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Protein

Proteinase-activated receptor 3

Gene

F2RL2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Receptor for activated thrombin coupled to G proteins that stimulate phosphoinositide hydrolysis.1 Publication

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei38 – 392Cleavage; by thrombinBy similarity

GO - Molecular functioni

  • phosphatidylinositol phospholipase C activity Source: ProtInc
  • thrombin receptor activity Source: ProtInc

GO - Biological processi

  • blood coagulation Source: Reactome
  • metabolic process Source: GOC
  • platelet activation Source: Reactome
  • response to wounding Source: ProtInc
Complete GO annotation...

Keywords - Molecular functioni

G-protein coupled receptor, Receptor, Transducer

Keywords - Biological processi

Blood coagulation, Hemostasis

Enzyme and pathway databases

ReactomeiREACT_14819. Peptide ligand-binding receptors.
REACT_18283. G alpha (q) signalling events.
REACT_21384. Thrombin signalling through proteinase activated receptors (PARs).

Names & Taxonomyi

Protein namesi
Recommended name:
Proteinase-activated receptor 3
Short name:
PAR-3
Alternative name(s):
Coagulation factor II receptor-like 2
Thrombin receptor-like 2
Gene namesi
Name:F2RL2
Synonyms:PAR3
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 5

Organism-specific databases

HGNCiHGNC:3539. F2RL2.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini39 – 9456ExtracellularSequence AnalysisAdd
BLAST
Transmembranei95 – 12026Helical; Name=1Sequence AnalysisAdd
BLAST
Topological domaini121 – 1288CytoplasmicSequence Analysis
Transmembranei129 – 14820Helical; Name=2Sequence AnalysisAdd
BLAST
Topological domaini149 – 16719ExtracellularSequence AnalysisAdd
BLAST
Transmembranei168 – 18922Helical; Name=3Sequence AnalysisAdd
BLAST
Topological domaini190 – 20617CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei207 – 23024Helical; Name=4Sequence AnalysisAdd
BLAST
Topological domaini231 – 26030ExtracellularSequence AnalysisAdd
BLAST
Transmembranei261 – 28020Helical; Name=5Sequence AnalysisAdd
BLAST
Topological domaini281 – 29717CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei298 – 32225Helical; Name=6Sequence AnalysisAdd
BLAST
Topological domaini323 – 33614ExtracellularSequence AnalysisAdd
BLAST
Transmembranei337 – 36125Helical; Name=7Sequence AnalysisAdd
BLAST
Topological domaini362 – 37413CytoplasmicSequence AnalysisAdd
BLAST

GO - Cellular componenti

  • apical plasma membrane Source: Ensembl
  • extracellular region Source: Reactome
  • integral component of plasma membrane Source: ProtInc
  • plasma membrane Source: Reactome
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi39 – 391T → P: No proteolytic cleavage by thrombin. 1 Publication
Mutagenesisi40 – 401F → A: Altered signal upon thrombin cleavage. 1 Publication

Organism-specific databases

PharmGKBiPA27948.

Polymorphism and mutation databases

BioMutaiF2RL2.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2121Sequence AnalysisAdd
BLAST
Propeptidei22 – 3817Removed for receptor activationBy similarityPRO_0000012756Add
BLAST
Chaini39 – 374336Proteinase-activated receptor 3PRO_0000012757Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi25 – 251N-linked (GlcNAc...)Sequence Analysis
Glycosylationi82 – 821N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi166 ↔ 245PROSITE-ProRule annotation
Glycosylationi331 – 3311N-linked (GlcNAc...)Sequence Analysis

Post-translational modificationi

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

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PRIDEiO00254.

PTM databases

PhosphoSiteiO00254.

Miscellaneous databases

PMAP-CutDBO00254.

Expressioni

Tissue specificityi

Highest expression in the megakaryocytes of the bone marrow, lower in mature megakaryocytes, in platelets and in a variety of other tissues such as heart and gut.1 Publication

Gene expression databases

BgeeiO00254.
CleanExiHS_F2RL2.
GenevisibleiO00254. HS.

Interactioni

Subunit structurei

Interacts with INSC/inscuteable and probably GPSM2.1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
NCK1P163332EBI-1751853,EBI-389883

Protein-protein interaction databases

BioGridi108450. 1 interaction.
DIPiDIP-44337N.
IntActiO00254. 9 interactions.
MINTiMINT-3380783.
STRINGi9606.ENSP00000296641.

