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PLAT Gene

protein-coding   GIFtS: 74
GCID: GC08M042032

Plasminogen Activator, Tissue

  See related diseases
at  

(According to 1HGNC, 2Entrez Gene,
3UniProtKB/Swiss-Prot, 4UniProtKB/TrEMBL, 5OMIM, 6GeneLoc, 7Ensembl, 8DME, 9miRBase, 10fRNAdb, 12H-InvDB, 13NCBI, 14NONCODE, and/or 15RNAdb)
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Aliases
Plasminogen Activator, Tissue1 2     Tissue Plasminogen Activator (T-PA)2
T-Plasminogen Activator2 3     Tissue-Type Plasminogen Activator2
EC 3.4.21.683 8     Alteplase3
TPA2 5     Reteplase3
T-PA2     t-PA3
alteplase2     tPA3
Plasminogen Activator, Tissue Type2     EC 3.4.218
reteplase2     

External Ids:    HGNC: 90511   Entrez Gene: 53272   Ensembl: ENSG000001043687   OMIM: 1733705   UniProtKB: P007503   

Export aliases for PLAT gene to outside databases

Previous GC identifers: GC08M041417 GC08M042061 GC08M041773 GC08M042050 GC08M042151 GC08M040559


(According to Entrez Gene, GeneCards, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
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Entrez Gene summary for PLAT Gene:
This gene encodes tissue-type plasminogen activator, a secreted serine protease which converts the proenzyme
plasminogen to plasmin, a fibrinolytic enzyme. Tissue-type plasminogen activator is synthesized as a single chain
which is cleaved by plasmin to a two chain disulfide linked protein. This enzyme plays a role in cell migration
and tissue remodeling. Increased enzymatic activity causes hyperfibrinolysis, which manifests as excessive
bleeding; decreased activity leads to hypofibrinolysis which can result in thrombosis or embolism. Alternative
splicing of this gene results in multiple transcript variants encoding different isoforms. (provided by RefSeq,
Jul 2008)

GeneCards Summary for PLAT Gene:
PLAT (plasminogen activator, tissue) is a protein-coding gene. Diseases associated with PLAT include pulmonary embolism, and venous thoracic outlet syndrome. GO annotations related to this gene include serine-type endopeptidase activity. An important paralog of this gene is PLG.

UniProtKB/Swiss-Prot: TPA_HUMAN, P00750
Function: 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. Plays a direct role in facilitating
neuronal migration

Gene Wiki entry for PLAT (Tissue plasminogen activator) Gene


(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 75), Regulatory elements and Epigenetics data according to QIAGEN, and/or SwitchGear Genomics)
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RefSeq DNA sequence:
NC_000008.11  NC_018919.2  NT_167187.2  
Regulatory elements:
   Regulatory transcription factor binding sites in the PLAT gene promoter:
         CREB   deltaCREB   
         Other transcription factors

SwitchGear Promoter luciferase reporter plasmidPLAT promoter sequence
   Search Chromatin IP Primers for PLAT

Epigenetics:
DNA Methylation CpG Assay Predesigned for Pyrosequencing in human, mouse, rat PLAT


Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 8p12   Ensembl cytogenetic band:  8p11.21   HGNC cytogenetic band: 8p11.21

PLAT Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
PLAT gene location

GeneLoc information about chromosome 8         GeneLoc Exon Structure

GeneLoc location for GC08M042032:  view genomic region     (about GC identifiers)

Start:
42,032,236 bp from pter      End:
42,065,242 bp from pter
Size:
33,007 bases      Orientation:
minus strand

(According to 1UniProtKB, HORDE, 2neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, and/or Cloud-Clone Corp.,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Cloud-Clone Corp., Antibodies by EMD Millipore, R&D Systems, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, LSBio, Abcam, Cloud-Clone Corp, and/or others.)
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UniProtKB/Swiss-Prot: TPA_HUMAN, P00750 (See protein sequence)
Recommended Name: Tissue-type plasminogen activator precursor  
Size: 562 amino acids; 62917 Da
Subunit: Heterodimer of chain A and chain B held by a disulfide bond. Forms a heterodimer with SERPINA5. Binds to
fibrin with high affinity. This interaction leads to an increase in the catalytic efficiency of the enzyme
between 100-fold and 1000-fold, 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. Yet unidentified interactions on endothelial cells and vascular smooth muscle cells (VSMC) lead to
a 100-fold stimulation of plasminogen activation. In addition, binding to VSMC reduces TPA inhibition by PAI-1 by
30-fold. Binds LRP1B; binding is followed by internalization and degradation
Selected PDB 3D structures from and Proteopedia for PLAT (see all 9):
1A5H (3D)        1BDA (3D)        1PK2 (3D)        1PML (3D)        1RTF (3D)        1TPG (3D)    
Secondary accessions: A8K022 B2R8E8 Q15103 Q503B0 Q6PJA5 Q7Z7N2 Q86YK8 Q9BU99 Q9BZW1
Alternative splicing: 4 isoforms:  P00750-1   P00750-2   P00750-3   P00750-4   (No experimental confirmation available)

