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Browse SOCS3

Summary
SymbolSOCS3
Namesuppressor of cytokine signaling 3
Aliases SSI-3; CIS3; SOCS-3; Cish3; ATOD4; SSI3; STAT-induced STAT inhibitor 3; cytokine-inducible SH2 protein 3; CI ......
Chromosomal Location17q25.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Basic function annotation.
> Subcellular Location, Domain and Function
> Gene Ontology
> KEGG and Reactome Pathway
> Subcellular Location, Domain and Function
 
Subcellular Location -
Domain PF00017 SH2 domain
PF07525 SOCS box
Function

SOCS family proteins form part of a classical negative feedback system that regulates cytokine signal transduction. SOCS3 is involved in negative regulation of cytokines that signal through the JAK/STAT pathway. Inhibits cytokine signal transduction by binding to tyrosine kinase receptors including gp130, LIF, erythropoietin, insulin, IL12, GCSF and leptin receptors. Binding to JAK2 inhibits its kinase activity. Suppresses fetal liver erythropoiesis. Regulates onset and maintenance of allergic responses mediated by T-helper type 2 cells. Regulates IL-6 signaling in vivo (By similarity). Probable substrate recognition component of a SCF-like ECS (Elongin BC-CUL2/5-SOCS-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins. Seems to recognize IL6ST (By similarity).

> Gene Ontology
 
Biological Process GO:0001701 in utero embryonic development
GO:0001763 morphogenesis of a branching structure
GO:0001890 placenta development
GO:0001892 embryonic placenta development
GO:0001933 negative regulation of protein phosphorylation
GO:0001959 regulation of cytokine-mediated signaling pathway
GO:0006469 negative regulation of protein kinase activity
GO:0007259 JAK-STAT cascade
GO:0007260 tyrosine phosphorylation of STAT protein
GO:0008286 insulin receptor signaling pathway
GO:0018108 peptidyl-tyrosine phosphorylation
GO:0018212 peptidyl-tyrosine modification
GO:0031348 negative regulation of defense response
GO:0032102 negative regulation of response to external stimulus
GO:0032868 response to insulin
GO:0032869 cellular response to insulin stimulus
GO:0033673 negative regulation of kinase activity
GO:0034341 response to interferon-gamma
GO:0042326 negative regulation of phosphorylation
GO:0042503 tyrosine phosphorylation of Stat3 protein
GO:0042508 tyrosine phosphorylation of Stat1 protein
GO:0042509 regulation of tyrosine phosphorylation of STAT protein
GO:0042510 regulation of tyrosine phosphorylation of Stat1 protein
GO:0042512 negative regulation of tyrosine phosphorylation of Stat1 protein
GO:0042516 regulation of tyrosine phosphorylation of Stat3 protein
GO:0042517 positive regulation of tyrosine phosphorylation of Stat3 protein
GO:0042518 negative regulation of tyrosine phosphorylation of Stat3 protein
GO:0042531 positive regulation of tyrosine phosphorylation of STAT protein
GO:0042532 negative regulation of tyrosine phosphorylation of STAT protein
GO:0043434 response to peptide hormone
GO:0045088 regulation of innate immune response
GO:0046425 regulation of JAK-STAT cascade
GO:0046426 negative regulation of JAK-STAT cascade
GO:0046427 positive regulation of JAK-STAT cascade
GO:0046626 regulation of insulin receptor signaling pathway
GO:0046627 negative regulation of insulin receptor signaling pathway
GO:0048568 embryonic organ development
GO:0048608 reproductive structure development
GO:0050727 regulation of inflammatory response
GO:0050728 negative regulation of inflammatory response
GO:0050730 regulation of peptidyl-tyrosine phosphorylation
GO:0050731 positive regulation of peptidyl-tyrosine phosphorylation
GO:0050732 negative regulation of peptidyl-tyrosine phosphorylation
GO:0051348 negative regulation of transferase activity
GO:0060330 regulation of response to interferon-gamma
GO:0060333 interferon-gamma-mediated signaling pathway
GO:0060334 regulation of interferon-gamma-mediated signaling pathway
GO:0060669 embryonic placenta morphogenesis
GO:0060670 branching involved in labyrinthine layer morphogenesis
GO:0060674 placenta blood vessel development
GO:0060706 cell differentiation involved in embryonic placenta development
GO:0060707 trophoblast giant cell differentiation
GO:0060708 spongiotrophoblast differentiation
GO:0060711 labyrinthine layer development
GO:0060712 spongiotrophoblast layer development
GO:0060713 labyrinthine layer morphogenesis
GO:0060759 regulation of response to cytokine stimulus
GO:0061138 morphogenesis of a branching epithelium
GO:0061458 reproductive system development
GO:0071346 cellular response to interferon-gamma
GO:0071375 cellular response to peptide hormone stimulus
GO:0071417 cellular response to organonitrogen compound
GO:0097696 STAT cascade
GO:1900076 regulation of cellular response to insulin stimulus
GO:1900077 negative regulation of cellular response to insulin stimulus
GO:1901652 response to peptide
GO:1901653 cellular response to peptide
GO:1902532 negative regulation of intracellular signal transduction
GO:1904892 regulation of STAT cascade
GO:1904893 negative regulation of STAT cascade
GO:1904894 positive regulation of STAT cascade
Molecular Function GO:0004857 enzyme inhibitor activity
GO:0004860 protein kinase inhibitor activity
GO:0019207 kinase regulator activity
GO:0019210 kinase inhibitor activity
GO:0019887 protein kinase regulator activity
Cellular Component -
> KEGG and Reactome Pathway
 
