PLAT

Protein identityUniProt · HPA

UniProt accession

P00750

Gene

PLAT

Ensembl

ENSG00000104368

Chromosome

8

Canonical length

562 aa

Protein class

Cancer-related genes, Candidate cardiovascular disease genes, Disease related genes, Enzymes, FDA approved drug targets, Plasma proteins, Predicted secreted proteins

Subcellular location

Actin filaments

Secretome location

Secreted to blood

OverviewNCBI 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]

Canonical amino-acid sequenceUniProt

562 residues, UniProt reviewed canonical sequence.

>P00750|PLAT
     1  MDAMKRGLCC VLLLCGAVFV SPSQEIHARF RRGARSYQVI CRDEKTQMIY QQHQSWLRPV
    61  LRSNRVEYCW CNSGRAQCHS VPVKSCSEPR CFNGGTCQQA LYFSDFVCQC PEGFAGKCCE
   121  IDTRATCYED QGISYRGTWS TAESGAECTN WNSSALAQKP YSGRRPDAIR LGLGNHNYCR
   181  NPDRDSKPWC YVFKAGKYSS EFCSTPACSE GNSDCYFGNG SAYRGTHSLT ESGASCLPWN
   241  SMILIGKVYT AQNPSAQALG LGKHNYCRNP DGDAKPWCHV LKNRRLTWEY CDVPSCSTCG
   301  LRQYSQPQFR IKGGLFADIA SHPWQAAIFA KHRRSPGERF LCGGILISSC WILSAAHCFQ
   361  ERFPPHHLTV ILGRTYRVVP GEEEQKFEVE KYIVHKEFDD DTYDNDIALL QLKSDSSRCA
   421  QESSVVRTVC LPPADLQLPD WTECELSGYG KHEALSPFYS ERLKEAHVRL YPSSRCTSQH
   481  LLNRTVTDNM LCAGDTRSGG PQANLHDACQ GDSGGPLVCL NDGRMTLVGI ISWGLGCGQK
   541  DVPGVYTKVT NYLDWIRDNM RP

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against PLAT can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Secreted

Secreted

Yes

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.31

Highest tissue expression

231 nTPM

Expression across tissuesHPA

ReferencesPubMed · IEDB

Publications for PLAT from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.63

gnomAD pLI

0

gnomAD missense Z

0.42

DepMap mean gene effect

0.01

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• blood coagulation
• fibrinolysis
• negative regulation of fibrinolysis
• negative regulation of plasminogen activation
• negative regulation of proteolysis
• plasminogen activation
• platelet-derived growth factor receptor signaling pathway
• prevention of polyspermy
• protein modification process
• proteolysis
• response to hypoxia
• smooth muscle cell migration
• trans-synaptic signaling by BDNF, modulating synaptic transmission

Molecular functions

• phosphoprotein binding
• serine-type endopeptidase activity
• signaling receptor binding

Cellular components

• apical part of cell
• cell surface
• cytoplasm
• extracellular exosome
• extracellular region
• extracellular space
• glutamatergic synapse
• Schaffer collateral - CA1 synapse
• secretory granule
• serine protease inhibitor complex

Protein domainsUniProt · Pfam · InterPro

• Kringle
• Fibronectin, type I
• EGF-like domain
• Serine proteases, trypsin domain
• Peptidase S1A, chymotrypsin family
• Peptidase S1, PA clan
• Kringle-like fold
• Kringle, conserved site
• Serine proteases, trypsin family, histidine active site
• Serine proteases, trypsin family, serine active site
• Kringle superfamily
• Serine Proteases (Peptidase S1 Family)
• EGF-like domain
• Fibronectin type I domain
• Kringle domain
• Trypsin
• Tissue plasminogen activator

KeywordsUniProt

• Cleavage on pair of basic residues
• Disulfide bond
• EGF-like domain
• Glycoprotein
• Hydrolase
• Kringle
• Pharmaceutical
• Plasminogen activation
• Protease
• Repeat
• Secreted
• Serine protease
• Signal
• Zymogen

InteractionsUniProt · HPA

Protein binding partners of PLAT in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• SERPINE1
• SORL1
• PLGRKT