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Symbol F2R contributors: mct - updated : 18-01-2017
HGNC name coagulation factor II (thrombin) receptor
HGNC id 3537
Location 5q13.3      Physical location : 76.011.867 - 76.031.594
Synonym name
  • thrombin receptor, proteinase activated receptor 1
  • protease-activated receptor-1
  • Synonym symbol(s) TRBR, PAR1, CF2R, TR, HTR, PAR
    TYPE functioning gene
    STRUCTURE 19.73 kb     2 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter
    Binding site   HRE
    text structure functional androgen response element (ARE) located in the promoter upstream of the transcription start site at -1791 to -1777
    MAPPING cloned Y linked   status confirmed
    Map see F2RL1
    regionally located centrometric to the common proximal breakpoint
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    2 - 3847 - 425 - 2001 11533492
    3 - 3942 - 304 - 2001 11533492
    Rna function mRNA appears to be expressed by a subset of neurons, including granule cells in the dentate gyrus
    Type widely
       expressed in (based on citations)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularvessel   highly Homo sapiens
    Digestiveintestine     Homo sapiens
    Lymphoid/Immunespleen   moderately
    Nervousbrainlimbic systemhippocampusdentate gyrushighly Homo sapiens
    SystemCellPubmedSpeciesStageRna symbol
    Blood/Hematopoieticplatelet Homo sapiens
    Cardiovascularendothelial cell Homo sapiens
    Digestiveenterocyte Homo sapiens
    Lymphoid/Immunelymphocyte Homo sapiens
    Nervousastrocyte Homo sapiens
    Nervousglia Homo sapiens
    cell lineage
    cell lines
    at STAGE
  • seven transmembrane segments (7TM) receptor
  • mono polymer heteromer , dimer
  • G protein coupled receptor superfamily
  • PAR family
  • CATEGORY protooncogene , receptor membrane G
        plasma membrane
    basic FUNCTION
  • high activity receptor for activated thrombin
  • modulate endothelial cell, function in developing blood vessels
  • involved in the invasive phase of placentation
  • involved in STAT protein nuclear translocation
  • involved in the invasive and metastatic processes of various cancers
  • distinct roles of F2R, F2RL1 in signal transduction regulation of endothelial nitric oxide synthase
  • PROC induces F2R phosphorylation and desensitizes endothelial cells to thrombin signaling but promotes limited receptor cleavage and negligible internalization and degradation even after prolonged PROC exposure
  • in microglia may be involved in the regulation of inflammatory reactions modulating the balance between pro- and anti-inflammatory cytokines possibly through SOCS induction
  • plays critical roles in cancer, angiogenesis, inflammation, and thrombosis
  • involved in a PAR1-dependent Ca2+ signals and migration
  • plays a role in malignant and physiological invasion processes
  • in gastric carcinoma cells, its activation can trigger an array of responses that would promote tumor cell growth and invasion
  • its activation during normal function or pathological conditions, such as during ischemia or hemorrhage, can increase the excitability of dentate granule cells
  • its activation promotes EPN1 de-ubiquitination, which may increase its endocytic adaptor activity to facilitate receptor internalization
  • F2R and F2RL3 stimulate different signaling pathways in platelets and likely cooperate to mediate the complete response of the platelets to thrombin
  • has a role in remodelling the vasculature in the small intestine
  • displays constitutive and agonist-induced internalization
  • critical and novel role for the coagulation cascade, mediated in part by thrombin-F2R interaction, and regulates hematopoietic stem cells (HSCs) maintenance and a reciprocal interplay between HSCs and the dynamic bone structure
  • in addition to desensitization, internalization and lysosomal sorting of activated F2R are critical for the termination of signaling
  • contributes to leukemic stem cell maintenance
  • F2R-stimulated platelet releasate promotes angiogenic activities of endothelial progenitor cells
  • F2R signaling pathway contributes to epileptogenesis following status epilepticus (SE)
  • key role for F2R during S. pneumoniae lung infection that is mediated, at least in part, by influencing multiple downstream inflammatory mediators
  • CELLULAR PROCESS cell life, cell death/apoptosis
    cell migration & motility
    PHYSIOLOGICAL PROCESS coagulation/hemostasis , development , inflammation
