ID IL17_HUMAN Reviewed; 155 AA. AC Q16552; Q5T2P0; DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1996, sequence version 1. DT 02-OCT-2024, entry version 202. DE RecName: Full=Interleukin-17A; DE Short=IL-17; DE Short=IL-17A; DE AltName: Full=Cytotoxic T-lymphocyte-associated antigen 8; DE Short=CTLA-8; DE Flags: Precursor; GN Name=IL17A; Synonyms=CTLA8, IL17; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, AND PTM. RX PubMed=8676080; DOI=10.1084/jem.183.6.2593; RA Fossiez F., Djossou O., Chomarat P., Flores-Romo L., Ait-Yahia S., Maat C., RA Pin J.-J., Garrone P., Garcia E., Saeland S., Blanchard D., Gaillard C., RA Das Mahapatra B., Rouvier E., Golstein P., Banchereau J., Lebecque S.; RT "T cell interleukin-17 induces stromal cells to produce proinflammatory and RT hematopoietic cytokines."; RL J. Exp. Med. 183:2593-2603(1996). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=T-cell; RX PubMed=7499828; RA Yao Z., Painter S.L., Fanslow W.C., Ulrich D., Macduff B.M., Spriggs M.K., RA Armitage R.J.; RT "Human IL-17: a novel cytokine derived from T cells."; RL J. Immunol. 155:5483-5486(1995). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RG SeattleSNPs variation discovery resource; RL Submitted (NOV-2003) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=14574404; DOI=10.1038/nature02055; RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., RA Rogers J., Beck S.; RT "The DNA sequence and analysis of human chromosome 6."; RL Nature 425:805-811(2003). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [7] RP PROTEIN SEQUENCE OF 24-38. RX PubMed=15340161; DOI=10.1110/ps.04682504; RA Zhang Z., Henzel W.J.; RT "Signal peptide prediction based on analysis of experimentally verified RT cleavage sites."; RL Protein Sci. 13:2819-2824(2004). RN [8] RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND INDUCTION BY IL23A-IL12B. RX PubMed=17763419; DOI=10.1002/art.22866; RA Chen Z., Tato C.M., Muul L., Laurence A., O'Shea J.J.; RT "Distinct regulation of interleukin-17 in human T helper lymphocytes."; RL Arthritis Rheum. 56:2936-2946(2007). RN [9] RP SUBUNIT. RX PubMed=17355969; DOI=10.1074/jbc.m700499200; RA Wright J.F., Guo Y., Quazi A., Luxenberg D.P., Bennett F., Ross J.F., RA Qiu Y., Whitters M.J., Tomkinson K.N., Dunussi-Joannopoulos K., RA Carreno B.M., Collins M., Wolfman N.M.; RT "Identification of an interleukin 17F/17A heterodimer in activated human RT CD4+ T cells."; RL J. Biol. Chem. 282:13447-13455(2007). RN [10] RP FUNCTION. RX PubMed=17911633; DOI=10.4049/jimmunol.179.8.5462; RA Kuestner R.E., Taft D.W., Haran A., Brandt C.S., Brender T., Lum K., RA Harder B., Okada S., Ostrander C.D., Kreindler J.L., Aujla S.J., RA Reardon B., Moore M., Shea P., Schreckhise R., Bukowski T.R., Presnell S., RA Guerra-Lewis P., Parrish-Novak J., Ellsworth J.L., Jaspers S., Lewis K.E., RA Appleby M., Kolls J.K., Rixon M., West J.W., Gao Z., Levin S.D.; RT "Identification of the IL-17 receptor related molecule IL-17RC as the RT receptor for IL-17F."; RL J. Immunol. 