Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

P25116 (PAR1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 164. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Proteinase-activated receptor 1

Short name=PAR-1
Alternative name(s):
Coagulation factor II receptor
Thrombin receptor
Gene names
Name:F2R
Synonyms:CF2R, PAR1, TR
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length425 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

High affinity receptor for activated thrombin coupled to G proteins that stimulate phosphoinositide hydrolysis. May play a role in platelets activation and in vascular development. Ref.6

Subcellular location

Cell membrane; Multi-pass membrane protein.

Tissue specificity

Platelets and vascular endothelial cells.

Domain

The cleaved signal peptide may not be degraded and may function as an intracellular angiogenesis inhibitor peptide known as parstatin.

Post-translational modification

A proteolytic cleavage generates a new N-terminus that functions as a tethered ligand.

Phosphorylated in the C-terminal tail; probably mediating desensitization prior to the uncoupling and internalization of the receptor. Ref.5

Sequence similarities

Belongs to the G-protein coupled receptor 1 family.

Ontologies

Keywords
   Biological processBlood coagulation
Hemostasis
   Cellular componentCell membrane
Membrane
   Coding sequence diversityPolymorphism
   DomainSignal
Transmembrane
Transmembrane helix
   Molecular functionG-protein coupled receptor
Receptor
Transducer
   PTMDisulfide bond
Glycoprotein
Phosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processG-protein coupled receptor signaling pathway

Inferred from sequence or structural similarity. Source: UniProtKB

STAT protein import into nucleus

Inferred from direct assay PubMed 10692450. Source: BHF-UCL

activation of MAPKK activity

Inferred from sequence or structural similarity. Source: UniProtKB

activation of cysteine-type endopeptidase activity involved in apoptotic process

Inferred from direct assay PubMed 10692450. Source: BHF-UCL

anatomical structure morphogenesis

Traceable author statement PubMed 9701242. Source: ProtInc

blood coagulation

Traceable author statement. Source: Reactome

connective tissue replacement involved in inflammatory response wound healing

Inferred from direct assay PubMed 9639571. Source: BHF-UCL

establishment of synaptic specificity at neuromuscular junction

Inferred from sequence or structural similarity. Source: UniProtKB

homeostasis of number of cells within a tissue

Inferred from sequence or structural similarity. Source: UniProtKB

inflammatory response

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of cell proliferation

Inferred from direct assay PubMed 10692450. Source: BHF-UCL

negative regulation of glomerular filtration

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of neuron apoptotic process

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of renin secretion into blood stream

Inferred from sequence or structural similarity. Source: UniProtKB

phospholipase C-activating G-protein coupled receptor signaling pathway

Inferred from direct assay PubMed 20164183. Source: BHF-UCL

platelet activation

Inferred from direct assay PubMed 9038223. Source: BHF-UCL

platelet dense granule organization

Inferred by curator Ref.1. Source: BHF-UCL

positive regulation of ERK1 and ERK2 cascade

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of I-kappaB kinase/NF-kappaB signaling

Inferred from expression pattern PubMed 12761501. Source: UniProtKB

positive regulation of JAK-STAT cascade

Inferred from direct assay PubMed 10692450. Source: BHF-UCL

positive regulation of MAPK cascade

Inferred from direct assay PubMed 17848177. Source: BHF-UCL

positive regulation of Rho protein signal transduction

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of blood coagulation

Inferred from direct assay PubMed 9038223. Source: BHF-UCL

positive regulation of calcium ion transport

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of cell migration

Inferred from mutant phenotype PubMed 9701242. Source: BHF-UCL

positive regulation of cell proliferation

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of collagen biosynthetic process

Inferred from direct assay PubMed 9639571. Source: BHF-UCL

positive regulation of cysteine-type endopeptidase activity involved in apoptotic process

Inferred from direct assay PubMed 10692450. Source: BHF-UCL

positive regulation of cytosolic calcium ion concentration

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of cytosolic calcium ion concentration involved in phospholipase C-activating G-protein coupled signaling pathway

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of interleukin-6 secretion

Inferred from direct assay PubMed 11447194. Source: UniProtKB

positive regulation of interleukin-8 secretion

Inferred from direct assay PubMed 17404307. Source: UniProtKB

positive regulation of phosphatidylinositol 3-kinase signaling

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of release of sequestered calcium ion into cytosol

