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P11214

- TPA_MOUSE

UniProt

P11214 - TPA_MOUSE

Protein

Tissue-type plasminogen activator

Gene

Plat

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 151 (01 Oct 2014)
      Sequence version 3 (02 Oct 2007)
      Previous versions | rss
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    Functioni

    Converts the abundant, but inactive, zymogen plasminogen to plasmin by hydrolyzing a single Arg-Val bond in plasminogen. By controlling plasmin-mediated proteolysis, it plays an important role in tissue remodeling and degradation, in cell migration and many other physiopathological events.

    Catalytic activityi

    Specific cleavage of Arg-|-Val bond in plasminogen to form plasmin.

    Enzyme regulationi

    Inhibited by SERPINA5.By similarity

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sitei99 – 991Important for binding to LRP1By similarity
    Active sitei355 – 3551Charge relay system
    Active sitei404 – 4041Charge relay system
    Sitei462 – 4621Important for single-chain activityBy similarity
    Sitei509 – 5091Important for single-chain activityBy similarity
    Active sitei510 – 5101Charge relay system

    GO - Molecular functioni

    1. serine-type endopeptidase activity Source: MGI

    GO - Biological processi

    1. negative regulation of proteolysis Source: Ensembl
    2. plasminogen activation Source: Ensembl
    3. platelet-derived growth factor receptor signaling pathway Source: MGI
    4. positive regulation of ovulation Source: Ensembl
    5. proteolysis Source: MGI
    6. regulation of synaptic plasticity Source: Ensembl
    7. response to cAMP Source: Ensembl
    8. response to glucocorticoid Source: Ensembl
    9. response to hypoxia Source: MGI
    10. response to peptide hormone Source: Ensembl
    11. smooth muscle cell migration Source: MGI
    12. synaptic transmission, glutamatergic Source: Ensembl
    13. wound healing Source: Ensembl

    Keywords - Molecular functioni

    Hydrolase, Protease, Serine protease

    Keywords - Biological processi

    Plasminogen activation

    Enzyme and pathway databases

    BRENDAi3.4.21.68. 3474.

    Protein family/group databases

    MEROPSiS01.232.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Tissue-type plasminogen activator (EC:3.4.21.68)
    Short name:
    t-PA
    Short name:
    t-plasminogen activator
    Short name:
    tPA
    Cleaved into the following 2 chains:
    Gene namesi
    Name:Plat
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Chromosome 8

    Organism-specific databases

    MGIiMGI:97610. Plat.

    Subcellular locationi

    GO - Cellular componenti

    1. apical part of cell Source: MGI
    2. cell surface Source: Ensembl
    3. cytoplasm Source: MGI
    4. extracellular space Source: MGI
    5. secretory granule Source: MGI
    6. synapse Source: Ensembl

    Keywords - Cellular componenti

    Secreted

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Signal peptidei1 – 1717Sequence AnalysisAdd
    BLAST
    Propeptidei18 – 2912By similarityPRO_0000028353Add
    BLAST
    Propeptidei30 – 323Removed by plasmin1 PublicationPRO_0000285906
    Chaini33 – 559527Tissue-type plasminogen activatorPRO_0000028354Add
    BLAST
    Chaini33 – 308276Tissue-type plasminogen activator chain APRO_0000028355Add
    BLAST
    Chaini309 – 559251Tissue-type plasminogen activator chain BPRO_0000028356Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Disulfide bondi38 ↔ 68By similarity
    Disulfide bondi66 ↔ 75By similarity
    Disulfide bondi83 ↔ 94By similarity
    Disulfide bondi88 ↔ 105By similarity
    Disulfide bondi107 ↔ 116By similarity
    Disulfide bondi124 ↔ 205By similarity
    Disulfide bondi145 ↔ 187By similarity
    Glycosylationi149 – 1491N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi176 ↔ 200By similarity
    Disulfide bondi213 ↔ 294By similarity
    Disulfide bondi234 ↔ 276By similarity
    Disulfide bondi265 ↔ 289By similarity
    Disulfide bondi297 ↔ 428Interchain (between A and B chains)PROSITE-ProRule annotation
    Disulfide bondi340 ↔ 356By similarity
    Disulfide bondi348 ↔ 417By similarity
    Disulfide bondi442 ↔ 516By similarity
    Disulfide bondi474 ↔ 490By similarity
    Glycosylationi481 – 4811N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi506 ↔ 534By similarity

    Post-translational modificationi

    The single chain, almost fully active enzyme, can be further processed into a two-chain fully active form by a cleavage after Arg-308 catalyzed by plasmin, tissue kallikrein or factor Xa.

