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

    Gene ID: 5327, updated on 3-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
    mouse all
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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. Regulation of local availability of active tissue-type plasminogen activator in vivo in man. Hrafnkelsdottir T, et al. J Thromb Haemost, 2004 Nov. PMID 15550028
    2. Acute tissue-type plasminogen activator release in human microvascular endothelial cells: the roles of Galphaq, PLC-beta, IP3 and 5,6-epoxyeicosatrienoic acid. Muldowney JA 3rd, et al. Thromb Haemost, 2007 Feb. PMID 17264956
    3. Tissue plasminogen activator on admission is an important predictor of 30-day mortality in patients with acute myocardial infarction undergoing primary angioplasty. Lee CW, et al. Atherosclerosis, 2008 Jan. PMID 17145060
    4. Changes in blood viscosity with the recombinant tissue plasminogen activator alteplase. Hitosugi M, et al. Thromb Res, 2007. PMID 17064755
    5. Haplotypes of the plasminogen activator gene associated with ischemic stroke. Saito K, et al. Thromb Haemost, 2006 Sep. PMID 16953275

    See all (387) 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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    NEW Try the new Transcript table

    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

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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