This gene encodes a member of the protease-activated receptor subfamily, part of the G-protein coupled receptor 1 family of proteins. The encoded receptor is proteolytically processed to reveal an extracellular N-terminal tethered ligand that binds to and activates the receptor. This receptor plays a role in blood coagulation, inflammation and response to pain. Hypomethylation ... See more...

Aliases for F2RL3 Gene

Aliases for F2RL3 Gene

  • F2R Like Thrombin Or Trypsin Receptor 3 2 3 5
  • PAR4 2 3 4
  • Coagulation Factor II (Thrombin) Receptor-Like 3 2 3
  • F2R Like Thrombin/Trypsin Receptor 3 2 3
  • Proteinase-Activated Receptor 4 3 4
  • Thrombin Receptor-Like 3 3 4
  • PAR-4 3 4
  • Coagulation Factor II Receptor-Like 3 4
  • Proteinase-Activated Receptor-4 2
  • Protease-Activated Receptor-4 3
  • F2RL3 5

External Ids for F2RL3 Gene

Previous GeneCards Identifiers for F2RL3 Gene

  • GC19P017493
  • GC19P017392
  • GC19P016845
  • GC19P016860
  • GC19P017000
  • GC19P016568
  • GC19P017001
  • GC19P017109
  • GC19P017365
  • GC19P017898

Summaries for F2RL3 Gene

Entrez Gene Summary for F2RL3 Gene

  • This gene encodes a member of the protease-activated receptor subfamily, part of the G-protein coupled receptor 1 family of proteins. The encoded receptor is proteolytically processed to reveal an extracellular N-terminal tethered ligand that binds to and activates the receptor. This receptor plays a role in blood coagulation, inflammation and response to pain. Hypomethylation at this gene may be associated with lung cancer in human patients. [provided by RefSeq, Sep 2016]

GeneCards Summary for F2RL3 Gene

F2RL3 (F2R Like Thrombin Or Trypsin Receptor 3) is a Protein Coding gene. Diseases associated with F2RL3 include Asthma and Lung Cancer. Among its related pathways are RET signaling and Signaling by GPCR. Gene Ontology (GO) annotations related to this gene include G protein-coupled receptor activity and thrombin-activated receptor activity. An important paralog of this gene is F2RL1.

UniProtKB/Swiss-Prot Summary for F2RL3 Gene

  • Receptor for activated thrombin or trypsin coupled to G proteins that stimulate phosphoinositide hydrolysis. May play a role in platelets activation.

Tocris Summary for F2RL3 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 affects transmembrane signaling.

Gene Wiki entry for F2RL3 Gene

No data available for CIViC Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for F2RL3 Gene

Genomics for F2RL3 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for F2RL3 Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH19J016885 Promoter/Enhancer 2 EPDnew Ensembl ENCODE CraniofacialAtlas dbSUPER 600.7 -0.7 -716 5.4 SP1 HNRNPL ATF7 TFE3 LEF1 IKZF1 POLR2A JUND LARP7 DDX20 F2RL3 CHERP C19orf44 ENSG00000268743 SIN3B ENSG00000269578 LOC100507551 ENSG00000267904 GTPBP3 ENSG00000268087
GH19J017264 Promoter/Enhancer 2.2 EPDnew Ensembl ENCODE CraniofacialAtlas 11.1 +376.7 376728 6.7 SP1 CREB1 GATAD2A PRDM10 ZNF629 TFE3 SIX5 LEF1 IKZF1 KDM1A BABAM1 ENSG00000269307 NONHSAG025076.2 lnc-NR2F6-2 USHBP1 CHERP C19orf44 ENSG00000268743 ABHD8 PLVAP
GH19J017762 Promoter/Enhancer 1.6 EPDnew Ensembl ENCODE dbSUPER 11.1 +873.7 873711 1.1 PRDM10 RFX1 RFX5 KDM1A DDX20 PKNOX1 POLR2A ZNF24 HDAC1 SOX6 FCHO1 MAP1S B3GNT3 INSL3 PLVAP NXNL1 F2RL3 lnc-MAP1S-1 piR-35674-251 L13712-013
GH19J017487 Promoter/Enhancer 1.5 Ensembl ENCODE CraniofacialAtlas dbSUPER 5.1 +600.5 600510 3.6 CTCF KDM1A PATZ1 ZNF341 SCRT2 ZBTB44 KLF9 MGA SP2 SMARCC1 LOC100507551 SLC27A1 F2RL3 piR-38005-022 PGLS
GH19J016863 Promoter 0.3 Ensembl 12.2 -25.5 -25499 0.2 SIN3B F2RL3 HSALNG0124471 ENSG00000268743
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around F2RL3 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for F2RL3