Explore the universe of human proteins at neXtProt for PLAT: NX_P00750

Explore proteomics data for PLAT at MOPED

Post-translational modifications: 

  • The single chain, almost fully active enzyme, can be further processed into a two-chain fully active form by a
    cleavage after Arg-310 catalyzed by plasmin, tissue kallikrein or factor Xa1
  • Differential cell-specific N-linked glycosylation gives rise to two glycoforms, type I (glycosylated at Asn-219)
    and type II (not glycosylated at Asn-219). The single chain type I glycoform is less readily converted into the
    two-chain form by plasmin, and the two-chain type I glycoform has a lower activity than the two-chain type II
    glycoform in the presence of fibrin1
  • N-glycosylation of Asn-152; the bound oligomannosidic glycan is involved in the interaction with the mannose
    receptor1
  • Characterization of O-linked glycan was studied in Bowes melanoma cell line1
  • Glycosylation2 at Thr96, Asn152, Asn219, Asn483, Thr487
  • Modification sites at PhosphoSitePlus
  • Selected DME Specific Peptides for PLAT (P00750) (see all 22)
     CRNPDGD  DNDIALL  CFNGGTC  NYCRNPD 


    See PLAT Protein Expression from SPIRE MOPED, PaxDB, and MaxQB

    REFSEQ proteins (2 alternative transcripts): 
    NP_000921.1  NP_127509.1  

    ENSEMBL proteins: 
     ENSP00000392045   ENSP00000220809   ENSP00000270188   ENSP00000428886   ENSP00000407861  
     ENSP00000429401   ENSP00000429542   ENSP00000428797   ENSP00000429801   ENSP00000270189  
    Reactome Protein details: P00750

    PLAT Human Recombinant Protein Products:

    Browse Purified and Recombinant Proteins at EMD Millipore
    R&D Systems Recombinant & Natural Proteins for PLAT (t-Plasminogen Activator/tPA)
    Browse recombinant and purified proteins available from Enzo Life Sciences
    Browse OriGene full length recombinant human proteins expressed in human HEK293 cells
    OriGene Protein Over-expression Lysate for PLAT
    OriGene Custom MassSpec
    OriGene Custom Protein Services for PLAT
    GenScript Custom Purified and Recombinant Proteins Services for PLAT
    Novus Biologicals PLAT Protein
    Novus Biologicals PLAT Lysates
    Sino Biological Recombinant Protein for PLAT
    Sino Biological Cell Lysate for PLAT
    ProSpec Recombinant Protein for PLAT
    Browse Proteins at Cloud-Clone Corp.

    PLAT Antibody Products:

    EMD Millipore Mono- and Polyclonal Antibodies for the study of PLAT
    R&D Systems Antibodies for PLAT (t-Plasminogen Activator/tPA)
    OriGene Antibodies for PLAT
    OriGene Custom Antibody Services for PLAT
    Novus Biologicals PLAT Antibodies
    Abcam antibodies for PLAT
    Browse Antibodies at Cloud-Clone Corp.
    ThermoFisher Antibodies for PLAT
    LSBio Antibodies in human, mouse, rat for PLAT

    PLAT Assay Products:

    Browse Kits and Assays available from EMD Millipore
    OriGene Custom Assay Services for PLAT
    Browse R&D Systems for biochemical assays
    GenScript Custom Assay Services for PLAT
    Browse Enzo Life Sciences for kits & assays
    Browse ELISAs at Cloud-Clone Corp.
    Browse CLIAs at Cloud-Clone Corp.


    (According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
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    Selected InterPro protein domains (see all 11):
     IPR000083 Fibronectin_type1
     IPR001314 Peptidase_S1A
     IPR000742 EG-like_dom
     IPR026280 Tissue_plasm_act
     IPR018056 Kringle_CS

    Graphical View of Domain Structure for InterPro Entry P00750

    ProtoNet protein and cluster: P00750

    5 Blocks protein domains:
    IPB000001 Kringle
    IPB000083 Fibronectin
    IPB001254 Serine protease
    IPB001314 Chymotrypsin serine protease family (S1) signature
    IPB006210 Type I EGF


    UniProtKB/Swiss-Prot: TPA_HUMAN, P00750
    Domain: Both FN1 and one of the kringle domains are required for binding to fibrin
    Domain: Both FN1 and EGF-like domains are important for binding to LRP1
    Domain: The FN1 domain mediates binding to annexin A2
    Domain: The second kringle domain is implicated in binding to cytokeratin-8 and to the endothelial cell surface
    binding site
    Similarity: Belongs to the peptidase S1 family
    Similarity: Contains 1 EGF-like domain
    Similarity: Contains 1 fibronectin type-I domain
    Similarity: Contains 2 kringle domains
    Similarity: Contains 1 peptidase S1 domain


    PLAT for domains           About GeneDecksing


    (According to 1UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or 2DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, inGenious Targeting Laboratory, genOway,
    transcription factor targeting from QIAGEN and/or HOMER, miRNA Gene Targets from miRTarBase, shRNA from OriGene, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, SwitchGear Genomics, Gene Editing from DNA2.0, Clones from OriGene, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, ESI BIO, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Molecular Function:

