Interleukin-17F

Details

Name
Interleukin-17F
Synonyms
  • Cytokine ML-1
  • IL-17F
Gene Name
IL17F
Organism
Humans
Amino acid sequence
>lcl|BSEQ0052770|Interleukin-17F
MTVKTLHGPAMVKYLLLSILGLAFLSEAAARKIPKVGHTFFQKPESCPPVPGGSMKLDIG
IINENQRVSMSRNIESRSTSPWNYTVTWDPNRYPSEVVQAQCRNLGCINAQGKEDISMNS
VPIQQETLVVRRKHQGCSVSFQLEKVLVTVGCTCVTPVIHHVQ
Number of residues
163
Molecular Weight
18044.88
Theoretical pI
Not Available
GO Classification
Functions
cytokine activity / cytokine binding / cytokine receptor binding / protein heterodimerization activity / protein homodimerization activity
Processes
adaptive immune response / cartilage development / defense response to Gram-negative bacterium / defense response to Gram-positive bacterium / inflammatory response / innate immune response / interleukin-17-mediated signaling pathway / negative regulation of angiogenesis / positive regulation of antimicrobial peptide production / positive regulation of chemokine (C-X-C motif) ligand 1 production / positive regulation of cytokine production / positive regulation of cytokine production involved in inflammatory response / positive regulation of interleukin-6 production / positive regulation of lymphotoxin A production / positive regulation of transcription by RNA polymerase II / regulation of granulocyte macrophage colony-stimulating factor production / regulation of interleukin-2 production / regulation of interleukin-6 production / regulation of interleukin-8 production / regulation of transforming growth factor beta receptor signaling pathway
Components
extracellular region / extracellular space
General Function
Effector cytokine of innate and adaptive immune system involved in antimicrobial host defense and maintenance of tissue integrity (PubMed:21350122). IL17A-IL17F signals via IL17RA-IL17RC heterodimeric receptor complex, triggering homotypic interaction of IL17RA and IL17RC chains with TRAF3IP2 adapter through SEFIR domains. This leads to downstream TRAF6-mediated activation of NF-kappa-B and MAPkinase pathways ultimately resulting in transcriptional activation of cytokines, chemokines, antimicrobial peptides and matrix metalloproteinases, with potential strong immune inflammation (PubMed:18684971, PubMed:21350122, PubMed:11591732, PubMed:11591768, PubMed:17911633, PubMed:11574464, PubMed:28827714). IL17A-IL17F is primarily involved in host defense against extracellular bacteria and fungi by inducing neutrophilic inflammation (By similarity). As signature effector cytokine of T-helper 17 cells (Th17), primarily induces neutrophil activation and recruitment at infection and inflammatory sites (By similarity). Stimulates the production of antimicrobial beta-defensins DEFB1, DEFB103A, and DEFB104A by mucosal epithelial cells, limiting the entry of microbes through the epithelial barriers (By similarity). IL17F homodimer can signal via IL17RC homodimeric receptor complex, triggering downstream activation of TRAF6 and NF-kappa-B signaling pathway (PubMed:32187518). Via IL17RC induces transcriptional activation of IL33, a potent cytokine that stimulates group 2 innate lymphoid cells and adaptive T-helper 2 cells involved in pulmonary allergic response to fungi. Likely via IL17RC, promotes sympathetic innervation of peripheral organs by coordinating the communication between gamma-delta T cells and parenchymal cells. Stimulates sympathetic innervation of thermogenic adipose tissue by driving TGFB1 expression (By similarity). Regulates the composition of intestinal microbiota and immune tolerance by inducing antimicrobial proteins that specifically control the growth of commensal Firmicutes and Bacteroidetes (By similarity).
