Interleukin 36 receptor antagonist

IL36RN
Available structures
PDB	Ortholog search: PDBe RCSB
List of PDB id codes
	4P0J, 4P0K, 4P0L
Identifiers
Aliases	IL36RN, FIL1, FIL1(DELTA), FIL1D, IL1F5, IL1HY1, IL1L1, IL1RP3, IL36RA, PSORP, IL-36Ra, PSORS14, interleukin 36 receptor antagonist
External IDs	OMIM: 605507 MGI: 1859325 HomoloGene: 10453 GeneCards: IL36RN
Gene location (Human)
Chr.	Chromosome 2 (human)[1]
End	113,065,382 bp[1]
Gene location (Mouse)
Chr.	Chromosome 2 (mouse)[2]
End	24,283,426 bp[2]
RNA expression pattern
	More reference expression data
Gene ontology
Molecular function	• cytokine activity; • GO:0001948 protein binding; • interleukin-1 receptor binding; • interleukin-1 receptor antagonist activity;
Cellular component	• extracellular; • extracellular region;
Biological process	• negative regulation of interleukin-6 production; • negative regulation of cytokine-mediated signaling pathway; • innate immune system; • negative regulation of interleukin-17 production; • antifungal humoral response; • immune system process; • inflammatory response; • immune response; • regulation of receptor activity; • cytokine-mediated signaling pathway; • neutrophil chemotaxis; • positive regulation of interleukin-6 production; • positive regulation of I-kappaB kinase/NF-kappaB signaling; • positive regulation of JNK cascade; • cellular response to lipopolysaccharide;
	Sources:Amigo / QuickGO
Orthologs
	26525
	54450
	ENSG00000136695
	ENSMUSG00000026983
	Q9UBH0
	Q9QYY1
	NM_173170; NM_012275
	NM_001146087; NM_001146088; NM_019451
	NP_036407; NP_775262
	NP_001139559; NP_001139560; NP_062324
	Wikidata
View/Edit Human	View/Edit Mouse

Interleukin 36 receptor antagonist (IL-36RA) is a member of the interleukin-36 family of cytokines. It was previously named Interleukin-1 family member 5 (IL1F5).[5][6][7][8]

The protein is known to inhibit the effects of Interleukin-36 cytokines (IL-36α, IL-36β and IL-36γ) via competing with their receptor IL-36R/IL1RL2 and thereby inhibiting their proinflammatory effects.[9]

Roles in disease

Mutations in the IL-36RN gene resulting in a decrease or production of defective IL-36RA protein have been shown to cause inflammatory skin diseases including generalised pustular psoriasis, acrodermatitis continua suppurativa Hallopeau (ACH) and acute generalized exanthematous pustulosis (AGEP).[10]

References

GRCh38: Ensembl release 89: ENSG00000136695 - Ensembl, May 2017
GRCm38: Ensembl release 89: ENSMUSG00000026983 - 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.
Smith DE, Renshaw BR, Ketchem RR, Kubin M, Garka KE, Sims JE (Feb 2000). "Four new members expand the interleukin-1 superfamily". J Biol Chem. 275 (2): 1169–75. doi:10.1074/jbc.275.2.1169. PMID 10625660.
Mulero JJ, Pace AM, Nelken ST, Loeb DB, Correa TR, Drmanac R, Ford JE (Nov 1999). "IL1HY1: A novel interleukin-1 receptor antagonist gene". Biochem Biophys Res Commun. 263 (3): 702–6. doi:10.1006/bbrc.1999.1440. PMID 10512743.
Sims JE, Nicklin MJ, Bazan JF, Barton JL, Busfield SJ, Ford JE, Kastelein RA, Kumar S, Lin H, Mulero JJ, Pan J, Pan Y, Smith DE, Young PR (Sep 2001). "A new nomenclature for IL-1-family genes". Trends Immunol. 22 (10): 536–7. doi:10.1016/S1471-4906(01)02040-3. PMID 11574262.
"Entrez Gene: IL36RN interleukin 36 receptor antagonist".
Towne, JE; Garka, KE; Renshaw, BR; Virca, GD; Sims, JE (2 April 2004). "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". The Journal of Biological Chemistry. 279 (14): 13677–88. doi:10.1074/jbc.M400117200. PMID 14734551.
Navarini, AA; Valeyrie-Allanore, L; Setta-Kaffetzi, N; Barker, JN; Capon, F; Creamer, D; Roujeau, JC; Sekula, P; Simpson, MA; Trembath, RC; Mockenhaupt, M; Smith, CH (July 2013). "Rare variations in IL36RN in severe adverse drug reactions manifesting as acute generalized exanthematous pustulosis". The Journal of Investigative Dermatology. 133 (7): 1904–7. doi:10.1038/jid.2013.44. PMID 23358093.