         UniProtKB/Swiss-Prot Summary: TPA_HUMAN, P00750
    Function: 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. Plays a direct role in facilitating
    neuronal migration
    Catalytic activity: Specific cleavage of Arg- -Val bond in plasminogen to form plasmin
    Enzyme regulation: Inhibited by SERPINA5

         Genatlas biochemistry entry for PLAT:
    plasminogen activator,tissue-type

         Enzyme Numbers (IUBMB): EC 3.4.21.681 2 EC 3.4.212

         Gene Ontology (GO): 3 molecular function terms:    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0003824catalytic activity ----
    GO:0004252serine-type endopeptidase activity TAS--
    GO:0005515protein binding IPI10340997
         
    PLAT for ontologies           About GeneDecksing


    Phenotypes:
         1 GenomeRNAi human phenotype for PLAT:
     Increased G1 DNA content 

         Selected MGI mutant phenotypes (inferred from 1 allele(MGI details for Plat) (see all 17):
     behavior/neurological  cardiovascular system  cellular  craniofacial  digestive/alimentary 
     growth/size/body  hearing/vestibular/ear  hematopoietic system  homeostasis/metabolism  immune system 
     mortality/aging  muscle  nervous system  reproductive system  respiratory system 

    PLAT for phenotypes           About GeneDecksing

    Animal Models:
         MGI mouse knock-out Plattm1Mlg for PLAT

       inGenious Targeting Laboratory: Let us create your new Knockout/Knockin mouse model for PLAT
       inGenious Targeting Laboratory: Contact us about creating complex and humanized mouse models for PLAT

       genOway customized KO model: permanent, tissue-specific or time-controlled inactivation for PLAT
       genOway customized Knockin model: humanization, point mutation, expression monitoring, etc. for PLAT

    miRNA
    Products:
        
    miRTarBase miRNAs that target PLAT:
    hsa-mir-21-5p (MIRT005953), hsa-mir-204-5p (MIRT005838), hsa-mir-335-5p (MIRT017829)

    Block miRNA regulation of human, mouse, rat PLAT using miScript Target Protectors
    Selected qRT-PCR Assays for microRNAs that regulate PLAT (see all 23):
    hsa-miR-548j hsa-miR-3194-5p hsa-miR-642a hsa-miR-548i hsa-miR-3660 hsa-miR-138-2* hsa-miR-340 hsa-miR-144
    SwitchGear 3'UTR luciferase reporter plasmidPLAT 3' UTR sequence
    Inhib. RNA
    Products:
        
    OriGene RNAi products in human, mouse, rat for PLAT
    Predesigned siRNA for gene silencing in human, mouse, rat PLAT

    Gene Editing
    Products:
    DNA2.0 Custom Protein Engineering Service for PLAT

    Clone
    Products:
         
    OriGene clones in human, mouse for PLAT (see all 13)
    OriGene ORF clones in mouse, rat for PLAT
    OriGene custom cloning services - gene synthesis, subcloning, mutagenesis, variant library, vector shuttling
    GenScript: all cDNA clones in your preferred vector (see all 2): PLAT (NM_033011)
    Sino Biological Human cDNA Clone for PLAT
    DNA2.0 Custom Codon Optimized Gene Synthesis Service for PLAT
    Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat PLAT

    Cell Line
    Products:
         
    GenScript Custom overexpressing Cell Line Services for PLAT
    Browse ESI BIO Cell Lines and PureStem Progenitors for PLAT 
    In Situ Assay
    Products:
       

     
    Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for PLAT


    (According to UniProtKB, COMPARTMENTS Subcellular localization database, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Subcellular locations from UniProtKB/Swiss-Prot
    TPA_HUMAN, P00750: Secreted, extracellular space
    Subcellular locations from COMPARTMENTS: 

    CompartmentConfidence
    extracellular5
    cytoskeleton2
    nucleus2
    plasma membrane2
    cytosol1
    endoplasmic reticulum1
    lysosome1

    Gene Ontology (GO): Selected cellular component terms (see all 9):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005576extracellular region TAS--
    GO:0005615extracellular space IEA--
    GO:0005737cytoplasm IDA1632457
    GO:0009986cell surface IDA1632457
    GO:0030141secretory granule IEA--

    PLAT for ontologies           About GeneDecksing


    (SuperPaths according to PathCards, Pathways according to R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Sino Biological, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to QIAGEN, and/or STRING, Interactions according to 1UniProtKB, 2MINT, 3I2D, and/or 4STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene).
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    SuperPaths for PLAT About   (see all 15)  
    See pathways by source

    SuperPathContained pathways About
    1Complement and coagulation cascades
    Complement and coagulation cascades0.71
    Complement and Coagulation Cascades0.71
    2Formation of Fibrin Clot (Clotting Cascade)
    Blood Coagulation Signaling Pathways0.51
    Blood Clotting Cascade0.42
    3Signaling by FGFR
    Signaling by PDGF0.87
    4Signaling by GPCR
    Signal Transduction0.58
    5Hemostasis
    Hemostasis0.43

