Human Gene PLAT (ENST00000220809.9) from GENCODE V44
  Description: Homo sapiens plasminogen activator, tissue type (PLAT), transcript variant 1, mRNA. (from RefSeq NM_000930)
RefSeq Summary (NM_000930): 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].
Gencode Transcript: ENST00000220809.9
Gencode Gene: ENSG00000104368.19
Transcript (Including UTRs)
   Position: hg38 chr8:42,174,718-42,207,565 Size: 32,848 Total Exon Count: 14 Strand: -
Coding Region
   Position: hg38 chr8:42,175,993-42,193,185 Size: 17,193 Coding Exon Count: 13 

Page IndexSequence and LinksUniProtKB CommentsPrimersMalaCardsCTD
RNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther SpeciesGO Annotations
mRNA DescriptionsPathwaysOther NamesMethods
Data last updated at UCSC: 2023-08-18 00:09:47

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr8:42,174,718-42,207,565)mRNA (may differ from genome)Protein (562 aa)
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-  Comments and Description Text from UniProtKB
  ID: TPA_HUMAN
DESCRIPTION: RecName: Full=Tissue-type plasminogen activator; Short=t-PA; Short=t-plasminogen activator; Short=tPA; EC=3.4.21.68; AltName: INN=Alteplase; AltName: INN=Reteplase; Contains: RecName: Full=Tissue-type plasminogen activator chain A; Contains: RecName: Full=Tissue-type plasminogen activator chain B; Flags: Precursor;
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.
SUBUNIT: Heterodimer of chain A and chain B held by a disulfide bond. Forms 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.
SUBCELLULAR LOCATION: Secreted, extracellular space.
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.
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.
PTM: 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.
PTM: 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.
PTM: N-glycosylation of Asn-152; the bound oligomannosidic glycan is involved in the interaction with the mannose receptor.
PTM: Characterization of O-linked glycan was studied in Bowes melanoma cell line.
DISEASE: 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.
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.
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.
WEB RESOURCE: Name=Wikipedia; Note=Tissue plasminogen activator entry; URL="http://en.wikipedia.org/wiki/Tissue_plasminogen_Activator";
WEB RESOURCE: Name=SeattleSNPs; URL="http://pga.gs.washington.edu/data/plat/";
WEB RESOURCE: Name=SHMPD; Note=The Singapore human mutation and polymorphism database; URL="http://shmpd.bii.a-star.edu.sg/gene.php?genestart=A&genename=PLAT";
WEB RESOURCE: Name=Activase; Note=Clinical information on Activase; URL="http://www.gene.com/gene/products/information/cardiovascular/activase/insert.jsp#pharmacology";
WEB RESOURCE: Name=Retavase; Note=Clinical information on Retavase; URL="http://www.retavase.com/pdf/Retavase_PI.pdf";

-  Primer design for this transcript
 

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-  MalaCards Disease Associations
  MalaCards Gene Search: PLAT
Diseases sorted by gene-association score: acute myocardial infarction (50), thrombophilia, familial, due to decreased release of plat* (50), pulmonary embolism (45), thrombosis (34), coronary thrombosis (33), hepatic veno-occlusive disease (26), basilar artery occlusion (25), venous insufficiency (24), cardiac rupture (21), cardiogenic shock (16), anterior cerebral artery infarction (14), hemorrhage, intracerebral (13), chronic venous insufficiency (13), disseminated intravascular coagulation (13), argentine hemorrhagic fever (13), ligneous conjunctivitis (13), plasminogen activator inhibitor-1 deficiency (13), myocardial infarction 2 (12), myocardial infarction (12), stroke, ischemic (11), miller syndrome (11), peripheral vascular disease (11), middle cerebral artery infarction (11), adhesive otitis media (10), gingivitis (10), intracranial vasospasm (10), thrombophlebitis (10), occlusion precerebral artery (9), mercury poisoning (9), deafness, autosomal recessive 77 (9), lipodermatosclerosis (9), posterior myocardial infarction (8), heart block, progressive, type ia (8), cerebrovascular disease (8), central serous chorioretinopathy (8), central retinal artery occlusion (8), coronary restenosis (8), antiphospholipid syndrome (8), intracranial embolism (7), thrombophilia due to thrombin defect (7), thrombotic thrombocytopenic purpura (7), ovarian cyst (7), eisenmenger syndrome (6), coronary artery disease (6), encephalopathy, familial, with neuroserpin inclusion bodies (6), atherosclerosis (6), acute pulmonary heart disease (6), inferior myocardial infarction (6), angina pectoris (6), brain compression (6), acute cor pulmonale (5), dysfibrinogenemia (5), carotid artery thrombosis (5), dressler's syndrome (5), intermediate coronary syndrome (5), vascular disease (5), marantic endocarditis (4), vein disease (4), thrombophilia due to activated protein c resistance (4), carotid artery dissection (4), retinitis pigmentosa, y-linked (4), lung sarcoma (4), ischemia (4), pleuropneumonia (4), dirofilariasis (3), artery disease (3), atrial fibrillation (3), pulmonary hypertension (3), endocarditis (2), speech and communication disorders (2), diabetes mellitus, noninsulin-dependent (1), hypertension, essential (1), retinitis pigmentosa (0)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 38.13 RPKM in Kidney - Cortex
Total median expression: 651.69 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -19.2098-0.196 Picture PostScript Text
3' UTR -357.901275-0.281 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR016060 - Complement_control_module
IPR000742 - EG-like_dom
IPR013032 - EGF-like_CS
IPR000083 - Fibronectin_type1
IPR000001 - Kringle
IPR013806 - Kringle-like
IPR018056 - Kringle_CS
IPR009003 - Pept_cys/ser_Trypsin-like
IPR018114 - Peptidase_S1/S6_AS
IPR001254 - Peptidase_S1_S6
IPR001314 - Peptidase_S1A
IPR026280 - Tissue_plasm_act

