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Browse SOCS1

Summary
SymbolSOCS1
Namesuppressor of cytokine signaling 1
Aliases SOCS-1; SSI-1; JAB; TIP3; Cish1; CIS1; SSI1; JAK binding protein; JAK-binding protein; STAT induced SH3 prot ......
Chromosomal Location16p13.13
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 Nucleus Cytoplasmic vesicle Note=Detected in perinuclear cytoplasmic vesicles upon interaction with FGFR3.
Domain PF00017 SH2 domain
PF07525 SOCS box
Function

SOCS family proteins form part of a classical negative feedback system that regulates cytokine signal transduction. SOCS1 is involved in negative regulation of cytokines that signal through the JAK/STAT3 pathway. Through binding to JAKs, inhibits their kinase activity. In vitro, also suppresses Tec protein-tyrosine activity. Appears to be a major regulator of signaling by interleukin 6 (IL6) and leukemia inhibitory factor (LIF). Regulates interferon-gamma mediated sensory neuron survival (By similarity). Probable substrate recognition component of an ECS (Elongin BC-CUL2/5-SOCS-box protein) E3 ubiquitin ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins. Seems to recognize JAK2. SOCS1 appears to be a negative regulator in IGF1R signaling pathway.

> Gene Ontology
 
Biological Process GO:0001101 response to acid chemical
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:0009306 protein secretion
GO:0010533 regulation of activation of Janus kinase activity
GO:0010534 regulation of activation of JAK2 kinase activity
GO:0018108 peptidyl-tyrosine phosphorylation
GO:0018212 peptidyl-tyrosine modification
GO:0032147 activation of protein kinase activity
GO:0032868 response to insulin
GO:0032869 cellular response to insulin stimulus
GO:0033673 negative regulation of kinase activity
GO:0033674 positive 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:0042518 negative regulation of tyrosine phosphorylation of Stat3 protein
GO:0042532 negative regulation of tyrosine phosphorylation of STAT protein
GO:0042976 activation of Janus kinase activity
GO:0042977 activation of JAK2 kinase activity
GO:0043200 response to amino acid
GO:0043434 response to peptide hormone
GO:0045088 regulation of innate immune response
GO:0045444 fat cell differentiation
GO:0045860 positive regulation of protein kinase activity
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:0050663 cytokine secretion
GO:0050707 regulation of cytokine secretion
GO:0050708 regulation of protein secretion
GO:0050730 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:0060759 regulation of response to cytokine stimulus
GO:0071229 cellular response to acid chemical
GO:0071230 cellular response to amino acid stimulus
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:0005159 insulin-like growth factor receptor binding
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
hsa04910 Insulin signaling pathway
hsa04917 Prolactin signaling pathway
Reactome R-HSA-166054: Activated TLR4 signalling
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-168249: Innate 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-166058: MyD88
R-HSA-912694: Regulation of IFNA signaling
R-HSA-877312: Regulation of IFNG signaling
R-HSA-1433559: Regulation of KIT signaling
R-HSA-162582: Signal Transduction
R-HSA-449147: Signaling by Interleukins
R-HSA-1433557: Signaling by SCF-KIT
R-HSA-181438: Toll Like Receptor 2 (TLR2) Cascade
R-HSA-166016: Toll Like Receptor 4 (TLR4) Cascade
R-HSA-168179: Toll Like Receptor TLR1
R-HSA-168188: Toll Like Receptor TLR6
R-HSA-168898: Toll-Like Receptors Cascades
Summary
SymbolSOCS1
Namesuppressor of cytokine signaling 1
Aliases SOCS-1; SSI-1; JAB; TIP3; Cish1; CIS1; SSI1; JAK binding protein; JAK-binding protein; STAT induced SH3 prot ......
Chromosomal Location16p13.13
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Literatures that report relations between SOCS1 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 SOCS1 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.
23601686MelanomaInhibit immunity (T cell function)Consistently, enforced expression of SOCS-1 in CD8(+) T?cells phenocopied the miRNA-155 deficiency, whereas SOCS-1 silencing augmented tumor destruction. These findings identify miRNA-155 and its target SOCS-1 as key regulators of effector CD8(+) T?cells that can be modulated to potentiate immunotherapies for infectious diseases and cancer.
20826039LymphomaInhibit immunity (T cell function)Gene knockdown of the suppressor of cytokine signaling 1 (SOCS1), a negative-feedback regulator of the immune response in BMDCs resulted in an enhanced phosphorylation of STAT1, and the production of proinflammatory cytokines. Moreover, SOCS1-silenced BMDCs were more potent in suppressing tumor growth.
20651070Plasma Cell MyelomaInhibit immunitySOCS1 negatively regulates IL-6 signaling and is silenced by hypermethylation in MM cells. To define the mechanism of inhibitory-cytokine signaling in effector cells and MM cells, we next analyzed the interaction of immune cells with MM cells that were epigenetically modified to re-express SOCS1; IMiDs induced more potent CTL responses against SOCS1 re-expressing-MM cells than unmodified MM cells.
17483365Acute Myeloid LeukemiaInhibit immunityDormant tumor cells develop cross-resistance to apoptosis induced by CTLs or imatinib mesylate via methylation of suppressor of cytokine signaling 1. Dormant tumor cells also show a progressive decrease of suppressor of cytokine signaling 1 (SOCS1) gene expression and a deregulation of the Janus-activated kinase/signal transducers and activators of transcription (JAK/STAT) pathway due to methylation of the SOCS1 gene. Dormant tumor cells were more resistant to apoptosis induced by specific CTLs, but resistance decreased when SOCS1 expression was restored via demethylation or gene transfer. Thus, SOCS1 regulation of the JAK/STAT pathways contributes to the resistance of tumor cells to CTL-mediated killing.
Summary
SymbolSOCS1
Namesuppressor of cytokine signaling 1
Aliases SOCS-1; SSI-1; JAB; TIP3; Cish1; CIS1; SSI1; JAK binding protein; JAK-binding protein; STAT induced SH3 prot ......
Chromosomal Location16p13.13
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 SOCS1 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 logFC: -1.64; FDR: 0.02150 Resistant to T cell-mediated killing
28783722CRISPR-Cas9 melanomaMel6242CT-CRISPR NA/NS NA/NS
28723893CRISPR-Cas9 melanomaB16GVAX+Anti-PD1 STARS Score: 3.80; FDR: 0.026 Resistant to T cell-mediated killing
28723893CRISPR-Cas9 melanomaB16GVAX NA/NS NA/NS
25691366RNAiBreast cancerMCF7Luc-CTL assay NA/NS NA/NS
24476824shRNAmelanomaB16Primary screen Total # shRNA with >= 4-fold: 1 Resistant to T-cell proliferation
24476824shRNAmelanomaB16Secondary screen Total # shRNA with >= 4-fold: 5 Resistant to T-cell proliferation
Summary
SymbolSOCS1
Namesuppressor of cytokine signaling 1
Aliases SOCS-1; SSI-1; JAB; TIP3; Cish1; CIS1; SSI1; JAK binding protein; JAK-binding protein; STAT induced SH3 prot ......
Chromosomal Location16p13.13
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 SOCS1 in various data sets.
No PMID Cancer type Group Drug # Res # NRes Log2 (Fold Change) P value Anno
126997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)1412-0.7140.283
226997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)65-1.2710.413
326997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)87-0.3210.818
428552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 9160.5160.36
528552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 590.6020.619
628552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470.4180.8
729033130MelanomaallAnti-PD-1 (nivolumab) 26230.8570.11
829033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 15111.3490.0887
929033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 11120.2850.739
1029301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 481.0710.251
1129301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 2001
1229301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 280.2610.851
1329443960Urothelial cancerallAnti-PD-L1 (atezolizumab) 682300.150.428
> Mutation difference between responders and non-responders
 
