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F2RL1 Gene

protein-coding   GIFtS: 64
GCID: GC05P076120

Coagulation Factor II (Thrombin) Receptor-Like 1


(Previous symbol: GPR11)
  See related diseases
at  

(According to 1HGNC, 2Entrez Gene,
3UniProtKB/Swiss-Prot, 4UniProtKB/TrEMBL, 5OMIM, 6GeneLoc, 7Ensembl, 8DME, 9miRBase, 10fRNAdb, 12H-InvDB, 13NCBI, 14NONCODE, and/or 15RNAdb)
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Aliases
Coagulation Factor II (Thrombin) Receptor-Like 11 2     G-Protein Coupled Receptor 112 3
GPR111 2 3 5     Proteinase-Activated Receptor-21
PAR22 3 5     Protease-Activated Receptor 22
Coagulation Factor II Receptor-Like 12 3     Proteinase-Activated Receptor 22
Thrombin Receptor-Like 12 3     PAR-23

External Ids:    HGNC: 35381   Entrez Gene: 21502   Ensembl: ENSG000001642517   OMIM: 6009335   UniProtKB: P550853   

Export aliases for F2RL1 gene to outside databases

Previous GC identifers: GC05P074920 GC05P076349 GC05P076153 GC05P076198 GC05P076150 GC05P071322


(According to Entrez Gene, GeneCards, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
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Entrez Gene summary for F2RL1 Gene:
Coagulation factor II (thrombin) receptor-like 1 (F2RL1) is a member of the large family of 7-transmembrane-region
receptors that couple to guanosine-nucleotide-binding proteins. F2RL1 is also a member of the protease-activated
receptor family. It is activated by trypsin, but not by thrombin. It is activated by proteolytic cleavage of its
extracellular amino terminus. The new amino terminus functions as a tethered ligand and activates the receptor.
The F2RL1 gene contains two exons and is widely expressed in human tissues. The predicted protein sequence is 83%
identical to the mouse receptor sequence. (provided by RefSeq, Jul 2008)

GeneCards Summary for F2RL1 Gene:
F2RL1 (coagulation factor II (thrombin) receptor-like 1) is a protein-coding gene. Diseases associated with F2RL1 include pulmonary vein stenosis, and prostatic hypertrophy. GO annotations related to this gene include G-protein coupled receptor activity and receptor activity. An important paralog of this gene is FFAR3.

UniProtKB/Swiss-Prot: PAR2_HUMAN, P55085
Function: Receptor for trypsin and trypsin-like enzymes coupled to G proteins. Its function is mediated through
the activation of several signaling pathways including phospholipase C (PLC), intracellular calcium,
mitogen-activated protein kinase (MAPK), I-kappaB kinase/NF-kappaB and Rho. Can also be transactivated by cleaved
F2R/PAR1. Involved in modulation of inflammatory responses and regulation of innate and adaptive immunity, and
acts as a sensor for proteolytic enzymes generated during infection. Generally is promoting inflammation. Can
signal synergistically with TLR4 and probably TLR2 in inflammatory responses and modulates TLR3 signaling. Has a
protective role in establishing the endothelial barrier; the activity involves coagulation factor X. Proposed to
have a bronchoprotective role in airway epithelium, but also shown to compromise the airway epithelial barrier by
interrupting E-cadherin adhesion. Involved in the regulation of vascular tone; activation results in hypotension
presumably mediated by vasodilation. Associates with a subset of G proteins alpha subunits such as G alpha-q, G
alpha-11, G alpha-14, G alpha-12 and G alpha-13, but probably not with G(o) alpha, G(i) subunit alpha-1 and G(i)
subunit alpha-2. However, according to PubMed:21627585 can signal through G(i) subunit alpha. Believed to be a
class B receptor which internalizes as a complex with arrestin and traffic with it to endosomal vesicles,
presumably as desensitized receptor, for extended periods of time. Mediates inhibition of TNF-alpha stimulated
JNK phosphorylation via coupling to G alpha-q/11; the function involves dissociation of RIPK1 and TRADD from
TNFR1. Mediates phosphorylation of nuclear factor NF-kappa-B RELA subunit at 'Ser-536'; the function involves
IKBKB and is predominantly independent of G proteins. Involved in cellular migration. Involved in cytoskeletal
rearrangement and chemotaxis through beta-arrestin-promoted scaffolds; the function is independent of G
alpha-q/11 and involves promotion of cofilin dephosphoryltaion and actin filament severing. Induces
redistribution of COPS5 from the plasma membrane to the cytosol and activation of the JNK cascade is mediated by
COPS5. Involved in the recruitment of leukocytes to the sites of inflammation and is the major PAR receptor
capable of modulating eosinophil function such as proinflammatory cytokine secretion, superoxide production and
degranulation. During inflammation promotes dendritic cell maturation, trafficking to the lymph nodes and
subsequent T-cell activation. Involved in antimicrobial response of innate immnune cells; activation enhances
phagocytosis of Gram-positive and killing of Gram-negative bacteria. Acts synergistically with interferon-gamma
in enhancing antiviral responses. Implicated in a number of acute and chronic inflammatory diseases such as of
the joints, lungs, brain, gastrointestinal tract, periodontium, skin, and vascular systems, and in autoimmune
disorders

