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Aliases for PLAT Gene

Aliases for PLAT Gene

  • Plasminogen Activator, Tissue Type 2 3 5
  • T-Plasminogen Activator 3 4
  • EC 3.4.21.68 4 61
  • Alteplase 3 4
  • Reteplase 3 4
  • T-PA 3 4
  • TPA 3 4
  • Tissue-Type Plasminogen Activator 3
  • Plasminogen Activator, Tissue 2
  • Plasminogen/Activator Kringle 3
  • EC 3.4.21 61

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 amb2 Integrin signaling and Formation of Fibrin Clot (Clotting Cascade). GO annotations related to this gene include serine-type endopeptidase activity. An important paralog of this gene is PLAU.

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 CIViC summary , 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 Enhancer Score Enhancer Sources Gene-Enhancer Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor Binding Sites within enhancer Gene Targets for Enhancer
GH08G042245 0.9 Ensembl ENCODE 26.1 -38.8 -38767 2.5 PKNOX1 TSHZ1 EP300 OSR2 ZNF121 NFIC PRDM6 ZNF318 SMARCA4 PBX2 PLAT POLB IKBKB LOC101929897 AP3M2
GH08G042171 1.3 Ensembl ENCODE dbSUPER 13.1 +35.9 35882 1.1 ATF1 SIN3A ARID4B NFXL1 ZNF2 RAD21 ZNF121 SCRT2 ZNF391 ZNF263 IKBKB POLB ENSG00000254165 PLAT HOOK3 LOC101929897 VDAC3 DKK4 KAT6A PIR61234
GH08G042251 0.6 ENCODE 25.5 -45.0 -44997 1.6 TAL1 JUN CEBPB ZEB2 DPF2 TCF12 ARID1B JUND FOS TRIM24 PLAT POLB LOC101929897
GH08G042172 0.9 ENCODE dbSUPER 13.1 +34.3 34341 1.2 CBFB ZIC2 ZFHX2 EGR1 POLR2A EED CREM EGR2 SP7 AP3M2 PLAT POLB IKBKB LOC101929897 VDAC3 DKK4 SMIM19 PIR61234
GH08G042256 0.8 Ensembl ENCODE 14.5 -49.0 -48970 1.3 JUND JUN FOS RAD21 MAFK POLB PLAT DKK4 LOC101929897
- Elite enhancer and/or Elite enhancer-gene association Download GeneHancer data dump

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
ENSR00000224048 224 201 SIN3A RAD21 ZNF366 FOS SP3 ZEB2 ZFP69B NFIC KLF16 ZNF341

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

Selected DME Specific Peptides for PLAT Gene

P00750:
  • CRNPDGD
  • DNDIALL
  • PGVYTKVTNYL
  • DACQGDSGG
  • PGVYTKV
  • SDFVCQCP
  • FEVEKYI
  • QCHSVPV
  • GDSGGPL
  • YRGTWST
  • CRDEKTQMIYQQ
  • HVRLYPSSRC
  • CFNGGTC
  • CQGDSGGP
  • NDIALLQLKS
  • NYCRNPD
  • YQQHQSWLRP
  • LGLGNHNYCRNP
  • LGLGKHN
  • AAHCFQER
  • SGGPLVC
  • PQFRIKGGL

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 Thr96, Asn152, posLast=219219, posLast=483483, and posLast=487487
  • Modification sites at PhosphoSitePlus

Antibody Products

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

Protein Products

Assay Products

  • Cloud-Clone Corp. Assay Kits for PLAT

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.
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:0001948 glycoprotein binding TAS 8186264
GO:0004252 serine-type endopeptidase activity TAS,IEA --
GO:0005102 receptor binding IPI 8186264
GO:0005515 protein binding IPI 2503541
GO:0008233 peptidase activity IEA --
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

CRISPR Products

miRNA for PLAT Gene

miRTarBase miRNAs that target PLAT

Inhibitory RNA Products

Clone Products

  • Applied Biological Materials Clones for 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
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for PLAT gene
Compartment Confidence
extracellular 5
plasma membrane 3
cytoskeleton 3
nucleus 2
cytosol 2
lysosome 2
endoplasmic reticulum 1

Gene Ontology (GO) - Cellular Components for PLAT Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005576 extracellular region TAS,IEA --
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 & 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:0001666 response to hypoxia IEA --
GO:0006464 cellular protein modification process TAS 3087818
GO:0006508 proteolysis TAS,IEA 3087818
GO:0007596 blood coagulation TAS 3839198
GO:0014909 smooth muscle cell migration 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

(82) Drugs for PLAT Gene - From: DrugBank, ApexBio, 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 79
Urokinase Approved, Investigational, Withdrawn Pharma activator, Target 0
Tranexamic Acid Approved Pharma inhibitor 277
Aminocaproic Acid Approved, Investigational Pharma Target, antagonist 26
C1 Esterase Inhibitor (Human) Approved Pharma Target, Inhibitor 0