Structurei

3D structure databases

ProteinModelPortaliO00254.
SMRiO00254. Positions 86-363.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the G-protein coupled receptor 1 family.PROSITE-ProRule annotation

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG146611.
GeneTreeiENSGT00760000119001.
HOGENOMiHOG000116291.
HOVERGENiHBG105658.
InParanoidiO00254.
KOiK04235.
OMAiANAVTLW.
OrthoDBiEOG7QC7WD.
PhylomeDBiO00254.
TreeFamiTF330775.

Family and domain databases

InterProiIPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
IPR003943. Prot_act_rcpt_3.
IPR003912. Protea_act_rcpt.
[Graphical view]
PfamiPF00001. 7tm_1. 1 hit.
[Graphical view]
PRINTSiPR00237. GPCRRHODOPSN.
PR01428. PROTEASEAR.
PR01429. PROTEASEAR3.
PROSITEiPS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: O00254-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MKALIFAAAG LLLLLPTFCQ SGMENDTNNL AKPTLPIKTF RGAPPNSFEE
60 70 80 90 100
FPFSALEGWT GATITVKIKC PEESASHLHV KNATMGYLTS SLSTKLIPAI
110 120 130 140 150
YLLVFVVGVP ANAVTLWMLF FRTRSICTTV FYTNLAIADF LFCVTLPFKI
160 170 180 190 200
AYHLNGNNWV FGEVLCRATT VIFYGNMYCS ILLLACISIN RYLAIVHPFT
210 220 230 240 250
YRGLPKHTYA LVTCGLVWAT VFLYMLPFFI LKQEYYLVQP DITTCHDVHN
260 270 280 290 300
TCESSSPFQL YYFISLAFFG FLIPFVLIIY CYAAIIRTLN AYDHRWLWYV
310 320 330 340 350
KASLLILVIF TICFAPSNII LIIHHANYYY NNTDGLYFIY LIALCLGSLN
360 370
SCLDPFLYFL MSKTRNHSTA YLTK
Length:374
Mass (Da):42,508
Last modified:July 1, 1997 - v1
Checksum:iC45C15A695DD1ABB
GO
Isoform 2 (identifier: O00254-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-22: Missing.

Show »
Length:352
Mass (Da):40,247
Checksum:i36F6931ABB5C5393
GO

Sequence cautioni

The sequence CAD97628.1 differs from that shown. Reason: Frameshift at position 374. Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti15 – 151L → S.1 Publication
Corresponds to variant rs2069649 [ dbSNP | Ensembl ].
VAR_012849
Natural varianti177 – 1771M → V.1 Publication
Corresponds to variant rs2069700 [ dbSNP | Ensembl ].
VAR_012850
Natural varianti250 – 2501N → D.1 Publication
Corresponds to variant rs2069683 [ dbSNP | Ensembl ].
VAR_012851

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 2222Missing in isoform 2. 1 PublicationVSP_045116Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U92971 mRNA. Translation: AAC51218.1.
AK312848 mRNA. Translation: BAG35701.1.
AK298585 mRNA. Translation: BAG60775.1.
BX537386 mRNA. Translation: CAD97628.1. Frameshift.
AF374726 Genomic DNA. Translation: AAK51564.1.
AC026725 Genomic DNA. No translation available.
CH471084 Genomic DNA. Translation: EAW95778.1.
BC093648 mRNA. Translation: AAH93648.1.
BC093650 mRNA. Translation: AAH93650.1.
CCDSiCCDS4031.1. [O00254-1]
CCDS58959.1. [O00254-2]
RefSeqiNP_001243495.1. NM_001256566.1. [O00254-2]
NP_004092.1. NM_004101.3. [O00254-1]
UniGeneiHs.42502.

Genome annotation databases

EnsembliENST00000296641; ENSP00000296641; ENSG00000164220. [O00254-1]
ENST00000504899; ENSP00000426703; ENSG00000164220. [O00254-2]
GeneIDi2151.
KEGGihsa:2151.
UCSCiuc003kem.4. human. [O00254-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

SeattleSNPs

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U92971 mRNA. Translation: AAC51218.1.
AK312848 mRNA. Translation: BAG35701.1.
AK298585 mRNA. Translation: BAG60775.1.
BX537386 mRNA. Translation: CAD97628.1. Frameshift.
AF374726 Genomic DNA. Translation: AAK51564.1.
AC026725 Genomic DNA. No translation available.
CH471084 Genomic DNA. Translation: EAW95778.1.
BC093648 mRNA. Translation: AAH93648.1.
BC093650 mRNA. Translation: AAH93650.1.
CCDSiCCDS4031.1. [O00254-1]
CCDS58959.1. [O00254-2]
RefSeqiNP_001243495.1. NM_001256566.1. [O00254-2]
NP_004092.1. NM_004101.3. [O00254-1]
UniGeneiHs.42502.

