ID   IL17C_MOUSE             Reviewed;         194 AA.
AC   Q8K4C5; A6H6F0;
DT   06-MAR-2013, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-2002, sequence version 1.
DT   25-MAY-2022, entry version 91.
DE   RecName: Full=Interleukin-17C;
DE            Short=Il-17c;
DE   AltName: Full=Cytokine CX2;
DE   Flags: Precursor;
GN   Name=Il17c;
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].
RX   PubMed=12077275; DOI=10.4049/jimmunol.169.1.443;
RA   Hurst S.D., Muchamuel T., Gorman D.M., Gilbert J.M., Clifford T., Kwan S.,
RA   Menon S., Seymour B., Jackson C., Kung T.T., Brieland J.K., Zurawski S.M.,
RA   Chapman R.W., Zurawski G., Coffman R.L.;
RT   "New IL-17 family members promote Th1 or Th2 responses in the lung: in vivo
RT   function of the novel cytokine IL-25.";
RL   J. Immunol. 169:443-453(2002).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=C57BL/6J;
RX   PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA   Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA   Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA   Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA   Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA   Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA   Eichler E.E., Ponting C.P.;
RT   "Lineage-specific biology revealed by a finished genome assembly of the
RT   mouse.";
RL   PLoS Biol. 7:E1000112-E1000112(2009).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 2-194.
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   [4]
RP   FUNCTION, INTERACTION WITH IL17RA AND IL17RE, AND DISRUPTION PHENOTYPE.
RX   PubMed=21982598; DOI=10.1016/j.immuni.2011.09.010;
RA   Chang S.H., Reynolds J.M., Pappu B.P., Chen G., Martinez G.J., Dong C.;
RT   "Interleukin-17C promotes Th17 cell responses and autoimmune disease via
RT   interleukin-17 receptor E.";
RL   Immunity 35:611-621(2011).
RN   [5]
RP   FUNCTION, INTERACTION WITH IL17RA AND IL17RE, AND 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, AND TISSUE 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 NFKB and MAPK pathways. Acts synergically with IL22, TNF and IL1B
CC       in inducing antibacterial peptides. May have protective function by
CC       maintaining epithelial homeostasis after an inflammatory challenge,
CC       such as that caused in the intestine by dextran sulfate sodium in a
CC       colitis model. May also promote an inflammatory phenotype, such as skin
CC       in a psoriasis model. Enhanced IL17C/IL17RE signaling may also lead to
CC       greater susceptibility to autoimmune diseases, such as autoimmune
CC       encephalitis. {ECO:0000269|PubMed:21982598,
CC       ECO:0000269|PubMed:21993848, ECO:0000269|PubMed:21993849}.
CC   -!- SUBUNIT: Binds to a heterodimer formed by IL17RA and IL17RE.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000305}.
CC   -!- TISSUE SPECIFICITY: Expressed by epithelial cells after bacterial
CC       challenge. Low expression, if any, in lymphocytes.
CC       {ECO:0000269|PubMed:21993848}.
CC   -!- INDUCTION: Up-regulated in the colon, but not in spleen or liver,
CC       during infection with Citrobacter rodentium. Up-regulated by various
CC       inflammatory cytokines, including TNF, IL1B, IL17A and IL17F in colon
CC       epithelial cells. {ECO:0000269|PubMed:21993849}.
CC   -!- DISRUPTION PHENOTYPE: Mutant animals develop normally and do not
CC       exhibit any pronounced immunological deficiency.
CC       {ECO:0000269|PubMed:21982598}.
CC   -!- SIMILARITY: Belongs to the IL-17 family. {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=AAI45854.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR   EMBL; AF458061; AAM77565.1; -; mRNA.
DR   EMBL; AL591003; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC145853; AAI45854.1; ALT_INIT; mRNA.
DR   RefSeq; NP_665833.3; NM_145834.3.
DR   AlphaFoldDB; Q8K4C5; -.
DR   SMR; Q8K4C5; -.
DR   IntAct; Q8K4C5; 2.
DR   STRING; 10090.ENSMUSP00000056008; -.
DR   PaxDb; Q8K4C5; -.
DR   PRIDE; Q8K4C5; -.
DR   DNASU; 234836; -.
DR   GeneID; 234836; -.
DR   KEGG; mmu:234836; -.
DR   UCSC; uc012gmc.1; mouse.
DR   CTD; 27189; -.
DR   MGI; MGI:2446486; Il17c.
DR   eggNOG; ENOG502S2UJ; Eukaryota.
DR   InParanoid; Q8K4C5; -.
DR   OrthoDB; 1298853at2759; -.
DR   PhylomeDB; Q8K4C5; -.
DR   TreeFam; TF314701; -.
DR   BioGRID-ORCS; 234836; 2 hits in 53 CRISPR screens.
DR   PRO; PR:Q8K4C5; -.
DR   Proteomes; UP000000589; Unplaced.
DR   RNAct; Q8K4C5; protein.
DR   GO; GO:0005615; C:extracellular space; IDA:MGI.
DR   GO; GO:0005125; F:cytokine activity; IDA:MGI.
DR   GO; GO:0006954; P:inflammatory response; IEA:UniProtKB-KW.
DR   GO; GO:0030223; P:neutrophil differentiation; IDA:MGI.
DR   GO; GO:1900017; P:positive regulation of cytokine production involved in inflammatory response; IDA: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   Cytokine; Disulfide bond; Inflammatory response; Reference proteome;
KW   Secreted; Signal.
FT   SIGNAL          1..16
FT                   /evidence="ECO:0000255"
FT   CHAIN           17..194
FT                   /note="Interleukin-17C"
FT                   /id="PRO_0000421684"
FT   DISULFID        125..185
FT                   /evidence="ECO:0000250"
FT   DISULFID        130..187
FT                   /evidence="ECO:0000250"
SQ   SEQUENCE   194 AA;  21592 MW;  95797A630574BD1E CRC64;
     MSLLLLGWLP TGMTHQDPPS WGKPRSHRTL RCYSAEELSH GQAPPHLLTR SARWEQALPV
     ALVASLEATG HRRQHEGPLA GTQCPVLRPE EVLEADTHER SISPWRYRID TDENRYPQKL
     AVAECLCRGC INAKTGRETA ALNSVQLLQS LLVLRRQPCS RDGTADPTPG SFAFHTEFIR
     VPVGCTCVLP RSTQ