CISH

Cytokine inducible SH2-containing protein
Identifiers
Symbols	CISH; CIS; CIS-1; G18; SOCS
External IDs	OMIM: 602441 MGI: 103159 HomoloGene: 7667 GeneCards: CISH Gene
Gene Ontology Molecular function • molecular_function Cellular component • cellular_component • intracellular Biological process • regulation of cell growth • negative regulation of signal transduction • intracellular signal transduction Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	1154	12700
Ensembl	ENSG00000114737	ENSMUSG00000032578
UniProt	Q9NSE2	Q8C3F4
RefSeq (mRNA)	NM_013324.5	NM_009895.3
RefSeq (protein)	NP_037456.5	NP_034025.1
Location (UCSC)	Chr 3: 50.64 – 50.65 Mb	Chr 9: 107.2 – 107.21 Mb
PubMed search	[1]	[2]

Cytokine-inducible SH2-containing protein is a protein that in humans is encoded by the CISH gene.^[1][2][3] CISH orthologs ^[4] have been identified in most mammals with sequenced genomes. CISH controls interleukin-2 signaling, and variations of CISH with certain SNPs are associated with susceptibility to bacteremia, tuberculosis and malaria.^[5]

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 IL2, IL3, 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.^[3]

Interactions

CISH has been shown to interact with IL2RB^[6] and Growth hormone receptor.^[7]

References

1. ^ Uchida K, Yoshimura A, Inazawa J, Yanagisawa K, Osada H, Masuda A, Saito T, Takahashi T, Miyajima A, Takahashi T (Mar 1998). "Molecular cloning of CISH, chromosome assignment to 3p21.3, and analysis of expression in fetal and adult tissues". Cytogenet Cell Genet 78 (3–4): 209–12. doi:10.1159/000134658. PMID 9465889. 
2. ^ Yoshimura A, Ohkubo T, Kiguchi T, Jenkins NA, Gilbert DJ, Copeland NG, Hara T, Miyajima A (Aug 1995). "A novel cytokine-inducible gene CIS encodes an SH2-containing protein that binds to tyrosine-phosphorylated interleukin 3 and erythropoietin receptors". EMBO J 14 (12): 2816–26. PMC 398400. PMID 7796808. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=398400. 
3. ^ ^{a b} "Entrez Gene: CISH cytokine inducible SH2-containing protein". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1154. 
4. ^ "OrthoMaM phylogenetic marker: CISH coding sequence". http://www.orthomam.univ-montp2.fr/orthomam/data/cds/detailMarkers/ENSG00000114737_CISH.xml. 
5. ^ Khor CC, Vannberg FO, Chapman SJ et al. (June 2010). "CISH and susceptibility to infectious diseases". N. Engl. J. Med. 362 (22): 2092–101. doi:10.1056/NEJMoa0905606. PMID 20484391. http://content.nejm.org/cgi/pmidlookup?view=short&pmid=20484391&promo=ONFLNS19.  [Free Text]
6. ^ Aman, M J; Migone T S, Sasaki A, Ascherman D P, Zhu M h, Soldaini E, Imada K, Miyajima A, Yoshimura A, Leonard W J (Oct. 1999). "CIS associates with the interleukin-2 receptor beta chain and inhibits interleukin-2-dependent signaling". J. Biol. Chem. (UNITED STATES) 274 (42): 30266–72. doi:10.1074/jbc.274.42.30266. ISSN 0021-9258. PMID 10514520. 
7. ^ Ram, P A; Waxman D J (Dec. 1999). "SOCS/CIS protein inhibition of growth hormone-stimulated STAT5 signaling by multiple mechanisms". J. Biol. Chem. (UNITED STATES) 274 (50): 35553–61. doi:10.1074/jbc.274.50.35553. ISSN 0021-9258. PMID 10585430. 

