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PLAT plasminogen activator, tissue type [ Homo sapiens (human) ]

Gene ID: 5327, updated on 2-Nov-2024

Summary

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Official Symbol
PLATprovided by HGNC
Official Full Name
plasminogen activator, tissue typeprovided by HGNC
Primary source
HGNC:HGNC:9051
See related
Ensembl:ENSG00000104368 MIM:173370; AllianceGenome:HGNC:9051
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
TPA; T-PA
Summary
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]
Expression
Broad expression in urinary bladder (RPKM 61.1), placenta (RPKM 41.3) and 18 other tissues See more
Orthologs
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Genomic context

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See PLAT in Genome Data Viewer
Location:
8p11.21
Exon count:
14
Annotation release Status Assembly Chr Location
RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 8 NC_000008.11 (42174718..42207565, complement)
RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 8 NC_060932.1 (42449037..42481874, complement)
RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 8 NC_000008.10 (42032236..42065083, complement)

Chromosome 8 - NC_000008.11Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC107986939 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 27297 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 27298 Neighboring gene ReSE screen-validated silencer GRCh37_chr8:41998279-41998506 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 27299 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 19153 Neighboring gene adaptor related protein complex 3 subunit mu 2 Neighboring gene Sharpr-MPRA regulatory region 3603 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr8:42029745-42030244 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 27300 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr8:42036916-42037740 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 27301 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 27302 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr8:42044581-42045152 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr8:42045153-42045723 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr8:42065584-42066102 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr8:42066103-42066621 Neighboring gene small nucleolar RNA U13 Neighboring gene IKBKB divergent transcript Neighboring gene ATAC-STARR-seq lymphoblastoid active region 27303 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 27304 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr8:42127815-42128314

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. Intraventricular tissue plasminogen activator for the prevention of vasospasm and hydrocephalus after aneurysmal subarachnoid hemorrhage. Ramakrishna R, et al. Neurosurgery, 2010 Jul. PMID 20559098
  2. Low-dose recombinant tissue-type plasminogen activator enhances clot resolution in brain hemorrhage: the intraventricular hemorrhage thrombolysis trial. Naff N, et al. Stroke, 2011 Nov. PMID 21868730, Free PMC Article
  3. Dramatic changes of a DWI lesion in a patient with acute ischemic stroke treated with IV t-PA. Sakamoto Y, et al. J Neuroimaging, 2013 Apr. PMID 21848677
  4. Surface-retained tPA is essential for effective fibrinolysis on vascular endothelial cells. Suzuki Y, et al. Blood, 2011 Sep 15. PMID 21791417
  5. Allelic imbalance of tissue-type plasminogen activator (t-PA) gene expression in human brain tissue. Tjarnlund-Wolf A, et al. Thromb Haemost, 2011 Jun. PMID 21437359

See all (386) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Fibrinolytic and Non-fibrinolytic Roles of Tissue-type Plasminogen Activator in the Ischemic Brain.
    Title: Fibrinolytic and Non-fibrinolytic Roles of Tissue-type Plasminogen Activator in the Ischemic Brain.
  2. Association of pro-fibrinolytic receptor AnnexinA2 with tissue plasminogen activator/Inhibitor-1 in pre-eclampsia.
    Title: Association of pro-fibrinolytic receptor AnnexinA2 with tissue plasminogen activator/Inhibitor-1 in pre-eclampsia.
  3. Correlations between the Changing Levels of Tissue Plasminogen Activator and Adiposity Following Exercise-Induced Weight Loss.
    Title: Correlations between the Changing Levels of Tissue Plasminogen Activator and Adiposity Following Exercise-Induced Weight Loss.
  4. Relationship between serum and tear levels of tissue plasminogen activator and plasminogen activator inhibitor-1 in diabetic retinopathy.
    Title: Relationship between serum and tear levels of tissue plasminogen activator and plasminogen activator inhibitor-1 in diabetic retinopathy.
  5. Roles of the tissue-type plasminogen activator in immune response.
    Title: Roles of the tissue-type plasminogen activator in immune response.
  6. Tissue plasminogen activator is a ligand of cation-independent mannose 6-phosphate receptor and consists of glycoforms that contain mannose 6-phosphate.
    Title: Tissue plasminogen activator is a ligand of cation-independent mannose 6-phosphate receptor and consists of glycoforms that contain mannose 6-phosphate.
  7. A novel commentary: Investigation of the role of a balance between neurotrophic and apoptotic proteins in the pathogenesis of psychosis via the tPA-BDNF pathway.
    Title: A novel commentary: Investigation of the role of a balance between neurotrophic and apoptotic proteins in the pathogenesis of psychosis via the tPA-BDNF pathway.
  8. PAI-1 and tPA gene polymorphisms and susceptibility to chronic obstructive pulmonary disease in a sample of Turkish population.
    Title: PAI-1 and tPA gene polymorphisms and susceptibility to chronic obstructive pulmonary disease in a sample of Turkish population.
  9. Recombinant Tissue Plasminogen Activator (r-tPA) Induces In-Vitro Human Neutrophil Migration via Low Density Lipoprotein Receptor-Related Protein 1 (LRP-1).
    Title: Recombinant Tissue Plasminogen Activator (r-tPA) Induces In-Vitro Human Neutrophil Migration via Low Density Lipoprotein Receptor-Related Protein 1 (LRP-1).
  10. Interacting hepatic PAI-1/tPA gene regulatory pathways influence impaired fibrinolysis severity in obesity.
    Title: Interacting hepatic PAI-1/tPA gene regulatory pathways influence impaired fibrinolysis severity in obesity.
Submit: New GeneRIF Correction See all GeneRIFs (253)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

