CCR8_HUMAN
ID CCR8_HUMAN Reviewed; 355 AA.
AC P51685; B2RC64; Q3KNQ8; Q3KNR3; Q9BYX5;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 1.
DT 03-AUG-2022, entry version 178.
DE RecName: Full=C-C chemokine receptor type 8;
DE Short=C-C CKR-8;
DE Short=CC-CKR-8;
DE Short=CCR-8;
DE AltName: Full=CC chemokine receptor CHEMR1;
DE AltName: Full=CMKBRL2;
DE AltName: Full=Chemokine receptor-like 1;
DE Short=CKR-L1;
DE AltName: Full=GPR-CY6;
DE Short=GPRCY6;
DE AltName: Full=TER1;
DE AltName: CD_antigen=CDw198;
GN Name=CCR8; Synonyms=CKRL1, CMKBR8, CMKBRL2;
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 [GENOMIC DNA].
RX PubMed=8886020; DOI=10.1006/bbrc.1996.1595;
RA Zaballos A., Varona R., Gutierrez J., Lind P., Marquez G.;
RT "Molecular cloning and RNA expression of two new human chemokine receptor-
RT like genes.";
RL Biochem. Biophys. Res. Commun. 227:846-853(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=8977299; DOI=10.1002/eji.1830261230;
RA Samson M., Stordeur P., Labbe O., Soularue P., Vassart G., Parmentier M.;
RT "Molecular cloning and chromosomal mapping of a novel human gene, ChemR1,
RT expressed in T lymphocytes and polymorphonuclear cells and encoding a
RT putative chemokine receptor.";
RL Eur. J. Immunol. 26:3021-3028(1996).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1), AND FUNCTION AS A
RP RECEPTOR FOR CCL1.
RC TISSUE=Thymus;
RX PubMed=9207005; DOI=10.1084/jem.186.1.165;
RA Tiffany H.L., Lautens L.L., Gao J.-L., Pease J., Locati M., Combadiere C.,
RA Modi W., Bonner T.I., Murphy P.M.;
RT "Identification of CCR8: a human monocyte and thymus receptor for the CC
RT chemokine I-309.";
RL J. Exp. Med. 186:165-170(1997).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=8816377;
RA Napolitano M., Zingoni A., Bernardini G., Spinetti G., Nista A.,
RA Storlazzi C.T., Rocchi M., Santoni A.;
RT "Molecular cloning of TER1, a chemokine receptor-like gene expressed by
RT lymphoid tissues.";
RL J. Immunol. 157:2759-2763(1996).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA Nakajima T., Yoshida R., Harada S.;
RT "Molecular cloning of a human novel C-C chemokine receptor.";
RL Submitted (NOV-1997) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT GLY-27.
RX PubMed=12551893; DOI=10.1074/jbc.m211422200;
RA DeVries M.E., Cao H., Wang J., Xu L., Kelvin A.A., Ran L., Chau L.A.,
RA Madrenas J., Hegele R.A., Kelvin D.J.;
RT "Genomic organization and evolution of the CX3CR1/CCR8 chemokine receptor
RT locus.";
RL J. Biol. Chem. 278:11985-11994(2003).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16641997; DOI=10.1038/nature04728;
RA Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J.,
RA Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P.,
RA Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A.,
RA Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L.,
RA Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G.,
RA Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W.,
RA Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M.,
RA Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P.,
RA Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H.,
RA Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J.,
RA Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W.,
RA Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B.,
RA Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O.,
RA Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B.,
RA Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H.,
RA Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J.,
RA Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X.,
RA Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R.,
RA Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A.;
RT "The DNA sequence, annotation and analysis of human chromosome 3.";
RL Nature 440:1194-1198(2006).
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [10]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
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 [11]
RP FUNCTION.
RX PubMed=9521068;
RX DOI=10.1002/(sici)1521-4141(199802)28:02<582::aid-immu582>3.0.co;2-a;
RA Bernardini G., Hedrick J., Sozzani S., Luini W., Spinetti G., Weiss M.,
RA Menon S., Zlotnik A., Mantovani A., Santoni A., Napolitano M.;
RT "Identification of the CC chemokines TARC and macrophage inflammatory
RT protein-1 beta as novel functional ligands for the CCR8 receptor.";
RL Eur. J. Immunol. 28:582-588(1998).
RN [12]
RP FUNCTION AS A RECEPTOR FOR CCL1.
RX PubMed=9469461;
RA Goya I., Gutierrez J., Varona R., Kremer L., Zaballos A., Marquez G.;
RT "Identification of CCR8 as the specific receptor for the human beta-
RT chemokine I-309: cloning and molecular characterization of murine CCR8 as
RT the receptor for TCA-3.";
RL J. Immunol. 160:1975-1981(1998).
