CISH (protein)

This article is about the CISH gene. For other uses, see CISH.

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]

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; OMA:CISH - orthologs
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 Human Mouse (ortholog) Top expressed in granulocyte left lobe of thyroid gland right lobe of thyroid gland human kidney tibialis anterior muscle right lobe of liver upper lobe of left lung blood placenta apex of heart Top expressed in interventricular septum triceps brachii muscle sternocleidomastoid muscle temporal muscle myocardium of ventricle digastric muscle cardiac muscles choroid plexus of fourth ventricle right ventricle right kidney More reference expression data BioGPS More reference expression data
Gene ontology Molecular function protein kinase inhibitor activity 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 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
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Function

The protein encoded by this gene contains a SH2 domain and a SOCS box domain. The protein thus belongs to the cytokine-induced STAT inhibitor (CIS), also known as suppressor of cytokine signaling (SOCS) or STAT-induced STAT inhibitor (SSI), protein family. CIS 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 synergistically results in profound tumor regressing in a pre-clinical tumor model ^[11]

Interactions

CISH has been shown to interact with IL2RB^[12] and Growth hormone receptor.^[13] and PLCG1.^[10]