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 functi... See more...

Aliases for CCR4 Gene

Aliases for CCR4 Gene

  • C-C Motif Chemokine Receptor 4 2 3 5
  • CC-CKR-4 2 3 4
  • CMKBR4 2 3 4
  • K5-5 2 3 4
  • Chemokine (C-C Motif) Receptor 4 2 3
  • C-C Chemokine Receptor Type 4 3 4
  • C-C CKR-4 3 4
  • ChemR13 2 3
  • CD194 2 3
  • CCR-4 3 4
  • CKR4 2 3
  • Chemokine (C-C) Receptor 4 3
  • CD194 Antigen 4
  • HGCN:14099 3
  • CCR4 5

External Ids for CCR4 Gene

Previous GeneCards Identifiers for CCR4 Gene

  • GC03U990019
  • GC03P032841
  • GC03P032966
  • GC03P032964
  • GC03P032968

Summaries for CCR4 Gene

Entrez Gene Summary for CCR4 Gene

  • 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]

GeneCards Summary for CCR4 Gene

CCR4 (C-C Motif Chemokine Receptor 4) is a Protein Coding gene. Diseases associated with CCR4 include Mycosis Fungoides and Peripheral T-Cell Lymphoma. Among its related pathways are Peptide ligand-binding receptors and Signaling by GPCR. Gene Ontology (GO) annotations related to this gene include G protein-coupled receptor activity and C-C chemokine receptor activity. An important paralog of this gene is CCR1.

UniProtKB/Swiss-Prot Summary for CCR4 Gene

  • 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.

Tocris Summary for CCR4 Gene

  • Chemokine CC receptors (CCRs) predominantly recognize CC chemokines. CC chemokines are distinguished by having four conserved cysteines, with the first two cysteines being adjacent to each other. There are 10 chemokine CC receptors.

Gene Wiki entry for CCR4 Gene

No data available for CIViC Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for CCR4 Gene

Genomics for CCR4 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for CCR4 Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH03J032951 Promoter/Enhancer 1.4 EPDnew Ensembl ENCODE 250.7 +2.2 2223 5.2 NCOR1 ZNF592 NFIC TAL1 SMARCA4 ZBTB33 TCF12 ATF2 TEAD4 ZNF3 CCR4 HSALNG0025036 TMPPE
GH03J032940 Promoter 0.3 EPDnew 250.4 -10.8 -10822 0.1 piR-39099-156 piR-33422-268 piR-31470-330 CCR4 SUGT1P2 CNOT10-AS1 CNOT10 TRIM71
GH03J033044 Enhancer 1.5 FANTOM5 Ensembl ENCODE dbSUPER 21.9 +98.6 98646 13.6 NCOR1 MYC IKZF1 ZNF592 NFIC NONO REST HES1 MBD2 MNT HSALNG0025043 piR-38051-185 CNOT10 CCR4 GLB1 CLASP2 SEC13P1 TMPPE SUGT1P2 CNOT10-AS1
GH03J033716 Promoter/Enhancer 1.9 FANTOM5 Ensembl ENCODE CraniofacialAtlas 11.4 +766.1 766145 3.4 ZNF654 MYC ZNF600 IKZF1 JUND ZNF592 ATF2 CEBPA BRCA1 NFIC CLASP2 UBP1 PDCD6IP GLB1 CCR4 ENSG00000271643 TMPPE FBXL2 HSALNG0025072 lnc-UBP1-5
GH03J033019 Enhancer 0.5 FANTOM5 Ensembl 22 +68.0 68046 2 FOXA2 FOXA1 LOC107986073 CCR4 SUGT1P2 CNOT10-AS1 CNOT10 GLB1 TMPPE SEC13P1 CRTAP RF00017-3570
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around CCR4 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for CCR4

Top Transcription factor binding sites by QIAGEN in the CCR4 gene promoter:
  • AhR
  • c-Ets-1
  • Pax-2
  • Pax-2a
  • Pax-2b
  • POU6F1 (c2)
  • PPAR-alpha
  • STAT1
  • XBP-1
  • Zic3

Genomic Locations for CCR4 Gene

Latest Assembly
chr3:32,951,555-32,956,349
(GRCh38/hg38)
Size:
4,795 bases
Orientation:
Plus strand

