseases : HGMDSOCS1
Mutations and Diseases : intOGenSOCS1
Genomic VariantsSOCS1  SOCS1 [DGVbeta]
dbVarSOCS1
ClinVarSOCS1
Pred. of missensesPolyPhen-2  SIFT(SG)  SIFT(JCVI)  Align-GVGD  MutAssessor  Mutanalyser  
Pred. splicesGeneSplicer  Human Splicing Finder  MaxEntScan  
Diseases
OMIM603597   
MedgenSOCS1
GENETestsSOCS1
Disease Genetic AssociationSOCS1
Huge Navigator SOCS1 [HugePedia]  SOCS1 [HugeCancerGEM]
General knowledge
Homologs : HomoloGeneSOCS1
Homology/Alignments : Family Browser (UCSC)SOCS1
Phylogenetic Trees/Animal Genes : TreeFamSOCS1
Chemical/Protein Interactions : CTD8651
Chemical/Pharm GKB GenePA134863068
Drug Sensitivity SOCS1
Clinical trialSOCS1
Cancer Resource (Charite)ENSG00000185338
Other databases
Other databaseHREF="http://www.biocarta.com/pathfiles/h_il2rbPathway.asp">BIOCARTA: IL-2 Receptor Beta Chain in T cell Activation
Probes
Litterature
PubMed258 Pubmed reference(s) in Entrez
CoreMineSOCS1
iHOPSOCS1
OncoSearchSOCS1

Bibliography

A novel cytokine-inducible gene CIS encodes an SH2-containing protein that binds to tyrosine-phosphorylated interleukin 3 and erythropoietin receptors.
Yoshimura A, Ohkubo T, Kiguchi T, Jenkins NA, Gilbert DJ, Copeland NG, Hara T, Miyajima A
The EMBO journal. 1995 ; 14 (12) : 2816-2826.
PMID 7796808
 
A new protein containing an SH2 domain that inhibits JAK kinases.
Endo TA, Masuhara M, Yokouchi M, Suzuki R, Sakamoto H, Mitsui K, Matsumoto A, Tanimura S, Ohtsubo M, Misawa H, Miyazaki T, Leonor N, Taniguchi T, Fujita T, Kanakura Y, Komiya S, Yoshimura A
Nature. 1997 ; 387 (6636) : 921-924.
PMID 9202126
 
SOCS-1/JAB/SSI-1 can bind to and suppress Tec protein-tyrosine kinase.
Ohya K, Kajigaya S, Yamashita Y, Miyazato A, Hatake K, Miura Y, Ikeda U, Shimada K, Ozawa K, Mano H
The Journal of biological chemistry. 1997 ; 272 (43) : 27178-27182.
PMID 9341160
 
A family of cytokine-inducible inhibitors of signalling.
Starr R, Willson TA, Viney EM, Murray LJ, Rayner JR, Jenkins BJ, Gonda TJ, Alexander WS, Metcalf D, Nicola NA, Hilton DJ
Nature. 1997 ; 387 (6636) : 917-921.
PMID 9202125
 
Twenty proteins containing a C-terminal SOCS box form five structural classes.
Hilton DJ, Richardson RT, Alexander WS, Viney EM, Willson TA, Sprigg NS, Starr R, Nicholson SE, Metcalf D, Nicola NA
Proceedings of the National Academy of Sciences of the United States of America. 1998 ; 95 (1) : 114-119.
PMID 9419338
 
A matrix associated region localizes the human SOCS-1 gene to chromosome 16p13.13.
Kramer JA, Adams MD, Singh GB, Doggett NA, Krawetz SA
Somatic cell and molecular genetics. 1998 ; 24 (2) : 131-133.
PMID 9919312
 
Liver degeneration and lymphoid deficiencies in mice lacking suppressor of cytokine signaling-1.
Starr R, Metcalf D, Elefanty AG, Brysha M, Willson TA, Nicola NA, Hilton DJ, Alexander WS
Proceedings of the National Academy of Sciences of the United States of America. 1998 ; 95 (24) : 14395-14399.
PMID 9826711
 