EBI GWAS Catalog

Description
Genome-wide association study for circulating tissue plasminogen activator levels and functional follow-up implicates endothelial STXBP5 and STX2.
EBI GWAS Catalog

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Clone Names

  • DKFZp686I03148

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables phosphoprotein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables protein binding TAS
Traceable Author Statement
more info
 PubMed 
enables serine-type endopeptidase activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables serine-type endopeptidase activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables serine-type endopeptidase activity TAS
Traceable Author Statement
more info
  
enables signaling receptor binding IPI
Inferred from Physical Interaction
more info
 PubMed 
Process Evidence Code Pubs
involved_in blood coagulation TAS
Traceable Author Statement
more info
 PubMed 
involved_in fibrinolysis TAS
Traceable Author Statement
more info
  
involved_in negative regulation of fibrinolysis NAS
Non-traceable Author Statement
more info
 PubMed 
involved_in negative regulation of plasminogen activation NAS
Non-traceable Author Statement
more info
 PubMed 
involved_in negative regulation of proteolysis IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in plasminogen activation IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in plasminogen activation IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in platelet-derived growth factor receptor signaling pathway IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in prevention of polyspermy ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in protein modification process TAS
Traceable Author Statement
more info
 PubMed 
involved_in proteolysis TAS
Traceable Author Statement
more info
 PubMed 
involved_in response to hypoxia IEA
Inferred from Electronic Annotation
more info
  
involved_in smooth muscle cell migration IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in trans-synaptic signaling by BDNF, modulating synaptic transmission IEA
Inferred from Electronic Annotation
more info
  
Component Evidence Code Pubs
located_in Schaffer collateral - CA1 synapse IEA
Inferred from Electronic Annotation
more info
  
located_in apical part of cell IEA
Inferred from Electronic Annotation
more info
  
located_in cell surface IDA
Inferred from Direct Assay
more info
 PubMed 
NOT located_in collagen-containing extracellular matrix IDA
Inferred from Direct Assay
more info
 PubMed 
located_in cytoplasm IDA
Inferred from Direct Assay
more info
 PubMed 
located_in extracellular exosome HDA PubMed 
located_in extracellular region TAS
Traceable Author Statement
more info
  
is_active_in extracellular space IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in glutamatergic synapse IEA
Inferred from Electronic Annotation
more info
  
located_in secretory granule IEA
Inferred from Electronic Annotation
more info
  
part_of serine protease inhibitor complex IPI
Inferred from Physical Interaction
more info
 PubMed 

General protein information

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Preferred Names
tissue-type plasminogen activator
Names
alteplase
plasminogen/activator kringle
reteplase
t-plasminogen activator
NP_000921.1
NP_001306118.1
NP_127509.1

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

  1. NG_023264.1 RefSeqGene

    Range
    5001..37959
    Download
    GenBank, FASTA, Sequence Viewer (Graphics), LRG_570

mRNA and Protein(s)

