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CCR3 C-C motif chemokine receptor 3 [ Homo sapiens (human) ]

Gene ID: 1232, updated on 17-Jun-2019

Summary

Official Symbol
CCR3provided by HGNC
Official Full Name
C-C motif chemokine receptor 3provided by HGNC
Primary source
HGNC:HGNC:1604
See related
Ensembl:ENSG00000183625 MIM:601268
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
CKR3; CD193; CMKBR3; CC-CKR-3
Summary
The protein encoded by this gene is a receptor for C-C type chemokines. It belongs to family 1 of the G protein-coupled receptors. This receptor binds and responds to a variety of chemokines, including eotaxin (CCL11), eotaxin-3 (CCL26), MCP-3 (CCL7), MCP-4 (CCL13), and RANTES (CCL5). It is highly expressed in eosinophils and basophils, and is also detected in TH1 and TH2 cells, as well as in airway epithelial cells. This receptor may contribute to the accumulation and activation of eosinophils and other inflammatory cells in the allergic airway. It is also known to be an entry co-receptor for HIV-1. This gene and seven other chemokine receptor genes form a chemokine receptor gene cluster on the chromosomal region 3p21. Alternatively spliced transcript variants have been described. [provided by RefSeq, Sep 2009]
Expression
Low expression observed in reference dataset See more
Orthologs

Genomic context

See CCR3 in Genome Data Viewer
Location:
3p21.31
Exon count:
6
Annotation release Status Assembly Chr Location
109.20190607 current GRCh38.p13 (GCF_000001405.39) 3 NC_000003.12 (46210699..46266706)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 3 NC_000003.11 (46283872..46308197)

Chromosome 3 - NC_000003.12Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC105377067 Neighboring gene fms related tyrosine kinase 1 pseudogene 1 Neighboring gene C-C motif chemokine receptor 1 Neighboring gene ubiquinol-cytochrome c reductase core protein 2 pseudogene 1 Neighboring gene C-C motif chemokine receptor 2

Genomic regions, transcripts, and products

Expression

  • 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

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

Phenotypes

NHGRI GWAS Catalog

Description
Genome-wide association analysis identifies new susceptibility loci for Behçet's disease and epistasis between HLA-B*51 and ERAP1.
NHGRI GWA Catalog
Genome-wide association replicates the association of Duffy antigen receptor for chemokines (DARC) polymorphisms with serum monocyte chemoattractant protein-1 (MCP-1) levels in Hispanic children.
NHGRI GWA Catalog
Genome-wide association study of celiac disease in North America confirms FRMD4B as new celiac locus.
NHGRI GWA Catalog
Genome-Wide Association Study of CSF Levels of 59 Alzheimer's Disease Candidate Proteins: Significant Associations with Proteins Involved in Amyloid Processing and Inflammation.
NHGRI GWA Catalog
Multiple common variants for celiac disease influencing immune gene expression.
NHGRI GWA Catalog
Newly identified genetic risk variants for celiac disease related to the immune response.
NHGRI GWA Catalog
Novel genetic loci identified for the pathophysiology of childhood obesity in the Hispanic population.
NHGRI GWA Catalog