    Pathways by source                                                                                                                                                                 See SuperPaths
    Show all pathways

    2 R&D Systems Pathways for PLAT
        Blood Coagulation Signaling Pathways
    A-beta Plaque Formation & APP Metabolism


    3 GeneGo (Thomson Reuters) Pathways for PLAT
        Cell adhesion PLAU signaling
    Cell adhesion ECM remodeling
    Cell adhesion Plasmin signaling

    Selected BioSystems Pathways for PLAT (see all 6)
        Senescence and Autophagy
    Blood Clotting Cascade
    Selenium Pathway
    Endochondral Ossification
    Complement and Coagulation Cascades


    2 Reactome Pathways for PLAT
        Signaling by PDGF
    Dissolution of Fibrin Clot


    2 Kegg Pathways  (Kegg details for PLAT):
        Complement and coagulation cascades
    Transcriptional misregulation in cancer


    PLAT for pathways           About GeneDecksing

        Pathway & Disease-focused RT2 Profiler PCR Arrays including PLAT (see all 9): 
              Fibrosis in human mouse rat
              TGFB/BMP Signaling Pathway in human mouse rat
              Wound Healing in human mouse rat
              cAMP / Ca2+ Signaling PathwayFinder in human mouse rat
              Endothelial Cell Biology in human mouse rat

    Interactions:

        GeneGlobe Interaction Network for PLAT

    STRING Interaction Network Preview (showing 5 interactants - click image to see 25)

    Selected Interacting proteins for PLAT (P007502, 3 ENSP000002208094) via UniProtKB, MINT, STRING, and/or I2D (see all 53)
    InteractantInteraction Details
    GeneCardExternal ID(s)
    SERPINE1P051212, 3, ENSP000002230954MINT-8309311 I2D: score=3 STRING: ENSP00000223095
    ANXA2P073553, ENSP000003460324I2D: score=3 STRING: ENSP00000346032
    CALRP277973, ENSP000003208664I2D: score=3 STRING: ENSP00000320866
    LRP1Q079543, ENSP000002430774I2D: score=3 STRING: ENSP00000243077
    SERPINI1Q995743, ENSP000002957774I2D: score=3 STRING: ENSP00000295777
    About this table

    Gene Ontology (GO): Selected biological process terms (see all 16):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0001666response to hypoxia IEA--
    GO:0006464cellular protein modification process TAS3087818
    GO:0006508proteolysis TAS3087818
    GO:0007596blood coagulation TAS--
    GO:0014909smooth muscle cell migration IEA--

    PLAT for ontologies           About GeneDecksing



    (Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience, ApexBio, HMDB, BitterDB, and/or Novoseek, Ligands according to IUPHAR, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB)
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    Browse Small Molecules at EMD Millipore
       Browse drugs & compounds from Enzo Life Sciences
      Browse compounds at ApexBio 

    Browse Tocris compounds for PLAT (TPA)

    UniProtKB/Swiss-Prot: TPA_HUMAN, P00750
    Pharmaceutical: Available under the names Activase (Genentech) and Retavase (Centocor and Roche) [Retavase is a
    fragment of TPA that contains kringle 2 and the protease domain; it was also known as BM 06.022]. Used in Acute
    Myocardial Infarction (AMI), in Acute Ischemic Stroke (AIS) and Pulmonary Embolism (PE) to initiate fibrinolysis

    6 DrugBank Compounds for PLAT    About this table
    CompoundSynonyms CAS #TypeActionsPubMed Ids
    Iloprost-- 78919-13-8targetother/unknown1726988 1689620 1370924 1717784 17510465
    UrokinaseU-plasminogen activator (see all 3)9039-53-6target--12893898 14507109 12826021 12745435 12787697
    Aminocaproic Acid6-aminohexanoic acid (see all 7)60-32-2targetantagonist3146348 8073394 7962113 2502209
    6-Amino Hexanoic Acid-- --target--17139284 17016423
    5-(DIMETHYLAMINO)-2-NAPHTHALENESULFONIC ACID-- --target--10592235
    IbuprofenIbuprophen (see all 3)15687-27-1targetnegative modulator22668799

    Selected Novoseek inferred chemical compound relationships for PLAT gene (see all 138)    About this table
    Compound   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    fibrinogen 87.7 732 1708387 (6), 7774110 (5), 14592559 (4), 9159836 (4) (see all 99)
    heparin 79 684 1512328 (7), 1708387 (6), 8874867 (6), 17068072 (6) (see all 99)
    abciximab 77.8 337 14982910 (9), 15353917 (8), 15028807 (7), 11071800 (7) (see all 78)
    epsilon aminocaproic acid 73.4 47 14743974 (5), 1525179 (4), 8533120 (3), 8112348 (2) (see all 18)
    aspirin 61.4 85 9054741 (3), 11680515 (3), 16480745 (3), 8277097 (2) (see all 61)
    serine 61.2 182 2110366 (2), 1901356 (2), 15268626 (2), 7495809 (2) (see all 99)
    aprotinin 61.1 18 9308747 (2), 15668193 (2), 8641034 (1), 1720262 (1) (see all 13)
    nplg 60.1 2 2148848 (1), 2107598 (1)
    desmopressin 59.1 90 9427706 (6), 1606286 (5), 10959689 (4), 8854651 (3) (see all 38)
    eaca 58.9 7 2123871 (2), 8073394 (2), 7804168 (1), 7759476 (1)



