CISH

CISH
Identifiers
Aliases	CISH, BACTS2, CIS, CIS-1, G18, SOCS, cytokine inducible SH2 containing protein
External IDs	OMIM: 602441 MGI: 103159 HomoloGene: 7667 GeneCards: CISH
Gene location (Human) Chr. Chromosome 3 (human)[1] Band 3p21.2 Start 50,606,489 bp[1] End 50,611,774 bp[1]
Gene location (Mouse) Chr. Chromosome 9 (mouse)[2] Band 9 F1|9 57.99 cM Start 107,173,225 bp[2] End 107,179,983 bp[2]
RNA expression pattern Bgee Top expressed in Right lobe of liver kidney upper lobe of left lung liver More reference expression data BioGPS More reference expression data
Gene ontology Molecular function protein kinase inhibitor activity GO:0001948 protein binding molecular function 1-phosphatidylinositol-3-kinase regulator activity Cellular component cytoplasm cytosol plasma membrane cellular component phosphatidylinositol 3-kinase complex Biological process regulation of growth negative regulation of insulin receptor signaling pathway protein kinase C-activating G protein-coupled receptor signaling pathway GO:0007243 intracellular signal transduction negative regulation of signal transduction regulation of cell growth protein ubiquitination negative regulation of protein kinase activity negative regulation of receptor signaling pathway via JAK-STAT cytokine-mediated signaling pathway post-translational protein modification interleukin-7-mediated signaling pathway regulation of phosphatidylinositol 3-kinase activity phosphatidylinositol phosphate biosynthetic process Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	1154	12700
Ensembl	ENSG00000114737	ENSMUSG00000032578
UniProt	Q9NSE2	Q62225
RefSeq (mRNA)	NM_013324 NM_145071	NM_009895 NM_001317354
RefSeq (protein)	NP_037456 NP_659508	NP_001304283 NP_034025
Location (UCSC)	Chr 3: 50.61 – 50.61 Mb	Chr 9: 107.17 – 107.18 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

Cytokine-inducible SH2-containing protein is a protein that in humans is encoded by the CISH gene.^[5][6][7] CISH orthologs^[8] have been identified in most mammals with sequenced genomes. CISH controls T cell receptor (TCR) signaling, and variations of CISH with certain SNPs are associated with susceptibility to bacteremia, tuberculosis and malaria.^[9]

Function[]

The protein encoded by this gene contains a SH2 domain and a SOCS box domain. The protein thus belongs to the (CIS), also known as suppressor of cytokine signaling (SOCS) or STAT-induced STAT inhibitor (SSI), protein family. members are known to be cytokine-inducible negative regulators of cytokine signaling.

The expression of this gene can be induced by IL-2, IL-3, GM-CSF and EPO in hematopoietic cells. Proteasome-mediated degradation of this protein has been shown to be involved in the inactivation of the erythropoietin receptor.^[7]

CISH is induced by T cell receptor (TCR) ligation and negatively regulates it by targeting the critical signaling intermediate PLC-gamma-1 for degradation.^[10] The deletion of Cish in effector T cells has been shown to augment TCR signaling and subsequent effector cytokine release, proliferation and survival. The adoptive transfer of tumor-specific effector T cells knocked out or knocked down for CISH resulted in a significant increase in functional avidity and long-term tumor immunity. There are no changes in activity or phosphorylation of Cish's purported target, STAT5 in either the presence or absence of Cish.

In human tumor-infiltrating lymphocytes (TIL), CISH expression has been reported to be inversely expressed with known T cell activation/exhaustion markers and regulates their expression and neoantigen reactivity. Combination therapy with checkpoint blockade synergestically results in profound tumor regressing in a pre-clinical tumor model ^[11]

Model organisms[]

Model organisms have been used in the study of CISH function. A conditional knockout mouse line, called Cish^{tm1a(KOMP)Wtsi[16][17]} was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists — at the Wellcome Trust Sanger Institute.^[18][19][20]

Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.^[14][21] Twenty four tests were carried out on mutant mice, however no significant abnormalities were observed.^[14]

Interactions[]

CISH has been shown to interact with IL2RB^[22] and Growth hormone receptor.^[23] and PLCG1.^[10]

References[]

Further reading[]

External links[]

• Human CISH genome location and CISH gene details page in the UCSC Genome Browser.