SOCS1 is a critical inhibitor of interferon gamma signaling and prevents the potentially fatal neonatal actions of this cytokine.
Alexander WS, Starr R, Fenner JE, Scott CL, Handman E, Sprigg NS, Corbin JE, Cornish AL, Darwiche R, Owczarek CM, Kay TW, Nicola NA, Hertzog PJ, Metcalf D, Hilton DJ
Cell. 1999 ; 98 (5) : 597-608.
PMID 10490099
 
SOCS1 deficiency causes a lymphocyte-dependent perinatal lethality.
Marine JC, Topham DJ, McKay C, Wang D, Parganas E, Stravopodis D, Yoshimura A, Ihle JN
Cell. 1999 ; 98 (5) : 609-616.
PMID 10490100
 
Inactivation of SSI-1, a JAK/STAT inhibitor, in human hepatocellular carcinomas, as revealed by two-dimensional electrophoresis.
Nagai H, Kim YS, Lee KT, Chu MY, Konishi N, Fujimoto J, Baba M, Matsubara K, Emi M
Journal of hepatology. 2001 ; 34 (3) : 416-421.
PMID 11322203
 
SOCS-1, a negative regulator of the JAK/STAT pathway, is silenced by methylation in human hepatocellular carcinoma and shows growth-suppression activity.
Yoshikawa H, Matsubara K, Qian GS, Jackson P, Groopman JD, Manning JE, Harris CC, Herman JG
Nature genetics. 2001 ; 28 (1) : 29-35.
PMID 11326271
 
Polycystic kidneys and chronic inflammatory lesions are the delayed consequences of loss of the suppressor of cytokine signaling-1 (SOCS-1).
Metcalf D, Mifsud S, Di Rago L, Nicola NA, Hilton DJ, Alexander WS
Proceedings of the National Academy of Sciences of the United States of America. 2002 ; 99 (2) : 943-948.
PMID 11782537
 
TRIM8/GERP RING finger protein interacts with SOCS-1.
Toniato E, Chen XP, Losman J, Flati V, Donahue L, Rothman P
The Journal of biological chemistry. 2002 ; 277 (40) : 37315-37322.
PMID 12163497
 
Integrated genomic and epigenomic analyses pinpoint biallelic gene inactivation in tumors.
Zardo G, Tiirikainen MI, Hong C, Misra A, Feuerstein BG, Volik S, Collins CC, Lamborn KR, Bollen A, Pinkel D, Albertson DG, Costello JF
Nature genetics. 2002 ; 32 (3) : 453-458.
PMID 12355068
 
Persistence of lesions in suppressor of cytokine signaling-1-deficient mice infected with Leishmania major.
Bullen DV, Baldwin TM, Curtis JM, Alexander WS, Handman E
Journal of immunology (Baltimore, Md. : 1950). 2003 ; 170 (8) : 4267-4272.
PMID 12682261
 
SOCS1 methylation in patients with newly diagnosed acute myeloid leukemia.
Chen CY, Tsay W, Tang JL, Shen HL, Lin SW, Huang SY, Yao M, Chen YC, Shen MC, Wang CH, Tien HF
Genes, chromosomes & cancer. 2003 ; 37 (3) : 300-305.
PMID 12759928
 
Aberrant methylation of suppressor of cytokine signalling-1 (SOCS-1) gene in pancreatic ductal neoplasms.
Fukushima N, Sato N, Sahin F, Su GH, Hruban RH, Goggins M
British journal of cancer. 2003 ; 89 (2) : 338-343.
PMID 12865927
 
SOCS-1, a negative regulator of cytokine signaling, is frequently silenced by methylation in multiple myeloma.
Galm O, Yoshikawa H, Esteller M, Osieka R, Herman JG
Blood. 2003 ; 101 (7) : 2784-2788.
PMID 12456503
 
