SOCS3 (suppressor of cytokine signaling 3)
2012-02-01 Zoran Culig AffiliationExperimental Urology, Department of Urology, Innsbruck Medical University, Anichstrasse 35, A-6020 Innsbruck, Austria
Identity
HGNC
LOCATION
17q25.3
LOCUSID
ALIAS
ATOD4,CIS3,Cish3,MGC71791,SOCS-3,SSI-3,SSI3
FUSION GENES
DNA/RNA
Description
Size: 3300 bases.
Transcription
2 introns. Transcription generates 3 different mRNAs, 2 spliced variants and 1 unspliced form.
Proteins
KIR = kinase inhibitory region.
Description
225 amino acids, 24770 Da.
Expression
Widely expressed in normal and tumor tissues. Expression in tumors is variable due to its different functions.
Localisation
Cytoplasm.
Function
SOCS is a negative regulator of cytokines that signal through the JAK/STAT pathway. It binds to tyrosine kinase receptors such as gp130 subunit of receptors. It interacts with cytokine receptors or JAK kinases and interaction with growth factor receptors (insulin-like growth factor-I, insulin, fibroblast growth factor). It inhibits JAK2 kinase activity. Part of the ubiquitin-protein ligase complex which contains elongin, RNF7, and CUL5. Binding to leptin. Tumor promoting or tumor suppressive functions. Antagonizing cAMP-antiproliferative effects. SOCS3 suppresses erythropoietin in fetal liver and IL-6 signaling in vivo.
Mutations
Note
Mutations not detected.
Implicated in
Entity name
Lung cancer
Note
SOCS-3 acts as a tumor suppressor and is frequently lost in the disease. Its transient transfection in lung cancer cell lines leads to a decrease in proliferation.
Entity name
Liver cancer
Note
SOCS-3 is silenced by methylation. SOCS-3 is a tumor suppressor in this malignancy. It is implicated in regulation of migration of cancer cells. SOCS-3 deletion enhances JAK/STAT and FAK signaling.
Entity name
Barrets adenocarcinoma
Note
SOCS-3 is methylated. It is considered as a tumor suppressor.
Entity name
Glioblastoma multiforme
Note
SOCS-3 expression is lost through promoter methylation.
Entity name
Head and neck squamous cell cancer
Note
SOCS-3 is frequently down-regulated as a result of promoter methylation. It causes a growth inhibition.
Entity name
Hematological malignancies
Note
SOCS-3 inhibits megakaryocytic growth, overexpression of SOCS-3 is associated with a decreased survival of patients with follicular lymphoma.
Entity name
Melanoma
Note
SOCS-3 is a tumor promoter in melanoma and is constitutively expressed in several cell lines.
Entity name
Prostate cancer
Note
SOCS-3 stimulates proliferation and inhibits apoptosis in prostate cancer cells which do not express the androgen receptor. It may also antagonize the effects of fibroblasts growth factor and mitogen-activated protein kinases. In androgen-sensitive prostate cancer cells, SOCS-3 is induced by androgen and may inhibit androgen-stimulated proliferation and secretion.
Entity name
Diabetes
Note
SOCS-3 may antagonize function of insulin-like growth factors.
Entity name
Various cancers
Prognosis
Loss of protein expression and promoter hypermethylation occur in lung, liver cancer, head and neck squamous cell cancer. Overexpression occurs in melanoma and prostate cancer.
