Nomenclature: CCR3

Family: Chemokine receptors

Annotation status:  image of a green circle Annotated and expert reviewed. Please contact us if you can help with updates. 

Contents

Gene and Protein Information
class A G protein-coupled receptor
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 355 3p21.3 CCR3 chemokine (C-C motif) receptor 3 10,12,37
Mouse 7 359 9 F Ccr3 chemokine (C-C motif) receptor 3 18
Rat 7 359 8q32 Ccr3 chemokine (C-C motif) receptor 3 23
Previous and Unofficial Names
Names References
CC CK3
CC CKR3 10,12
MIP-1αRL-2 (mouse) 18
CKR3
CC CK3
CMKBR3
CC-CKR-3
CD193
ccr3
C-C CKR-3
C-C chemokine receptor type 3
CCR-3
chemokine (C-C) receptor 3
MIP-1 alphaRL2
CC-CKR3
Database Links
ChEMBL Target
Ensembl Gene
Entrez Gene
GPCRDB
GeneCards
GenitoUrinary Development Molecular Anatomy Project
HomoloGene
Human Protein Reference Database
InterPro
KEGG Gene
OMIM
PharmGKB Gene
Protein Ontology (PRO)
RefSeq Nucleotide
RefSeq Protein
TreeFam
UniGene Hs.
UniProtKB
Wikipedia
Natural/Endogenous Ligands
CCL11 {Sp: Rat} , CCL11 {Sp: Mouse} , CCL11 {Sp: Human}
CCL13 {Sp: Human}
CCL15 {Sp: Human}
CCL2 {Sp: Rat} , CCL2 {Sp: Mouse} , CCL2 {Sp: Human}
CCL24 {Sp: Mouse} , CCL24 {Sp: Human}
CCL26 {Sp: Human}
CCL28 {Sp: Human} , CCL28 {Sp: Mouse}
CCL5 {Sp: Human} , CCL5 {Sp: Mouse, Rat}
CCL7 {Sp: Rat} , CCL7 {Sp: Mouse} , CCL7 {Sp: Human}
CCL8 {Sp: Human} , CCL8 {Sp: Mouse}
CXCL10 {Sp: Mouse} , CXCL10 {Sp: Human} , CXCL10 {Sp: Rat}
CXCL11 {Sp: Mouse} , CXCL11 {Sp: Human}
CXCL9 {Sp: Human} , CXCL9 {Sp: Mouse}
Comments: CCL11, CCL24 and CCL26 are the principal endogenous agonists
Agonists
Key to terms and symbols Click column headers to sort
Ligand Sp. Action Affinity Units Reference
CCL11 {Sp: Human} Hs Full agonist 9.7 – 10.0 pKi 12
pKi 9.7 – 10.0 [12]
CCL11 {Sp: Mouse} Hs Full agonist 9.5 – 10.0 pKi 12
pKi 9.5 – 10.0 [12]
CCL7 {Sp: Human} Hs Full agonist 8.6 – 9.2 pKi 12
pKi 8.6 – 9.2 [12]
CCL5 {Sp: Human} Hs Full agonist 8.5 – 9.3 pKi 12
pKi 8.5 – 9.3 [12]
CCL2 {Sp: Human} Hs Full agonist 7.2 – 7.8 pKi 12
pKi 7.2 – 7.8 [12]
CCL13 {Sp: Human} Hs Full agonist 8.7 – 10.3 pIC50 29,38
pIC50 8.7 – 10.3 [29,38]
CCL11 {Sp: Human} Hs Full agonist 8.7 – 9.0 pIC50 13,26,29,35,38
pIC50 8.7 – 9.0 [13,26,29,35,38]
CCL24 {Sp: Human} Hs Full agonist 8.0 – 9.4 pIC50 29,33
pIC50 8.0 – 9.4 [29,33]
CCL15 {Sp: Human} Hs Full agonist 8.6 pIC50 11
pIC50 8.6 [11]
CCL26 {Sp: Human} Hs Full agonist 7.9 – 8.9 pIC50 26,29,33
pIC50 7.9 – 8.9 [26,29,33]
HIV-Tat Hs Full agonist 7.2 pIC50 1
pIC50 7.2 [1]
CCL8 {Sp: Human} Hs Full agonist - -
CCL28 {Sp: Human} Hs Full agonist - -
Agonist Comments
It has been shown that CCL8 (MCP-2) is a ligand for the CCR3 receptor [20].
Antagonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
[125I]CCL11 (human) Hs Antagonist 8.3 pKd 40
pKd 8.3 (Kd 5.01x10-9 M) [40]
[3H]banyu (I) Hs Inverse agonist 8.3 pKd 40
pKd 8.3 [40]
banyu (I) Hs Inverse agonist 8.5 pKi 40
pKi 8.5 [40]
BMS compound 87b Hs Antagonist 8.1 pKi 39
pKi 8.1 [39]
RO116-9132/238 Hs Antagonist 9.0 pIC50 7
pIC50 9.0 [7]
RO320-2947/001 Hs Antagonist 8.4 pIC50 7
pIC50 8.4 [7]
RO330-0802/001 Hs Antagonist 8.3 pIC50 7
pIC50 8.3 [7]
Met-Ckβ7 Hs Antagonist 8.2 pIC50 31
pIC50 8.2 [31]
YM-355179 Hs Antagonist 7.6 – 8.1 pIC50 29
pIC50 7.6 – 8.1 [29]
RO116-4875/608 Hs Antagonist 7.2 pIC50 7
pIC50 7.2 [7]
CXCL11 {Sp: Human} Hs Antagonist - -
CXCL10 {Sp: Human} Hs Antagonist - -
CXCL9 {Sp: Human} Hs Antagonist - -
Antagonist Comments
CCL9 and CCL10 are CCR3 antagonists.
Primary Transduction Mechanisms
Transducer Effector/Response
Gi/Go family Calcium channel
References: 
Tissue Distribution
Platelets.
Species:  Human
Technique:  RT-PCR and flow cytometry.
References:  9
Primary adult microglia and astrocytes.
Species:  Human
Technique:  Flow cytometry.
References:  14
Basophils.
Species:  Human
Technique:  Flow cytometry.
References:  22,32
Basophils.
Species:  Human
Technique:  RT-PCR.
References:  22
Blood dendritic cells.
Species:  Human
Technique:  RT-PCR.
References:  3
Microvascular endothelial cells.
Species:  Human
Technique:  RNase protection assay.
References:  36
Microglia.
Species:  Human
Technique:  Flow cytometry.
References:  2
Th2-type lymphocytes.
Species:  Human
Technique:  Flow cytometry.
References:  19
Basophils and eosinophils.
Species:  Human
Technique:  Flow cytometry and Northern blotting.
References:  38
Th2-type lymphocytes.
Species:  Human
Technique:  RT-PCR.
References:  30
Osteoblasts.
Species:  Rat
Technique:  RT-PCR.
References:  41
Spleen.
Species:  Rat
Technique:  Northern blotting.
References:  23
Expression Datasets