Inferred from direct assay Ref.1. Source: BHF-UCL

positive regulation of smooth muscle contraction

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of transcription, DNA-templated

Inferred from direct assay PubMed 17848177. Source: BHF-UCL

positive regulation of vasoconstriction

Inferred from sequence or structural similarity. Source: UniProtKB

protein kinase C-activating G-protein coupled receptor signaling pathway

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of blood coagulation

Inferred from direct assay PubMed 17848177. Source: BHF-UCL

regulation of interleukin-1 beta production

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of sensory perception of pain

Inferred from sequence or structural similarity. Source: UniProtKB

release of sequestered calcium ion into cytosol

Inferred from sequence or structural similarity. Source: UniProtKB

response to lipopolysaccharide

Inferred from sequence or structural similarity. Source: UniProtKB

response to wounding

Inferred from direct assay PubMed 9639571. Source: BHF-UCL

tyrosine phosphorylation of STAT protein

Inferred from direct assay PubMed 10692450. Source: BHF-UCL

   Cellular_componentGolgi apparatus

Traceable author statement PubMed 7961693. Source: ProtInc

caveola

Inferred from direct assay PubMed 17848177. Source: BHF-UCL

extracellular region

Traceable author statement. Source: Reactome

integral component of plasma membrane

Traceable author statement Ref.1. Source: ProtInc

neuromuscular junction

Inferred from sequence or structural similarity. Source: UniProtKB

plasma membrane

Inferred from direct assay PubMed 9038223. Source: BHF-UCL

platelet dense tubular network

Inferred from direct assay PubMed 9038223. Source: BHF-UCL

postsynaptic membrane

Inferred from sequence or structural similarity. Source: UniProtKB

   Molecular_functionG-protein alpha-subunit binding

Inferred from sequence or structural similarity. Source: UniProtKB

G-protein beta-subunit binding

Inferred from sequence or structural similarity. Source: UniProtKB

G-protein coupled receptor activity

Inferred from sequence or structural similarity. Source: UniProtKB

protein binding

Inferred from physical interaction PubMed 20826780. Source: IntAct

receptor binding

Inferred from physical interaction Ref.1. Source: BHF-UCL

thrombin receptor activity

Inferred from direct assay PubMed 10692450Ref.1. Source: BHF-UCL

Complete GO annotation...

Binary interactions

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2121
Propeptide22 – 4120
PRO_0000012740
Chain42 – 425384Proteinase-activated receptor 1
PRO_0000012741

Regions

Topological domain42 – 10261Extracellular Potential
Transmembrane103 – 12826Helical; Name=1; Potential
Topological domain129 – 1379Cytoplasmic Potential
Transmembrane138 – 15720Helical; Name=2; Potential
Topological domain158 – 17619Extracellular Potential
Transmembrane177 – 19822Helical; Name=3; Potential
Topological domain199 – 21820Cytoplasmic Potential
Transmembrane219 – 23921Helical; Name=4; Potential
Topological domain240 – 26829Extracellular Potential
Transmembrane269 – 28820Helical; Name=5; Potential
Topological domain289 – 31123Cytoplasmic Potential
Transmembrane312 – 33423Helical; Name=6; Potential
Topological domain335 – 35016Extracellular Potential
Transmembrane351 – 37424Helical; Name=7; Potential
Topological domain375 – 42551Cytoplasmic Potential
Compositional bias57 – 604Asp/Glu-rich (acidic)

Sites

Site41 – 422Cleavage; by thrombin

Amino acid modifications

Glycosylation351N-linked (GlcNAc...) Potential
Glycosylation621N-linked (GlcNAc...) Potential
Glycosylation751N-linked (GlcNAc...) Potential
Glycosylation2501N-linked (GlcNAc...) Potential
Glycosylation2591N-linked (GlcNAc...) Potential
Disulfide bond175 ↔ 254 By similarity

Natural variations

Natural variant1661S → G. Ref.9
Corresponds to variant rs5893 [ dbSNP | Ensembl ].
VAR_014167
Natural variant1871Y → N.
Corresponds to variant rs2230849 [ dbSNP | Ensembl ].
VAR_049432
Natural variant2571V → L.
Corresponds to variant rs2227832 [ dbSNP | Ensembl ].
VAR_049433
Natural variant2681A → P.
Corresponds to variant rs1055103 [ dbSNP | Ensembl ].
VAR_060680
Natural variant3351A → V. Ref.3 Ref.4
Corresponds to variant rs17849599 [ dbSNP | Ensembl ].
VAR_060681
Natural variant4121S → Y.
Corresponds to variant rs2227799 [ dbSNP | Ensembl ].
VAR_049434

Experimental info

Sequence conflict2381L → V in AAA36743. Ref.1
Sequence conflict3641C → S in AAA36743. Ref.1

Secondary structure

.................................. 425
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P25116 [UniParc].