[1]==Further reading==

Nicklin MJ, Weith A, Duff GW (1994). "A physical map of the region encompassing the human interleukin-1 alpha, interleukin-1 beta, and interleukin-1 receptor antagonist genes". Genomics. 19 (2): 382–4. doi:10.1006/geno.1994.1076. PMID 8188271.
Nothwang HG, Strahm B, Denich D, et al. (1997). "Molecular cloning of the interleukin-1 gene cluster: construction of an integrated YAC/PAC contig and a partial transcriptional map in the region of chromosome 2q13". Genomics. 41 (3): 370–8. doi:10.1006/geno.1997.4654. PMID 9169134.
Kumar S, McDonnell PC, Lehr R, et al. (2000). "Identification and initial characterization of four novel members of the interleukin-1 family". J. Biol. Chem. 275 (14): 10308–14. doi:10.1074/jbc.275.14.10308. PMID 10744718.
Busfield SJ, Comrack CA, Yu G, et al. (2000). "Identification and gene organization of three novel members of the IL-1 family on human chromosome 2". Genomics. 66 (2): 213–6. doi:10.1006/geno.2000.6184. PMID 10860666.
Mulero JJ, Nelken ST, Ford JE (2000). "Organization of the human interleukin-1 receptor antagonist gene IL1HY1". Immunogenetics. 51 (6): 425–8. doi:10.1007/s002510050640. PMID 10866108. S2CID 37207859.
Barton JL, Herbst R, Bosisio D, et al. (2001). "A tissue specific IL-1 receptor antagonist homolog from the IL-1 cluster lacks IL-1, IL-1ra, IL-18 and IL-18 antagonist activities". Eur. J. Immunol. 30 (11): 3299–308. doi:10.1002/1521-4141(200011)30:11<3299::AID-IMMU3299>3.0.CO;2-S. PMID 11093146.
Pan G, Risser P, Mao W, et al. (2001). "IL-1H, an interleukin 1-related protein that binds IL-18 receptor/IL-1Rrp". Cytokine. 13 (1): 1–7. doi:10.1006/cyto.2000.0799. PMID 11145836.
Lin H, Ho AS, Haley-Vicente D, et al. (2001). "Cloning and characterization of IL-1HY2, a novel interleukin-1 family member". J. Biol. Chem. 276 (23): 20597–602. doi:10.1074/jbc.M010095200. PMID 11278614.
Debets R, Timans JC, Homey B, et al. (2001). "Two novel IL-1 family members, IL-1 delta and IL-1 epsilon, function as an antagonist and agonist of NF-kappa B activation through the orphan IL-1 receptor-related protein 2". J. Immunol. 167 (3): 1440–6. doi:10.4049/jimmunol.167.3.1440. PMID 11466363.
Tazi-Ahnini R, Cox A, McDonagh AJ, et al. (2002). "Genetic analysis of the interleukin-1 receptor antagonist and its homologue IL-1L1 in alopecia areata: strong severity association and possible gene interaction". Eur. J. Immunogenet. 29 (1): 25–30. doi:10.1046/j.1365-2370.2002.00271.x. PMID 11841485.
Nicklin MJ, Barton JL, Nguyen M, et al. (2002). "A sequence-based map of the nine genes of the human interleukin-1 cluster". Genomics. 79 (5): 718–25. doi:10.1006/geno.2002.6751. PMID 11991722.
Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
Clark HF, Gurney AL, Abaya E, et al. (2003). "The Secreted Protein Discovery Initiative (SPDI), a Large-Scale Effort to Identify Novel Human Secreted and Transmembrane Proteins: A Bioinformatics Assessment". Genome Res. 13 (10): 2265–70. doi:10.1101/gr.1293003. PMC 403697. PMID 12975309.
Zee RY, Fernandez-Ortiz A, Macaya C, et al. (2004). "IL-1 cluster genes and occurrence of post-percutaneous transluminal coronary angioplasty restenosis: a prospective, angiography-based evaluation". Atherosclerosis. 171 (2): 259–64. doi:10.1016/S0021-9150(03)00294-6. PMID 14644395.
Ota T, Suzuki Y, Nishikawa T, et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nat. Genet. 36 (1): 40–5. doi:10.1038/ng1285. PMID 14702039.
Colland F, Jacq X, Trouplin V, et al. (2004). "Functional Proteomics Mapping of a Human Signaling Pathway". Genome Res. 14 (7): 1324–32. doi:10.1101/gr.2334104. PMC 442148. PMID 15231748.
Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The Status, Quality, and Expansion of the NIH Full-Length cDNA Project: The Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334.

