Interleukin 20 receptor, alpha subunit

IL20RA
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 4DOH
Identifiers
Aliases	IL20RA, CRF2-8, IL-20R-alpha, IL-20R1, IL-20RA, Interleukin 20 receptor, alpha subunit, interleukin 20 receptor subunit alpha
External IDs	OMIM: 605620; MGI: 3605069; HomoloGene: 8685; GeneCards: IL20RA; OMA:IL20RA - orthologs
Gene location (Human) Chr. Chromosome 6 (human)[1] Band 6q23.3 Start 136,999,971 bp[1] End 137,045,180 bp[1]
Gene location (Mouse) Chr. Chromosome 10 (mouse)[2] Band 10|10 A3 Start 19,588,318 bp[2] End 19,635,801 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in olfactory zone of nasal mucosa skin of abdomen right uterine tube skin of leg bronchial epithelial cell testicle endometrium skin of thigh palpebral conjunctiva skin of arm Top expressed in embryo embryo skin of external ear lumbar subsegment of spinal cord spermatid lip neural layer of retina superior frontal gyrus skin of abdomen epiblast More reference expression data BioGPS More reference expression data
Gene ontology Molecular function cytokine receptor activity interleukin-20 binding protein binding Cellular component integral component of membrane membrane plasma membrane Biological process regulation of bone resorption positive regulation of intrinsic apoptotic signaling pathway cytokine-mediated signaling pathway Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 53832 237313 Ensembl ENSG00000016402 ENSMUSG00000020007 UniProt Q9UHF4 Q6PHB0 RefSeq (mRNA) NM_001278722 NM_001278723 NM_001278724 NM_014432 NM_172786 RefSeq (protein) NP_001265651 NP_001265652 NP_001265653 NP_055247 NP_766374 Location (UCSC) Chr 6: 137 – 137.05 Mb Chr 10: 19.59 – 19.64 Mb PubMed search [3] [4]
Wikidata
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Interleukin 20 receptor, alpha subunit, is a subunit of the interleukin-20 receptor, the interleukin-26 receptor, and the interleukin-24 receptor.^[5] The interleukin 20 receptor, alpha subunit is also referred to as IL20R1^[6] or IL20RA.^[7] The IL20RA receptor is involved in both pro-inflammatory and anti-inflammatory responses, signaling through the JAK-STAT pathway.^[5]

Tissue distribution

IL20RA is found in the skin, lungs, ovaries, testes and placenta, with low gene expression in the intestine and liver.^[7] IL20RB is found in many organ resident effector cells such as keratinocytes at the skin epidermis, osteoclasts, found in bones, and epithelial cells of the intestine and trachea. IL20RA is also found in some immune cells.^[8]

Structure and function

IL20RA is an alpha-chain with a long intracellular domain. IL20RA, along with the IL-20 receptor, beta subunit, form the heterodimeric interleukin-20 receptor, which binds the cytokines IL-19, IL-20 and IL-24. IL20RA also forms a complex with the IL-10 receptor, beta subunit, which binds the cytokine IL-26.^[5]

Signaling

Receptors made up of IL20RA signal through a JAK-STAT signaling pathway.^[5] In this pathway, after a cytokine binds IL20RA and the beta subunit, JAKs linked to intracellular domains of IL20R activate and phosphorylate tyrosine residues found in the longer alpha chains of IL20RA. STAT then binds to docking sites created by JAK phosphorylation and becomes phosphorylated by JAK. STATs then dimerize and move to the nucleus to act as transcription factors. The specific genes expressed are dependent on the specific JAK, STAT, as well as by SOCS proteins, which can inhibit the JAK-STAT signal, regulating it.where the transcription factor STAT3 binds to IL20RA and STAT3 becomes activated.^[1] IL20RA has multiple docking sites for STAT3.^[5][9]

Clinical signficance

Research indicates that IL20RA is found in some immune cells. For example, IL20RA is sometimes found in lung macrophages. Research indicates that IL20RA presence may be related to disease. In people with rheumatoid arthiritis, IL20RA is present in blood monocytes.^[8]

IL20RA has also been linked with psoriasis, and atherosclerosis, all diseases associated with inflammation. The specific role of IL20RA in these diseases is unknown.^[7]

References

1. GRCh38: Ensembl release 89: ENSG00000016402 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000020007 – 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. Wegenka UM (2010-10-01). "IL-20: Biological functions mediated through two types of receptor complexes". Cytokine & Growth Factor Reviews. IL-10 Family of Cytokines. 21 (5): 353–363. doi:10.1016/j.cytogfr.2010.08.001. ISSN 1359-6101. PMID 20864382.
6. Wirtz MK, Keller KE (2016). "The Role of the IL-20 Subfamily in Glaucoma". Mediators of Inflammation. 2016: 4083735. doi:10.1155/2016/4083735. ISSN 0962-9351. PMC 4745377. PMID 26903709.
7. Rutz S, Wang X, Ouyang W (December 2014). "The IL-20 subfamily of cytokines — from host defence to tissue homeostasis". Nature Reviews. Immunology. 14 (12): 783–795. doi:10.1038/nri3766. ISSN 1474-1741. PMID 25421700. S2CID 29114703.
8. Kragstrup TW, Andersen T, Heftdal LD, Hvid M, Gerwien J, Sivakumar P, et al. (2018-09-25). "The IL-20 Cytokine Family in Rheumatoid Arthritis and Spondyloarthritis". Frontiers in Immunology. 9: 2226. doi:10.3389/fimmu.2018.02226. ISSN 1664-3224. PMC 6167463. PMID 30319661.
9. Blumberg H, Conklin D, Xu W, Grossmann A, Brender T, Carollo S, et al. (2001-01-12). "Interleukin 20: Discovery, Receptor Identification, and Role in Epidermal Function". Cell. 104 (1): 9–19. doi:10.1016/S0092-8674(01)00187-8. ISSN 0092-8674. PMID 11163236.