summary for F2RL1 Gene:
Protease-activated receptors (PARs, also known as thrombin receptors) are G-protein-coupled receptors,
activated by cleavage of their N-terminal domains by serine proteases. Hydrolysis reveals a tethered peptide
ligand, which interacts with the receptor within extracellular loop-2 to affect transmembrane signaling.
Four subtypes of receptors have so far been cloned (PAR1-4). PAR2 is expressed in vascular tissue and highly
vascular organs, which indicates a role for this receptor in the regulation of vascular tone. Trypsin is the
endogenous agonist for PAR2 and receptor activation has been coupled to the nitric oxide signaling pathway,
causing vasodilation and hypotension. PAR2 is implicated in chronic responses associated with vessel
inflammation and wound healing. This receptor stimulates activation of T-cells and neutrophils, promotes
leukocyte rolling, adhesion and extravasation, increases capillary permeability and enhances production of
cytokines. In addition to its vascular roles, PAR2 has multiple functions in the gastrointestinal tract. It
is strongly expressed in enterocytes and stimulates prostaglandin (PG) E2 and PGF1alpha synthesis.
Pancreatic PAR2 expression and activation promotes secretory function, in particular increases amylin
secretion.

Gene Wiki entry for F2RL1 (Protease activated receptor 2) Gene


(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 75), Regulatory elements and Epigenetics data according to QIAGEN, and/or SwitchGear Genomics)
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Regulatory elements:
   Regulatory transcription factor binding sites in the F2RL1 gene promoter:
         AREB6   c-Fos   RFX1   AP-1   HNF-1   Sox9   c-Jun   HNF-1A   GATA-1   
         Other transcription factors

SwitchGear Promoter luciferase reporter plasmidF2RL1 promoter sequence
   Search Chromatin IP Primers for F2RL1

Epigenetics:
DNA Methylation CpG Assay Predesigned for Pyrosequencing in human, mouse, rat F2RL1


Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 5q13   Ensembl cytogenetic band:  5q13.3   HGNC cytogenetic band: 5q13

F2RL1 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
F2RL1 gene location

GeneLoc information about chromosome 5         GeneLoc Exon Structure

GeneLoc location for GC05P076120:  view genomic region     (about GC identifiers)

Start:
76,114,758 bp from pter      End:
76,131,140 bp from pter
Size:
16,383 bases      Orientation:
plus strand

(According to 1UniProtKB, HORDE, 2neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, and/or Cloud-Clone Corp.,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Cloud-Clone Corp., Antibodies by EMD Millipore, R&D Systems, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, LSBio, Abcam, Cloud-Clone Corp, and/or others.)
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UniProtKB/Swiss-Prot: PAR2_HUMAN, P55085 (See protein sequence)
Recommended Name: Proteinase-activated receptor 2 precursor  
Size: 397 amino acids; 44126 Da
Subunit: Interacts with TLR4, COPS5 and TMED2. Interacts with GNAQ, GNA11, GNA12, GNA13 and GNA14 (By similarity)
Miscellaneous: Synthetic PAR agonist peptides (APs) that mimic the first six amino acids of the newly formed
N-terminus activate the native, uncleaved receptor nonenzymatically by binding directly to the corresponding
second extracellular loop to mediate signaling
Secondary accessions: Q13317 Q13346 Q53XJ8

Explore the universe of human proteins at neXtProt for F2RL1: NX_P55085

Explore proteomics data for F2RL1 at MOPED

Post-translational modifications: 

  • A proteolytic cleavage generates a new N-terminus that functions as a tethered ligand. Activating serine proteases
    include trypsin, mast cell tryptase, coagulation factors VII and Xa, myeloblastin/PRTN3 and membrane-type serine
    protease 1/ST14. Proposed subsequent cleaveage by serine proteases is leading to receptor deactivation and
    include neutrophil elastase and cathepsin G. At least in part, implicated proteases are also shown to activate
    the receptor; the glycosylation status of the receptor is thought to contribute to the difference. In addition to
    conventional trypsin-like proteases is proposed to be activated by other proteases and glycosidases derived from
    bacteria, fungi and insects: serine protease allergens such as dust mite Der p3 and Der p9 and mold Pen c13,
    Porphyromonas gingivalis arginine-specific (trypsin-like) cysteine proteinases called gingipains, Streptomyces
    griseus exogenous chitinase, and an Alternaria alternata aspartate protease. Cleavage by the Alternaria alternata
    aspartate protease generates non-conventional processed forms1
  • N-glycosylated and sialylated1
  • Multiple phosphorylated on serine and threonine residues in the cytoplasmic region upon receptor activation;
    required for receptor desensitization and recruitment of beta-arrestin1
  • Monoubiquitinated by CBL at the plasma membrane and in early endosomes; not required for receptor endocytosis but
    for translocation to late endosomes or lysosomes. Deubiquitination involves STAMBP and USP8; required for
    lysosomal trafficking and receptor degradation1
  • Ubiquitination2 at Lys368
  • Glycosylation2 at Asn30, Thr45, Ser46, Thr49, Thr54, Asn222
  • Modification sites at PhosphoSitePlus