Previous Assembly
chr3:32,993,136-32,997,841
(GRCh37/hg19 by Entrez Gene)
Size:
4,706 bases
Orientation:
Plus strand

chr3:32,993,066-32,997,841
(GRCh37/hg19 by Ensembl)
Size:
4,776 bases
Orientation:
Plus strand

Genomic View for CCR4 Gene

Genes around CCR4 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
CCR4 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for CCR4 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for CCR4 Gene

Proteins for CCR4 Gene

  • Protein details for CCR4 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P51679-CCR4_HUMAN
    Recommended name:
    C-C chemokine receptor type 4
    Protein Accession:
    P51679
    Secondary Accessions:
    • Q9ULY6
    • Q9ULY7

    Protein attributes for CCR4 Gene

    Size:
    360 amino acids
    Molecular mass:
    41403 Da
    Quaternary structure:
    No Data Available

neXtProt entry for CCR4 Gene

Post-translational modifications for CCR4 Gene

  • In natural killer cells, CCL22 binding induces phosphorylation on yet undefined Ser/Thr residues, most probably by beta-adrenergic receptor kinases 1 and 2.
  • Glycosylation at Asn183 and Asn194
  • Modification sites at PhosphoSitePlus

Other Protein References for CCR4 Gene

ENSEMBL proteins:
REFSEQ proteins:

Antibodies for research

  • Abcam antibodies for CCR4

No data available for DME Specific Peptides for CCR4 Gene

Domains & Families for CCR4 Gene

Gene Families for CCR4 Gene

HGNC:
IUPHAR :
Human Protein Atlas (HPA):
  • CD markers
  • G-protein coupled receptors
  • Predicted membrane proteins

Protein Domains for CCR4 Gene

InterPro:
Blocks:
  • Chemokine receptor signature
  • C-C chemokine receptor type 4 signature

Suggested Antigen Peptide Sequences for CCR4 Gene

GenScript: Design optimal peptide antigens:
  • cDNA FLJ75821, highly similar to Homo sapiens chemokine (C-C motif) receptor 4 (CCR4), mRNA (A0N0Q1_HUMAN)
  • K5-5 (CCR4_HUMAN)

Graphical View of Domain Structure for InterPro Entry

P51679

UniProtKB/Swiss-Prot:

CCR4_HUMAN :
  • Belongs to the G-protein coupled receptor 1 family.
Family:
  • Belongs to the G-protein coupled receptor 1 family.
genes like me logo Genes that share domains with CCR4: view

Function for CCR4 Gene

Molecular function for CCR4 Gene

UniProtKB/Swiss-Prot Function:
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.
GENATLAS Biochemistry:
chemokine CC,beta,receptor 4,with high affinity binding for basophil chemoattractant,G protein coupled receptor superfamily,specific receptor for thymus and activation-regulated chemokine

Phenotypes From GWAS Catalog for CCR4 Gene

Gene Ontology (GO) - Molecular Function for CCR4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004930 G protein-coupled receptor activity IEA --
GO:0004950 chemokine receptor activity TAS 7642634
GO:0005515 protein binding IPI 28381538
GO:0016493 C-C chemokine receptor activity IBA 21873635
GO:0019957 C-C chemokine binding IBA 21873635
genes like me logo Genes that share ontologies with CCR4: view
genes like me logo Genes that share phenotypes with CCR4: view

Animal Models for CCR4 Gene

MGI Knock Outs for CCR4:

Animal Models for research

  • Taconic Biosciences Mouse Models for CCR4

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for CCR4

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for CCR4 Gene

Localization for CCR4 Gene

Subcellular locations from UniProtKB/Swiss-Prot for CCR4 Gene

Cell membrane. Multi-pass membrane protein.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for CCR4 gene
Compartment Confidence
plasma membrane 5
extracellular 2
nucleus 2
cytoskeleton 1
mitochondrion 1
endoplasmic reticulum 1
endosome 1
cytosol 1
lysosome 1
golgi apparatus 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Plasma membrane (3)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for CCR4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005886 plasma membrane TAS --
GO:0005887 integral component of plasma membrane TAS 7642634
GO:0009897 external side of plasma membrane IEA,IBA 21873635
GO:0016020 membrane IEA --
GO:0016021 integral component of membrane IEA --
genes like me logo Genes that share ontologies with CCR4: view