Further reading

• Bonaldo MF, Lennon G, Soares MB (Sep 1996). "Normalization and subtraction: two approaches to facilitate gene discovery". Genome Research. 6 (9): 791–806. doi:10.1101/gr.6.9.791. PMID 8889548.
• Aggarwal S, Ho WH, Foster J, Zhang Z, Stinson J, Wood W, et al. (Oct 2000). "Interleukin (IL)-22, a novel human cytokine that signals through the interferon receptor-related proteins CRF2-4 and IL-22R". Journal of Biological Chemistry. 275 (40): 31335–31339. doi:10.1074/jbc.M005304200. PMID 10875937.
• Conklin D, Xu WF, Grossmann A, Brender T, Carollo S, Eagan M, et al. (Jan 2001). "Interleukin 20: discovery, receptor identification, and role in epidermal function". Cell. 104 (1): 9–19. doi:10.1016/S0092-8674(01)00187-8. PMID 11163236. S2CID 7460710.
• Leemans C, Lejeune D, Kotenko S, Renauld J, Dumoutier L (Oct 2001). "Cutting edge: STAT activation by IL-19, IL-20 and mda-7 through IL-20 receptor complexes of two types". Journal of Immunology. 167 (7). Baltimore, Md.: 3545–3549. doi:10.4049/jimmunol.167.7.3545. PMID 11564763.
• Tan Z, Zhang R, Kotenko S, Liang P, Wang M (Mar 2002). "Interleukin 24 (MDA-7/MOB-5) signals through two heterodimeric receptors, IL-22R1/IL-20R2 and IL-20R1/IL-20R2". Journal of Biological Chemistry. 277 (9): 7341–7347. doi:10.1074/jbc.M106043200. PMID 11706020.
• Xu W, Brender T, Yao L, Jones C, West J, Brandt C, et al. (Dec 2002). "Interleukins 19, 20, and 24 signal through two distinct receptor complexes. Differences in receptor-ligand interactions mediate unique biological functions". Journal of Biological Chemistry. 277 (49): 47517–47523. doi:10.1074/jbc.M205114200. PMID 12351624.
• Feingold EA, Grouse LH, Derge J, Klausner R, Collins F, Wagner L, et al. (Dec 2002). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proceedings of the National Academy of Sciences of the United States of America. 99 (26): 16899–16903. Bibcode:2002PNAS...9916899M. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
• Gurney AL, Abaya E, Baker K, Baldwin D, Brush J, Chen J, et al. (Oct 2003). "The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment". Genome Research. 13 (10): 2265–2270. doi:10.1101/gr.1293003. PMC 403697. PMID 12975309.
• Palmer SA, Sims SK, Edwards CA, Ashurst JL, Wilming L, Jones MC, et al. (Oct 2003). "The DNA sequence and analysis of human chromosome 6". Nature. 425 (6960): 805–811. doi:10.1038/nature02055. PMID 14574404.
• Magracheva E, Kozlov S, Tobin G, Kotenko SV, Wlodawer A, Zdanov A, et al. (Nov 2003). "Characterization of the recombinant extracellular domains of human interleukin-20 receptors and their complexes with interleukin-19 and interleukin-20". Biochemistry. 42 (43): 12617–12624. doi:10.1021/bi0354583. PMID 14580208.
• Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, et al. (Jan 2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nature Genetics. 36 (1): 40–45. doi:10.1038/ng1285. PMID 14702039.
• Baurin VV, Lewis-Antes A, Shah N, Smirnov S, Anantha S, Dickensheets H, et al. (Feb 2004). "Cutting edge: IL-26 signals through a novel receptor complex composed of IL-20 receptor 1 and IL-10 receptor 2". Journal of Immunology. 172 (4). Baltimore, Md.: 2006–2010. doi:10.4049/jimmunol.172.4.2006. PMID 14764663.
• Pirzer H, Dumoutier L, Bauer F, Wittmann S, Sticht H, Renauld J, et al. (Aug 2004). "The T-cell lymphokine interleukin-26 targets epithelial cells through the interleukin-20 receptor 1 and interleukin-10 receptor 2 chains". Journal of Biological Chemistry. 279 (32): 33343–33351. doi:10.1074/jbc.M405000200. PMID 15178681.
• Zhang Z, Henzel WJ (Oct 2004). "Signal peptide prediction based on analysis of experimentally verified cleavage sites". Protein Science : a Publication of the Protein Society. 13 (10): 2819–2824. doi:10.1110/ps.04682504. PMC 2286551. PMID 15340161.