179:5462-5473(2007). RN [11] RP FUNCTION. RX PubMed=18684971; DOI=10.4049/jimmunol.181.4.2799; RA Wright J.F., Bennett F., Li B., Brooks J., Luxenberg D.P., Whitters M.J., RA Tomkinson K.N., Fitz L.J., Wolfman N.M., Collins M., RA Dunussi-Joannopoulos K., Chatterjee-Kishore M., Carreno B.M.; RT "The human IL-17F/IL-17A heterodimeric cytokine signals through the IL- RT 17RA/IL-17RC receptor complex."; RL J. Immunol. 181:2799-2805(2008). RN [12] RP FUNCTION. RX PubMed=19825828; DOI=10.1126/scisignal.2000382; RA Liu C., Qian W., Qian Y., Giltiay N.V., Lu Y., Swaidani S., Misra S., RA Deng L., Chen Z.J., Li X.; RT "Act1, a U-box E3 ubiquitin ligase for IL-17 signaling."; RL Sci. Signal. 2:ra63-ra63(2009). RN [13] RP FUNCTION. RX PubMed=21350122; DOI=10.1126/science.1200439; RA Puel A., Cypowyj S., Bustamante J., Wright J.F., Liu L., Lim H.K., RA Migaud M., Israel L., Chrabieh M., Audry M., Gumbleton M., Toulon A., RA Bodemer C., El-Baghdadi J., Whitters M., Paradis T., Brooks J., Collins M., RA Wolfman N.M., Al-Muhsen S., Galicchio M., Abel L., Picard C., RA Casanova J.L.; RT "Chronic mucocutaneous candidiasis in humans with inborn errors of RT interleukin-17 immunity."; RL Science 332:65-68(2011). RN [14] RP FUNCTION. RX PubMed=24120361; DOI=10.1016/j.immuni.2013.09.002; RA Boisson B., Wang C., Pedergnana V., Wu L., Cypowyj S., Rybojad M., RA Belkadi A., Picard C., Abel L., Fieschi C., Puel A., Li X., Casanova J.L.; RT "An ACT1 mutation selectively abolishes interleukin-17 responses in humans RT with chronic mucocutaneous candidiasis."; RL Immunity 39:676-686(2013). RN [15] RP INDUCTION. RX PubMed=27795421; DOI=10.1128/jvi.01529-16; RA Acharya D., Wang P., Paul A.M., Dai J., Gate D., Lowery J.E., Stokic D.S., RA Leis A.A., Flavell R.A., Town T., Fikrig E., Bai F.; RT "Interleukin-17A Promotes CD8+ T Cell Cytotoxicity To Facilitate West Nile RT Virus Clearance."; RL J. Virol. 91:0-0(2017). RN [16] RP INTERACTION WITH IL17F; IL17RA AND IL17RC. RX PubMed=32187518; DOI=10.1016/j.immuni.2020.02.004; RA Goepfert A., Lehmann S., Blank J., Kolbinger F., Rondeau J.M.; RT "Structural Analysis Reveals that the Cytokine IL-17F Forms a Homodimeric RT Complex with Receptor IL-17RC to Drive IL-17RA-Independent Signaling."; RL Immunity 52:499-512.e5(2020). RN [17] RP X-RAY CRYSTALLOGRAPHY (2.63 ANGSTROMS) OF 20-155 IN COMPLEX WITH ANTIBODY, RP DISULFIDE BONDS, AND SUBUNIT. RX PubMed=19835883; DOI=10.1016/j.jmb.2009.10.008; RA Gerhardt S., Abbott W.M., Hargreaves D., Pauptit R.A., Davies R.A., RA Needham M.R., Langham C., Barker W., Aziz A., Snow M.J., Dawson S., RA Welsh F., Wilkinson T., Vaugan T., Beste G., Bishop S., Popovic B., RA Rees G., Sleeman M., Tuske S.J., Coales S.J., Hamuro Y., Russell C.; RT "Structure of IL-17A in complex with a potent, fully human neutralizing RT antibody."; RL J. Mol. Biol. 394:905-921(2009). RN [18] RP X-RAY CRYSTALLOGRAPHY (2.48 ANGSTROMS) OF 34-155 IN COMPLEX WITH IL17RA, RP DISULFIDE BONDS, SUBUNIT, AND MUTAGENESIS OF ARG-78; TRP-90; TYR-108 AND RP HIS-109. RX PubMed=23695682; DOI=10.1038/ncomms2880; RA Liu S., Song X., Chrunyk B.A., Shanker S., Hoth L.R., Marr E.S., RA Griffor M.C.; RT "Crystal structures of interleukin 17A and its complex with IL-17 receptor RT A."; RL Nat. Commun. 