Pathways & Interactions for CCR4 Gene

genes like me logo Genes that share pathways with CCR4: view

Pathways by source for CCR4 Gene

SIGNOR curated interactions for CCR4 Gene

Is activated by:

Gene Ontology (GO) - Biological Process for CCR4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001764 neuron migration IEA --
GO:0002507 tolerance induction IEA --
GO:0006935 chemotaxis TAS 7642634
GO:0006954 inflammatory response TAS,IEA --
GO:0006955 immune response TAS,IBA 21873635
genes like me logo Genes that share ontologies with CCR4: view

Drugs & Compounds for CCR4 Gene

(29) Drugs for CCR4 Gene - From: DrugBank, ClinicalTrials, ApexBio, DGIdb, IUPHAR, HMDB, Tocris, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Mogamulizumab Approved, Investigational Pharma Target, antagonist, antibody Therapeutic Antibodies 29
Fludarabine Approved Pharma DNA synthsis inhibitor 1633,1633
Procaine Approved, Investigational, Vet_approved Pharma 52
Plerixafor Approved Pharma antagonist 0
FLX475 Investigational Pharma Target, antagonist 0

(12) Additional Compounds for CCR4 Gene - From: IUPHAR and Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
[<sup>125</sup>I]CCL17
Agonist, Full agonist
[<sup>125</sup>I]CCL27
Agonist

(5) Tocris Compounds for CCR4 Gene

Compound Action Cas Number
DAPTA Chemokine receptor 5 (CCR5) antagonist 106362-34-9
J 113863 Potent CCR1 chemokine receptor antagonist 353791-85-2
RS 102895 hydrochloride CCR2b chemokine receptor antagonist 1173022-16-6
RS 504393 Highly selective CCR2 chemokine receptor antagonist 300816-15-3
ZK 756326 Selective, non-peptide CCR8 agonist 874911-96-3

(1) ApexBio Compounds for CCR4 Gene

Compound Action Cas Number
C 021 dihydrochloride Potent CCR4 antagonist 864289-85-0
genes like me logo Genes that share compounds with CCR4: view

Drug products for research

Transcripts for CCR4 Gene

mRNA/cDNA for CCR4 Gene

1 REFSEQ mRNAs :
6 NCBI additional mRNA sequence :
1 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for CCR4

Alternative Splicing Database (ASD) splice patterns (SP) for CCR4 Gene

No ASD Table

Relevant External Links for CCR4 Gene

GeneLoc Exon Structure for
CCR4

Expression for CCR4 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for CCR4 Gene

mRNA differential expression in normal tissues according to GTEx for CCR4 Gene

This gene is overexpressed in Whole Blood (x15.8), Spleen (x4.7), and Lung (x4.6).

Protein differential expression in normal tissues from HIPED for CCR4 Gene

This gene is overexpressed in Peripheral blood mononuclear cells (69.0).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB and MOPED for CCR4 Gene



Protein tissue co-expression partners for CCR4 Gene

- Elite partner

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for CCR4

SOURCE GeneReport for Unigene cluster for CCR4 Gene:

Hs.184926

mRNA Expression by UniProt/SwissProt for CCR4 Gene:

P51679-CCR4_HUMAN
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.

Evidence on tissue expression from TISSUES for CCR4 Gene

  • Blood(4.4)
  • Spleen(4.4)
  • Lymph node(2.1)
genes like me logo Genes that share expression patterns with CCR4: view

Primer products for research

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery and Phenotype-based relationships between genes and organs from Gene ORGANizer for CCR4 Gene

Orthologs for CCR4 Gene

This gene was present in the common ancestor of chordates.

