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PLAU plasminogen activator, urokinase [ Homo sapiens (human) ]

Gene ID: 5328, updated on 4-Nov-2018

Summary

Official Symbol
PLAUprovided by HGNC
Official Full Name
plasminogen activator, urokinaseprovided by HGNC
Primary source
HGNC:HGNC:9052
See related
Ensembl:ENSG00000122861 MIM:191840; Vega:OTTHUMG00000018494
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
ATF; QPD; UPA; URK; u-PA; BDPLT5
Summary
This gene encodes a secreted serine protease that converts plasminogen to plasmin. The encoded preproprotein is proteolytically processed to generate A and B polypeptide chains. These chains associate via a single disulfide bond to form the catalytically inactive high molecular weight urokinase-type plasminogen activator (HMW-uPA). HMW-uPA can be further processed into the catalytically active low molecular weight urokinase-type plasminogen activator (LMW-uPA). This low molecular weight form does not bind to the urokinase-type plasminogen activator receptor. Mutations in this gene may be associated with Quebec platelet disorder and late-onset Alzheimer's disease. Alternative splicing 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 appendix (RPKM 23.1), urinary bladder (RPKM 22.7) and 23 other tissues See more
Orthologs

Genomic context

See PLAU in Genome Data Viewer
Location:
10q22.2
Exon count:
12
Annotation release Status Assembly Chr Location
109 current GRCh38.p12 (GCF_000001405.38) 10 NC_000010.11 (73909182..73917501)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 10 NC_000010.10 (75670862..75677259)

Chromosome 10 - NC_000010.11Genomic Context describing neighboring genes Neighboring gene N-deacetylase and N-sulfotransferase 2 Neighboring gene calcium/calmodulin dependent protein kinase II gamma Neighboring gene chromosome 10 open reading frame 55 Neighboring gene VISTA enhancer hs2142 Neighboring gene vinculin Neighboring gene uncharacterized LOC107984244

Genomic regions, transcripts, and products

Expression

  • 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 Jun 15 11:32:44 2016

Bibliography

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

Phenotypes

Associated conditions

Description Tests
Alzheimer's disease Compare labs
Quebec platelet disorder
MedGen: C1866423 OMIM: 601709 GeneReviews: Not available
Compare labs

NHGRI GWAS Catalog

Description
Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease.
NHGRI GWA Catalog

HIV-1 interactions

Protein interactions

Protein Gene Interaction Pubs
Envelope surface glycoprotein gp120 env Urokinase-type plasminogen activator (uPA), a proteinase that activates plasminogen, cleaves HIV-1 gp120 within the V3 loop PubMed
Pr55(Gag) gag The amino-terminal fragment of urokinase-type plasminogen activator is hypothesized to inhibit the assembly of HIV-1 Gag and the budding of HIV-1 from infected cells PubMed
Tat tat HIV-1 Tat and methamphetamine enhance the release of MMP-1, MMP-2, and uPA from human brain cells PubMed
tat HIV-1 Tat affects the fibrinolytic activity of tumor cell lines derived from BKV/tat-transgenic mice by upregulating/modulating the production of both urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor 1 (PAI-1) PubMed
Vif vif HIV-1 Vif upregulates the expression of plasminogen activator, urokinase (PLAU) in Vif-expression T cells PubMed