Article Bibliography
| Pubmed ID | Last Year | Title | Authors |
|---|---|---|---|
| 17148681 | 2006 | Suppressor of cytokine signaling-3 antagonizes cAMP effects on proliferation and apoptosis and is expressed in human prostate cancer. | Bellezza I et al |
| 11159537 | 2001 | STAT3-mediated constitutive expression of SOCS-3 in cutaneous T-cell lymphoma. | Brender C et al |
| 18318760 | 2008 | Epigenetic inactivation of suppressors of cytokine signalling in Philadelphia-negative chronic myeloproliferative disorders. | Capello D et al |
| 14617776 | 2003 | SOCS-3 is frequently silenced by hypermethylation and suppresses cell growth in human lung cancer. | He B et al |
| 17374732 | 2007 | Constitutive suppressor of cytokine signaling 3 expression confers a growth advantage to a human melanoma cell line. | Komyod W et al |
| 18770864 | 2008 | Prognostic relevance of SOCS3 hypermethylation in patients with glioblastoma multiforme. | Martini M et al |
| 16007195 | 2005 | Methylation silencing of SOCS-3 promotes cell growth and migration by enhancing JAK/STAT and FAK signalings in human hepatocellular carcinoma. | Niwa Y et al |
| 17513737 | 2007 | Type 2 diabetes impairs insulin receptor substrate-2-mediated phosphatidylinositol 3-kinase activity in primary macrophages to induce a state of cytokine resistance to IL-4 in association with overexpression of suppressor of cytokine signaling-3. | O'Connor JC et al |
| 19738059 | 2009 | Down-regulation of suppressor of cytokine signaling-3 causes prostate cancer cell death through activation of the extrinsic and intrinsic apoptosis pathways. | Puhr M et al |
| 16007169 | 2005 | SOCS-3 is frequently methylated in head and neck squamous cell carcinoma and its precursor lesions and causes growth inhibition. | Weber A et al |
Other Information
Locus ID:
NCBI: 9021
MIM: 604176
HGNC: 19391
Ensembl: ENSG00000184557
Variants:
dbSNP: 9021
ClinVar: 9021
TCGA: ENSG00000184557
COSMIC: SOCS3
RNA/Proteins
| Gene ID | Transcript ID | Uniprot |
|---|---|---|
| ENSG00000184557 | ENST00000330871 | O14543 |
| ENSG00000184557 | ENST00000330871 | Q6FI39 |
| ENSG00000184557 | ENST00000587578 | K7EIF6 |
Expression (GTEx)
Pathways
Protein levels (Protein atlas)
PharmGKB
| Entity ID | Name | Type | Evidence | Association | PK | PD | PMIDs |
|---|---|---|---|---|---|---|---|
| PA36184 | STAT2 | Gene | Pathway | associated | 26111151 |
References
| Pubmed ID | Year | Title | Citations |
|---|---|---|---|
| 37910276 | 2024 | E3 ligase SOCS3 regulates NOD2 expression by ubiquitin proteasome system in lung cancer progression. | 0 |
| 37950514 | 2024 | DNMTs-mediated SOCS3 methylation promotes the occurrence and development of AML. | 0 |
| 38229336 | 2024 | SOCS3, Transcriptionally Activated by NR4A1, Induces Apoptosis and Extracellular Matrix Degradation of Vaginal Fibroblasts in Pelvic Organ Prolapse. | 0 |
| 38533493 | 2024 | Suppressor of cytokine signaling-3 expression and its regulation in relation to inflammation in Chronic Obstructive Pulmonary Disease. | 0 |
| 38637274 | 2024 | Exploring the clinical and cellular mechanisms of LncRNA-KCNQ1OT1/miR-29a-3p/SOCS3 molecular axis in cases of unexplained recurrent spontaneous abortion. | 0 |
| 37910276 | 2024 | E3 ligase SOCS3 regulates NOD2 expression by ubiquitin proteasome system in lung cancer progression. | 0 |
| 37950514 | 2024 | DNMTs-mediated SOCS3 methylation promotes the occurrence and development of AML. | 0 |
| 38229336 | 2024 | SOCS3, Transcriptionally Activated by NR4A1, Induces Apoptosis and Extracellular Matrix Degradation of Vaginal Fibroblasts in Pelvic Organ Prolapse. | 0 |
| 38533493 | 2024 | Suppressor of cytokine signaling-3 expression and its regulation in relation to inflammation in Chronic Obstructive Pulmonary Disease. | 0 |
| 38637274 | 2024 | Exploring the clinical and cellular mechanisms of LncRNA-KCNQ1OT1/miR-29a-3p/SOCS3 molecular axis in cases of unexplained recurrent spontaneous abortion. | 0 |
| 35226171 | 2023 | Tissue levels of suppressor of cytokine signaling-3 (SOCS-3) in mycosis fungoides. | 0 |
| 35366780 | 2023 | The Relationship Between FoxP3 and SOCs3 Gene Expressions and Disease Activity in Rheumatoid Arthritis. | 1 |
| 35731142 | 2023 | Upregulated expression of FFAR2 and SOC3 genes is associated with gout. | 0 |
| 36484970 | 2023 | Oncogenic role of microRNA-19b-3p-mediated SOCS3 in glioma through activation of JAK-STAT pathway. | 2 |
| 36538174 | 2023 | Obesity is associated with IL-6 gene polymorphisms rs1800795 and rs1800796 but not SOCS3 rs4969170. | 1 |
Citation
Zoran Culig
SOCS3 (suppressor of cytokine signaling 3)
Atlas Genet Cytogenet Oncol Haematol. 2012-02-01
Online version: http://atlasgeneticsoncology.org/gene/44124/socs3-(suppressor-of-cytokine-signaling-3)
