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F2RL2 coagulation factor II thrombin receptor like 2 [ Homo sapiens (human) ]

Gene ID: 2151, updated on 11-Apr-2024

Summary

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Official Symbol
F2RL2provided by HGNC
Official Full Name
coagulation factor II thrombin receptor like 2provided by HGNC
Primary source
HGNC:HGNC:3539
See related
Ensembl:ENSG00000164220 MIM:601919; AllianceGenome:HGNC:3539
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
PAR3; PAR-3
Summary
This gene encodes a member of the protease-activated receptor (PAR) family which is a subfamily of the seven transmembrane G protein-coupled cell surface receptor family. The encoded protein acts as a cofactor in the thrombin-mediated cleavage and activation of the protease-activated receptor family member PAR4. The encoded protein plays an essential role in hemostasis and thrombosis. Alternate splicing results in multiple transcript variants that encode different isoforms. [provided by RefSeq, Feb 2012]
Expression
Biased expression in gall bladder (RPKM 4.3), endometrium (RPKM 1.5) and 10 other tissues See more
Orthologs
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Genomic context

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Location:
5q13.3
Exon count:
2
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 5 NC_000005.10 (76615482..76623403, complement)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 5 NC_060929.1 (77097223..77105145, complement)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 5 NC_000005.9 (75911307..75919228, complement)

Chromosome 5 - NC_000005.10Genomic Context describing neighboring genes Neighboring gene IQ motif containing GTPase activating protein 2 Neighboring gene sulfiredoxin 1 pseudogene Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 16105 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 22690 Neighboring gene ReSE screen-validated silencer GRCh37_chr5:75852604-75853098 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 22692 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 22693 Neighboring gene uncharacterized LOC101929109 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 22694 Neighboring gene Sharpr-MPRA regulatory region 1022 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 16106 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr5:76013800-76014300 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr5:76014301-76014801 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 16107 Neighboring gene non-protein coding RNA, upstream of F2R/PAR1 Neighboring gene coagulation factor II thrombin receptor

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. Noncanonical PAR3 activation by factor Xa identifies a novel pathway for Tie2 activation and stabilization of vascular integrity. Stavenuiter F, et al. Blood, 2014 Nov 27. PMID 25320242, Free PMC Article
  2. Novel mechanisms for activated protein C cytoprotective activities involving noncanonical activation of protease-activated receptor 3. Burnier L, et al. Blood, 2013 Aug 1. PMID 23788139, Free PMC Article
  3. Lower concentrations of thrombin-antithrombin complex (TAT) correlate to higher recanalisation rates among ischaemic stroke patients treated with t-PA. Fernandez-Cadenas I, et al. Thromb Haemost, 2009 Oct. PMID 19806263
  4. Expressions of connexin and par-3 in the distal margin of rectal cancer after ultra-low anterior resection. Liu J, et al. J Huazhong Univ Sci Technolog Med Sci, 2009 Jun. PMID 19513616
  5. Stabilization of the E* form turns thrombin into an anticoagulant. Bah A, et al. J Biol Chem, 2009 Jul 24. PMID 19473969, Free PMC Article

See all (64) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. PAR3 is essential in thrombin stimulated insulin secretion.
    Title: Thrombin stimulates insulin secretion via protease-activated receptor-3.
  2. TFRGAP, a PAR-3 mimicking peptide significantly induced the phosphorylation of eNOS-Thr-495 with minimal phosphorylation of eNOS-Ser-1177 with no change in nitric oxide production.
    Title: Featured Article: Differential regulation of endothelial nitric oxide synthase phosphorylation by protease-activated receptors in adult human endothelial cells.
  3. These data provide intriguing novel insights into the diversification of functional selectivity of protease signaling achievable by canonical and noncanonical PAR activation, such as the activation of vascular-protective Tie2 by noncanonical PAR3 activation.
    Title: Noncanonical PAR3 activation by factor Xa identifies a novel pathway for Tie2 activation and stabilization of vascular integrity.
  4. In pancreatic adenocarcinoma cells, PAR3 knockdown enhances cell adhesion. We propose this is due to increased expression of E-cadherin, leading to a greater adhesion of free-floating cells to cells bound to the surface via integrins, particularly ITGalphav.
    Title: PAR-3 knockdown enhances adhesion rate of PANC-1 cells via increased expression of integrinαv and E-cadherin.
  5. Data indicate that knockdowns of all three PARs PAR-1, PAR-2, and PAR-3 exhibited changes in the expression of CDC42, which correlated with the changes in their invasion.
    Title: Proteinase-activated receptors differentially modulate in vitro invasion of human pancreatic adenocarcinoma PANC-1 cells in correlation with changes in the expression of CDC42 protein.
  6. Elevated expression of PAR-3, but not PAR-4, was detected in the lungs of idiopathic pulmonary fibrosis patients.
    Title: Protease-activated receptors (PAR)-1 and -3 drive epithelial-mesenchymal transition of alveolar epithelial cells - potential role in lung fibrosis.
  7. A unique contributory role for PAR3 in the complex mechanisms underlying Activated protein C cytoprotective effects.
    Title: Novel mechanisms for activated protein C cytoprotective activities involving noncanonical activation of protease-activated receptor 3.
  8. PAR-3 receptors interact with thrombin and increase heme oxygenase-1 expression in synovial fibroblasts.
    Title: Thrombin induces heme oxygenase-1 expression in human synovial fibroblasts through protease-activated receptor signaling pathways.
  9. Human PAR-3 is regulated post-transcriptionally via the mRNA-stabilizing factor HuR, whereas transcriptional control involves nuclear factor of activated T cells (NFAT).
    Title: Regulation of human vascular protease-activated receptor-3 through mRNA stabilization and the transcription factor nuclear factor of activated T cells (NFAT).
  10. FXa bound in a punctate manner to thrombi under shear, while thrombin and fibrin(ogen) distributed ubiquitously over platelet-fibrin thrombi
    Title: Spatial distribution of factor Xa, thrombin, and fibrin(ogen) on thrombi at venous shear.
Submit: New GeneRIF Correction See all GeneRIFs (32)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

