SOCS1 (Suppressor of cytokine signaling 1)

2007-09-01   Liang-In Lin , Hwei-Fang Tien 

Department of Clinical Laboratory Sciences, Medical Biotechnology, National Taiwan University, Taiwan (LIL); Department of Internal Medicine, National Taiwan University Hospital, No.7, Chung-Shan S. Road, Taipei, Taiwan (HFT)

Identity

HGNC
LOCATION
16p13.13
LOCUSID
ALIAS
CIS1,CISH1,JAB,SOCS-1,SSI-1,SSI1,TIP-3,TIP3

DNA/RNA

Atlas Image
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 5untranslated region. The exon 2 contains part of 5untranslated region, the translation initiation ATG, the stop codon, and the 3untranslated 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.

Proteins

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 name
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.
Note
Somatic origin.
Oncogenesis
Loss-of-function mutations.

Bibliography

Pubmed IDLast YearTitleAuthors
104900991999SOCS1 is a critical inhibitor of interferon gamma signaling and prevents the potentially fatal neonatal actions of this cytokine.Alexander WS et al
160294492005Hypermethylation of the suppressor of cytokine signalling-1 (SOCS-1) in myelodysplastic syndrome.Brakensiek K et al
126822612003Persistence of lesions in suppressor of cytokine signaling-1-deficient mice infected with Leishmania major.Bullen DV et al
127599282003SOCS1 methylation in patients with newly diagnosed acute myeloid leukemia.Chen CY et al
92021261997A new protein containing an SH2 domain that inhibits JAK kinases.Endo TA et al
163579402006SOCS1 restricts dendritic cells' ability to break self tolerance and induce antitumor immunity by regulating IL-12 production and signaling.Evel-Kabler K et al
150743072004Aberrant methylation of SOCS-1 was observed in younger colorectal cancer patients.Fujitake S et al
128659272003Aberrant methylation of suppressor of cytokine signalling-1 (SOCS-1) gene in pancreatic ductal neoplasms.Fukushima N et al
124565032003SOCS-1, a negative regulator of cytokine signaling, is frequently silenced by methylation in multiple myeloma.Galm O et al
167171192006IFNgamma-dependent, spontaneous development of colorectal carcinomas in SOCS1-deficient mice.Hanada T et al
173152162007The SOCS-1 gene methylation in chronic myeloid leukemia patients.Hatirnaz O et al
164072642006SOCS1 inhibits tumor necrosis factor-induced activation of ASK1-JNK inflammatory signaling by mediating ASK1 degradation.He Y et al
94193381998Twenty proteins containing a C-terminal SOCS box form five structural classes.Hilton DJ et al
126704052003Regulation of cytokine receptor signaling by SOCS1.Ilangumaran S et al
158019562005Aberrant methylation of the negative regulators RASSFIA, SHP-1 and SOCS-1 in myelodysplastic syndromes and acute myeloid leukaemia.Johan MF et al
151217542004Hypermethylation-associated inactivation of the SOCS-1 gene, a JAK/STAT inhibitor, in human pancreatic cancers.Komazaki T et al
99193121998A matrix associated region localizes the human SOCS-1 gene to chromosome 16p13.13.Kramer JA et al
146169692003Epigenetic alteration of the SOCS1 gene in chronic myeloid leukaemia.Liu TC et al
104901001999SOCS1 deficiency causes a lymphocyte-dependent perinatal lethality.Marine JC et al
162870702006Biallelic deletion within 16p13.13 including SOCS-1 in Karpas1106P mediastinal B-cell lymphoma line is associated with delayed degradation of JAK2 protein.Melzner I et al
117825372002Polycystic kidneys and chronic inflammatory lesions are the delayed consequences of loss of the suppressor of cytokine signaling-1 (SOCS-1).Metcalf D et al
152358742004Methylation status of suppressor of cytokine signaling-1 gene in hepatocellular carcinoma.Miyoshi H et al
113222032001Inactivation of SSI-1, a JAK/STAT inhibitor, in human hepatocellular carcinomas, as revealed by two-dimensional electrophoresis.Nagai H et al
126015492003Hypermethylation associated with inactivation of the SOCS-1 gene, a JAK/STAT inhibitor, in human hepatoblastomas.Nagai H et al
93411601997SOCS-1/JAB/SSI-1 can bind to and suppress Tec protein-tyrosine kinase.Ohya Ki et al
146140122003Methylation-mediated silencing of SOCS-1 gene in hepatocellular carcinoma derived from cirrhosis.Okochi O et al
153863452004Epigenetic inactivation of SOCS-1 by CpG island hypermethylation in human gastric carcinoma.Oshimo Y et al
98267111998Liver degeneration and lymphoid deficiencies in mice lacking suppressor of cytokine signaling-1.Starr R et al
92021251997A family of cytokine-inducible inhibitors of signalling.Starr R et al
121634972002TRIM8/GERP RING finger protein interacts with SOCS-1.Toniato E et al
154568822004SOCS-1 localizes to the microtubule organizing complex-associated 20S proteasome.Vuong BQ et al
165320382006Mutations of the tumor suppressor gene SOCS-1 in classical Hodgkin lymphoma are frequent and associated with nuclear phospho-STAT5 accumulation.Weniger MA et al
169782232006Clinical implications of SOCS1 methylation in myelodysplastic syndrome.Wu SJ et al
125888852003The suppressor of cytokine signaling-1 (SOCS1) is a novel therapeutic target for enterovirus-induced cardiac injury.Yasukawa H et al
151972282004SOCS1 is a suppressor of liver fibrosis and hepatitis-induced carcinogenesis.Yoshida T et al
113262712001SOCS-1, a negative regulator of the JAK/STAT pathway, is silenced by methylation in human hepatocellular carcinoma and shows growth-suppression activity.Yoshikawa H et al
77968081995A novel cytokine-inducible gene CIS encodes an SH2-containing protein that binds to tyrosine-phosphorylated interleukin 3 and erythropoietin receptors.Yoshimura A et al
123550682002Integrated genomic and epigenomic analyses pinpoint biallelic gene inactivation in tumors.Zardo G et al