Points in the above scatter plot represent the mutation difference of SOCS1 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) 141705.9-5.91
225765070Non-small cell lung cancer (NSCLC)smokingAnti-PD-1 (pembrolizumab) 1030001
325765070Non-small cell lung cancer (NSCLC)non-smokingAnti-PD-1 (pembrolizumab) 41407.1-7.11
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
SymbolSOCS1
Namesuppressor of cytokine signaling 1
Aliases SOCS-1; SSI-1; JAB; TIP3; Cish1; CIS1; SSI1; JAK binding protein; JAK-binding protein; STAT induced SH3 prot ......
Chromosomal Location16p13.13
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of SOCS1. 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
SymbolSOCS1
Namesuppressor of cytokine signaling 1
Aliases SOCS-1; SSI-1; JAB; TIP3; Cish1; CIS1; SSI1; JAK binding protein; JAK-binding protein; STAT induced SH3 prot ......
Chromosomal Location16p13.13
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of SOCS1. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by SOCS1.
> Immunoinhibitor
> Immunostimulator
> MHC molecule
> Immunoinhibitor
 
> Immunostimulator
 
> MHC molecule
 
Summary
SymbolSOCS1
Namesuppressor of cytokine signaling 1
Aliases SOCS-1; SSI-1; JAB; TIP3; Cish1; CIS1; SSI1; JAK binding protein; JAK-binding protein; STAT induced SH3 prot ......
Chromosomal Location16p13.13
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of SOCS1. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene.
> Chemokine
> Receptor
> Chemokine
 
> Receptor
 
Summary
SymbolSOCS1
Namesuppressor of cytokine signaling 1
Aliases SOCS-1; SSI-1; JAB; TIP3; Cish1; CIS1; SSI1; JAK binding protein; JAK-binding protein; STAT induced SH3 prot ......
Chromosomal Location16p13.13
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Distribution of SOCS1 expression across immune and molecular subtypes.
> Immune subtype
> Molecular subtype
> Immune subtype
 
> Molecular subtype
 
Summary
SymbolSOCS1
Namesuppressor of cytokine signaling 1
Aliases SOCS-1; SSI-1; JAB; TIP3; Cish1; CIS1; SSI1; JAK binding protein; JAK-binding protein; STAT induced SH3 prot ......
Chromosomal Location16p13.13
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Associations between SOCS1 and clinical features.
> Overall survival analysis
> Cancer stage
> Tumor grade
> Overall survival
 
> Stage
 
> Grade
 
Summary
SymbolSOCS1
Namesuppressor of cytokine signaling 1
Aliases SOCS-1; SSI-1; JAB; TIP3; Cish1; CIS1; SSI1; JAK binding protein; JAK-binding protein; STAT induced SH3 prot ......
Chromosomal Location16p13.13
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Drugs targeting SOCS1 collected from DrugBank database.
> Drugs from DrugBank database
 

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