    Keywords - PTMi

    Cleavage on pair of basic residues, Disulfide bond, Glycoprotein, Zymogen

    Proteomic databases

    MaxQBiP11214.
    PaxDbiP11214.
    PRIDEiP11214.

    PTM databases

    PhosphoSiteiP11214.

    Expressioni

    Gene expression databases

    BgeeiP11214.
    CleanExiMM_PLAT.
    GenevestigatoriP11214.

    Interactioni

    Subunit structurei

    Heterodimer of chain A and chain B held by a disulfide bond. Binds to fibrin with high affinity. This interaction leads to an increase in the catalytic efficiency of the enzyme due to an increase in affinity for plasminogen. Similarly, binding to heparin increases the activation of plasminogen. Binds to annexin A2, cytokeratin-8, fibronectin and laminin. Binds to mannose receptor and the low-density lipoprotein receptor-related protein (LRP1); these proteins are involved in TPA clearance. Binds LRP1B; binding is followed by internalization and degradation. Forms heterodimer with SERPINA5 By similarity.By similarity

    Protein-protein interaction databases

    IntActiP11214. 2 interactions.
    MINTiMINT-8178492.

    Structurei

    3D structure databases

    ProteinModelPortaliP11214.
    SMRiP11214. Positions 33-558.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini36 – 7843Fibronectin type-IPROSITE-ProRule annotationAdd
    BLAST
    Domaini79 – 11739EGF-likePROSITE-ProRule annotationAdd
    BLAST
    Domaini124 – 20582Kringle 1PROSITE-ProRule annotationAdd
    BLAST
    Domaini213 – 29482Kringle 2PROSITE-ProRule annotationAdd
    BLAST
    Domaini309 – 558250Peptidase S1PROSITE-ProRule annotationAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni39 – 4911Important for binding to annexin A2By similarityAdd
    BLAST

    Domaini

    Both FN1 and one of the kringle domains are required for binding to fibrin.By similarity
    Both FN1 and EGF-like domains are important for binding to LRP1.By similarity
    The FN1 domain mediates binding to annexin A2.By similarity
    The second kringle domain is implicated in binding to cytokeratin-8 and to the endothelial cell surface binding site.By similarity

    Sequence similaritiesi

    Belongs to the peptidase S1 family.PROSITE-ProRule annotation
    Contains 1 EGF-like domain.PROSITE-ProRule annotation
    Contains 1 fibronectin type-I domain.PROSITE-ProRule annotation
    Contains 2 kringle domains.PROSITE-ProRule annotation
    Contains 1 peptidase S1 domain.PROSITE-ProRule annotation

    Keywords - Domaini

    EGF-like domain, Kringle, Repeat, Signal

    Phylogenomic databases

    eggNOGiCOG5640.
    GeneTreeiENSGT00740000115235.
    HOGENOMiHOG000237314.
    HOVERGENiHBG008633.
    InParanoidiP11214.
    KOiK01343.
    OMAiAHVRLYP.
    OrthoDBiEOG75B84T.
    PhylomeDBiP11214.
    TreeFamiTF329901.

    Family and domain databases

    Gene3Di2.40.20.10. 2 hits.
    InterProiIPR000742. EG-like_dom.
    IPR013032. EGF-like_CS.
    IPR000083. Fibronectin_type1.
    IPR000001. Kringle.
    IPR013806. Kringle-like.
    IPR018056. Kringle_CS.
    IPR001254. Peptidase_S1.
    IPR018114. Peptidase_S1_AS.
    IPR001314. Peptidase_S1A.
    IPR026280. Tissue_plasm_act.
    IPR009003. Trypsin-like_Pept_dom.
    [Graphical view]
    PfamiPF00008. EGF. 1 hit.
    PF00039. fn1. 1 hit.
    PF00051. Kringle. 2 hits.
    PF00089. Trypsin. 1 hit.
    [Graphical view]
    PIRSFiPIRSF001145. Tissue_plasm_act. 1 hit.
    PRINTSiPR00722. CHYMOTRYPSIN.
    SMARTiSM00181. EGF. 1 hit.
    SM00058. FN1. 1 hit.
    SM00130. KR. 2 hits.
    SM00020. Tryp_SPc. 1 hit.
    [Graphical view]
    SUPFAMiSSF50494. SSF50494. 1 hit.
    SSF57440. SSF57440. 2 hits.
    PROSITEiPS00022. EGF_1. 1 hit.
    PS01186. EGF_2. 1 hit.
    PS50026. EGF_3. 1 hit.
    PS01253. FN1_1. 1 hit.
    PS51091. FN1_2. 1 hit.
    PS00021. KRINGLE_1. 2 hits.
    PS50070. KRINGLE_2. 2 hits.
    PS50240. TRYPSIN_DOM. 1 hit.
    PS00134. TRYPSIN_HIS. 1 hit.
    PS00135. TRYPSIN_SER. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

