I17RC_MOUSE
ID I17RC_MOUSE Reviewed; 698 AA.
AC Q8K4C2; G3X9C0; Q99J43;
DT 21-JUN-2005, integrated into UniProtKB/Swiss-Prot.
DT 16-MAR-2016, sequence version 3.
DT 03-AUG-2022, entry version 120.
DE RecName: Full=Interleukin-17 receptor C;
DE Short=IL-17 receptor C;
DE Short=IL-17RC;
DE AltName: Full=Interleukin-17 receptor-like protein;
DE Short=IL-17RL;
DE AltName: Full=ZcytoR14;
DE Flags: Precursor;
GN Name=Il17rc;
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 3).
RA Gilbert J.M., Gorman D.M.;
RT "Identification of novel IL-17 related receptors.";
RL Submitted (DEC-2001) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 3).
RA Gao Z.;
RL Patent number WO0204519, 17-JAN-2002.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2 AND 4).
RA Presnell S.R., Burkhead S.K., Levin S.D., Kuestner R.E., Gao Z.,
RA Jaspers S.R., Billsborough J.;
RL Patent number WO2005123778, 29-DEC-2005.
RN [4]
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 5).
RC STRAIN=129; TISSUE=Mammary tumor;
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 FUNCTION, SUBCELLULAR LOCATION, AND ALTERNATIVE SPLICING (ISOFORMS 1; 2; 3
RP AND 4).
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 [8]
RP FUNCTION, 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 [9]
RP FUNCTION, SUBUNIT, AND INTERACTION WITH TRAF3IP2.
RX PubMed=20554964; DOI=10.4049/jimmunol.0903739;
RA Ho A.W., Shen F., Conti H.R., Patel N., Childs E.E., Peterson A.C.,
RA Hernandez-Santos N., Kolls J.K., Kane L.P., Ouyang W., Gaffen S.L.;
RT "IL-17RC is required for immune signaling via an extended SEF/IL-17R
RT signaling domain in the cytoplasmic tail.";
RL J. Immunol. 185:1063-1070(2010).
RN [10]
RP FUNCTION.
RX PubMed=27923703; DOI=10.1016/j.chom.2016.10.003;
RA Chen K., Eddens T., Trevejo-Nunez G., Way E.E., Elsegeiny W., Ricks D.M.,
RA Garg A.V., Erb C.J., Bo M., Wang T., Chen W., Lee J.S., Gaffen S.L.,
RA Kolls J.K.;
RT "IL-17 Receptor Signaling in the Lung Epithelium Is Required for Mucosal
RT Chemokine Gradients and Pulmonary Host Defense against K. pneumoniae.";
RL Cell Host Microbe 20:596-605(2016).
RN [11]
RP TISSUE SPECIFICITY.
RX PubMed=26735852; DOI=10.1371/journal.ppat.1005367;
RA Wang X., Ma K., Chen M., Ko K.H., Zheng B.J., Lu L.;
RT "IL-17A Promotes Pulmonary B-1a Cell Differentiation via Induction of
RT Blimp-1 Expression during Influenza Virus Infection.";
RL PLoS Pathog. 12:e1005367-e1005367(2016).
RN [12]
RP FUNCTION, TISSUE SPECIFICITY, 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 [13]
RP FUNCTION.
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: Receptor for IL17A and IL17F, major effector cytokines of
CC innate and adaptive immune system involved in antimicrobial host
CC defense and maintenance of tissue integrity (PubMed:27923703,
CC PubMed:19144317). Receptor for IL17A and IL17F homodimers as part of a
CC heterodimeric complex with IL17RA (PubMed:17911633, PubMed:20554964).
CC Receptor for the heterodimer formed by IL17A and IL17B as part of a
CC heterodimeric complex with IL17RA (By similarity). Has also been shown
CC to be the cognate receptor for IL17F and to bind IL17A with high
CC affinity without the need for IL17RA (By similarity). Upon binding of
CC IL17F homodimer triggers downstream activation of TRAF6 and NF-kappa-B
CC signaling pathway (PubMed:28813677). Induces transcriptional activation
CC of IL33, a potent cytokine that stimulates group 2 innate lymphoid
CC cells and adaptive T-helper 2 cells involved in pulmonary allergic
CC response to fungi (PubMed:28813677). Promotes sympathetic innervation
CC of peripheral organs by coordinating the communication between gamma-
CC delta T cells and parenchymal cells. Stimulates sympathetic innervation
CC of thermogenic adipose tissue by driving TGFB1 expression
CC (PubMed:32076265). Binding of IL17A-IL17F to IL17RA-IL17RC
CC heterodimeric receptor complex triggers homotypic interaction of IL17RA
CC and IL17RC chains with TRAF3IP2 adapter through SEFIR domains. This
CC leads to downstream TRAF6-mediated activation of NF-kappa-B and
CC MAPkinase pathways ultimately resulting in transcriptional activation
CC of cytokines, chemokines, antimicrobial peptides and matrix
CC metalloproteinases, with potential strong immune inflammation
CC (PubMed:20554964). Primarily induces neutrophil activation and
CC recruitment at infection and inflammatory sites (PubMed:27923703).
