IL13RA2 explained

Interleukin-13 receptor subunit alpha-2 (IL-13Rα2), also known as CD213A2 (cluster of differentiation 213A2), is a membrane bound protein that in humans is encoded by the IL13RA2 gene.^[1]

Function

IL-13Rα2 is closely related to IL-13Rα1, a subunit of the interleukin-13 receptor complex. This protein binds IL13 with high affinity, but lacks any significant cytoplasmic domain, and does not appear to function as a signal mediator. It is, however, able to regulate the effects of both IL-13 and IL-4, despite the fact it is unable to bind directly to the latter. It is also reported to play a role in the internalization of IL13.

Clinical Significance

IL-13Rα2 has been found to be over-expressed in a variety of cancers, including pancreatic, ovarian, melanomas, and malignant gliomas. ^{[2] [3] [4] [5]}

See also

• Interleukin-13 receptor

Further reading

• Andrews AL, Nasir T, Bucchieri F, Holloway JW, Holgate ST, Davies DE . IL-13 receptor alpha 2: a regulator of IL-13 and IL-4 signal transduction in primary human fibroblasts . The Journal of Allergy and Clinical Immunology . 118 . 4 . 858–65 . October 2006 . 17030238 . 10.1016/j.jaci.2006.06.041 . free .
• Caput D, Laurent P, Kaghad M, Lelias JM, Lefort S, Vita N, Ferrara P . Cloning and characterization of a specific interleukin (IL)-13 binding protein structurally related to the IL-5 receptor alpha chain . The Journal of Biological Chemistry . 271 . 28 . 16921–6 . July 1996 . 8663118 . 10.1074/jbc.271.28.16921 . free .
• Zhang JG, Hilton DJ, Willson TA, McFarlane C, Roberts BA, Moritz RL, Simpson RJ, Alexander WS, Metcalf D, Nicola NA . Identification, purification, and characterization of a soluble interleukin (IL)-13-binding protein. Evidence that it is distinct from the cloned Il-13 receptor and Il-4 receptor alpha-chains . The Journal of Biological Chemistry . 272 . 14 . 9474–80 . April 1997 . 9083087 . 10.1074/jbc.272.14.9474 . free.
• Gauchat JF, Schlagenhauf E, Feng NP, Moser R, Yamage M, Jeannin P, Alouani S, Elson G, Notarangelo LD, Wells T, Eugster HP, Bonnefoy JY . A novel 4-kb interleukin-13 receptor alpha mRNA expressed in human B, T, and endothelial cells encoding an alternate type-II interleukin-4/interleukin-13 receptor . European Journal of Immunology . 27 . 4 . 971–8 . April 1997 . 9130652 . 10.1002/eji.1830270425 . 23762963 .
• Guo J, Apiou F, Mellerin MP, Lebeau B, Jacques Y, Minvielle S . Chromosome mapping and expression of the human interleukin-13 receptor . Genomics . 42 . 1 . 141–5 . May 1997 . 9177784 . 10.1006/geno.1997.4628 .
• Donaldson DD, Whitters MJ, Fitz LJ, Neben TY, Finnerty H, Henderson SL, O'Hara RM, Beier DR, Turner KJ, Wood CR, Collins M . The murine IL-13 receptor alpha 2: molecular cloning, characterization, and comparison with murine IL-13 receptor alpha 1 . Journal of Immunology . 161 . 5 . 2317–24 . September 1998 . 10.4049/jimmunol.161.5.2317 . 9725226 . 255357984 .
• Osawa M, Miyoshi S, Copeland NG, Gilbert DJ, Jenkins NA, Hiroyama T, Motohashi T, Nakamura Y, Iwama A, Nakauchi H . Characterization of the mouse interleukin-13 receptor alpha1 gene . Immunogenetics . 51 . 11 . 974–81 . September 2000 . 11003391 . 10.1007/s002510000225 . 9030454 .
• Kawakami K, Takeshita F, Puri RK . Identification of distinct roles for a dileucine and a tyrosine internalization motif in the interleukin (IL)-13 binding component IL-13 receptor alpha 2 chain . The Journal of Biological Chemistry . 276 . 27 . 25114–20 . July 2001 . 11352909 . 10.1074/jbc.M100936200 . free .
• Daines MO, Hershey GK . A novel mechanism by which interferon-gamma can regulate interleukin (IL)-13 responses. Evidence for intracellular stores of IL-13 receptor alpha -2 and their rapid mobilization by interferon-gamma . The Journal of Biological Chemistry . 277 . 12 . 10387–93 . March 2002 . 11786536 . 10.1074/jbc.M108109200 . free .
• Okano F, Storkus WJ, Chambers WH, Pollack IF, Okada H . Identification of a novel HLA-A*0201-restricted, cytotoxic T lymphocyte epitope in a human glioma-associated antigen, interleukin 13 receptor alpha2 chain . Clinical Cancer Research . 8 . 9 . 2851–5 . September 2002 . 12231526 .
• Cancino-Díaz JC, Reyes-Maldonado E, Bañuelos-Pánuco CA, Jiménez-Zamudio L, García-Latorre E, León-Dorantes G, Blancas-González F, Paredes-Cabrera G, Cancino-Díaz ME . Interleukin-13 receptor in psoriatic keratinocytes: overexpression of the mRNA and underexpression of the protein . The Journal of Investigative Dermatology . 119 . 5 . 1114–20 . November 2002 . 12445201 . 10.1046/j.1523-1747.2002.19509.x . free .
• David M, Bertoglio J, Pierre J . TNF-alpha potentiates IL-4/IL-13-induced IL-13Ralpha2 expression . Annals of the New York Academy of Sciences . 973 . 207–9 . November 2002 . 1 . 12485861 . 10.1111/j.1749-6632.2002.tb04633.x . 2002NYASA.973..207D . 86154739 .
• Wu AH, Low WC . Molecular cloning and identification of the human interleukin 13 alpha 2 receptor (IL-13Ra2) promoter . Neuro-Oncology . 5 . 3 . 179–87 . July 2003 . 12816724 . 1920687 . 10.1215/s1152851702000510 .
• Arima K, Sato K, Tanaka G, Kanaji S, Terada T, Honjo E, Kuroki R, Matsuo Y, Izuhara K . Characterization of the interaction between interleukin-13 and interleukin-13 receptors . The Journal of Biological Chemistry . 280 . 26 . 24915–22 . July 2005 . 15870068 . 10.1074/jbc.M502571200 . free .
• Fichtner-Feigl S, Strober W, Kawakami K, Puri RK, Kitani A . IL-13 signaling through the IL-13alpha2 receptor is involved in induction of TGF-beta1 production and fibrosis . Nature Medicine . 12 . 1 . 99–106 . January 2006 . 16327802 . 10.1038/nm1332 . 38397076 .
• Daines MO, Tabata Y, Walker BA, Chen W, Warrier MR, Basu S, Hershey GK . Level of expression of IL-13R alpha 2 impacts receptor distribution and IL-13 signaling . Journal of Immunology . 176 . 12 . 7495–501 . June 2006 . 16751396 . 10.4049/jimmunol.176.12.7495 . free .
• Kioi M, Kawakami M, Shimamura T, Husain SR, Puri RK . Interleukin-13 receptor alpha2 chain: a potential biomarker and molecular target for ovarian cancer therapy . Cancer . 107 . 6 . 1407–18 . September 2006 . 16902988 . 10.1002/cncr.22134 . 70773746 . free .
• Granel B, Allanore Y, Chevillard C, Arnaud V, Marquet S, Weiller PJ, Durand JM, Harlé JR, Grange C, Frances Y, Berbis P, Gaudart J, de Micco P, Kahan A, Dessein A . IL13RA2 gene polymorphisms are associated with systemic sclerosis . The Journal of Rheumatology . 33 . 10 . 2015–9 . October 2006 . 16981293 .

