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Aliases for PLAT Gene

Aliases for PLAT Gene

  • Plasminogen Activator, Tissue 2 3
  • TPA 3 4 6
  • T-Plasminogen Activator 3 4
  • EC 3.4.21.68 4 64
  • Alteplase 3 4
  • Reteplase 3 4
  • T-PA 3 4
  • Tissue Plasminogen Activator (T-PA) 3
  • Plasminogen Activator, Tissue Type 3
  • Tissue-Type Plasminogen Activator 3
  • EC 3.4.21 64

External Ids for PLAT Gene

Summaries for PLAT Gene

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 venous thoracic outlet syndrome and intracranial embolism. Among its related pathways are Signaling by FGFR and Signaling by GPCR. 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

Genomic Location for PLAT Gene

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

UCSC Golden Path with GeneCards custom track
Cytogenetic band:
Genomic Location for PLAT Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for PLAT Gene

Regulatory Elements 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
  • Modification sites at PhosphoSitePlus
  • Glycosylation at Thr96, Asn152, Asn219, Asn483, and Thr487

Other Protein References for PLAT Gene

Domains for PLAT Gene

UniProtKB/Swiss-Prot:

TPA_HUMAN
Domain:
  • Both FN1 and one of the kringle domains are required for binding to fibrin:
    • P00750
  • Both FN1 and EGF-like domains are important for binding to LRP1:
    • P00750
  • The FN1 domain mediates binding to annexin A2:
    • P00750
  • The second kringle domain is implicated in binding to cytokeratin-8 and to the endothelial cell surface binding site:
    • P00750
  • Contains 1 EGF-like domain.:
    • P00750
  • Contains 1 fibronectin type-I domain.:
    • P00750
  • Contains 2 kringle domains.:
    • P00750
  • Contains 1 peptidase S1 domain.:
    • P00750
Family:
  • Belongs to the peptidase S1 family.:
    • P00750
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:0003824 catalytic activity --
GO:0004252 serine-type endopeptidase activity TAS --
GO:0005515 protein binding IPI 10340997
genes like me logo Genes that share ontologies with PLAT: view
genes like me logo Genes that share phenotypes with PLAT: view

Animal Models for PLAT Gene

MGI Knock Outs for PLAT:

miRNA for PLAT Gene

miRTarBase miRNAs that target PLAT

No data available for Transcription Factor Targeting 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 2
nucleus 2
plasma membrane 2
cytosol 1
endoplasmic reticulum 1
lysosome 1

Gene Ontology (GO) - Cellular Components for PLAT Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005576 extracellular region TAS --
GO:0005615 extracellular space IEA --
GO:0005737 cytoplasm IDA 1632457
GO:0009986 cell surface IDA 1632457
GO:0030141 secretory granule IEA --
genes like me logo Genes that share ontologies with PLAT: view

Pathways 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:0001666 response to hypoxia IEA --
GO:0006464 cellular protein modification process TAS 3087818
GO:0006508 proteolysis TAS 3087818
GO:0007596 blood coagulation TAS --
GO:0014909 smooth muscle cell migration IEA --
genes like me logo Genes that share ontologies with PLAT: view

Compounds for PLAT Gene

UniProtKB/Swiss-Prot:

P00750-TPA_HUMAN
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 Gene

Compound Synonyms Cas Number Type Actions PubMed IDs
5-(DIMETHYLAMINO)-2-NAPHTHALENESULFONIC ACID
target
6-Amino Hexanoic Acid
target
Aminocaproic Acid
  • 6-aminohexanoic acid
60-32-2 target antagonist
Ibuprofen
  • Ibuprophen
15687-27-1 target negative modulator
Iloprost
78919-13-8 target other/unknown

(138) Novoseek inferred chemical compound relationships for PLAT Gene

Compound -log(P) Hits PubMed IDs
fibrinogen 87.7 242
heparin 79 265
abciximab 77.8 176
epsilon aminocaproic acid 73.4 30
aspirin 61.4 71
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

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Integrated Proteomics: protein expression 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 expressions with PLAT: view

Orthologs for PLAT Gene

This gene was present in the common ancestor of chordates.

Orthologs for PLAT Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia PLAT 36
  • 99.47 (n)
  • 99.64 (a)
PLAT 37
  • 100 (a)
OneToOne
cow
(Bos Taurus)
Mammalia PLAT 36
  • 81.55 (n)
  • 82.03 (a)
PLAT 37
  • 81 (a)
OneToOne
dog
(Canis familiaris)
Mammalia -- 37
  • 80 (a)
OneToMany
-- 37
  • 70 (a)
OneToMany
PLAT 36
  • 81.94 (n)
  • 81.11 (a)
mouse
(Mus musculus)
Mammalia Plat 36
  • 79.71 (n)
  • 80.61 (a)
Plat 16
Plat 37
  • 80 (a)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia PLAT 37
  • 70 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia PLAT 37
  • 62 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Plat 36
  • 79.77 (n)
  • 81.87 (a)
chicken
(Gallus gallus)
Aves PLAT 36
  • 64.61 (n)
  • 62.36 (a)
PLAT 37
  • 61 (a)
OneToOne
lizard
(Anolis carolinensis)
Reptilia PLAT 37
  • 61 (a)
OneToOne
African clawed frog
(Xenopus laevis)
Amphibia Xl.9397 36
tropical clawed frog
(Silurana tropicalis)
Amphibia plat 36
  • 60.12 (n)
  • 56.67 (a)
zebrafish
(Danio rerio)
Actinopterygii plat 36
  • 56.71 (n)
  • 55.56 (a)
plat 37
  • 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 MAF
rs732612 -- 42,191,850(-) TCTCC(A/C)ACAGG intron-variant
rs879293 -- 42,197,628(-) GCTGT(A/G)CCCAA intron-variant
rs1004922 -- 42,208,684(-) GCCAA(A/G)CTTCT upstream-variant-2KB
rs1058720 -- 42,187,436(-) CCAGA(C/T)GCCAT reference, synonymous-codon
rs1136159 -- 42,179,059(-) GTGTC(C/T)CCTTT synonymous-codon, reference

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

Relevant External Links for PLAT Gene

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

Disorders for PLAT Gene

(1) OMIM Diseases for PLAT Gene (173370)

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.

(97) Novoseek inferred disease relationships for PLAT Gene

Disease -log(P) Hits PubMed IDs
acute myocardial infarction 85.1 193
stroke acute 84 119
stroke 81.4 364
intracranial hemorrhages 80.5 64
venous occlusion 79.6 104

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

Publications for PLAT Gene

  1. Lysine 156 promotes the anomalous proenzyme activity of tPA: X-ray crystal structure of single-chain human tPA. (PMID: 9305622) Renatus M. … Bode W. (EMBO J. 1997) 3 4 23
  2. Linkage disequilibrium and haplotype analysis among eight novel single-nucleotide polymorphisms in the human tissue-type plasminogen activator (t-PA) gene. (PMID: 11450845) Nakazawa I. … Emi M. (J. Hum. Genet. 2001) 3 23 49
  3. The solution structure and backbone dynamics of the fibronectin type I and epidermal growth factor-like pair of modules of tissue-type plasminogen activator. (PMID: 7582899) Smith B.O. … Campbell I.D. (Structure 1995) 3 4 23
  4. Influence of the Alu-repeat I/D polymorphism in t-PA gene intron 8 on the stimulated t-PA release after venous occlusion. (PMID: 12643326) Sartori M.T. … Girolami A. (Clin. Appl. Thromb. Hemost. 2003) 3 23 49
  5. 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 49

Products for PLAT Gene

Sources for PLAT Gene

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