4:1888-1888(2013). RN [19] RP X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) OF 24-155 IN COMPLEX WITH IL17F; RP IL17RA AND IL17RC, SUBUNIT, AND MUTAGENESIS OF ARG-69. RX PubMed=28827714; DOI=10.1038/s41598-017-08360-9; RA Goepfert A., Lehmann S., Wirth E., Rondeau J.M.; RT "The human IL-17A/F heterodimer: a two-faced cytokine with unique receptor RT recognition properties."; RL Sci. Rep. 7:8906-8906(2017). CC -!- FUNCTION: Effector cytokine of innate and adaptive immune system CC involved in antimicrobial host defense and maintenance of tissue CC integrity (PubMed:24120361). Signals via IL17RA-IL17RC heterodimeric CC receptor complex, triggering homotypic interaction of IL17RA and IL17RC CC chains with TRAF3IP2 adapter. This leads to downstream TRAF6-mediated CC activation of NF-kappa-B and MAPkinase pathways ultimately resulting in CC transcriptional activation of cytokines, chemokines, antimicrobial CC peptides and matrix metalloproteinases, with potential strong immune CC inflammation (PubMed:17911633, PubMed:18684971, PubMed:19825828, CC PubMed:21350122, PubMed:24120361, PubMed:8676080). Plays an important CC role in connecting T cell-mediated adaptive immunity and acute CC inflammatory response to destroy extracellular bacteria and fungi. As a CC signature effector cytokine of T-helper 17 cells (Th17), primarily CC induces neutrophil activation and recruitment at infection and CC inflammatory sites (By similarity). In airway epithelium, mediates CC neutrophil chemotaxis via induction of CXCL1 and CXCL5 chemokines (By CC similarity). In secondary lymphoid organs, contributes to germinal CC center formation by regulating the chemotactic response of B cells to CC CXCL12 and CXCL13, enhancing retention of B cells within the germinal CC centers, B cell somatic hypermutation rate and selection toward plasma CC cells (By similarity). Effector cytokine of a subset of gamma-delta T CC cells that functions as part of an inflammatory circuit downstream CC IL1B, TLR2 and IL23A-IL12B to promote neutrophil recruitment for CC efficient bacterial clearance (By similarity). Effector cytokine of CC innate immune cells including invariant natural killer cell (iNKT) and CC group 3 innate lymphoid cells that mediate initial neutrophilic CC inflammation (By similarity). Involved in the maintenance of the CC integrity of epithelial barriers during homeostasis and pathogen CC infection (PubMed:21350122). Upon acute injury, has a direct role in CC epithelial barrier formation by regulating OCLN localization and tight CC junction biogenesis (By similarity). As part of the mucosal immune CC response induced by commensal bacteria, enhances host's ability to CC resist pathogenic bacterial and fungal infections by promoting CC neutrophil recruitment and antimicrobial peptides release (By CC similarity). In synergy with IL17F, mediates the production of CC antimicrobial beta-defensins DEFB1, DEFB103A, and DEFB104A by mucosal CC epithelial cells, limiting the entry of microbes through the epithelial CC barriers (By similarity). Involved in antiviral host defense through CC various mechanisms (By similarity). Enhances immunity against West Nile CC virus by promoting T cell cytotoxicity (By similarity). May play a CC beneficial role in influenza A virus (H5N1) infection by enhancing B CC cell recruitment and immune response in the lung (By similarity). CC Contributes to influenza A virus (H1N1) clearance by driving the CC differentiation of B-1a B cells, providing for production of virus- CC specific IgM antibodies at first line of host defense (By similarity). CC {ECO:0000250|UniProtKB:Q62386, ECO:0000269|PubMed:17911633, CC ECO:0000269|PubMed:18684971, ECO:0000269|PubMed:19825828, CC ECO:0000269|PubMed:21350122, ECO:0000269|PubMed:24120361, CC ECO:0000269|PubMed:8676080}. CC -!