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CCR4 C-C motif chemokine receptor 4 [ Homo sapiens (human) ]

Gene ID: 1233, updated on 11-Apr-2024

Summary

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Official Symbol
CCR4provided by HGNC
Official Full Name
C-C motif chemokine receptor 4provided by HGNC
Primary source
HGNC:HGNC:1605
See related
Ensembl:ENSG00000183813 MIM:604836; AllianceGenome:HGNC:1605
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
CKR4; K5-5; CD194; CMKBR4; ChemR13; CC-CKR-4; HGCN:14099
Summary
The protein encoded by this gene belongs to the G-protein-coupled receptor family . It is a receptor for the CC chemokine - MIP-1, RANTES, TARC and MCP-1. Chemokines are a group of small polypeptide, structurally related molecules that regulate cell trafficking of various types of leukocytes. The chemokines also play fundamental roles in the development, homeostasis, and function of the immune system, and they have effects on cells of the central nervous system as well as on endothelial cells involved in angiogenesis or angiostasis. [provided by RefSeq, Jul 2008]
Expression
Biased expression in appendix (RPKM 6.5), urinary bladder (RPKM 6.3) and 12 other tissues See more
Orthologs
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Genomic context

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Location:
3p22.3
Exon count:
2
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 3 NC_000003.12 (32951644..32956349)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 3 NC_060927.1 (32953438..32958143)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 3 NC_000003.11 (32993136..32997841)

Chromosome 3 - NC_000003.12Genomic Context describing neighboring genes Neighboring gene ReSE screen-validated silencer GRCh37_chr3:32828513-32828689 Neighboring gene ribosomal protein L23a pseudogene 43 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr3:32841241-32842000 Neighboring gene Sharpr-MPRA regulatory region 2511 Neighboring gene H3K27ac hESC enhancer GRCh37_chr3:32859949-32860530 Neighboring gene MPRA-validated peak4592 silencer Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr3:32877349-32877906 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr3:32878590-32879187 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr3:32879188-32879784 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr3:32880383-32880978 Neighboring gene tripartite motif containing 71 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr3:32885158-32885753 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:32888797-32889377 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:32895307-32895816 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:32897845-32898520 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr3:32902307-32902911 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:32905556-32906320 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr3:32910977-32911780 Neighboring gene NANOG-H3K4me1 hESC enhancer GRCh37_chr3:32914193-32914996 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 14179 Neighboring gene ReSE screen-validated silencer GRCh37_chr3:32944496-32944651 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 14180 Neighboring gene MPRA-validated peak4594 silencer Neighboring gene ReSE screen-validated silencer GRCh37_chr3:32978284-32978481 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr3:32981295-32981797 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 14181 Neighboring gene uncharacterized LOC107986072 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 19640 Neighboring gene galactosidase beta 1 Neighboring gene H3K27ac hESC enhancer GRCh37_chr3:33038929-33039428 Neighboring gene SEC13 homolog, nuclear pore and COPII coat complex component pseudogene 1

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. Blockade of CCR4 breaks immune tolerance in chronic hepatitis B patients by modulating regulatory pathways. Khanam A, et al. J Transl Med, 2023 Apr 21. PMID 37081509, Free PMC Article
  2. Upregulation of CCR4 in activated CD8(+) T cells indicates enhanced lung homing in patients with severe acute SARS-CoV-2 infection. Spoerl S, et al. Eur J Immunol, 2021 Jun. PMID 33784417, Free PMC Article
  3. C-C chemokine receptor 4 expression in CD8+ cutaneous T-cell lymphomas and lymphoproliferative disorders, and its implications for diagnosis and treatment. Geller S, et al. Histopathology, 2020 Jan. PMID 31355940, Free PMC Article
  4. CCR4 Expression in Tumor-Infiltrating Regulatory T Cells in Patients with Squamous Cell Carcinoma of the Lung: A Prognostic Factor for Relapse and Survival. Asai N, et al. Cancer Invest, 2019. PMID 30907146
  5. CCR4 Expression Is Associated With Poor Prognosis in Patients With Early Stage (pN0) Oral Tongue Cancer. Wang L, et al. J Oral Maxillofac Surg, 2019 Feb. PMID 30395826

See all (120) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. CCR4-NOT differentially controls host versus virus poly(a)-tail length and regulates HCMV infection.
    Title: CCR4-NOT differentially controls host versus virus poly(a)-tail length and regulates HCMV infection.
  2. Blockade of CCR4 breaks immune tolerance in chronic hepatitis B patients by modulating regulatory pathways.
    Title: Blockade of CCR4 breaks immune tolerance in chronic hepatitis B patients by modulating regulatory pathways.
  3. Contributions of Ccr4 and Gcn2 to the Translational Response of C. neoformans to Host-Relevant Stressors and Integrated Stress Response Induction.
    Title: Contributions of Ccr4 and Gcn2 to the Translational Response of C. neoformans to Host-Relevant Stressors and Integrated Stress Response Induction.
  4. FOXP3/HAT1 Axis Controls Treg Infiltration in the Tumor Microenvironment by Inducing CCR4 Expression in Breast Cancer.
    Title: FOXP3/HAT1 Axis Controls Treg Infiltration in the Tumor Microenvironment by Inducing CCR4 Expression in Breast Cancer.
  5. Targeting CCL2-CCR4 axis suppress cell migration of head and neck squamous cell carcinoma.
    Title: Targeting CCL2-CCR4 axis suppress cell migration of head and neck squamous cell carcinoma.
  6. RNF219 attenuates global mRNA decay through inhibition of CCR4-NOT complex-mediated deadenylation.
    Title: RNF219 attenuates global mRNA decay through inhibition of CCR4-NOT complex-mediated deadenylation.
  7. Immune signature of CCR7(+) central memory T cells associates with disease severity and Immunoglobulin E in bronchial asthma.
    Title: Immune signature of CCR7(+) central memory T cells associates with disease severity and Immunoglobulin E in bronchial asthma.
  8. Tumors establish resistance to immunotherapy by regulating Treg recruitment via CCR4.
    Title: Tumors establish resistance to immunotherapy by regulating T(reg) recruitment via CCR4.
  9. Identification of Phosphorylated Amino Acids in Human TNRC6A C-Terminal Region and Their Effects on the Interaction with the CCR4-NOT Complex.
    Title: Identification of Phosphorylated Amino Acids in Human TNRC6A C-Terminal Region and Their Effects on the Interaction with the CCR4-NOT Complex.
  10. MiR-532-5p Suppresses Migration and Invasion of Lung Cancer Cells Through Inhibiting CCR4.
    Title: MiR-532-5p Suppresses Migration and Invasion of Lung Cancer Cells Through Inhibiting CCR4.
Submit: New GeneRIF Correction See all GeneRIFs (92)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