    PLAT for compounds           About GeneDecksing



    (Secondary structures according to fRNAdb,
    GenBank/EMBL/DDBJ Accessions according to
    Unigene (Build 236 Homo sapiens; Apr 25 2013) or GenBank,
    RefSeq according to Entrez Gene,
    DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
    exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
    siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN, SwitchGear Genomics,
    Tagged/untagged cDNA clones from OriGene, GenScript, DNA2.0, Vector BioLabs, Primers from OriGene, and/or QIAGEN )
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    REFSEQ mRNAs for PLAT gene (3 alternative transcripts): 
    NM_000930.3  NM_033011.2  NM_000931.2  

    Unigene Cluster for PLAT:

    Plasminogen activator, tissue
    Hs.491582  [show with all ESTs]
    Unigene Representative Sequence: BX641021
    13 Ensembl transcripts including schematic representations, and UCSC links where relevant:
    ENST00000429089 ENST00000220809 ENST00000352041 ENST00000519510 ENST00000429710
    ENST00000524009 ENST00000522812 ENST00000521042 ENST00000524261 ENST00000521647
    ENST00000520523 ENST00000521694 ENST00000270189(uc010lxf.1 uc010lxg.1 uc003xos.2 uc003xot.2 uc011lcm.1 uc011lcn.1)

    miRNA
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    Block miRNA regulation of human, mouse, rat PLAT using miScript Target Protectors
    Selected qRT-PCR Assays for microRNAs that regulate PLAT (see all 23):
    hsa-miR-548j hsa-miR-3194-5p hsa-miR-642a hsa-miR-548i hsa-miR-3660 hsa-miR-138-2* hsa-miR-340 hsa-miR-144
    SwitchGear 3'UTR luciferase reporter plasmidPLAT 3' UTR sequence
    Inhib. RNA
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    OriGene RNAi products in human, mouse, rat for PLAT
    Predesigned siRNA for gene silencing in human, mouse, rat PLAT
    Clone
    Products:
         
    OriGene clones in human, mouse for PLAT (see all 13)
    OriGene ORF clones in mouse, rat for PLAT
    OriGene custom cloning services - gene synthesis, subcloning, mutagenesis, variant library, vector shuttling
    GenScript: all cDNA clones in your preferred vector (see all 2): PLAT (NM_033011)
    DNA2.0 Custom Codon Optimized Gene Synthesis Service for PLAT
    Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat PLAT
    Primer
    Products:
        
    OriGene qPCR primer pairs and template standards for PLAT
    OriGene qSTAR qPCR primer pairs in human, mouse for PLAT
    Pre-validated RT2 qPCR Primer Assay in human, mouse, rat PLAT
      QuantiTect SYBR Green Assays in human, mouse, rat PLAT
      QuantiFast Probe-based Assays in human, mouse, rat PLAT

    Additional mRNA sequence: 

    AF260825.1 AF282882.1 AK289387.1 AK290575.1 AK297738.1 AK297937.1 AK299205.1 AK300984.1 
    AK313342.1 AY221101.1 BC002795.2 BC007231.1 BC013968.2 BC018636.2 BC095403.1 BT007060.1 
    BX641021.1 D01096.1 FM956488.1 M15518.1 M18182.1 V00570.1 X02901.1 X07393.1 
    X13097.1 

    20 DOTS entries:

    DT.97768693  DT.118738  DT.95257885  DT.100817321  DT.100817313  DT.95257876  DT.95261443  DT.101963746 
    DT.92447062  DT.95257877  DT.99933134  DT.100817320  DT.95257857  DT.102828184  DT.120645473  DT.120645543 
    DT.95257856  DT.95257863  DT.95296556  DT.97845240 

    Selected AceView cDNA sequences (see all 486):

    AW236436 CA428179 AI394152 BU167954 BU845014 NM_000931 AA370689 CB140923 
    AU131736 BI765247 BC013968 NM_033011 CA424143 AL047284 BC002795 BQ687808 
    AW341283 BF447656 BE277041 AI348537 BE549489 BQ072488 BU160825 CO248131 

    GeneLoc Exon Structure

    Selected Alternative Splicing Database (ASD) splice patterns (SP) for PLAT (see all 8)    About this scheme

    ExUns: 1a · 1b · 1c · 1d ^ 2 ^ 3 ^ 4a · 4b ^ 5a · 5b · 5c · 5d ^ 6 ^ 7a · 7b ^ 8a · 8b ^ 9a · 9b ^ 10a · 10b ^ 11a · 11b · 11c ^ 12a · 12b ^
    SP1:                                                                                                                    -                       -               
    SP2:                                      -     -                                                                       -                       -               
    SP3:                                                                                                        -     -     -     -     -     -     -     -         
    SP4:                                      -     -                       -     -     -     -     -                       -                                       
    SP5:                                                              -     -     -     -     -     -     -     -           -                                       

