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Gene Review

IL1RAP  -  interleukin 1 receptor accessory protein

Homo sapiens

Synonyms: C3orf13, IL-1 receptor accessory protein, IL-1R-3, IL-1R3, IL-1RAcP, ...
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Disease relevance of IL1RAP


High impact information on IL1RAP

  • We show here that IL-1beta-mediated activation of the protein tyrosine kinase Src depended on a MyD88 interaction with the IL-1RI/IL-1RAcP complex [4].
  • Interleukin-1 receptor (IL-1RI) is a master regulator of inflammation and innate immunity . When triggered by IL-1beta, IL-1RI aggregates with IL-1R-associated protein (IL-1RAcP) and forms a membrane proximal signalosome that potently activates downstream signaling cascades [5].
  • Antibodies directed against IL-1RAcP and transfection of cytoplasmically deleted IL-1RAcP both blocked activation of the pathway leading to NF-kappaB by the three cytokines [6].
  • Proportional expression of the different IL-1RAcP splice variants may be an important determinant of responsiveness to IL-1 [7].
  • Signal transduction is initiated at the cell membrane by complex formation between extracellular IL-1 and the transmembrane IL-1R type I (IL-1RI) and IL-1R accessory protein (IL-1RAcP) [8].

Biological context of IL1RAP


Anatomical context of IL1RAP

  • By expression cloning in COS-7 cells, we have isolated a cDNA from mouse 3T3-LI cells encoding this putative auxiliary molecule, which we term the IL-1 receptor accessory protein (IL-1R AcP) [13].
  • The physical association of ligated IL-1RII with IL-1RAcP was proven by crosslinking experiments with radio-iodinated IL-1 and subsequent immunoprecipitations in normal human B cells and in EL-4 D6/76 cells transiently cotransfected with IL-1RII and IL-1RAcP, respectively [14].
  • IL-1 signaling cascade in liver cells and the involvement of a soluble form of the IL-1 receptor accessory protein [8].
  • Constitutive expression of IL-1RI, IL-1RAcP, and IL-1Ra was detected in both immortalized and primary human airway epithelial cells [15].

Associations of IL1RAP with chemical compounds


Physical interactions of IL1RAP

  • The IL-1R accessory protein (IL-1RAcP) plays a role in IL-1R signaling by forming a complex with IL-1RI bound to the IL-1 ligand [17].

