CCR6_MOUSE
ID CCR6_MOUSE Reviewed; 367 AA.
AC O54689;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-1998, sequence version 1.
DT 03-AUG-2022, entry version 165.
DE RecName: Full=C-C chemokine receptor type 6;
DE Short=C-C CKR-6;
DE Short=CC-CKR-6;
DE Short=CCR-6;
DE AltName: Full=KY411;
DE AltName: CD_antigen=CD196;
GN Name=Ccr6; Synonyms=Cmkbr6;
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.
RA Yanagihara S., Komura E., Yamaguchi Y.;
RT "Mouse G protein-coupled receptor KY411.";
RL Submitted (DEC-1997) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=9862452; DOI=10.1016/s0014-5793(98)01450-1;
RA Varona R., Zaballos A., Gutierrez J., Martin P., Roncal F., Albar J.P.,
RA Ardavin C., Marquez G.;
RT "Molecular cloning, functional characterization and mRNA expression
RT analysis of the murine chemokine receptor CCR6 and its specific ligand MIP-
RT 3alpha.";
RL FEBS Lett. 440:188-194(1998).
RN [3]
RP FUNCTION, TISSUE SPECIFICITY, AND INDUCTION.
RX PubMed=19050256; DOI=10.4049/jimmunol.181.12.8391;
RA Yamazaki T., Yang X.O., Chung Y., Fukunaga A., Nurieva R., Pappu B.,
RA Martin-Orozco N., Kang H.S., Ma L., Panopoulos A.D., Craig S.,
RA Watowich S.S., Jetten A.M., Tian Q., Dong C.;
RT "CCR6 regulates the migration of inflammatory and regulatory T cells.";
RL J. Immunol. 181:8391-8401(2008).
RN [4]
RP FUNCTION, TISSUE SPECIFICITY, AND INDUCTION.
RX PubMed=19129757; DOI=10.1038/mi.2008.84;
RA Wang C., Kang S.G., Lee J., Sun Z., Kim C.H.;
RT "The roles of CCR6 in migration of Th17 cells and regulation of effector T-
RT cell balance in the gut.";
RL Mucosal Immunol. 2:173-183(2009).
RN [5]
RP FUNCTION, AND BINDING TO CCL20; DEFB4 AND DEFB4A.
RX PubMed=20068036; DOI=10.1074/jbc.m109.091090;
RA Roehrl J., Yang D., Oppenheim J.J., Hehlgans T.;
RT "Specific binding and chemotactic activity of mBD4 and its functional
RT orthologue hBD2 to CCR6-expressing cells.";
RL J. Biol. Chem. 285:7028-7034(2010).
RN [6]
RP REVIEW, AND FUNCTION.
RX PubMed=21376174; DOI=10.1016/j.yexcr.2010.12.018;
RA Ito T., Carson W.F. IV, Cavassani K.A., Connett J.M., Kunkel S.L.;
RT "CCR6 as a mediator of immunity in the lung and gut.";
RL Exp. Cell Res. 317:613-619(2011).
RN [7]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=24638065; DOI=10.1038/icb.2014.14;
RA Bunting M.D., Comerford I., Kara E.E., Korner H., McColl S.R.;
RT "CCR6 supports migration and differentiation of a subset of DN1 early
RT thymocyte progenitors but is not required for thymic nTreg development.";
RL Immunol. Cell Biol. 92:489-498(2014).
RN [8]
RP FUNCTION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=23765988; DOI=10.1002/jcp.24418;
RA Caballero-Campo P., Buffone M.G., Benencia F., Conejo-Garcia J.R.,
RA Rinaudo P.F., Gerton G.L.;
RT "A role for the chemokine receptor CCR6 in mammalian sperm motility and
RT chemotaxis.";
RL J. Cell. Physiol. 229:68-78(2014).
RN [9]
RP FUNCTION.
RX PubMed=25122636; DOI=10.1126/scitranslmed.3009071;
RA Diao R., Fok K.L., Chen H., Yu M.K., Duan Y., Chung C.M., Li Z., Wu H.,
RA Li Z., Zhang H., Ji Z., Zhen W., Ng C.F., Gui Y., Cai Z., Chan H.C.;
RT "Deficient human beta-defensin 1 underlies male infertility associated with
RT poor sperm motility and genital tract infection.";
RL Sci. Transl. Med. 6:249RA108-249RA108(2014).