    ExUns: 13 ^ 14
    SP1:            
    SP2:            
    SP3:            
    SP4:            
    SP5:            


    ECgene alternative splicing isoforms for PLAT

    (RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, Protein expression images according to data from SPIRE 1MOPED, 2PaxDb, and 3MaxQB, plus additional links to SOURCE, and/or BioGPS, and/or UniProtKB,
    PCR Arrays from QIAGEN, Primers from OriGene, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
    About This Section

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    PLAT expression in normal human tissues (normalized intensities)
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS <intensity>2/3
    CGAP TAG: TTAGTTTTTA
    PLAT Expression
    About this image


    PLAT expression in embryonic tissues and stem cells    About this table
    Data from LifeMap, the Embryonic Development and Stem Cells Database
     selected tissues (see all 13) fully expand
     
     Hypoblast (Extraembryonic Tissues)    fully expand to see all 2 entries
             Parietal Endoderm Cells Hypoblast
             Extraembryonic endoderm-like cells
     
     Kidney (Urinary System)    fully expand to see all 4 entries
             Metanephric Mesenchyme Cells Metanephric Mesenchyme
             S-shaped Body
     
     Brain (Nervous System)    fully expand to see all 2 entries
             Oligodendrocyte Precursor Cells Forebrain White Matter
             Oligodendrocyte progenitor cells
     
     Inner Cell Mass (Early Embryonic Tissues)    fully expand to see all 2 entries
             Line H9 (Naive)
     
     Epithelial Cells
             Podocytes Podocyte Layer
    PLAT Protein expression data from MOPED1, PaxDb2 and MaxQB3    About this image

    PLAT Protein Expression

    SOURCE GeneReport for Unigene cluster: Hs.491582

    UniProtKB/Swiss-Prot: TPA_HUMAN, P00750
    Tissue specificity: Synthesized in numerous tissues (including tumors) and secreted into most extracellular body
    fluids, such as plasma, uterine fluid, saliva, gingival crevicular fluid, tears, seminal fluid, and milk

        Pathway & Disease-focused RT2 Profiler PCR Arrays including PLAT (see all 9): 
              Fibrosis in human mouse rat
              TGFB/BMP Signaling Pathway in human mouse rat
              Wound Healing in human mouse rat
              cAMP / Ca2+ Signaling PathwayFinder in human mouse rat
              Endothelial Cell Biology in human mouse rat

    Primer
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    Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for PLAT

    (Orthologs according to 1,2HomoloGene (2older version, for species not in 1newer version), 3euGenes, 4SGD , 5MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or 6Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
    About This Section

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    This gene was present in the common ancestor of chordates.

    Orthologs for PLAT gene from Selected species (see all 12)    About this table
    Organism Taxonomic
    classification
    Gene Description Human
    Similarity
    Orthology
    Type
    Details
    mouse
    (Mus musculus)
    Mammalia Plat1 , 5 plasminogen activator, tissue1, 5 79.71(n)1
    80.61(a)1
      8 (11.42 cM)5
    187911  NM_008872.21  NP_032898.21 
     227577445 
    chicken
    (Gallus gallus)
    Aves PLAT1 plasminogen activator, tissue 64.61(n)
    62.36(a)
      426791  XM_004947613.1  XP_004947670.1 
    lizard
    (Anolis carolinensis)
    Reptilia PLAT6
    plasminogen activator, tissue
    61(a)
    1 ↔ 1
    GL343545.1(301208-313980)
    African clawed frog
    (Xenopus laevis)
    Amphibia Xl.93972 Xenopus laevis transcribed sequence with moderate similarity more 79.35(n)    BG347744.1 
    zebrafish
    (Danio rerio)
    Actinopterygii plat1 plasminogen activator, tissue 56.71(n)
    55.56(a)
      100320028  XM_002663051.2  XP_002663097.1 


    ENSEMBL Gene Tree for PLAT (if available)
    TreeFam Gene Tree for PLAT (if available)

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
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    Paralogs for PLAT gene
    PLG2  HGFAC2  HABP22  LPA2  PLAU2  MST12  F122  HGF2  
    Selected SIMAP similar genes for PLAT using alignment to 9 protein entries:     TPA_HUMAN (see all proteins) (see all similar genes):
    DKFZp686I03148    HGF    PLG    DKFZp586F0824    APOA    F12
    TMPRSS5    ATF    TMPRSS11D    KLK13    HABP2    PRSS2
    TRY8    PLAU    KLK9    PRSS1    KLK12    LPAL2

    PLAT for paralogs           About GeneDecksing



    (SNPs/Variants according to the 1NCBI SNP Database, 2Ensembl, 3PupaSUITE, 4UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD), the Human Cytochrome P450 Allele Nomenclature Database, and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers, Cancer Mutation PCR Arrays and Assays, and Copy Number PCR Arrays from QIAGEN)
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    Selected SNPs for PLAT (see all 989)    About this table    
    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance
    Chr 8 posSequence#AA
    Chg
    TypeMore#Allele
    freq
    PopTotal
    sample
    More
    ----------
    rs1406534511,2
    C--40572196(+) TCATT-/TATC  
            