- SUBUNIT: Homodimer (PubMed:19835883). Forms complexes with IL17RA and CC IL17RC receptors with 2:1 binding stoichiometry: two receptor chains CC for one interleukin molecule (PubMed:32187518). IL17A homodimer CC preferentially drives the formation of IL17RA-IL17RC heterodimeric CC receptor complex (PubMed:32187518). IL17A homodimer adopts an CC asymmetrical ternary structure with one IL17RA molecule, allowing for CC high affinity interactions of one IL17A monomer with one IL17RA CC molecule (via D1 and D2 domains), while disfavoring binding of a second CC IL17RA molecule on the other IL17A monomer (PubMed:23695682). CC Heterodimer with IL17F (PubMed:17355969). IL17A-IL17F forms complexes CC with IL17RA-IL17RC, but with lower affinity when compared to IL17A CC homodimer (PubMed:32187518). IL17RA and IL17RC chains cannot CC distinguish between IL17A and IL17F molecules, potentially enabling the CC formation of topologically distinct complexes (PubMed:17355969, CC PubMed:28827714). {ECO:0000269|PubMed:17355969, CC ECO:0000269|PubMed:19835883, ECO:0000269|PubMed:23695682, CC ECO:0000269|PubMed:28827714, ECO:0000269|PubMed:32187518}. CC -!- INTERACTION: CC Q16552; Q9BQC3: DPH2; NbExp=3; IntAct=EBI-10237926, EBI-10237931; CC Q16552; Q6PIL6: KCNIP4; NbExp=3; IntAct=EBI-10237926, EBI-1051469; CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:17763419, CC ECO:0000269|PubMed:8676080}. CC -!- TISSUE SPECIFICITY: Expressed in memory Th17 cells (at protein level). CC {ECO:0000269|PubMed:17763419}. CC -!- INDUCTION: Induced upon differentiation of CD4-positive T cells. Up- CC regulated by IL23A-IL12B (PubMed:17763419). Up-regulated in peripheral CC blood mononuclear cells upon West Nile virus infection CC (PubMed:27795421). {ECO:0000269|PubMed:17763419, CC ECO:0000269|PubMed:27795421}. CC -!- PTM: N-glycosylated. Found both in glycosylated and nonglycosylated CC forms. {ECO:0000269|PubMed:8676080}. CC -!- SIMILARITY: Belongs to the IL-17 family. {ECO:0000305}. CC -!- WEB RESOURCE: Name=Wikipedia; Note=Interleukin-17 entry; CC URL="https://en.wikipedia.org/wiki/Interleukin_17"; CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and CC Haematology; CC URL="https://atlasgeneticsoncology.org/gene/40945/IL17A"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; Z58820; CAA91233.1; -; mRNA. DR EMBL; U32659; AAC50341.1; -; mRNA. DR EMBL; AY460616; AAR23263.1; -; Genomic_DNA. DR EMBL; AL391221; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471081; EAX04362.1; -; Genomic_DNA. DR EMBL; BC066251; AAH66251.1; -; mRNA. DR EMBL; BC066252; AAH66252.1; -; mRNA. DR EMBL; BC067503; AAH67503.1; -; mRNA. DR EMBL; BC067504; AAH67504.1; -; mRNA. DR EMBL; BC067505; AAH67505.1; -; mRNA. DR CCDS; CCDS4937.1; -. DR RefSeq; NP_002181.1; NM_002190.2. DR PDB; 