Pfam Domains:
PF00008 - EGF-like domain
PF00039 - Fibronectin type I domain
PF00051 - Kringle domain
PF00089 - Trypsin

Protein Data Bank (PDB) 3-D Structure
MuPIT help
1A5H - X-ray MuPIT 1BDA - X-ray MuPIT 1PK2 - NMR MuPIT 1PML - X-ray MuPIT 1RTF - X-ray MuPIT 1TPG - NMR 1TPK - X-ray MuPIT 1TPM - NMR MuPIT 1TPN - NMR MuPIT


ModBase Predicted Comparative 3D Structure on P00750
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-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
Genome BrowserGenome BrowserNo orthologNo orthologNo orthologNo ortholog
Gene Details     
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MGIRGD    
Protein SequenceProtein Sequence    
AlignmentAlignment    

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0004252 serine-type endopeptidase activity
GO:0005102 receptor binding
GO:0005515 protein binding
GO:0008233 peptidase activity
GO:0008236 serine-type peptidase activity
GO:0016787 hydrolase activity
GO:0051219 phosphoprotein binding

Biological Process:
GO:0001666 response to hypoxia
GO:0006464 cellular protein modification process
GO:0006508 proteolysis
GO:0007596 blood coagulation
GO:0014909 smooth muscle cell migration
GO:0031639 plasminogen activation
GO:0042730 fibrinolysis
GO:0045861 negative regulation of proteolysis
GO:0048008 platelet-derived growth factor receptor signaling pathway

Cellular Component:
GO:0005576 extracellular region
GO:0005615 extracellular space
GO:0005737 cytoplasm
GO:0009986 cell surface
GO:0030141 secretory granule
GO:0045177 apical part of cell
GO:0070062 extracellular exosome
GO:0031012 extracellular matrix


