CCR4_HUMAN
ID CCR4_HUMAN Reviewed; 360 AA.
AC P51679; Q9ULY6; Q9ULY7;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 1.
DT 03-AUG-2022, entry version 180.
DE RecName: Full=C-C chemokine receptor type 4;
DE Short=C-C CKR-4;
DE Short=CC-CKR-4;
DE Short=CCR-4;
DE Short=CCR4;
DE AltName: Full=K5-5;
DE AltName: CD_antigen=CD194;
GN Name=CCR4; Synonyms=CMKBR4;
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].
RC TISSUE=Spleen;
RX PubMed=7642634; DOI=10.1074/jbc.270.33.19495;
RA Power C.A., Meyer A., Nemeth K., Bacon K.B., Hoogewerf A.J.,
RA Proudfoot A.E.I., Wells T.N.C.;
RT "Molecular cloning and functional expression of a novel CC chemokine
RT receptor cDNA from a human basophilic cell line.";
RL J. Biol. Chem. 270:19495-19500(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS VAL-130 AND SER-178.
RX PubMed=11196669; DOI=10.1038/sj.gene.6363638;
RA Kato H., Tsuchiya N., Izumi S., Miyamasu M., Nakajima T., Kawasaki H.,
RA Hirai K., Tokunaga K.;
RT "New variations of human CC-chemokine receptors CCR3 and CCR4.";
RL Genes Immun. 1:97-104(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Kopatz S.A., Aronstam R.S., Sharma S.V.;
RT "cDNA clones of human proteins involved in signal transduction sequenced by
RT the Guthrie cDNA resource center (www.cdna.org).";
RL Submitted (JUN-2003) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Blood;
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 FUNCTION.
RX PubMed=9169480; DOI=10.1074/jbc.272.23.15036;
RA Imai T., Baba M., Nishimura M., Kakizaki M., Takagi S., Yoshie O.;
RT "The T cell-directed CC chemokine TARC is a highly specific biological
RT ligand for CC chemokine receptor 4.";
RL J. Biol. Chem. 272:15036-15042(1997).
RN [6]
RP FUNCTION.
RX PubMed=9430724; DOI=10.1074/jbc.273.3.1764;
RA Imai T., Chantry D., Raport C.J., Wood C.L., Nishimura M., Godiska R.,
RA Yoshie O., Gray P.W.;
RT "Macrophage-derived chemokine is a functional ligand for the CC chemokine
RT receptor 4.";
RL J. Biol. Chem. 273:1764-1768(1998).
RN [7]
RP FUNCTION.
RX PubMed=10466728; DOI=10.1038/23495;
RA Campbell J.J., Haraldsen G., Pan J., Rottman J., Qin S., Ponath P.,
RA Andrew D.P., Warnke R., Ruffing N., Kassam N., Wu L., Butcher E.C.;
RT "The chemokine receptor CCR4 in vascular recognition by cutaneous but not
RT intestinal memory T cells.";
RL Nature 400:776-780(1999).
RN [8]
RP FUNCTION, TISSUE SPECIFICITY, AND PHOSPHORYLATION.
RX PubMed=10754297; DOI=10.4049/jimmunol.164.8.4048;
RA Inngjerdingen M., Damaj B., Maghazachi A.A.;
RT "Human NK cells express CC chemokine receptors 4 and 8 and respond to
RT thymus and activation-regulated chemokine, macrophage-derived chemokine,
RT and I-309.";
RL J. Immunol. 164:4048-4054(2000).
RN [9]
RP FUNCTION.
RX PubMed=16137713; DOI=10.1016/j.lfs.2005.05.070;
RA Wang Y., Zhang Y., Yang X., Han W., Liu Y., Xu Q., Zhao R., Di C., Song Q.,
RA Ma D.;
RT "Chemokine-like factor 1 is a functional ligand for CC chemokine receptor 4
RT (CCR4).";
RL Life Sci. 78:614-621(2006).
CC -!- FUNCTION: High affinity receptor for the C-C type chemokines
CC CCL17/TARC, CCL22/MDC and CKLF isoform 1/CKLF1. The activity of this
CC receptor is mediated by G(i) proteins which activate a
CC phosphatidylinositol-calcium second messenger system. Can function as a
CC chemoattractant homing receptor on circulating memory lymphocytes and
CC as a coreceptor for some primary HIV-2 isolates. In the CNS, could
CC mediate hippocampal-neuron survival. {ECO:0000269|PubMed:10466728,
CC ECO:0000269|PubMed:10754297, ECO:0000269|PubMed:16137713,
CC ECO:0000269|PubMed:9169480, ECO:0000269|PubMed:9430724}.
