SOCS1 (Suppressor of cytokine signaling 1)
2007-09-01 Liang-In Lin , Hwei-Fang Tien AffiliationDepartment 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
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.
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.
Entity name
Note
Somatic origin.
Oncogenesis
Loss-of-function mutations.
Article Bibliography
| Pubmed ID | Last Year | Title | Authors |
|---|---|---|---|
| 10490099 | 1999 | SOCS1 is a critical inhibitor of interferon gamma signaling and prevents the potentially fatal neonatal actions of this cytokine. | Alexander WS et al |
| 16029449 | 2005 | Hypermethylation of the suppressor of cytokine signalling-1 (SOCS-1) in myelodysplastic syndrome. | Brakensiek K et al |
| 12682261 | 2003 | Persistence of lesions in suppressor of cytokine signaling-1-deficient mice infected with Leishmania major. | Bullen DV et al |
| 12759928 | 2003 | SOCS1 methylation in patients with newly diagnosed acute myeloid leukemia. | Chen CY et al |
| 9202126 | 1997 | A new protein containing an SH2 domain that inhibits JAK kinases. | Endo TA et al |
| 16357940 | 2006 | SOCS1 restricts dendritic cells' ability to break self tolerance and induce antitumor immunity by regulating IL-12 production and signaling. | Evel-Kabler K et al |
| 15074307 | 2004 | Aberrant methylation of SOCS-1 was observed in younger colorectal cancer patients. | Fujitake S et al |
| 12865927 | 2003 | Aberrant methylation of suppressor of cytokine signalling-1 (SOCS-1) gene in pancreatic ductal neoplasms. | Fukushima N et al |
| 12456503 | 2003 | SOCS-1, a negative regulator of cytokine signaling, is frequently silenced by methylation in multiple myeloma. | Galm O et al |
| 16717119 | 2006 | IFNgamma-dependent, spontaneous development of colorectal carcinomas in SOCS1-deficient mice. | Hanada T et al |
| 17315216 | 2007 | The SOCS-1 gene methylation in chronic myeloid leukemia patients. | Hatirnaz O et al |
| 16407264 | 2006 | SOCS1 inhibits tumor necrosis factor-induced activation of ASK1-JNK inflammatory signaling by mediating ASK1 degradation. | He Y et al |
| 9419338 | 1998 | Twenty proteins containing a C-terminal SOCS box form five structural classes. | Hilton DJ et al |
| 12670405 | 2003 | Regulation of cytokine receptor signaling by SOCS1. | Ilangumaran S et al |
| 15801956 | 2005 | Aberrant methylation of the negative regulators RASSFIA, SHP-1 and SOCS-1 in myelodysplastic syndromes and acute myeloid leukaemia. | Johan MF et al |
| 15121754 | 2004 | Hypermethylation-associated inactivation of the SOCS-1 gene, a JAK/STAT inhibitor, in human pancreatic cancers. | Komazaki T et al |
| 9919312 | 1998 | A matrix associated region localizes the human SOCS-1 gene to chromosome 16p13.13. | Kramer JA et al |
| 14616969 | 2003 | Epigenetic alteration of the SOCS1 gene in chronic myeloid leukaemia. | Liu TC et al |
| 10490100 | 1999 | SOCS1 deficiency causes a lymphocyte-dependent perinatal lethality. | Marine JC et al |
| 16287070 | 2006 | 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 et al |
| 11782537 | 2002 | Polycystic kidneys and chronic inflammatory lesions are the delayed consequences of loss of the suppressor of cytokine signaling-1 (SOCS-1). | Metcalf D et al |
| 15235874 | 2004 | Methylation status of suppressor of cytokine signaling-1 gene in hepatocellular carcinoma. | Miyoshi H et al |
| 11322203 | 2001 | Inactivation of SSI-1, a JAK/STAT inhibitor, in human hepatocellular carcinomas, as revealed by two-dimensional electrophoresis. | Nagai H et al |
| 12601549 | 2003 | Hypermethylation associated with inactivation of the SOCS-1 gene, a JAK/STAT inhibitor, in human hepatoblastomas. | Nagai H et al |
| 9341160 | 1997 | SOCS-1/JAB/SSI-1 can bind to and suppress Tec protein-tyrosine kinase. | Ohya Ki et al |
| 14614012 | 2003 | Methylation-mediated silencing of SOCS-1 gene in hepatocellular carcinoma derived from cirrhosis. | Okochi O et al |
| 15386345 | 2004 | Epigenetic inactivation of SOCS-1 by CpG island hypermethylation in human gastric carcinoma. | Oshimo Y et al |
| 9826711 | 1998 | Liver degeneration and lymphoid deficiencies in mice lacking suppressor of cytokine signaling-1. | Starr R et al |