-  Descriptions from all associated GenBank mRNAs
  X13097 - Human mRNA for tissue type plasminogen activator.
E02027 - cDNA sequence coding for human tPA.
X07393 - Human fetal lung plasminogen activator (t-PA) mRNA (EC 3.4.21.31).
E01092 - cDNA encoding human tissue plasminogen activator.
E01163 - cDNA encoding human tissue plasminogen activator.
BC007231 - Homo sapiens plasminogen activator, tissue, mRNA (cDNA clone MGC:15287 IMAGE:3161005), complete cds.
BC002795 - Homo sapiens plasminogen activator, tissue, mRNA (cDNA clone MGC:3677 IMAGE:3618149), complete cds.
BC013968 - Homo sapiens plasminogen activator, tissue, mRNA (cDNA clone MGC:1681 IMAGE:3163742), complete cds.
BC018636 - Homo sapiens plasminogen activator, tissue, mRNA (cDNA clone MGC:15288 IMAGE:3637273), complete cds.
BC095403 - Homo sapiens plasminogen activator, tissue, mRNA (cDNA clone MGC:110886 IMAGE:30528441), complete cds.
E00629 - DNA encoding Plasminogen activator,tissue-type.
M15518 - Human tissue-type plasminogen activator (t-PA) mRNA, complete cds.
E00880 - DNA encoding polypeptide having plasminogen activator activity from human pharynx cancer cells.
E01466 - DNA encoding human tissue plasminogen activator.
X02901 - Human mRNA for finger-domain lacking tissue-type plasminogen activator (t-PA).
AK299205 - Homo sapiens cDNA FLJ58123 complete cds, highly similar to Tissue-type plasminogen activator precursor (EC 3.4.21.68).
AK300984 - Homo sapiens cDNA FLJ59440 complete cds, highly similar to Tissue-type plasminogen activator precursor (EC3.4.21.68).
AK289387 - Homo sapiens cDNA FLJ78225 complete cds, highly similar to Homo sapiens plasminogen activator, tissue (PLAT), transcript variant 1, mRNA.
E08757 - cDNA of tissue plasminogen activator(t-PA).
E00654 - cDNA encoding human tissue plasminogen activator.
AK297937 - Homo sapiens cDNA FLJ59358 complete cds, highly similar to Tissue-type plasminogen activator precursor (EC 3.4.21.68).
AK290575 - Homo sapiens cDNA FLJ75455 complete cds, highly similar to Homo sapiens plasminogen activator, tissue (PLAT), transcript variant 1, mRNA.
AK297738 - Homo sapiens cDNA FLJ59355 complete cds, highly similar to Tissue-type plasminogen activator precursor (EC 3.4.21.68).
E04506 - DNA encoding human tissue plasminogen activator.
AK313342 - Homo sapiens cDNA, FLJ93864, Homo sapiens plasminogen activator, tissue (PLAT), transcriptvariant 3, mRNA.
E02025 - DNA sequence coding for human tPA.
E00896 - cDNA encoding the human placenta tissue plasminogen activator.
E01221 - cDNA human uterine tissue plasminogen activater.
D01096 - Homo sapiens mRNA for tissue plasminogen activator, partial cds.
M18182 - Human plasminogen activator mRNA, complete cds.
JD507930 - Sequence 488954 from Patent EP1572962.
A03776 - H.sapiens mRNA for tissue plasminogen activator (t-PA).
A07197 - H.sapiens mRNA for tissue plasminogen activator.
JD310115 - Sequence 291139 from Patent EP1572962.
JD149612 - Sequence 130636 from Patent EP1572962.
JD145891 - Sequence 126915 from Patent EP1572962.
JD153139 - Sequence 134163 from Patent EP1572962.
E02247 - cDNA sequence coding for plasminogen activation factor PA(NB315).
JD358220 - Sequence 339244 from Patent EP1572962.
KJ897340 - Synthetic construct Homo sapiens clone ccsbBroadEn_06734 PLAT gene, encodes complete protein.
FM956488 - Homo sapiens mRNA for tissue plasminogen activator precursor (PLAT gene).
AY221101 - Homo sapiens tissue plasminogen activator mRNA, complete cds.
E01118 - cDNA encoding human tissue-plasminogen activator.
E02448 - DNA encoding t-PA021 gene (human tissue plasminogen activating factor).
E02663 - DNA encoding tissue plasminogen activator analogue,tPAO23.
E02664 - DNA encoding tissue plasminogen activator analogue,tPAO24.
EU831423 - Synthetic construct Homo sapiens clone HAIB:100066452; DKFZo008B1017 plasminogen activator, tissue protein (PLAT) gene, encodes complete protein.
EU831516 - Synthetic construct Homo sapiens clone HAIB:100066545; DKFZo004B1018 plasminogen activator, tissue protein (PLAT) gene, encodes complete protein.
BT007060 - Homo sapiens plasminogen activator, tissue mRNA, complete cds.
DQ893499 - Synthetic construct clone IMAGE:100006129; FLH194787.01X; RZPDo839F0180D plasminogen activator, tissue (PLAT) gene, encodes complete protein.
DQ896487 - Synthetic construct Homo sapiens clone IMAGE:100010947; FLH194783.01L; RZPDo839F0170D plasminogen activator, tissue (PLAT) gene, encodes complete protein.
AF260825 - Homo sapiens neonatal thrombolytic agent alpha-form mRNA, partial cds.
E01204 - DNA sequence of human plasminogen activator.
AB527265 - Synthetic construct DNA, clone: pF1KB5684, Homo sapiens PLAT gene for plasminogen activator, tissue, without stop codon, in Flexi system.
JD514625 - Sequence 495649 from Patent EP1572962.
JD084650 - Sequence 65674 from Patent EP1572962.
JD295066 - Sequence 276090 from Patent EP1572962.
JD265621 - Sequence 246645 from Patent EP1572962.
JD524227 - Sequence 505251 from Patent EP1572962.
JD526054 - Sequence 507078 from Patent EP1572962.
V00570 - Human mRNA encoding tissue plasminogen activator (fragment).
CU675571 - Synthetic construct Homo sapiens gateway clone IMAGE:100018364 5' read PLAT mRNA.
AF282882 - Homo sapiens plasminogen/activator kringle mRNA, complete cds.
JD446944 - Sequence 427968 from Patent EP1572962.
BX641021 - Homo sapiens mRNA; cDNA DKFZp686I03148 (from clone DKFZp686I03148).
FW340003 - Screening.
JD118465 - Sequence 99489 from Patent EP1572962.
JD204867 - Sequence 185891 from Patent EP1572962.
JD540250 - Sequence 521274 from Patent EP1572962.
JD278782 - Sequence 259806 from Patent EP1572962.
JD471059 - Sequence 452083 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa04610 - Complement and coagulation cascades