CC -!- INTERACTION:
CC P51679; Q92583: CCL17; NbExp=2; IntAct=EBI-7847466, EBI-16640146;
CC P51679; A5PKU2: TUSC5; NbExp=3; IntAct=EBI-7847466, EBI-11988865;
CC -!- SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein.
CC -!- TISSUE SPECIFICITY: Predominantly expressed in the thymus, in
CC peripheral blood leukocytes, including T-cells, mostly CD4+ cells, and
CC basophils, and in platelets; at lower levels, in the spleen and in
CC monocytes. Detected also in macrophages, IL-2-activated natural killer
CC cells and skin-homing memory T-cells, mostly the ones expressing the
CC cutaneous lymphocyte antigen (CLA). Expressed in brain microvascular
CC and coronary artery endothelial cells. {ECO:0000269|PubMed:10754297}.
CC -!- PTM: In natural killer cells, CCL22 binding induces phosphorylation on
CC yet undefined Ser/Thr residues, most probably by beta-adrenergic
CC receptor kinases 1 and 2. {ECO:0000269|PubMed:10754297}.
CC -!- SIMILARITY: Belongs to the G-protein coupled receptor 1 family.
CC {ECO:0000255|PROSITE-ProRule:PRU00521}.
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; X85740; CAA59743.1; -; mRNA.
DR EMBL; AB023888; BAA86965.1; -; Genomic_DNA.
DR EMBL; AB023889; BAA86966.1; -; Genomic_DNA.
DR EMBL; AB023890; BAA86967.1; -; Genomic_DNA.
DR EMBL; AB023891; BAA86968.1; -; Genomic_DNA.
DR EMBL; AB023892; BAA86969.1; -; Genomic_DNA.
DR EMBL; AY322539; AAP84352.1; -; Genomic_DNA.
DR EMBL; BC069139; AAH69139.1; -; mRNA.
DR EMBL; BC071751; AAH71751.1; -; mRNA.
DR EMBL; BC074935; AAH74935.1; -; mRNA.
DR CCDS; CCDS2656.1; -.
DR PIR; A57160; A57160.
DR RefSeq; NP_005499.1; NM_005508.4.
DR RefSeq; XP_016861176.1; XM_017005687.1.
DR AlphaFoldDB; P51679; -.
DR SMR; P51679; -.
DR BioGRID; 107638; 37.
DR DIP; DIP-5848N; -.
DR IntAct; P51679; 33.
DR MINT; P51679; -.
DR STRING; 9606.ENSP00000332659; -.
DR BindingDB; P51679; -.
DR ChEMBL; CHEMBL2414; -.
DR DrugBank; DB15570; FLX475.
DR DrugBank; DB12498; Mogamulizumab.
DR DrugCentral; P51679; -.
DR GuidetoPHARMACOLOGY; 61; -.
DR GlyGen; P51679; 2 sites.
DR iPTMnet; P51679; -.
DR PhosphoSitePlus; P51679; -.
DR BioMuta; CCR4; -.
DR DMDM; 1705894; -.
DR MassIVE; P51679; -.
DR PaxDb; P51679; -.
DR PeptideAtlas; P51679; -.
DR PRIDE; P51679; -.
DR ProteomicsDB; 56366; -.
DR ABCD; P51679; 1 sequenced antibody.
DR Antibodypedia; 11668; 684 antibodies from 38 providers.
DR DNASU; 1233; -.
DR Ensembl; ENST00000330953.6; ENSP00000332659.5; ENSG00000183813.7.
DR GeneID; 1233; -.
DR KEGG; hsa:1233; -.
DR MANE-Select; ENST00000330953.6; ENSP00000332659.5; NM_005508.5; NP_005499.1.
DR UCSC; uc003cfg.2; human.
DR CTD; 1233; -.
DR DisGeNET; 1233; -.
DR GeneCards; CCR4; -.
DR HGNC; HGNC:1605; CCR4.
DR HPA; ENSG00000183813; Tissue enhanced (lymphoid tissue, urinary bladder).
DR MIM; 604836; gene.
DR neXtProt; NX_P51679; -.
DR OpenTargets; ENSG00000183813; -.
DR PharmGKB; PA26169; -.
DR VEuPathDB; HostDB:ENSG00000183813; -.
DR eggNOG; KOG3656; Eukaryota.
DR GeneTree; ENSGT01020000230359; -.
DR HOGENOM; CLU_009579_8_3_1; -.
DR InParanoid; P51679; -.
DR OMA; FHTQSTG; -.
DR OrthoDB; 900867at2759; -.
DR PhylomeDB; P51679; -.
