SOCS3 (suppressor of cytokine signaling 3)

2012-02-01   Zoran Culig  

Experimental Urology, Department of Urology, Innsbruck Medical University, Anichstrasse 35, A-6020 Innsbruck, Austria

Identity

HGNC
SOCS3
LOCATION
17q25.3
LOCUSID
9021
ALIAS
ATOD4,CIS3,Cish3,MGC71791,SOCS-3,SSI-3,SSI3
FUSION GENES
Show Gene Fusions

DNA/RNA

Description

Size: 3300 bases.

Transcription

2 introns. Transcription generates 3 different mRNAs, 2 spliced variants and 1 unspliced form.

Proteins

Atlas Image
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.

Bibliography

Pubmed IDLast YearTitleAuthors
171486812006Suppressor of cytokine signaling-3 antagonizes cAMP effects on proliferation and apoptosis and is expressed in human prostate cancer.Bellezza I et al
111595372001STAT3-mediated constitutive expression of SOCS-3 in cutaneous T-cell lymphoma.Brender C et al
183187602008Epigenetic inactivation of suppressors of cytokine signalling in Philadelphia-negative chronic myeloproliferative disorders.Capello D et al
146177762003SOCS-3 is frequently silenced by hypermethylation and suppresses cell growth in human lung cancer.He B et al
173747322007Constitutive suppressor of cytokine signaling 3 expression confers a growth advantage to a human melanoma cell line.Komyod W et al
187708642008Prognostic relevance of SOCS3 hypermethylation in patients with glioblastoma multiforme.Martini M et al
160071952005Methylation silencing of SOCS-3 promotes cell growth and migration by enhancing JAK/STAT and FAK signalings in human hepatocellular carcinoma.Niwa Y et al
175137372007Type 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
197380592009Down-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
160071692005SOCS-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 IDTranscript IDUniprot
ENSG00000184557ENST00000330871O14543
ENSG00000184557ENST00000330871Q6FI39
ENSG00000184557ENST00000587578K7EIF6

Expression (GTEx)

0
100
200
300
400
500
600
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

PathwaySourceExternal ID
Ubiquitin mediated proteolysisKEGGko04120
Jak-STAT signaling pathwayKEGGko04630
Insulin signaling pathwayKEGGko04910
Adipocytokine signaling pathwayKEGGko04920
Type II diabetes mellitusKEGGko04930
Ubiquitin mediated proteolysisKEGGhsa04120
Jak-STAT signaling pathwayKEGGhsa04630
Insulin signaling pathwayKEGGhsa04910
Adipocytokine signaling pathwayKEGGhsa04920
Type II diabetes mellitusKEGGhsa04930
Hepatitis CKEGGko05160
Hepatitis CKEGGhsa05160
Osteoclast differentiationKEGGko04380
Osteoclast differentiationKEGGhsa04380
Influenza AKEGGko05164
Influenza AKEGGhsa05164
Herpes simplex infectionKEGGko05168
Herpes simplex infectionKEGGhsa05168
ECS complexKEGGhsa_M00388
ECS complexKEGGM00388
TNF signaling pathwayKEGGhsa04668
TNF signaling pathwayKEGGko04668
Prolactin signaling pathwayKEGGhsa04917
Prolactin signaling pathwayKEGGko04917
Non-alcoholic fatty liver disease (NAFLD)KEGGhsa04932
Non-alcoholic fatty liver disease (NAFLD)KEGGko04932
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
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
Interleukin-6 signalingREACTOMER-HSA-1059683
Growth hormone receptor signalingREACTOMER-HSA-982772
Signal TransductionREACTOMER-HSA-162582
Signaling by LeptinREACTOMER-HSA-2586552
Insulin resistanceKEGGhsa04931
Interleukin-6 family signalingREACTOMER-HSA-6783589
Signaling by PTK6REACTOMER-HSA-8848021
PTK6 Activates STAT3REACTOMER-HSA-8849474
Interleukin-4 and 13 signalingREACTOMER-HSA-6785807

Protein levels (Protein atlas)

Not detected
Low
Medium
High
cerebral cortex
cerebellum
hippocampus
caudate
thyroid gland
adrenal gland
nasopharynx
bronchus
lung
oral mucosa
salivary gland
esophagus
stomach 1
stomach 2
duodenum
small intestine
colon
rectum
liver
gallbladder
pancreas
kidney
urinary bladder
testis
epididymis
seminal vesicle
prostate
vagina
ovary
fallopian tube
endometrium 1
endometrium 2
cervix, uterine
placenta
breast
heart muscle
smooth muscle
skeletal muscle
soft tissue 1
soft tissue 2
adipose tissue
skin 2
appendix
spleen
lymph node
tonsil
bone marrow

PharmGKB

Entity IDNameTypeEvidenceAssociationPKPDPMIDs
PA36184STAT2GenePathwayassociated26111151

References

Pubmed IDYearTitleCitations
379102762024E3 ligase SOCS3 regulates NOD2 expression by ubiquitin proteasome system in lung cancer progression.0
379505142024DNMTs-mediated SOCS3 methylation promotes the occurrence and development of AML.0
382293362024SOCS3, Transcriptionally Activated by NR4A1, Induces Apoptosis and Extracellular Matrix Degradation of Vaginal Fibroblasts in Pelvic Organ Prolapse.0
385334932024Suppressor of cytokine signaling-3 expression and its regulation in relation to inflammation in Chronic Obstructive Pulmonary Disease.0
386372742024Exploring the clinical and cellular mechanisms of LncRNA-KCNQ1OT1/miR-29a-3p/SOCS3 molecular axis in cases of unexplained recurrent spontaneous abortion.0
379102762024E3 ligase SOCS3 regulates NOD2 expression by ubiquitin proteasome system in lung cancer progression.0
379505142024DNMTs-mediated SOCS3 methylation promotes the occurrence and development of AML.0
382293362024SOCS3, Transcriptionally Activated by NR4A1, Induces Apoptosis and Extracellular Matrix Degradation of Vaginal Fibroblasts in Pelvic Organ Prolapse.0
385334932024Suppressor of cytokine signaling-3 expression and its regulation in relation to inflammation in Chronic Obstructive Pulmonary Disease.0
386372742024Exploring the clinical and cellular mechanisms of LncRNA-KCNQ1OT1/miR-29a-3p/SOCS3 molecular axis in cases of unexplained recurrent spontaneous abortion.0
352261712023Tissue levels of suppressor of cytokine signaling-3 (SOCS-3) in mycosis fungoides.0
353667802023The Relationship Between FoxP3 and SOCs3 Gene Expressions and Disease Activity in Rheumatoid Arthritis.1
357311422023Upregulated expression of FFAR2 and SOC3 genes is associated with gout.0
364849702023Oncogenic role of microRNA-19b-3p-mediated SOCS3 in glioma through activation of JAK-STAT pathway.2
365381742023Obesity 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/gene-explorer/css/css/lib/dataTables.bootstrap.min.css