P25116 (PAR1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	425 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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.5
Subcellular location	Cell membrane; Multi-pass membrane protein.
Tissue specificity	Platelets and vascular endothelial cells.
Post-translational modification	A proteolytic cleavage generates a new N-terminus that functions as a tethered ligand. Phosphorylated; probably mediating desensitization prior to the uncoupling and internalization of the receptor.
Sequence similarities	Belongs to the G-protein coupled receptor 1 family.

Ontologies

Keywords
Biological process	Blood coagulation
Cellular component	Cell membrane Membrane
Coding sequence diversity	Polymorphism
Domain	Signal Transmembrane Transmembrane helix
Molecular function	G-protein coupled receptor Receptor Transducer
PTM	Disulfide bond Glycoprotein Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	STAT protein import into nucleus Inferred from direct assay. Source: BHF-UCL activation of cysteine-type endopeptidase activity involved in apoptotic process Inferred from direct assay. Source: BHF-UCL anatomical structure morphogenesis Traceable author statement. Source: ProtInc connective tissue replacement involved in inflammatory response wound healing Inferred from direct assay. Source: BHF-UCL negative regulation of cell proliferation Inferred from direct assay. Source: BHF-UCL platelet activation Inferred from direct assay. 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 cascade Inferred from expression pattern. Source: UniProtKB positive regulation of JAK-STAT cascade Inferred from direct assay. 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. Source: BHF-UCL positive regulation of cell migration Inferred from mutant phenotype. Source: BHF-UCL positive regulation of collagen biosynthetic process Inferred from direct assay. Source: BHF-UCL positive regulation of interleukin-6 secretion Inferred from direct assay. Source: UniProtKB positive regulation of interleukin-8 secretion Inferred from direct assay. Source: UniProtKB positive regulation of phosphatidylinositol 3-kinase cascade 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 transcription, DNA-dependent Inferred from direct assay. Source: BHF-UCL tyrosine phosphorylation of STAT protein Inferred from direct assay. Source: BHF-UCL
Cellular component	Golgi apparatus Traceable author statement. Source: ProtInc caveola Inferred from direct assay. Source: BHF-UCL extracellular region Traceable author statement. Source: Reactome integral to plasma membrane Traceable author statement. Source: ProtInc platelet dense tubular network Inferred from direct assay. Source: BHF-UCL
Molecular function	G-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 receptor binding Inferred from physical interaction Ref.1. Source: BHF-UCL thrombin receptor activity Inferred from direct assay Ref.1. Source: BHF-UCL
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
CAV1	Q03135	3	EBI-2803960,EBI-603614
PROCR	Q9UNN8	3	EBI-2803960,EBI-719705

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 26

26

Potential

Propeptide

27 – 41

15

Removed for receptor activation

PRO_0000012740

Chain

42 – 425

384

Proteinase-activated receptor 1

PRO_0000012741

Regions

Topological domain

42 – 102

61

Extracellular Potential

Transmembrane

103 – 128

26

Helical; Name=1; Potential

Topological domain

129 – 137

9

Cytoplasmic Potential

Transmembrane

138 – 157

20

Helical; Name=2; Potential

Topological domain

158 – 176

19

Extracellular Potential

Transmembrane

177 – 198

22

Helical; Name=3; Potential

Topological domain

199 – 218

20

Cytoplasmic Potential

Transmembrane

219 – 239

21

Helical; Name=4; Potential

Topological domain

240 – 268

29

Extracellular Potential

Transmembrane

269 – 288

20

Helical; Name=5; Potential

Topological domain

289 – 311

23

Cytoplasmic Potential

Transmembrane

312 – 334

23

Helical; Name=6; Potential

Topological domain

335 – 350

16

Extracellular Potential

Transmembrane

351 – 374

24

Helical; Name=7; Potential

Topological domain

375 – 425

51

Cytoplasmic Potential

Compositional bias

57 – 60

4

Asp/Glu-rich (acidic)

Sites

Site

41 – 42

2

Cleavage; by thrombin

Amino acid modifications

Glycosylation

35

1

N-linked (GlcNAc...) Potential

Glycosylation

62

1

N-linked (GlcNAc...) Potential

Glycosylation

75

1

N-linked (GlcNAc...) Potential

Glycosylation

250

1

N-linked (GlcNAc...) Potential

Glycosylation

259

1

N-linked (GlcNAc...) Potential

Disulfide bond

175 ↔ 254

By similarity

Natural variations

Natural variant

166

1

S → G. [dbSNP:rs5893] Ref.6

VAR_014167

Natural variant

187

1

Y → N. [dbSNP:rs2230849]