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

Name Synonyms Role CAS Number PubChem IDs PubMed IDs

(1) ApexBio Compounds for PLAT Gene

Compound Action Cas Number
Tiplaxtinin(PAI-039) Orally efficacious inhibitor of PAI-1 393105-53-8
genes like me logo Genes that share compounds with PLAT: view

Drug Products

Transcripts for PLAT Gene

Unigene Clusters for PLAT Gene

Plasminogen activator, tissue:
Representative Sequences:

CRISPR Products

Inhibitory RNA Products

Clone Products

  • Applied Biological Materials Clones for PLAT

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 from GTEx, Illumina, BioGPS, and CGAP SAGE 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, MaxQB, and MOPED for PLAT Gene



Protein tissue co-expression partners for PLAT Gene

NURSA nuclear receptor signaling pathways regulating expression of PLAT Gene:

PLAT

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.

Evidence on tissue expression from TISSUES for PLAT Gene

  • Skin(4.9)
  • Nervous system(4.9)
  • Lung(4.8)
  • Kidney(4)
  • Intestine(3.5)
  • Heart(3.3)
  • Blood(3.2)
  • Pancreas(3.2)
  • Liver(3)
  • Muscle(2.7)
  • Eye(2.1)

Phenotype-based relationships between genes and organs from Gene ORGANizer for PLAT Gene

Germ Layers:
  • mesoderm
Systems:
  • cardiovascular
Organs:
General:
  • blood
  • blood vessel
  • coagulation system
genes like me logo Genes that share expression patterns with PLAT: view

Primer 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
chimpanzee
(Pan troglodytes)
Mammalia PLAT 34 35
  • 99.47 (n)
dog
(Canis familiaris)
Mammalia PLAT 34
  • 81.94 (n)
-- 35
  • 80 (a)
OneToMany
-- 35
  • 70 (a)
OneToMany
cow
(Bos Taurus)
Mammalia PLAT 34 35
  • 81.55 (n)
rat
(Rattus norvegicus)
Mammalia Plat 34
  • 79.77 (n)
mouse
(Mus musculus)
Mammalia Plat 34 16 35
  • 79.71 (n)
oppossum
(Monodelphis domestica)
Mammalia PLAT 35
  • 70 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia PLAT 35
  • 62 (a)
OneToOne
chicken
(Gallus gallus)
Aves PLAT 34 35
  • 64.61 (n)
lizard
(Anolis carolinensis)
Reptilia PLAT 35
  • 61 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia plat 34
  • 60.12 (n)
African clawed frog
(Xenopus laevis)
Amphibia Xl.9397 34
zebrafish
(Danio rerio)
Actinopterygii plat 34 35
  • 56.71 (n)
Species where no ortholog for PLAT was found in the sources mined by GeneCards:
  • 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

Variants for PLAT Gene

Sequence variations from dbSNP and Humsavar for PLAT Gene

SNP ID Clin Chr 08 pos Sequence Context AA Info Type
rs886041071 Uncertain significance 42,191,384(-) GGAGC(-/CA)GATCT reference, frameshift-variant
rs1000012336 -- 42,192,610(+) TTACA(C/T)AGCAT intron-variant
rs1000068928 -- 42,199,378(+) GAGGC(A/G)GGAGC intron-variant
rs1000089465 -- 42,197,218(+) TAGGC(A/G)CCTGT intron-variant
rs1000167980 -- 42,208,710(+) ATGAC(C/G)GACTA upstream-variant-2KB

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

Variant ID Type Subtype PubMed ID
nsv1132143 CNV deletion 24896259
nsv398046 CNV deletion 16902084
nsv824616 CNV loss 20364138

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

Human Gene Mutation Database (HGMD)
PLAT
SNPedia medical, phenotypic, and genealogical associations of SNPs for
PLAT

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

Disorders for PLAT Gene

MalaCards: The human disease database

(72) 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. 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 22 46 64
  2. Tissue plasminogen activator genetic polymorphisms do not influence tissue plasminogen activator release in patients with coronary heart disease. (PMID: 16836660) Robinson S.D. … Newby D.E. (J. Thromb. Haemost. 2006) 3 22 46 64
  3. Common genetic variation in five thrombosis genes and relations to plasma hemostatic protein level and cardiovascular disease risk. (PMID: 16614319) Kathiresan S. … O'Donnell C.J. (Arterioscler. Thromb. Vasc. Biol. 2006) 3 22 46 64
  4. Is tissue-plasminogen activator gene polymorphism a risk factor for venous thromboembolism in every population? (PMID: 15976969) Oguzulgen I.K. … Akar N. (J. Thromb. Thrombolysis 2005) 3 22 46 64
  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 22 46 64

Products for PLAT Gene

Sources for PLAT Gene

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