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FLASH GENE
Symbol F2RL3 contributors: mct - updated : 14-11-2015
HGNC name coagulation factor II (thrombin) receptor-like 3
HGNC id 3540
Location 19p13.11      Physical location : 16.999.825 - 17.002.828
Synonym name
  • protease-activated receptor-4
  • thrombin receptor-like 3
    • Synonym symbol(s) PAR4
    DNA
    TYPE like-sequence
    STRUCTURE 3.00 kb     2 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked   status provisional
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    2 - 2731 - 385 - 2003 12871418
    EXPRESSION
    Type restricted
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart     Homo sapiens
    Digestiveintestinelarge intestinecolon  
    Nervousbrain     Homo sapiens
    Reproductivemale systemtestis   
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / hematopoieticbone marrow   
    Muscularsmooth    Homo sapiens
    Muscularstriatumcardiac   Homo sapiens
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Blood/Hematopoieticmonocyte
    Blood/Hematopoieticplatelet Homo sapiens
    Cardiovascularendothelial cell Homo sapiens
    Lymphoid/Immunemacrophage
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
    		seven transmembrane segments (7TM) receptor
    HOMOLOGY
    Homologene
    FAMILY G protein coupled receptor superfamily
    CATEGORY receptor
    SUBCELLULAR LOCALIZATION extracellular
        plasma membrane
    basic FUNCTION
  • cofactor for the cleavage and activation of PAR4 (F2RL3) by F2 (mouse)
  • thrombin activated receptor
  • activating platelets after binding thrombin
  • is a previously unknown modulator of visceral nociception
  • involved in signaling of platelet aggregation via Ca2+ mobilization and synergistic P2Y12 receptor activation
  • F2R and F2RL3 stimulate different signaling pathways in platelets and likely cooperate to mediate the complete response of the platelets to thrombin
  • is involved in sustained platelet activation, and it invokes sustained intracellular calcium response in platelets, phosphyltidylserine exposure, thrombin generation, and fibrin deposition
    • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • F2RL2 cofactor for activation by thrombin
  • mediating cathepsin G dependent platelet secretion and aggregation
  • interaction between F2R and F2RL3, F2RL3 also interacts with the P2Y12 receptor on platelets to alter signaling
  • uses its anionic cluster to interact with alpha-thrombin and this interaction is important even in the presence of F2R
  • is a target of MASP1 (MASP1-induced F2RL3 activation could contribute to the development of the inflammatory reaction)
  • F2R and F2RL3 are functionally expressed in large myelinated fibre neurons, and are also expressed in small nociceptors of the peptidergic subclass, where they are able to potentiate TRPV1 activity
  • promotes cell migration via F2RL3
  • thrombin activates platelets by binding and cleaving protease-activated receptors F2R and F2RL3
  • KLK1 gain de function in tubular epithelial cells may mediate pro-inflammatory pathway and F2RL3 activation during diabetic nephropathy
  • PCTP is a regulator of platelet F2RL3 function
    • cell & other
    REGULATION
    activated by thrombin or trypsin,mediates platelets response to cathepsin G
    proteases including thrombin (proteolytic cleavage of its extracellular N terminus,generating a new receptor N terminus which functions as a tethered ligand and activates the receptor
    independently of GPIbalpha and ADP
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    during the progression of colon and prostate cancers
    tumoral     --low  
    occurs frequently in gastric cancers, may result from hypermethylation of the promoter and exhibits association with more aggressive gastric cancer
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • blood-brain barrier disruption and cerebral edema were also attenuated in PAR4-/- mice compared with wild-type animals