EBI GWAS Catalog

Description
A genome-wide association study for age-related hearing impairment in the Saami.
EBI GWAS Catalog

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

HIV-1 interactions

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Protein interactions

Protein Gene Interaction Pubs
Vif vif HIV-1 Vif downregulates the expression of coagulation factor II (thrombin) receptor-like 2 (F2RL2) in Vif-expression T cells PubMed

Go to the HIV-1, Human Interaction Database

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Clone Names

  • FLJ51933

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables G protein-coupled receptor activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables G protein-coupled receptor activity TAS
Traceable Author Statement
more info
  
enables phosphatidylinositol phospholipase C activity TAS
Traceable Author Statement
more info
 PubMed 
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables receptor ligand activity IEA
Inferred from Electronic Annotation
more info
  
enables thrombin-activated receptor activity IEA
Inferred from Electronic Annotation
more info
  
Process Evidence Code Pubs
involved_in blood coagulation TAS
Traceable Author Statement
more info
 PubMed 
involved_in ligand-gated ion channel signaling pathway IEA
Inferred from Electronic Annotation
more info
  
involved_in phospholipase C-activating G protein-coupled receptor signaling pathway IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in platelet activation TAS
Traceable Author Statement
more info
  
involved_in positive regulation of Rho protein signal transduction IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in positive regulation of insulin secretion IEA
Inferred from Electronic Annotation
more info
  
involved_in response to wounding TAS
Traceable Author Statement
more info
 PubMed 
involved_in thrombin-activated receptor signaling pathway IEA
Inferred from Electronic Annotation
more info
  
Component Evidence Code Pubs
located_in apical plasma membrane IEA
Inferred from Electronic Annotation
more info
  
located_in extracellular region TAS
Traceable Author Statement
more info
  
is_active_in plasma membrane IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in plasma membrane TAS
Traceable Author Statement
more info
  
part_of protein-containing complex IDA
Inferred from Direct Assay
more info
 PubMed 

General protein information

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Preferred Names
proteinase-activated receptor 3
Names
Coagulation factor II receptor-like 2 (protease-actovated receptor 3)
protease-activated receptor 3
thrombin receptor-like 2

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

  1. NM_001256566.2 → NP_001243495.1  proteinase-activated receptor 3 isoform 2

    See identical proteins and their annotated locations for NP_001243495.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) uses an alternate exon in the 5' UTR and coding region, compared to variant 1. These differences cause translation initiation at a downstream AUG and result in an isoform (2) with a shorter N-terminus, compared to isoform 1.
    Source sequence(s)
    AC026725, AK298585, AL048674
    Consensus CDS
    CCDS58959.1
    UniProtKB/TrEMBL
    Q4VBN6
    Related
    ENSP00000426703.1, ENST00000504899.1
    Conserved Domains (1) summary
    cd15371
    Location:73 → 346
    7tmA_PAR3; protease-activated receptor 3, member of the class A family of seven-transmembrane G protein-coupled receptors

  2. NM_004101.4 → NP_004092.1  proteinase-activated receptor 3 isoform 1 precursor

    See identical proteins and their annotated locations for NP_004092.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).
    Source sequence(s)
    AC026725, AL048674, BC093650, DC419029
    Consensus CDS
    CCDS4031.1
    UniProtKB/Swiss-Prot
    B2R754, B4DQ13, O00254, Q52M68, Q7Z3W3
    UniProtKB/TrEMBL
    Q4VBN6
    Related
    ENSP00000296641.3, ENST00000296641.5
    Conserved Domains (1) summary
    cd15371
    Location:95 → 368
    7tmA_PAR3; protease-activated receptor 3, member of the class A family of seven-transmembrane G protein-coupled receptors

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000005.10 Reference GRCh38.p14 Primary Assembly

    Range
    76615482..76623403 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060929.1 Alternate T2T-CHM13v2.0

    Range
    77097223..77105145 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
O00254.1 GenPept UniProtKB/Swiss-Prot:O00254

Gene LinkOut

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