RN [13]
RP FUNCTION.
RX PubMed=10540332;
RX DOI=10.1002/(sici)1521-4141(199910)29:10<3210::aid-immu3210>3.0.co;2-w;
RA Garlisi C.G., Xiao H., Tian F., Hedrick J.A., Billah M.M., Egan R.W.,
RA Umland S.P.;
RT "The assignment of chemokine-chemokine receptor pairs: TARC and MIP-1 beta
RT are not ligands for human CC-chemokine receptor 8.";
RL Eur. J. Immunol. 29:3210-3215(1999).
CC -!- FUNCTION: Receptor for the chemokine CCL1/SCYA1/I-309. May regulate
CC monocyte chemotaxis and thymic cell line apoptosis. Alternative
CC coreceptor with CD4 for HIV-1 infection. {ECO:0000269|PubMed:10540332,
CC ECO:0000269|PubMed:9207005, ECO:0000269|PubMed:9469461,
CC ECO:0000269|PubMed:9521068}.
CC -!- SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P51685-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P51685-2; Sequence=VSP_056340;
CC -!- SIMILARITY: Belongs to the G-protein coupled receptor 1 family.
CC {ECO:0000255|PROSITE-ProRule:PRU00521}.
CC -!- CAUTION: Was originally thought to be a receptor for SCYA3 and SCYA17.
CC {ECO:0000305|PubMed:9521068}.
CC -!- WEB RESOURCE: Name=Wikipedia; Note=CC chemokine receptors entry;
CC URL="https://en.wikipedia.org/wiki/CC_chemokine_receptors";
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DR EMBL; Z79782; CAB02142.1; -; Genomic_DNA.
DR EMBL; Y08456; CAA69712.1; -; Genomic_DNA.
DR EMBL; U45983; AAB61962.1; -; Genomic_DNA.
DR EMBL; AF005210; AAB62547.1; -; mRNA.
DR EMBL; U62556; AAB05542.1; -; Genomic_DNA.
DR EMBL; D49919; BAA23387.1; -; mRNA.
DR EMBL; AY016370; AAK08628.1; -; Genomic_DNA.
DR EMBL; AK314957; BAG37461.1; -; mRNA.
DR EMBL; AC104850; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471055; EAW64577.1; -; Genomic_DNA.
DR EMBL; BC069067; AAH69067.1; -; mRNA.
DR EMBL; BC074743; AAH74743.1; -; mRNA.
DR EMBL; BC107152; AAI07153.1; -; mRNA.
DR EMBL; BC107159; AAI07160.1; -; mRNA.
DR CCDS; CCDS2684.1; -. [P51685-1]
DR PIR; JC5067; JC5067.
DR RefSeq; NP_005192.1; NM_005201.3. [P51685-1]
DR AlphaFoldDB; P51685; -.
DR SMR; P51685; -.
DR BioGRID; 107642; 13.
DR DIP; DIP-5836N; -.
DR IntAct; P51685; 13.
DR MINT; P51685; -.
DR STRING; 9606.ENSP00000326432; -.
DR BindingDB; P51685; -.
DR ChEMBL; CHEMBL4596; -.
DR GuidetoPHARMACOLOGY; 65; -.
DR iPTMnet; P51685; -.
DR PhosphoSitePlus; P51685; -.
DR BioMuta; CCR8; -.
DR DMDM; 1707884; -.
DR PaxDb; P51685; -.
DR PeptideAtlas; P51685; -.
DR PRIDE; P51685; -.
DR Antibodypedia; 12174; 545 antibodies from 38 providers.
DR DNASU; 1237; -.
DR Ensembl; ENST00000326306.5; ENSP00000326432.4; ENSG00000179934.7. [P51685-1]
DR GeneID; 1237; -.
DR KEGG; hsa:1237; -.
DR MANE-Select; ENST00000326306.5; ENSP00000326432.4; NM_005201.4; NP_005192.1.
DR UCSC; uc010hhr.3; human. [P51685-1]
DR CTD; 1237; -.
DR DisGeNET; 1237; -.
DR GeneCards; CCR8; -.
DR HGNC; HGNC:1609; CCR8.
DR HPA; ENSG00000179934; Tissue enriched (lymphoid).
DR MIM; 601834; gene.
DR neXtProt; NX_P51685; -.
DR OpenTargets; ENSG00000179934; -.
DR PharmGKB; PA26173; -.
DR VEuPathDB; HostDB:ENSG00000179934; -.
DR eggNOG; KOG3656; Eukaryota.
DR GeneTree; ENSGT01020000230359; -.
DR HOGENOM; CLU_009579_8_3_1; -.
DR InParanoid; P51685; -.
