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FLASH GENE

Symbol

CCR2

contributors: mct - updated : 25-04-2016

HGNC name	chemokine (C-C motif) receptor 2
HGNC id	1603

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Location	3p21.31      Physical location : 46.395.234 - 46.402.412
Synonym name	small inducible cytokine (SCYA2, SCYA7) common receptor
	monocyte chemotactic protein 1 receptor
	MCP-1 receptor
	CD192 antigen
Synonym symbol(s)	CMKBR2, CCR2A, CCR2B, CKR2, MCP1R, CD192, CKR2B, CCCKR2, FLJ78302, MGC103828, MGC168006, MGC111760

DNA

TYPE	functioning gene
SPECIAL FEATURE	component of a cluster
STRUCTURE	7.18 kb     3 Exon(s)

10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

N

status

confirmed

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_001123041 3 splicing 2689 NP_001116513 41 374 . cytoplasmic isoform . expressed in vessel walls and by some mononuclear cells, especially in cells involved in partial invasion in polymyosititis (PM) and inclusion body myositis (IBM) 2001 11603815 also called variant A a 3 exon variant containing exon 2b (shorter than 2a) alternatively spliced leading to a frameshift and use of a downstream stop codon NM_001123396 2 splicing 2335 NP_001116868 40.9 360 . observed in all satellite cells, in the muscular domain of neuromuscular junctions and in some regenerative fibers of idiopathic inflammatory myopathies, but not in inflammatory exudates 2001 11603815 also called variant B a 2 exons variant containing exon 2a (longer than 2b) lacking exon 3 encoding for the predominant isoform B localized to the plasma membrane FLNA is a protein that associates with the carboxyl-terminal tail of CCR2B (PMID: 20808917)

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 spinal cord posterior horn     highly Mus musculus Adult Visual eye retina       Mus musculus Adult

tissue

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

cells

System Cell Pubmed Species Stage Rna symbol Blood/Hematopoietic monocyte Homo sapiens Adult Nervous astrocyte Mus musculus Adult Nervous neuron Mus musculus Adult

cell lineage

cell lines

fluid/secretion

at STAGE

physiological period

fetal

Text	astrocytes

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains

a seven transmembrane segments (7TM) receptor

mono polymer

dimer

HOMOLOGY

interspecies	homolog to rattus Ccr2 (80.00 pc)
	homolog to murine Ccr2 (79.72 pc)

Homologene

FAMILY

G protein coupled receptor I family

CATEGORY

receptor membrane G

SUBCELLULAR LOCALIZATION	plasma membrane
	intracellular
	intracellular,cytoplasm,cytosolic
	intracellular,nuclear envelope
text	isoform A localized in cytoplasm
	isoform B localized in plasma membrane

basic FUNCTION	mediating agonist-dependent calcium mobilization and inhibition of adenylyl cyclase
	involved in muscle precursor cell activities necessary for complete and rapid regeneration of injured skeletal muscle
	mediating increases in glial activation caused by exposure to HIV-1 Tat and opiates
	chemokine receptor expressed on microglia, which mediates the accumulation of mononuclear phagocytes at sites of inflammation
	important role for CCR2-driven activation of NF-kappaB in the regulation of dendritic cell/Langerhans cell maturation processes that regulate protective immunity against intracellular pathogens
	essential to acute skeletal muscle injury repair
	direct involvement in muscle regeneration or angiogenesis
	involved in regulation of the inflammatory response
	potentially involved in cocaine sensitization
	plays a pivotal role in the pathogenesis of angiotensin II-induced cardiac fibrosis through regulation of bone marrow-derived fibroblast precursors
	pleiotropic role of CCR2 in monocyte/macrophage accumulation and regulation of adipose tissue inflammation (
	recruits an inflammatory macrophage subpopulation critical for angiogenesis in tissue repair
	during chemotaxis CCR2 acts as scavenger consuming the chemokine forming the attracting cue
	chemokine receptors CCR2 and CX3CR1 are critical for the recruitment of "inflammatory" and "resident" monocytes, respectively
	both CCR2 and CX3CR1 regulate arteriole growth, but only bone marrow-derived cell-expressed CX3CR1 impacts small venule growth
	key role for the CCL2/CCR2 pathway in establishing osteoarthritis pain
	CCL2 and CCR2 have been shown to be induced and involved in various neurodegenerative disorders including Alzheimer disease, multiple sclerosis, and ischemic brain injury
	CCR2 and CCR5 are required for collaboration between macrophages and pulmonary-artery smooth muscle cells (PASMCs) to initiate and amplify PASMC migration and proliferation during pulmonary arterial hypertension (PAH) development