KEGG hsa04120 Ubiquitin mediated proteolysis
hsa04380 Osteoclast differentiation
hsa04630 Jak-STAT signaling pathway
hsa04668 TNF signaling pathway
hsa04910 Insulin signaling pathway
hsa04917 Prolactin signaling pathway
hsa04920 Adipocytokine signaling pathway
Reactome R-HSA-1280218: Adaptive Immune System
R-HSA-983168: Antigen processing
R-HSA-983169: Class I MHC mediated antigen processing & presentation
R-HSA-1280215: Cytokine Signaling in Immune system
R-HSA-982772: Growth hormone receptor signaling
R-HSA-168256: Immune System
R-HSA-913531: Interferon Signaling
R-HSA-909733: Interferon alpha/beta signaling
R-HSA-877300: Interferon gamma signaling
R-HSA-6785807: Interleukin-4 and 13 signaling
R-HSA-6783589: Interleukin-6 family signaling
R-HSA-1059683: Interleukin-6 signaling
R-HSA-8849474: PTK6 Activates STAT3
R-HSA-912694: Regulation of IFNA signaling
R-HSA-877312: Regulation of IFNG signaling
R-HSA-162582: Signal Transduction
R-HSA-449147: Signaling by Interleukins
R-HSA-2586552: Signaling by Leptin
R-HSA-8848021: Signaling by PTK6
Summary
SymbolSOCS3
Namesuppressor of cytokine signaling 3
Aliases SSI-3; CIS3; SOCS-3; Cish3; ATOD4; SSI3; STAT-induced STAT inhibitor 3; cytokine-inducible SH2 protein 3; CI ......
Chromosomal Location17q25.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Literatures that report relations between SOCS3 and anti-tumor immunity. The specific mechanism were also collected if the literature reports that a gene specifically promotes or inhibits the infiltration or function of T/NK cells.
> Text Mining
 