  • See F2RL1 Protein Expression from SPIRE MOPED, PaxDB, and MaxQB

    REFSEQ proteins: NP_005233.3  
    ENSEMBL proteins: 
     ENSP00000425622   ENSP00000296677  
    Reactome Protein details: P55085

    F2RL1 Human Recombinant Protein Products:

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    F2RL1 Antibody Products:

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    Abcam antibodies for F2RL1
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    F2RL1 Assay Products:

    Browse Kits and Assays available from EMD Millipore
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    GenScript F2RL1-overexpressing Cell Line for Assay
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    Browse ELISAs at Cloud-Clone Corp.
    Browse CLIAs at Cloud-Clone Corp.


    (According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
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    HGNC Gene Families:
    F2R: GPCR / Class A : Protease activated receptors

    IUPHAR Guide to PHARMACOLOGY protein family classification: PAR2
    Protease-activated receptors

    4 InterPro protein domains:
     IPR002281 Pro_rcpt_2
     IPR017452 GPCR_Rhodpsn_7TM
     IPR003912 Protea_act_rcpt
     IPR000276 GPCR_Rhodpsn

    Graphical View of Domain Structure for InterPro Entry P55085

    ProtoNet protein and cluster: P55085

    2 Blocks protein domains:
    IPB002281 Protease activated receptor 2 precursor signature
    IPB003912 Protease activated receptor precursor signature


    UniProtKB/Swiss-Prot: PAR2_HUMAN, P55085
    Similarity: Belongs to the G-protein coupled receptor 1 family


    F2RL1 for domains           About GeneDecksing


    (According to 1UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or 2DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, inGenious Targeting Laboratory, genOway,
    transcription factor targeting from QIAGEN and/or HOMER, miRNA Gene Targets from miRTarBase, shRNA from OriGene, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, SwitchGear Genomics, Gene Editing from DNA2.0, Clones from OriGene, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, ESI BIO, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Molecular Function:

         UniProtKB/Swiss-Prot Summary: PAR2_HUMAN, P55085
    Function: Receptor for trypsin and trypsin-like enzymes coupled to G proteins. Its function is mediated through
    the activation of several signaling pathways including phospholipase C (PLC), intracellular calcium,
    mitogen-activated protein kinase (MAPK), I-kappaB kinase/NF-kappaB and Rho. Can also be transactivated by cleaved
    F2R/PAR1. Involved in modulation of inflammatory responses and regulation of innate and adaptive immunity, and
    acts as a sensor for proteolytic enzymes generated during infection. Generally is promoting inflammation. Can
    signal synergistically with TLR4 and probably TLR2 in inflammatory responses and modulates TLR3 signaling. Has a
    protective role in establishing the endothelial barrier; the activity involves coagulation factor X. Proposed to
    have a bronchoprotective role in airway epithelium, but also shown to compromise the airway epithelial barrier by
    interrupting E-cadherin adhesion. Involved in the regulation of vascular tone; activation results in hypotension
    presumably mediated by vasodilation. Associates with a subset of G proteins alpha subunits such as G alpha-q, G
    alpha-11, G alpha-14, G alpha-12 and G alpha-13, but probably not with G(o) alpha, G(i) subunit alpha-1 and G(i)
    subunit alpha-2. However, according to PubMed:21627585 can signal through G(i) subunit alpha. Believed to be a
    class B receptor which internalizes as a complex with arrestin and traffic with it to endosomal vesicles,
    presumably as desensitized receptor, for extended periods of time. Mediates inhibition of TNF-alpha stimulated
    JNK phosphorylation via coupling to G alpha-q/11; the function involves dissociation of RIPK1 and TRADD from
    TNFR1. Mediates phosphorylation of nuclear factor NF-kappa-B RELA subunit at 'Ser-536'; the function involves
    IKBKB and is predominantly independent of G proteins. Involved in cellular migration. Involved in cytoskeletal
    rearrangement and chemotaxis through beta-arrestin-promoted scaffolds; the function is independent of G
    alpha-q/11 and involves promotion of cofilin dephosphoryltaion and actin filament severing. Induces
    redistribution of COPS5 from the plasma membrane to the cytosol and activation of the JNK cascade is mediated by
    COPS5. Involved in the recruitment of leukocytes to the sites of inflammation and is the major PAR receptor
    capable of modulating eosinophil function such as proinflammatory cytokine secretion, superoxide production and
    degranulation. During inflammation promotes dendritic cell maturation, trafficking to the lymph nodes and
    subsequent T-cell activation. Involved in antimicrobial response of innate immnune cells; activation enhances
    phagocytosis of Gram-positive and killing of Gram-negative bacteria. Acts synergistically with interferon-gamma
    in enhancing antiviral responses. Implicated in a number of acute and chronic inflammatory diseases such as of
    the joints, lungs, brain, gastrointestinal tract, periodontium, skin, and vascular systems, and in autoimmune
    disorders