  1. NM_000930.5 → NP_000921.1  tissue-type plasminogen activator isoform 1 preproprotein

    See identical proteins and their annotated locations for NP_000921.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1).
    Source sequence(s)
    BC013968, DA031108, DC424502
    Consensus CDS
    CCDS6126.1
    UniProtKB/Swiss-Prot
    A8K022, B2R8E8, P00750, Q15103, Q503B0, Q6PJA5, Q7Z7N2, Q86YK8, Q9BU99, Q9BZW1
    UniProtKB/TrEMBL
    B8ZX62
    Related
    ENSP00000220809.4, ENST00000220809.9
    Conserved Domains (4) summary
    smart00058
    Location:41 → 83
    FN1; Fibronectin type 1 domain
    cd00108
    Location:125 → 209
    KR; Kringle domain; Kringle domains are believed to play a role in binding mediators, such as peptides, other proteins, membranes, or phospholipids. They are autonomous structural domains, found in a varying number of copies, in blood clotting and ...
    cd00190
    Location:313 → 559
    Tryp_SPc; Trypsin-like serine protease; Many of these are synthesized as inactive precursor zymogens that are cleaved during limited proteolysis to generate their active forms. Alignment contains also inactive enzymes that have substitutions of the catalytic triad ...
    pfam00051
    Location:215 → 296
    Kringle; Kringle domain

  2. NM_001319189.2 → NP_001306118.1  tissue-type plasminogen activator isoform 4 precursor

    Status: REVIEWED

    Description
    Transcript Variant: This variant (4) lacks two alternate in-frame exons in the 5' coding region compared to variant 1. The encoded isoform (4) is shorter than isoform 1. This isoform (4) may undergo proteolytic processing similar to isoform 1.
    Source sequence(s)
    AK297738, BC002795, DA031108
    Consensus CDS
    CCDS83291.1
    UniProtKB/TrEMBL
    B4DN26, B4DV92, E7ESF4
    Related
    ENSP00000429401.1, ENST00000524009.5
    Conserved Domains (3) summary
    smart00058
    Location:41 → 83
    FN1; Fibronectin type 1 domain
    cd00190
    Location:224 → 470
    Tryp_SPc; Trypsin-like serine protease; Many of these are synthesized as inactive precursor zymogens that are cleaved during limited proteolysis to generate their active forms. Alignment contains also inactive enzymes that have substitutions of the catalytic triad ...
    pfam00051
    Location:126 → 207
    Kringle; Kringle domain

  3. NM_033011.4 → NP_127509.1  tissue-type plasminogen activator isoform 3 precursor

    See identical proteins and their annotated locations for NP_127509.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) lacks an alternate in-frame exon in the 5' coding region compared to variant 1. The encoded isoform (3) is shorter than isoform 1. This isoform (3) may undergo proteolytic processing similar to isoform 1.
    Source sequence(s)
    BC002795, DA031108, DC424502
    Consensus CDS
    CCDS6127.1
    UniProtKB/TrEMBL
    B8ZX62
    Related
    ENSP00000270188.6, ENST00000352041.7
    Conserved Domains (4) summary
    smart00020
    Location:264 → 510
    Tryp_SPc; Trypsin-like serine protease
    cd00108
    Location:79 → 163
    KR; Kringle domain; Kringle domains are believed to play a role in binding mediators, such as peptides, other proteins, membranes, or phospholipids. They are autonomous structural domains, found in a varying number of copies, in blood clotting and ...
    cd00190
    Location:267 → 513
    Tryp_SPc; Trypsin-like serine protease; Many of these are synthesized as inactive precursor zymogens that are cleaved during limited proteolysis to generate their active forms. Alignment contains also inactive enzymes that have substitutions of the catalytic triad ...
    pfam00051
    Location:169 → 250
    Kringle; Kringle domain

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000008.11 Reference GRCh38.p14 Primary Assembly

    Range
    42174718..42207565 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060932.1 Alternate T2T-CHM13v2.0

    Range
    42449037..42481874 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

  1. NM_000931.2: Suppressed sequence

    Description
    NM_000931.2: This RefSeq was permanently suppressed because it is a nonsense-mediated mRNA decay (NMD) candidate.
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
P00750.1 GenPept UniProtKB/Swiss-Prot:P00750

Gene LinkOut

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