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

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; AllianceGenome:HGNC:1604
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]
Annotation information: Note: This gene has been reviewed for its involvement in coronavirus biology, and is locus in the vicinity of disease-associated variant(s).
Expression: Low expression observed in reference dataset See more
Orthologs: mouse all
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Genomic context

Location:: 3p21.31

Exon count:: 5

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	3	NC_000003.12 (46210696..46266706)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	3	NC_060927.1 (46226558..46282568)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	3	NC_000003.11 (46283872..46308197)

Chromosome 3 - NC_000003.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

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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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Critically-ill COVID-19 susceptibility gene CCR3 shows natural selection in sub-Saharan Africans.
Title: Critically-ill COVID-19 susceptibility gene CCR3 shows natural selection in sub-Saharan Africans.
CCL24/CCR3 axis plays a central role in angiotensin II-induced heart failure by stimulating M2 macrophage polarization and fibroblast activation.
Title: CCL24/CCR3 axis plays a central role in angiotensin II-induced heart failure by stimulating M2 macrophage polarization and fibroblast activation.
CD193 (CCR3) expression by B cells correlates with reduced IgE production in paediatric schistosomiasis.
Title: CD193 (CCR3) expression by B cells correlates with reduced IgE production in paediatric schistosomiasis.
CCR3 blockage elicits polyploidization associated with the signatures of epithelial-mesenchymal transition in carcinoma cell lines.
Title: CCR3 blockage elicits polyploidization associated with the signatures of epithelial-mesenchymal transition in carcinoma cell lines.
The rs13075270 and rs13092160 polymorphisms of CCR1 and CCR3 genes on oral aphthous-like lesions in PFAPA syndrome.
Title: The rs13075270 and rs13092160 polymorphisms of CCR1 and CCR3 genes on oral aphthous-like lesions in PFAPA syndrome.
CCR3 gene overexpression in patients with Down syndrome.
Title: CCR3 gene overexpression in patients with Down syndrome.
Platelets Independently Recruit into Asthmatic Lungs and Models of Allergic Inflammation via CCR3.
Title: Platelets Independently Recruit into Asthmatic Lungs and Models of Allergic Inflammation via CCR3.
Stromal CCL5 Promotes Breast Cancer Progression by Interacting with CCR3 in Tumor Cells.
Title: Stromal CCL5 Promotes Breast Cancer Progression by Interacting with CCR3 in Tumor Cells.
The Chemokine Receptor CCR3 Is Potentially Involved in the Homing of Prostate Cancer Cells to Bone: Implication of Bone-Marrow Adipocytes.
Title: The Chemokine Receptor CCR3 Is Potentially Involved in the Homing of Prostate Cancer Cells to Bone: Implication of Bone-Marrow Adipocytes.
KSHV enhances mesenchymal stem cell homing and promotes KS-like pathogenesis.
Title: KSHV enhances mesenchymal stem cell homing and promotes KS-like pathogenesis.

Submit: New GeneRIF Correction See all GeneRIFs (91)

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
Genome-wide association analysis identifies new susceptibility loci for Beh&#x000e7;et's disease and epistasis between HLA-B*51 and ERAP1. EBI GWAS Catalog EBI GWAS CatalogPubMed
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. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study of celiac disease in North America confirms FRMD4B as new celiac locus. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-Wide Association Study of CSF Levels of 59 Alzheimer's Disease Candidate Proteins: Significant Associations with Proteins Involved in Amyloid Processing and Inflammation. EBI GWAS Catalog EBI GWAS CatalogPubMed
Multiple common variants for celiac disease influencing immune gene expression. EBI GWAS Catalog EBI GWAS CatalogPubMed
Newly identified genetic risk variants for celiac disease related to the immune response. EBI GWAS Catalog EBI GWAS CatalogPubMed
Novel genetic loci identified for the pathophysiology of childhood obesity in the Hispanic population. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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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

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

SHGC-76880 (e-PCR)
- UniSTS:70151

NoName (e-PCR)
- UniSTS:486460

D3S4503 (e-PCR)
- UniSTS:474432

PMC109434P2 (e-PCR)
- UniSTS:270164

PMC109444P2 (e-PCR)
- UniSTS:270167

PMC110312P1 (e-PCR)
- UniSTS:270186

CCR3_515 (e-PCR)
- UniSTS:280480

NoName (e-PCR)
- UniSTS:494496

PMC135988P6 (e-PCR)
- UniSTS:270792

PMC155019P3 (e-PCR)
- UniSTS:271322

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 binding	IDA Inferred from Direct Assay more info	PubMed
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 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
involved_in cell adhesion	TAS Traceable Author Statement more info	PubMed
involved_in cell chemotaxis	IBA Inferred from Biological aspect of Ancestor more info
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
involved_in inflammatory response	IBA Inferred from Biological aspect of Ancestor more info
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
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
is_active_in external side of plasma membrane	IBA Inferred from Biological aspect of Ancestor 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 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)

NM_001164680.2 → NP_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:75 → 319

7tm_1; 7 transmembrane receptor (rhodopsin family)
NM_001837.4 → NP_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

B3KVQ1, F5GWL6, P51677, Q15748, Q2YDB9, Q86WD2, Q8TDP6, Q9ULY8

Conserved Domains (2) summary

cd14964
Location:37 → 61

7tm_GPCRs; TM helix 1 [structural motif]

cl28897
Location:35 → 312

7tm_GPCRs; seven-transmembrane G protein-coupled receptor superfamily
NM_178328.1 → NP_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:78 → 322

7tm_1; 7 transmembrane receptor (rhodopsin family)
NM_178329.3 → NP_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

B3KVQ1, F5GWL6, P51677, Q15748, Q2YDB9, Q86WD2, Q8TDP6, Q9ULY8

Related

ENSP00000379271.2, ENST00000395940.3

Conserved Domains (2) summary

cd14964
Location:37 → 61

7tm_GPCRs; TM helix 1 [structural motif]

cl28897
Location:35 → 312

7tm_GPCRs; seven-transmembrane G protein-coupled receptor superfamily