Other Information

Locus ID:

NCBI: 8651
MIM: 603597
HGNC: 19383
Ensembl: ENSG00000185338

Variants:

dbSNP: 8651
ClinVar: 8651
TCGA: ENSG00000185338
COSMIC: SOCS1

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000185338ENST00000332029O15524
ENSG00000185338ENST00000332029Q4JHT5
ENSG00000185338ENST00000644787O15524
ENSG00000185338ENST00000644787Q4JHT5

Expression (GTEx)

0
10
20
30
40
50
60

Pathways

PathwaySourceExternal ID
Ubiquitin mediated proteolysisKEGGko04120
Jak-STAT signaling pathwayKEGGko04630
Insulin signaling pathwayKEGGko04910
Type II diabetes mellitusKEGGko04930
Ubiquitin mediated proteolysisKEGGhsa04120
Jak-STAT signaling pathwayKEGGhsa04630
Insulin signaling pathwayKEGGhsa04910
Type II diabetes mellitusKEGGhsa04930
ToxoplasmosisKEGGko05145
ToxoplasmosisKEGGhsa05145
Osteoclast differentiationKEGGko04380
Osteoclast differentiationKEGGhsa04380
ECS complexKEGGhsa_M00388
ECS complexKEGGM00388
Prolactin signaling pathwayKEGGhsa04917
Prolactin signaling pathwayKEGGko04917
MicroRNAs in cancerKEGGhsa05206
MicroRNAs in cancerKEGGko05206
JAK-STAT signalingKEGGhsa_M00684
JAK-STAT signalingKEGGM00684
Immune SystemREACTOMER-HSA-168256
Adaptive Immune SystemREACTOMER-HSA-1280218
Class I MHC mediated antigen processing & presentationREACTOMER-HSA-983169
Antigen processing: Ubiquitination & Proteasome degradationREACTOMER-HSA-983168
Innate Immune SystemREACTOMER-HSA-168249
Toll-Like Receptors CascadesREACTOMER-HSA-168898
Toll Like Receptor 4 (TLR4) CascadeREACTOMER-HSA-166016
Activated TLR4 signallingREACTOMER-HSA-166054
MyD88:Mal cascade initiated on plasma membraneREACTOMER-HSA-166058
Toll Like Receptor 2 (TLR2) CascadeREACTOMER-HSA-181438
Toll Like Receptor TLR1:TLR2 CascadeREACTOMER-HSA-168179
Toll Like Receptor TLR6:TLR2 CascadeREACTOMER-HSA-168188
Cytokine Signaling in Immune systemREACTOMER-HSA-1280215
Interferon SignalingREACTOMER-HSA-913531
Interferon alpha/beta signalingREACTOMER-HSA-909733
Regulation of IFNA signalingREACTOMER-HSA-912694
Interferon gamma signalingREACTOMER-HSA-877300
Regulation of IFNG signalingREACTOMER-HSA-877312
Signaling by InterleukinsREACTOMER-HSA-449147
Growth hormone receptor signalingREACTOMER-HSA-982772
Signal TransductionREACTOMER-HSA-162582
Signaling by SCF-KITREACTOMER-HSA-1433557
Regulation of KIT signalingREACTOMER-HSA-1433559
Interleukin-4 and 13 signalingREACTOMER-HSA-6785807

Protein levels (Protein atlas)

Not detected
Low
Medium
High

References

Pubmed IDYearTitleCitations
203541882010MicroRNA-155 functions as an OncomiR in breast cancer by targeting the suppressor of cytokine signaling 1 gene.232
213550952011miR-221 and miR-155 regulate human dendritic cell development, apoptosis, and IL-12 production through targeting of p27kip1, KPC1, and SOCS-1.100
199131212009Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip.85
153618432004Differential hypermethylation of SOCS genes in ovarian and breast carcinomas.78
165320382006Mutations of the tumor suppressor gene SOCS-1 in classical Hodgkin lymphoma are frequent and associated with nuclear phospho-STAT5 accumulation.78
192400612009Coeliac disease-associated risk variants in TNFAIP3 and REL implicate altered NF-kappaB signalling.75
182504072008Cutting edge: innate immune response triggered by influenza A virus is negatively regulated by SOCS1 and SOCS3 through a RIG-I/IFNAR1-dependent pathway.72
124565032003SOCS-1, a negative regulator of cytokine signaling, is frequently silenced by methylation in multiple myeloma.71
198465292010Interaction between Ebola virus glycoprotein and host toll-like receptor 4 leads to induction of proinflammatory cytokines and SOCS1.67
149760492004SOCS1 and SHP1 hypermethylation in multiple myeloma: implications for epigenetic activation of the Jak/STAT pathway.60

Citation

Liang-In Lin ; Hwei-Fang Tien

SOCS1 (Suppressor of cytokine signaling 1)

Atlas Genet Cytogenet Oncol Haematol. 2007-09-01

Online version: http://atlasgeneticsoncology.org/gene/42350/socs1-(suppressor-of-cytokine-signaling-1)