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FLASH GENE
Symbol CCR2 contributors: mct - updated : 25-04-2013
HGNC name chemokine (C-C motif) receptor 2
HGNC id 1603
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
    Physical map
    CCR2 3p21.31 chemokine (C-C motif) receptor 2 CCR5 3p21.31 chemokine (C-C motif) receptor 5 CCRL2 3p21.32-p21.31 chemokine (C-C motif) receptor-like 2 CHL1 3p26 cell adhesion molecule with homology to L1CAM (close homolog of L1) LOC391503 3 similar to 40S ribosomal protein SA (P40) (34/67 kDa laminin receptor) CNTN6 3p26-p25 contactin 6 LOC391504 3 similar to 60S ribosomal protein L23a LOC391505 3 similar to 60S ribosomal protein L21 CNTN4 3p26.2 contactin 4 IL5RA 3p26-p25 interleukin 5 receptor, alpha TRNT1 3p25.1 tRNA nucleotidyl transferase, CCA-adding, 1 LOC51185 3p26.2 protein x 0001 LRRN1 3p26.2 leucine rich repeat neuronal 1 SETMAR 3p26.1 SET domain and mariner transposase fusion gene SUMF1 3p26.2 SET domain and mariner transposase fusion gene MRPS10P2 3p26 mitochondrial ribosomal protein S10 pseudogene 2 ITPR1 3p26-p25 inositol 1,4,5-triphosphate receptor, type 1 BHLHB2 3p26.1-p25.3 basic helix-loop-helix domain containing, class B, 2 LOC391506 3 similar to autoantigen NOR-90 FLJ10702 EDEM1 3p26.1 ER degradation enhancer, mannosidase alpha-like 1 MRPS35P1 3p25.3 mitochondrial ribosomal protein S35 pseudogene 1 MRPS36P1 3p25.3 mitochondrial ribosomal protein S36 pseudogene GRM7 3p26.1-p25.2 glutamate receptor, metabotropic 7 LOC389092 3 LOC389092 LMCD1 3p26-p24 LIM and cysteine-rich domains 1 LOH3CR2A 3 loss of heterozygosity, 3, chromosomal region 2, gene A LOC51066 3p25.3 fls485 LOC391507 3 similar to seven transmembrane helix receptor CAV3 3p25 caveolin 3 OXTR 3p25 oxytocin receptor RAD18 3p25-p24 RAD18 homolog (S. cerevisiae)
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    3 splicing 2689 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
  • 2 splicing 2335 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)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Nervousspinal cordposterior horn  highly Mus musculusAdult
    Visualeyeretina    Mus musculusAdult
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / Hematopoieticbone marrow   
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Blood/Hematopoieticmonocyte Homo sapiensAdult
    Nervousastrocyte Mus musculusAdult
    Nervousneuron Mus musculusAdult
    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
  • 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
  • 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)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein 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
    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
    SystemTypeDisorderPubmed
    miscelleaneouspain 
    antagonists of CCL2/CCR2 are promising agents from treating neuropathic pain
    immunologyinflammatory 
    CCR2 antagonists are currently undergoing clinical trials for the treatment of a variety of chronic inflammatory diseases
    miscelleaneouspain 
    targeting CCL2-CCR2 signaling may be a potentially important new treatment strategy for trigeminal neuralgia
    diabetetype 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