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P51679 (CCR4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 123. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length360 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

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.

Ontologies

Keywords
   Cellular componentCell membrane
Membrane
   Coding sequence diversityPolymorphism
   DomainTransmembrane
Transmembrane helix
   Molecular functionG-protein coupled receptor
Receptor
Transducer
   PTMDisulfide bond
Glycoprotein
Phosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processchemokine-mediated signaling pathway

Traceable author statement Ref.1. Source: GOC

chemotaxis

Traceable author statement Ref.1. Source: ProtInc

immune response

Traceable author statement Ref.1. Source: ProtInc

inflammatory response

Traceable author statement Ref.1. Source: ProtInc

neuron migration

Inferred from electronic annotation. Source: Ensembl

positive regulation of cytosolic calcium ion concentration

Traceable author statement Ref.1. Source: ProtInc

positive regulation of positive chemotaxis

Inferred from electronic annotation. Source: Ensembl

response to antibiotic

Inferred from electronic annotation. Source: Ensembl

response to bacterium

Inferred from electronic annotation. Source: Ensembl

response to radiation

Inferred from electronic annotation. Source: Ensembl

tolerance induction

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentexternal side of plasma membrane

Inferred from electronic annotation. Source: Ensembl

integral component of plasma membrane

Traceable author statement Ref.1. Source: ProtInc

neuronal cell body

Inferred from electronic annotation. Source: Ensembl

plasma membrane

Traceable author statement. Source: Reactome

   Molecular_functionC-C chemokine receptor activity

Inferred from electronic annotation. Source: Ensembl

chemokine receptor activity

Traceable author statement Ref.1. Source: ProtInc

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 360360C-C chemokine receptor type 4
PRO_0000069245

Regions

Topological domain1 – 3939Extracellular Potential
Transmembrane40 – 6728Helical; Name=1; Potential
Topological domain68 – 7710Cytoplasmic Potential
Transmembrane78 – 9821Helical; Name=2; Potential
Topological domain99 – 11113Extracellular Potential
Transmembrane112 – 13322Helical; Name=3; Potential
Topological domain134 – 15017Cytoplasmic Potential
Transmembrane151 – 17525Helical; Name=4; Potential
Topological domain176 – 20631Extracellular Potential
Transmembrane207 – 22620Helical; Name=5; Potential
Topological domain227 – 24216Cytoplasmic Potential
Transmembrane243 – 26725Helical; Name=6; Potential
Topological domain268 – 28417Extracellular Potential
Transmembrane285 – 30824Helical; Name=7; Potential
Topological domain309 – 36052Cytoplasmic Potential

Amino acid modifications

Glycosylation1831N-linked (GlcNAc...) Potential
Glycosylation1941N-linked (GlcNAc...) Potential
Disulfide bond110 ↔ 187 By similarity

Natural variations

Natural variant1301L → V. Ref.2
VAR_010669
Natural variant1781C → S. Ref.2
VAR_010670

Sequences

Sequence LengthMass (Da)Tools
P51679 [UniParc].

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

FASTA36041,403
        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

References

« Hide '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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [Abstract]
Cited for: FUNCTION, TISSUE SPECIFICITY, PHOSPHORYLATION.
+Additional computationally mapped references.

Web resources

Wikipedia

CC chemokine receptors entry

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
PIRA57160.
RefSeqNP_005499.1. NM_005508.4.
UniGeneHs.184926.

3D structure databases

ProteinModelPortalP51679.
SMRP51679. Positions 13-320.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid107638. 5 interactions.
DIPDIP-5848N.
IntActP51679. 1 interaction.
MINTMINT-1525168.
STRING9606.ENSP00000332659.

Chemistry

BindingDBP51679.
ChEMBLCHEMBL2414.
GuidetoPHARMACOLOGY61.

Protein family/group databases

GPCRDBSearch...

Polymorphism databases

DMDM1705894.

Proteomic databases

PaxDbP51679.
PRIDEP51679.

Protocols and materials databases

DNASU1233.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000330953; ENSP00000332659; ENSG00000183813.
GeneID1233.
KEGGhsa:1233.
UCSCuc003cfg.1. human.

Organism-specific databases

CTD1233.
GeneCardsGC03P032968.
HGNCHGNC:1605. CCR4.
HPAHPA031613.
MIM604836. gene.
neXtProtNX_P51679.
PharmGKBPA26169.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG148353.
HOGENOMHOG000234122.
HOVERGENHBG106917.
InParanoidP51679.
KOK04179.
OMALCKIISW.
OrthoDBEOG738051.
PhylomeDBP51679.
TreeFamTF330966.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.

Gene expression databases

ArrayExpressP51679.
BgeeP51679.
CleanExHS_CCR4.
GenevestigatorP51679.

Family and domain databases

Gene3D1.20.1070.10. 1 hit.
InterProIPR002239. Chemokine_CCR4.
IPR000355. Chemokine_rcpt.
IPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
[Graphical view]
PANTHERPTHR24227. PTHR24227. 1 hit.
PTHR24227:SF12. PTHR24227:SF12. 1 hit.
PfamPF00001. 7tm_1. 1 hit.
[Graphical view]
PRINTSPR00657. CCCHEMOKINER.
PR01109. CHEMOKINER4.
PR00237. GPCRRHODOPSN.
PROSITEPS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiCCR4.
GenomeRNAi1233.
NextBio5031.
PROP51679.
SOURCESearch...

Entry information

Entry nameCCR4_HUMAN
AccessionPrimary (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: April 16, 2014
This is version 123 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 3

Human chromosome 3: entries, gene names and cross-references to MIM

Human cell differentiation molecules

CD nomenclature of surface proteins of human leucocytes and list of entries

7-transmembrane G-linked receptors

List of 7-transmembrane G-linked receptor entries