Regulation of cytokine receptor signaling by SOCS1.
Ilangumaran S, Rottapel R
Immunological reviews. 2003 ; 192 : 196-211.
PMID 12670405
 
Epigenetic alteration of the SOCS1 gene in chronic myeloid leukaemia.
Liu TC, Lin SF, Chang JG, Yang MY, Hung SY, Chang CS
British journal of haematology. 2003 ; 123 (4) : 654-661.
PMID 14616969
 
Hypermethylation associated with inactivation of the SOCS-1 gene, a JAK/STAT inhibitor, in human hepatoblastomas.
Nagai H, Naka T, Terada Y, Komazaki T, Yabe A, Jin E, Kawanami O, Kishimoto T, Konishi N, Nakamura M, Kobayashi Y, Emi M
Journal of human genetics. 2003 ; 48 (2) : 65-69.
PMID 12601549
 
Methylation-mediated silencing of SOCS-1 gene in hepatocellular carcinoma derived from cirrhosis.
Okochi O, Hibi K, Sakai M, Inoue S, Takeda S, Kaneko T, Nakao A
Clinical cancer research : an official journal of the American Association for Cancer Research. 2003 ; 9 (14) : 5295-5298.
PMID 14614012
 
The suppressor of cytokine signaling-1 (SOCS1) is a novel therapeutic target for enterovirus-induced cardiac injury.
Yasukawa H, Yajima T, Duplain H, Iwatate M, Kido M, Hoshijima M, Weitzman MD, Nakamura T, Woodard S, Xiong D, Yoshimura A, Chien KR, Knowlton KU
The Journal of clinical investigation. 2003 ; 111 (4) : 469-478.
PMID 12588885
 
Aberrant methylation of SOCS-1 was observed in younger colorectal cancer patients.
Fujitake S, Hibi K, Okochi O, Kodera Y, Ito K, Akiyama S, Nakao A
Journal of gastroenterology. 2004 ; 39 (2) : 120-124.
PMID 15074307
 
Hypermethylation-associated inactivation of the SOCS-1 gene, a JAK/STAT inhibitor, in human pancreatic cancers.
Komazaki T, Nagai H, Emi M, Terada Y, Yabe A, Jin E, Kawanami O, Konishi N, Moriyama Y, Naka T, Kishimoto T
Japanese journal of clinical oncology. 2004 ; 34 (4) : 191-194.
PMID 15121754
 
Methylation status of suppressor of cytokine signaling-1 gene in hepatocellular carcinoma.
Miyoshi H, Fujie H, Moriya K, Shintani Y, Tsutsumi T, Makuuchi M, Kimura S, Koike K
Journal of gastroenterology. 2004 ; 39 (6) : 563-569.
PMID 15235874
 
Epigenetic inactivation of SOCS-1 by CpG island hypermethylation in human gastric carcinoma.
Oshimo Y, Kuraoka K, Nakayama H, Kitadai Y, Yoshida K, Chayama K, Yasui W
International journal of cancer. Journal international du cancer. 2004 ; 112 (6) : 1003-1009.
PMID 15386345
 
SOCS-1 localizes to the microtubule organizing complex-associated 20S proteasome.
Vuong BQ, Arenzana TL, Showalter BM, Losman J, Chen XP, Mostecki J, Banks AS, Limnander A, Fernandez N, Rothman PB
Molecular and cellular biology. 2004 ; 24 (20) : 9092-9101.
PMID 15456882
 
SOCS1 is a suppressor of liver fibrosis and hepatitis-induced carcinogenesis.
Yoshida T, Ogata H, Kamio M, Joo A, Shiraishi H, Tokunaga Y, Sata M, Nagai H, Yoshimura A
The Journal of experimental medicine. 2004 ; 199 (12) : 1701-1707.
PMID 15197228
 
