Common gamma chain
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Location (UCSC) | Chr X: 71.11 – 71.11 Mb | Chr X: 100.31 – 100.31 Mb | |||||||
PubMed search | [3] | [4] |
View/Edit Human | View/Edit Mouse |
The common gamma chain (γc) (or CD132), also known as interleukin-2 receptor subunit gamma or IL-2RG, is a
This protein is located on the surface of immature blood-forming cells in bone marrow. One end of the protein resides outside the cell where it binds to cytokines and the other end of the protein resides in the interior of the cell where it transmits signals to the cell's nucleus. The common gamma chain partners with other proteins to direct blood-forming cells to form lymphocytes (a type of white blood cell). The receptor also directs the growth and maturation of lymphocyte subtypes: T cells, B cells, and natural killer cells. These cells kill viruses, make antibodies, and help regulate the entire immune system.
Gene
Cytokine receptor common subunit gamma also known as interleukin-2 receptor subunit gamma or IL-2RG is a protein that in humans is encoded by the IL2RG gene.[8] The human IL2RG gene is located on the long (q) arm of the X chromosome at position 13.1, from base pair 70,110,279 to base pair 70,114,423.
Structure
The γc chain is an integral membrane protein that contains extracellular, transmembrane, and intracellular domains.
Function
Lymphocytes expressing the common gamma chain can form functional receptors for these cytokine proteins, which transmit signals from one cell to another and direct programs of cellular differentiation.
Ligands
The γc chain partners with other ligand-specific receptors to direct lymphocytes to respond to cytokines including IL-2, IL-4, IL-7, IL-9, IL-15 and IL-21.[9]
Signalling
IL2RG has been shown to
Clinical significance
X-linked severe combined immunodeficiency
Experiments in animal models have shown X-SCID to occur similarly in dogs, but not in mice.[14]
Schizophrenia
Alterations in the immune response are involved in pathogenesis of many neuropsychiatric disorders including schizophrenia. Distinct gene variants of a number of pro-inflammatory and chemotactic cytokines together with their receptors associate with this disorder. IL2RG represents an important signaling component of many interleukin receptors and so far, no data on the functional state of this receptor in schizophrenia have been reported. Over-expression of the IL2RG gene may be implicated in altered immune response in schizophrenia and contribute to the pathogenesis of this disorder.[15]
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000147168 - Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000031304 - Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- PMID 8266078.
- PMID 8266077.
- PMID 7641685.
- PMID 1631559.
- PMID 11418623.
- PMID 7973659.
- PMID 7973658.
- )
- PMID 7883965.
- PMID 7829104.
- S2CID 44296846.
Further reading
- Buckley RH (2004). "Molecular defects in human severe combined immunodeficiency and approaches to immune reconstitution". Annu Rev Immunol. 22: 625–55. PMID 15032591.
- Kalman L, Lindegren ML, Kobrynski L, Vogt R, Hannon H, Howard JT, Buckley R (2004). "Mutations in genes required for T-cell development: IL7R, CD45, IL2RG, JAK3, RAG1, RAG2, ARTEMIS, and ADA and severe combined immunodeficiency: HuGE review". Genet Med. 6 (1): 16–26. PMID 14726805.
- Ellery JM, Nicholls PJ (2002). "Alternate signalling pathways from the interleukin-2 receptor". Cytokine Growth Factor Rev. 13 (1): 27–40. PMID 11750878.
- Takeshita T, Asao H, Ohtani K, Ishii N, Kumaki S, Tanaka N, Munakata H, Nakamura M, Sugamura K (July 1992). "Cloning of the gamma chain of the human IL-2 receptor". Science. 257 (5068): 379–82. PMID 1631559.
- Burton J, Goldman CK, Rao P, Moos M, Waldmann TA (September 1990). "Association of intercellular adhesion molecule 1 with the multichain high-affinity interleukin 2 receptor". Proc. Natl. Acad. Sci. U.S.A. 87 (18): 7329–33. PMID 1976256.
