IL17F_MOUSE
ID IL17F_MOUSE Reviewed; 161 AA.
AC Q7TNI7; Q8K4C3;
DT 16-JUN-2009, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2003, sequence version 1.
DT 03-AUG-2022, entry version 112.
DE RecName: Full=Interleukin-17F;
DE Short=IL-17F;
DE Flags: Precursor;
GN Name=Il17f;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA Kawaguchi M., Kokubu F., Suzuki S., Watanabe S., Ieki K., Matsukura S.,
RA Kurokawa M., Adachi M.;
RT "Expression of IL-17F like cytokine in a mouse model of asthma.";
RL Submitted (AUG-2003) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND FUNCTION.
RX PubMed=15477493; DOI=10.1164/rccm.200406-778oc;
RA Oda N., Canelos P.B., Essayan D.M., Plunkett B.A., Myers A.C., Huang S.K.;
RT "Interleukin-17F induces pulmonary neutrophilia and amplifies antigen-
RT induced allergic response.";
RL Am. J. Respir. Crit. Care Med. 171:12-18(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RA Gilbert J.M., Gorman D.M.;
RL Submitted (DEC-2001) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP INDUCTION BY IL6 AND TGFB1, AND TISSUE SPECIFICITY.
RX PubMed=16990136; DOI=10.1016/j.cell.2006.07.035;
RA Ivanov I.I., McKenzie B.S., Zhou L., Tadokoro C.E., Lepelley A.,
RA Lafaille J.J., Cua D.J., Littman D.R.;
RT "The orphan nuclear receptor RORgammat directs the differentiation program
RT of proinflammatory IL-17+ T helper cells.";
RL Cell 126:1121-1133(2006).
RN [5]
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 [6]
RP FUNCTION, SUBUNIT, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND INDUCTION.
RX PubMed=18025225; DOI=10.4049/jimmunol.179.11.7791;
RA Liang S.C., Long A.J., Bennett F., Whitters M.J., Karim R., Collins M.,
RA Goldman S.J., Dunussi-Joannopoulos K., Williams C.M., Wright J.F.,
RA Fouser L.A.;
RT "An IL-17F/A heterodimer protein is produced by mouse Th17 cells and
RT induces airway neutrophil recruitment.";
RL J. Immunol. 179:7791-7799(2007).
RN [7]
RP FUNCTION, DISRUPTION PHENOTYPE, AND TISSUE SPECIFICITY.
RX PubMed=19144317; DOI=10.1016/j.immuni.2008.11.009;
RA Ishigame H., Kakuta S., Nagai T., Kadoki M., Nambu A., Komiyama Y.,
RA Fujikado N., Tanahashi Y., Akitsu A., Kotaki H., Sudo K., Nakae S.,
RA Sasakawa C., Iwakura Y.;
RT "Differential roles of interleukin-17A and -17F in host defense against
RT mucoepithelial bacterial infection and allergic responses.";
RL Immunity 30:108-119(2009).
RN [8]
RP FUNCTION, TISSUE SPECIFICITY, AND INDUCTION.
RX PubMed=23255360; DOI=10.4049/jimmunol.1202924;
RA Gladiator A., Wangler N., Trautwein-Weidner K., LeibundGut-Landmann S.;
RT "IL-17-secreting innate lymphoid cells are essential for host defense
RT against fungal infection.";
RL J. Immunol. 190:521-525(2013).
RN [9]
RP FUNCTION, DISRUPTION PHENOTYPE, AND INDUCTION.
RX PubMed=28813677; DOI=10.1016/j.celrep.2017.07.063;
RA De Luca A., Pariano M., Cellini B., Costantini C., Villella V.R.,
RA Jose S.S., Palmieri M., Borghi M., Galosi C., Paolicelli G., Maiuri L.,
RA Fric J., Zelante T.;
RT "The IL-17F/IL-17RC Axis Promotes Respiratory Allergy in the Proximal
RT Airways.";
RL Cell Rep. 20:1667-1680(2017).
RN [10]
RP FUNCTION, DISRUPTION PHENOTYPE, AND TISSUE SPECIFICITY.
