SOCS1 (Suppressor of cytokine signaling 1)

Identity

Other names	JAB (JAK binding protein)
	CIS1 (cytokine-inducible SH2 protein 1)
	SSI1 (STAT-induced STAT inhibitor)
	TIP3 (Tec-interacting protein 3)
	CISH1
	SSI-1
HGNC	SOCS1
Location	16p13.13

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, NOTE Somatic origin.
Oncogenesis	Loss-of-function mutations.

External links

	Nomenclature
HGNC	SOCS1   19383
Entrez_Gene	SOCS1  8651  suppressor of cytokine signaling 1
	Cards
Atlas	SOCS1ID42350ch16p13
GeneCards	SOCS1
Ensembl	SOCS1 [Search_View]   ENSG00000185338 [Gene_View]
Genatlas	SOCS1
GeneLynx	SOCS1
eGenome	SOCS1
euGene	8651
	Genomic and cartography
GoldenPath	SOCS1  -  16p13.13   chr16:11255775-11257540 -  16p13.13   [Description]    (hg18-Mar_2006)
Ensembl	SOCS1 - 16p13.13 [CytoView]
NCBI	Mapview
OMIM	Disease map [OMIM]
HomoloGene	SOCS1
	Gene and transcription
Genbank	AB000676 [ ENTREZ ]
Genbank	AB000734 [ ENTREZ ]
Genbank	AB005043 [ ENTREZ ]
Genbank	AK127621 [ ENTREZ ]
Genbank	BC029307 [ ENTREZ ]
RefSeq	NM_003745 [ SRS ]    NM_003745 [ ENTREZ ]
RefSeq	AC_000059 [ SRS ]    AC_000059 [ ENTREZ ]
RefSeq	AC_000148 [ SRS ]    AC_000148 [ ENTREZ ]
RefSeq	NC_000016 [ SRS ]    NC_000016 [ ENTREZ ]
RefSeq	NT_010393 [ SRS ]    NT_010393 [ ENTREZ ]
RefSeq	NW_001838343 [ SRS ]    NW_001838343 [ ENTREZ ]
RefSeq	NW_926018 [ SRS ]    NW_926018 [ ENTREZ ]
AceView	SOCS1 AceView - NCBI
Unigene	Hs.50640 [ SRS ]    Hs.50640 [ NCBI ]     HS50640 [ spliceNest ]
Fast-db	3574 (alternative variants)
	Protein : pattern, domain, 3D structure
SwissProt	O15524 [ SRS]    O15524 [ EXPASY ]     O15524 [ INTERPRO ]     O15524 [ UNIPROT ]
Prosite	PS50001 SH2 [ SRS ]    PS50001 SH2 [ Expasy ]
Prosite	PS50225 SOCS [ SRS ]    PS50225 SOCS [ Expasy ]
Interpro	IPR000980 SH2 [ SRS ]    IPR000980 SH2 [ EBI ]
Interpro	IPR001496 SOCS_C [ SRS ]    IPR001496 SOCS_C [ EBI ]
CluSTr	O15524
Pfam	PF00017 SH2 [ SRS ]    PF00017 SH2 [ Sanger ]    pfam00017 [ NCBI-CDD ]
Pfam	PF07525 SOCS_box [ SRS ]    PF07525 SOCS_box [ Sanger ]    pfam07525 [ NCBI-CDD ]
Smart	SM00252 SH2 [EMBL]
Smart	SM00253 SOCS [EMBL]
Prodom	PD000093 SH2[INRA-Toulouse]
Prodom	O15524 SOCS1_HUMAN [ Domain structure ]   O15524 SOCS1_HUMAN  [ sequences sharing at least 1 domain ]
Blocks	O15524
HPRD	04669
	Protein Interaction databases
DIP	O15524
IntAct	O15524
	Polymorphism : SNP, mutations, diseases
OMIM	603597    [ map ]
GENECLINICS	603597
SNP	SOCS1 [dbSNP-NCBI]
SNP	NM_003745 [SNP-NCI]
SNP	SOCS1 [GeneSNPs - Utah]  SOCS1] [HGBASE - SRS]
HAPMAP	SOCS1 [HAPMAP]
COSMIC	SOCS1 [Somatic mutation (COSMIC-CGP-Sanger)]
HGMD	SOCS1
	General knowledge
Family Browser	SOCS1 [UCSC Family Browser]
SOURCE	NM_003745
SMD	Hs.50640
SAGE	Hs.50640
GO	regulation of cell growth [Amigo]  regulation of cell growth
GO	regulation of protein amino acid phosphorylation [Amigo]  regulation of protein amino acid phosphorylation
GO	protein kinase inhibitor activity [Amigo]  protein kinase inhibitor activity
GO	insulin-like growth factor receptor binding [Amigo]  insulin-like growth factor receptor binding
GO	protein binding [Amigo]  protein binding
GO	cytoplasm [Amigo]  cytoplasm
GO	intracellular signaling cascade [Amigo]  intracellular signaling cascade
GO	cytokine and chemokine mediated signaling pathway [Amigo]  cytokine and chemokine mediated signaling pathway
GO	protein kinase binding [Amigo]  protein kinase binding
GO	negative regulation of tyrosine phosphorylation of Stat3 protein [Amigo]  negative regulation of tyrosine phosphorylation of Stat3 protein
GO	fat cell differentiation [Amigo]  fat cell differentiation
GO	negative regulation of JAK-STAT cascade [Amigo]  negative regulation of JAK-STAT cascade
GO	negative regulation of JAK-STAT cascade [Amigo]  negative regulation of JAK-STAT cascade
GO	negative regulation of insulin receptor signaling pathway [Amigo]  negative regulation of insulin receptor signaling pathway
KEGG	Jak-STAT signaling pathway
KEGG	Insulin signaling pathway
KEGG	Type II diabetes mellitus
PubGene	SOCS1
TreeFam	SOCS1
CTD	8651 [Comparative ToxicoGenomics Database]
	Other databases
Other database	HREF="http://www.biocarta.com/pathfiles/h_il2rbPathway.asp">BIOCARTA: IL-2 Receptor Beta Chain in T cell Activation
	Probes
Probe	SOCS1 Related clones (RZPD - Berlin)
	PubMed
PubMed	96 Pubmed reference(s) in LocusLink

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)

Written	09-2007	Liang-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. September 2007 . URL : http://AtlasGeneticsOncology.org/Genes/SOCS1ID42350ch16p13.html

© Atlas of Genetics and Cytogenetics in Oncology and Haematology

indexed on : Mon Aug 11 21:17:37 2008