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Aliases for PLAT Gene

Aliases for PLAT Gene

  • Plasminogen Activator, Tissue Type 2 3
  • Plasminogen Activator, Tissue 2 5
  • T-Plasminogen Activator 3 4
  • EC 3.4.21.68 4 63
  • Alteplase 3 4
  • Reteplase 3 4
  • T-PA 3 4
  • TPA 3 4
  • Plasminogen/Activator Kringle 3
  • EC 3.4.21 63

External Ids for PLAT Gene

Previous GeneCards Identifiers for PLAT Gene

  • GC08M041417
  • GC08M042061
  • GC08M041773
  • GC08M042050
  • GC08M042151
  • GC08M040559
  • GC08M042032

Summaries for PLAT Gene

Entrez Gene Summary for PLAT Gene

  • This gene encodes tissue-type plasminogen activator, a secreted serine protease that converts the proenzyme plasminogen to plasmin, a fibrinolytic enzyme. The encoded preproprotein is proteolytically processed by plasmin or trypsin to generate heavy and light chains. These chains associate via disulfide linkages to form the heterodimeric enzyme. This enzyme plays a role in cell migration and tissue remodeling. Increased enzymatic activity causes hyperfibrinolysis, which manifests as excessive bleeding, while decreased activity leads to hypofibrinolysis, which can result in thrombosis or embolism. Alternative splicing of this gene results in multiple transcript variants, at least one of which encodes an isoform that is proteolytically processed. [provided by RefSeq, Jan 2016]

GeneCards Summary for PLAT Gene

PLAT (Plasminogen Activator, Tissue Type) is a Protein Coding gene. Diseases associated with PLAT include thrombophilia, familial, due to decreased release of plat and acute myocardial infarction. Among its related pathways are Complement and coagulation cascades and Transcriptional misregulation in cancer. GO annotations related to this gene include serine-type endopeptidase activity. An important paralog of this gene is HGFAC.

UniProtKB/Swiss-Prot for PLAT Gene

  • 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 Gene

No data available for Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for PLAT Gene

Genomics for PLAT Gene

Regulatory Elements for PLAT Gene

Enhancers for PLAT Gene
GeneHancer Identifier Score Enhancer Sources TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor Binding Sites within enhancer Other Gene Targets for Enhancer

Enhancers around PLAT on UCSC Golden Path with GeneCards custom track

Promoters for PLAT Gene
Ensembl Regulatory Elements (ENSRs) TSS Distance (bp) Size (bp) Binding Sites for Transcription Factors within promoters

ENSRs around PLAT on UCSC Golden Path with GeneCards custom track

Genomic Location for PLAT Gene

Chromosome:
8
Start:
42,174,718 bp from pter
End:
42,207,724 bp from pter
Size:
33,007 bases
Orientation:
Minus strand

Genomic View for PLAT Gene

Genes around PLAT on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
PLAT Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for PLAT Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for PLAT Gene

Proteins for PLAT Gene

  • Protein details for PLAT Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P00750-TPA_HUMAN
    Recommended name:
    Tissue-type plasminogen activator
    Protein Accession:
    P00750
    Secondary Accessions:
    • A8K022
    • B2R8E8
    • Q15103
    • Q503B0
    • Q6PJA5
    • Q7Z7N2
    • Q86YK8
    • Q9BU99
    • Q9BZW1

    Protein attributes for PLAT Gene

    Size:
    562 amino acids
    Molecular mass:
    62917 Da
    Quaternary structure:
    • 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.

    Three dimensional structures from OCA and Proteopedia for PLAT Gene

    Alternative splice isoforms for PLAT Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for PLAT Gene

Proteomics data for PLAT Gene at MOPED

Post-translational modifications for PLAT Gene

  • Characterization of O-linked glycan was studied in Bowes melanoma cell line.
  • 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 fibrin.
  • N-glycosylation of Asn-152; the bound oligomannosidic glycan is involved in the interaction with the mannose receptor.
  • 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 Xa.
  • Glycosylation at Thr 96, Asn 152, Asn 219, Asn 483, and Thr 487
  • Modification sites at PhosphoSitePlus

Antibody Products

  • R&D Systems Antibodies for PLAT (t-Plasminogen Activator/tPA)

Domains & Families for PLAT Gene

Graphical View of Domain Structure for InterPro Entry

P00750

UniProtKB/Swiss-Prot:

TPA_HUMAN :
  • Both FN1 and one of the kringle domains are required for binding to fibrin.
  • Belongs to the peptidase S1 family.
Domain:
  • Both FN1 and one of the kringle domains are required for binding to fibrin.
  • Both FN1 and EGF-like domains are important for binding to LRP1.
  • The FN1 domain mediates binding to annexin A2.
  • The second kringle domain is implicated in binding to cytokeratin-8 and to the endothelial cell surface binding site.
  • Contains 1 EGF-like domain.
  • Contains 1 fibronectin type-I domain.
  • Contains 2 kringle domains.
  • Contains 1 peptidase S1 domain.
Family:
  • Belongs to the peptidase S1 family.
genes like me logo Genes that share domains with PLAT: view

No data available for Gene Families for PLAT Gene

Function for PLAT Gene

Molecular function for PLAT Gene

GENATLAS Biochemistry:
plasminogen activator,tissue-type
UniProtKB/Swiss-Prot CatalyticActivity:
Specific cleavage of Arg- -Val bond in plasminogen to form plasmin.
UniProtKB/Swiss-Prot EnzymeRegulation:
Inhibited by SERPINA5.
UniProtKB/Swiss-Prot 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.