Top Transcription factor binding sites by QIAGEN in the F2RL3 gene promoter:
  • C/EBPbeta
  • COMP1
  • CUTL1
  • E2F
  • E2F-1
  • E47
  • GR
  • GR-alpha
  • Msx-1
  • STAT3

Genomic Locations for F2RL3 Gene

Genomic Locations for F2RL3 Gene
chr19:16,888,999-16,892,606
(GRCh38/hg38)
Size:
3,608 bases
Orientation:
Plus strand
chr19:16,999,671-17,003,417
(GRCh37/hg19)
Size:
3,747 bases
Orientation:
Plus strand

Genomic View for F2RL3 Gene

Genes around F2RL3 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
F2RL3 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for F2RL3 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for F2RL3 Gene

Proteins for F2RL3 Gene

  • Protein details for F2RL3 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q96RI0-PAR4_HUMAN
    Recommended name:
    Proteinase-activated receptor 4
    Protein Accession:
    Q96RI0
    Secondary Accessions:
    • O76067
    • Q6DK42

    Protein attributes for F2RL3 Gene

    Size:
    385 amino acids
    Molecular mass:
    41133 Da
    Quaternary structure:
    No Data Available

    Three dimensional structures from OCA and Proteopedia for F2RL3 Gene

neXtProt entry for F2RL3 Gene

Post-translational modifications for F2RL3 Gene

  • A proteolytic cleavage generates a new N-terminus that functions as a tethered ligand.
  • Glycosylation at Asn56
  • Modification sites at PhosphoSitePlus

Other Protein References for F2RL3 Gene

ENSEMBL proteins:
REFSEQ proteins:

No data available for DME Specific Peptides for F2RL3 Gene

Domains & Families for F2RL3 Gene

Gene Families for F2RL3 Gene

HGNC:
IUPHAR :
Human Protein Atlas (HPA):
  • G-protein coupled receptors
  • Plasma proteins
  • Predicted intracellular proteins
  • Predicted membrane proteins

Protein Domains for F2RL3 Gene

InterPro:
Blocks:
  • Protease activated receptor precursor signature
  • Protease activated receptor 2 precursor signature
ProtoNet:

Suggested Antigen Peptide Sequences for F2RL3 Gene

GenScript: Design optimal peptide antigens:
  • Thrombin receptor-like 3 (PAR4_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q96RI0

UniProtKB/Swiss-Prot:

PAR4_HUMAN :
  • Belongs to the G-protein coupled receptor 1 family.
Family:
  • Belongs to the G-protein coupled receptor 1 family.
genes like me logo Genes that share domains with F2RL3: view

Function for F2RL3 Gene

Molecular function for F2RL3 Gene

UniProtKB/Swiss-Prot Function:
Receptor for activated thrombin or trypsin coupled to G proteins that stimulate phosphoinositide hydrolysis. May play a role in platelets activation.
GENATLAS Biochemistry:
proteinase-activated receptor 4,expressed in pancreas,testis,lung,thyroid,small intestine,G protein coupled receptor superfamily,activated by thrombin or trypsin

Phenotypes From GWAS Catalog for F2RL3 Gene

Gene Ontology (GO) - Molecular Function for F2RL3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004930 G protein-coupled receptor activity IBA 21873635
GO:0015057 thrombin-activated receptor activity IEA --
genes like me logo Genes that share ontologies with F2RL3: view
genes like me logo Genes that share phenotypes with F2RL3: view

Animal Models for F2RL3 Gene

MGI Knock Outs for F2RL3:

Animal Model Products

  • Taconic Biosciences Mouse Models for F2RL3

CRISPR Products

miRNA for F2RL3 Gene

miRTarBase miRNAs that target F2RL3

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for F2RL3

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for F2RL3 Gene

Localization for F2RL3 Gene

Subcellular locations from UniProtKB/Swiss-Prot for F2RL3 Gene

Cell membrane. Multi-pass membrane protein.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for F2RL3 gene
Compartment Confidence
plasma membrane 5
extracellular 4
cytosol 4
cytoskeleton 1
mitochondrion 1
nucleus 1
endoplasmic reticulum 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Plasma membrane (4)
  • Cytosol (2)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for F2RL3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005576 extracellular region TAS --
GO:0005623 cell IEA --
GO:0005829 cytosol IDA --
GO:0005886 plasma membrane TAS --
GO:0005887 integral component of plasma membrane TAS,IBA 21873635
genes like me logo Genes that share ontologies with F2RL3: view

