C-C chemokine receptor type 4 - Homo sapiens (Human)

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Reviewed, UniProtKB/Swiss-Prot P51679 (CCR4_HUMAN)

Last modified June 16, 2009. Version 77. History...

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Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents

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Names and origin

Protein names

Recommended name:
    C-C chemokine receptor type 4
      Short name=C-C CKR-4
      Short name=CC-CKR-4
      Short name=CCR-4
      Short name=CCR4
Alternative name(s):
    K5-5
    CD_antigen=CD194

Gene names

Name:	CCR4
Synonyms:	CMKBR4

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

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Protein attributes

Sequence length	360 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

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General annotation (Comments)

Function	High affinity receptor for the C-C type chemokines CCL17/TARC and CCL22/MDC. The activity of this receptor is mediated by G(i) proteins which activate a phosphatidylinositol-calcium second messenger system. Can function as a chemoattractant homing receptor on circulating memory lymphocytes and as a coreceptor for some primary HIV-2 isolates. In the CNS, could mediate hippocampal-neuron survival. Ref.5 Ref.6 Ref.7 Ref.8
Subcellular location	Cell membrane; Multi-pass membrane protein.
Tissue specificity	Predominantly expressed in the thymus, in peripheral blood leukocytes, including T-cells, mostly CD4+ cells, and basophils, and in platelets; at lower levels, in the spleen and in monocytes. Detected also in macrophages, IL-2-activated natural killer cells and skin-homing memory T-cells, mostly the ones expressing the cutaneous lymphocyte antigen (CLA). Expressed in brain microvascular and coronary artery endothelial cells. Ref.8
Post-translational modification	In natural killer cells, CCL22 binding induces phosphorylation on yet undefined Ser/Thr residues, most probably by beta-adrenergic receptor kinases 1 and 2.
Sequence similarities	Belongs to the G-protein coupled receptor 1 family.

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Ontologies

Keywords
Cellular component	Cell membrane Membrane
Coding sequence diversity	Polymorphism
Domain	Transmembrane
Molecular function	G-protein coupled receptor Receptor Transducer
PTM	Disulfide bond Glycoprotein Phosphoprotein
Gene Ontology (GO)
Biological process	G-protein coupled receptor protein signaling pathway Inferred from electronic annotation. Source: UniProtKB-KW chemotaxis Ref.1 Traceable author statement. Source: ProtInc elevation of cytosolic calcium ion concentration Ref.1 Traceable author statement. Source: ProtInc immune response Ref.1 Traceable author statement. Source: ProtInc inflammatory response Ref.1 Traceable author statement. Source: ProtInc
Cellular component	integral to plasma membrane Ref.1 Traceable author statement. Source: ProtInc
Complete GO annotation...

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Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 360

360

C-C chemokine receptor type 4

PRO_0000069245

Regions

Topological domain

1 – 39

Extracellular Potential

Transmembrane

40 – 67

1 Potential

Topological domain

68 – 77

Cytoplasmic Potential

Transmembrane

78 – 98

2 Potential

Topological domain

99 – 111

Extracellular Potential

Transmembrane

112 – 133

3 Potential

Topological domain

134 – 150

Cytoplasmic Potential

Transmembrane

151 – 175

4 Potential

Topological domain

176 – 206

Extracellular Potential

Transmembrane

207 – 226

5 Potential

Topological domain

227 – 242

Cytoplasmic Potential

Transmembrane

243 – 267

6 Potential

Topological domain

268 – 284

Extracellular Potential

Transmembrane

285 – 308

7 Potential

Topological domain

309 – 360

Cytoplasmic Potential

Amino acid modifications

Glycosylation

183

N-linked (GlcNAc...) Potential

Glycosylation

194

N-linked (GlcNAc...) Potential

Disulfide bond

110 ↔ 187

By similarity

Natural variations

Natural variant

130

L → V Ref.2

VAR_010669

Natural variant

178

C → S Ref.2

VAR_010670

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Sequences

Sequence

Length

Mass (Da)

Tools

P51679-1 [UniParc].

Last modified October 1, 1996. Version 1.
Checksum: 51EBE12AD1FAFABF
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FASTA

360

41,403

        10         20         30         40         50         60 
MNPTDIADTT LDESIYSNYY LYESIPKPCT KEGIKAFGEL FLPPLYSLVF VFGLLGNSVV 

        70         80         90        100        110        120 
VLVLFKYKRL RSMTDVYLLN LAISDLLFVF SLPFWGYYAA DQWVFGLGLC KMISWMYLVG 

       130        140        150        160        170        180 
FYSGIFFVML MSIDRYLAIV HAVFSLRART LTYGVITSLA TWSVAVFASL PGFLFSTCYT 

       190        200        210        220        230        240 
ERNHTYCKTK YSLNSTTWKV LSSLEINILG LVIPLGIMLF CYSMIIRTLQ HCKNEKKNKA 

       250        260        270        280        290        300 
VKMIFAVVVL FLGFWTPYNI VLFLETLVEL EVLQDCTFER YLDYAIQATE TLAFVHCCLN 

       310        320        330        340        350        360 
PIIYFFLGEK FRKYILQLFK TCRGLFVLCQ YCGLLQIYSA DTPSSSYTQS TMDHDLHDAL