         Genatlas biochemistry entry for F2RL1:
    coagulation factor II (thrombin) receptor proteinase-activated receptor 2,G protein coupled receptor superfamily

         Gene Ontology (GO): Selected molecular function terms (see all 7):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0001965G-protein alpha-subunit binding ISS--
    GO:0004872receptor activity TAS8615752
    GO:0004930G-protein coupled receptor activity ISS--
    GO:0005102receptor binding TAS8615752
    GO:0005515protein binding IPI15708858
         
    F2RL1 for ontologies           About GeneDecksing


    Phenotypes:
         1 GenomeRNAi human phenotype for F2RL1:
     Decreased viability of wild-ty 

         Selected MGI mutant phenotypes (inferred from 7 alleles(MGI details for F2rl1) (see all 17):
     behavior/neurological  cardiovascular system  cellular  embryogenesis  endocrine/exocrine gland 
     hematopoietic system  homeostasis/metabolism  immune system  integument  limbs/digits/tail 
     liver/biliary system  mortality/aging  nervous system  no phenotypic analysis  renal/urinary system 

    F2RL1 for phenotypes           About GeneDecksing

    Animal Models:
         MGI mouse knock-outs for F2RL1: F2rl1tm1Jkaw F2rl1tm1Bpd F2rl1tm1Cgh F2rl1tm1Mslb

       inGenious Targeting Laboratory: Let us create your new Knockout/Knockin mouse model for F2RL1
       inGenious Targeting Laboratory: Contact us about creating complex and humanized mouse models for F2RL1

       genOway customized KO model: permanent, tissue-specific or time-controlled inactivation for F2RL1
       genOway customized Knockin model: humanization, point mutation, expression monitoring, etc. for F2RL1

    miRNA
    Products:
        
    miRTarBase miRNAs that target F2RL1:
    hsa-mir-1 (MIRT023577)

    Block miRNA regulation of human, mouse, rat F2RL1 using miScript Target Protectors
    Selected qRT-PCR Assays for microRNAs that regulate F2RL1 (see all 10):
    hsa-miR-142-5p hsa-miR-4324 hsa-miR-548e hsa-miR-548o hsa-miR-551b* hsa-miR-340 hsa-miR-4282 hsa-miR-3921
    SwitchGear 3'UTR luciferase reporter plasmidF2RL1 3' UTR sequence
    Inhib. RNA
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    Predesigned siRNA for gene silencing in human, mouse, rat F2RL1

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    DNA2.0 Custom Protein Engineering Service for F2RL1

    Clone
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    GenScript: all cDNA clones in your preferred vector: F2RL1 (NM_005242)
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    Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat F2RL1

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    Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for F2RL1


    (According to UniProtKB, COMPARTMENTS Subcellular localization database, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Subcellular locations from UniProtKB/Swiss-Prot
    PAR2_HUMAN, P55085: Cell membrane; Multi-pass membrane protein
    Subcellular locations from COMPARTMENTS: 

    CompartmentConfidence
    plasma membrane5
    golgi apparatus4
    extracellular2
    cytoskeleton1
    cytosol1
    endosome1
    nucleus1

    Gene Ontology (GO): 5 cellular component terms:    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005794Golgi apparatus TAS8615752
    GO:0005886plasma membrane TAS--
    GO:0005887integral component of plasma membrane IDA17848177
    GO:0016021integral component of membrane ----
    GO:0031143pseudopodium ISS--

    F2RL1 for ontologies           About GeneDecksing


    (SuperPaths according to PathCards, Pathways according to R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Sino Biological, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to QIAGEN, and/or STRING, Interactions according to 1UniProtKB, 2MINT, 3I2D, and/or 4STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene).
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    SuperPaths for F2RL1 About   (see all 9)  
    See pathways by source

