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

Gene ID: 1232, updated on 8-Jul-2021

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; CKR 3; CMKBR3; C C CKR3; 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
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Genomic context

See CCR3 in Genome Data Viewer
Location:
3p21.31
Exon count:
6
Annotation release Status Assembly Chr Location
109.20210514 current GRCh38.p13 (GCF_000001405.39) 3 NC_000003.12 (46210699..46266706)
105.20201022 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 FLT1 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 Functions

What's a GeneRIF?

Phenotypes

Associated conditions

Description Tests
Genome-wide association analysis identifies new susceptibility loci for Behçet's disease and epistasis between HLA-B*51 and ERAP1.
GeneReviews: Not available
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.
GeneReviews: Not available
Genome-wide association study of celiac disease in North America confirms FRMD4B as new celiac locus.
GeneReviews: Not available
Genome-Wide Association Study of CSF Levels of 59 Alzheimer's Disease Candidate Proteins: Significant Associations with Proteins Involved in Amyloid Processing and Inflammation.
GeneReviews: Not available
Multiple common variants for celiac disease influencing immune gene expression.
GeneReviews: Not available
Newly identified genetic risk variants for celiac disease related to the immune response.
GeneReviews: Not available
Novel genetic loci identified for the pathophysiology of childhood obesity in the Hispanic population.
GeneReviews: Not available

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 PubChem

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

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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_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 (2) summary
    cd14964
    Location:3761
    7tm_GPCRs; TM helix 1 [structural motif]
    cl28897
    Location:35312
    7tm_GPCRs; seven-transmembrane G protein-coupled receptor superfamily
  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 (2) summary
    cd14964
    Location:3761
    7tm_GPCRs; TM helix 1 [structural motif]
    cl28897
    Location:35312
    7tm_GPCRs; seven-transmembrane G protein-coupled receptor superfamily

RefSeqs of Annotated Genomes: Homo sapiens Updated Annotation Release 109.20210514

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 (2) summary
    cd14964
    Location:3761
    7tm_GPCRs; TM helix 1 [structural motif]
    cl28897
    Location:35312
    7tm_GPCRs; seven-transmembrane G protein-coupled receptor superfamily
  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 (2) summary
    cd14964
    Location:3761
    7tm_GPCRs; TM helix 1 [structural motif]
    cl28897
    Location:35312
    7tm_GPCRs; seven-transmembrane G protein-coupled receptor superfamily
  4. XM_017005685.1XP_016861174.1  C-C chemokine receptor type 3 isoform X1

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