3D structure databases

ProteinModelPortaliO00254.
SMRiO00254. Positions 86-363.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi108450. 1 interaction.
DIPiDIP-44337N.
IntActiO00254. 9 interactions.
MINTiMINT-3380783.
STRINGi9606.ENSP00000296641.

Chemistry

ChEMBLiCHEMBL5477.
GuidetoPHARMACOLOGYi349.

Protein family/group databases

GPCRDBiSearch...

PTM databases

PhosphoSiteiO00254.

Polymorphism and mutation databases

BioMutaiF2RL2.

Proteomic databases

PRIDEiO00254.

Protocols and materials databases

DNASUi2151.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000296641; ENSP00000296641; ENSG00000164220. [O00254-1]
ENST00000504899; ENSP00000426703; ENSG00000164220. [O00254-2]
GeneIDi2151.
KEGGihsa:2151.
UCSCiuc003kem.4. human. [O00254-1]

Organism-specific databases

CTDi2151.
GeneCardsiGC05M075947.
HGNCiHGNC:3539. F2RL2.
MIMi601919. gene.
neXtProtiNX_O00254.
PharmGKBiPA27948.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG146611.
GeneTreeiENSGT00760000119001.
HOGENOMiHOG000116291.
HOVERGENiHBG105658.
InParanoidiO00254.
KOiK04235.
OMAiANAVTLW.
OrthoDBiEOG7QC7WD.
PhylomeDBiO00254.
TreeFamiTF330775.

Enzyme and pathway databases

ReactomeiREACT_14819. Peptide ligand-binding receptors.
REACT_18283. G alpha (q) signalling events.
REACT_21384. Thrombin signalling through proteinase activated receptors (PARs).

Miscellaneous databases

GeneWikiiF2RL2.
GenomeRNAii2151.
NextBioi8693.
PMAP-CutDBO00254.
PROiO00254.
SOURCEiSearch...

Gene expression databases

BgeeiO00254.
CleanExiHS_F2RL2.
GenevisibleiO00254. HS.

Family and domain databases

InterProiIPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
IPR003943. Prot_act_rcpt_3.
IPR003912. Protea_act_rcpt.
[Graphical view]
PfamiPF00001. 7tm_1. 1 hit.
[Graphical view]
PRINTSiPR00237. GPCRRHODOPSN.
PR01428. PROTEASEAR.
PR01429. PROTEASEAR3.
PROSITEiPS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Protease-activated receptor 3 is a second thrombin receptor in humans."
    Ishihara H., Connolly A.J., Zeng D., Kahn M.L., Zheng Y.-W., Timmons C., Tram T., Coughlin S.R.
    Nature 386:502-506(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), MUTAGENESIS OF THR-39 AND PHE-40.
  2. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
    Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
    , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
    Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
    Tissue: Thymus.
  3. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
    Tissue: Retina.
  4. SeattleSNPs variation discovery resource
    Submitted (JUN-2001) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS SER-15; VAL-177 AND ASP-250.
  5. "The DNA sequence and comparative analysis of human chromosome 5."
    Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S., Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M., She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S.
    , Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M., Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R., Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J., Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A., Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M.
    Nature 431:268-274(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  6. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  7. "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] (ISOFORM 1).
  8. "The human proteinase-activated receptor-3 (PAR-3) gene. Identification within a PAR gene cluster and characterization in vascular endothelial cells and platelets."
    Schmidt V.A., Nierman W.C., Maglott D.R., Cupit L.D., Moskowitz K.A., Wainer J.A., Bahou W.F.
    J. Biol. Chem. 273:15061-15068(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: TISSUE SPECIFICITY.
  9. "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.
  10. "Two forms of human Inscuteable-related protein that links Par3 to the Pins homologues LGN and AGS3."
    Izaki T., Kamakura S., Kohjima M., Sumimoto H.
    Biochem. Biophys. Res. Commun. 341:1001-1006(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH INSC.

Entry informationi

Entry nameiPAR3_HUMAN
AccessioniPrimary (citable) accession number: O00254
Secondary accession number(s): B2R754
, B4DQ13, Q52M68, Q7Z3W3
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: July 1, 1997
Last modified: June 24, 2015
This is version 143 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. 7-transmembrane G-linked receptors
    List of 7-transmembrane G-linked receptor entries
  2. Human chromosome 5
    Human chromosome 5: entries, gene names and cross-references to MIM
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.