CC Stimulates the production of antimicrobial beta-defensins DEFB1,
CC DEFB103A, and DEFB104A by mucosal epithelial cells, limiting the entry
CC of microbes through the epithelial barriers (PubMed:19144317).
CC {ECO:0000250|UniProtKB:Q8NAC3, ECO:0000269|PubMed:17911633,
CC ECO:0000269|PubMed:19144317, ECO:0000269|PubMed:20554964,
CC ECO:0000269|PubMed:27923703, ECO:0000269|PubMed:28813677,
CC ECO:0000269|PubMed:32076265}.
CC -!- SUBUNIT: Homodimer; disulfide-linked (By similarity). Heterodimer with
CC IL17RA (PubMed:20554964). Heterodimerization with IL17RA is independent
CC of the cytoplasmic tail. Associates with non-glycosylated IL17RA
CC constitutively. Binding of IL17A and IL17F induces association with
CC glycosylated IL17RA (PubMed:20554964). Forms complexes with 2:1 binding
CC stoichiometry: two receptor chains for one interleukin molecule (By
CC similarity). IL17A homodimer preferentially drives the formation of
CC IL17RA-IL17RC heterodimeric receptor complex, whereas IL17F homodimer
CC forms predominantly complexes with IL17RC homodimer (By similarity).
CC IL17A-IL17F forms complexes with IL17RA-IL17RC, but with lower affinity
CC when compared to IL17A homodimer (By similarity). IL17RC chain cannot
CC distinguish between IL17A and IL17F molecules, potentially enabling the
CC formation of topologically distinct complexes (By similarity).
CC Interacts (through SEFIR domain and extended downstream region) with
CC TRAF3IP2/ACT1 (phosphorylated) (PubMed:20554964).
CC {ECO:0000250|UniProtKB:Q8NAC3, ECO:0000269|PubMed:20554964}.
CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Cell membrane
CC {ECO:0000269|PubMed:17911633}; Single-pass type I membrane protein
CC {ECO:0000255}.
CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Cell membrane
CC {ECO:0000269|PubMed:17911633}; Single-pass type I membrane protein
CC {ECO:0000255}.
CC -!- SUBCELLULAR LOCATION: [Isoform 3]: Cell membrane
CC {ECO:0000269|PubMed:17911633}; Single-pass type I membrane protein
CC {ECO:0000255}.
CC -!- SUBCELLULAR LOCATION: [Isoform 4]: Cell membrane
CC {ECO:0000269|PubMed:17911633}; Single-pass type I membrane protein
CC {ECO:0000255}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=5;
CC Name=1; Synonyms=IL17RC {ECO:0000303|PubMed:17911633};
CC IsoId=Q8K4C2-3; Sequence=Displayed;
CC Name=2; Synonyms=IL17RC-delta7 {ECO:0000303|PubMed:17911633};
CC IsoId=Q8K4C2-4; Sequence=VSP_058139;
CC Name=3; Synonyms=IL17RC-delta7,8 {ECO:0000303|PubMed:17911633};
CC IsoId=Q8K4C2-1; Sequence=VSP_058140;
CC Name=4; Synonyms=IL17RC-delta8 {ECO:0000303|PubMed:17911633};
CC IsoId=Q8K4C2-5; Sequence=VSP_058141;
CC Name=5;
CC IsoId=Q8K4C2-2; Sequence=VSP_058142;
CC -!- TISSUE SPECIFICITY: Highly expressed in colonic epithelial cells
CC (PubMed:19144317). Expressed in lung epithelial cells
CC (PubMed:28813677). Expressed in macrophages (PubMed:19144317). Highly
CC expressed in B-1a B cells and at a lower extent in B-1b and B-2 B cells
CC (at protein level) (PubMed:26735852). {ECO:0000269|PubMed:19144317,
CC ECO:0000269|PubMed:26735852, ECO:0000269|PubMed:28813677}.
CC -!- INDUCTION: Induced in lung epithelial cells upon bacterial and fungal
CC infection. Up-regulated in lung epithelial cells by IL17F; this might
CC account for a persistent activation via a positive feedback loop.
