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FLASH GENE
Symbol F2RL1 contributors: mct/npt - updated : 24-10-2015
HGNC name coagulation factor II (thrombin) receptor-like 1
HGNC id 3538
Location 5q13.3      Physical location : 76.114.832 - 76.131.139
Synonym name
  • thrombin-receptor, proteinase activated receptor 2
  • G-protein coupled receptor 11
  • Synonym symbol(s) GPR11, PAR2, PAR-2
    DNA
    TYPE like-sequence
    STRUCTURE 16.31 kb     2 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked   status confirmed
    Map cen - D5S1977 - D5S424 - F2RL1 - F2R - F2RL2 - D5S2529 - D5S2596 - qter
    Authors Schmidt (97),Guyonnet Duperat (98)
    Physical map
    EFG2 5q13 lipoma HMGIC fusion partner-like 2 TINP1 5q13.3 TGF beta-inducible nuclear protein 1 KIAA0888 5q13.3 KIAA0888 protein LOC260421 5q13 actin related protein 2/3 complex subunit 1A pseudogene LOC389303 5 hypothetical gene supported by BC039003 LOC391796 5 similar to hypothetical protein FLJ10891 C2GNT3 5q12 similar to hypothetical protein FLJ10891 FLJ40191 5q13.3 hypothetical protein FLJ40191 HMGCR 5q13.3-q14 3-hydroxy-3-methylglutaryl-Coenzyme A reductase COL4A3BP 5q13.1 collagen, type IV, alpha 3 (Goodpasture antigen) binding protein POLK 5q13 polymerase (DNA directed) kappa LOC391797 5 similar to hypothetical protein LOC348094 FLJ35779 5q13.3 hypothetical protein FLJ35779 LOC389304 5 hypothetical gene supported by AK125735 LOC391798 5 similar to importin alpha 1b LOC134356 5q13.3 similar to breast cancer associated protein BRAP1; bridging integrator-2 LOC134357 5q13.3 similar to mitochondrial aconitase LOC391799 5 similar to spermine synthase; spermidine aminopropyltransferase SV2C 5q13.3-q14.1 similar to spermine synthase; spermidine aminopropyltransferase LOC391800 5 similar to U1 snRNP-specific protein C IQGAP2 5q13.3 IQ motif containing GTPase activating protein 2 F2RL2 5q13 coagulation factor II (thrombin) receptor-like 2 F2R 5q13 coagulation factor II (thrombin) receptor F2RL1 5q13 coagulation factor II (thrombin) receptor-like 1 S100Z 5q14.1 S100Z protein CRHBP 5q11.2-q13.3 corticotropin releasing hormone binding protein HSU84971 5q14.1 vasculogenesis gene on 5q ZBED3 5q13.2 zinc finger, BED domain containing 3 LOC285711 5q14.1 hypothetical LOC285711 PDE8B 5q13.2 phosphodiesterase 8B ATQL1 5q14 antiquitin-like 1 FLJ10904 5q14.1 hypothetical protein FLJ10904 LOC391801 5 similar to ribosomal protein S2 LOC389305 5 similar to 60S ribosomal protein L7 OTP 5q13.3 orthopedia homolog (Drosophila) TBCA 5q13.3 tubulin-specific chaperone A ACTBP2 5q14.1 actin, beta pseudogene 2 AP3B1 5q12-q13.2 adaptor-related protein complex 3, beta 1 subunit SCAMP1 5q13.3-q14.1 secretory carrier membrane protein 1 LHFPL2 5q13.3 lipoma HMGIC fusion partner-like 2
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    2 - 2883 44.1 397 - Moriyuki (2008)
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveintestinesmall intestine  moderately
     intestinelarge intestinecolon moderately
     liver   moderately
    Endocrinepancreas   moderately
    Respiratoryrespiratory tract     Homo sapiens
    Urinarykidney   highly Homo sapiens
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Epithelialbarrier/liningendothelium  
    Muscularsmooth    Homo sapiens
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Blood/Hematopoieticeosinophil
    Blood/Hematopoieticmonocyte
    Lymphoid/Immunemacrophage
    Skin/Tegumentkeratinocyte
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • seven transmembrane segments (7TM) receptor, orphan receptor, coagulation
  • multiple intracellular domains required for the interaction with COPS5
  • mono polymer heteromer , dimer
    HOMOLOGY