EBI GWAS Catalog

Description
Multiple common variants for celiac disease influencing immune gene expression.
EBI GWAS Catalog

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

HIV-1 interactions

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Protein interactions

Protein Gene Interaction Pubs
Envelope surface glycoprotein gp120 env An envelope-mediated fusion assay demonstrates low HIV-1 gp120 use of CCR4 as a coreceptor for some primary HIV-1 isolates; treatment of PBMC with CCL22 causes down-modulation of endogenous CCR4 but has no significant effect on HIV-1 entry PubMed
Tat tat CCR4 is upregulated by HIV-1 Tat treatment in human epithelial cells PubMed
Vif vif HIV-1 Vif upregulates the expression of chemokine (C-C motif) receptor 4 (CCR4) in Vif-expression T cells PubMed

Go to the HIV-1, Human Interaction Database

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Clone Names

  • MGC88293

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables C-C chemokine binding IBA
Inferred from Biological aspect of Ancestor
more info
  
enables C-C chemokine receptor activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables chemokine receptor activity TAS
Traceable Author Statement
more info
 PubMed 
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
Process Evidence Code Pubs
involved_in calcium-mediated signaling IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in cell chemotaxis IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in chemokine-mediated signaling pathway IEA
Inferred from Electronic Annotation
more info
  
involved_in chemotaxis TAS
Traceable Author Statement
more info
 PubMed 
involved_in homeostasis of number of cells IEA
Inferred from Electronic Annotation
more info
  
involved_in immune response IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in inflammatory response IEA
Inferred from Electronic Annotation
more info
  
involved_in interneuron migration IEA
Inferred from Electronic Annotation
more info
  
involved_in positive regulation of cytosolic calcium ion concentration IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in positive regulation of positive chemotaxis IEA
Inferred from Electronic Annotation
more info
  
involved_in response to bacterium IEA
Inferred from Electronic Annotation
more info
  
involved_in tolerance induction IEA
Inferred from Electronic Annotation
more info
  
Component Evidence Code Pubs
is_active_in external side of plasma membrane IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in neuronal cell body IEA
Inferred from Electronic Annotation
more info
  
located_in plasma membrane IDA
Inferred from Direct Assay
more info
  
located_in plasma membrane TAS
Traceable Author Statement
more info
  

General protein information

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Preferred Names
C-C chemokine receptor type 4
Names
C-C CKR-4
CCR-4
chemokine (C-C motif) receptor 4
chemokine (C-C) receptor 4
NP_005499.1
XP_016861176.1
XP_054201145.1

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

  1. NM_005508.5 → NP_005499.1  C-C chemokine receptor type 4

    See identical proteins and their annotated locations for NP_005499.1

    Status: REVIEWED

    Source sequence(s)
    AC137560, BC071751
    Consensus CDS
    CCDS2656.1
    UniProtKB/Swiss-Prot
    P51679, Q9ULY6, Q9ULY7
    UniProtKB/TrEMBL
    A0A024R2J7, A0N0Q1
    Related
    ENSP00000332659.5, ENST00000330953.6
    Conserved Domains (1) summary
    cd14984
    Location:40 → 315
    7tmA_Chemokine_R; classical and atypical chemokine receptors, member of the class A family of seven-transmembrane G protein-coupled receptors

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000003.12 Reference GRCh38.p14 Primary Assembly

    Range
    32951644..32956349
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_017005687.2 → XP_016861176.1  C-C chemokine receptor type 4 isoform X1

    UniProtKB/Swiss-Prot
    P51679, Q9ULY6, Q9ULY7
    UniProtKB/TrEMBL
    A0A024R2J7, A0N0Q1
    Conserved Domains (1) summary
    cd14984
    Location:40 → 315
    7tmA_Chemokine_R; classical and atypical chemokine receptors, member of the class A family of seven-transmembrane G protein-coupled receptors

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060927.1 Alternate T2T-CHM13v2.0

    Range
    32953438..32958143
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054345170.1 → XP_054201145.1  C-C chemokine receptor type 4 isoform X1

    UniProtKB/Swiss-Prot
    P51679, Q9ULY6, Q9ULY7
    UniProtKB/TrEMBL
    A0A024R2J7, A0N0Q1
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
P51679.1 GenPept UniProtKB/Swiss-Prot:P51679

Gene LinkOut

The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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