RN [10]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=25505290; DOI=10.4049/jimmunol.1401553;
RA Elgueta R., Marks E., Nowak E., Menezes S., Benson M., Raman V.S.,
RA Ortiz C., O'Connell S., Hess H., Lord G.M., Noelle R.;
RT "CCR6-dependent positioning of memory B cells is essential for their
RT ability to mount a recall response to antigen.";
RL J. Immunol. 194:505-513(2015).
RN [11]
RP FUNCTION, AND INDUCTION.
RX PubMed=27174992; DOI=10.1126/science.aaf4822;
RA Reboldi A., Arnon T.I., Rodda L.B., Atakilit A., Sheppard D., Cyster J.G.;
RT "IgA production requires B cell interaction with subepithelial dendritic
RT cells in Peyer's patches.";
RL Science 352:0-0(2016).
CC -!- FUNCTION: Receptor for the C-C type chemokine CCL20. Binds to CCL20 and
CC subsequently transduces a signal by increasing the intracellular
CC calcium ion levels (PubMed:20068036). Although CCL20 is its major
CC ligand it can also act as a receptor for non-chemokine ligands such as
CC beta-defensins (PubMed:25122636). Binds to defensin DEFB1 leading to
CC increase in intracellular calcium ions and cAMP levels. Its binding to
CC DEFB1 is essential for the function of DEFB1 in regulating sperm
CC motility and bactericidal activity (By similarity). Binds to defensins
CC DEFB4 and DEFB4A/B and mediates their chemotactic effects
CC (PubMed:20068036). The ligand-receptor pair CCL20-CCR6 is responsible
CC for the chemotaxis of dendritic cells (DC), effector/memory T-cells and
CC B-cells and plays an important role at skin and mucosal surfaces under
CC homeostatic and inflammatory conditions, as well as in pathology,
CC including cancer and various autoimmune diseases. CCR6-mediated signals
CC are essential for immune responses to microbes in the intestinal mucosa
CC and in the modulation of inflammatory responses initiated by tissue
CC insult and trauma (PubMed:21376174). CCR6 is essential for the
CC recruitment of both the pro-inflammatory IL17 producing helper T-cells
CC (Th17) and the regulatory T-cells (Treg) to sites of inflammation
CC (PubMed:19050256). Required for the normal migration of Th17 cells in
CC Peyers patches and other related tissue sites of the intestine and
CC plays a role in regulating effector T-cell balance and distribution in
CC inflamed intestine (PubMed:19129757). Plays an important role in the
CC coordination of early thymocyte precursor migration events important
CC for normal subsequent thymocyte precursor development, but is not
CC required for the formation of normal thymic natural regulatory T-cells
CC (nTregs). Required for optimal differentiation of DN2 and DN3 thymocyte
CC precursors (PubMed:24638065). Essential for B-cell localization in the
CC subepithelial dome of Peyers-patches and for efficient B-cell isotype
CC switching to IgA in the Peyers-patches (PubMed:27174992). Essential for
CC appropriate anatomical distribution of memory B-cells in the spleen and
CC for the secondary recall response of memory B-cells (PubMed:25505290).
CC Positively regulates sperm motility and chemotaxis via its binding to
CC CCL20 (PubMed:23765988). {ECO:0000250|UniProtKB:P51684,
CC ECO:0000269|PubMed:19050256, ECO:0000269|PubMed:19129757,
CC ECO:0000269|PubMed:20068036, ECO:0000269|PubMed:23765988,
CC ECO:0000269|PubMed:24638065, ECO:0000269|PubMed:25122636,
CC ECO:0000269|PubMed:25505290, ECO:0000269|PubMed:27174992,
CC ECO:0000303|PubMed:21376174}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:23765988};
CC Multi-pass membrane protein {ECO:0000255}. Cell surface
CC {ECO:0000250|UniProtKB:P51684}.
CC -!- TISSUE SPECIFICITY: Sperm. Mainly localized in the principal piece and
CC neck region of the tail but is also found in the acrosomal region in a
CC small percentage of sperm cells. Expressed in natural regulatory T
CC cells (nTregs) and a subset of early thymocyte progenitor double-
CC negative 1 (DN1) cells. Expressed in memory B cells. Expressed by IL17
CC producing helper T-cells (Th17), type 1 effector cells (Th1), type 2
CC effector cells (Th2) and regulatory T-cells (Treg) (at protein level).
CC Expressed by Th17 cells in spleen, Peyers patches, and lamina propria
CC of small and large intestine. Highly expressed in testis, lung, colon,
CC and dendritic cells. {ECO:0000269|PubMed:19050256,
CC ECO:0000269|PubMed:19129757, ECO:0000269|PubMed:23765988,
CC ECO:0000269|PubMed:24638065, ECO:0000269|PubMed:25505290}.