    SuperPathContained pathways About
    1Peptide ligand-binding receptors
    Class A/1 (Rhodopsin-like receptors)0.71
    GPCRs, Class A Rhodopsin-like0.43
    GPCR ligand binding0.71
    Neuroactive ligand-receptor interaction0.36
    Peptide ligand-binding receptors0.60
    2Signaling by GPCR
    Signaling by GPCR0.90
    Signal Transduction0.58
    GPCR downstream signaling0.90
    3Gastrin-CREB signalling pathway via PKC and MAPK
    Gastrin-CREB signalling pathway via PKC and MAPK0.90
    G alpha (q) signalling events0.90
    4p70S6K Signaling
    p70S6K Signaling0.60
    5Neuropeptides signaling through G protein alpha i and G protein alpha q
    Neuropeptides signaling through G protein alpha i and G protein alpha q0.46

    Pathways by source                                                                                                                                                                 See SuperPaths
    Show all pathways

    1 Downloadable PowerPoint Slide of GeneGlobe Pathway Central Maps for F2RL1
        p70S6K Signaling

    2 Cell Signaling Technology (CST) Pathways for F2RL1
        Angiogenesis
    Cytoskeletal Signaling

    1 BioSystems Pathway for F2RL1
        GPCRs, Class A Rhodopsin-like


    2 Reactome Pathways for F2RL1
        Peptide ligand-binding receptors
    G alpha (q) signalling events


    3 Kegg Pathways  (Kegg details for F2RL1):
        Neuroactive ligand-receptor interaction
    Inflammatory mediator regulation of TRP channels
    African trypanosomiasis


    F2RL1 for pathways           About GeneDecksing

        Pathway & Disease-focused RT2 Profiler PCR Arrays including F2RL1: 
              G Protein Coupled Receptors 384HT in human mouse rat
              Endothelial Cell Biology in human mouse rat
              Antifungal Response in human mouse rat

    Interactions:

        GeneGlobe Interaction Network for F2RL1

    STRING Interaction Network Preview (showing 5 interactants - click image to see 25)

    Selected Interacting proteins for F2RL1 (P550851, 3 ENSP000002966774) via UniProtKB, MINT, STRING, and/or I2D (see all 144)
    InteractantInteraction Details
    GeneCardExternal ID(s)
    COPS5Q929051, 3, ENSP000003505124EBI-4303189,EBI-594661 I2D: score=1 STRING: ENSP00000350512
    CBLP226811, 3, ENSP000002640334EBI-4303189,EBI-518228 I2D: score=1 STRING: ENSP00000264033
    GPRASP1Q5JY773, ENSP000003551464I2D: score=2 STRING: ENSP00000355146
    CAPN1P073843, ENSP000002792474I2D: score=1 STRING: ENSP00000279247
    F2P007343, ENSP000003085414I2D: score=1 STRING: ENSP00000308541
    About this table

    Gene Ontology (GO): Selected biological process terms (see all 49):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0002286T cell activation involved in immune response ISS--
    GO:0002690positive regulation of leukocyte chemotaxis IDA17991872
    GO:0002741positive regulation of cytokine secretion involved in immune response IDA11441110
    GO:0003104positive regulation of glomerular filtration ISS--
    GO:0006954inflammatory response IEA--

    F2RL1 for ontologies           About GeneDecksing



    (Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience, ApexBio, HMDB, BitterDB, and/or Novoseek, Ligands according to IUPHAR, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB)
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    Browse Small Molecules at EMD Millipore
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      Browse compounds at ApexBio 

    Compounds for F2RL1 available from Tocris Bioscience    About this table
    CompoundAction CAS #
    SCH 79797 dihydrochloride Potent, selective non-peptide PAR1 antagonist [245520-69-8]
    SLIGKV-NH2PAR2 receptor agonist[190383-13-2]
    TFLLR-NH2PAR1-activating peptide[197794-83-5]
    2-Furoyl-LIGRLO-amidePotent and selective PAR2 agonist[729589-58-6]
    TRAP-6PAR1 peptide fragment (residues 42-47); acts as a PAR1 agonist[141136-83-6]

    6 IUPHAR Ligands for F2RL1 (PAR2)    About this table
    LigandTypeActionAffinityPubmed IDs
    2-furoyl-LIGRLO-amide
    AgonistFull agonist5.414976230
    SLIGRL-NH2
    AgonistAgonist5.418179608
    2-furoyl-LIGRL[N[3H]propionyl]-O-NH2
    NoneNone5.418477767
    SLIGKV-NH2
    AgonistAgonist5.418179608
    2-furoyl-LIGRL[N-(Alexa Fluor 594)-O]-NH2
    NoneNone5.418477767
    trans-cinnamoyl-LIGRLO [N-[3H]propionyl]-NH2
    NoneNone5.410411588