Other interactions of IL1RAP


Analytical, diagnostic and therapeutic context of IL1RAP


  1. Human Hepatitis B Viral e Antigen Interacts with Cellular Interleukin-1 Receptor Accessory Protein and Triggers Interleukin-1 Response. Yang, C.Y., Kuo, T.H., Ting, L.P. J. Biol. Chem. (2006) [Pubmed]
  2. Activation of acid sphingomyelinase by interleukin-1 (IL-1) requires the IL-1 receptor accessory protein. Hofmeister, R., Wiegmann, K., Korherr, C., Bernardo, K., Krönke, M., Falk, W. J. Biol. Chem. (1997) [Pubmed]
  3. Surveillance of transcriptomes in basic military trainees with normal, febrile respiratory illness, and convalescent phenotypes. Thach, D.C., Agan, B.K., Olsen, C., Diao, J., Lin, B., Gomez, J., Jesse, M., Jenkins, M., Rowley, R., Hanson, E., Tibbetts, C., Stenger, D.A., Walter, E. Genes Immun. (2005) [Pubmed]
  4. MyD88-dependent and -independent signaling by IL-1 in neurons probed by bifunctional Toll/IL-1 receptor domain/BB-loop mimetics. Davis, C.N., Mann, E., Behrens, M.M., Gaidarova, S., Rebek, M., Rebek, J., Bartfai, T. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  5. Intracellular trafficking of interleukin-1 receptor I requires tollip. Brissoni, B., Agostini, L., Kropf, M., Martinon, F., Swoboda, V., Lippens, S., Everett, H., Aebi, N., Janssens, S., Meylan, E., Felberbaum-Corti, M., Hirling, H., Gruenberg, J., Tschopp, J., Burns, K. Curr. Biol. (2006) [Pubmed]
  6. Interleukin (IL)-1F6, IL-1F8, and IL-1F9 signal through IL-1Rrp2 and IL-1RAcP to activate the pathway leading to NF-kappaB and MAPKs. Towne, J.E., Garka, K.E., Renshaw, B.R., Virca, G.D., Sims, J.E. J. Biol. Chem. (2004) [Pubmed]
  7. The 3' untranslated region of the membrane-bound IL-1R accessory protein mRNA confers tissue-specific destabilization. Jensen, L.E., Whitehead, A.S. J. Immunol. (2004) [Pubmed]
  8. IL-1 signaling cascade in liver cells and the involvement of a soluble form of the IL-1 receptor accessory protein. Jensen, L.E., Muzio, M., Mantovani, A., Whitehead, A.S. J. Immunol. (2000) [Pubmed]
  9. Expression of alternatively spliced interleukin-1 receptor accessory protein mRNAs is differentially regulated during inflammation and apoptosis. Jensen, L.E., Whitehead, A.S. Cell. Signal. (2003) [Pubmed]
  10. The human gene encoding the interleukin-1 receptor accessory protein (IL1RAP) maps to chromosome 3q28 by fluorescence in situ hybridization and radiation hybrid mapping. Dale, M., Hammond, D.W., Cox, A., Nicklin, M.J. Genomics (1998) [Pubmed]
  11. Interleukin-1 receptor accessory protein is constitutively expressed in human endometrium throughout the menstrual cycle. Bigonnesse, F., Marois, M., Maheux, R., Akoum, A. Mol. Hum. Reprod. (2001) [Pubmed]
  12. The interleukin-1 receptor accessory protein (IL-1RAcP) is essential for IL-1-induced activation of interleukin-1 receptor-associated kinase (IRAK) and stress-activated protein kinases (SAP kinases). Wesche, H., Korherr, C., Kracht, M., Falk, W., Resch, K., Martin, M.U. J. Biol. Chem. (1997) [Pubmed]
  13. Molecular cloning and characterization of a second subunit of the interleukin 1 receptor complex. Greenfeder, S.A., Nunes, P., Kwee, L., Labow, M., Chizzonite, R.A., Ju, G. J. Biol. Chem. (1995) [Pubmed]
  14. The type II IL-1 receptor interacts with the IL-1 receptor accessory protein: a novel mechanism of regulation of IL-1 responsiveness. Lang, D., Knop, J., Wesche, H., Raffetseder, U., Kurrle, R., Boraschi, D., Martin, M.U. J. Immunol. (1998) [Pubmed]
  15. Extracellular regulation of interleukin (IL)-1beta through lung epithelial cells and defective IL-1 type II receptor expression. Coulter, K.R., Wewers, M.D., Lowe, M.P., Knoell, D.L. Am. J. Respir. Cell Mol. Biol. (1999) [Pubmed]
  16. Interleukin 1 receptor accessory protein (IL-1RAcP) is necessary for centrally mediated neuroendocrine and immune responses to IL-1beta. Liège, S., Layé, S., Li, K.S., Moze, E., Neveu, P.J. J. Neuroimmunol. (2000) [Pubmed]
  17. Antibodies to domains II and III of the IL-1 receptor accessory protein inhibit IL-1 beta activity but not binding: regulation of IL-1 responses is via type I receptor, not the accessory protein. Yoon, D.Y., Dinarello, C.A. J. Immunol. (1998) [Pubmed]
  18. Insertion of a structural domain of interleukin (IL)-1 beta confers agonist activity to the IL-1 receptor antagonist. Implications for IL-1 bioactivity. Greenfeder, S.A., Varnell, T., Powers, G., Lombard-Gillooly, K., Shuster, D., McIntyre, K.W., Ryan, D.E., Levin, W., Madison, V., Ju, G. J. Biol. Chem. (1995) [Pubmed]
  19. Interleukin-1beta activates a short STAT-3 isoform in clonal insulin-secreting cells. Morton, N.M., de Groot, R.P., Cawthorne, M.A., Emilsson, V. FEBS Lett. (1999) [Pubmed]
  20. Differential expression of the IL-1 system components during in vitro myogenesis: implication of IL-1beta in induction of myogenic cell apoptosis. Authier, F.J., Chazaud, B., Plonquet, A., Eliezer-Vanerot, M.C., Poron, F., Belec, L., Barlovatz-Meimon, G., Gherardi, R.K. Cell Death Differ. (1999) [Pubmed]
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