Last modified April 16, 2002. Version 2.
Checksum: 41B742A99EEC96AB

FASTA42547,441
        10         20         30         40         50         60 
MGPRRLLLVA ACFSLCGPLL SARTRARRPE SKATNATLDP RSFLLRNPND KYEPFWEDEE 

        70         80         90        100        110        120 
KNESGLTEYR LVSINKSSPL QKQLPAFISE DASGYLTSSW LTLFVPSVYT GVFVVSLPLN 

       130        140        150        160        170        180 
IMAIVVFILK MKVKKPAVVY MLHLATADVL FVSVLPFKIS YYFSGSDWQF GSELCRFVTA 

       190        200        210        220        230        240 
AFYCNMYASI LLMTVISIDR FLAVVYPMQS LSWRTLGRAS FTCLAIWALA IAGVVPLLLK 

       250        260        270        280        290        300 
EQTIQVPGLN ITTCHDVLNE TLLEGYYAYY FSAFSAVFFF VPLIISTVCY VSIIRCLSSS 

       310        320        330        340        350        360 
AVANRSKKSR ALFLSAAVFC IFIICFGPTN VLLIAHYSFL SHTSTTEAAY FAYLLCVCVS 

       370        380        390        400        410        420 
SISCCIDPLI YYYASSECQR YVYSILCCKE SSDPSSYNSS GQLMASKMDT CSSNLNNSIY 


KKLLT 

« Hide

References

« Hide 'large scale' references
[1]"Molecular cloning of a functional thrombin receptor reveals a novel proteolytic mechanism of receptor activation."
Vu T.-K.H., Hung D.T., Wheaton V.I., Coughlin S.R.
Cell 64:1057-1068(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]SeattleSNPs variation discovery resource
Submitted (JUL-2001) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]"Cloning of human full-length CDSs in BD Creator(TM) system donor vector."
Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A.
Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT VAL-335.
[4]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT VAL-335.
Tissue: Eye.
[5]"Role of the thrombin receptor's cytoplasmic tail in intracellular trafficking. Distinct determinants for agonist-triggered versus tonic internalization and intracellular localization."
Shapiro M.J., Trejo J., Zeng D., Coughlin S.R.
J. Biol. Chem. 271:32874-32880(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION.
[6]"Protease-activated receptors 1 and 4 mediate activation of human platelets by thrombin."
Kahn M.L., Nakanishi-Matsui M., Shapiro M.J., Ishihara H., Coughlin S.R.
J. Clin. Invest. 103:879-887(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[7]"Parstatin, the cleaved peptide on proteinase-activated receptor 1 activation, is a potent inhibitor of angiogenesis."
Zania P., Gourni D., Aplin A.C., Nicosia R.F., Flordellis C.S., Maragoudakis M.E., Tsopanoglou N.E.
J. Pharmacol. Exp. Ther. 328:378-389(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: ANGIOGENESIS INHIBITION PROPERTIES OF PARSTATIN.
[8]"The protease-activated receptor 1 possesses a functional and cleavable signal peptide which is necessary for receptor expression."
Zampatis D.E., Rutz C., Furkert J., Schmidt A., Wustenhagen D., Kubick S., Tsopanoglou N.E., Schulein R.
FEBS Lett. 586:2351-2359(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: SIGNAL SEQUENCE CLEAVAGE SITE.
[9]"Characterization of single-nucleotide polymorphisms in coding regions of human genes."
Cargill M., Altshuler D., Ireland J., Sklar P., Ardlie K., Patil N., Shaw N., Lane C.R., Lim E.P., Kalyanaraman N., Nemesh J., Ziaugra L., Friedland L., Rolfe A., Warrington J., Lipshutz R., Daley G.Q., Lander E.S.
Nat. Genet. 22:231-238(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT GLY-166.
[10]Erratum
Cargill M., Altshuler D., Ireland J., Sklar P., Ardlie K., Patil N., Shaw N., Lane C.R., Lim E.P., Kalyanaraman N., Nemesh J., Ziaugra L., Friedland L., Rolfe A., Warrington J., Lipshutz R., Daley G.Q., Lander E.S.
Nat. Genet. 23:373-373(1999)
[11]"Crystallographic structures of thrombin complexed with thrombin receptor peptides: existence of expected and novel binding modes."
Mathews I.I., Padmanabhan K.P., Ganesh V., Tulinsky A., Ishii M., Chen J., Turck C.W., Coughlin S.R., Fenton J.W. II
Biochemistry 33:3266-3279(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 38-64 IN COMPLEX WITH THROMBIN.
+Additional computationally mapped references.