Macleod, T; Doble, R; McGonagle, D; Wasson, CW; Alase, A; Stacey, M; Wittmann, M (22 April 2016). "Neutrophil Elastase-mediated proteolysis activates the anti-inflammatory cytokine IL-36 Receptor antagonist". Scientific Reports. 6: 24880. doi:10.1038/srep24880. PMC 4840362. PMID 27101808.

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[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000136695 - Ensembl, May 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000026983 - 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.

[pmid10625660-5] Smith DE, Renshaw BR, Ketchem RR, Kubin M, Garka KE, Sims JE (Feb 2000). "Four new members expand the interleukin-1 superfamily". J Biol Chem. 275 (2): 1169–75. doi:10.1074/jbc.275.2.1169. PMID 10625660.

[pmid10512743-6] Mulero JJ, Pace AM, Nelken ST, Loeb DB, Correa TR, Drmanac R, Ford JE (Nov 1999). "IL1HY1: A novel interleukin-1 receptor antagonist gene". Biochem Biophys Res Commun. 263 (3): 702–6. doi:10.1006/bbrc.1999.1440. PMID 10512743.

[pmid11574262-7] Sims JE, Nicklin MJ, Bazan JF, Barton JL, Busfield SJ, Ford JE, Kastelein RA, Kumar S, Lin H, Mulero JJ, Pan J, Pan Y, Smith DE, Young PR (Sep 2001). "A new nomenclature for IL-1-family genes". Trends Immunol. 22 (10): 536–7. doi:10.1016/S1471-4906(01)02040-3. PMID 11574262.

[entrez-8] "Entrez Gene: IL36RN interleukin 36 receptor antagonist".

[9] Towne, JE; Garka, KE; Renshaw, BR; Virca, GD; Sims, JE (2 April 2004). "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". The Journal of Biological Chemistry. 279 (14): 13677–88. doi:10.1074/jbc.M400117200. PMID 14734551.

[10] Navarini, AA; Valeyrie-Allanore, L; Setta-Kaffetzi, N; Barker, JN; Capon, F; Creamer, D; Roujeau, JC; Sekula, P; Simpson, MA; Trembath, RC; Mockenhaupt, M; Smith, CH (July 2013). "Rare variations in IL36RN in severe adverse drug reactions manifesting as acute generalized exanthematous pustulosis". The Journal of Investigative Dermatology. 133 (7): 1904–7. doi:10.1038/jid.2013.44. PMID 23358093.

[11] Macleod, T; Doble, R; McGonagle, D; Wasson, CW; Alase, A; Stacey, M; Wittmann, M (22 April 2016). "Neutrophil Elastase-mediated proteolysis activates the anti-inflammatory cytokine IL-36 Receptor antagonist". Scientific Reports. 6: 24880. doi:10.1038/srep24880. PMC 4840362. PMID 27101808.