Pathways & Interactions for F2RL3 Gene

genes like me logo Genes that share pathways with F2RL3: view

Pathways by source for F2RL3 Gene

1 GeneGo (Thomson Reuters) pathway for F2RL3 Gene
  • Cell adhesion Integrin inside-out signaling
3 Qiagen pathways for F2RL3 Gene
  • G12-G13 in Cellular Signaling
  • JAK-STAT Pathway
  • Thrombin Signaling

SIGNOR curated interactions for F2RL3 Gene

Activates:
Is activated by:

Gene Ontology (GO) - Biological Process for F2RL3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0007165 signal transduction TAS 9618465
GO:0007186 G protein-coupled receptor signaling pathway TAS --
GO:0007200 phospholipase C-activating G protein-coupled receptor signaling pathway TAS 9618465
GO:0007596 blood coagulation IEA,TAS 10500152
GO:0007599 hemostasis IEA --
genes like me logo Genes that share ontologies with F2RL3: view

Drugs & Compounds for F2RL3 Gene

(20) Drugs for F2RL3 Gene - From: DrugBank, ApexBio, DGIdb, Tocris, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Vorapaxar Approved Pharma PAR-1 antagonist,potent and orally active 15
Thrombin Approved, Investigational Pharma Target 411
Argatroban Approved, Investigational Pharma Thrombin mediated fibrinogen cleavage inhibitor 27
AY-NH2 Pharma Selective PAR4 agonist 0
Thrombin Receptor Agonist Peptide Pharma Causes platelet aggregation and secretion 0

(9) Additional Compounds for F2RL3 Gene - From: Novoseek and IUPHAR

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
AYPGKF-NH2
Agonist, Full agonist
GYPGKF-NH2
Agonist, Full agonist
GYPGQV-NH<sub>2</sub>
Agonist, Full agonist

(5) Tocris Compounds for F2RL3 Gene

Compound Action Cas Number
AY-NH2 Selective PAR4 agonist 352017-71-1
SLIGKV-NH2 PAR2 receptor agonist 190383-13-2
SLIGRL-NH2 PAR2-activating peptide 171436-38-7
TFLLR-NH2 PAR1-activating peptide 197794-83-5
Thrombin Receptor Agonist Peptide Causes platelet aggregation and secretion 137339-65-2

(7) ApexBio Compounds for F2RL3 Gene

Compound Action Cas Number
Argatroban Thrombin mediated fibrinogen cleavage inhibitor 74863-84-6
AY-NH2 Selective PAR4 agonist 352017-71-1
BIBR 953 (Dabigatran, Pradaxa) Thrombin inhibitor,potent,reversible and direct 211914-51-1
BIBR-1048 Thrombin inhibitor 211915-06-9
Thrombin Receptor Activator for Peptide 5 (TRAP-5) 141685-53-2
Thrombin Receptor Agonist Peptide 137339-65-2
Vorapaxar PAR-1 antagonist,potent and orally active 618385-01-6
genes like me logo Genes that share compounds with F2RL3: view

Drug Products

Transcripts for F2RL3 Gene

mRNA/cDNA for F2RL3 Gene

1 REFSEQ mRNAs :
6 NCBI additional mRNA sequence :
2 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for F2RL3

Alternative Splicing Database (ASD) splice patterns (SP) for F2RL3 Gene

No ASD Table

Relevant External Links for F2RL3 Gene

GeneLoc Exon Structure for
F2RL3

Expression for F2RL3 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for F2RL3 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for F2RL3 Gene

This gene is overexpressed in Lung (x9.6), Adipose - Subcutaneous (x5.5), Thyroid (x5.3), Breast - Mammary Tissue (x4.9), and Adipose - Visceral (Omentum) (x4.2).

Protein differential expression in normal tissues from HIPED for F2RL3 Gene

This gene is overexpressed in Peripheral blood mononuclear cells (51.1), Monocytes (10.2), and Platelet (7.7).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB and MOPED for F2RL3 Gene



Protein tissue co-expression partners for F2RL3 Gene

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for F2RL3

SOURCE GeneReport for Unigene cluster for F2RL3 Gene:

Hs.137574

mRNA Expression by UniProt/SwissProt for F2RL3 Gene:

Q96RI0-PAR4_HUMAN
Tissue specificity: Widely expressed, with highest levels in lung, pancreas, thyroid, testis and small intestine. Not expressed in brain, kidney, spinal cord and peripheral blood leukocytes. Also detected in platelets.

Evidence on tissue expression from TISSUES for F2RL3 Gene

  • Lung(4.3)
  • Blood(2.5)
genes like me logo Genes that share expression patterns with F2RL3: view

No data available for Phenotype-based relationships between genes and organs from Gene ORGANizer for F2RL3 Gene

Orthologs for F2RL3 Gene

This gene was present in the common ancestor of chordates.

