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

    Gene ID: 1233, updated on 2-Nov-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
    mouse all
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    Genomic context

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    See CCR4 in Genome Data Viewer
    Location:
    3p22.3
    Exon count:
    2
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 3 NC_000003.12 (32951644..32956349)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 3 NC_060927.1 (32953438..32958143)
    RS_2024_09 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 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. Adenoid-derived TH2 cells reactive to allergen and recall antigen express CC chemokine receptor 4. Banwell ME, et al. J Allergy Clin Immunol, 2003 Dec. PMID 14657875
    2. PABP Cooperates with the CCR4-NOT Complex to Promote mRNA Deadenylation and Block Precocious Decay. Yi H, et al. Mol Cell, 2018 Jun 21. PMID 29932901
    3. CCR4 mutations associated with superior outcome of adult T-cell leukemia/lymphoma under mogamulizumab treatment. Sakamoto Y, et al. Blood, 2018 Aug 16. PMID 29930010
    4. Frequent expression of CCR4 in adult T-cell leukemia and human T-cell leukemia virus type 1-transformed T cells. Yoshie O, et al. Blood, 2002 Mar 1. PMID 11861261
    5. Circulating allergen-specific T(H)2 lymphocytes: CCR4(+) rather than CLA(+) is the predominant phenotype in peanut-allergic subjects. Blom LH, et al. J Allergy Clin Immunol, 2018 Apr. PMID 29225086

    See all (122) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. The CCL2-CCR4 axis promotes Regulatory T cell trafficking to canine glioma tissues.
      Title: The CCL2-CCR4 axis promotes Regulatory T cell trafficking to canine glioma tissues.
    2. 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.
    3. 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.
    4. 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.
    5. 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.
    6. 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.
    7. 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.
    8. 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.
    9. Tumors establish resistance to immunotherapy by regulating Treg recruitment via CCR4.
      Title: Tumors establish resistance to immunotherapy by regulating T(reg) recruitment via CCR4.
    10. 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.
    Submit: New GeneRIF Correction See all GeneRIFs (93)

    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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    NEW Try the new Transcript table

    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_2024_08

    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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