    Selected Novoseek inferred chemical compound relationships for F2RL1 gene (see all 79)    About this table
    Compound   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    apc-366 79 2 9020112 (1)
    serine 70.3 93 12759451 (3), 17304351 (2), 11356985 (2), 11441110 (2) (see all 65)
    calcium 51.1 85 12630574 (3), 20056842 (3), 12595338 (2), 10408902 (2) (see all 55)
    pd 98,059 50.6 5 17982475 (1), 18031579 (1), 15655297 (1), 16467309 (1) (see all 5)
    trypsinogen 50 2 17699557 (1), 14583448 (1)
    butaprost 49.4 3 18981149 (1), 17028262 (1), 15539459 (1)
    sbti 48 1 12415569 (1)
    vegf 47.6 33 16650817 (3), 16525644 (2), 15971170 (1), 16625496 (1) (see all 29)
    leupeptin 47.5 1 16303958 (1)
    benzamidine 42.3 1 16303958 (1)



    F2RL1 for compounds           About GeneDecksing



    (Secondary structures according to fRNAdb,
    GenBank/EMBL/DDBJ Accessions according to
    Unigene (Build 236 Homo sapiens; Apr 25 2013) or GenBank,
    RefSeq according to Entrez Gene,
    DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
    exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
    siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN, SwitchGear Genomics,
    Tagged/untagged cDNA clones from OriGene, GenScript, DNA2.0, Vector BioLabs, Primers from OriGene, and/or QIAGEN )
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    REFSEQ mRNAs for F2RL1 gene: 
    NM_005242.4  

    2 Ensembl transcripts including schematic representations, and UCSC links where relevant:
    ENST00000514165 ENST00000296677(uc003keo.3)
    miRNA
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    5 AceView cDNA sequences:

    BE005953 AW272877 AI921544 AW578520 BE005956 

    GeneLoc Exon Structure


    (RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, Protein expression images according to data from SPIRE 1MOPED, 2PaxDb, and 3MaxQB, plus additional links to SOURCE, and/or BioGPS, and/or UniProtKB,
    PCR Arrays from QIAGEN, Primers from OriGene, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
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    F2RL1 expression in normal human tissues (normalized intensities)
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS <intensity>2/3
    CGAP TAG: TAAATACAAA
    F2RL1 Expression
    About this image


    F2RL1 expression in embryonic tissues and stem cells    About this table
    Data from LifeMap, the Embryonic Development and Stem Cells Database
     selected tissues (see all 9) fully expand
     
     Kidney (Urinary System)    fully expand to see all 4 entries
             Ureteric Bud Cells Ureteric Bud
             Renal Collecting Duct System
     
     Epiblast (Early Embryonic Tissues)    fully expand to see all 2 entries
             Epiblast Cells Epiblast
             Epiblast Stem Cell line 5
     
     Placenta (Extraembryonic Tissues)    fully expand to see all 2 entries
             Placenta-derived mesenchymal stem cells (family)
     
     Skeletal Muscle (Muscoskeletal System)    fully expand to see all 2 entries
             Muscle Progenitor Cells Mandibular Arch Muscles
     
     Mesenchymal Stem Cells (Uncategorized)    fully expand to see all 2 entries
             Placenta-derived mesenchymal stem cells (family)
    F2RL1 Protein expression data from MOPED1, PaxDb2 and MaxQB3    About this image

    F2RL1 Protein Expression

    UniProtKB/Swiss-Prot: PAR2_HUMAN, P55085
    Tissue specificity: Widely expressed in tissues with especially high levels in pancreas, liver, kidney, small
    intestine, and colon. Moderate expression is detected in many organs, but none in brain or skeletal muscle

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    (Orthologs according to 1,2HomoloGene (2older version, for species not in 1newer version), 3euGenes, 4SGD , 5MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or 6Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
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    This gene was present in the common ancestor of chordates.

    Orthologs for F2RL1 gene from Selected species (see all 13)    About this table
    Organism Taxonomic
    classification
    Gene Description Human
    Similarity
    Orthology
    Type
    Details
    mouse
    (Mus musculus)
    Mammalia F2rl11 , 5 coagulation factor II (thrombin) receptor-like 11, 5 82.17(n)1
    83.96(a)1
      13 (49.53 cM)5
    140631  NM_007974.41  NP_032000.31 
     955117325 
    chicken
    (Gallus gallus)
    Aves F2RL11 coagulation factor II (thrombin) receptor-like 1 71.02(n)
    73(a)
      427213  NM_001012608.1  NP_001012626.1 
    lizard
    (Anolis carolinensis)
    Reptilia --
    Uncharacterized protein
    27(a)
    many ↔ many
    3(113323258-113324292)
    African clawed frog
    (Xenopus laevis)
    Amphibia Xl.55072 Xenopus laevis transcribed sequence with weak similarity more 73.25(n)    BX850546.1 
    zebrafish
    (Danio rerio)
    Actinopterygii f2rl1.21 coagulation factor II (thrombin) receptor-like 1, tandem more 58.69(n)
    54.85(a)
      100073342  NM_001098778.1  NP_001092248.1 


    ENSEMBL Gene Tree for F2RL1 (if available)
    TreeFam Gene Tree for F2RL1 (if available)