CC -!- INDUCTION: Up-regulated on pre-germinal center B-cells in a CD40-
CC dependent manner. Up-regulated and down-regulated in Th17 cells by
CC TGFB1 and IL2 respectively. {ECO:0000269|PubMed:19050256,
CC ECO:0000269|PubMed:19129757, ECO:0000269|PubMed:27174992}.
CC -!- SIMILARITY: Belongs to the G-protein coupled receptor 1 family.
CC {ECO:0000255|PROSITE-ProRule:PRU00521}.
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DR EMBL; AB009369; BAA23776.1; -; mRNA.
DR EMBL; AJ222714; CAA10956.1; -; Genomic_DNA.
DR CCDS; CCDS28381.1; -.
DR RefSeq; NP_001177262.1; NM_001190333.1.
DR RefSeq; NP_001177263.1; NM_001190334.1.
DR RefSeq; NP_001177264.1; NM_001190335.1.
DR RefSeq; NP_001177265.1; NM_001190336.1.
DR RefSeq; NP_001177266.1; NM_001190337.1.
DR RefSeq; NP_033965.1; NM_009835.4.
DR RefSeq; XP_006523349.1; XM_006523286.3.
DR RefSeq; XP_006523351.1; XM_006523288.3.
DR RefSeq; XP_006523353.1; XM_006523290.3.
DR RefSeq; XP_006523354.1; XM_006523291.1.
DR RefSeq; XP_006523355.1; XM_006523292.3.
DR RefSeq; XP_011244488.1; XM_011246186.2.
DR RefSeq; XP_011244490.1; XM_011246188.1.
DR RefSeq; XP_017172707.1; XM_017317218.1.
DR RefSeq; XP_017172708.1; XM_017317219.1.
DR RefSeq; XP_017172709.1; XM_017317220.1.
DR AlphaFoldDB; O54689; -.
DR SMR; O54689; -.
DR STRING; 10090.ENSMUSP00000095029; -.
DR GlyGen; O54689; 2 sites.
DR iPTMnet; O54689; -.
DR PhosphoSitePlus; O54689; -.
DR PaxDb; O54689; -.
DR PRIDE; O54689; -.
DR ProteomicsDB; 279950; -.
DR Antibodypedia; 2930; 822 antibodies from 39 providers.
DR DNASU; 12458; -.
DR Ensembl; ENSMUST00000097418; ENSMUSP00000095029; ENSMUSG00000040899.
DR Ensembl; ENSMUST00000164411; ENSMUSP00000131153; ENSMUSG00000040899.
DR Ensembl; ENSMUST00000166348; ENSMUSP00000128559; ENSMUSG00000040899.
DR Ensembl; ENSMUST00000167956; ENSMUSP00000128529; ENSMUSG00000040899.
DR Ensembl; ENSMUST00000177568; ENSMUSP00000137249; ENSMUSG00000040899.
DR Ensembl; ENSMUST00000180103; ENSMUSP00000135945; ENSMUSG00000040899.
DR Ensembl; ENSMUST00000231545; ENSMUSP00000156324; ENSMUSG00000040899.
DR GeneID; 12458; -.
DR KEGG; mmu:12458; -.
DR UCSC; uc008ajd.2; mouse.
DR CTD; 1235; -.
DR MGI; MGI:1333797; Ccr6.
DR VEuPathDB; HostDB:ENSMUSG00000040899; -.
DR eggNOG; KOG3656; Eukaryota.
DR GeneTree; ENSGT01030000234667; -.
DR HOGENOM; CLU_009579_8_3_1; -.
DR InParanoid; O54689; -.
DR OMA; KEICDHR; -.
DR OrthoDB; 981680at2759; -.
DR PhylomeDB; O54689; -.
DR TreeFam; TF330966; -.
DR Reactome; R-MMU-1461957; Beta defensins.
DR Reactome; R-MMU-380108; Chemokine receptors bind chemokines.
DR Reactome; R-MMU-418594; G alpha (i) signalling events.
DR BioGRID-ORCS; 12458; 0 hits in 108 CRISPR screens.
DR PRO; PR:O54689; -.
DR Proteomes; UP000000589; Chromosome 17.
DR RNAct; O54689; protein.
DR Bgee; ENSMUSG00000040899; Expressed in spleen and 71 other tissues.
DR ExpressionAtlas; O54689; baseline and differential.
DR Genevisible; O54689; MM.
DR GO; GO:0009986; C:cell surface; IDA:MGI.
DR GO; GO:0009897; C:external side of plasma membrane; IDA:MGI.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0036126; C:sperm flagellum; IDA:UniProtKB.
