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CISH (protein)

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Protein-coding gene in the species Homo sapiens

This article is about the CISH gene. For other uses, see CISH.
CISH
Identifiers
AliasesCISH, BACTS2, CIS, CIS-1, G18, SOCS, cytokine inducible SH2 containing protein
External IDsOMIM: 602441; MGI: 103159; HomoloGene: 7667; GeneCards: CISH; OMA:CISH - orthologs
Gene location (Human)
Chromosome 3 (human)
Chr.Chromosome 3 (human)
Chromosome 3 (human)Genomic location for CISHGenomic location for CISH
Band3p21.2Start50,606,489 bp
End50,611,774 bp
Gene location (Mouse)
Chromosome 9 (mouse)
Chr.Chromosome 9 (mouse)
Chromosome 9 (mouse)Genomic location for CISHGenomic location for CISH
Band9 F1|9 57.99 cMStart107,173,225 bp
End107,179,983 bp
RNA expression pattern
Bgee
HumanMouse (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
Cellular component
Biological process
Sources:Amigo / QuickGO
Orthologs
SpeciesHumanMouse
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 MbChr 9: 107.17 – 107.18 Mb
PubMed search
Wikidata
View/Edit HumanView/Edit Mouse

Cytokine-inducible SH2-containing protein is a protein that in humans is encoded by the CISH gene. CISH orthologs 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.

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.

CISH is induced by T cell receptor (TCR) ligation and negatively regulates it by targeting the critical signaling intermediate PLC-gamma-1 for degradation. 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

Interactions

CISH has been shown to interact with IL2RB and Growth hormone receptor. and PLCG1.

References

  1. ^ GRCh38: Ensembl release 89: ENSG00000114737Ensembl, May 2017
  2. ^ GRCm38: Ensembl release 89: ENSMUSG00000032578Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. Uchida K, Yoshimura A, Inazawa J, Yanagisawa K, Osada H, Masuda A, et al. (Mar 1998). "Molecular cloning of CISH, chromosome assignment to 3p21.3, and analysis of expression in fetal and adult tissues". Cytogenetics and Cell Genetics. 78 (3–4): 209–212. doi:10.1159/000134658. PMID 9465889.
  6. Yoshimura A, Ohkubo T, Kiguchi T, Jenkins NA, Gilbert DJ, Copeland NG, et al. (June 1995). "A novel cytokine-inducible gene CIS encodes an SH2-containing protein that binds to tyrosine-phosphorylated interleukin 3 and erythropoietin receptors". The EMBO Journal. 14 (12): 2816–2826. doi:10.1002/j.1460-2075.1995.tb07281.x. PMC 398400. PMID 7796808.
  7. ^ "Entrez Gene: CISH cytokine inducible SH2-containing protein".
  8. "OrthoMaM phylogenetic marker: CISH coding sequence". Archived from the original on 2016-03-04. Retrieved 2010-02-17.
  9. Khor CC, Vannberg FO, Chapman SJ, Guo H, Wong SH, Walley AJ, et al. (June 2010). "CISH and susceptibility to infectious diseases". The New England Journal of Medicine. 362 (22): 2092–2101. doi:10.1056/NEJMoa0905606. PMC 3646238. PMID 20484391.
  10. ^ Palmer DC, Guittard GC, Franco Z, Crompton JG, Eil RL, Patel SJ, et al. (November 2015). "Cish actively silences TCR signaling in CD8+ T cells to maintain tumor tolerance". The Journal of Experimental Medicine. 212 (12): 2095–2113. doi:10.1084/jem.20150304. PMC 4647263. PMID 26527801.
  11. Palmer DC, Webber BR, Patel Y, Johnson MJ, Kariya CM, Lahr WS, et al. (2022). "Internal checkpoint regulates T cell neoantigen reactivity and susceptibility to PD1 blockade". Med. 3 (10): 682–704.e8. doi:10.1016/j.medj.2022.07.008. PMC 9847506. PMID 36007524.{{cite journal}}: CS1 maint: overridden setting (link)
  12. Aman MJ, Migone TS, Sasaki A, Ascherman DP, Zhu M, Soldaini E, et al. (October 1999). "CIS associates with the interleukin-2 receptor beta chain and inhibits interleukin-2-dependent signaling". The Journal of Biological Chemistry. 274 (42): 30266–30272. doi:10.1074/jbc.274.42.30266. PMID 10514520.
  13. Ram PA, Waxman DJ (December 1999). "SOCS/CIS protein inhibition of growth hormone-stimulated STAT5 signaling by multiple mechanisms". The Journal of Biological Chemistry. 274 (50): 35553–35561. doi:10.1074/jbc.274.50.35553. PMID 10585430.

Further reading

External links

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