  Literatures describing the relation between SOCS3 and anti-tumor immunity in human cancer.
PMID Cancer type Relation to immunity Evidence sentences
18381452Breast CarcinomaInhibit immunityInterestingly, the tumor tolerance model instead displayed immune suppression pathways through activation of regulatory mechanisms that included in particular the overexpression of interleukin-10 (IL-10), IL-10 receptor, and suppressor of cytokine signaling (SOCS)-1 and SOCS-3.
Summary
SymbolSOCS3
Namesuppressor of cytokine signaling 3
Aliases SSI-3; CIS3; SOCS-3; Cish3; ATOD4; SSI3; STAT-induced STAT inhibitor 3; cytokine-inducible SH2 protein 3; CI ......
Chromosomal Location17q25.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content High-throughput screening data (e.g. CRISPR-Cas9, shRNA and RNAi) for T cell-mediated killing. Genetic screen techniques can identify mechanisms of tumor cell resistance (e.g., PTPN2) and sensitivity (e.g., APLNR) to killing by cytotoxic T cells, the central effectors of anti-tumor immunity. After comprehensively searching, eight groups of screening data sets were collected in the current database. In this tab, users can check whether their selected genes cause resistance or increase sensitivity to T cell-mediated killing in various data sets.
> High-throughput Screening
  Statistical results of SOCS3 in screening data sets for detecting immune reponses.
PMID Screening System Cancer Type Cell Line Data Set Statistical Results Relation to immunity
29301958CRISPR-Cas9 melanomaB16F10Pmel-1 T cell NA/NS NA/NS
29301958CRISPR-Cas9 melanomaB16F10OT-1 T cell NA/NS NA/NS
28783722CRISPR-Cas9 melanomaMel6242CT-CRISPR NA/NS NA/NS
28723893CRISPR-Cas9 melanomaB16GVAX+Anti-PD1 NA/NS NA/NS
28723893CRISPR-Cas9 melanomaB16GVAX NA/NS NA/NS
25691366RNAiBreast cancerMCF7Luc-CTL assay NA/NS NA/NS
24476824shRNAmelanomaB16Primary screen Total # shRNA with >= 4-fold: 2 Resistant to T-cell proliferation
24476824shRNAmelanomaB16Secondary screen Total # shRNA with >= 4-fold: 4 Resistant to T-cell proliferation
Summary
SymbolSOCS3
Namesuppressor of cytokine signaling 3
Aliases SSI-3; CIS3; SOCS-3; Cish3; ATOD4; SSI3; STAT-induced STAT inhibitor 3; cytokine-inducible SH2 protein 3; CI ......
Chromosomal Location17q25.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Transcriptomic and genomic profiling of pre-treated tumor biopsies from responders and non-responders to immunotherapy. These data were used to identify signatures and mechanisms of response to checkpoint blockade (e.g., anti-PDL1 and anti-PD1). One example is that mutations in the gene PBRM1 benefit clinical survival of patients with clear cell renal cell carcinoma. After comprehensively searching, we collected 5 and 6 of transcriptomic and genomic data sets, respectively. In this tab, users can check whether their selected genes have significant difference of expression or mutation between responders and non-responders in various data sets.
> Expression difference between responders and non-responders
> Mutation difference between responders and non-responders
> Expression difference between responders and non-responders
 
Points in the above scatter plot represent the expression difference of SOCS3 in various data sets.
No PMID Cancer type Group Drug # Res # NRes Log2 (Fold Change) P value Anno
126997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)1412-0.4660.395
226997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)65-1.0880.634
326997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)87-0.0020.999
428552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 916-0.6560.403
528552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 59-0.9620.684
628552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 47-0.2570.937
729033130MelanomaallAnti-PD-1 (nivolumab) 2623-0.140.804
829033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 1511-0.7520.619
929033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 11120.590.712
1029301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 480.6250.658
1129301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 2001
1229301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 281.1740.572
1329443960Urothelial cancerallAnti-PD-L1 (atezolizumab) 68230-0.4340.0193
> Mutation difference between responders and non-responders
 