Go to the HIV-1, Human Interaction Database

Pathways from BioSystems

  • ATF-2 transcription factor network, organism-specific biosystem (from Pathway Interaction Database)
    ATF-2 transcription factor network, organism-specific biosystem
    ATF-2 transcription factor network
  • Blood Clotting Cascade, organism-specific biosystem (from WikiPathways)
    Blood Clotting Cascade, organism-specific biosystemCoagulation is a complex process by which blood forms clots. It is an important part of hemostasis (the cessation of blood loss from a damaged vessel), wherein a damaged blood vessel wall is covered ...
  • Complement and Coagulation Cascades, organism-specific biosystem (from WikiPathways)
    Complement and Coagulation Cascades, organism-specific biosystemBlood coagulation is a series of coordinated and calcium-dependent proenzyme-to-serine protease conversions likely to be localized on the surfaces of activated cells in vivo. It culminates in the for...
  • Complement and coagulation cascades, organism-specific biosystem (from KEGG)
    Complement and coagulation cascades, organism-specific biosystemThe complement system is a proteolytic cascade in blood plasma and a mediator of innate immunity, a nonspecific defense mechanism against pathogens. There are three pathways of complement activation:...
  • Complement and coagulation cascades, conserved biosystem (from KEGG)
    Complement and coagulation cascades, conserved biosystemThe complement system is a proteolytic cascade in blood plasma and a mediator of innate immunity, a nonspecific defense mechanism against pathogens. There are three pathways of complement activation:...
  • DNA Damage Response (only ATM dependent), organism-specific biosystem (from WikiPathways)
    DNA Damage Response (only ATM dependent), organism-specific biosystemThis is the second pathway out of two pathways which deals with DNA damage response. It has two central gene products (ATM and TP53) which are connected with the first DNA damage response pathway. In...
  • Dissolution of Fibrin Clot, organism-specific biosystem (from REACTOME)
    Dissolution of Fibrin Clot, organism-specific biosystemThe crosslinked fibrin multimers in a clot are broken down to soluble polypeptides by plasmin, a serine protease. Plasmin can be generated from its inactive precursor plasminogen and recruited to the...
  • E2F transcription factor network, organism-specific biosystem (from Pathway Interaction Database)
    E2F transcription factor network, organism-specific biosystem
    E2F transcription factor network
  • Endochondral Ossification, organism-specific biosystem (from WikiPathways)
    Endochondral Ossification, organism-specific biosystemEndochondral ossification is the process by which the embryonic cartilaginous model of most bones contributes to longitudinal growth and is gradually replaced by bone. During endochondral ossificatio...
  • FGF signaling pathway, organism-specific biosystem (from Pathway Interaction Database)
    FGF signaling pathway, organism-specific biosystem
    FGF signaling pathway
  • Hemostasis, organism-specific biosystem (from REACTOME)
    Hemostasis, organism-specific biosystemHemostasis is a physiological response that culminates in the arrest of bleeding from an injured vessel. Under normal conditions the vascular endothelium supports vasodilation, inhibits platelet adhe...
  • Immune System, organism-specific biosystem (from REACTOME)
    Immune System, organism-specific biosystemHumans are exposed to millions of potential pathogens daily, through contact, ingestion, and inhalation. Our ability to avoid infection depends on the adaptive immune system and during the first crit...
  • Innate Immune System, organism-specific biosystem (from REACTOME)
    Innate Immune System, organism-specific biosystemInnate immunity encompases the nonspecific part of immunity tha are part of an individual's natural biologic makeup
  • Lung fibrosis, organism-specific biosystem (from WikiPathways)
    Lung fibrosis, organism-specific biosystemLung fibrosis pathway linked to events (molecular initiating event, key events and associative events) in a putative Adverse Outcome Pathway for lung fibrosis.
  • MicroRNAs in cancer, organism-specific biosystem (from KEGG)
    MicroRNAs in cancer, organism-specific biosystemMicroRNA (miRNA) is a cluster of small non-encoding RNA molecules of 21 - 23 nucleotides in length, which controls gene expression post-transcriptionally either via the degradation of target mRNAs or...
  • MicroRNAs in cancer, conserved biosystem (from KEGG)
    MicroRNAs in cancer, conserved biosystemMicroRNA (miRNA) is a cluster of small non-encoding RNA molecules of 21 - 23 nucleotides in length, which controls gene expression post-transcriptionally either via the degradation of target mRNAs or...
  • NF-kappa B signaling pathway, organism-specific biosystem (from KEGG)
    NF-kappa B signaling pathway, organism-specific biosystemNuclear factor-kappa B (NF-kappa B) is the generic name of a family of transcription factors that function as dimers and regulate genes involved in immunity, inflammation and cell survival. There are...
  • NF-kappa B signaling pathway, conserved biosystem (from KEGG)
    NF-kappa B signaling pathway, conserved biosystemNuclear factor-kappa B (NF-kappa B) is the generic name of a family of transcription factors that function as dimers and regulate genes involved in immunity, inflammation and cell survival. There are...
  • Neutrophil degranulation, organism-specific biosystem (from REACTOME)
    Neutrophil degranulation, organism-specific biosystemNeutrophils are the most abundant leukocytes (white blood cells), indispensable in defending the body against invading microorganisms. In response to infection, neutrophils leave the circulation and ...
  • Osteopontin Signaling, organism-specific biosystem (from WikiPathways)
    Osteopontin Signaling, organism-specific biosystemStudy of regulation of promatrix metalloproteinase-9 (MMP-9) by osteopontin (OPN) through IKK signaling pathway.
  • Osteopontin-mediated events, organism-specific biosystem (from Pathway Interaction Database)
    Osteopontin-mediated events, organism-specific biosystem
    Osteopontin-mediated events
  • Proteoglycans in cancer, organism-specific biosystem (from KEGG)
    Proteoglycans in cancer, organism-specific biosystemMany proteoglycans (PGs) in the tumor microenvironment have been shown to be key macromolecules that contribute to biology of various types of cancer including proliferation, adhesion, angiogenesis a...
  • Proteoglycans in cancer, conserved biosystem (from KEGG)
    Proteoglycans in cancer, conserved biosystemMany proteoglycans (PGs) in the tumor microenvironment have been shown to be key macromolecules that contribute to biology of various types of cancer including proliferation, adhesion, angiogenesis a...
  • Senescence and Autophagy in Cancer, organism-specific biosystem (from WikiPathways)
    Senescence and Autophagy in Cancer, organism-specific biosystemSenescense and Autophagy Pathways in Cancer
  • Transcriptional misregulation in cancer, organism-specific biosystem (from KEGG)
    Transcriptional misregulation in cancer, organism-specific biosystem
    Transcriptional misregulation in cancer
  • Transcriptional misregulation in cancer, conserved biosystem (from KEGG)
    Transcriptional misregulation in cancer, conserved biosystem
    Transcriptional misregulation in cancer
  • Validated transcriptional targets of AP1 family members Fra1 and Fra2, organism-specific biosystem (from Pathway Interaction Database)
    Validated transcriptional targets of AP1 family members Fra1 and Fra2, organism-specific biosystem
    Validated transcriptional targets of AP1 family members Fra1 and Fra2
  • Wnt Signaling Pathway, organism-specific biosystem (from WikiPathways)
    Wnt Signaling Pathway, organism-specific biosystemWnt proteins are secreted morphogens that are required for basic developmental processes, such as cell-fate specification, progenitor-cell proliferation and the control of asymmetric cell division, i...
  • Wnt Signaling Pathway and Pluripotency, organism-specific biosystem (from WikiPathways)
    Wnt Signaling Pathway and Pluripotency, organism-specific biosystemThis pathway was adapted from several resources and is designed to provide a theoretical frame-work for examining Wnt signaling and interacting components in the context of embryonic stem-cell plurip...
  • amb2 Integrin signaling, organism-specific biosystem (from Pathway Interaction Database)
    amb2 Integrin signaling, organism-specific biosystem
    amb2 Integrin signaling

