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FLASH GENE
Symbol P2RY12 contributors: mct - updated : 23-01-2013
HGNC name purinergic receptor P2Y, G-protein coupled, 12
HGNC id 18124
RNA
TRANSCRIPTS type messenger
text the two variants encode the same protein
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
3 splicing 1502 39.4 342 - -
2 splicing 1474 39.4 342 - -
  • differing in the 5' UTR compared to variant 1
  • EXPRESSION
    Type restricted
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Nervousbrain    
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Blood/Hematopoieticplatelet Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • four extracellular cysteine residues
  • seven transmembrane segments
  • at extreme C-terminus, a putative PSD95/disc large/zonula occludens-1 (PDZ)-binding motif, important to ensure correct receptor traffic
  • conjugated GlycoP
    HOMOLOGY
    interspecies ortholog to murine P2ry12
    ortholog to rattus P2ry12
    Homologene
    FAMILY G-protein coupled receptor 1 family
    CATEGORY regulatory , receptor membrane G
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm
    basic FUNCTION
  • receptor for ADP and ATP coupled to G-proteins inhibiting the adenylyl cyclase second messenger system
  • critical for the formation and stabilization of large platelet aggregates
  • P2RX4 as well as P2RY12 is involved in ATP-induced microglial chemotaxis
  • role in the vessel wall response to arterial injury and thrombosis
  • play a crucial role in the stabilization of thrombi formed on atherosclerotic plaques
  • not only is central to ADP-induced platelet activation but also may mediate platelet-independent responses, specifically under conditions of enhanced thrombin formation, such as local vessel injury and atherosclerotic plaque rupture
  • P2RY12 pathway substantially involved in platelet hyperreactivity associated with mild and severe hypercholesterolemia
  • plays a crucial role in hemostasis, undergoing internalization and subsequent recycling to maintain receptor responsiveness, processes that are essential for normal platelet function
  • plays a critical role in platelet aggregation, and P2RY12 inhibitors are used clinically to prevent cardiac and cerebral thrombotic events
  • is the primary ADP receptor in osteoclasts
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS coagulation/hemostasis
    PATHWAY
    metabolism
    signaling signal transduction
  • G-protein coupled receptor protein signaling pathway
  • a component
    INTERACTION
    DNA
    RNA
    small molecule nucleotide,
  • ATP
  • ADP
  • protein
  • interaction of ADORA2A, P2RY1, P2RY12
  • SLC9A3R1 interacts with the C-tail of the P2RY12 and unlike many other GPCRs, SLC9A3R1 interaction is required for effective P2RY12 internalization
  • novel function of ARF6 in the internalization of P2RY1, P2RY12 purinoceptors, demonstrating the integral importance of this small GTPase upon platelet ADP receptor function
  • P2RY12 signaling is required to inhibit RASA3 and enable sustained RABGEF1-dependent platelet activation and thrombus formation at sites of vascular injury
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) P2RY12
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --low  
    might be detrimental to tissue integrity in cortical gray matter lesions in multiple sclerosis
    constitutional       gain of function
    in spinal microglia may be a critical event in the pathogenesis of neuropathic pain
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    bloodcoagulation 
    potential target for the treatment of thromboembolisms and other clotting disorders
    osteoarticularboneostéoporosis
    P2RY12 inhibition is a potential therapeutic target for pathologic bone loss
    miscelleaneouspain 
    might be a viable therapeutic strategy for treating neuropathic pain
    ANIMAL & CELL MODELS
  • mice lacking P2ry12 had decreased osteoclast activity and were partially protected from age-associated bone loss
  • blocking of P2ry12 in mice resulted in strongly reduced platelet aggregation in mice with elevated cholesterol levels compared with normocholesterolemic controls