« Hide

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References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning and functional expression of a novel CC chemokine receptor cDNA from a human basophilic cell line." Power C.A., Meyer A., Nemeth K., Bacon K.B., Hoogewerf A.J., Proudfoot A.E.I., Wells T.N.C. J. Biol. Chem. 270:19495-19500(1995) [PubMed: 7642634] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Spleen.
[2]	"New variations of human CC-chemokine receptors CCR3 and CCR4." Kato H., Tsuchiya N., Izumi S., Miyamasu M., Nakajima T., Kawasaki H., Hirai K., Tokunaga K. Genes Immun. 1:97-104(1999) [PubMed: 11196669] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS VAL-130 AND SER-178.
[3]	"cDNA clones of human proteins involved in signal transduction sequenced by the Guthrie cDNA resource center (www.cdna.org)." Kopatz S.A., Aronstam R.S., Sharma S.V. Submitted (JUN-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[4]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Blood.
[5]	"The T cell-directed CC chemokine TARC is a highly specific biological ligand for CC chemokine receptor 4." Imai T., Baba M., Nishimura M., Kakizaki M., Takagi S., Yoshie O. J. Biol. Chem. 272:15036-15042(1997) [PubMed: 9169480] [Abstract] Cited for: FUNCTION.
[6]	"Macrophage-derived chemokine is a functional ligand for the CC chemokine receptor 4." Imai T., Chantry D., Raport C.J., Wood C.L., Nishimura M., Godiska R., Yoshie O., Gray P.W. J. Biol. Chem. 273:1764-1768(1998) [PubMed: 9430724] [Abstract] Cited for: FUNCTION.
[7]	"The chemokine receptor CCR4 in vascular recognition by cutaneous but not intestinal memory T cells." Campbell J.J., Haraldsen G., Pan J., Rottman J., Qin S., Ponath P., Andrew D.P., Warnke R., Ruffing N., Kassam N., Wu L., Butcher E.C. Nature 400:776-780(1999) [PubMed: 10466728] [Abstract] Cited for: FUNCTION.
[8]	"Human NK cells express CC chemokine receptors 4 and 8 and respond to thymus and activation-regulated chemokine, macrophage-derived chemokine, and I-309." Inngjerdingen M., Damaj B., Maghazachi A.A. J. Immunol. 164:4048-4054(2000) [PubMed: 10754297] [Abstract] Cited for: FUNCTION, TISSUE SPECIFICITY, PHOSPHORYLATION.
+	Additional computationally mapped references.

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Web resources

Wikipedia

CC chemokine receptors entry

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Cross-references

Sequence databases
	X85740 mRNA. Translation: CAA59743.1. AB023888 Genomic DNA. Translation: BAA86965.1. AB023889 Genomic DNA. Translation: BAA86966.1. AB023890 Genomic DNA. Translation: BAA86967.1. AB023891 Genomic DNA. Translation: BAA86968.1. AB023892 Genomic DNA. Translation: BAA86969.1. AY322539 Genomic DNA. Translation: AAP84352.1. BC069139 mRNA. Translation: AAH69139.1. BC071751 mRNA. Translation: AAH71751.1. BC074935 mRNA. Translation: AAH74935.1.
IPI	IPI00019958.
PIR	A57160.
RefSeq	NP_005499.1.
UniGene	Hs.184926
3D structure databases
ModBase	Search...
Protein-protein interaction databases
DIP	DIP:5848N.
Protein family/group databases
GPCRDB	Search...
Proteomic databases
PRIDE	P51679.
Genome annotation databases
Ensembl	ENSG00000183813. Homo sapiens. [Contig view]
GeneID	1233.
KEGG	hsa:1233.
Organism-specific databases
GeneCards	GC03P032968.
H-InvDB	HIX0030840.
HGNC	HGNC:1605. CCR4.
MIM	604836. gene.
PharmGKB	PA26169.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	P51679.
HOVERGEN	P51679.
OMA	P51679. KYKRLKS.
Enzyme and pathway databases
Reactome	REACT_14797. Signaling by GPCR.
Gene expression databases
ArrayExpress	P51679.
Bgee	P51679.
CleanEx	HS_CCR4.
GermOnline	ENSG00000183813. Homo sapiens.
Family and domain databases
InterPro	IPR000276. 7TM_GPCR_Rhodpsn. IPR002239. CC_4_rcpt. IPR000355. Chmkine_rcpt. IPR017452. GPCR_Rhodpsn_supfam. [Graphical view]
PANTHER	PTHR19264:SF203. CC_4_rcpt. 1 hit.
Pfam	PF00001. 7tm_1. 1 hit. [Graphical view]
PRINTS	PR00657. CCCHEMOKINER. PR01109. CHEMOKINER4. PR00237. GPCRRHODOPSN.
PROSITE	PS00237. G_PROTEIN_RECEP_F1_1. 1 hit. PS50262. G_PROTEIN_RECEP_F1_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	5031.
SOURCE	Search...

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Entry information

Entry name

CCR4_HUMAN

Accession

Primary (citable) accession number: P51679
Secondary accession number(s): Q9ULY6, Q9ULY7

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	October 1, 1996
Last modified:	June 16, 2009
This is version 77 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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