TISIDB

Summary
Symbol	CISH
Name	cytokine inducible SH2-containing protein
Aliases	CIS; CIS-1; SOCS; BACTS2; cytokine-inducible inhibitor of signaling type 1B; suppressor of cytokine signalin ......
Chromosomal Location	3p21.3
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 [ TOP ]
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. CIS is involved in the negative regulation of cytokines that signal through the JAK-STAT5 pathway such as erythropoietin, prolactin and interleukin 3 (IL3) receptor. Inhibits STAT5 trans-activation by suppressing its tyrosine phosphorylation. May be a 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 (By similarity).

> Gene Ontology [ TOP ]
Biological Process	GO:0001558 regulation of cell growth GO:0001933 negative regulation of protein phosphorylation GO:0006469 negative regulation of protein kinase activity GO:0007205 protein kinase C-activating G-protein coupled receptor signaling pathway GO:0007259 JAK-STAT cascade GO:0008286 insulin receptor signaling pathway GO:0016049 cell growth GO:0032868 response to insulin GO:0032869 cellular response to insulin stimulus GO:0033673 negative regulation of kinase activity GO:0042326 negative regulation of phosphorylation GO:0043434 response to peptide hormone GO:0046425 regulation of JAK-STAT cascade GO:0046426 negative regulation of JAK-STAT cascade GO:0046626 regulation of insulin receptor signaling pathway GO:0046627 negative regulation of insulin receptor signaling pathway GO:0051348 negative regulation of transferase activity 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
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 [ TOP ]
KEGG	hsa04630 Jak-STAT signaling pathway hsa04917 Prolactin signaling pathway
Reactome	R-HSA-1280215: Cytokine Signaling in Immune system R-HSA-982772: Growth hormone receptor signaling R-HSA-168256: Immune System

Summary
Symbol	CISH
Name	cytokine inducible SH2-containing protein
Aliases	CIS; CIS-1; SOCS; BACTS2; cytokine-inducible inhibitor of signaling type 1B; suppressor of cytokine signalin ......
Chromosomal Location	3p21.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between CISH 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

[ TOP ]

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

PMID	Cancer type	Relation to immunity	Evidence sentences
26527801	Melanoma	Inhibit immunity (T cell function)	Genetic deletion of Cish in CD8(+) T cells enhances their expansion, functional avidity, and cytokine polyfunctionality, resulting in pronounced and durable regression of established tumors.
27213690	Melanoma; Prostate Carcinoma; Breast Carcinoma	Inhibit immunity (NK cell function)	We identified cytokine-inducible SH2-containing protein (CIS, encoded by Cish) as a critical negative regulator of IL-15 signaling in NK cells. Cish was rapidly induced in response to IL-15, and deletion of Cish rendered NK cells hypersensitive to IL-15, as evidenced by enhanced proliferation, survival, IFN-γ production and cytotoxicity toward tumors.

Summary
Symbol	CISH
Name	cytokine inducible SH2-containing protein
Aliases	CIS; CIS-1; SOCS; BACTS2; cytokine-inducible inhibitor of signaling type 1B; suppressor of cytokine signalin ......
Chromosomal Location	3p21.3
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

[ TOP ]

Statistical results of CISH 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	NA/NS	NA/NS
28783722	CRISPR-Cas9	melanoma	Mel624	2CT-CRISPR	NA/NS	NA/NS
28723893	CRISPR-Cas9	melanoma	B16	GVAX+Anti-PD1	NA/NS	NA/NS
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	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Secondary screen	NA/NS	NA/NS

Summary
Symbol	CISH
Name	cytokine inducible SH2-containing protein
Aliases	CIS; CIS-1; SOCS; BACTS2; cytokine-inducible inhibitor of signaling type 1B; suppressor of cytokine signalin ......
Chromosomal Location	3p21.3
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

[ TOP ]

Points in the above scatter plot represent the expression difference of CISH 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	-0.059	0.857
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-0.563	0.617
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	0.305	0.74
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.23	0.605
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0.086	0.957
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.415	0.841
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	-0.126	0.689
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	-0.584	0.477
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	0.275	0.788
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0.343	0.73
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	0.312	0.834
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.407	0.0014

> Mutation difference between responders and non-responders

[ TOP ]

Points in the above scatter plot represent the mutation difference of CISH 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	0	0	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	0	0	1
4	26359337	Melanoma	all	Anti-CTLA-4 (ipilimumab)	27	73	1.4	-1.4	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	1.7	-1.7	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	7.7	-7.7	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	8.3	-8.3	1

Summary
Symbol	CISH
Name	cytokine inducible SH2-containing protein
Aliases	CIS; CIS-1; SOCS; BACTS2; cytokine-inducible inhibitor of signaling type 1B; suppressor of cytokine signalin ......
Chromosomal Location	3p21.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of CISH. 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	CISH
Name	cytokine inducible SH2-containing protein
Aliases	CIS; CIS-1; SOCS; BACTS2; cytokine-inducible inhibitor of signaling type 1B; suppressor of cytokine signalin ......
Chromosomal Location	3p21.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of CISH. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by CISH. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	CISH
Name	cytokine inducible SH2-containing protein
Aliases	CIS; CIS-1; SOCS; BACTS2; cytokine-inducible inhibitor of signaling type 1B; suppressor of cytokine signalin ......
Chromosomal Location	3p21.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of CISH. 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	CISH
Name	cytokine inducible SH2-containing protein
Aliases	CIS; CIS-1; SOCS; BACTS2; cytokine-inducible inhibitor of signaling type 1B; suppressor of cytokine signalin ......
Chromosomal Location	3p21.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of CISH expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	CISH
Name	cytokine inducible SH2-containing protein
Aliases	CIS; CIS-1; SOCS; BACTS2; cytokine-inducible inhibitor of signaling type 1B; suppressor of cytokine signalin ......
Chromosomal Location	3p21.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between CISH and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	CISH
Name	cytokine inducible SH2-containing protein
Aliases	CIS; CIS-1; SOCS; BACTS2; cytokine-inducible inhibitor of signaling type 1B; suppressor of cytokine signalin ......
Chromosomal Location	3p21.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting CISH collected from DrugBank database.

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

Browse CISH