Hypermethylation of the suppressor of cytokine signalling-1 (SOCS-1) in myelodysplastic syndrome.
Brakensiek K, Lˆ§nger F, Schlegelberger B, Kreipe H, Lehmann U
British journal of haematology. 2005 ; 130 (2) : 209-217.
PMID 16029449
 
Aberrant methylation of the negative regulators RASSFIA, SHP-1 and SOCS-1 in myelodysplastic syndromes and acute myeloid leukaemia.
Johan MF, Bowen DT, Frew ME, Goodeve AC, Reilly JT
British journal of haematology. 2005 ; 129 (1) : 60-65.
PMID 15801956
 
SOCS1 restricts dendritic cells' ability to break self tolerance and induce antitumor immunity by regulating IL-12 production and signaling.
Evel-Kabler K, Song XT, Aldrich M, Huang XF, Chen SY
The Journal of clinical investigation. 2006 ; 116 (1) : 90-100.
PMID 16357940
 
IFNgamma-dependent, spontaneous development of colorectal carcinomas in SOCS1-deficient mice.
Hanada T, Kobayashi T, Chinen T, Saeki K, Takaki H, Koga K, Minoda Y, Sanada T, Yoshioka T, Mimata H, Kato S, Yoshimura A
The Journal of experimental medicine. 2006 ; 203 (6) : 1391-1397.
PMID 16717119
 
SOCS1 inhibits tumor necrosis factor-induced activation of ASK1-JNK inflammatory signaling by mediating ASK1 degradation.
He Y, Zhang W, Zhang R, Zhang H, Min W
The Journal of biological chemistry. 2006 ; 281 (9) : 5559-5566.
PMID 16407264
 
Biallelic deletion within 16p13.13 including SOCS-1 in Karpas1106P mediastinal B-cell lymphoma line is associated with delayed degradation of JAK2 protein.
Melzner I, Weniger MA, Bucur AJ, Brˆºderlein S, Dorsch K, Hasel C, Leithˆ§user F, Ritz O, Dyer MJ, Barth TF, Mˆller P
International journal of cancer. Journal international du cancer. 2006 ; 118 (8) : 1941-1944.
PMID 16287070
 
Mutations of the tumor suppressor gene SOCS-1 in classical Hodgkin lymphoma are frequent and associated with nuclear phospho-STAT5 accumulation.
Weniger MA, Melzner I, Menz CK, Wegener S, Bucur AJ, Dorsch K, Mattfeldt T, Barth TF, Mˆller P
Oncogene. 2006 ; 25 (18) : 2679-2684.
PMID 16532038
 
Clinical implications of SOCS1 methylation in myelodysplastic syndrome.
Wu SJ, Yao M, Chou WC, Tang JL, Chen CY, Ko BS, Huang SY, Tsay W, Chen YC, Shen MC, Wang CH, Yeh YC, Tien HF
British journal of haematology. 2006 ; 135 (3) : 317-323.
PMID 16978223
 
The SOCS-1 gene methylation in chronic myeloid leukemia patients.
Hatirnaz O, Ure U, Ar C, Akyerli C, Soysal T, FerhanoŸülu B, Ozˆßelik T, Ozbek U
American journal of hematology. 2007 ; 82 (8) : 729-730.
PMID 17315216
 
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Contributor(s)

Written09-2007Liang-In Lin, Hwei-Fang Tien
Department of Clinical Laboratory Sciences and Medical Biotechnology, National Taiwan University, Taiwan (LIL); Department of Internal Medicine, National Taiwan University Hospital, No.7, Chung-Shan S. Road, Taipei, Taiwan (HFT)

Citation

This paper should be referenced as such :
Lin, LI ; Tien, HF
SOCS1 (suppressor of cytokine signaling 1)
Atlas Genet Cytogenet Oncol Haematol. 2008;12(2):156-158.
Free online version   Free pdf version   [Bibliographic record ]
URL : http://AtlasGeneticsOncology.org/Genes/SOCS1ID42350ch16p13.html

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indexed on : Tue Aug 26 15:29:02 CEST 2014

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