Common gamma chain

The common gamma chain (γ_c) (or CD132), also known as interleukin-2 receptor subunit gamma or IL-2RG, is a cytokine receptor sub-unit that is common to the receptor complexes for at least six different interleukin receptors: IL-2, IL-4, IL-7, IL-9, IL-15 and interleukin-21 receptor. The γ_c glycoprotein is a member of the type I cytokine receptor family expressed on most lymphocyte (white blood cell) populations, and its gene is found on the X-chromosome of mammals.

IL2RG
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2B5I, 2ERJ, 3BPL, 3QAZ, 3QB7, 4GS7
Identifiers
Aliases	IL2RG, CD132, CIDX, IL-2RG, IMD4, P64, SCIDX, SCIDX1, interleukin 2 receptor subunit gamma
External IDs	OMIM: 308380; MGI: 96551; HomoloGene: 172; GeneCards: IL2RG; OMA:IL2RG - orthologs
Gene location (Human) Chr. X chromosome (human) Band Xq13.1 Start 71,107,404 bp End 71,112,108 bp
Gene location (Mouse) Chr. X chromosome (mouse) Band X D|X 43.9 cM Start 100,307,984 bp End 100,311,861 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in granulocyte lymph node appendix rectum thymus spleen bone marrow cells mucosa of ileum blood jejunal mucosa Top expressed in mesenteric lymph nodes thymus spleen blood decidua granulocyte right lung right lung lobe subcutaneous adipose tissue left lung More reference expression data BioGPS More reference expression data
Gene ontology Molecular function interleukin-7 receptor activity interleukin-2 receptor activity protein binding cytokine receptor activity interleukin-4 receptor activity interleukin-2 binding cytokine binding interleukin-15 receptor activity Cellular component integral component of membrane membrane plasma membrane integral component of plasma membrane external side of plasma membrane endosome cytosol cell surface receptor complex Biological process MAPK cascade immune response viral process signal transduction interleukin-2-mediated signaling pathway interleukin-4-mediated signaling pathway interleukin-7-mediated signaling pathway interleukin-15-mediated signaling pathway interleukin-9-mediated signaling pathway regulation of molecular function cytokine-mediated signaling pathway interleukin-21-mediated signaling pathway positive regulation of phagocytosis Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 3561 16186 Ensembl ENSG00000147168 ENSMUSG00000031304 UniProt P31785 P34902 RefSeq (mRNA) NM_000206 NM_013563 NM_001308535 RefSeq (protein) NP_000197 NP_001295464 NP_038591 Location (UCSC) Chr X: 71.11 – 71.11 Mb Chr X: 100.31 – 100.31 Mb PubMed search
Wikidata
View/Edit Human View/Edit Mouse

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. 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.

IL-7 receptor and signaling, common γ chain (blue) and IL-7 receptor-α (green)

Structure

The γ_c 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 γ_c 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.

Signalling

IL2RG has been shown to interact with Janus kinase 3.

Clinical significance

X-linked severe combined immunodeficiency

X-linked severe combined immunodeficiency is caused by mutations in the IL2RG gene. More than 200 different mutations in the IL2RG gene have been identified in people with X-linked severe combined immunodeficiency (SCID). Most of these mutations involve changes in one or a few nucleotides (DNA building blocks) in the gene. These changes lead to the production of a nonfunctional version of the common gamma chain protein or no production of protein. Without the common gamma chain, important chemical signals are not relayed to the nucleus and lymphocytes cannot develop normally. A lack of functional mature lymphocytes disrupts the immune system's ability to protect the body from infection. Affected people have no functional immunity and can die within months after birth without successful bone marrow transplantation or alternatively, isolation from exposure to pathogens. Without important developmental signals from IL-7 and IL-15, T-cell and NK cell populations respectively fail to develop.

Experiments in animal models have shown X-SCID to occur similarly in dogs, but not in mice.

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.

Further reading

• Buckley RH (2004). "Molecular defects in human severe combined immunodeficiency and approaches to immune reconstitution". Annu Rev Immunol. 22: 625–55. doi:10.1146/annurev.immunol.22.012703.104614. 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. doi:10.1097/01.GIM.0000105752.80592.A3. PMID 14726805.
• Ellery JM, Nicholls PJ (2002). "Alternate signalling pathways from the interleukin-2 receptor". Cytokine Growth Factor Rev. 13 (1): 27–40. doi:10.1016/S1359-6101(01)00023-5. 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. Bibcode:1992Sci...257..379T. doi:10.1126/science.1631559. 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. Bibcode:1990PNAS...87.7329B. doi:10.1073/pnas.87.18.7329. PMC 54737. 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. Bibcode:1990PNAS...87.2379O. doi:10.1073/pnas.87.6.2379. PMC 53690. 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. Bibcode:1988Natur.335..445K. doi:10.1038/335445a0. PMID 2843775. 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. doi:10.1016/S0969-2126(94)00085-9. 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. doi:10.1007/BF00191801. PMID 7557965. 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. PMC 1801277. 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. doi:10.1074/jbc.270.13.7479. 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. doi:10.1172/JCI117740. PMC 295580. 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. Bibcode:1994PNAS...91.9466D. doi:10.1073/pnas.91.20.9466. PMC 44833. 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. Bibcode:1994Sci...266.1042R. doi:10.1126/science.7973658. 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. doi:10.4049/jimmunol.153.3.1310. PMID 8027558. 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. doi:10.1006/geno.1994.1265. 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. Bibcode:1993Sci...262.1874K. doi:10.1126/science.8266076. 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.