HIV-1 interactions

Protein interactions

Protein Gene Interaction Pubs
Envelope surface glycoprotein gp120 env The coreceptor-binding site in HIV-1 gp120 is centered around an anti-parallel beta-sheet structure 'bridging sheet domain'; mutations in and adjacent to this domain affect the use of coreceptors CCR3 and CCR8 by gp120 for virus entry PubMed
env CCR3 is an alternative coreceptor usage by R5-tropic HIV-1 type C gp120/gp41, although its usage frequency is less than that of CCR5 coreceptor PubMed
env HIV-1 gp120 utilization of CCR3 as a coreceptor facilitates infection by a more restricted subset of primary viruses, and binding of the CCR3 ligand, eotaxin, inhibits infection by these isolates PubMed
env Utilization of CCR3 and CCR5 as coreceptors of HIV-1 binding/fusion depends upon the sequence of the third variable (V3) region of the HIV-1 gp120 exterior envelope glycoprotein PubMed
env Macrophage-tropic HIV-1 can use CCR2b, and to a lesser extent CCR3, STRL33, and APJ, to infect cells; the V1/2 region of HIV-1 gp120 plays a more important role in governing the use of CCR2b, CCR3, STRL33, and APJ than for CXCR4 PubMed
env Amino acid N356 in conserved region 3 of HIV-1 gp120 and amino acids R440 and N448 in conserved region 4 of gp120 are three amino-acid determinants for CCR3 use as a coreceptor for HIV-1 entry into cells PubMed
env HIV-1 isolates showing CCR3 tropism are particularly efficient in using CMKLR1/ChemR23 as a co-receptor; some HIV-2 and SIV isolates also use CMKLR1/ChemR23 PubMed
Envelope transmembrane glycoprotein gp41 env CCR3 is an alternative coreceptor usage by R5-tropic HIV-1 type C gp120/gp41, although its usage frequency is less than that of CCR5 coreceptor PubMed
Nef nef HIV-1 Nef induces variable levels of CCR3 downregulation in different cell types PubMed
Tat tat HIV-1 Tat-mediated activation of the CB2R leads to altered expression and compartmentation of the beta-chemokine receptor CCR-3 PubMed
tat HIV-1 Tat-induced platelet activation requires the chemokine receptor CCR3 and beta3-integrin expression on platelets and calcium flux in platelets PubMed
tat HIV-1 Tat binds to CCR3 and displaces MCP-3 from this beta-chemokine receptor, an effect mediated by Tat amino acids 24-51 PubMed
tat HIV-1 Tat upregulates CCR3 expression on monocytes/macrophages, Fc epsilonRI+ cells and blood brain barrier cultures, and acts as a potent chemoattractant, indicating a role for Tat in HIV-1 pathogenesis and in promoting HIV-1 infectivity PubMed

Go to the HIV-1, Human Interaction Database

Pathways from BioSystems

  • Chemokine receptors bind chemokines, organism-specific biosystem (from REACTOME)
    Chemokine receptors bind chemokines, organism-specific biosystemChemokine receptors are cytokine receptors found on the surface of certain cells, which interact with a type of cytokine called a chemokine. Following interaction, these receptors trigger a flux of i...
  • Chemokine signaling pathway, organism-specific biosystem (from KEGG)
    Chemokine signaling pathway, organism-specific biosystemInflammatory immune response requires the recruitment of leukocytes to the site of inflammation upon foreign insult. Chemokines are small chemoattractant peptides that provide directional cues for th...
  • Chemokine signaling pathway, conserved biosystem (from KEGG)
    Chemokine signaling pathway, conserved biosystemInflammatory immune response requires the recruitment of leukocytes to the site of inflammation upon foreign insult. Chemokines are small chemoattractant peptides that provide directional cues for th...
  • Class A/1 (Rhodopsin-like receptors), organism-specific biosystem (from REACTOME)
    Class A/1 (Rhodopsin-like receptors), organism-specific biosystemRhodopsin-like receptors (class A/1) are the largest group of GPCRs and are the best studied group from a functional and structural point of view. They show great diversity at the sequence level and ...
  • Cytokine-cytokine receptor interaction, organism-specific biosystem (from KEGG)
    Cytokine-cytokine receptor interaction, organism-specific biosystemCytokines are soluble extracellular proteins or glycoproteins that are crucial intercellular regulators and mobilizers of cells engaged in innate as well as adaptive inflammatory host defenses, cell ...
  • Cytokine-cytokine receptor interaction, conserved biosystem (from KEGG)
    Cytokine-cytokine receptor interaction, conserved biosystemCytokines are soluble extracellular proteins or glycoproteins that are crucial intercellular regulators and mobilizers of cells engaged in innate as well as adaptive inflammatory host defenses, cell ...
  • G alpha (i) signalling events, organism-specific biosystem (from REACTOME)
    G alpha (i) signalling events, organism-specific biosystemThe classical signalling mechanism for G alpha (i) is inhibition of the cAMP dependent pathway through inhibition of adenylate cyclase. Decreased production of cAMP from ATP results in decreased act...
  • GPCR downstream signaling, organism-specific biosystem (from REACTOME)
    GPCR downstream signaling, organism-specific biosystemG protein-coupled receptors (GPCRs) are classically defined as the receptor, G-protein and downstream effectors, the alpha subunit of the G-protein being the primary signaling molecule. However, it h...
  • GPCR ligand binding, organism-specific biosystem (from REACTOME)
    GPCR ligand binding, organism-specific biosystemThere are more than 800 G-protein coupled receptor (GPCRs) in the human genome, making it the largest receptor superfamily. GPCRs are also the largest class of drug targets, involved in virtually all...
  • GPCRs, Class A Rhodopsin-like, organism-specific biosystem (from WikiPathways)
    GPCRs, Class A Rhodopsin-like, organism-specific biosystemThis pathway was created using the GPCRDB (Horn et al., 1998), http://www.gpcr.org/7tm/ (originally at http://www.cmbi.kun.nl/7tm/). The groupings are based on the GPCR phylogenetic tree available fr...
  • IL-3 Signaling Pathway, organism-specific biosystem (from WikiPathways)
    IL-3 Signaling Pathway, organism-specific biosystemInterleukin 3 (IL-3) is a potent growth factor belonging to the super family of cytokines. IL-3 is a 20- 32kDa glycoprotein involved in the process of hematopoiesis. It is involved in the proliferati...
  • IL1 and megakaryocytes in obesity, organism-specific biosystem (from WikiPathways)
    IL1 and megakaryocytes in obesity, organism-specific biosystemSchematic of the effects of interleukin (IL)1-beta/IL1R1 on megakaryocyte and platelet function. A high fat diet will cause megakaryocytes to produce platelets with an increase in both inflammatory a...
  • Lung fibrosis, organism-specific biosystem (from WikiPathways)
    Lung fibrosis, organism-specific biosystemLung fibrosis pathway linked to events (molecular initiating event, key events and associative events) in a putative Adverse Outcome Pathway for lung fibrosis.
  • Peptide GPCRs, organism-specific biosystem (from WikiPathways)
    Peptide GPCRs, organism-specific biosystem
    Peptide GPCRs
  • Peptide ligand-binding receptors, organism-specific biosystem (from REACTOME)
    Peptide ligand-binding receptors, organism-specific biosystemThese receptors, a subset of the Class A/1 (Rhodopsin-like) family, all bind peptide ligands which include the chemokines, opioids and somatostatins.
  • Signal Transduction, organism-specific biosystem (from REACTOME)
    Signal Transduction, organism-specific biosystemSignal transduction is a process in which extracellular signals elicit changes in cell state and activity. Transmembrane receptors sense changes in the cellular environment by binding ligands, such a...
  • Signaling by GPCR, organism-specific biosystem (from REACTOME)
    Signaling by GPCR, organism-specific biosystemG protein-coupled receptors (GPCRs; 7TM receptors; seven transmembrane domain receptors; heptahelical receptors; G protein-linked receptors [GPLR]) are the largest family of transmembrane receptors i...
  • Viral carcinogenesis, organism-specific biosystem (from KEGG)
    Viral carcinogenesis, organism-specific biosystemThere is a strong association between viruses and the development of human malignancies. We now know that at least six human viruses, Epstein-Barr virus (EBV), hepatitis B virus (HBV), hepatitis C vi...
  • Viral carcinogenesis, conserved biosystem (from KEGG)
    Viral carcinogenesis, conserved biosystemThere is a strong association between viruses and the development of human malignancies. We now know that at least six human viruses, Epstein-Barr virus (EBV), hepatitis B virus (HBV), hepatitis C vi...