Enzyme Numbers (IUBMB) for PLAT Gene

Gene Ontology (GO) - Molecular Function for PLAT Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0051219 phosphoprotein binding IPI 8186264
genes like me logo Genes that share ontologies with PLAT: view
genes like me logo Genes that share phenotypes with PLAT: view

Human Phenotype Ontology for PLAT Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for PLAT Gene

MGI Knock Outs for PLAT:

Animal Model Products

miRNA for PLAT Gene

miRTarBase miRNAs that target PLAT

No data available for Transcription Factor Targets and HOMER Transcription for PLAT Gene

Localization for PLAT Gene

Subcellular locations from UniProtKB/Swiss-Prot for PLAT Gene

Secreted, extracellular space.

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for PLAT Gene COMPARTMENTS Subcellular localization image for PLAT gene
Compartment Confidence
extracellular 5
cytoskeleton 3
plasma membrane 2
cytosol 1
endoplasmic reticulum 1
lysosome 1
nucleus 1
vacuole 1

Gene Ontology (GO) - Cellular Components for PLAT Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005576 extracellular region IEA,TAS --
GO:0005737 cytoplasm IDA 1632457
GO:0045177 apical part of cell IEA --
genes like me logo Genes that share ontologies with PLAT: view

Pathways & Interactions for PLAT Gene

genes like me logo Genes that share pathways with PLAT: view

Gene Ontology (GO) - Biological Process for PLAT Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0045861 negative regulation of proteolysis IDA 1695900
GO:0048008 platelet-derived growth factor receptor signaling pathway IEA --
genes like me logo Genes that share ontologies with PLAT: view

No data available for SIGNOR curated interactions for PLAT Gene

Drugs & Compounds for PLAT Gene

(72) Drugs for PLAT Gene - From: DrugBank, DGIdb, HMDB, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Iloprost Approved, Investigational Pharma Full agonist, Agonist, Target, other/unknown Others, Prostacyclin (PGI2) analog 77
Urokinase Approved, Investigational, Withdrawn Pharma activator, Target 0
Tranexamic Acid Approved Pharma inhibitor 232
Aminocaproic Acid Approved, Investigational Pharma Target, antagonist 26
Ibuprofen Approved Pharma Channel blocker, Target, negative modulator 467

(71) Additional Compounds for PLAT Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
genes like me logo Genes that share compounds with PLAT: view

Transcripts for PLAT Gene

Unigene Clusters for PLAT Gene

Plasminogen activator, tissue:
Representative Sequences:

Alternative Splicing Database (ASD) splice patterns (SP) for PLAT Gene

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: - - - - - - - - -
SP6: - -
SP7: - - - -
SP8:

ExUns: 13 ^ 14
SP1:
SP2:
SP3:
SP4:
SP5:
SP6:
SP7:
SP8:

Relevant External Links for PLAT Gene

GeneLoc Exon Structure for
PLAT
ECgene alternative splicing isoforms for
PLAT

Expression for PLAT Gene

mRNA expression in normal human tissues for PLAT Gene

Protein differential expression in normal tissues from HIPED for PLAT Gene

This gene is overexpressed in Amniocyte (33.3) and Breast (23.6).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, MOPED, and MaxQB for PLAT Gene



SOURCE GeneReport for Unigene cluster for PLAT Gene Hs.491582

mRNA Expression by UniProt/SwissProt for PLAT Gene

P00750-TPA_HUMAN
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.
genes like me logo Genes that share expression patterns with PLAT: view

Protein tissue co-expression partners for PLAT Gene

Primer Products

In Situ Assay Products

No data available for mRNA differential expression in normal tissues for PLAT Gene

Orthologs for PLAT Gene

This gene was present in the common ancestor of chordates.