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

    P11214-1 [UniParc]FASTAAdd to Basket

    « Hide

    MKRELLCVLL LCGLAFPLPD QGIHGRFRRG ARSYRATCRD EPTQTTYQQH    50
    QSWLRPMLRS SRVEYCRCNS GLVQCHSVPV RSCSEPRCFN GGTCQQALYF 100
    SDFVCQCPDG FVGKRCDIDT RATCFEEQGI TYRGTWSTAE SGAECINWNS 150
    SVLSLKPYNA RRPNAIKLGL GNHNYCRNPD RDLKPWCYVF KAGKYTTEFC 200
    STPACPKGKS EDCYVGKGVT YRGTHSLTTS QASCLPWNSI VLMGKSYTAW 250
    RTNSQALGLG RHNYCRNPDG DARPWCHVMK DRKLTWEYCD MSPCSTCGLR 300
    QYKRPQFRIK GGLYTDITSH PWQAAIFVKN KRSPGERFLC GGVLISSCWV 350
    LSAAHCFLER FPPNHLKVVL GRTYRVVPGE EEQTFEIEKY IVHEEFDDDT 400
    YDNDIALLQL RSQSKQCAQE SSSVGTACLP DPNLQLPDWT ECELSGYGKH 450
    EASSPFFSDR LKEAHVRLYP SSRCTSQHLF NKTVTNNMLC AGDTRSGGNQ 500
    DLHDACQGDS GGPLVCMINK QMTLTGIISW GLGCGQKDVP GVYTKVTNYL 550
    DWIHDNMKQ 559
    Length:559
    Mass (Da):63,097
    Last modified:October 2, 2007 - v3
    Checksum:i0A158A5A273CFAA0
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti260 – 2601G → A in AAA40470. (PubMed:2826484)Curated
    Sequence conflicti325 – 3251A → P in AAH11256. (PubMed:15489334)Curated

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    J03520 mRNA. Translation: AAA40470.1.
    AK135857 mRNA. Translation: BAE22698.1.
    AK135965 mRNA. Translation: BAE22749.1.
    BC011256 mRNA. Translation: AAH11256.1.
    BC057967 mRNA. Translation: AAH57967.1.
    BC061508 mRNA. Translation: AAH61508.1.
    CCDSiCCDS22183.1.
    PIRiA29941.
    RefSeqiNP_032898.2. NM_008872.2.
    UniGeneiMm.154660.

    Genome annotation databases

    EnsembliENSMUST00000033941; ENSMUSP00000033941; ENSMUSG00000031538.
    GeneIDi18791.
    KEGGimmu:18791.
    UCSCiuc009ldx.2. mouse.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    J03520 mRNA. Translation: AAA40470.1 .
    AK135857 mRNA. Translation: BAE22698.1 .
    AK135965 mRNA. Translation: BAE22749.1 .
    BC011256 mRNA. Translation: AAH11256.1 .
    BC057967 mRNA. Translation: AAH57967.1 .
    BC061508 mRNA. Translation: AAH61508.1 .
    CCDSi CCDS22183.1.
    PIRi A29941.
    RefSeqi NP_032898.2. NM_008872.2.
    UniGenei Mm.154660.

    3D structure databases

    ProteinModelPortali P11214.
    SMRi P11214. Positions 33-558.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    IntActi P11214. 2 interactions.
    MINTi MINT-8178492.

    Protein family/group databases

    MEROPSi S01.232.