DR TreeFam; TF330966; -.
DR PathwayCommons; P51679; -.
DR Reactome; R-HSA-380108; Chemokine receptors bind chemokines.
DR Reactome; R-HSA-418594; G alpha (i) signalling events.
DR SignaLink; P51679; -.
DR SIGNOR; P51679; -.
DR BioGRID-ORCS; 1233; 8 hits in 1066 CRISPR screens.
DR GeneWiki; CCR4; -.
DR GenomeRNAi; 1233; -.
DR Pharos; P51679; Tclin.
DR PRO; PR:P51679; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; P51679; protein.
DR Bgee; ENSG00000183813; Expressed in vermiform appendix and 70 other tissues.
DR ExpressionAtlas; P51679; baseline and differential.
DR Genevisible; P51679; 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:0043025; C:neuronal cell body; IEA:Ensembl.
DR GO; GO:0005886; C:plasma membrane; IDA:HPA.
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:0019722; P:calcium-mediated signaling; IBA:GO_Central.
DR GO; GO:0060326; P:cell chemotaxis; IBA:GO_Central.
DR GO; GO:0006935; P:chemotaxis; TAS:ProtInc.
DR GO; GO:0048872; P:homeostasis of number of cells; IEA:Ensembl.
DR GO; GO:0006955; P:immune response; IBA:GO_Central.
DR GO; GO:0006954; P:inflammatory response; TAS:ProtInc.
DR GO; GO:1904936; P:interneuron migration; IEA:Ensembl.
DR GO; GO:0007204; P:positive regulation of cytosolic calcium ion concentration; IBA:GO_Central.
DR GO; GO:0050927; P:positive regulation of positive chemotaxis; IEA:Ensembl.
DR GO; GO:0046677; P:response to antibiotic; IEA:Ensembl.
DR GO; GO:0009617; P:response to bacterium; IEA:Ensembl.
DR GO; GO:0009314; P:response to radiation; IEA:Ensembl.
DR GO; GO:0002507; P:tolerance induction; IEA:Ensembl.
DR InterPro; IPR002239; Chemokine_CCR4.
DR InterPro; IPR000355; Chemokine_rcpt.
DR InterPro; IPR000276; GPCR_Rhodpsn.
DR InterPro; IPR017452; GPCR_Rhodpsn_7TM.
DR PANTHER; PTHR10489:SF608; PTHR10489:SF608; 1.
DR Pfam; PF00001; 7tm_1; 1.
DR PRINTS; PR00657; CCCHEMOKINER.
DR PRINTS; PR01109; CHEMOKINER4.
DR PRINTS; PR00237; GPCRRHODOPSN.
DR SMART; SM01381; 7TM_GPCR_Srsx; 1.
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; Phosphoprotein; Receptor; Reference proteome; Transducer;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..360
FT /note="C-C chemokine receptor type 4"
FT /id="PRO_0000069245"
FT TOPO_DOM 1..39
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 40..67
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 68..77
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 78..98
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 99..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..150
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 151..175
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 176..206
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 207..226
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 227..242
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 243..267
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 268..284
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 285..308
FT /note="Helical; Name=7"
FT /evidence="ECO:0000255"
FT TOPO_DOM 309..360
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT CARBOHYD 183
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 194
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 110..187
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00521"
FT VARIANT 130
FT /note="L -> V"
FT /evidence="ECO:0000269|PubMed:11196669"
FT /id="VAR_010669"
FT VARIANT 178
FT /note="C -> S (in dbSNP:rs753825374)"
FT /evidence="ECO:0000269|PubMed:11196669"
FT /id="VAR_010670"
SQ SEQUENCE 360 AA; 41403 MW; 51EBE12AD1FAFABF CRC64;
MNPTDIADTT LDESIYSNYY LYESIPKPCT KEGIKAFGEL FLPPLYSLVF VFGLLGNSVV
VLVLFKYKRL RSMTDVYLLN LAISDLLFVF SLPFWGYYAA DQWVFGLGLC KMISWMYLVG
FYSGIFFVML MSIDRYLAIV HAVFSLRART LTYGVITSLA TWSVAVFASL PGFLFSTCYT
ERNHTYCKTK YSLNSTTWKV LSSLEINILG LVIPLGIMLF CYSMIIRTLQ HCKNEKKNKA
VKMIFAVVVL FLGFWTPYNI VLFLETLVEL EVLQDCTFER YLDYAIQATE TLAFVHCCLN
PIIYFFLGEK FRKYILQLFK TCRGLFVLCQ YCGLLQIYSA DTPSSSYTQS TMDHDLHDAL