| 9202125 | 1997 | A family of cytokine-inducible inhibitors of signalling. | Starr R et al |
| 12163497 | 2002 | TRIM8/GERP RING finger protein interacts with SOCS-1. | Toniato E et al |
| 15456882 | 2004 | SOCS-1 localizes to the microtubule organizing complex-associated 20S proteasome. | Vuong BQ et al |
| 16532038 | 2006 | Mutations of the tumor suppressor gene SOCS-1 in classical Hodgkin lymphoma are frequent and associated with nuclear phospho-STAT5 accumulation. | Weniger MA et al |
| 16978223 | 2006 | Clinical implications of SOCS1 methylation in myelodysplastic syndrome. | Wu SJ et al |
| 12588885 | 2003 | The suppressor of cytokine signaling-1 (SOCS1) is a novel therapeutic target for enterovirus-induced cardiac injury. | Yasukawa H et al |
| 15197228 | 2004 | SOCS1 is a suppressor of liver fibrosis and hepatitis-induced carcinogenesis. | Yoshida T et al |
| 11326271 | 2001 | 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 et al |
| 7796808 | 1995 | A novel cytokine-inducible gene CIS encodes an SH2-containing protein that binds to tyrosine-phosphorylated interleukin 3 and erythropoietin receptors. | Yoshimura A et al |
| 12355068 | 2002 | Integrated 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 ID | Transcript ID | Uniprot |
|---|---|---|
| ENSG00000185338 | ENST00000332029 | O15524 |
| ENSG00000185338 | ENST00000332029 | Q4JHT5 |
| ENSG00000185338 | ENST00000644787 | O15524 |
| ENSG00000185338 | ENST00000644787 | Q4JHT5 |
Expression (GTEx)
Pathways
Protein levels (Protein atlas)
References
| Pubmed ID | Year | Title | Citations |
|---|---|---|---|
| 38244240 | 2024 | EP300 improves endothelial injury and mitochondrial dysfunction in coronary artery disease by regulating histone acetylation of SOCS1 promoter via inhibiting JAK/STAT pathway. | 0 |
| 38436805 | 2024 | Downregulation of lncRNA CDKN2B-AS1 attenuates inflammatory response in mice with allergic rhinitis by regulating miR-98-5p/SOCS1 axis. | 0 |
| 38484644 | 2024 | IL-13 facilitates ferroptotic death in asthmatic epithelial cells via SOCS1-mediated ubiquitinated degradation of SLC7A11. | 0 |
| 38774752 | 2024 | The Role of JAK-STAT-SOCS1 Axis in Tumorigenesis, Malignant Progression and Lymphatic Metastasis of Penile Cancer. | 0 |
| 38874740 | 2024 | Unmasking early colorectal cancer clues: in silico and in vitro investigation of downregulated IGF2, SOCS1, MLH1, and CACNA1G in SSA polyps. | 0 |
| 38244240 | 2024 | EP300 improves endothelial injury and mitochondrial dysfunction in coronary artery disease by regulating histone acetylation of SOCS1 promoter via inhibiting JAK/STAT pathway. | 0 |
| 38436805 | 2024 | Downregulation of lncRNA CDKN2B-AS1 attenuates inflammatory response in mice with allergic rhinitis by regulating miR-98-5p/SOCS1 axis. | 0 |
| 38484644 | 2024 | IL-13 facilitates ferroptotic death in asthmatic epithelial cells via SOCS1-mediated ubiquitinated degradation of SLC7A11. | 0 |
| 38774752 | 2024 | The Role of JAK-STAT-SOCS1 Axis in Tumorigenesis, Malignant Progression and Lymphatic Metastasis of Penile Cancer. | 0 |
| 38874740 | 2024 | Unmasking early colorectal cancer clues: in silico and in vitro investigation of downregulated IGF2, SOCS1, MLH1, and CACNA1G in SSA polyps. | 0 |
| 35593996 | 2023 | Quantitative detection of methylated SOCS-1 in schizophrenia and bipolar disorder considering SOCS-1 -1478CA/del polymorphism and clinical parameters. | 1 |
| 36064035 | 2023 | MicroRNA-29b regulates pyroptosis involving calcific aortic valve disease through the STAT3/SOCS1 pathway. | 3 |
| 36448222 | 2023 | The suppressor of cytokine signaling-1 (SOCS1) gene polymorphism and promoter methylation correlate with the course of COVID-19. | 1 |
| 36546418 | 2023 | Growth hormone inhibits the JAK/STAT3 pathway by regulating SOCS1 in endometrial cells in vitro: a clue to enhance endometrial receptivity in recurrent implantation failure. | 2 |
| 36609306 | 2023 | Alterations of SOCS1 and SOCS3 transcript levels, but not promoter methylation levels in subcutaneous adipose tissues in obese women. | 1 |
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