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
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    Paralogs for F2RL1 gene
    FFAR32  GPR42  GPR682  P2RY82  GPR652  FFAR22  F2RL22  GPR1322  
    FFAR12  GPR422  F2RL32  F2R2  
    Selected SIMAP similar genes for F2RL1 using alignment to 2 protein entries:     PAR2_HUMAN (see all proteins) (see all similar genes):
    GPR18    C3AR1    F2RL2    GPR33    CCR2    CCR7
    F2R    P2RY6    CCR5    F2RL3    GPR68    CYSLTR2
    KPG_011    LPAR4    P2RY8    SSTR5    FPR1    GPR174

    F2RL1 for paralogs           About GeneDecksing



    (SNPs/Variants according to the 1NCBI SNP Database, 2Ensembl, 3PupaSUITE, 4UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD), the Human Cytochrome P450 Allele Nomenclature Database, and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers, Cancer Mutation PCR Arrays and Assays, and Copy Number PCR Arrays from QIAGEN)
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    Selected SNPs for F2RL1 (see all 464)    About this table    
    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance
    Chr 5 posSequence#AA
    Chg
    TypeMore#Allele
    freq
    PopTotal
    sample
    More
    ----------
    rs781796461,2
    C,F--76112834(+) CCTACG/AAGAGA 1 -- us2k11Minor allele frequency- A:0.03WA 118
    rs6393421,2
    C,F,O,H--76112869(+) TAGATG/ATAATA 1 -- us2k121Minor allele frequency- A:0.07NS MN EA NA 2576
    rs22429831,2
    C,F,H--76112933(+) TAGGAA/GTCAGT 1 -- us2k18Minor allele frequency- G:0.01NS EA CSA WA 632
    rs3759451511,2
    C--76112981(+) TCCCTA/GCAGGA 1 -- us2k10--------
    rs1874508481,2
    --76113019(+) AGGTTA/CCTGTT 1 -- us2k10--------
    rs1423443211,2
    --76113039(+) GAAGTC/TAGCTT 1 -- us2k10--------
    rs22429841,2
    C,F,H--76113080(+) GGTGAG/CAGCTG 1 -- us2k17Minor allele frequency- C:0.01NS EA WA 614
    rs1125279801,2
    C--76113193(+) ATCCT-/CAGA  
            
    CAGAC
    1 -- us2k11Minor allele frequency- CAGA:0.50CSA 2
    rs1898585831,2
    --76113212(+) TAAACC/TTTTAA 1 -- us2k10--------
    rs2006861501,2
    --76113222(+) ACCAC-/GTGTGTG 1 -- us2k10--------

    HapMap Linkage Disequilibrium report for F2RL1 (76114758 - 76131140 bp)

    Structural Variations
         Database of Genomic Variants (DGV) 3 variations for F2RL1:    About this table    
    Variant IDTypeSubtypePubMed ID
    esv994503CNV Deletion20482838
    nsv882211CNV Loss21882294
    nsv882210CNV Gain21882294

    Human Gene Mutation Database (HGMD): F2RL1
    Site Specific Mutation Identification with PCR Assays
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    (in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
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    OMIM gene information: 600933    OMIM disorders: --

    Selected diseases for F2RL1 (see all 97):    
    About MalaCards
    pulmonary vein stenosis    prostatic hypertrophy    papillary adenocarcinoma    growth hormone secreting pituitary adenoma
    neuroleptic malignant syndrome    h. pylori infection    irritable bowel syndrome    pulmonary disease, chronic obstructive
    aids dementia complex    ovarian hyperstimulation syndrome    craniosynostosis    trypanosomiasis
    erythrocytosis    gastroesophageal reflux disease    pancreatitis    acute pancreatitis
    keratoconjunctivitis    periodontal disease    keratoderma    rhinitis

    3 diseases from the University of Copenhagen DISEASES database for F2RL1:
    Pancreatitis     Asthma     Irritable bowel syndrome

    F2RL1 for disorders           About GeneDecksing

    Selected Novoseek inferred disease relationships for F2RL1 gene (see all 76)    About this table

    Disease   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    inflammation 63.6 96 15753914 (5), 11841560 (3), 15654951 (3), 11698614 (2) (see all 70)
    airways disease 48.3 4 14500256 (1), 15809358 (1), 11704532 (1), 16336275 (1)
    necrosis 43.2 51 8663011 (2), 12176089 (1), 13130473 (1), 17979070 (1) (see all 44)
    tumors 40.6 129 17761706 (5), 15250939 (4), 19795460 (4), 17203172 (3) (see all 79)
    asthma 35.9 20 11673222 (2), 11692107 (2), 15753914 (2), 12783571 (1) (see all 12)
    keratoconjunctivitis vernal 26 1 16303958 (1)
    hyperalgesia 23.3 14 15128844 (6), 16967049 (3), 15898281 (1), 18363639 (1) (see all 5)
    inflammatory bowel diseases 22 3 11804840 (1), 19184329 (1)
    apert syndrome 22 1 16373332 (1)
    osteoarthritis 21.1 6 17205215 (2), 17195212 (1), 17328048 (1), 18031579 (1)