  • angiogenesis
  • morphogenesis
  • KLK6-signaling axis in CNS neurons that is mediated by F2R and F2RL1 and is positioned to contribute to neurodegeneration
  • a component
  • F2R and F2RL1 form a heterodimer that exhibits unique trafficking and signaling behaviors compared with receptor protomers
  • role for F8 and thrombin/F2R in regulating hematopoiesis and its interplay with the bone structure
  • undergoing proteolytic irreversible activation by coagulant and anti-coagulant proteases
  • MMP1/F2R axis may play a role in neurogenesis following physiological and/or pathological stimuli
    small molecule
  • thrombin
  • coupled to calcium, ERK, and AKT signaling (modulating growth in native lens tissue and cultured cells)
  • F2R stimulation upregulates the expression of the suppressor of cytokine signaling-3 (SOCS3)
  • interacting with EDG3, SPHK1 (signaling controls dissemination of inflammation from the lymphatics)
  • BICD1 is a direct interactor with the C-terminal cytoplasmic domain of F2R
  • link between F2R signal termination and internalization through the non-G protein effector, BICD1
  • 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
  • occupancy of PROCR by its natural ligand modulates the F2R-dependent signaling specificity of coagulation proteases
  • MMP1 is an important activator of F2R in sepsis
  • interaction between F2R and F2RL3, F2RL3 also interacts with the P2Y12 receptor on platelets to alter signaling
  • interacting with GZMK (extracellular GZMK is capable of activating F2R and inducing fibroblast cytokine secretion and proliferation)
  • interacting with EPN1 (adaptor protein complex-2 and EPN1 are both critical mediators of agonist-stimulated F2R internalization)
  • thrombin activates platelets by binding and cleaving protease-activated receptors F2R and F2RL3
  • F3 mediates signalling through coagulation proteases that activate the G-protein-coupled receptors F2R and F2RL1
  • MMP1 is a collagenase and activator of the G protein-coupled protease activated receptor-1 (F2R)
  • PDCD6IP binds to F2R, recruits ESCRT-III, and mediates receptor sorting to intraluminal vesicles (ILVs) of multivesicular bodies (MVBs)/lysosomes
  • AP3B1 facilitates F2R interaction with PDCD6IP, suggesting that AP3B1 functions before F2R engagement of PDCD6IP and multivesicular bodies (MVBs)/lysosomes sorting
  • F3 participates in protease-activated receptor F2R and F2RL1 activation
  • correlation between F2R and FGFR1 suggests an association of the two receptors with a more aggressive breast cancer phenotype and, consequently, a potential role during tumor progression
  • thrombin binds to and cleaves the N terminus of F2R, generating a new N terminus that functions as a tethered ligand that cannot diffuse away
  • TFAP2A regulates activated F2R signaling by altering receptor surface expression and through recruitment of regulator of G protein signaling (RGS) proteins
  • RAB11B is a critical regulator of F2R trafficking
  • RAB11A and RAB11B differentially regulate intracellular trafficking of PAR1 through distinct endosomal sorting mechanisms
  • F2R agonist is MMP1
  • thrombin upregulates LCN2 through F2R activation and causes brain damage in brain injury
  • KLK6-F2R-mediated inflammation in the skin alone is sufficient to drive inflammatory joint disease
  • cell & other
    activated by
  • 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
  • MMP1 (cleaving the receptor at the proper site to generate PAR1-dependent Ca2+ signals and migration)
  • cleaved and activated by thrombin and other extracellular proteases which are released during tissue trauma and inflammation
    Other regulated transcriptionally by androgens
    regulated by F2RL1 (F2RL1 regulates the F2R hyperplastic response to arterial injury leading to stenosis)
    palmitoylation of F2R regulates appropriate utilization of tyrosine-based motifs by adaptor proteins and endocytic trafficking, processes that are critical for maintaining appropriate expression of F2R at the cell surface
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in prostate cancer progression in androgen-dependent and -independent phases
    tumoral     --over  
    in blasts from acute myeloid leukemia, and in chronic myeloid leukemia patients in blast phase
    Variant & Polymorphism
    Candidate gene
    Therapy target
    therapeutics that target MMP1-F2R may prove beneficial in the treatment of sepsis
    potentially important therapeutic target for the treatment of gastric cancer.