Points in the above scatter plot represent the mutation difference of SOCS3 in various data sets.
No PMID Cancer type Group Drug # Res # NRes % Mut/Res % Mut/NRes % Diff (R vs NR) Pval Anno
125765070Non-small cell lung cancer (NSCLC)allAnti-PD-1 (pembrolizumab) 14170001
225765070Non-small cell lung cancer (NSCLC)smokingAnti-PD-1 (pembrolizumab) 1030001
325765070Non-small cell lung cancer (NSCLC)non-smokingAnti-PD-1 (pembrolizumab) 4140001
426359337MelanomaallAnti-CTLA-4 (ipilimumab) 27730001
526359337MelanomaBRAFiAnti-CTLA-4 (ipilimumab) 0140001
626359337Melanomanon-BRAFiAnti-CTLA-4 (ipilimumab) 27590001
726997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)21170001
826997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)860001
926997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)13110001
1028552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 9160001
1128552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 590001
1228552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470001
1329033130MelanomaallAnti-PD-1 (nivolumab) 38270001
1429033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 22130001
1529033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 16140001
1629301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 11130001
1729301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 610001
1829301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 5120001
Summary
SymbolSOCS3
Namesuppressor of cytokine signaling 3
Aliases SSI-3; CIS3; SOCS-3; Cish3; ATOD4; SSI3; STAT-induced STAT inhibitor 3; cytokine-inducible SH2 protein 3; CI ......
Chromosomal Location17q25.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of SOCS3. The immune-related signatures of 28 TIL types from Charoentong's study, which can be viewed in the download page. For each cancer type, the relative abundance of TILs were inferred by using gene set variation analysis (GSVA) based on gene expression profile. In this tab, users can examine which kinds of TILs might be regulated by the current gene.
> Lymphocyte
 
Summary
SymbolSOCS3
Namesuppressor of cytokine signaling 3
Aliases SSI-3; CIS3; SOCS-3; Cish3; ATOD4; SSI3; STAT-induced STAT inhibitor 3; cytokine-inducible SH2 protein 3; CI ......
Chromosomal Location17q25.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of SOCS3. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by SOCS3.
> Immunoinhibitor
> Immunostimulator
> MHC molecule
> Immunoinhibitor
 
> Immunostimulator
 
> MHC molecule
 
Summary
SymbolSOCS3
Namesuppressor of cytokine signaling 3
Aliases SSI-3; CIS3; SOCS-3; Cish3; ATOD4; SSI3; STAT-induced STAT inhibitor 3; cytokine-inducible SH2 protein 3; CI ......
Chromosomal Location17q25.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of SOCS3. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene.
> Chemokine
> Receptor
> Chemokine
 
> Receptor
 
Summary
SymbolSOCS3
Namesuppressor of cytokine signaling 3
Aliases SSI-3; CIS3; SOCS-3; Cish3; ATOD4; SSI3; STAT-induced STAT inhibitor 3; cytokine-inducible SH2 protein 3; CI ......
Chromosomal Location17q25.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Distribution of SOCS3 expression across immune and molecular subtypes.
> Immune subtype
> Molecular subtype
> Immune subtype
 
> Molecular subtype
 
Summary
SymbolSOCS3
Namesuppressor of cytokine signaling 3
Aliases SSI-3; CIS3; SOCS-3; Cish3; ATOD4; SSI3; STAT-induced STAT inhibitor 3; cytokine-inducible SH2 protein 3; CI ......
Chromosomal Location17q25.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Associations between SOCS3 and clinical features.
> Overall survival analysis
> Cancer stage
> Tumor grade
> Overall survival
 
> Stage
 
> Grade
 
Summary
SymbolSOCS3
Namesuppressor of cytokine signaling 3
Aliases SSI-3; CIS3; SOCS-3; Cish3; ATOD4; SSI3; STAT-induced STAT inhibitor 3; cytokine-inducible SH2 protein 3; CI ......
Chromosomal Location17q25.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Drugs targeting SOCS3 collected from DrugBank database.
> Drugs from DrugBank database
 

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