- Oyaizu N, Chirmule N, Kalyanaraman VS, Hall WW, Pahwa R, Shuster M, Pahwa S (March 1990). "Human immunodeficiency virus type 1 envelope glycoprotein gp120 produces immune defects in CD4+ T lymphocytes by inhibiting interleukin 2 mRNA". Proc. Natl. Acad. Sci. U.S.A. 87 (6): 2379–83. PMID 2315327.
- Kornfeld H, Cruikshank WW, Pyle SW, Berman JS, Center DM (September 1988). "Lymphocyte activation by HIV-1 envelope glycoprotein". Nature. 335 (6189): 445–8. S2CID 4326650.
- Bamborough P, Hedgecock CJ, Richards WG (1995). "The interleukin-2 and interleukin-4 receptors studied by molecular modelling". Structure. 2 (9): 839–51. PMID 7529123.
- Clark PA, Lester T, Genet S, Jones AM, Hendriks R, Levinsky RJ, Kinnon C (October 1995). "Screening for mutations causing X-linked severe combined immunodeficiency in the IL-2R gamma chain gene by single-strand conformation polymorphism analysis". Hum. Genet. 96 (4): 427–32. S2CID 29039832.
- Pepper AE, Buckley RH, Small TN, Puck JM (September 1995). "Two mutational hotspots in the interleukin-2 receptor gamma chain gene causing human X-linked severe combined immunodeficiency". Am. J. Hum. Genet. 57 (3): 564–71. PMID 7668284.
- Ohbo K, Takasawa N, Ishii N, Tanaka N, Nakamura M, Sugamura K (March 1995). "Functional analysis of the human interleukin 2 receptor gamma chain gene promoter". J. Biol. Chem. 270 (13): 7479–86. PMID 7706294.
- Puck JM, Pepper AE, Bédard PM, Laframboise R (February 1995). "Female germ line mosaicism as the origin of a unique IL-2 receptor gamma-chain mutation causing X-linked severe combined immunodeficiency". J. Clin. Invest. 95 (2): 895–9. PMID 7860773.
- DiSanto JP, Rieux-Laucat F, Dautry-Varsat A, Fischer A, de Saint Basile G (September 1994). "Defective human interleukin 2 receptor gamma chain in an atypical X chromosome-linked severe combined immunodeficiency with peripheral T cells". Proc. Natl. Acad. Sci. U.S.A. 91 (20): 9466–70. PMID 7937790.
- Russell SM, Johnston JA, Noguchi M, Kawamura M, Bacon CM, Friedmann M, Berg M, McVicar DW, Witthuhn BA, Silvennoinen O (November 1994). "Interaction of IL-2R beta and gamma c chains with Jak1 and Jak3: implications for XSCID and XCID". Science. 266 (5187): 1042–5. PMID 7973658.
- Ishii N, Asao H, Kimura Y, Takeshita T, Nakamura M, Tsuchiya S, Konno T, Maeda M, Uchiyama T, Sugamura K (August 1994). "Impairment of ligand binding and growth signaling of mutant IL-2 receptor gamma-chains in patients with X-linked severe combined immunodeficiency". J. Immunol. 153 (3): 1310–7. S2CID 24092176.
- Johnson K, Choi Y, Wu Z, Ciardelli T, Granzow R, Whalen C, Sana T, Pardee G, Smith K, Creasey A (1994). "Soluble IL-2 receptor beta and gamma subunits: ligand binding and cooperativity". Eur. Cytokine Netw. 5 (1): 23–34. PMID 8049354.
- Markiewicz S, Subtil A, Dautry-Varsat A, Fischer A, de Saint Basile G (May 1994). "Detection of three nonsense mutations and one missense mutation in the interleukin-2 receptor gamma chain gene in SCIDX1 that differently affect the mRNA processing". Genomics. 21 (1): 291–3. PMID 8088810.
- Kondo M, Takeshita T, Ishii N, Nakamura M, Watanabe S, Arai K, Sugamura K (December 1993). "Sharing of the interleukin-2 (IL-2) receptor gamma chain between receptors for IL-2 and IL-4". Science. 262 (5141): 1874–7. PMID 8266076.
External links
- Interleukin+Receptor+Common+gamma+Subunit at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
- Overview of all the structural information available in the PDB for UniProt: P31785 (Human Cytokine receptor common subunit gamma) at the PDBe-KB.