ID   IL17C_HUMAN             Reviewed;         197 AA.
AC   Q9P0M4; Q3MIG8; Q9HC75;
DT   31-JAN-2002, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-2000, sequence version 1.
DT   24-JAN-2024, entry version 152.
DE   RecName: Full=Interleukin-17C;
DE            Short=IL-17C;
DE   AltName: Full=Cytokine CX2;
DE   Flags: Precursor;
GN   Name=IL17C; ORFNames=UNQ561/PRO1122;
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].
RX   PubMed=10639155; DOI=10.1073/pnas.97.2.773;
RA   Li H., Chen J., Huang A., Stinson J., Heldens S., Foster J., Dowd P.,
RA   Gurney A.L., Wood W.I.;
RT   "Cloning and characterization of IL-17B and IL-17C, two new members of the
RT   IL-17 cytokine family.";
RL   Proc. Natl. Acad. Sci. U.S.A. 97:773-778(2000).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RA   Zhang W., He L., Wan T., Yuan Z., Cao X.;
RT   "Novel human cytokine CX2 with homology to IL-17.";
RL   Submitted (APR-1999) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX   PubMed=12975309; DOI=10.1101/gr.1293003;
RA   Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J.,
RA   Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P.,
RA   Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A.,
RA   Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D.,
RA   Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L.,
RA   Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C.,
RA   Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J.,
RA   Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.;
RT   "The secreted protein discovery initiative (SPDI), a large-scale effort to
RT   identify novel human secreted and transmembrane proteins: a bioinformatics
RT   assessment.";
RL   Genome Res. 13:2265-2270(2003).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Lung;
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   [5]
RP   INDUCTION.
RX   PubMed=21993849; DOI=10.1038/ni.2155;
RA   Song X., Zhu S., Shi P., Liu Y., Shi Y., Levin S.D., Qian Y.;
RT   "IL-17RE is the functional receptor for IL-17C and mediates mucosal
RT   immunity to infection with intestinal pathogens.";
RL   Nat. Immunol. 12:1151-1158(2011).
RN   [6]
RP   FUNCTION, INTERACTION WITH IL17RA AND IL17RE, INDUCTION, AND TISSUE
RP   SPECIFICITY.
RX   PubMed=21993848; DOI=10.1038/ni.2156;
RA   Ramirez-Carrozzi V., Sambandam A., Luis E., Lin Z., Jeet S., Lesch J.,
RA   Hackney J., Kim J., Zhou M., Lai J., Modrusan Z., Sai T., Lee W., Xu M.,
RA   Caplazi P., Diehl L., de Voss J., Balazs M., Gonzalez L. Jr., Singh H.,
RA   Ouyang W., Pappu R.;
RT   "IL-17C regulates the innate immune function of epithelial cells in an
RT   autocrine manner.";
RL   Nat. Immunol. 12:1159-1166(2011).
CC   -!- FUNCTION: Cytokine that plays a crucial role in innate immunity of the
CC       epithelium, including to intestinal bacterial pathogens, in an
CC       autocrine manner. Stimulates the production of antibacterial peptides
CC       and pro-inflammatory molecules for host defense by signaling through
CC       the NF-kappa-B and MAPK pathways. Acts synergically with IL22 in
CC       inducing the expression of antibacterial peptides, including S100A8,
CC       S100A9, REG3A and REG3G. Synergy is also observed with TNF and IL1B in
CC       inducing DEFB2 from keratinocytes. Depending on the type of insult, may
CC       have both protective and pathogenic properties, either by maintaining
CC       epithelial homeostasis after an inflammatory challenge or by promoting
CC       inflammatory phenotype. Enhanced IL17C/IL17RE signaling may also lead
CC       to greater susceptibility to autoimmune diseases.
CC       {ECO:0000269|PubMed:21993848}.
CC   -!- SUBUNIT: Binds to a heterodimer formed by IL17RA and IL17RE.
CC   -!- SUBCELLULAR LOCATION: Secreted.
CC   -!- INDUCTION: Up-regulated by bacterial stimuli, including by
CC       lipopolysaccharides (LPS) in gut epithelial cell lines. This up-
CC       regulation may be mediated by Toll-like receptors TLR2 and TLR5. Up-
CC       regulated by various pro-inflammatory cytokines, including TNF, IL1B
CC       and IL17F. Up-regulation by IL17A in colon epithelial cells has been
CC       observed in some cases (PubMed:21993849), but not in others
CC       (PubMed:21993848). {ECO:0000269|PubMed:21993848,
CC       ECO:0000269|PubMed:21993849}.
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";
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DR   EMBL; AF152099; AAF28105.1; -; mRNA.
DR   EMBL; AF142410; AAG27921.1; -; mRNA.
DR   EMBL; AY358471; AAQ88835.1; -; mRNA.