Interactions

Products Interactant Other Gene Complex Source Pubs Description

General gene information

Markers

Homology

Clone Names

  • MGC102841

Gene Ontology Provided by GOA

Function Evidence Code Pubs
C-C chemokine binding IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
C-C chemokine binding IDA
Inferred from Direct Assay
more info
PubMed 
C-C chemokine receptor activity IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
chemokine binding IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
chemokine receptor activity TAS
Traceable Author Statement
more info
PubMed 
protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
Process Evidence Code Pubs
G protein-coupled receptor signaling pathway TAS
Traceable Author Statement
more info
 
adenylate cyclase-modulating G protein-coupled receptor signaling pathway TAS
Traceable Author Statement
more info
PubMed 
calcium-mediated signaling IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
cell adhesion TAS
Traceable Author Statement
more info
PubMed 
cell chemotaxis IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
cellular defense response TAS
Traceable Author Statement
more info
PubMed 
chemokine-mediated signaling pathway IEA
Inferred from Electronic Annotation
more info
 
chemotaxis IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
immune response IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
inflammatory response IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
positive regulation of angiogenesis IMP
Inferred from Mutant Phenotype
more info
PubMed 
positive regulation of cytosolic calcium ion concentration IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
positive regulation of endothelial cell proliferation IEA
Inferred from Electronic Annotation
more info
 
viral process IEA
Inferred from Electronic Annotation
more info
 
Component Evidence Code Pubs
cytoplasm IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
external side of plasma membrane IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
integral component of plasma membrane TAS
Traceable Author Statement
more info
PubMed 
plasma membrane TAS
Traceable Author Statement
more info
 