    interspecies homolog to murine F2rl1
    Homologene
    FAMILY
  • G protein coupled receptor superfamily
  • protease activated receptor family
  • CATEGORY receptor membrane G
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,Golgi
    basic FUNCTION
  • mediating phagocytosis in a RhoA dependent manner in keratinocytes
  • involved in the invasive phase of placentation
  • modulating eosinophil function
  • may have a role in the regulation of vascular tone
  • may be an important regulator of skin mast cell function during cutaneous inflammation and hypersensitivity
  • distinct roles of F2R, F2RL1 in signal transduction regulation of endothelial nitric oxide synthase
  • regulates the F2R hyperplastic response to arterial injury leading to stenosis
  • its activation contributes to determination of cells of both osteoblast and osteoclast lineages within bone marrow, and thereby participates in the regulation of skeletal growth and bone repair
  • important role in the pathogenesis of collagen-induced arthritis
  • receptor for inflammatory proteases, and is a major mediator of neurogenic inflammation and pain
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS inflammation
    text
  • organogenesis
  • anti-inflammatory signal
  • PATHWAY
    metabolism
    signaling signal transduction
    mediating signal transduction by RhoA (ARHA)
    a component
  • F2R and F2RL1 form a heterodimer that exhibits unique trafficking and signaling behaviors compared with receptor protomers
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • F2RL1 and TMED2 interaction occurs between the N-terminal region of TMED2 p24A-GL (GOLD domain with a small linker)) and the second extracellular loop of F2RL1, and after receptor activation, F2RL1 dissociates from TMED2
  • collectively, membrane PRTN3 acts as a non-opsonic phagocytosis receptor for bacteria probably by activating F2RL1 in neutrophils
  • F3 mediates signalling through coagulation proteases that activate the G-protein-coupled receptors F2R and F2RL1
  • F3-binding to its ligand F7 induces activation of F2RL1 and this event is thought to considerably influence atherosclerosis and tumor angiogenesis
  • F3 participates in protease-activated receptor F2R and F2RL1 activation
  • F2RL1 activation generates a signal that induces sustained activation of TRPV4, which requires a key tyrosine residue (TRPV4-Tyr-110)
  • ELANE stimulates the secretion of MUC5AC from airway epithelial cells, and can increase F2RL1 expression and MUC5AC release
  • extra-pancreatic PRSS3 is produced by esophageal adenocarcinoma (EA) and activates likely F2RL1 in an autocrine manner (F2RL1 activation increases cancer cell proliferation, and promotes cancer cell survival)
  • novel functional network of ELANE, secretases, and F2RL1 that regulate CXCR1 expression on neutrophils
  • CTSS is a biased agonist of F2RL1 that causes F2RL1- and TRPV4-dependent inflammation and pain
  • ELANE activates protease-activated receptor-2 (F2RL1) and transient receptor potential vanilloid 4 (TRPV4) to cause inflammation and pain
  • cell & other
    REGULATION
    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
    TMPRSS2
    Other regulated by plasmin and elastase
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional       gain of function
    induced the redistribution of COPS5 from the plasma membrane to the cytosol, but did not influence expression of COPS5
    Susceptibility
  • to arthritis
  • to atopic dermatitis
  • Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    miscelleaneousurinarychronic kidney disease
    F2RL1 antagonists could be useful disease-modifying, anti-inflammatory agents in kidney disease
    ANIMAL & CELL MODELS