TISIDB

Summary
Symbol	SOCS1
Name	suppressor 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 Location	16p13.13
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 [ TOP ]
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 [ TOP ]
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 [ TOP ]
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

> KEGG and Reactome Pathway

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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
Symbol	SOCS1
Name	suppressor 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 Location	16p13.13
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

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Literatures describing the relation between SOCS1 and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
18381452	Breast Carcinoma	Inhibit immunity	Interestingly, 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.
23601686	Melanoma	Inhibit 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.
20826039	Lymphoma	Inhibit 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.
20651070	Plasma Cell Myeloma	Inhibit immunity	SOCS1 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.
17483365	Acute Myeloid Leukemia	Inhibit immunity	Dormant 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
Symbol	SOCS1
Name	suppressor 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 Location	16p13.13
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

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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
29301958	CRISPR-Cas9	melanoma	B16F10	Pmel-1 T cell	NA/NS	NA/NS
29301958	CRISPR-Cas9	melanoma	B16F10	OT-1 T cell	logFC: -1.64; FDR: 0.02150	Resistant to T cell-mediated killing
28783722	CRISPR-Cas9	melanoma	Mel624	2CT-CRISPR	NA/NS	NA/NS
28723893	CRISPR-Cas9	melanoma	B16	GVAX+Anti-PD1	STARS Score: 3.80; FDR: 0.026	Resistant to T cell-mediated killing
28723893	CRISPR-Cas9	melanoma	B16	GVAX	NA/NS	NA/NS
25691366	RNAi	Breast cancer	MCF7	Luc-CTL assay	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Primary screen	Total # shRNA with >= 4-fold: 1	Resistant to T-cell proliferation
24476824	shRNA	melanoma	B16	Secondary screen	Total # shRNA with >= 4-fold: 5	Resistant to T-cell proliferation

Summary
Symbol	SOCS1
Name	suppressor 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 Location	16p13.13
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

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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
1	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	14	12	-0.714	0.283
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-1.271	0.413
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	-0.321	0.818
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.516	0.36
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0.602	0.619
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.418	0.8
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.857	0.11
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	1.349	0.0887
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	0.285	0.739
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	1.071	0.251
11	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	2	0	0	1
12	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	2	8	0.261	0.851
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	0.15	0.428

> Mutation difference between responders and non-responders

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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/NRes	% Diff (R vs NR)	Pval
1	25765070	Non-small cell lung cancer (NSCLC)	all	Anti-PD-1 (pembrolizumab)	14	17	5.9	-5.9	1
2	25765070	Non-small cell lung cancer (NSCLC)	smoking	Anti-PD-1 (pembrolizumab)	10	3	0	0	1
3	25765070	Non-small cell lung cancer (NSCLC)	non-smoking	Anti-PD-1 (pembrolizumab)	4	14	7.1	-7.1	1
4	26359337	Melanoma	all	Anti-CTLA-4 (ipilimumab)	27	73	0	0	1
5	26359337	Melanoma	BRAFi	Anti-CTLA-4 (ipilimumab)	0	14	0	0	1
6	26359337	Melanoma	non-BRAFi	Anti-CTLA-4 (ipilimumab)	27	59	0	0	1
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	0	0	1
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	0	0	1
9	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	13	11	0	0	1
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0	0	1
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0	0	1
12	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0	0	1
13	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	38	27	0	0	1
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	0	0	1
15	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	16	14	0	0	1
16	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	11	13	0	0	1
17	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	6	1	0	0	1
18	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	5	12	0	0	1

Summary
Symbol	SOCS1
Name	suppressor 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 Location	16p13.13
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 [ TOP ]

Summary
Symbol	SOCS1
Name	suppressor 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 Location	16p13.13
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 [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	SOCS1
Name	suppressor 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 Location	16p13.13
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 [ TOP ]

> Receptor [ TOP ]

Summary
Symbol	SOCS1
Name	suppressor 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 Location	16p13.13
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of SOCS1 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	SOCS1
Name	suppressor 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 Location	16p13.13
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between SOCS1 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	SOCS1
Name	suppressor 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 Location	16p13.13
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting SOCS1 collected from DrugBank database.

> Drugs from DrugBank database [ TOP ]
There is no record.

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