Specific Function
Cytokine activity
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Secreted
Gene sequence
>lcl|BSEQ0052771|Interleukin-17F (IL17F)
ATGACAGTGAAGACCCTGCATGGCCCAGCCATGGTCAAGTACTTGCTGCTGTCGATATTG
GGGCTTGCCTTTCTGAGTGAGGCGGCAGCTCGGAAAATCCCCAAAGTAGGACATACTTTT
TTCCAAAAGCCTGAGAGTTGCCCGCCTGTGCCAGGAGGTAGTATGAAGCTTGACATTGGC
ATCATCAATGAAAACCAGCGCGTTTCCATGTCACGTAACATCGAGAGCCGCTCCACCTCC
CCCTGGAATTACACTGTCACTTGGGACCCCAACCGGTACCCCTCGGAAGTTGTACAGGCC
CAGTGTAGGAACTTGGGCTGCATCAATGCTCAAGGAAAGGAAGACATCTCCATGAATTCC
GTTCCCATCCAGCAAGAGACCCTGGTCGTCCGGAGGAAGCACCAAGGCTGCTCTGTTTCT
TTCCAGTTGGAGAAGGTGCTGGTGACTGTTGGCTGCACCTGCGTCACCCCTGTCATCCAC
CATGTGCAGTAA
Chromosome Location
6
Locus
6p12.2
External Identifiers
ResourceLink
UniProtKB IDQ96PD4
UniProtKB Entry NameIL17F_HUMAN
HGNC IDHGNC:16404
General References
  1. Starnes T, Robertson MJ, Sledge G, Kelich S, Nakshatri H, Broxmeyer HE, Hromas R: Cutting edge: IL-17F, a novel cytokine selectively expressed in activated T cells and monocytes, regulates angiogenesis and endothelial cell cytokine production. J Immunol. 2001 Oct 15;167(8):4137-40. doi: 10.4049/jimmunol.167.8.4137. [Article]
  2. Mungall AJ, Palmer SA, Sims SK, Edwards CA, Ashurst JL, Wilming L, Jones MC, Horton R, Hunt SE, Scott CE, Gilbert JG, Clamp ME, Bethel G, Milne S, Ainscough R, Almeida JP, Ambrose KD, Andrews TD, Ashwell RI, Babbage AK, Bagguley CL, Bailey J, Banerjee R, Barker DJ, Barlow KF, Bates K, Beare DM, Beasley H, Beasley O, Bird CP, Blakey S, Bray-Allen S, Brook J, Brown AJ, Brown JY, Burford DC, Burrill W, Burton J, Carder C, Carter NP, Chapman JC, Clark SY, Clark G, Clee CM, Clegg S, Cobley V, Collier RE, Collins JE, Colman LK, Corby NR, Coville GJ, Culley KM, Dhami P, Davies J, Dunn M, Earthrowl ME, Ellington AE, Evans KA, Faulkner L, Francis MD, Frankish A, Frankland J, French L, Garner P, Garnett J, Ghori MJ, Gilby LM, Gillson CJ, Glithero RJ, Grafham DV, Grant M, Gribble S, Griffiths C, Griffiths M, Hall R, Halls KS, Hammond S, Harley JL, Hart EA, Heath PD, Heathcott R, Holmes SJ, Howden PJ, Howe KL, Howell GR, Huckle E, Humphray SJ, Humphries MD, Hunt AR, Johnson CM, Joy AA, Kay M, Keenan SJ, Kimberley AM, King A, Laird GK, Langford C, Lawlor S, Leongamornlert DA, Leversha M, Lloyd CR, Lloyd DM, Loveland JE, Lovell J, Martin S, Mashreghi-Mohammadi M, Maslen GL, Matthews L, McCann OT, McLaren SJ, McLay K, McMurray A, Moore MJ, Mullikin JC, Niblett D, Nickerson T, Novik KL, Oliver K, Overton-Larty EK, Parker A, Patel R, Pearce AV, Peck AI, Phillimore B, Phillips S, Plumb RW, Porter KM, Ramsey Y, Ranby SA, Rice CM, Ross MT, Searle SM, Sehra HK, Sheridan E, Skuce CD, Smith S, Smith M, Spraggon L, Squares SL, Steward CA, Sycamore N, Tamlyn-Hall G, Tester J, Theaker AJ, Thomas DW, Thorpe A, Tracey A, Tromans A, Tubby B, Wall M, Wallis JM, West AP, White SS, Whitehead SL, Whittaker H, Wild A, Willey DJ, Wilmer TE, Wood JM, Wray PW, Wyatt JC, Young L, Younger RM, Bentley DR, Coulson A, Durbin R, Hubbard T, Sulston JE, Dunham I, Rogers J, Beck S: The DNA sequence and analysis of human chromosome 6. Nature. 2003 Oct 23;425(6960):805-11. [Article]