VAR_049432

Natural variant

257

1

V → L. [dbSNP:rs2227832]

VAR_049433

Natural variant

268

1

A → P. [dbSNP:rs1055103]

VAR_060680

Natural variant

335

1

A → V. [dbSNP:rs17849599] Ref.3 Ref.4

VAR_060681

Natural variant

412

1

S → Y. [dbSNP:rs2227799]

VAR_049434

Experimental info

Sequence conflict

238

1

L → V in AAA36743. Ref.1

Sequence conflict

364

1

C → S in AAA36743. Ref.1

Secondary structure

1

.

.

.

.

.

425

Helix Strand Turn

Details...

Beta strand

40 – 42

3

Beta strand

46 – 48

3

Sequences

	Sequence		Length	Mass (Da)
	P25116 [UniParc]. Last modified April 16, 2002. Version 2. Checksum: 41B742A99EEC96AB	FASTA	425	47,441
	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

References

	« Hide 'large scale' referencesShow '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: 1672265] [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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT VAL-335. Tissue: Eye.
[5]	"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: 10079109] [Abstract] Cited for: FUNCTION.
[6]	"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: 10391209] [Abstract] Cited for: VARIANT GLY-166.
[7]	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)
[8]	"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: 8136362] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 38-64 IN COMPLEX WITH THROMBIN.
+	Additional computationally mapped references.

Web resources

SeattleSNPs

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.

IPI

IPI00296869.

PIR

A37912.

RefSeq

NP_001983.2. NM_001992.3.

UniGene

Hs.482562.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1NRN	X-ray	3.10	R	38-60	[»]
1NRO	X-ray	3.10	R	38-64	[»]
1NRP	X-ray	3.00	R	38-60	[»]
1NRQ	X-ray	3.50	R	40-60	[»]
1NRR	X-ray	2.40	R	43-60	[»]
3BEF	X-ray	2.20	C/F	49-57	[»]
3HKI	X-ray	2.20	C/F	42-62	[»]
3HKJ	X-ray	2.60	C/F	42-62	[»]
3LU9	X-ray	1.80	C/F	33-57	[»]

ProteinModelPortal

P25116.

SMR

P25116. Positions 187-218.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-29703N.

IntAct

P25116. 4 interactions.

STRING

P25116.

Protein family/group databases

GPCRDB

Search...

PTM databases

PhosphoSite

P25116.

Polymorphism databases

DMDM

20178318.

Proteomic databases

PRIDE

P25116.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000319211; ENSP00000321326; ENSG00000181104.

GeneID

2149.

KEGG

hsa:2149.

NMPDR

fig|9606.3.peg.25424.

UCSC

uc003ken.2. human.

Organism-specific databases

CTD

2149.

GeneCards

GC05P076047.

H-InvDB

HIX0004960.

HGNC

HGNC:3537. F2R.

HPA

CAB008973.

MIM

187930. gene.

neXtProt

NX_P25116.

PharmGKB

PA27946.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG19741.

HOGENOM

HBG714985.

HOVERGEN

HBG108233.

InParanoid

P25116.

OMA

DTCSSNL.

OrthoDB

EOG47SSFM.

PhylomeDB

P25116.

Enzyme and pathway databases

Reactome

REACT_111102. Signal Transduction.
REACT_604. Hemostasis.

Gene expression databases

ArrayExpress

P25116.

Bgee

P25116.

CleanEx

HS_F2R.

Genevestigator

P25116.

GermOnline

ENSG00000181104. Homo sapiens.

Family and domain databases

InterPro

IPR000276. 7TM_GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_supfam.
IPR003912. Protea_act_rcpt.
IPR000935. Thrmbn_rcpt.
[Graphical view]

KO

K03914.

Pfam

PF00001. 7tm_1. 1 hit.
[Graphical view]

PRINTS

PR00237. GPCRRHODOPSN.
PR01428. PROTEASEAR.
PR00908. THROMBINR.

PROSITE

PS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

DrugBank

DB00086. Streptokinase.

NextBio

8685.

PMAP-CutDB

P25116.

SOURCE

Search...

Entry information

Entry name

PAR1_HUMAN

Accession

Primary (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:	January 25, 2012
This is version 139 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.