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Protein

C-C chemokine receptor type 4

Gene

CCR4

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

High affinity receptor for the C-C type chemokines CCL17/TARC, CCL22/MDC and CKLF isoform 1/CKLF1. 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.5 Publications

GO - Molecular functioni

  • C-C chemokine receptor activity Source: Ensembl
  • chemokine receptor activity Source: ProtInc

GO - Biological processi

  • chemotaxis Source: ProtInc
  • homeostasis of number of cells Source: Ensembl
  • immune response Source: ProtInc
  • inflammatory response Source: ProtInc
  • neuron migration Source: Ensembl
  • positive regulation of cytosolic calcium ion concentration Source: ProtInc
  • positive regulation of positive chemotaxis Source: Ensembl
  • response to antibiotic Source: Ensembl
  • response to bacterium Source: Ensembl
  • response to radiation Source: Ensembl
  • tolerance induction Source: Ensembl
Complete GO annotation...

Keywords - Molecular functioni

G-protein coupled receptor, Receptor, Transducer

Enzyme and pathway databases

BioCyciZFISH:ENSG00000121966-MONOMER.
ReactomeiR-HSA-380108. Chemokine receptors bind chemokines.
R-HSA-418594. G alpha (i) signalling events.
SIGNORiP51679.

Names & Taxonomyi

Protein namesi
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 namesi
Name:CCR4
Synonyms:CMKBR4
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 3

Organism-specific databases

HGNCiHGNC:1605. CCR4.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 39ExtracellularSequence analysisAdd BLAST39
Transmembranei40 – 67Helical; Name=1Sequence analysisAdd BLAST28
Topological domaini68 – 77CytoplasmicSequence analysis10
Transmembranei78 – 98Helical; Name=2Sequence analysisAdd BLAST21
Topological domaini99 – 111ExtracellularSequence analysisAdd BLAST13
Transmembranei112 – 133Helical; Name=3Sequence analysisAdd BLAST22
Topological domaini134 – 150CytoplasmicSequence analysisAdd BLAST17
Transmembranei151 – 175Helical; Name=4Sequence analysisAdd BLAST25
Topological domaini176 – 206ExtracellularSequence analysisAdd BLAST31
Transmembranei207 – 226Helical; Name=5Sequence analysisAdd BLAST20
Topological domaini227 – 242CytoplasmicSequence analysisAdd BLAST16
Transmembranei243 – 267Helical; Name=6Sequence analysisAdd BLAST25
Topological domaini268 – 284ExtracellularSequence analysisAdd BLAST17
Transmembranei285 – 308Helical; Name=7Sequence analysisAdd BLAST24
Topological domaini309 – 360CytoplasmicSequence analysisAdd BLAST52

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Organism-specific databases

DisGeNETi1233.
OpenTargetsiENSG00000183813.
PharmGKBiPA26169.

Chemistry databases

ChEMBLiCHEMBL2414.
GuidetoPHARMACOLOGYi61.

Polymorphism and mutation databases

BioMutaiCCR4.
DMDMi1705894.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000692451 – 360C-C chemokine receptor type 4Add BLAST360

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi110 ↔ 187PROSITE-ProRule annotation
Glycosylationi183N-linked (GlcNAc...)Sequence analysis1
Glycosylationi194N-linked (GlcNAc...)Sequence analysis1

Post-translational modificationi

In natural killer cells, CCL22 binding induces phosphorylation on yet undefined Ser/Thr residues, most probably by beta-adrenergic receptor kinases 1 and 2.1 Publication

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

PaxDbiP51679.
PeptideAtlasiP51679.
PRIDEiP51679.

PTM databases

iPTMnetiP51679.
PhosphoSitePlusiP51679.

Expressioni

Tissue specificityi

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.1 Publication

Gene expression databases

BgeeiENSG00000183813.
CleanExiHS_CCR4.
ExpressionAtlasiP51679. baseline and differential.
GenevisibleiP51679. HS.

Organism-specific databases

HPAiHPA031613.

Interactioni

Protein-protein interaction databases

BioGridi107638. 6 interactors.
DIPiDIP-5848N.
IntActiP51679. 1 interactor.
MINTiMINT-1525168.
STRINGi9606.ENSP00000332659.

Chemistry databases

BindingDBiP51679.

Structurei

3D structure databases

ProteinModelPortaliP51679.
SMRiP51679.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the G-protein coupled receptor 1 family.PROSITE-ProRule annotation

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG3656. Eukaryota.
ENOG410XRW9. LUCA.
GeneTreeiENSGT00760000118785.
HOGENOMiHOG000234122.
HOVERGENiHBG106917.
InParanoidiP51679.
KOiK04179.
OMAiKFRKYIV.
OrthoDBiEOG091G0B7A.
PhylomeDBiP51679.
TreeFamiTF330966.