Orthologs for F2RL3 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia F2RL3 30 31
  • 99.22 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia F2RL3 30 31
  • 82.19 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia F2RL3 30 31
  • 79.79 (n)
OneToOne
Mouse
(Mus musculus)
Mammalia F2rl3 30 17 31
  • 77.07 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia F2rl3 30
  • 74.71 (n)
Platypus
(Ornithorhynchus anatinus)
Mammalia F2RL3 31
  • 55 (a)
OneToOne
Oppossum
(Monodelphis domestica)
Mammalia -- 31
  • 50 (a)
OneToMany
-- 31
  • 50 (a)
OneToMany
Chicken
(Gallus gallus)
Aves F2RL3 31
  • 45 (a)
OneToOne
Zebrafish
(Danio rerio)
Actinopterygii F2RL3 31
  • 36 (a)
OneToOne
Species where no ortholog for F2RL3 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Baker's yeast (Saccharomyces cerevisiae)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Fruit Fly (Drosophila melanogaster)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Lizard (Anolis carolinensis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Rainbow Trout (Oncorhynchus mykiss)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Squirt (Ciona savignyi)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Thale Cress (Arabidopsis thaliana)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Tropical Clawed Frog (Silurana tropicalis)
  • Wheat (Triticum aestivum)
  • Worm (Caenorhabditis elegans)

Evolution for F2RL3 Gene

ENSEMBL:
Gene Tree for F2RL3 (if available)
TreeFam:
Gene Tree for F2RL3 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for F2RL3: view image

Paralogs for F2RL3 Gene

(7) SIMAP similar genes for F2RL3 Gene using alignment to 2 proteins:

  • PAR4_HUMAN
  • M0R0Y0_HUMAN
genes like me logo Genes that share paralogs with F2RL3: view

Variants for F2RL3 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for F2RL3 Gene

SNP ID Clinical significance and condition Chr 19 pos Variation AA Info Type
714781 Benign: not provided 16,890,234(+) G/T SYNONYMOUS_VARIANT
779986 Likely Benign: not provided 16,890,006(+) G/A SYNONYMOUS_VARIANT
785617 Benign: not provided 16,890,573(+) G/A SYNONYMOUS_VARIANT
789853 Benign: not provided 16,890,429(+) C/T SYNONYMOUS_VARIANT
rs2227346 - p.Phe296Val

Additional dbSNP identifiers (rs#s) for F2RL3 Gene

Structural Variations from Database of Genomic Variants (DGV) for F2RL3 Gene

Variant ID Type Subtype PubMed ID
esv2666431 CNV deletion 23128226

Variation tolerance for F2RL3 Gene

Residual Variation Intolerance Score: 93.1% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 6.79; 79.07% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for F2RL3 Gene

Human Gene Mutation Database (HGMD)
F2RL3
SNPedia medical, phenotypic, and genealogical associations of SNPs for
F2RL3

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for F2RL3 Gene

Disorders for F2RL3 Gene

MalaCards: The human disease database

(3) MalaCards diseases for F2RL3 Gene - From: DISEASES and GeneCards

Disorder Aliases PubMed IDs
asthma
  • asthma, susceptibility to
lung cancer
  • adenocarcinoma of lung
hermansky-pudlak syndrome
  • albinism with hemorrhagic diathesis and pigmented reticuloendothelial cells
- elite association - COSMIC cancer census association via MalaCards
Search F2RL3 in MalaCards View complete list of genes associated with diseases

Additional Disease Information for F2RL3

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
genes like me logo Genes that share disorders with F2RL3: view

No data available for UniProtKB/Swiss-Prot and Genatlas for F2RL3 Gene

Publications for F2RL3 Gene

  1. Cloning and characterization of human protease-activated receptor 4. (PMID: 9618465) Xu WF … Foster DC (Proceedings of the National Academy of Sciences of the United States of America 1998) 2 3 4 23
  2. Protease-activated receptors 1 and 4 mediate activation of human platelets by thrombin. (PMID: 10079109) Kahn ML … Coughlin SR (The Journal of clinical investigation 1999) 3 4 23
  3. Annexin V binding to platelets is agonist, time and temperature dependent. (PMID: 20230207) Ramstrom S … Kenny D (Platelets 2010) 3 23
  4. Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study. (PMID: 20628086) Bailey SD … DREAM investigators (Diabetes care 2010) 3 41
  5. Complement protease MASP-1 activates human endothelial cells: PAR4 activation is a link between complement and endothelial function. (PMID: 19667088) Megyeri M … Gál P (Journal of immunology (Baltimore, Md. : 1950) 2009) 3 23

Products for F2RL3 Gene

  • Addgene plasmids for F2RL3

Sources for F2RL3 Gene