Interactions

Products Interactant Other Gene Complex Source Pubs Description

General gene information

Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
serine-type endopeptidase activity IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
serine-type endopeptidase activity TAS
Traceable Author Statement
more info
 
Process Evidence Code Pubs
blood coagulation IEA
Inferred from Electronic Annotation
more info
 
chemotaxis TAS
Traceable Author Statement
more info
PubMed 
fibrinolysis IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
fibrinolysis TAS
Traceable Author Statement
more info
 
neutrophil degranulation TAS
Traceable Author Statement
more info
 
plasminogen activation IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
plasminogen activation IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of cell migration IDA
Inferred from Direct Assay
more info
PubMed 
proteolysis IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
regulation of cell adhesion mediated by integrin IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
regulation of cell adhesion mediated by integrin IDA
Inferred from Direct Assay
more info
PubMed 
regulation of cell proliferation IEA
Inferred from Electronic Annotation
more info
 
regulation of signaling receptor activity IDA
Inferred from Direct Assay
more info
PubMed 
regulation of smooth muscle cell migration IDA
Inferred from Direct Assay
more info
PubMed 
regulation of smooth muscle cell-matrix adhesion IDA
Inferred from Direct Assay
more info
PubMed 
regulation of wound healing IC
Inferred by Curator
more info
PubMed 
response to hypoxia IEA
Inferred from Electronic Annotation
more info
 
signal transduction TAS
Traceable Author Statement
more info
PubMed 
smooth muscle cell migration IEA
Inferred from Electronic Annotation
more info
 