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Log average relative transcript abundance in mouse tissues measured by qPCR from Regard, J.B., Sato, I.T., and Coughlin, S.R. (2008). Anatomical profiling of G protein-coupled receptor expression. Cell, 135(3): 561-71. [PMID:18984166] [Raw data: website]

There should be a chart of expression data here, you may need to enable JavaScript!
Functional Assays
Measurement of Ca2+ levels in human CD34+ blood progenitor cells endogenously expressing the CCR3 receptor.
Species:  Human
Tissue:  CD34+ blood progenitor cells.
Response measured:  Ca2+ mobilisation.
References:  27
Measurement of chemotaxis of CD34+ blood progenitor cells endogenously expressing the CCR3 receptor.
Species:  Human
Tissue:  CD34+ blood progenitor cells.
Response measured:  Chemotaxis.
References:  27
Detection of HIV-1 fusion in HeLa cells transfected with CD4 and the CCR3 receptor.
Species:  Human
Tissue:  HeLa-CD4 cells.
Response measured:  HIV-1 fusion and infection.
References:  8
Measurement of chemotaxis of eosinophils endogenously expressing the CCR3 receptor.
Species:  Human
Tissue:  Eosinophils.
Response measured:  Chemotaxis.
References:  15,26,31
Measurement of MAP kinase activity in eosinophils endogenously expressing the CCR3 receptor.
Species:  Human
Tissue:  Eosinophils.
Response measured:  Activation of MAP kinases.
References:  5,24
Measurement of Ca2+ levels in eosinophils endogenously expressing the CCR3 receptor.
Species:  Human
Tissue:  Eosinophils.
Response measured:  Ca2+ influx.
References:  16,31
Measurement of superoxide anion levels in eosinophils endogenously expressing the CCR3 receptor.
Species:  Human
Tissue:  Eosinophils.
Response measured:  Superoxide anion production.
References:  4
Physiological Functions
Chemotaxis.
Species:  Human
Tissue:  Leukocytes.
References:  15
Degranulation.
Species:  Human
Tissue:  Eosinophils.
References:  4,16
Angiogenesis.
Species:  Rat
Tissue:  Aortic rings.
References:  36
Eosinophil recruitment.
Species:  Mouse
Tissue:  In vivo.
References:  6,21,28,34
Physiological Consequences of Altering Gene Expression
CCR3 receptor knockout mice with induced pulmonary inflammation exhibit reduced trafficking of eosinophils from the blood into the lung parenchyma and increased numbers of intraepithelial mast cells in the trachea. Cholinergic stimulation resulted in airway hyperresponsiveness.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  21
CCR3 knockout mice with induced skin inflammation exhibit impaired recruitment of eosinophils to lung parenchyma and bronchoalveolar lavage. Cholinergic stimulation did not result in airway hyperresponsiveness.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  28
CCR3 receptor knockout mice have decreased levels of eosinophils in the blood, spleen and jejunum. Following induced inflammation, the knockout mice exhibit a 6-fold increase in the number of eosinophils in the blood compared to the wild-type.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  34
CCR3 receptor knockout mice lack allergen-induced eosinophil accumulation in the esophagus normally seen with the wild-type eosinophilic esophagitis mouse model.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  6
Phenotypes, Alleles and Disease Models Mouse data from MGI