2VXS; X-ray; 2.63 A; A/B/C/D=20-155. DR PDB; 4HR9; X-ray; 2.48 A; A/B=34-155. DR PDB; 4HSA; X-ray; 3.15 A; A/B/D/E=34-155. DR PDB; 4QHU; X-ray; 2.20 A; C/D=24-154. DR PDB; 5HHV; X-ray; 2.20 A; A/B=34-155. DR PDB; 5HHX; X-ray; 3.00 A; A/B=20-155. DR PDB; 5HI3; X-ray; 2.15 A; A/B=24-155. DR PDB; 5HI4; X-ray; 1.80 A; A/B=24-155. DR PDB; 5HI5; X-ray; 1.80 A; A/B=24-155. DR PDB; 5N7W; X-ray; 1.96 A; X/Y=1-155. DR PDB; 5N92; X-ray; 2.30 A; A=24-155. DR PDB; 5NAN; X-ray; 3.30 A; A/D=24-155. DR PDB; 5VB9; X-ray; 1.70 A; A/B=38-155. DR PDB; 6WIO; X-ray; 2.17 A; C=1-155. DR PDB; 6WIR; X-ray; 2.96 A; C=1-155. DR PDB; 7AMA; X-ray; 2.48 A; A/B=42-150. DR PDB; 7AMG; X-ray; 3.18 A; A/B/C/D=42-150. DR PDB; 7UWM; EM; 2.50 A; A/B/D/E=25-155. DR PDB; 7UWN; EM; 3.01 A; A/B/D/E=24-155. DR PDB; 7WKX; X-ray; 2.81 A; E/F=20-155. DR PDB; 7Z2M; X-ray; 1.90 A; G/I/J/K=34-155. DR PDB; 7ZAN; X-ray; 5.06 A; A/B=34-155. DR PDB; 8B7W; X-ray; 2.85 A; C=34-155. DR PDB; 8CDG; X-ray; 2.90 A; A/B=34-155. DR PDB; 8DY1; X-ray; 2.68 A; A/B=35-155. DR PDB; 8DY5; X-ray; 2.20 A; C/D=35-155. DR PDB; 8DYF; X-ray; 2.02 A; A/B=34-155. DR PDB; 8DYG; X-ray; 1.49 A; A/B=34-155. DR PDB; 8DYH; X-ray; 1.94 A; A/B=34-155. DR PDB; 8DYI; X-ray; 2.28 A; A/B=34-155. DR PDB; 8USR; X-ray; 1.83 A; A/B/C/D=34-155. DR PDB; 8USS; X-ray; 1.47 A; A=34-155. DR PDBsum; 2VXS; -. DR PDBsum; 4HR9; -. DR PDBsum; 4HSA; -. DR PDBsum; 4QHU; -. DR PDBsum; 5HHV; -. DR PDBsum; 5HHX; -. DR PDBsum; 5HI3; -. DR PDBsum; 5HI4; -. DR PDBsum; 5HI5; -. DR PDBsum; 5N7W; -. DR PDBsum; 5N92; -. DR PDBsum; 5NAN; -. DR PDBsum; 5VB9; -. DR PDBsum; 6WIO; -. DR PDBsum; 6WIR; -. DR PDBsum; 7AMA; -. DR PDBsum; 7AMG; -. DR PDBsum; 7UWM; -. DR PDBsum; 7UWN; -. DR PDBsum; 7WKX; -. DR PDBsum; 7Z2M; -. DR PDBsum; 7ZAN; -. DR PDBsum; 8B7W; -. DR PDBsum; 8CDG; -. DR PDBsum; 8DY1; -. DR PDBsum; 8DY5; -. DR PDBsum; 8DYF; -. DR PDBsum; 8DYG; -. DR PDBsum; 8DYH; -. DR PDBsum; 8DYI; -. DR PDBsum; 8USR; -. DR PDBsum; 8USS; -. DR AlphaFoldDB; Q16552; -. DR EMDB; EMD-26836; -. DR EMDB; EMD-26837; -. DR SMR; Q16552; -. DR BioGRID; 109818; 11. DR ComplexPortal; CPX-8776; Interleukin-17A-F receptor-ligand complex. DR ComplexPortal; CPX-9201; Interleukin-17A receptor-ligand complex. DR ComplexPortal; CPX-9301; Interleukin-17A complex. DR ComplexPortal; CPX-9307; Interleukin-17A-F complex. DR DIP; DIP-6014N; -. DR IntAct; Q16552; 8. DR STRING; 9606.ENSP00000497968; -. DR BindingDB; Q16552; -. DR ChEMBL; CHEMBL3390822; -. DR DrugBank; DB12917; Bimekizumab. DR DrugBank; DB11569; Ixekizumab. DR DrugBank; DB09029; Secukinumab. DR DrugCentral; Q16552; -. DR GlyCosmos; Q16552; 1 site, No reported glycans. DR GlyGen; Q16552; 2 sites. DR iPTMnet; Q16552; -. DR PhosphoSitePlus; Q16552; -. DR BioMuta; IL17A; -. DR DMDM; 2498481; -. DR PaxDb; 9606-ENSP00000344192; -. DR PeptideAtlas; Q16552; -. DR ProteomicsDB; 60910; -. DR ABCD; Q16552; 183 sequenced antibodies. DR Antibodypedia; 17132; 2390 antibodies from 52 providers. DR DNASU; 3605; -. DR Ensembl; ENST00000648244.1; ENSP00000497968.1; ENSG00000112115.7. DR GeneID; 3605; -. DR KEGG; hsa:3605; -. DR MANE-Select; ENST00000648244.1; ENSP00000497968.1; NM_002190.3; NP_002181.1. DR UCSC; uc003pak.1; human. DR AGR; HGNC:5981; -. DR CTD; 3605; -. DR DisGeNET; 