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FLASH GENE

Symbol

CCR3

contributors: mct/npt/shn - updated : 02-05-2017

HGNC name	chemokine (C-C motif) receptor 3
HGNC id	1604

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

RNA

TRANSCRIPTS	type	messenger

text	variants 1, 2 encode the same protein

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_178329 2 splicing 1717 NP_847899 - 355 primary eosinophils - 8642344 NM_001164680 3 splicing 1777 NP_001158152 - 373 primary eosinophils - 8642344 NM_001837 3 - 1796 NP_001828 - 355 primary eosinophils - 8642344 NM_178328 3 splicing 1786 NP_847898 - 376 primary eosinophils - 8642344

EXPRESSION

Type	restricted

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Nervous brain         Reproductive female system placenta       Homo sapiens

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Blood / Hematopoietic bone marrow       Connective

cells

System Cell Pubmed Species Stage Rna symbol Blood/Hematopoietic basophil Blood/Hematopoietic eosinophil Blood/Hematopoietic monocyte Blood/Hematopoietic neutrophil Blood/Hematopoietic platelet Skin/Tegument keratinocyte

cell lineage	dendritic cells (
	Th2 cells (
cell lines	AML14.3D10 (
fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains

seven transmembrane segments (7TM) receptor

HOMOLOGY

interspecies	ortholog to Ccr3, Mus musculus
	ortholog to Ccr3, Rattus norvegicus
	ortholog to CCR3, Pan troglodytes

Homologene

FAMILY

G-protein coupled receptor 1 family

CATEGORY

receptor membrane G

SUBCELLULAR LOCALIZATION

plasma membrane

basic FUNCTION	eosinophil eotaxin receptor (
	important for the basal trafficking of eosinophils to the intestinal mucosa (
	plays an essential role in eosinophil recruitment to the skin and the lung and in the development of airway hyperresponsiveness (
	expressed by the thymocytes for the mobilization of lymphocytes within and from the thymus
	playing a role in allergic inflammatory diseases (eosinophil chemotactic)
	receptor for CCL11, CCL24, CCL5, CCL7, CCL13, MCP3
	promotes choroidal endothelial cell migration and Rac1 activation (
	potential role of CCR1, CCR3 genes in narcolepsy
	high affinity receptor CCR3 was significantly upregulated during osteoclast differentiation

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component

INTERACTION

DNA

RNA

small molecule

protein	MCP-1 (
	hck and c-fgr (
	CCL15 is a CC chemokine that binds to the CCR1 and CCR3
	CENPB is a CCR3 ligand (CENPB transactivation of the EGFR via CCR3 in vascular smooth muscle cells
	CCL26 is a functional ligand for CCR3 and abundantly produced by IL4-/IL13-stimulated vascular endothelial cells
	VEGFR2 (
	CCL11, CCL24, and CCL26 are chemokines involved in the recruitment of eosinophils into tissues and that mainly activate CCR3
	CCR3, an important receptor for CCL11, did not facilitate CCL11 transport across the BBB, although high concentrations of a CCR3 inhibitor increased brain uptake without causing blood-brain barrier (BBB) disruption
	CCL24/CCR3 promotes the proliferation, viability and invasiveness of trophoblasts

cell & other

REGULATION

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional     --over   in bullous pemphigoid constitutional     --other   specifically expressed in choroidal neovascular endothelial cells in Age-related macular degeneration (AMD) (Takeda (2009) constitutional     --low   in narcolepsy constitutional     --low   in narcolepsy

Susceptibility

to Kawasaki disease (KD)

Variant & Polymorphism SNP	two haplotypes of the CCR3-CCR2-CCR5 gene-cluster appear to be at risk haplotypes for KD and one a protective haplotype (Breunis 2007)

Candidate gene
Marker
Therapy target	post-transcriptional regulation of CCR3 receptors may be a potential therapeutic approach for interrupting proinflammatory signaling (Taka 2008)
	System Type Disorder Pubmed osteoarticular bone ostéoporosis CCL11/CCR3 pathway could be a new target for treatment of inflammatory bone resorption neurosensorial visual   CCR3 targeting might reduce vision loss due to AMD through early detection and therapeutic angioinhibition (its activation is essential for angiogenesis in the most widely used preclinical model of neovascular AMD)

ANIMAL & CELL MODELS

	mice deficient in CCR3 have a significant 7-fold reduction in the basal eosinophil content of the small intestine, concurrent with a 6-fold increase in the spleen (
	Eosinophils and the eosinophil product major basic protein were absent from the skin of sham and OVA-sensitized CCR3(-/-) mice and recruitment of eosinophils to lung parenchyma and bronchoalveolar lavage fluid was severely impaired in these mice (
	eosinophil trafficking to the heart in eosinophilic myocarditis depends on the chemokine receptor Ccr3 and expression of its ligands Ccl11, Ccl24, and Ccl26 in the heart in a mouse model and in patients with eosinophilic myocarditis