    Genetic Association Database (GAD): F2RL1
    Human Genome Epidemiology (HuGE) Navigator: F2RL1 (5 documents)

    Export disorders for F2RL1 gene to outside databases

    (in PubMed. Associations of this gene to articles via 1Entrez Gene, 2UniProtKB/Swiss-Prot, 3HGNC, 4GAD, 5PharmGKB, 6HMDB, 7DrugBank, 8UniProtKB/TrEMBL, 9 Novoseek, and/or 10fRNAdb)
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    PubMed articles for F2RL1 gene, integrated from 10 sources (see all 702):
    (articles sorted by number of sources associating them with F2RL1)
        Utopia: connect your pdf to the dynamic
    world of online information

    1. Molecular cloning and functional expression of the gene encoding the human proteinase-activated receptor 2. (PubMed id 7556175)1, 2, 3 Nystedt S.... Sundelin J. (Eur. J. Biochem. 1995)
    2. Interactions of mast cell tryptase with thrombin receptors and PAR- 2. (PubMed id 9020112)1, 2, 9 Molino M.... Brass L.F. (J. Biol. Chem. 1997)
    3. c-Cbl mediates ubiquitination, degradation, and down-regulation of human protease-activated receptor 2. (PubMed id 15708858)1, 2, 9 Jacob C....Bunnett N.W. (J. Biol. Chem. 2005)
    4. Analysis of proteinase-activated receptor 2 and TLR4 signal transduction: a novel paradigm for receptor cooperativity. (PubMed id 18622013)1, 2, 9 Rallabhandi P.... Vogel S.N. (J. Biol. Chem. 2008)
    5. Interaction of mite allergens Der p3 and Der p9 with protease- activated receptor-2 expressed by lung epithelial cells. (PubMed id 11441110)1, 2, 9 Sun G.... Mattoli S. (J. Immunol. 2001)
    6. Conserved structure and adjacent location of the thrombin receptor and protease-activated receptor 2 genes define a protease-activated receptor gene cluster. (PubMed id 8784787)1, 2, 9 Kahn M.L.... Coughlin S.R. (Mol. Med. 1996)
    7. Phosphorylation of protease-activated receptor-2 differentially regulates desensitization and internalization. (PubMed id 19815543)1, 2, 9 Ricks T.K. and Trejo J. (J. Biol. Chem. 2009)
    8. Agonists of proteinase-activated receptor-2 modulate human neutrophil cytokine secretion, expression of cell adhesion molecules, and migration within 3-D collagen lattices. (PubMed id 15155775)1, 2, 9 Shpacovitch V.M.... Steinhoff M. (J. Leukoc. Biol. 2004)
    9. Proteinase-activated receptor-2 mediated inhibition of TNFalpha- stimulated JNK activation - a novel paradigm for G(q/11) linked GPCRs. (PubMed id 19781631)1, 2, 9 McIntosh K.... Plevin R. (Cell. Signal. 2010)
    10. Protease-activated receptors-1 and -2 can mediate endothelial barrier protection: role in factor Xa signaling. (PubMed id 16359518)1, 2, 9 Feistritzer C.... Riewald M. (J. Thromb. Haemost. 2005)

    (in PubMed, OMIM, and NCBI Bookshelf)
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     ANDOR
    Aliases
    Disorders
    Free Text  

      Query String
    PubMed
    OMIM
    NCBI Bookshelf
      (Note: In FireFox, select the above section and copy using Ctrl-C)

    (According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
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    Entrez Gene: 2150 HGNC: 3538 AceView: F2RL1 Ensembl:ENSG00000164251 euGenes: HUgn2150
    ECgene: F2RL1 Kegg: 2150 H-InvDB: F2RL1

    (According to HUGE)
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      --

    (According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, UniProtKB/TrEMBL, and/or others, e.g. Wikipedia and GeneReviews, via UniProtKB/Swiss-Prot)
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    NameDescription
    PharmGKB entry for F2RL1 Pharmacogenomics, SNPs, Pathways
    Wikipedia http://en.wikipedia.org/wiki/Protease-activated_receptor
    SeattleSNPshttp://pga.gs.washington.edu/data/f2rl1/

    (Patent information from GeneIP,
    Licensable technologies from WIS Yeda, Salk, Tufts,
    IP news from LifeMap Sciences, Inc.)
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    Patent Information for F2RL1 gene:
    Search GeneIP for patents involving F2RL1

    GeneCards and IP:
    Japan Patent Office Licenses GeneCards     European Patent Office Licenses GeneCards     Improving the IP Search



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