CC {ECO:0000269|PubMed:28813677}.
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DR EMBL; AF458066; AAM77570.1; -; mRNA.
DR EMBL; CS251263; -; NOT_ANNOTATED_CDS; Unassigned_DNA.
DR EMBL; CS251267; -; NOT_ANNOTATED_CDS; Unassigned_DNA.
DR EMBL; AX360307; CAD23359.1; -; Unassigned_DNA.
DR EMBL; AX360310; CAD23360.1; -; Unassigned_DNA.
DR EMBL; AC153910; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH466523; EDK99478.1; -; Genomic_DNA.
DR EMBL; BC004759; AAH04759.1; -; mRNA.
DR CCDS; CCDS20422.1; -. [Q8K4C2-1]
DR RefSeq; NP_598920.3; NM_134159.4. [Q8K4C2-1]
DR RefSeq; NP_849273.1; NM_178942.1. [Q8K4C2-3]
DR RefSeq; XP_006505728.1; XM_006505665.1. [Q8K4C2-5]
DR RefSeq; XP_006505729.1; XM_006505666.1. [Q8K4C2-4]
DR AlphaFoldDB; Q8K4C2; -.
DR SMR; Q8K4C2; -.
DR BioGRID; 228481; 2.
DR IntAct; Q8K4C2; 2.
DR STRING; 10090.ENSMUSP00000055343; -.
DR GlyGen; Q8K4C2; 5 sites.
DR PhosphoSitePlus; Q8K4C2; -.
DR MaxQB; Q8K4C2; -.
DR PaxDb; Q8K4C2; -.
DR PRIDE; Q8K4C2; -.
DR ProteomicsDB; 273072; -. [Q8K4C2-3]
DR ProteomicsDB; 273073; -. [Q8K4C2-4]
DR ProteomicsDB; 273074; -. [Q8K4C2-1]
DR ProteomicsDB; 273075; -. [Q8K4C2-5]
DR ProteomicsDB; 273076; -. [Q8K4C2-2]
DR Antibodypedia; 10412; 333 antibodies from 34 providers.
DR DNASU; 171095; -.
DR Ensembl; ENSMUST00000058300; ENSMUSP00000055343; ENSMUSG00000030281. [Q8K4C2-1]
DR GeneID; 171095; -.
DR KEGG; mmu:171095; -.
DR UCSC; uc009dgl.3; mouse. [Q8K4C2-3]
DR CTD; 84818; -.
DR MGI; MGI:2159336; Il17rc.
DR VEuPathDB; HostDB:ENSMUSG00000030281; -.
DR eggNOG; ENOG502QWQ3; Eukaryota.
DR GeneTree; ENSGT00730000111286; -.
DR HOGENOM; CLU_026893_1_0_1; -.
DR InParanoid; Q8K4C2; -.
DR OMA; KEGLSCH; -.
DR TreeFam; TF335852; -.
DR BioGRID-ORCS; 171095; 1 hit in 72 CRISPR screens.
DR PRO; PR:Q8K4C2; -.
DR Proteomes; UP000000589; Chromosome 6.
DR RNAct; Q8K4C2; protein.
DR Bgee; ENSMUSG00000030281; Expressed in ileum and 78 other tissues.
DR ExpressionAtlas; Q8K4C2; baseline and differential.
DR Genevisible; Q8K4C2; MM.
DR GO; GO:0009986; C:cell surface; IDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; IDA:MGI.
DR GO; GO:0030368; F:interleukin-17 receptor activity; ISO:MGI.
DR GO; GO:0005102; F:signaling receptor binding; IPI:UniProtKB.
DR GO; GO:0050832; P:defense response to fungus; IMP:UniProtKB.
DR GO; GO:0071621; P:granulocyte chemotaxis; IMP:UniProtKB.
DR GO; GO:0006954; P:inflammatory response; IEA:UniProtKB-KW.
DR GO; GO:1900017; P:positive regulation of cytokine production involved in inflammatory response; IGI:MGI.
DR GO; GO:0032755; P:positive regulation of interleukin-6 production; IMP:UniProtKB.
DR InterPro; IPR039465; IL-17_rcpt-like.
DR InterPro; IPR027841; IL-17_rcpt_C/E_N.
DR InterPro; IPR013568; SEFIR_dom.
DR PANTHER; PTHR15583; PTHR15583; 1.
DR Pfam; PF15037; IL17_R_N; 1.
DR Pfam; PF08357; SEFIR; 1.
DR PROSITE; PS51534; SEFIR; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell membrane; Disulfide bond; Glycoprotein;
KW Inflammatory response; Membrane; Receptor; Reference proteome; Signal;
KW Transmembrane; Transmembrane helix.