RX PubMed=29915298; DOI=10.1038/s41590-018-0134-y;
RA Tang C., Kakuta S., Shimizu K., Kadoki M., Kamiya T., Shimazu T., Kubo S.,
RA Saijo S., Ishigame H., Nakae S., Iwakura Y.;
RT "Suppression of IL-17F, but not of IL-17A, provides protection against
RT colitis by inducing Treg cells through modification of the intestinal
RT microbiota.";
RL Nat. Immunol. 19:755-765(2018).
RN [11]
RP FUNCTION, AND INDUCTION BY COLD.
RX PubMed=32076265; DOI=10.1038/s41586-020-2028-z;
RA Hu B., Jin C., Zeng X., Resch J.M., Jedrychowski M.P., Yang Z., Desai B.N.,
RA Banks A.S., Lowell B.B., Mathis D., Spiegelman B.M.;
RT "gammadelta T cells and adipocyte IL-17RC control fat innervation and
RT thermogenesis.";
RL Nature 578:610-614(2020).
CC -!- FUNCTION: Effector cytokine of innate and adaptive immune system
CC involved in antimicrobial host defense and maintenance of tissue
CC integrity (PubMed:23255360, PubMed:18025225, PubMed:19144317). IL17A-
CC IL17F signals via IL17RA-IL17RC heterodimeric receptor complex,
CC triggering homotypic interaction of IL17RA and IL17RC chains with
CC TRAF3IP2 adapter through SEFIR domains. This leads to downstream TRAF6-
CC mediated activation of NF-kappa-B and MAPkinase pathways ultimately
CC resulting in transcriptional activation of cytokines, chemokines,
CC antimicrobial peptides and matrix metalloproteinases, with potential
CC strong immune inflammation (PubMed:17911633, PubMed:15477493,
CC PubMed:18025225). IL17A-IL17F is primarily involved in host defense
CC against extracellular bacteria and fungi by inducing neutrophilic
CC inflammation (PubMed:18025225, PubMed:23255360). As signature effector
CC cytokine of T-helper 17 cells (Th17), primarily induces neutrophil
CC activation and recruitment at infection and inflammatory sites
CC (PubMed:18025225). Stimulates the production of antimicrobial beta-
CC defensins DEFB1, DEFB103A, and DEFB104A by mucosal epithelial cells,
CC limiting the entry of microbes through the epithelial barriers
CC (PubMed:19144317). IL17F homodimer can signal via IL17RC homodimeric
CC receptor complex, triggering downstream activation of TRAF6 and NF-
CC kappa-B signaling pathway (PubMed:28813677). Via IL17RC induces
CC transcriptional activation of IL33, a potent cytokine that stimulates
CC group 2 innate lymphoid cells and adaptive T-helper 2 cells involved in
CC pulmonary allergic response to fungi (PubMed:28813677). Likely via
CC IL17RC, promotes sympathetic innervation of peripheral organs by
CC coordinating the communication between gamma-delta T cells and
CC parenchymal cells. Stimulates sympathetic innervation of thermogenic
CC adipose tissue by driving TGFB1 expression (PubMed:32076265). Regulates
CC the composition of intestinal microbiota and immune tolerance by
CC inducing antimicrobial proteins that specifically control the growth of
CC commensal Firmicutes and Bacteroidetes (PubMed:29915298).
CC {ECO:0000250|UniProtKB:Q96PD4, ECO:0000269|PubMed:15477493,
CC ECO:0000269|PubMed:17911633, ECO:0000269|PubMed:18025225,
CC ECO:0000269|PubMed:19144317, ECO:0000269|PubMed:23255360,
CC ECO:0000269|PubMed:28813677, ECO:0000269|PubMed:29915298,
CC ECO:0000269|PubMed:32076265}.
CC -!- SUBUNIT: Homodimer; disulfide-linked (By similarity). Heterodimer with
CC IL17A (IL17A-IL17F) (PubMed:18025225). Forms complexes with IL17RA and
CC IL17RC receptors with 2:1 binding stoichiometry: two receptor chains
CC for one interleukin molecule (By similarity). IL17F homodimer forms
CC predominantly complexes with IL17RC homodimer, whereas IL17A-IL17F
CC favors complexes with IL17RA-IL17RC (By similarity). IL17RA and IL17RC
CC chains cannot distinguish between IL17A and IL17F molecules,
CC potentially enabling the formation of topologically distinct complexes
CC (By similarity). {ECO:0000250|UniProtKB:Q96PD4,
CC ECO:0000269|PubMed:18025225}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:18025225}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q7TNI7-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q7TNI7-2; Sequence=VSP_037499;
CC -!- TISSUE SPECIFICITY: Expressed by T-helper 17 cells (Th17) (at protein
CC level). The expression pattern reflects the differentiation state. In
CC fully differentiated Th17 cells, IL17A-IL17F heterodimers are produced
CC at higher levels than IL17A-IL17A and IL17F-IL17F dimers
CC (PubMed:18025225). Dominantly secreted in intestine (PubMed:29915298).
