SOCS1 (Suppressor of cytokine signaling 1)

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

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

SOCS1

LOCATION

16p13.13

LOCUSID

8651

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.

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

Hodgkin lymphoma, primary mediastinal B-cell lymphoma

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)

Adipose - Subcutaneous

Adipose - Visceral

Adrenal Gland

Artery - Aorta

Artery - Tibial

Bladder

Brain - Amygdala

Brain - Anterior cingulate cortex

Brain - Caudate

Brain - Cerebellar Hemisphere

Brain - Cerebellum

Brain - Cortex

Brain - Frontal Cortex

Brain - Hippocampus

Brain - Hypothalamus

Brain - Nucleus accumbens

Brain - Putamen

Brain - Spinal cord

Brain - Substantia nigra

Breast - Mammary Tissue

Cells - Cultured fibroblasts

Cells - EBV - transformed lymphocytes

Cervix - Ectocervix

Cervix - Endocervix

Colon - Sigmoid

Colon - Transverse

Esophagus - Gastroesophageal Junction

Esophagus - Mucosa

Esophagus - Muscularis

Fallopian Tube

Heart - Atrial Appendage

Heart - Left Ventricle

Kidney - Cortex

Kidney - Medulla

Liver

Lung

Minor Salivary Gland

Muscle - Skeletal

Nerve - Tibial

Ovary

Pancreas

Pituitary

Prostate

Skin - Not Sun Exposed

Skin - Sun Exposed

Small Intestine - Terminal Ileum

Spleen

Stomach

Testis

Thyroid

Uterus

Vagina

Whole Blood

Pathways

Pathway	Source	External ID
Ubiquitin mediated proteolysis	KEGG	ko04120
Jak-STAT signaling pathway	KEGG	ko04630
Insulin signaling pathway	KEGG	ko04910
Type II diabetes mellitus	KEGG	ko04930
Ubiquitin mediated proteolysis	KEGG	hsa04120
Jak-STAT signaling pathway	KEGG	hsa04630
Insulin signaling pathway	KEGG	hsa04910
Type II diabetes mellitus	KEGG	hsa04930
Toxoplasmosis	KEGG	ko05145
Toxoplasmosis	KEGG	hsa05145
Osteoclast differentiation	KEGG	ko04380
Osteoclast differentiation	KEGG	hsa04380
ECS complex	KEGG	hsa_M00388
ECS complex	KEGG	M00388
Prolactin signaling pathway	KEGG	hsa04917
Prolactin signaling pathway	KEGG	ko04917
MicroRNAs in cancer	KEGG	hsa05206
MicroRNAs in cancer	KEGG	ko05206
JAK-STAT signaling	KEGG	hsa_M00684
JAK-STAT signaling	KEGG	M00684
Immune System	REACTOME	R-HSA-168256
Adaptive Immune System	REACTOME	R-HSA-1280218
Class I MHC mediated antigen processing & presentation	REACTOME	R-HSA-983169
Antigen processing: Ubiquitination & Proteasome degradation	REACTOME	R-HSA-983168
Innate Immune System	REACTOME	R-HSA-168249
Toll-Like Receptors Cascades	REACTOME	R-HSA-168898
Toll Like Receptor 4 (TLR4) Cascade	REACTOME	R-HSA-166016
Activated TLR4 signalling	REACTOME	R-HSA-166054
MyD88:Mal cascade initiated on plasma membrane	REACTOME	R-HSA-166058
Toll Like Receptor 2 (TLR2) Cascade	REACTOME	R-HSA-181438
Toll Like Receptor TLR1:TLR2 Cascade	REACTOME	R-HSA-168179
Toll Like Receptor TLR6:TLR2 Cascade	REACTOME	R-HSA-168188
Cytokine Signaling in Immune system	REACTOME	R-HSA-1280215
Interferon Signaling	REACTOME	R-HSA-913531
Interferon alpha/beta signaling	REACTOME	R-HSA-909733
Regulation of IFNA signaling	REACTOME	R-HSA-912694
Interferon gamma signaling	REACTOME	R-HSA-877300
Regulation of IFNG signaling	REACTOME	R-HSA-877312
Signaling by Interleukins	REACTOME	R-HSA-449147
Growth hormone receptor signaling	REACTOME	R-HSA-982772
Signal Transduction	REACTOME	R-HSA-162582
Signaling by SCF-KIT	REACTOME	R-HSA-1433557
Regulation of KIT signaling	REACTOME	R-HSA-1433559
Interleukin-4 and 13 signaling	REACTOME	R-HSA-6785807

Protein levels (Protein atlas)

Not detected

Low

Medium

High

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/socs1-(suppressor-of-cytokine-signaling-1)