3605; -. DR GeneCards; IL17A; -. DR HGNC; HGNC:5981; IL17A. DR HPA; ENSG00000112115; Tissue enhanced (lymphoid). DR MIM; 603149; gene. DR neXtProt; NX_Q16552; -. DR OpenTargets; ENSG00000112115; -. DR PharmGKB; PA29794; -. DR VEuPathDB; HostDB:ENSG00000112115; -. DR eggNOG; ENOG502S5A0; Eukaryota. DR GeneTree; ENSGT00940000161882; -. DR HOGENOM; CLU_118641_0_0_1; -. DR InParanoid; Q16552; -. DR OMA; QNPGCPN; -. DR OrthoDB; 5400717at2759; -. DR PhylomeDB; Q16552; -. DR TreeFam; TF314701; -. DR PathwayCommons; Q16552; -. DR Reactome; R-HSA-448424; Interleukin-17 signaling. DR Reactome; R-HSA-6785807; Interleukin-4 and Interleukin-13 signaling. DR Reactome; R-HSA-9705671; SARS-CoV-2 activates/modulates innate and adaptive immune responses. DR SignaLink; Q16552; -. DR SIGNOR; Q16552; -. DR BioGRID-ORCS; 3605; 11 hits in 1145 CRISPR screens. DR EvolutionaryTrace; Q16552; -. DR GeneWiki; IL17A; -. DR GenomeRNAi; 3605; -. DR Pharos; Q16552; Tclin. DR PRO; PR:Q16552; -. DR Proteomes; UP000005640; Chromosome 6. DR RNAct; Q16552; protein. DR Bgee; ENSG00000112115; Expressed in vermiform appendix and 24 other cell types or tissues. DR GO; GO:0009897; C:external side of plasma membrane; IEA:Ensembl. DR GO; GO:0005576; C:extracellular region; TAS:Reactome. DR GO; GO:0005615; C:extracellular space; IDA:UniProt. DR GO; GO:0005125; F:cytokine activity; IDA:UniProt. DR GO; GO:0046982; F:protein heterodimerization activity; IEA:Ensembl. DR GO; GO:0042803; F:protein homodimerization activity; IEA:Ensembl. DR GO; GO:0002250; P:adaptive immune response; IEA:UniProtKB-KW. DR GO; GO:0006915; P:apoptotic process; TAS:ProtInc. DR GO; GO:0008219; P:cell death; TAS:ProtInc. DR GO; GO:0007267; P:cell-cell signaling; TAS:ProtInc. DR GO; GO:0071347; P:cellular response to interleukin-1; IEA:Ensembl. DR GO; GO:0050832; P:defense response to fungus; IEA:Ensembl. DR GO; GO:0050829; P:defense response to Gram-negative bacterium; IEA:Ensembl. DR GO; GO:0050830; P:defense response to Gram-positive bacterium; IEA:Ensembl. DR GO; GO:0072537; P:fibroblast activation; IDA:BHF-UCL. DR GO; GO:0010467; P:gene expression; IEA:Ensembl. DR GO; GO:0097530; P:granulocyte migration; IEA:Ensembl. DR GO; GO:0006955; P:immune response; TAS:ProtInc. DR GO; GO:0006954; P:inflammatory response; IEA:UniProtKB-KW. DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW. DR GO; GO:0097400; P:interleukin-17-mediated signaling pathway; IDA:UniProtKB. DR GO; GO:0038173; P:interleukin-17A-mediated signaling pathway; IDA:UniProt. DR GO; GO:0060729; P:intestinal epithelial structure maintenance; IEA:Ensembl. DR GO; GO:0030216; P:keratinocyte differentiation; IEA:Ensembl. DR GO; GO:0043616; P:keratinocyte proliferation; IEA:Ensembl. DR GO; GO:0106015; P:negative regulation of inflammatory response to wounding; IEA:Ensembl. DR GO; GO:0007219; P:Notch signaling pathway; IEA:Ensembl. DR GO; GO:0002225; P:positive regulation of antimicrobial peptide production; IEA:Ensembl. DR GO; GO:1903348; P:positive regulation of bicellular tight junction assembly; IEA:Ensembl. DR GO; GO:2000340; P:positive regulation of chemokine (C-X-C motif) ligand 1 production; IDA:UniProtKB. DR GO; GO:1900017; P:positive regulation of cytokine production