CELLULAR PROCESS

cell migration & motility

PHYSIOLOGICAL PROCESS

immunity/defense

PATHWAY

metabolism

signaling

	JAK/STAT pathway
	CCL2-CCR2 signaling may be involved in the maintenance of orofacial neuropathic pain via astroglial-neuronal interactio

a component

INTERACTION

DNA

RNA

small molecule

protein	high affinity binding for chemokine (C-C motif) ligand 2 (CCL2)
	FLNA emerges as an important protein for controlling the internalization and spatial localization of the CCR2B receptor in different dynamic membrane structures
	interaction between the chemokine CCL2 and CCR2 plays a critical role in the recruitment of inflammatory monocytes into the injured/diseased brain
	CCL2 binding to primary adult human astrocytes is CCR2-independent and is likely to be mediated via the ACKR2 decoy chemokine receptor
	CCL2/CCR2 (interaction is responsible for the infiltration of peripheral cells to the thymus in the Th1-inflammatory/infectious situations
	functional binding element in helix 8 of CCR2 for the cytosolic regulator NUP85 that mediates chemotactic signalling
	NUP85 is a cytoplasmic protein that binds to the membrane-proximal C-terminal regions (Pro-Cs) of chemokine receptors, CCR2 and CCR5

cell & other

REGULATION

activated by

JAK2 triggeret by CCL2 (SCYA2)

Other

dimerizing in response to CCL2

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional     --over   in polymyositis and in inclusion body myositis constitutional     --low   leads to decreased microglial accumulation in the Alzheimer disease brain, resulting in increased A deposition particularly in and around blood vessels constitutional     --low   could play a potential role in the etiology of Alzheimer's disease, a neurodegenerative pathology that could be treated by a genetic upregulation of the transgene in monocytoid cells tumoral       gain of function of CCL2/CCR2 axis promotes prostate cancer growth in bone constitutional     --over   expression of CCR1 and CCR2 is up-regulated in peripheral blood B cells upon EBV infection

Susceptibility

HIV-1 infection for bone mass especially in middle-aged man and postmenopausal women to myocardial infarction and heart failure in patient sunder 65 years to Alzheimer disease to abdominal aortic aneurysms

Variant & Polymorphism	V64I increasing the risk of myocardial infarction and heart failure
	chronic CCR2 inhibition may hasten the progression of Alzheimer disease in susceptible individuals
	Significant relationship was observed between CCR2 V64I polymorphism and presence of abdominal aortic aneurysms

Candidate gene	a dominant protective effect of the CCR2-641 mutation
Marker
Therapy target
	System Type Disorder Pubmed miscelleaneous pain   antagonists of CCL2/CCR2 are promising agents from treating neuropathic pain immunology inflammatory   CCR2 antagonists are currently undergoing clinical trials for the treatment of a variety of chronic inflammatory diseases miscelleaneous pain   targeting CCL2-CCR2 signaling may be a potentially important new treatment strategy for trigeminal neuralgia diabete type 1   blocking CCR2 could be a novel therapeutic approach in the treatment of diabetic nephropathy

ANIMAL & CELL MODELS

	Ccr2 deficiency accelerates early disease progression and markedly impairs microglial accumulation in a transgenic mouse model of Alzheimer disease (Tg2576)
	locomotor sensitization is significantly reduced in CCR2(-/-) mice as well as the dopamine transporter regulation and the cocaine-induced p-ERK striatal activation
	mice with CCR2 deficiency are protected from insulin resistance but only after long periods of high-fat diet (HFD) feeding, despite the virtual absence of circulating inflammatory monocytes
	mice that lack Ccr2 developed mechanical allodynia, but this started to resolve from 8 wk onwards