FT SIGNAL 1..21
FT /evidence="ECO:0000255"
FT CHAIN 22..698
FT /note="Interleukin-17 receptor C"
FT /id="PRO_0000011035"
FT TOPO_DOM 22..464
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 465..485
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 486..698
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 496..645
FT /note="SEFIR"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00867"
FT CARBOHYD 182
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 209
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 249
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 255
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 259
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 190..202
FT /evidence="ECO:0000250|UniProtKB:Q8NAC3"
FT DISULFID 266..316
FT /evidence="ECO:0000250|UniProtKB:Q8NAC3"
FT DISULFID 268..284
FT /evidence="ECO:0000250|UniProtKB:Q8NAC3"
FT DISULFID 325..334
FT /evidence="ECO:0000250|UniProtKB:Q8NAC3"
FT DISULFID 364..378
FT /evidence="ECO:0000250|UniProtKB:Q8NAC3"
FT DISULFID 406..413
FT /evidence="ECO:0000250|UniProtKB:Q8NAC3"
FT DISULFID 440..455
FT /evidence="ECO:0000250|UniProtKB:Q8NAC3"
FT VAR_SEQ 189..212
FT /note="Missing (in isoform 3)"
FT /id="VSP_058140"
FT VAR_SEQ 189..203
FT /note="Missing (in isoform 2)"
FT /id="VSP_058139"
FT VAR_SEQ 204..212
FT /note="Missing (in isoform 4)"
FT /id="VSP_058141"
FT VAR_SEQ 490..698
FT /note="RKAARGSRTALLLHSADGAGYERLVGALASALSQMPLRVAVDLWSRRELSAH
FT GALAWFHHQRRRILQEGGVVILLFSPAAVAQCQQWLQLQTVEPGPHDALAAWLSCVLPD
FT FLQGRATGRYVGVYFDGLLHPDSVPSPFRVAPLFSLPSQLPAFLDALQGGCSTSAGRPA
FT DRVERVTQALRSALDSCTSSSEAPGCCEEWDLGPCTTLE -> MTPSPPGSAACYPISC
FT KAGRPAATSGSTSTGCCTQTLCPPRSASPRSSPCPRSCRLSWMHCREAAPLPRGDPRTG
FT WNE (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_058142"
FT CONFLICT 83
FT /note="C -> R (in Ref. 1; AAM77570 and 3; CAD23359/
FT CAD23360)"
FT /evidence="ECO:0000305"
FT CONFLICT 379
FT /note="L -> S (in Ref. 1; AAM77570 and 3; CAD23359/
FT CAD23360)"
FT /evidence="ECO:0000305"
FT CONFLICT 638
FT /note="S -> T (in Ref. 1; AAM77570 and 3; CAD23359/
FT CAD23360)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 698 AA; 77148 MW; 24EC9DA8B3A144E7 CRC64;
MPVSWFLLSL ALGRNPVVVS LERLMEPQDT ARCSLGLSCH LWDGDVLCLP GSLQSAPGPV
LVPTRLQTEL VLRCPQKTDC ALCVRVVVHL AVHGHWAEPE EAGKSDSELQ ESRNASLQAQ
VVLSFQAYPI ARCALLEVQV PADLVQPGQS VGSAVFDCFE ASLGAEVQIW SYTKPRYQKE
LNLTQQLPDC RGLEVRDSIQ SCWVLPWLNV STDGDNVLLT LDVSEEQDFS FLLYLRPVPD
ALKSLWYKNL TGPQNITLNH TDLVPCLCIQ VWSLEPDSER VEFCPFREDP GAHRNLWHIA
RLRVLSPGVW QLDAPCCLPG KVTLCWQAPD QSPCQPLVPP VPQKNATVNE PQDFQLVAGH
PNLCVQVSTW EKVQLQACLW ADSLGPFKDD MLLVEMKTGL NNTSVCALEP SGCTPLPSMA
STRAARLGEE LLQDFRSHQC MQLWNDDNMG SLWACPMDKY IHRRWVLVWL ACLLLAAALF
FFLLLKKDRR KAARGSRTAL LLHSADGAGY ERLVGALASA LSQMPLRVAV DLWSRRELSA
HGALAWFHHQ RRRILQEGGV VILLFSPAAV AQCQQWLQLQ TVEPGPHDAL AAWLSCVLPD
FLQGRATGRY VGVYFDGLLH PDSVPSPFRV APLFSLPSQL PAFLDALQGG CSTSAGRPAD
RVERVTQALR SALDSCTSSS EAPGCCEEWD LGPCTTLE