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  4. Kawaguchi M, Onuchic LF, Li XD, Essayan DM, Schroeder J, Xiao HQ, Liu MC, Krishnaswamy G, Germino G, Huang SK: Identification of a novel cytokine, ML-1, and its expression in subjects with asthma. J Immunol. 2001 Oct 15;167(8):4430-5. doi: 10.4049/jimmunol.167.8.4430. [Article]
  5. Zhang Z, Henzel WJ: Signal peptide prediction based on analysis of experimentally verified cleavage sites. Protein Sci. 2004 Oct;13(10):2819-24. Epub 2004 Aug 31. [Article]
  6. Wright JF, Guo Y, Quazi A, Luxenberg DP, Bennett F, Ross JF, Qiu Y, Whitters MJ, Tomkinson KN, Dunussi-Joannopoulos K, Carreno BM, Collins M, Wolfman NM: Identification of an interleukin 17F/17A heterodimer in activated human CD4+ T cells. J Biol Chem. 2007 May 4;282(18):13447-55. doi: 10.1074/jbc.M700499200. Epub 2007 Mar 13. [Article]
  7. Kuestner RE, Taft DW, Haran A, Brandt CS, Brender T, Lum K, Harder B, Okada S, Ostrander CD, Kreindler JL, Aujla SJ, Reardon B, Moore M, Shea P, Schreckhise R, Bukowski TR, Presnell S, Guerra-Lewis P, Parrish-Novak J, Ellsworth JL, Jaspers S, Lewis KE, Appleby M, Kolls JK, Rixon M, West JW, Gao Z, Levin SD: Identification of the IL-17 receptor related molecule IL-17RC as the receptor for IL-17F. J Immunol. 2007 Oct 15;179(8):5462-73. doi: 10.4049/jimmunol.179.8.5462. [Article]
  8. Wright JF, Bennett F, Li B, Brooks J, Luxenberg DP, Whitters MJ, Tomkinson KN, Fitz LJ, Wolfman NM, Collins M, Dunussi-Joannopoulos K, Chatterjee-Kishore M, Carreno BM: The human IL-17F/IL-17A heterodimeric cytokine signals through the IL-17RA/IL-17RC receptor complex. J Immunol. 2008 Aug 15;181(4):2799-805. doi: 10.4049/jimmunol.181.4.2799. [Article]
  9. Hymowitz SG, Filvaroff EH, Yin JP, Lee J, Cai L, Risser P, Maruoka M, Mao W, Foster J, Kelley RF, Pan G, Gurney AL, de Vos AM, Starovasnik MA: IL-17s adopt a cystine knot fold: structure and activity of a novel cytokine, IL-17F, and implications for receptor binding. EMBO J. 2001 Oct 1;20(19):5332-41. doi: 10.1093/emboj/20.19.5332. [Article]
  10. Ely LK, Fischer S, Garcia KC: Structural basis of receptor sharing by interleukin 17 cytokines. Nat Immunol. 2009 Dec;10(12):1245-51. doi: 10.1038/ni.1813. Epub 2009 Oct 18. [Article]
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  12. Goepfert A, Lehmann S, Blank J, Kolbinger F, Rondeau JM: Structural Analysis Reveals that the Cytokine IL-17F Forms a Homodimeric Complex with Receptor IL-17RC to Drive IL-17RA-Independent Signaling. Immunity. 2020 Mar 17;52(3):499-512.e5. doi: 10.1016/j.immuni.2020.02.004. [Article]
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Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB12917Bimekizumabapproved, investigationalyesantibodyDetails