Interleukin 15 receptor, alpha subunit

Interleukin 15 receptor, alpha subunit is a subunit of the interleukin 15 receptor that in humans is encoded by the IL15RA gene.[5]

IL15RA
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2ERS, 2Z3Q, 2Z3R, 4GS7
Identifiers
Aliases	IL15RA, CD215, Interleukin 15 receptor, alpha subunit, interleukin 15 receptor subunit alpha
External IDs	OMIM: 601070 MGI: 104644 HomoloGene: 1650 GeneCards: IL15RA
Gene location (Human) Chr. Chromosome 10 (human)[1] Band 10p15.1 Start 5,943,639 bp[1] End 5,978,187 bp[1]
Gene location (Mouse) Chr. Chromosome 2 (mouse)[2] Band 2 A1|2 8.97 cM Start 11,705,290 bp[2] End 11,734,317 bp[2]
RNA expression pattern More reference expression data
Gene ontology Molecular function • cytokine receptor activity • GO:0001948 protein binding • signal transducer activity • protein kinase binding • interleukin-15 receptor activity Cellular component • cytoplasmic vesicle • integral component of membrane • extracellular region • Golgi membrane • Golgi apparatus • nuclear membrane • endoplasmic reticulum membrane • cytoplasmic vesicle membrane • cell nucleus • endoplasmic reticulum • membrane • cell membrane • extracellular • endosome • cell surface Biological process • cellular proliferation • signal transduction • interleukin-15-mediated signaling pathway • positive regulation of phagocytosis Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	3601	16169
Ensembl	ENSG00000134470	ENSMUSG00000023206
UniProt	Q13261	Q60819
RefSeq (mRNA)	NM_001243539 NM_001256765 NM_002189 NM_172200 NM_001351095 NM_001351096 NM_001351097	NM_001271497 NM_001271498 NM_001271499 NM_001271500 NM_001271501 NM_008358 NM_133836
RefSeq (protein)	NP_001230468 NP_001243694 NP_002180 NP_751950 NP_001338024 NP_001338025 NP_001338026	NP_001258426 NP_001258427 NP_001258428 NP_001258429 NP_001258430 NP_032384 NP_598597
Location (UCSC)	Chr 10: 5.94 – 5.98 Mb	Chr 2: 11.71 – 11.73 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

Structure

The IL-15 receptor is composed of three subunits: IL-15R alpha, CD122, and CD132. Two of these subunits, CD122 and CD132, are shared with the receptor for IL-2, but IL-2 receptor has an additional subunit (CD25). The shared subunits contain the cytoplasmic motifs required for signal transduction, and this forms the basis of many overlapping biological activities of IL15 and IL2, although in vivo the two cytokines have separate biological effects. This may be due to effects of the respective alpha chains, which are unique to each receptor, the kinetics and affinity of cytokine-cytokine receptor binding, or due to the availability and concentration of each cytokine.

Function

IL-15Ralpha specifically binds IL15 with very high affinity,[6] and is capable of binding IL-15 independently of other subunits. It is suggested that this property allows IL-15 to be produced by one cell, endocytosed by another cell, and then presented to a third party cell.[7]

This receptor is reported to enhance cell proliferation and expression of apoptosis inhibitor BCL2L1/BCL2-XL and BCL2. Multiple alternatively spliced transcript variants of this gene have been reported. The full length sequences of only two variants encoding distinct isoforms are available.[5]

Isoforms

Several isoforms of the IL-15Ralpha protein have been detected. These isoforms can either result from alternative splicing of the mRNA encoding for the receptor or by shedding of the extra cellular domain of the receptor protein.

References

1. GRCh38: Ensembl release 89: ENSG00000134470 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000023206 - Ensembl, 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. EntrezGene 3601
6. Giri JG, Ahdieh M, Eisenman J, Shanebeck K, Grabstein K, Kumaki S, Namen A, Park LS, Cosman D, Anderson D (1994). "Utilization of the beta and gamma chains of the IL-2 receptor by the novel cytokine IL-15". EMBO J. 13 (12): 2822–30. doi:10.1002/j.1460-2075.1994.tb06576.x. PMC 395163. PMID 8026467.
7. Dubois S, Mariner J, Waldmann TA, Tagaya Y (2002). "IL-15Ralpha recycles and presents IL-15 In trans to neighboring cells". Immunity. 17 (5): 537–47. doi:10.1016/s1074-7613(02)00429-6. PMID 12433361. (primary source)