Orthologs for PLAT Gene

Organism Taxonomy Gene Similarity Type Details
cow
(Bos Taurus)
Mammalia PLAT 35
  • 81.55 (n)
  • 82.03 (a)
PLAT 36
  • 81 (a)
OneToOne
dog
(Canis familiaris)
Mammalia PLAT 35
  • 81.94 (n)
  • 81.11 (a)
-- 36
  • 80 (a)
OneToMany
-- 36
  • 70 (a)
OneToMany
mouse
(Mus musculus)
Mammalia Plat 35
  • 79.71 (n)
  • 80.61 (a)
Plat 16
Plat 36
  • 80 (a)
OneToOne
chimpanzee
(Pan troglodytes)
Mammalia PLAT 35
  • 99.47 (n)
  • 99.64 (a)
PLAT 36
  • 100 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Plat 35
  • 79.77 (n)
  • 81.87 (a)
oppossum
(Monodelphis domestica)
Mammalia PLAT 36
  • 70 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia PLAT 36
  • 62 (a)
OneToOne
chicken
(Gallus gallus)
Aves PLAT 35
  • 64.61 (n)
  • 62.36 (a)
PLAT 36
  • 61 (a)
OneToOne
lizard
(Anolis carolinensis)
Reptilia PLAT 36
  • 61 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia plat 35
  • 60.12 (n)
  • 56.67 (a)
African clawed frog
(Xenopus laevis)
Amphibia Xl.9397 35
zebrafish
(Danio rerio)
Actinopterygii plat 35
  • 56.71 (n)
  • 55.56 (a)
plat 36
  • 53 (a)
OneToOne
Species with no ortholog for PLAT:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • fruit fly (Drosophila melanogaster)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea squirt (Ciona intestinalis)
  • sea squirt (Ciona savignyi)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)

Evolution for PLAT Gene

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

Paralogs for PLAT Gene

Paralogs for PLAT Gene

genes like me logo Genes that share paralogs with PLAT: view

Variants for PLAT Gene

Sequence variations from dbSNP and Humsavar for PLAT Gene

SNP ID Clin Chr 08 pos Sequence Context AA Info Type
rs2020921 - 42,187,447(-) GCGGG(A/C/T)GGAGG reference, missense
rs8178733 - 42,191,386(-) AGGAG(A/C)CAGAT reference, missense
rs8178747 - 42,187,529(-) TACAG(C/G)GGCAC reference, missense
rs8178748 - 42,187,501(-) GTGGC(A/G)CCGAG reference, missense
rs2020919 -- 42,207,691(-) AGGCC(C/T)GCCTC upstream-variant-2KB

Structural Variations from Database of Genomic Variants (DGV) for PLAT Gene

Variant ID Type Subtype PubMed ID
nsv824616 CNV Loss 20364138
esv270558 CNV Insertion 20981092
esv274051 CNV Insertion 20981092
nsv398046 CNV Loss 16902084
nsv890845 CNV Loss 21882294

Variation tolerance for PLAT Gene

Residual Variation Intolerance Score: 45.5% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 2.72; 46.57% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for PLAT Gene

HapMap Linkage Disequilibrium report
PLAT
Human Gene Mutation Database (HGMD)
PLAT

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for PLAT Gene

Disorders for PLAT Gene

MalaCards: The human disease database

(36) MalaCards diseases for PLAT Gene - From: OMIM, DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
thrombophilia, familial, due to decreased release of plat
  • hyperfibrinolysis, familial, due to increased release of plat
acute myocardial infarction
pulmonary embolism
  • pulmonary artery embolism
coronary thrombosis
  • coronary artery thrombosis
basilar artery occlusion
- elite association - COSMIC cancer census association via MalaCards
Search PLAT in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

TPA_HUMAN
  • 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. {ECO:0000269 PubMed:1762144}.

Genatlas disease for PLAT Gene

thrombosis,recurrent

Relevant External Links for PLAT

Genetic Association Database (GAD)
PLAT
Human Genome Epidemiology (HuGE) Navigator
PLAT
Tumor Gene Database (TGDB):
PLAT
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
PLAT
genes like me logo Genes that share disorders with PLAT: view

Publications for PLAT Gene

  1. Genetic variation at the human tissue-type plasminogen activator (tPA) locus: haplotypes and analysis of association to plasma levels of tPA. (PMID: 12891381) Ladenvall P. … Jern C. (Eur. J. Hum. Genet. 2003) 3 23 48 67
  2. Activation of human platelets by misfolded proteins. (PMID: 17510465) Herczenik E. … Akkerman J.W. (Arterioscler. Thromb. Vasc. Biol. 2007) 23 25 26
  3. Pharmacokinetics of tissue-type plasminogen activator during acute myocardial infarction in men. Effect of a prostacyclin analogue. (PMID: 1370924) Kerins D.M. … Fitzgerald D.J. (Circulation 1992) 23 25 26
  4. Male-female differences in the genetic regulation of t-PA and PAI-1 levels in a Ghanaian population. (PMID: 18953568) Schoenhard J.A. … Williams S.M. (Hum. Genet. 2008) 3 23
  5. Effect of oxidative stress on the expression of t-PA, u-PA, u-PAR, and PAI-1 in endothelial cells. (PMID: 19088796) Oszajca K. … Szemraj J. (Biochem. Cell Biol. 2008) 3 23

Products for PLAT Gene

Sources for PLAT Gene

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