Component Evidence Code Pubs
cell surface IDA
Inferred from Direct Assay
more info
PubMed 
extracellular exosome HDA PubMed 
extracellular region TAS
Traceable Author Statement
more info
 
extracellular space IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
extracellular space IDA
Inferred from Direct Assay
more info
PubMed 
focal adhesion HDA PubMed 
plasma membrane TAS
Traceable Author Statement
more info
 
specific granule membrane TAS
Traceable Author Statement
more info
 
tertiary granule membrane TAS
Traceable Author Statement
more info
 

General protein information

Preferred Names
urokinase-type plasminogen activator
Names
U-plasminogen activator
plasminogen activator, urinary
NP_001138503.1
NP_001306120.1
NP_002649.1
XP_011538168.1

NCBI Reference Sequences (RefSeq)

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_011904.1 RefSeqGene

    Range
    5001..11398
    Download
    GenBank, FASTA, Sequence Viewer (Graphics), LRG_593

mRNA and Protein(s)

  1. NM_001145031.2NP_001138503.1  urokinase-type plasminogen activator isoform 2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) differs in the 5' UTR, lacks a portion of the 5' coding region, and initiates translation at an alternate start site compared to variant 1. The encoded isoform (2) has a shorter and distinct N-terminus, and lacks a predicted signal peptide compared to isoform 1.
    Source sequence(s)
    AB208961, AK298560, AW316981, BC013575, DC349055
    Consensus CDS
    CCDS44442.1
    UniProtKB/Swiss-Prot
    P00749
    UniProtKB/TrEMBL
    Q59GZ8
    Related
    ENSP00000388474.1, ENST00000446342.5
    Conserved Domains (3) summary
    smart00020
    Location:161402
    Tryp_SPc; Trypsin-like serine protease
    cd00108
    Location:50135
    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:162405
    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 ...
  2. NM_001319191.1NP_001306120.1  urokinase-type plasminogen activator isoform 3

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) differs in the 5' UTR, lacks a portion of the 5' coding region, and initiates translation at a downstream start site compared to variant 1. The encoded isoform (3) has a shorter N-terminus and lacks a predicted signal peptide compared to isoform 1.
    Source sequence(s)
    AB208961, AK297940, AW316981, BC013575, DC349055
    UniProtKB/Swiss-Prot
    P00749
    UniProtKB/TrEMBL
    B4DNJ4, Q59GZ8
    Conserved Domains (3) summary
    smart00020
    Location:92333
    Tryp_SPc; Trypsin-like serine protease
    cd00108
    Location:166
    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:93336
    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 ...
  3. NM_002658.4NP_002649.1  urokinase-type plasminogen activator isoform 1 preproprotein

    See identical proteins and their annotated locations for NP_002649.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) encodes the longest isoform (1).
    Source sequence(s)
    AB208961, AW316981, BC013575, DC349055
    Consensus CDS
    CCDS7339.1
    UniProtKB/Swiss-Prot
    P00749
    UniProtKB/TrEMBL
    A0A024QZM9, Q59GZ8
    Related
    ENSP00000361850.3, OTTHUMP00000019849, ENST00000372764.3, OTTHUMT00000048727
    Conserved Domains (2) summary
    cd00108
    Location:67152
    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:179422
    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 ...

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 109 details...Open this link in a new tab

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

Reference GRCh38.p12 Primary Assembly

Genomic

  1. NC_000010.11 Reference GRCh38.p12 Primary Assembly

    Range
    73909182..73917501
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_011539866.2XP_011538168.1  urokinase-type plasminogen activator isoform X1

    See identical proteins and their annotated locations for XP_011538168.1

    Conserved Domains (3) summary
    smart00020
    Location:178419
    Tryp_SPc; Trypsin-like serine protease
    cd00108
    Location:67152
    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:179422
    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 ...
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