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Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Ccr3tm1Cge Ccr3tm1Cge/Ccr3tm1Cge
involves: 129S4/SvJae * BALB/c
MGI:104616  MP:0002334 abnormal airway responsiveness PMID: 11877470 
Ccr3tm1Cge Ccr3tm1Cge/Ccr3tm1Cge
involves: 129S4/SvJae * BALB/c
MGI:104616  MP:0002602 abnormal eosinophil cell number PMID: 11830666 
Ccr3tm1Cge Ccr3tm1Cge/Ccr3tm1Cge
involves: 129S4/SvJae * BALB/c
MGI:104616  MP:0002465 abnormal eosinophil physiology PMID: 11830666  11877470 
Ccr3tm1Cge Ccr3tm1Cge/Ccr3tm1Cge
involves: 129S4/SvJae * BALB/c
MGI:104616  MP:0002423 abnormal mast cell physiology PMID: 11830666 
Ccr3tm1Cge Ccr3tm1Cge/Ccr3tm1Cge
involves: 129S4/SvJae * BALB/c
MGI:104616  MP:0005012 decreased eosinophil cell number PMID: 11830666  11877470 
Ccr3tm1Cge Ccr3tm1Cge/Ccr3tm1Cge
involves: 129S4/SvJae * BALB/c
MGI:104616  MP:0008724 impaired eosinophil migration PMID: 11830666 
Ccr3tm1Cge Ccr3tm1Cge/Ccr3tm1Cge
involves: 129S4/SvJae * BALB/c
MGI:104616  MP:0008723 impaired eosinophil recruitment PMID: 11830666  11877470 
Ccr3tm1Cge Ccr3tm1Cge/Ccr3tm1Cge
involves: 129S4/SvJae * BALB/c
MGI:104616  MP:0001952 increased airway responsiveness PMID: 11830666 
Ccr3tm1Cge Ccr3tm1Cge/Ccr3tm1Cge
involves: 129S4/SvJae * BALB/c
MGI:104616  MP:0005011 increased eosinophil cell number PMID: 11830666 
Ccr3tm1Cge Ccr3tm1Cge/Ccr3tm1Cge
involves: 129S4/SvJae * BALB/c
MGI:104616  MP:0008764 increased mast cell degranulation PMID: 11830666 
Biologically Significant Variants
Type:  Single nucleotide polymorphism.
Species:  Human
Description:  A Cys218 -> Ser polymorphism in the CCR3 gene has been identified in human, perhaps with reduced function at the protein level.
References:  25
Type:  Single nucleotide polymorphism.
Species:  Human
Description:  A Thr51 -> Cys polymorphism has been identified in humans and may be associated with the development of asthma.
References:  17
Available Assays
DiscoveRx PathHunter® CHO-K1 CCR3 β-Arrestin Cell Line (Cat no. 93-0629C2)
PathHunter® eXpress CCR3 CHO-K1 β-Arrestin GPCR Assay (Cat no. 93-0629E2CP2M)
more info

REFERENCES

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To cite this database page, please use the following:

Israel F. Charo, Rebecca Hills, Richard Horuk, Kouji Matsushima, Philip M. Murphy, Joost J. Oppenheim.
Chemokine receptors: CCR3. Last modified on 19/08/2013. Accessed on 23/10/2014. IUPHAR database (IUPHAR-DB), http://www.iuphar-db.org/DATABASE/ObjectDisplayForward?objectId=60.

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