CC Expressed by resident cells of the lamina propria, both epithelial
CC cells and immune cell subsets including natural killer cells, dendritic
CC cells, macrophages and various T and B cell subsets (PubMed:29915298,
CC PubMed:16990136). Expressed by epithelial cells and innate immune cells
CC in the colon (PubMed:19144317). Expressed in group 3 innate lymphoid
CC cells (PubMed:23255360, PubMed:29915298). {ECO:0000269|PubMed:16990136,
CC ECO:0000269|PubMed:18025225, ECO:0000269|PubMed:19144317,
CC ECO:0000269|PubMed:23255360, ECO:0000269|PubMed:29915298}.
CC -!- INDUCTION: Induced upon antigen receptor binding in the presence of IL6
CC and TGB1 (PubMed:16990136, PubMed:18025225). Up-regulated by IL23A-
CC IL12B, IL1B and TNF and inhibited by IFNG and IL4 in CD4-positive T
CC cells (PubMed:18025225). Induced upon fungal infection in innate
CC lymphoid cells (PubMed:23255360). Induced in lung epithelial cells upon
CC bacterial and fungal infection (PubMed:28813677). Induced in brown
CC adipose tissue upon cold exposure (PubMed:32076265).
CC {ECO:0000269|PubMed:16990136, ECO:0000269|PubMed:18025225,
CC ECO:0000269|PubMed:23255360, ECO:0000269|PubMed:28813677,
CC ECO:0000269|PubMed:32076265}.
CC -!- DISRUPTION PHENOTYPE: Mutant mice are born healthy at the expected
CC Mendelian ratio, are fertile, and have no apparent phenotypic
CC abnormalities (PubMed:19144317). They show increased susceptibility to
CC S. aureus upper respiratory infection (PubMed:28813677). Mutant mice
CC are protected from chemically induced colitis, a model of human
CC inflammatory bowel disease (PubMed:29915298).
CC {ECO:0000269|PubMed:19144317, ECO:0000269|PubMed:28813677,
CC ECO:0000269|PubMed:29915298}.
CC -!- SIMILARITY: Belongs to the IL-17 family. {ECO:0000305}.
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DR EMBL; AY380822; AAQ88439.1; -; mRNA.
DR EMBL; AB116259; BAC81535.1; -; mRNA.
DR EMBL; AF458064; AAM77568.1; -; mRNA.
DR CCDS; CCDS35522.1; -. [Q7TNI7-1]
DR RefSeq; NP_665855.2; NM_145856.2. [Q7TNI7-1]
DR RefSeq; XP_006495586.1; XM_006495523.2. [Q7TNI7-1]
DR AlphaFoldDB; Q7TNI7; -.
DR SMR; Q7TNI7; -.
DR IntAct; Q7TNI7; 2.
DR STRING; 10090.ENSMUSP00000046960; -.
DR GlyGen; Q7TNI7; 1 site.
DR PhosphoSitePlus; Q7TNI7; -.
DR PaxDb; Q7TNI7; -.
DR PRIDE; Q7TNI7; -.
DR Antibodypedia; 30885; 832 antibodies from 41 providers.
DR DNASU; 257630; -.
DR Ensembl; ENSMUST00000039046; ENSMUSP00000046960; ENSMUSG00000041872. [Q7TNI7-1]
DR GeneID; 257630; -.
DR KEGG; mmu:257630; -.
DR UCSC; uc007akz.2; mouse. [Q7TNI7-1]
DR CTD; 112744; -.
DR MGI; MGI:2676631; Il17f.
DR VEuPathDB; HostDB:ENSMUSG00000041872; -.
DR eggNOG; ENOG502S5A0; Eukaryota.
DR GeneTree; ENSGT00940000156618; -.
DR InParanoid; Q7TNI7; -.