    PTM databases

    PhosphoSitei P11214.

    Proteomic databases

    MaxQBi P11214.
    PaxDbi P11214.
    PRIDEi P11214.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000033941 ; ENSMUSP00000033941 ; ENSMUSG00000031538 .
    GeneIDi 18791.
    KEGGi mmu:18791.
    UCSCi uc009ldx.2. mouse.

    Organism-specific databases

    CTDi 5327.
    MGIi MGI:97610. Plat.

    Phylogenomic databases

    eggNOGi COG5640.
    GeneTreei ENSGT00740000115235.
    HOGENOMi HOG000237314.
    HOVERGENi HBG008633.
    InParanoidi P11214.
    KOi K01343.
    OMAi AHVRLYP.
    OrthoDBi EOG75B84T.
    PhylomeDBi P11214.
    TreeFami TF329901.

    Enzyme and pathway databases

    BRENDAi 3.4.21.68. 3474.

    Miscellaneous databases

    NextBioi 295068.
    PROi P11214.
    SOURCEi Search...

    Gene expression databases

    Bgeei P11214.
    CleanExi MM_PLAT.
    Genevestigatori P11214.

    Family and domain databases

    Gene3Di 2.40.20.10. 2 hits.
    InterProi IPR000742. EG-like_dom.
    IPR013032. EGF-like_CS.
    IPR000083. Fibronectin_type1.
    IPR000001. Kringle.
    IPR013806. Kringle-like.
    IPR018056. Kringle_CS.
    IPR001254. Peptidase_S1.
    IPR018114. Peptidase_S1_AS.
    IPR001314. Peptidase_S1A.
    IPR026280. Tissue_plasm_act.
    IPR009003. Trypsin-like_Pept_dom.
    [Graphical view ]
    Pfami PF00008. EGF. 1 hit.
    PF00039. fn1. 1 hit.
    PF00051. Kringle. 2 hits.
    PF00089. Trypsin. 1 hit.
    [Graphical view ]
    PIRSFi PIRSF001145. Tissue_plasm_act. 1 hit.
    PRINTSi PR00722. CHYMOTRYPSIN.
    SMARTi SM00181. EGF. 1 hit.
    SM00058. FN1. 1 hit.
    SM00130. KR. 2 hits.
    SM00020. Tryp_SPc. 1 hit.
    [Graphical view ]
    SUPFAMi SSF50494. SSF50494. 1 hit.
    SSF57440. SSF57440. 2 hits.
    PROSITEi PS00022. EGF_1. 1 hit.
    PS01186. EGF_2. 1 hit.
    PS50026. EGF_3. 1 hit.
    PS01253. FN1_1. 1 hit.
    PS51091. FN1_2. 1 hit.
    PS00021. KRINGLE_1. 2 hits.
    PS50070. KRINGLE_2. 2 hits.
    PS50240. TRYPSIN_DOM. 1 hit.
    PS00134. TRYPSIN_HIS. 1 hit.
    PS00135. TRYPSIN_SER. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Molecular cloning of complementary DNA to mouse tissue plasminogen activator mRNA and its expression during F9 teratocarcinoma cell differentiation."
      Rickles R.J., Darrow A.L., Strickland S.
      J. Biol. Chem. 263:1563-1569(1988) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    2. "The transcriptional landscape of the mammalian genome."
      Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
      , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
      Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
      Strain: C57BL/6J.
    3. "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].
      Strain: FVB/N and NMRI.
      Tissue: Mammary gland and Mammary tumor.
    4. "Characterization of the murine plasma fibrinolytic system."
      Lijnen H.R., van Hoef B., Beelen V., Collen D.
      Eur. J. Biochem. 224:863-871(1994) [PubMed] [Europe PMC] [Abstract]
      Cited for: PROTEIN SEQUENCE OF 33-40 AND 309-316.

    Entry informationi

    Entry nameiTPA_MOUSE
    AccessioniPrimary (citable) accession number: P11214
    Secondary accession number(s): Q6P7U0, Q91VP2
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: July 1, 1989
    Last sequence update: October 2, 2007
    Last modified: October 1, 2014
    This is version 151 of the entry and version 3 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Direct protein sequencing, Reference proteome

    Documents

    1. MGD cross-references
      Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
    2. Peptidase families
      Classification of peptidase families and list of entries
    3. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3