involved in inflammatory response; IDA:ARUK-UCL. DR GO; GO:0032731; P:positive regulation of interleukin-1 beta production; IDA:ARUK-UCL. DR GO; GO:0032735; P:positive regulation of interleukin-12 production; IDA:ARUK-UCL. DR GO; GO:0032739; P:positive regulation of interleukin-16 production; IDA:ARUK-UCL. DR GO; GO:0032747; P:positive regulation of interleukin-23 production; IDA:BHF-UCL. DR GO; GO:0032755; P:positive regulation of interleukin-6 production; IDA:UniProtKB. DR GO; GO:0045672; P:positive regulation of osteoclast differentiation; IDA:BHF-UCL. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:MGI. DR GO; GO:0032760; P:positive regulation of tumor necrosis factor production; IDA:ARUK-UCL. DR GO; GO:0009611; P:response to wounding; IDA:UniProt. DR Gene3D; 2.10.90.10; Cystine-knot cytokines; 1. DR InterPro; IPR029034; Cystine-knot_cytokine. DR InterPro; IPR020440; IL-17_chr. DR InterPro; IPR010345; IL-17_fam. DR Pfam; PF06083; IL17; 1. DR PRINTS; PR01932; INTRLEUKIN17. DR SUPFAM; SSF57501; Cystine-knot cytokines; 1. PE 1: Evidence at protein level; KW 3D-structure; Adaptive immunity; Cytokine; Direct protein sequencing; KW Disulfide bond; Glycoprotein; Immunity; Inflammatory response; KW Innate immunity; Proteomics identification; Reference proteome; Secreted; KW Signal. FT SIGNAL 1..23 FT /evidence="ECO:0000269|PubMed:15340161" FT CHAIN 24..155 FT /note="Interleukin-17A" FT /id="PRO_0000015423" FT CARBOHYD 68 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT DISULFID 94..144 FT /evidence="ECO:0000269|PubMed:19835883, FT ECO:0000269|PubMed:23695682" FT DISULFID 99..146 FT /evidence="ECO:0000269|PubMed:19835883, FT ECO:0000269|PubMed:23695682" FT MUTAGEN 69 FT /note="R->A: Impairs binding to IL17RA and IL17RC." FT /evidence="ECO:0000269|PubMed:28827714" FT MUTAGEN 78 FT /note="R->V: Decreases the affinity for IL17RA by 5-fold." FT /evidence="ECO:0000269|PubMed:23695682" FT MUTAGEN 90 FT /note="W->V: Has no effect on the affinity for IL17RA." FT /evidence="ECO:0000269|PubMed:23695682" FT MUTAGEN 108 FT /note="Y->I: Decreases the affinity for IL17RA." FT /evidence="ECO:0000269|PubMed:23695682" FT MUTAGEN 109 FT /note="H->S: Decreases the affinity for IL17RA." FT /evidence="ECO:0000269|PubMed:23695682" FT HELIX 35..39 FT /evidence="ECO:0007829|PDB:4QHU" FT STRAND 45..48 FT /evidence="ECO:0007829|PDB:8DYG" FT HELIX 51..53 FT /evidence="ECO:0007829|PDB:8USS" FT HELIX 60..67 FT /evidence="ECO:0007829|PDB:8USS" FT STRAND 70..72 FT /evidence="ECO:0007829|PDB:8USS" FT STRAND 74..80 FT /evidence="ECO:0007829|PDB:8USS" FT STRAND 84..95 FT /evidence="ECO:0007829|PDB:8USS" FT STRAND 97..100 FT /evidence="ECO:0007829|PDB:8USS" FT STRAND 104..107 FT /evidence="ECO:0007829|PDB:5VB9" FT STRAND 110..123 FT /evidence="ECO:0007829|PDB:8USS" FT STRAND 125..128 FT /evidence="ECO:0007829|PDB:8DYH" FT STRAND 130..132 FT /evidence="ECO:0007829|PDB:8DYH" FT STRAND 135..147 FT /evidence="ECO:0007829|PDB:8USS" FT STRAND 150..153 FT /evidence="ECO:0007829|PDB:7UWM" SQ SEQUENCE 155 AA; 17504 MW; 2BCAE9CB2F4886D1 CRC64; MTPGKTSLVS LLLLLSLEAI VKAGITIPRN PGCPNSEDKN FPRTVMVNLN IHNRNTNTNP KRSSDYYNRS TSPWNLHRNE DPERYPSVIW EAKCRHLGCI NADGNVDYHM NSVPIQQEIL VLRREPPHCP NSFRLEKILV SVGCTCVTPI VHHVA //