Web resources

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M62424 mRNA. Translation: AAA36743.1.
AF391809 Genomic DNA. Translation: AAK69768.1.
BT007279 mRNA. Translation: AAP35943.1.
BC002464 mRNA. Translation: AAH02464.1.
BC051909 mRNA. Translation: AAH51909.1.
CCDSCCDS4032.1.
PIRA37912.
RefSeqNP_001983.2. NM_001992.3.
UniGeneHs.482562.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1NRNX-ray3.10R38-60[»]
1NROX-ray3.10R38-64[»]
1NRPX-ray3.00R38-60[»]
1NRQX-ray3.50R40-60[»]
1NRRX-ray2.40R43-60[»]
3BEFX-ray2.20C/F49-57[»]
3HKIX-ray2.20C/F42-62[»]
3HKJX-ray2.60C/F42-62[»]
3LU9X-ray1.80C/F33-57[»]
3VW7X-ray2.20A86-395[»]
ProteinModelPortalP25116.
SMRP25116. Positions 62-389.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid108448. 14 interactions.
DIPDIP-29703N.
IntActP25116. 7 interactions.
STRING9606.ENSP00000321326.

Chemistry

BindingDBP25116.
ChEMBLCHEMBL3974.
DrugBankDB00086. Streptokinase.
GuidetoPHARMACOLOGY347.

Protein family/group databases

GPCRDBSearch...

PTM databases

PhosphoSiteP25116.

Polymorphism databases

DMDM20178318.

Proteomic databases

MaxQBP25116.
PaxDbP25116.
PRIDEP25116.

Protocols and materials databases

DNASU2149.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000319211; ENSP00000321326; ENSG00000181104.
GeneID2149.
KEGGhsa:2149.
UCSCuc003ken.4. human.

Organism-specific databases

CTD2149.
GeneCardsGC05P076047.
H-InvDBHIX0004960.
HGNCHGNC:3537. F2R.
HPACAB008973.
MIM187930. gene.
neXtProtNX_P25116.
PharmGKBPA27946.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG150457.
HOGENOMHOG000232200.
HOVERGENHBG108233.
InParanoidP25116.
KOK03914.
OMAASKMDTC.
OrthoDBEOG7V49ZD.
PhylomeDBP25116.
TreeFamTF330775.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.
REACT_604. Hemostasis.

Gene expression databases

ArrayExpressP25116.
BgeeP25116.
CleanExHS_F2R.
GenevestigatorP25116.

Family and domain databases

Gene3D1.20.1070.10. 1 hit.
InterProIPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
IPR003912. Protea_act_rcpt.
IPR000935. Thrmbn_rcpt.
[Graphical view]
PfamPF00001. 7tm_1. 1 hit.
[Graphical view]
PRINTSPR00237. GPCRRHODOPSN.
PR01428. PROTEASEAR.
PR00908. THROMBINR.
PROSITEPS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSF2R. human.
EvolutionaryTraceP25116.
GeneWikiCoagulation_factor_II_receptor.
GenomeRNAi2149.
NextBio8685.
PMAP-CutDBP25116.
PROP25116.
SOURCESearch...

Entry information

Entry namePAR1_HUMAN
AccessionPrimary (citable) accession number: P25116
Secondary accession number(s): Q53XV0, Q96RF7, Q9BUN4
Entry history
Integrated into UniProtKB/Swiss-Prot: May 1, 1992
Last sequence update: April 16, 2002
Last modified: July 9, 2014
This is version 164 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 5

Human chromosome 5: entries, gene names and cross-references to MIM

7-transmembrane G-linked receptors

List of 7-transmembrane G-linked receptor entries