BioCarta from NCI Cancer Genome Anatomy Project
h_amiPathway - Acute Myocardial Infarction
h_fibrinolysisPathway - Fibrinolysis Pathway
h_plateletAppPathway - Platelet Amyloid Precursor Protein Pathway

Reactome (by CSHL, EBI, and GO)

Protein P00750 (Reactome details) participates in the following event(s):

R-HSA-158781 crosslinked fibrin multimer + tissue plasminogen activator (one-chain) -> crosslinked fibrin multimer:tissue plasminogen activator (one-chain)
R-HSA-158747 crosslinked fibrin multimer:tissue plasminogen activator (one-chain) -> crosslinked fibrin multimer:tissue plasminogen activator (two-chain)
R-HSA-158784 crosslinked fibrin multimer:tissue plasminogen activator (one-chain) + plasminogen -> crosslinked fibrin multimer:tissue plasminogen activator (one-chain):plasminogen
R-HSA-158795 fibrin multimer, crosslinked:tissue plasminogen activator (one-chain) + plasminogen activator inhibitor 1 -> fibrin multimer, crosslinked:tissue plasminogen activator (one-chain):plasminogen activator inhibitor 1
R-HSA-158750 crosslinked fibrin multimer:tissue plasminogen activator (one-chain):plasminogen -> crosslinked fibrin multimer:tissue plasminogen activator (one-chain) + plasmin
R-HSA-382061 Extracellular processing of novel PDGFs
R-HSA-158756 crosslinked fibrin multimer:tissue plasminogen activator (two-chain) + plasminogen -> crosslinked fibrin multimer:tissue plasminogen activator (two-chain):plasminogen
R-HSA-158800 fibrin multimer, crosslinked:tissue plasminogen activator (two-chain) + plasminogen activator inhibitor 1 -> fibrin multimer, crosslinked:tissue plasminogen activator (two-chain):plasminogen activator inhibitor 1
R-HSA-158744 crosslinked fibrin multimer:tissue plasminogen activator (two-chain):plasminogen -> crosslinked fibrin multimer:tissue plasminogen activator (two-chain) + plasmin
R-HSA-75205 Dissolution of Fibrin Clot
R-HSA-109582 Hemostasis
R-HSA-186797 Signaling by PDGF
R-HSA-9006934 Signaling by Receptor Tyrosine Kinases
R-HSA-162582 Signal Transduction

-  Other Names for This Gene
  Alternate Gene Symbols: A8K022, B2R8E8, ENST00000220809.1, ENST00000220809.2, ENST00000220809.3, ENST00000220809.4, ENST00000220809.5, ENST00000220809.6, ENST00000220809.7, ENST00000220809.8, NM_000930, P00750, Q15103, Q503B0, Q6PJA5, Q7Z7N2, Q86YK8, Q9BU99, Q9BZW1, TPA_HUMAN, uc003xos.1, uc003xos.2, uc003xos.3, uc003xos.4
UCSC ID: ENST00000220809.9
RefSeq Accession: NM_000930
Protein: P00750 (aka TPA_HUMAN)
CCDS: CCDS6126.1

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.