General protein information

Preferred Names
C-C chemokine receptor type 3
Names
C-C CKR-3
CC chemokine receptor 3
CCR-3
b-chemokine receptor
chemokine (C-C motif) receptor 3
eosinophil CC chemokine receptor 3
eosinophil eotaxin receptor

NCBI Reference Sequences (RefSeq)

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_001164680.2NP_001158152.1  C-C chemokine receptor type 3 isoform 3

    See identical proteins and their annotated locations for NP_001158152.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (4) has an alternate internal exon, which includes an upstream in-frame AUG start codon, as compared to variant 1. The resulting isoform (3) has a longer N-terminus, as compared to isoform 1.
    Source sequence(s)
    AC104439, AF262303
    UniProtKB/TrEMBL
    Q8TDP4
    Conserved Domains (1) summary
    pfam00001
    Location:75319
    7tm_1; 7 transmembrane receptor (rhodopsin family)
  2. NM_001837.4NP_001828.1  C-C chemokine receptor type 3 isoform 1

    See identical proteins and their annotated locations for NP_001828.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) represents the longest transcript. It encodes the same isoform (1) as variant 2.
    Source sequence(s)
    AC104439, AF262302
    Consensus CDS
    CCDS2738.1
    UniProtKB/Swiss-Prot
    P51677
    UniProtKB/TrEMBL
    A0A024R2Z3, Q8TDP5
    Conserved Domains (1) summary
    cd15185
    Location:35312
    7tmA_CCR3; CC chemokine receptor type 3, member of the class A family of seven-transmembrane G protein-coupled receptors
  3. NM_178328.1NP_847898.1  C-C chemokine receptor type 3 isoform 2

    See identical proteins and their annotated locations for NP_847898.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) has an alternate internal exon, which includes an upstream in-frame AUG start codon, as compared to variant 1. The resulting isoform (2) has a longer N-terminus, as compared to isoform 1.
    Source sequence(s)
    AC104439, AF262301
    Consensus CDS
    CCDS54574.1
    UniProtKB/Swiss-Prot
    P51677
    Related
    ENSP00000441600.1, ENST00000545097.1
    Conserved Domains (1) summary
    pfam00001
    Location:78322
    7tm_1; 7 transmembrane receptor (rhodopsin family)
  4. NM_178329.3NP_847899.1  C-C chemokine receptor type 3 isoform 1

    See identical proteins and their annotated locations for NP_847899.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) lacks an internal exon in the 5' UTR, as compared to variant 1. Both variants encode the same isoform 1.
    Source sequence(s)
    AC104439, BC130320
    Consensus CDS
    CCDS2738.1
    UniProtKB/Swiss-Prot
    P51677
    UniProtKB/TrEMBL
    A0A024R2Z3
    Related
    ENSP00000379271.2, ENST00000395940.3
    Conserved Domains (1) summary
    cd15185
    Location:35312
    7tmA_CCR3; CC chemokine receptor type 3, member of the class A family of seven-transmembrane G protein-coupled receptors

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 109

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

Reference GRCh38.p13 Primary Assembly

Genomic

  1. NC_000003.12 Reference GRCh38.p13 Primary Assembly

    Range
    46210699..46266706
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_017005686.1XP_016861175.1  C-C chemokine receptor type 3 isoform X1

  2. XM_006712960.3XP_006713023.1  C-C chemokine receptor type 3 isoform X2

    See identical proteins and their annotated locations for XP_006713023.1

    UniProtKB/Swiss-Prot
    P51677
    UniProtKB/TrEMBL
    A0A024R2Z3
    Related
    ENSP00000350003.2, ENST00000357422.2
    Conserved Domains (1) summary
    cd15185
    Location:35312
    7tmA_CCR3; CC chemokine receptor type 3, member of the class A family of seven-transmembrane G protein-coupled receptors
  3. XM_011533335.2XP_011531637.1  C-C chemokine receptor type 3 isoform X2

    See identical proteins and their annotated locations for XP_011531637.1

    UniProtKB/Swiss-Prot
    P51677
    UniProtKB/TrEMBL
    A0A024R2Z3
    Conserved Domains (1) summary
    cd15185
    Location:35312
    7tmA_CCR3; CC chemokine receptor type 3, member of the class A family of seven-transmembrane G protein-coupled receptors
  4. XM_017005685.1XP_016861174.1  C-C chemokine receptor type 3 isoform X1

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