Further reading

• Giri JG, Kumaki S, Ahdieh M, Friend DJ, Loomis A, Shanebeck K, DuBose R, Cosman D, Park LS, Anderson DM (1995). "Identification and cloning of a novel IL-15 binding protein that is structurally related to the alpha chain of the IL-2 receptor". EMBO J. 14 (15): 3654–63. doi:10.1002/j.1460-2075.1995.tb00035.x. PMC 394440. PMID 7641685.
• Jacob CO, Mykytyn K, Varcony T, Drabkin HA (1993). "Mapping of the interleukin 5 receptor gene to human chromosome 3 p25-p26 and to mouse chromosome 6 close to the Raf-1 locus with polymorphic tandem repeat sequences". Mamm. Genome. 4 (8): 435–9. doi:10.1007/BF00296817. PMID 8104057.
• Anderson DM, Kumaki S, Ahdieh M, Bertles J, Tometsko M, Loomis A, Giri J, Copeland NG, Gilbert DJ, Jenkins NA (1995). "Functional characterization of the human interleukin-15 receptor alpha chain and close linkage of IL15RA and IL2RA genes". J. Biol. Chem. 270 (50): 29862–9. doi:10.1074/jbc.270.50.29862. PMID 8530383.
• Andersson B, Wentland MA, Ricafrente JY, Liu W, Gibbs RA (1996). "A "double adaptor" method for improved shotgun library construction". Anal. Biochem. 236 (1): 107–13. doi:10.1006/abio.1996.0138. PMID 8619474.
• Yu W, Andersson B, Worley KC, Muzny DM, Ding Y, Liu W, Ricafrente JY, Wentland MA, Lennon G, Gibbs RA (1997). "Large-scale concatenation cDNA sequencing". Genome Res. 7 (4): 353–8. doi:10.1101/gr.7.4.353. PMC 139146. PMID 9110174.
• Dubois S, Magrangeas F, Lehours P, Raher S, Bernard J, Boisteau O, Leroy S, Minvielle S, Godard A, Jacques Y (1999). "Natural splicing of exon 2 of human interleukin-15 receptor alpha-chain mRNA results in a shortened form with a distinct pattern of expression". J. Biol. Chem. 274 (38): 26978–84. doi:10.1074/jbc.274.38.26978. PMID 10480910.
• Pereno R, Giron-Michel J, Gaggero A, Cazes E, Meazza R, Monetti M, Monaco E, Mishal Z, Jasmin C, Indiveri F, Ferrini S, Azzarone B (2000). "IL-15/IL-15Ralpha intracellular trafficking in human melanoma cells and signal transduction through the IL-15Ralpha". Oncogene. 19 (45): 5153–62. doi:10.1038/sj.onc.1203873. PMID 11064452.
• Mariner JM, Lantz V, Waldmann TA, Azimi N (2001). "Human T cell lymphotropic virus type I Tax activates IL-15R alpha gene expression through an NF-kappa B site". J. Immunol. 166 (4): 2602–9. doi:10.4049/jimmunol.166.4.2602. PMID 11160322.
• Asao H, Okuyama C, Kumaki S, Ishii N, Tsuchiya S, Foster D, Sugamura K (2001). "Cutting edge: the common gamma-chain is an indispensable subunit of the IL-21 receptor complex". J. Immunol. 167 (1): 1–5. doi:10.4049/jimmunol.167.1.1. PMID 11418623.
• Wu TS, Lee JM, Lai YG, Hsu JC, Tsai CY, Lee YH, Liao NS (2002). "Reduced expression of Bcl-2 in CD8+ T cells deficient in the IL-15 receptor alpha-chain". J. Immunol. 168 (2): 705–12. doi:10.4049/jimmunol.168.2.705. PMID 11777964.
• Khan IA, Moretto M, Wei XQ, Williams M, Schwartzman JD, Liew FY (2002). "Treatment with soluble interleukin-15Ralpha exacerbates intracellular parasitic infection by blocking the development of memory CD8+ T cell response". J. Exp. Med. 195 (11): 1463–70. doi:10.1084/jem.20011915. PMC 2193543. PMID 12045244.
• Kurowska M, Rudnicka W, Maślińska D, Maśliński W (2002). "Expression of IL-15 and IL-15 receptor isoforms in select structures of human fetal brain". Ann. N. Y. Acad. Sci. 966 (1): 441–5. Bibcode:2002NYASA.966..441K. doi:10.1111/j.1749-6632.2002.tb04245.x. PMID 12114302.
• Comes A, Di Carlo E, Musiani P, Rosso O, Meazza R, Chiodoni C, Colombo MP, Ferrini S (2002). "IFN-gamma-independent synergistic effects of IL-12 and IL-15 induce anti-tumor immune responses in syngeneic mice". Eur. J. Immunol. 32 (7): 1914–23. doi:10.1002/1521-4141(200207)32:7<1914::AID-IMMU1914>3.0.CO;2-P. PMID 12115611.
• Bernard J, Harb C, Mortier E, Quéméner A, Meloen RH, Vermot-Desroches C, Wijdeness J, van Dijken P, Grötzinger J, Slootstra JW, Plet A, Jacques Y (2004). "Identification of an interleukin-15alpha receptor-binding site on human interleukin-15". J. Biol. Chem. 279 (23): 24313–22. doi:10.1074/jbc.M312458200. PMID 15039446.
• Vámosi G, Bodnár A, Vereb G, Jenei A, Goldman CK, Langowski J, Tóth K, Mátyus L, Szöllösi J, Waldmann TA, Damjanovich S (2004). "IL-2 and IL-15 receptor alpha-subunits are coexpressed in a supramolecular receptor cluster in lipid rafts of T cells". Proc. Natl. Acad. Sci. U.S.A. 101 (30): 11082–7. Bibcode:2004PNAS..10111082V. doi:10.1073/pnas.0403916101. PMC 503744. PMID 15263076.
• Mortier E, Bernard J, Plet A, Jacques Y (2004). "Natural, proteolytic release of a soluble form of human IL-15 receptor alpha-chain that behaves as a specific, high affinity IL-15 antagonist". J. Immunol. 173 (3): 1681–8. doi:10.4049/jimmunol.173.3.1681. PMID 15265897.