    ATCAT
    2 -- int10--------
    rs1504811481,2
    C--40572335(+) TATCA-/ATCT  
            
    TCTAT
    2 -- int10--------
    rs749023881,2
    C--40585832(+) CAAAAA/TATTAT 2 -- int10--------
    rs20277911,2
    C,F--40585833(-) aataaA/Tttttt 2 -- int13Minor allele frequency- T:0.48NA NS 94
    rs58911801,2
    C--42035783(+) ttttt-/Tttttt 2 -- int1 trp32Minor allele frequency- T:0.25NA 4
    rs81787901,2
    C,F--42035785(-) aaaaa-/Gaaaga 2 -- int1 trp32Minor allele frequency- G:0.10NS 94
    rs344069181,2
    C--42043672(+) CAAAG-/T/TT  
            
    TTTTT
    2 -- int12NA CSA 4
    rs1393528231,2
    C--42043672(+) CAAAG-/TTTTTTT 2 -- int10--------
    rs556985891,2
    C--42044406(+) TTATCTATC/-  
            
    ATCTA
    2 -- int11Minor allele frequency- -:0.50NA 2
    rs1461917871,2
    C--42044541(+) CTATC-/ATCT  
            
    ATCTA
    2 -- int10--------

    HapMap Linkage Disequilibrium report for PLAT (42032236 - 42065242 bp)

    Structural Variations
         Database of Genomic Variants (DGV) 5 variations for PLAT:    About this table    
    Variant IDTypeSubtypePubMed ID
    esv270558CNV Insertion20981092
    esv274051CNV Insertion20981092
    nsv824616CNV Loss20364138
    nsv398046CNV Loss16902084
    nsv890845CNV Loss21882294

    Human Gene Mutation Database (HGMD): PLAT
    Site Specific Mutation Identification with PCR Assays
    SeqTarget long-range PCR primers for resequencing PLAT
    DNA2.0 Custom Variant and Variant Library Synthesis for PLAT

    (in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
    About This Section

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    OMIM gene information: 173370   
    OMIM disorders: 612348  
    UniProtKB/Swiss-Prot: TPA_HUMAN, P00750
  • Note=Increased activity of TPA results in increased fibrinolysis of fibrin blood clots that is associated
    with excessive bleeding. Defective release of TPA results in hypofibrinolysis that can lead to thrombosis or
    embolism

  • Selected diseases for PLAT (see all 219):    
    About MalaCards
    pulmonary embolism    venous thoracic outlet syndrome    intracranial embolism    thrombophilia, familial, due to decreased release of plat
    vitreous detachment    locked-in syndrome    hyperfibrinolysis, familial, due to increased release of plat    thoracic outlet syndrome
    dissecting aortic aneurysm    cardiac rupture    myocardial infarction, decreased    superior vena cava syndrome
    central serous chorioretinopathy    myocardial infarction 2    central retinal vein occlusion    coronary thrombosis
    basilar artery occlusion    type 3 von willebrand disease    acute myocardial infarction    plasminogen activator inhibitor type 1 deficiency

    Selected diseases from the University of Copenhagen DISEASES database for PLAT (see all 23):
    Cerebrovascular accident     Myocardial infarction     Pulmonary embolism     Basilar artery occlusion
    Coronary heart disease     Atherosclerosis     Hypertension     Brain ischemia
    Intermediate coronary syndrome     Thrombophilia     Central retinal vein occlusion     Intracranial embolism
    Hemorrhagic disease     Central retinal artery occlusion     Diabetes mellitus     Aphasia
    Intracranial thrombosis     Hemiplegia     Age related macular degeneration     Retinal detachment

    PLAT for disorders           About GeneDecksing

    Selected Novoseek inferred disease relationships for PLAT gene (see all 97)    About this table

    Disease   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    acute myocardial infarction 85.1 514 7623530 (4), 7588083 (4), 7942523 (3), 9786806 (3) (see all 99)
    stroke acute 84 166 19407229 (4), 18062448 (4), 16728683 (3), 11244203 (3) (see all 99)
    stroke 81.4 1460 15699369 (6), 19804685 (6), 18208365 (6), 19423401 (6) (see all 99)
    intracranial hemorrhages 80.5 82 9786806 (3), 10024933 (3), 18815396 (2), 17596135 (2) (see all 53)
    venous occlusion 79.6 135 1631786 (4), 2128974 (3), 9893018 (3), 8706061 (3) (see all 83)
    thrombosis 75.9 149 8657763 (3), 7692999 (2), 11387618 (2), 11719681 (2) (see all 99)
    bleeding 75 391 17975562 (4), 11698625 (4), 11195747 (4), 16515019 (3) (see all 99)
    myocardial infarction 74.5 231 8763515 (3), 10172669 (3), 10079776 (2), 10342921 (2) (see all 99)
    intracerebral hemorrhage 72.7 68 1901466 (4), 9368550 (3), 11239197 (2), 16728683 (2) (see all 46)
    fibrinolytic defect 67.9 4 1452521 (1), 14630788 (1), 1909902 (1)