Further reading

• Kile BT, Schulman BA, Alexander WS et al. (2002). "The SOCS box: a tale of destruction and degradation". Trends Biochem. Sci. 27 (5): 235–41. doi:10.1016/S0968-0004(02)02085-6. PMID 12076535. 
• Verdier F, Chrétien S, Muller O et al. (1998). "Proteasomes regulate erythropoietin receptor and signal transducer and activator of transcription 5 (STAT5) activation. Possible involvement of the ubiquitinated Cis protein". J. Biol. Chem. 273 (43): 28185–90. doi:10.1074/jbc.273.43.28185. PMID 9774439. 
• Aman MJ, Migone TS, Sasaki A et al. (1999). "CIS associates with the interleukin-2 receptor beta chain and inhibits interleukin-2-dependent signaling". J. Biol. Chem. 274 (42): 30266–72. doi:10.1074/jbc.274.42.30266. PMID 10514520. 
• Okabe S, Tauchi T, Morita H et al. (1999). "Thrombopoietin induces an SH2-containing protein, CIS1, which binds to Mpl: involvement of the ubiquitin proteosome pathway". Exp. Hematol. 27 (10): 1542–7. doi:10.1016/S0301-472X(99)00094-6. PMID 10517496. 
• Jiang C, Yu L, Zhao Y et al. (2000). "Cloning and characterization of CIS 1b (cytokine inducible SH2-containing protein 1b), an alternative splicing form of CIS 1 gene". DNA Seq. 11 (1–2): 149–54. PMID 10902923. 
• Dogusan Z, Hooghe-Peters EL, Berus D et al. (2000). "Expression of SOCS genes in normal and leukemic human leukocytes stimulated by prolactin, growth hormone and cytokines". J. Neuroimmunol. 109 (1): 34–9. doi:10.1016/S0165-5728(00)00300-3. PMID 10969179. 
• Yousefi S, Cooper PR, Mueck B et al. (2000). "cDNA representational difference analysis of human neutrophils stimulated by GM-CSF". Biochem. Biophys. Res. Commun. 277 (2): 401–9. doi:10.1006/bbrc.2000.3678. PMID 11032736. 
• Dif F, Saunier E, Demeneix B et al. (2001). "Cytokine-inducible SH2-containing protein suppresses PRL signaling by binding the PRL receptor". Endocrinology 142 (12): 5286–93. doi:10.1210/en.142.12.5286. PMID 11713228. 
• Federici M, Giustizieri ML, Scarponi C et al. (2002). "Impaired IFN-gamma-dependent inflammatory responses in human keratinocytes overexpressing the suppressor of cytokine signaling 1". J. Immunol. 169 (1): 434–42. PMID 12077274. 
• Strausberg RL, Feingold EA, Grouse LH et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=139241. 
• Du L, Frick GP, Tai LR et al. (2003). "Interaction of the growth hormone receptor with cytokine-induced Src homology domain 2 protein in rat adipocytes". Endocrinology 144 (3): 868–76. doi:10.1210/en.2002-220830. PMID 12586763. 
• Chen S, Anderson PO, Li L et al. (2003). "Functional association of cytokine-induced SH2 protein and protein kinase C in activated T cells". Int. Immunol. 15 (3): 403–9. doi:10.1093/intimm/dxg039. PMID 12618484. 
• Yamasaki K, Hanakawa Y, Tokumaru S et al. (2003). "Suppressor of cytokine signaling 1/JAB and suppressor of cytokine signaling 3/cytokine-inducible SH2 containing protein 3 negatively regulate the signal transducers and activators of transcription signaling pathway in normal human epidermal keratinocytes". J. Invest. Dermatol. 120 (4): 571–80. doi:10.1046/j.1523-1747.2003.12100.x. PMID 12648219. 
• Cheng J, Zhang D, Zhou C, Marasco WA (2004). "Down-regulation of SHP1 and up-regulation of negative regulators of JAK/STAT signaling in HTLV-1 transformed cell lines and freshly transformed human peripheral blood CD4+ T-cells". Leuk. Res. 28 (1): 71–82. doi:10.1016/S0145-2126(03)00158-9. PMID 14630083. 
• Bayle J, Letard S, Frank R et al. (2004). "Suppressor of cytokine signaling 6 associates with KIT and regulates KIT receptor signaling". J. Biol. Chem. 279 (13): 12249–59. doi:10.1074/jbc.M313381200. PMID 14707129. 
• Colland F, Jacq X, Trouplin V et al. (2004). "Functional Proteomics Mapping of a Human Signaling Pathway". Genome Res. 14 (7): 1324–32. doi:10.1101/gr.2334104. PMC 442148. PMID 15231748. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=442148. 
• Hunter MG, Jacob A, O'donnell LC et al. (2004). "Loss of SHIP and CIS recruitment to the granulocyte colony-stimulating factor receptor contribute to hyperproliferative responses in severe congenital neutropenia/acute myelogenous leukemia". J. Immunol. 173 (8): 5036–45. PMID 15470047.