DR   EMBL; BC069152; AAH69152.1; -; mRNA.
DR   EMBL; BC101835; AAI01836.1; -; mRNA.
DR   EMBL; BC112196; AAI12197.1; -; mRNA.
DR   CCDS; CCDS42217.1; -.
DR   RefSeq; NP_037410.1; NM_013278.3.
DR   AlphaFoldDB; Q9P0M4; -.
DR   SMR; Q9P0M4; -.
DR   STRING; 9606.ENSP00000244241; -.
DR   BioMuta; IL17C; -.
DR   DMDM; 20138769; -.
DR   MassIVE; Q9P0M4; -.
DR   PaxDb; 9606-ENSP00000244241; -.
DR   PeptideAtlas; Q9P0M4; -.
DR   ProteomicsDB; 83579; -.
DR   Antibodypedia; 30734; 354 antibodies from 26 providers.
DR   DNASU; 27189; -.
DR   Ensembl; ENST00000244241.5; ENSP00000244241.4; ENSG00000124391.5.
DR   GeneID; 27189; -.
DR   KEGG; hsa:27189; -.
DR   MANE-Select; ENST00000244241.5; ENSP00000244241.4; NM_013278.4; NP_037410.1.
DR   UCSC; uc002fla.4; human.
DR   AGR; HGNC:5983; -.
DR   CTD; 27189; -.
DR   DisGeNET; 27189; -.
DR   GeneCards; IL17C; -.
DR   HGNC; HGNC:5983; IL17C.
DR   HPA; ENSG00000124391; Tissue enhanced (endometrium, urinary bladder).
DR   MIM; 604628; gene.
DR   neXtProt; NX_Q9P0M4; -.
DR   OpenTargets; ENSG00000124391; -.
DR   PharmGKB; PA29797; -.
DR   VEuPathDB; HostDB:ENSG00000124391; -.
DR   eggNOG; ENOG502S2UJ; Eukaryota.
DR   GeneTree; ENSGT00940000161887; -.
DR   HOGENOM; CLU_121730_0_0_1; -.
DR   InParanoid; Q9P0M4; -.
DR   OMA; FAFHAEF; -.
DR   OrthoDB; 2959916at2759; -.
DR   PhylomeDB; Q9P0M4; -.
DR   TreeFam; TF314701; -.
DR   PathwayCommons; Q9P0M4; -.
DR   Reactome; R-HSA-448424; Interleukin-17 signaling.
DR   BioGRID-ORCS; 27189; 12 hits in 1147 CRISPR screens.
DR   GenomeRNAi; 27189; -.
DR   Pharos; Q9P0M4; Tbio.
DR   PRO; PR:Q9P0M4; -.
DR   Proteomes; UP000005640; Chromosome 16.
DR   RNAct; Q9P0M4; Protein.
DR   Bgee; ENSG00000124391; Expressed in nasal cavity epithelium and 118 other cell types or tissues.
DR   GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR   GO; GO:0005615; C:extracellular space; TAS:ProtInc.
DR   GO; GO:0005125; F:cytokine activity; TAS:ProtInc.
DR   GO; GO:0007166; P:cell surface receptor signaling pathway; TAS:ProtInc.
DR   GO; GO:0007267; P:cell-cell signaling; TAS:ProtInc.
DR   GO; GO:0006954; P:inflammatory response; TAS:ProtInc.
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.
DR   Genevisible; Q9P0M4; HS.
PE   1: Evidence at protein level;
KW   Cytokine; Disulfide bond; Inflammatory response; Reference proteome;
KW   Secreted; Signal.
FT   SIGNAL          1..18
FT                   /evidence="ECO:0000255"
FT   CHAIN           19..197
FT                   /note="Interleukin-17C"
FT                   /id="PRO_0000015429"
FT   DISULFID        129..189
FT                   /evidence="ECO:0000250"
FT   DISULFID        134..191
FT                   /evidence="ECO:0000250"
FT   VARIANT         25
FT                   /note="R -> G (in dbSNP:rs11465492)"
FT                   /id="VAR_049598"
FT   CONFLICT        50
FT                   /note="H -> R (in Ref. 2; AAG27921)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   197 AA;  21765 MW;  BAE0152E18DE7D08 CRC64;
     MTLLPGLLFL TWLHTCLAHH DPSLRGHPHS HGTPHCYSAE ELPLGQAPPH LLARGAKWGQ
     ALPVALVSSL EAASHRGRHE RPSATTQCPV LRPEEVLEAD THQRSISPWR YRVDTDEDRY
     PQKLAFAECL CRGCIDARTG RETAALNSVR LLQSLLVLRR RPCSRDGSGL PTPGAFAFHT
     EFIHVPVGCT CVLPRSV
//