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O00254

- PAR3_HUMAN

UniProt

O00254 - PAR3_HUMAN

Protein

Proteinase-activated receptor 3

Gene

F2RL2

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
    • BLAST
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    • History
      Entry version 139 (01 Oct 2014)
      Sequence version 1 (01 Jul 1997)
      Previous versions | rss
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    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

    1. phosphatidylinositol phospholipase C activity Source: ProtInc
    2. protein binding Source: IntAct
    3. thrombin receptor activity Source: ProtInc

    GO - Biological processi

    1. blood coagulation Source: Reactome
    2. metabolic process Source: GOC
    3. platelet activation Source: Reactome
    4. response to wounding Source: ProtInc

    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: Chromosome 5

    Organism-specific databases

    HGNCiHGNC:3539. F2RL2.

    Subcellular locationi

    GO - Cellular componenti

    1. apical plasma membrane Source: Ensembl
    2. extracellular region Source: Reactome
    3. integral component of plasma membrane Source: ProtInc
    4. plasma membrane Source: Reactome

    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.

    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.
    GenevestigatoriO00254.

    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...

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini39 – 9456ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini121 – 1288CytoplasmicSequence Analysis
    Topological domaini149 – 16719ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini190 – 20617CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini231 – 26030ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini281 – 29717CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini323 – 33614ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini362 – 37413CytoplasmicSequence AnalysisAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei95 – 12026Helical; Name=1Sequence AnalysisAdd
    BLAST
    Transmembranei129 – 14820Helical; Name=2Sequence AnalysisAdd
    BLAST
    Transmembranei168 – 18922Helical; Name=3Sequence AnalysisAdd
    BLAST
    Transmembranei207 – 23024Helical; Name=4Sequence AnalysisAdd
    BLAST
    Transmembranei261 – 28020Helical; Name=5Sequence AnalysisAdd
    BLAST
    Transmembranei298 – 32225Helical; Name=6Sequence AnalysisAdd
    BLAST
    Transmembranei337 – 36125Helical; Name=7Sequence AnalysisAdd
    BLAST

    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.
    HOGENOMiHOG000116291.
    HOVERGENiHBG105658.
    InParanoidiO00254.
    KOiK04235.
    OMAiCRATTVI.
    OrthoDBiEOG7QC7WD.
    PhylomeDBiO00254.
    TreeFamiTF330775.

    Family and domain databases

    Gene3Di1.20.1070.10. 1 hit.
    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. Align

    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

    MKALIFAAAG LLLLLPTFCQ SGMENDTNNL AKPTLPIKTF RGAPPNSFEE    50
    FPFSALEGWT GATITVKIKC PEESASHLHV KNATMGYLTS SLSTKLIPAI 100
    YLLVFVVGVP ANAVTLWMLF FRTRSICTTV FYTNLAIADF LFCVTLPFKI 150
    AYHLNGNNWV FGEVLCRATT VIFYGNMYCS ILLLACISIN RYLAIVHPFT 200
    YRGLPKHTYA LVTCGLVWAT VFLYMLPFFI LKQEYYLVQP DITTCHDVHN 250
    TCESSSPFQL YYFISLAFFG FLIPFVLIIY CYAAIIRTLN AYDHRWLWYV 300
    KASLLILVIF TICFAPSNII LIIHHANYYY NNTDGLYFIY LIALCLGSLN 350
    SCLDPFLYFL MSKTRNHSTA YLTK 374
    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.

    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:
    EMBL
    GenBank
    DDBJ
    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:
    EMBL
    GenBank
    DDBJ
    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 .
    CCDSi CCDS4031.1. [O00254-1 ]
    CCDS58959.1. [O00254-2 ]
    RefSeqi NP_001243495.1. NM_001256566.1. [O00254-2 ]
    NP_004092.1. NM_004101.3. [O00254-1 ]
    UniGenei Hs.42502.

    3D structure databases

    ProteinModelPortali O00254.
    SMRi O00254. Positions 86-363.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 108450. 1 interaction.
    DIPi DIP-44337N.
    IntActi O00254. 9 interactions.
    MINTi MINT-3380783.
    STRINGi 9606.ENSP00000296641.

    Chemistry

    ChEMBLi CHEMBL5477.
    GuidetoPHARMACOLOGYi 349.

    Protein family/group databases

    GPCRDBi Search...

    PTM databases

    PhosphoSitei O00254.

    Proteomic databases

    PRIDEi O00254.

    Protocols and materials databases

    DNASUi 2151.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000296641 ; ENSP00000296641 ; ENSG00000164220 . [O00254-1 ]
    ENST00000504899 ; ENSP00000426703 ; ENSG00000164220 . [O00254-2 ]
    GeneIDi 2151.
    KEGGi hsa:2151.
    UCSCi uc003kem.4. human. [O00254-1 ]

    Organism-specific databases

    CTDi 2151.
    GeneCardsi GC05M075947.
    HGNCi HGNC:3539. F2RL2.
    MIMi 601919. gene.
    neXtProti NX_O00254.
    PharmGKBi PA27948.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG146611.
    HOGENOMi HOG000116291.
    HOVERGENi HBG105658.
    InParanoidi O00254.
    KOi K04235.
    OMAi CRATTVI.
    OrthoDBi EOG7QC7WD.
    PhylomeDBi O00254.
    TreeFami TF330775.

    Enzyme and pathway databases

    Reactomei REACT_14819. Peptide ligand-binding receptors.
    REACT_18283. G alpha (q) signalling events.
    REACT_21384. Thrombin signalling through proteinase activated receptors (PARs).

    Miscellaneous databases

    GeneWikii F2RL2.
    GenomeRNAii 2151.
    NextBioi 8693.
    PMAP-CutDB O00254.
    PROi O00254.
    SOURCEi Search...

    Gene expression databases

    Bgeei O00254.
    CleanExi HS_F2RL2.
    Genevestigatori O00254.

    Family and domain databases

    Gene3Di 1.20.1070.10. 1 hit.
    InterProi IPR000276. GPCR_Rhodpsn.
    IPR017452. GPCR_Rhodpsn_7TM.
    IPR003943. Prot_act_rcpt_3.
    IPR003912. Protea_act_rcpt.
    [Graphical view ]
    Pfami PF00001. 7tm_1. 1 hit.
    [Graphical view ]
    PRINTSi PR00237. GPCRRHODOPSN.
    PR01428. PROTEASEAR.
    PR01429. PROTEASEAR3.
    PROSITEi PS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
    PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    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: October 1, 2014
    This is version 139 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