Notes and References

1. Web site: Entrez Gene: IL13RA2 interleukin 13 receptor, alpha 2.
2. Fujisawa T, Joshi B, Nakajima A, Puri RK . A novel role of interleukin-13 receptor alpha2 in pancreatic cancer invasion and metastasis . Cancer Research . 69 . 22 . 8678–85 . November 2009 . 19887609 . 10.1158/0008-5472.CAN-09-2100 . free .
3. Kioi M, Kawakami M, Shimamura T, Husain SR, Puri RK . Interleukin-13 receptor alpha2 chain: a potential biomarker and molecular target for ovarian cancer therapy . Cancer . 107 . 6 . 1407–18 . September 2006 . 16902988 . 10.1002/cncr.22134 . 70773746 . free .
4. Okamoto H, Yoshimatsu Y, Tomizawa T, Kunita A, Takayama R, Morikawa T, Komura D, Takahashi K, Oshima T, Sato M, Komai M, Podyma-Inoue KA, Uchida H, Hamada H, Fujiu K, Ishikawa S, Fukayama M, Fukuhara T, Watabe T . Interleukin-13 receptor α2 is a novel marker and potential therapeutic target for human melanoma . Scientific Reports . 9 . 1 . 1281 . February 2019 . 30718742 . 6362032 . 10.1038/s41598-019-39018-3 . 2019NatSR...9.1281O .
5. Joshi BH, Plautz GE, Puri RK . Interleukin-13 receptor alpha chain: a novel tumor-associated transmembrane protein in primary explants of human malignant gliomas . Cancer Research . 60 . 5 . 1168–72 . March 2000 . 10728667 .