Orthologs for CCR4 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia CCR4 29 30
  • 99.91 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia CCR4 29 30
  • 87.59 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia CCR4 29 30
  • 87.09 (n)
OneToOne
Mouse
(Mus musculus)
Mammalia Ccr4 29 16 30
  • 82.96 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Ccr4 29
  • 81.48 (n)
Oppossum
(Monodelphis domestica)
Mammalia CCR4 30
  • 77 (a)
OneToOne
Platypus
(Ornithorhynchus anatinus)
Mammalia CCR4 30
  • 72 (a)
OneToOne
Chicken
(Gallus gallus)
Aves CCR4 29 30
  • 63.29 (n)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia CCR4 30
  • 58 (a)
OneToOne
Zebrafish
(Danio rerio)
Actinopterygii LOC100329837 29
  • 52.35 (n)
BX511173.1 30
  • 40 (a)
ManyToMany
BX537113.1 30 30
  • 40 (a)
ManyToMany
ccr8.1 30 30
  • 37 (a)
ManyToMany
CABZ01093075.1 30
  • 34 (a)
ManyToMany
Species where no ortholog for CCR4 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Baker's yeast (Saccharomyces cerevisiae)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Fruit Fly (Drosophila melanogaster)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Rainbow Trout (Oncorhynchus mykiss)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Squirt (Ciona savignyi)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Thale Cress (Arabidopsis thaliana)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Tropical Clawed Frog (Silurana tropicalis)
  • Wheat (Triticum aestivum)
  • Worm (Caenorhabditis elegans)

Evolution for CCR4 Gene

ENSEMBL:
Gene Tree for CCR4 (if available)
TreeFam:
Gene Tree for CCR4 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for CCR4: view image
Alliance of Genome Resources:
Additional Orthologs for CCR4

Paralogs for CCR4 Gene

genes like me logo Genes that share paralogs with CCR4: view

Variants for CCR4 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for CCR4 Gene

SNP ID Clinical significance and condition Chr 03 pos Variation AA Info Type
rs753825374 -- p.Cys178Ser
VAR_010669 -- p.Leu130Val

dbSNP identifiers (rs#s) for variants without ClinVar clinical significance for CCR4 Gene

All consequence types are included: molecular consequences (e.g. missense, synonymous), and location-based (e.g. intron, upstream).

Structural Variations from Database of Genomic Variants (DGV) for CCR4 Gene

Variant ID Type Subtype PubMed ID
nsv1003285 CNV gain 25217958
nsv508909 CNV insertion 20534489
nsv998302 CNV gain 25217958

Variation tolerance for CCR4 Gene

Residual Variation Intolerance Score: 18.5% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 0.89; 18.53% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for CCR4 Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
CCR4
Leiden Open Variation Database (LOVD)
CCR4

SNP Genotyping and Copy Number Assays for research

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for CCR4 Gene

Disorders for CCR4 Gene

MalaCards: The human disease database

(31) MalaCards diseases for CCR4 Gene - From: COP and GCD

Disorder Aliases PubMed IDs
mycosis fungoides
  • mycosis fungoides lymphoma
peripheral t-cell lymphoma
  • peripheral t cell lymphoma
cutaneous t cell lymphoma
  • cutaneous t-cell lymphoma
allergic contact dermatitis
  • contact dermatitis, allergic
intermediate uveitis
  • chronic cyclitis
- elite association - COSMIC cancer census association via MalaCards
Search CCR4 in MalaCards View complete list of genes associated with diseases

Additional Disease Information for CCR4

Human Genome Epidemiology Navigator
(HuGE)
Atlas
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
Open Targets Platform
genes like me logo Genes that share disorders with CCR4: view

No data available for UniProtKB/Swiss-Prot and Genatlas for CCR4 Gene

Publications for CCR4 Gene

  1. New variations of human CC-chemokine receptors CCR3 and CCR4. (PMID: 11196669) Kato H … Tokunaga K (Genes and immunity 1999) 3 4 22 40
  2. Association screen for atopic dermatitis candidate gene regions using microsatellite markers in pooled DNA samples. (PMID: 17117949) Hoffjan S … Epplen JT (International journal of immunogenetics 2006) 3 22 40
  3. Lack of association of CCR4 single nucleotide polymorphism with atopic dermatitis in Japanese patients. (PMID: 15202833) Tsunemi Y … Tamaki K (Acta dermato-venereologica 2004) 3 22 40
  4. Human NK cells express CC chemokine receptors 4 and 8 and respond to thymus and activation-regulated chemokine, macrophage-derived chemokine, and I-309. (PMID: 10754297) Inngjerdingen M … Maghazachi AA (Journal of immunology (Baltimore, Md. : 1950) 2000) 3 4 22
  5. The chemokine receptor CCR4 in vascular recognition by cutaneous but not intestinal memory T cells. (PMID: 10466728) Campbell JJ … Butcher EC (Nature 1999) 3 4 22

Products for CCR4 Gene

Sources for CCR4 Gene