DR OMA; DPHRFPT; -.
DR OrthoDB; 1469254at2759; -.
DR PhylomeDB; Q7TNI7; -.
DR TreeFam; TF314701; -.
DR BioGRID-ORCS; 257630; 0 hits in 72 CRISPR screens.
DR PRO; PR:Q7TNI7; -.
DR Proteomes; UP000000589; Chromosome 1.
DR RNAct; Q7TNI7; protein.
DR Bgee; ENSMUSG00000041872; Expressed in animal zygote and 33 other tissues.
DR ExpressionAtlas; Q7TNI7; baseline and differential.
DR GO; GO:0005615; C:extracellular space; IDA:UniProtKB.
DR GO; GO:0005125; F:cytokine activity; ISO:MGI.
DR GO; GO:0019955; F:cytokine binding; ISO:MGI.
DR GO; GO:0005126; F:cytokine receptor binding; IPI:MGI.
DR GO; GO:0046982; F:protein heterodimerization activity; IDA:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB.
DR GO; GO:0002250; P:adaptive immune response; IEA:UniProtKB-KW.
DR GO; GO:0051216; P:cartilage development; ISO:MGI.
DR GO; GO:0050829; P:defense response to Gram-negative bacterium; IMP:UniProtKB.
DR GO; GO:0050830; P:defense response to Gram-positive bacterium; IMP:UniProtKB.
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; ISO:MGI.
DR GO; GO:0016525; P:negative regulation of angiogenesis; ISO:MGI.
DR GO; GO:0002225; P:positive regulation of antimicrobial peptide production; IDA:UniProtKB.
DR GO; GO:2000340; P:positive regulation of chemokine (C-X-C motif) ligand 1 production; ISO:MGI.
DR GO; GO:0001819; P:positive regulation of cytokine production; ISO:MGI.
DR GO; GO:1900017; P:positive regulation of cytokine production involved in inflammatory response; IDA:MGI.
DR GO; GO:0032755; P:positive regulation of interleukin-6 production; IMP:UniProtKB.
DR GO; GO:0032761; P:positive regulation of lymphotoxin A production; ISO:MGI.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:MGI.
DR GO; GO:0032645; P:regulation of granulocyte macrophage colony-stimulating factor production; ISO:MGI.
DR GO; GO:0032663; P:regulation of interleukin-2 production; ISO:MGI.
DR GO; GO:0032675; P:regulation of interleukin-6 production; ISO:MGI.
DR GO; GO:0032677; P:regulation of interleukin-8 production; ISO:MGI.
DR GO; GO:0017015; P:regulation of transforming growth factor beta receptor signaling pathway; ISO:MGI.
DR Gene3D; 2.10.90.10; -; 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; SSF57501; 1.
PE 1: Evidence at protein level;
KW Adaptive immunity; Alternative splicing; Cytokine; Disulfide bond;
KW Glycoprotein; Immunity; Inflammatory response; Innate immunity;
KW Reference proteome; Secreted; Signal.
FT SIGNAL 1..28
FT /evidence="ECO:0000255"
FT CHAIN 29..161
FT /note="Interleukin-17F"
FT /evidence="ECO:0000255"
FT /id="PRO_0000378104"
FT CARBOHYD 83
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000250"
FT DISULFID 45
FT /note="Interchain (with C-135)"
FT /evidence="ECO:0000250|UniProtKB:Q96PD4"
FT DISULFID 100..150
FT /evidence="ECO:0000250|UniProtKB:Q96PD4"
FT DISULFID 105..152
FT /evidence="ECO:0000250|UniProtKB:Q96PD4"
FT DISULFID 135
FT /note="Interchain (with C-45)"
FT /evidence="ECO:0000250|UniProtKB:Q96PD4"
FT VAR_SEQ 1..8
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|Ref.3"
FT /id="VSP_037499"
SQ SEQUENCE 161 AA; 17941 MW; 649D57E491301CAA CRC64;
MKCTRETAMV KSLLLLMLGL AILREVAARK NPKAGVPALQ KAGNCPPLED NTVRVDIRIF
NQNQGISVPR EFQNRSSSPW DYNITRDPHR FPSEIAEAQC RHSGCINAQG QEDSTMNSVA
IQQEILVLRR EPQGCSNSFR LEKMLLKVGC TCVKPIVHQA A
