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

Summary

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

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_000008.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: 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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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

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.
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.
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.
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.
Roles of the tissue-type plasminogen activator in immune response.
Title: Roles of the tissue-type plasminogen activator in immune response.
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.
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.
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.
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).
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 EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

GDB:185497 (e-PCR)
- UniSTS:155450

GDB:185498 (e-PCR)
- UniSTS:155451

PLAT_65.3 (e-PCR)
- UniSTS:280914

GDB:186200 (e-PCR)
- UniSTS:155478

RH40525 (e-PCR)
- UniSTS:89268

GDB:176412 (e-PCR)
- UniSTS:154808

D2S2567 (e-PCR)
- UniSTS:58560

NIB234 (e-PCR)
- UniSTS:55777

GDB:386840 (e-PCR)
- UniSTS:157154

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 more info	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

EC 3.4.21.68

NP_001306118.1

EC 3.4.21.68

NP_127509.1

EC 3.4.21.68

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

NG_023264.1 RefSeqGene

Range

5001..37959

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GenBank, FASTA, Sequence Viewer (Graphics), LRG_570

mRNA and Protein(s)

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
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
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

NC_000008.11 Reference GRCh38.p14 Primary Assembly

Range

42174718..42207565 complement

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GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

NC_060932.1 Alternate T2T-CHM13v2.0

Range

42449037..42481874 complement

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GenBank, FASTA, Sequence Viewer (Graphics)

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

NM_000931.2: Suppressed sequence

Description

NM_000931.2: This RefSeq was permanently suppressed because it is a nonsense-mediated mRNA decay (NMD) candidate.