IL36G
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesIL36G, interleukin 36, gamma, IL-1F9, IL-1H1, IL-1RP2, IL1E, IL1H1, IL1RP2, IL1F9, interleukin 36 gamma
External IDsOMIM: 605542 MGI: 2449929 HomoloGene: 49595 GeneCards: IL36G
Orthologs
SpeciesHumanMouse
Entrez

56300

215257

Ensembl

ENSG00000136688

ENSMUSG00000044103

UniProt

Q9NZH8

Q8R460
Q3U0P4

RefSeq (mRNA)

NM_001278568
NM_019618

NM_153511

RefSeq (protein)

NP_001265497
NP_062564

NP_705731

Location (UCSC)Chr 2: 112.97 – 112.99 MbChr 2: 24.08 – 24.08 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Interleukin-36 gamma previously known as interleukin-1 family member 9 (IL1F9) is a protein that in humans is encoded by the IL36G gene.[5][6][7][8]

Expression

IL36G is well-expressed in the epithelium of the skin, gut, and lung.[9] In the skin IL36G is predominantly expressed in epidermal granular layer keratinocytes with little to no expression in basal layer keratinocytes.[10]

Function

The protein encoded by this gene is a member of the interleukin-1 cytokine family. This gene and eight other interleukin-1 family genes form a cytokine gene cluster on chromosome 2.[11] The activity of this cytokine is mediated via the interleukin-1 receptor-like 2 (IL1RL2/IL1R-rp2/IL-36 receptor), and is specifically inhibited by interleukin-36 receptor antagonist, (IL-36RA/IL1F5/IL-1 delta). Interferon-gamma, tumor necrosis factor-alpha and interleukin-1 β (IL-1β) are reported to stimulate the expression of this cytokine in keratinocytes. The expression of this cytokine in keratinocytes can also be induced by a multiple Pathogen-Associated Molecular Patterns (PAMPs).[12] Both IL-36γ mRNA and protein have been linked to psoriasis lesions and has been used as a biomarker for differentiating between eczema and psoriasis.[13][14] As with many other interleukin-1 family cytokines IL-36γ requires proteolytic cleavage of its N-terminus for full biological activity.[15] However, unlike IL-1β the activation of IL-36γ is inflammasome-independent. IL-36γ is specifically cleaved by the endogenous protease cathepsin S as well exogenous proteases derived from fungal and bacterial pathogens.[16][17]

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000136688 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000044103 - 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. ↑ Busfield SJ, Comrack CA, Yu G, Chickering TW, Smutko JS, Zhou H, Leiby KR, Holmgren LM, Gearing DP, Pan Y (June 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.
  6. ↑ Kumar S, McDonnell PC, Lehr R, Tierney L, Tzimas MN, Griswold DE, Capper EA, Tal-Singer R, Wells GI, Doyle ML, Young PR (April 2000). "Identification and initial characterization of four novel members of the interleukin-1 family". The Journal of Biological Chemistry. 275 (14): 10308–14. doi:10.1074/jbc.275.14.10308. PMID 10744718.
  7. ↑ Nicklin MJ, Barton JL, Nguyen M, FitzGerald MG, Duff GW, Kornman K (May 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.
  8. ↑ Taylor SL, Renshaw BR, Garka KE, Smith DE, Sims JE (May 2002). "Genomic organization of the interleukin-1 locus". Genomics. 79 (5): 726–33. doi:10.1006/geno.2002.6752. PMID 11991723.
  9. ↑ Yuan ZC, Xu WD, Liu XY, Liu XY, Huang AF, Su LC (2019). "Biology of IL-36 Signaling and Its Role in Systemic Inflammatory Diseases". Frontiers in Immunology. 10: 2532. doi:10.3389/fimmu.2019.02532. PMC 6839525. PMID 31736959.
  10. ↑ Merleev A, Ji-Xu A, Toussi A, Tsoi LC, Le ST, Luxardi G, et al. (August 2022). "Proprotein convertase subtilisin/kexin type 9 is a psoriasis-susceptibility locus that is negatively related to IL36G". JCI Insight. 7 (16). doi:10.1172/jci.insight.141193. PMC 9462487. PMID 35862195.
  11. ↑ Garlanda C, Dinarello CA, Mantovani A (December 2013). "The interleukin-1 family: back to the future". Immunity. 39 (6): 1003–18. doi:10.1016/j.immuni.2013.11.010. PMC 3933951. PMID 24332029.
  12. ↑ Gabay C, Towne JE (April 2015). "Regulation and function of interleukin-36 cytokines in homeostasis and pathological conditions". Journal of Leukocyte Biology. 97 (4): 645–52. doi:10.1189/jlb.3RI1014-495R. PMID 25673295. S2CID 36594830.
  13. ↑ Berekméri A, Latzko A, Alase A, Macleod T, Ainscough JS, Laws P, et al. (September 2018). "Detection of IL-36γ through noninvasive tape stripping reliably discriminates psoriasis from atopic eczema" (PDF). The Journal of Allergy and Clinical Immunology. 142 (3): 988–991.e4. doi:10.1016/j.jaci.2018.04.031. hdl:2164/10849. PMC 6127028. PMID 29782895.
  14. ↑ D'Erme AM, Wilsmann-Theis D, Wagenpfeil J, Hölzel M, Ferring-Schmitt S, Sternberg S, et al. (April 2015). "IL-36γ (IL-1F9) is a biomarker for psoriasis skin lesions". The Journal of Investigative Dermatology. 135 (4): 1025–1032. doi:10.1038/jid.2014.532. PMID 25525775.
  15. ↑ Towne JE, Renshaw BR, Douangpanya J, Lipsky BP, Shen M, Gabel CA, Sims JE (December 2011). "Interleukin-36 (IL-36) ligands require processing for full agonist (IL-36α, IL-36β, and IL-36γ) or antagonist (IL-36Ra) activity". The Journal of Biological Chemistry. 286 (49): 42594–602. doi:10.1074/jbc.M111.267922. PMC 3234937. PMID 21965679.
  16. ↑ Ainscough JS, Macleod T, McGonagle D, Brakefield R, Baron JM, Alase A, et al. (March 2017). "Cathepsin S is the major activator of the psoriasis-associated proinflammatory cytokine IL-36γ". Proceedings of the National Academy of Sciences of the United States of America. 114 (13): E2748–E2757. Bibcode:2017PNAS..114E2748A. doi:10.1073/pnas.1620954114. PMC 5380102. PMID 28289191.
  17. ↑ Macleod T, Ainscough JS, Hesse C, Konzok S, Braun A, Buhl AL, et al. (December 2020). "The Proinflammatory Cytokine IL-36γ Is a Global Discriminator of Harmless Microbes and Invasive Pathogens within Epithelial Tissues". Cell Reports. 33 (11): 108515. doi:10.1016/j.celrep.2020.108515. PMC 7758160. PMID 33326792.

Further reading


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