DR OMA; CQNHNKT; -.
DR OrthoDB; 900867at2759; -.
DR PhylomeDB; P51685; -.
DR TreeFam; TF330966; -.
DR PathwayCommons; P51685; -.
DR Reactome; R-HSA-380108; Chemokine receptors bind chemokines.
DR Reactome; R-HSA-418594; G alpha (i) signalling events.
DR SignaLink; P51685; -.
DR SIGNOR; P51685; -.
DR BioGRID-ORCS; 1237; 9 hits in 1062 CRISPR screens.
DR GeneWiki; CCR8_(gene); -.
DR GenomeRNAi; 1237; -.
DR Pharos; P51685; Tchem.
DR PRO; PR:P51685; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; P51685; protein.
DR Bgee; ENSG00000179934; Expressed in granulocyte and 32 other tissues.
DR ExpressionAtlas; P51685; baseline and differential.
DR Genevisible; P51685; HS.
DR GO; GO:0009897; C:external side of plasma membrane; IBA:GO_Central.
DR GO; GO:0005887; C:integral component of plasma membrane; TAS:ProtInc.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0019957; F:C-C chemokine binding; IBA:GO_Central.
DR GO; GO:0016493; F:C-C chemokine receptor activity; IBA:GO_Central.
DR GO; GO:0004950; F:chemokine receptor activity; TAS:ProtInc.
DR GO; GO:0015026; F:coreceptor activity; TAS:ProtInc.
DR GO; GO:0019722; P:calcium-mediated signaling; IBA:GO_Central.
DR GO; GO:0007155; P:cell adhesion; TAS:ProtInc.
DR GO; GO:0060326; P:cell chemotaxis; IBA:GO_Central.
DR GO; GO:0006935; P:chemotaxis; TAS:ProtInc.
DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; TAS:ProtInc.
DR GO; GO:0006955; P:immune response; IBA:GO_Central.
DR GO; GO:0007204; P:positive regulation of cytosolic calcium ion concentration; IBA:GO_Central.
DR InterPro; IPR004068; Chemokine_CCR8.
DR InterPro; IPR000355; Chemokine_rcpt.
DR InterPro; IPR000276; GPCR_Rhodpsn.
DR InterPro; IPR017452; GPCR_Rhodpsn_7TM.
DR Pfam; PF00001; 7tm_1; 1.
DR PRINTS; PR00657; CCCHEMOKINER.
DR PRINTS; PR01530; CHEMOKINER8.
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 Alternative splicing; Cell membrane; Disulfide bond;
KW G-protein coupled receptor; Membrane; Receptor; Reference proteome;
KW Transducer; Transmembrane; Transmembrane helix.
FT CHAIN 1..355
FT /note="C-C chemokine receptor type 8"
FT /id="PRO_0000069288"
FT TOPO_DOM 1..35
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 36..63
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 64..73
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 74..93
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 94..107
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 108..129
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 130..146
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 147..171
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 172..202
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 203..222
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 223..238
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 239..263
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 264..280
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 281..304
FT /note="Helical; Name=7"
FT /evidence="ECO:0000255"
FT TOPO_DOM 305..355
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DISULFID 106..183
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00521"
FT VAR_SEQ 1..91
FT /note="MDYTLDLSVTTVTDYYYPDIFSSPCDAELIQTNGKLLLAVFYCLLFVFSLLG
FT NSLVILVLVVCKKLRSITDVYLLNLALSDLLFVFSFPFQ -> MRNLFRQM (in
FT isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_056340"
FT VARIANT 27
FT /note="A -> G (in dbSNP:rs2853699)"
FT /evidence="ECO:0000269|PubMed:12551893"
FT /id="VAR_049384"
SQ SEQUENCE 355 AA; 40844 MW; BC14A153CF695361 CRC64;
MDYTLDLSVT TVTDYYYPDI FSSPCDAELI QTNGKLLLAV FYCLLFVFSL LGNSLVILVL
VVCKKLRSIT DVYLLNLALS DLLFVFSFPF QTYYLLDQWV FGTVMCKVVS GFYYIGFYSS
MFFITLMSVD RYLAVVHAVY ALKVRTIRMG TTLCLAVWLT AIMATIPLLV FYQVASEDGV
LQCYSFYNQQ TLKWKIFTNF KMNILGLLIP FTIFMFCYIK ILHQLKRCQN HNKTKAIRLV
LIVVIASLLF WVPFNVVLFL TSLHSMHILD GCSISQQLTY ATHVTEIISF THCCVNPVIY
AFVGEKFKKH LSEIFQKSCS QIFNYLGRQM PRESCEKSSS CQQHSSRSSS VDYIL