DR GO; GO:0097225; C:sperm midpiece; ISO:MGI.
DR GO; GO:0097524; C:sperm plasma membrane; IDA:UniProtKB.
DR GO; GO:0097228; C:sperm principal piece; IDA:UniProtKB.
DR GO; GO:0019957; F:C-C chemokine binding; IDA:UniProtKB.
DR GO; GO:0016493; F:C-C chemokine receptor activity; IDA:UniProtKB.
DR GO; GO:0019722; P:calcium-mediated signaling; ISS:UniProtKB.
DR GO; GO:0060326; P:cell chemotaxis; ISS:UniProtKB.
DR GO; GO:0006935; P:chemotaxis; IDA:UniProtKB.
DR GO; GO:1904155; P:DN2 thymocyte differentiation; IMP:UniProtKB.
DR GO; GO:1904156; P:DN3 thymocyte differentiation; IMP:UniProtKB.
DR GO; GO:0006955; P:immune response; IBA:GO_Central.
DR GO; GO:0048290; P:isotype switching to IgA isotypes; IMP:UniProtKB.
DR GO; GO:0002523; P:leukocyte migration involved in inflammatory response; IMP:UniProtKB.
DR GO; GO:0072676; P:lymphocyte migration; IMP:UniProtKB.
DR GO; GO:0007204; P:positive regulation of cytosolic calcium ion concentration; ISO:MGI.
DR GO; GO:2000510; P:positive regulation of dendritic cell chemotaxis; ISO:MGI.
DR GO; GO:0010634; P:positive regulation of epithelial cell migration; ISO:MGI.
DR GO; GO:0060474; P:positive regulation of flagellated sperm motility involved in capacitation; IDA:UniProtKB.
DR GO; GO:2000404; P:regulation of T cell migration; IMP:UniProtKB.
DR GO; GO:0072678; P:T cell migration; IDA:UniProtKB.
DR GO; GO:0072679; P:thymocyte migration; IDA:UniProtKB.
DR InterPro; IPR004067; Chemokine_CCR6.
DR InterPro; IPR000355; Chemokine_rcpt.
DR InterPro; IPR000276; GPCR_Rhodpsn.
DR InterPro; IPR017452; GPCR_Rhodpsn_7TM.
DR PANTHER; PTHR10489:SF611; PTHR10489:SF611; 1.
DR Pfam; PF00001; 7tm_1; 1.
DR PRINTS; PR00657; CCCHEMOKINER.
DR PRINTS; PR01529; CHEMOKINER6.
DR PRINTS; PR00237; GPCRRHODOPSN.
DR PROSITE; PS00237; G_PROTEIN_RECEP_F1_1; 1.
DR PROSITE; PS50262; G_PROTEIN_RECEP_F1_2; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Disulfide bond; G-protein coupled receptor; Glycoprotein;
KW Membrane; Receptor; Reference proteome; Transducer; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..367
FT /note="C-C chemokine receptor type 6"
FT /id="PRO_0000069287"
FT TOPO_DOM 1..39
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 40..66
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 67..75
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 76..96
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 97..111
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 112..133
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 134..151
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 152..172
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 173..203
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 204..230
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 231..246
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 247..271
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 272..295
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 296..313
FT /note="Helical; Name=7"
FT /evidence="ECO:0000255"
FT TOPO_DOM 314..367
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT CARBOHYD 2
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 35
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 110..189
FT /evidence="ECO:0000250|UniProtKB:P51684,
FT ECO:0000255|PROSITE-ProRule:PRU00521"
SQ SEQUENCE 367 AA; 42103 MW; 6A309AF833B1117E CRC64;
MNSTESYFGT DDYDNTEYYS IPPDHGPCSL EEVRNFTKVF VPIAYSLICV FGLLGNIMVV
MTFAFYKKAR SMTDVYLLNM AITDILFVLT LPFWAVTHAT NTWVFSDALC KLMKGTYAVN
FNCGMLLLAC ISMDRYIAIV QATKSFRVRS RTLTHSKVIC VAVWFISIII SSPTFIFNKK
YELQDRDVCE PRYRSVSEPI TWKLLGMGLE LFFGFFTPLL FMVFCYLFII KTLVQAQNSK
RHRAIRVVIA VVLVFLACQI PHNMVLLVTA VNTGKVGRSC STEKVLAYTR NVAEVLAFLH
CCLNPVLYAF IGQKFRNYFM KIMKDVWCMR RKNKMPGFLC ARVYSESYIS RQTSETVEND
NASSFTM