    Genatlas disease: PLAT
    thrombosis,recurrent

    Genetic Association Database (GAD): PLAT
    Human Genome Epidemiology (HuGE) Navigator: PLAT (102 documents)
    Tumor Gene Database (TGDB): PLAT

    Export disorders for PLAT gene to outside databases

    (in PubMed. Associations of this gene to articles via 1Entrez Gene, 2UniProtKB/Swiss-Prot, 3HGNC, 4GAD, 5PharmGKB, 6HMDB, 7DrugBank, 8UniProtKB/TrEMBL, 9 Novoseek, and/or 10fRNAdb)
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    PubMed articles for PLAT gene, integrated from 10 sources (see all 2855):
    (articles sorted by number of sources associating them with PLAT)
        Utopia: connect your pdf to the dynamic
    world of online information

    1. Genetic variation at the human tissue-type plasminogen activator (tPA) locus: haplotypes and analysis of association to plasma levels of tPA. (PubMed id 12891381)1, 4, 9 Ladenvall P....Jern C. (Eur. J. Hum. Genet. 2003)
    2. Is tissue-plasminogen activator gene polymorphism a risk factor for venous thromboembolism in every population? (PubMed id 15976969)1, 4, 9 Oguzulgen I.K....Akar N. (J. Thromb. Thrombolysis 2005)
    3. Influence of the Alu-repeat I/D polymorphism in t-PA gene intron 8 on the stimulated t-PA release after venous occlusion. (PubMed id 12643326)1, 4, 9 Sartori M.T....Girolami A. (Clin. Appl. Thromb. Hemost. 2003)
    4. Tissue plasminogen activator and plasminogen activator inhibitor type 1 gene polymorphism in patients with gastric ulcer complicated with bleeding. (PubMed id 12589088)1, 4, 9 Kim H.S....Hong S.Y. (J. Korean Med. Sci. 2003)
    5. Functionally inactive protein C inhibitor in seminal plasma may be associated with infertility. (PubMed id 10340997)1, 2, 9 He S.... Liu Y.X. (Mol. Hum. Reprod. 1999)
    6. Common genetic variation in five thrombosis genes and relations to plasma hemostatic protein level and cardiovascular disease risk. (PubMed id 16614319)1, 4, 9 Kathiresan S....O'Donnell C.J. (Arterioscler. Thromb. Vasc. Biol. 2006)
    7. Alu-repeat polymorphism in the gene coding for tissue-type plasminogen activator and the risk of hypertension in a Chinese Han population. (PubMed id 12484521)1, 4, 9 Wang B....He R. (Hypertens. Res. 2002)
    8. Lysine 156 promotes the anomalous proenzyme activity of tPA: X-ray crystal structure of single-chain human tPA. (PubMed id 9305622)1, 2, 9 Renatus M....Bode W. (EMBO J. 1997)
    9. Male-female differences in the genetic regulation of t-PA and PAI-1 levels in a Ghanaian population. (PubMed id 18953568)1, 4, 9 Schoenhard J.A....Williams S.M. (Hum. Genet. 2008)
    10. Tissue plasminogen activator genetic polymorphisms do not influence tissue plasminogen activator release in patients with coronary heart disease. (PubMed id 16836660)1, 4, 9 Robinson S.D....Newby D.E. (J. Thromb. Haemost. 2006)

    (in PubMed, OMIM, and NCBI Bookshelf)
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     ANDOR
    Aliases
    Disorders
    Free Text  

      Query String
    PubMed
    OMIM
    NCBI Bookshelf
      (Note: In FireFox, select the above section and copy using Ctrl-C)

    (According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
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    Entrez Gene: 5327 HGNC: 9051 AceView: PLAT Ensembl:ENSG00000104368 euGenes: HUgn5327
    ECgene: PLAT Kegg: 5327 H-InvDB: PLAT

    (According to HUGE)
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      --

    (According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, UniProtKB/TrEMBL, and/or others, e.g. Wikipedia and GeneReviews, via UniProtKB/Swiss-Prot)
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    NameDescription
    PharmGKB entry for PLAT Pharmacogenomics, SNPs, Pathways
    ATLAS Chromosomes in Cancer entry for PLAT Genetics and Cytogenetics in Oncology and Haematology
    Wikipedia http://en.wikipedia.org/wiki/Tissue_plasminogen_Activator
    SeattleSNPshttp://pga.gs.washington.edu/data/plat/
    SHMPDhttp://shmpd.bii.a-star.edu.sg/gene.php?genestart=A&genename=PLAT
    Activasehttp://www.gene.com/gene/products/information/cardiovascular/activase/insert.jsp#pharmacology
    Retavasehttp://www.retavase.com/pdf/Retavase_PI.pdf

    (Patent information from GeneIP,
    Licensable technologies from WIS Yeda, Salk, Tufts,
    IP news from LifeMap Sciences, Inc.)
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    Patent Information for PLAT gene:
    Search GeneIP for patents involving PLAT

    GeneCards and IP:
    Japan Patent Office Licenses GeneCards     European Patent Office Licenses GeneCards     Improving the IP Search



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