Family and domain databases

InterProiIPR002239. Chemokine_CCR4.
IPR000355. Chemokine_rcpt.
IPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
[Graphical view]
PfamiPF00001. 7tm_1. 1 hit.
[Graphical view]
PRINTSiPR00657. CCCHEMOKINER.
PR01109. CHEMOKINER4.
PR00237. GPCRRHODOPSN.
SMARTiSM01381. 7TM_GPCR_Srsx. 1 hit.
[Graphical view]
PROSITEiPS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

P51679-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MNPTDIADTT LDESIYSNYY LYESIPKPCT KEGIKAFGEL FLPPLYSLVF
60 70 80 90 100
VFGLLGNSVV VLVLFKYKRL RSMTDVYLLN LAISDLLFVF SLPFWGYYAA
110 120 130 140 150
DQWVFGLGLC KMISWMYLVG FYSGIFFVML MSIDRYLAIV HAVFSLRART
160 170 180 190 200
LTYGVITSLA TWSVAVFASL PGFLFSTCYT ERNHTYCKTK YSLNSTTWKV
210 220 230 240 250
LSSLEINILG LVIPLGIMLF CYSMIIRTLQ HCKNEKKNKA VKMIFAVVVL
260 270 280 290 300
FLGFWTPYNI VLFLETLVEL EVLQDCTFER YLDYAIQATE TLAFVHCCLN
310 320 330 340 350
PIIYFFLGEK FRKYILQLFK TCRGLFVLCQ YCGLLQIYSA DTPSSSYTQS
360
TMDHDLHDAL
Length:360
Mass (Da):41,403
Last modified:October 1, 1996 - v1
Checksum:i51EBE12AD1FAFABF
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_010669130L → V.1 Publication1
Natural variantiVAR_010670178C → S.1 PublicationCorresponds to variant rs753825374dbSNPEnsembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS2656.1.
PIRiA57160.
RefSeqiNP_005499.1. NM_005508.4.
XP_016861176.1. XM_017005687.1.
UniGeneiHs.184926.

Genome annotation databases

EnsembliENST00000330953; ENSP00000332659; ENSG00000183813.
GeneIDi1233.
KEGGihsa:1233.
UCSCiuc003cfg.2. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Web resourcesi

Wikipedia

CC chemokine receptors entry

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS2656.1.
PIRiA57160.
RefSeqiNP_005499.1. NM_005508.4.
XP_016861176.1. XM_017005687.1.
UniGeneiHs.184926.

3D structure databases

ProteinModelPortaliP51679.
SMRiP51679.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi107638. 6 interactors.
DIPiDIP-5848N.
IntActiP51679. 1 interactor.
MINTiMINT-1525168.
STRINGi9606.ENSP00000332659.

Chemistry databases

BindingDBiP51679.
ChEMBLiCHEMBL2414.
GuidetoPHARMACOLOGYi61.

Protein family/group databases

GPCRDBiSearch...

PTM databases

iPTMnetiP51679.
PhosphoSitePlusiP51679.

Polymorphism and mutation databases

BioMutaiCCR4.
DMDMi1705894.

Proteomic databases

PaxDbiP51679.
PeptideAtlasiP51679.
PRIDEiP51679.

Protocols and materials databases

DNASUi1233.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000330953; ENSP00000332659; ENSG00000183813.
GeneIDi1233.
KEGGihsa:1233.
UCSCiuc003cfg.2. human.

Organism-specific databases

CTDi1233.
DisGeNETi1233.
GeneCardsiCCR4.
HGNCiHGNC:1605. CCR4.
HPAiHPA031613.
MIMi604836. gene.
neXtProtiNX_P51679.
OpenTargetsiENSG00000183813.
PharmGKBiPA26169.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3656. Eukaryota.
ENOG410XRW9. LUCA.
GeneTreeiENSGT00760000118785.
HOGENOMiHOG000234122.
HOVERGENiHBG106917.
InParanoidiP51679.
KOiK04179.
OMAiKFRKYIV.
OrthoDBiEOG091G0B7A.
PhylomeDBiP51679.
TreeFamiTF330966.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000121966-MONOMER.
ReactomeiR-HSA-380108. Chemokine receptors bind chemokines.
R-HSA-418594. G alpha (i) signalling events.
SIGNORiP51679.

Miscellaneous databases

GeneWikiiCCR4.
GenomeRNAii1233.
PROiP51679.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000183813.
CleanExiHS_CCR4.
ExpressionAtlasiP51679. baseline and differential.
GenevisibleiP51679. HS.

Family and domain databases

InterProiIPR002239. Chemokine_CCR4.
IPR000355. Chemokine_rcpt.
IPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
[Graphical view]
PfamiPF00001. 7tm_1. 1 hit.
[Graphical view]
PRINTSiPR00657. CCCHEMOKINER.
PR01109. CHEMOKINER4.
PR00237. GPCRRHODOPSN.
SMARTiSM01381. 7TM_GPCR_Srsx. 1 hit.
[Graphical view]
PROSITEiPS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiCCR4_HUMAN
AccessioniPrimary (citable) accession number: P51679
Secondary accession number(s): Q9ULY6, Q9ULY7
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: October 1, 1996
Last modified: November 2, 2016
This is version 145 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. 7-transmembrane G-linked receptors
    List of 7-transmembrane G-linked receptor entries
  2. Human cell differentiation molecules
    CD nomenclature of surface proteins of human leucocytes and list of entries
  3. Human chromosome 3
    Human chromosome 3: entries, gene names and cross-references to MIM
  4. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  5. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  6. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  7. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.