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

    Gene ID: 5328, updated on 3-Apr-2024

    Summary

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    Official Symbol
    PLAUprovided by HGNC
    Official Full Name
    plasminogen activator, urokinaseprovided by HGNC
    Primary source
    HGNC:HGNC:9052
    See related
    Ensembl:ENSG00000122861 MIM:191840; AllianceGenome:HGNC:9052
    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
    mouse all
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    Genomic context

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    Location:
    10q22.2
    Exon count:
    12
    Annotation release Status Assembly Chr Location
    RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 10 NC_000010.11 (73909164..73917494)
    RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 10 NC_060934.1 (74779718..74788885)
    105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 10 NC_000010.10 (75670890..75677252)

    Chromosome 10 - NC_000010.11Genomic Context describing neighboring genes Neighboring gene ReSE screen-validated silencer GRCh37_chr10:75574449-75574702 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr10:75579102-75579602 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr10:75579603-75580103 Neighboring gene MPRA-validated peak1013 silencer Neighboring gene calcium/calmodulin dependent protein kinase II gamma Neighboring gene H3K27ac hESC enhancer GRCh37_chr10:75617818-75618318 Neighboring gene H3K27ac hESC enhancer GRCh37_chr10:75618319-75618819 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 3577 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 2491 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 2492 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 2493 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 2494 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 3578 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 3579 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 3580 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr10:75646944-75648143 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr10:75648172-75649130 Neighboring gene uncharacterized LOC124902454 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr10:75668366-75669565 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 2495 Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr10:75672789-75673988 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr10:75679930-75680578 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr10:75680579-75681225 Neighboring gene chromosome 10 putative open reading frame 55 Neighboring gene P300/CBP strongly-dependent group 1 enhancer GRCh37_chr10:75691709-75692908 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 3584 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 3585 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr10:75716666-75717173 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 3586 Neighboring gene Sharpr-MPRA regulatory region 4338 Neighboring gene VISTA enhancer hs2142 Neighboring gene Sharpr-MPRA regulatory region 295 Neighboring gene CRISPRi-validated cis-regulatory element chr10.2661 Neighboring gene CRISPRi-validated cis-regulatory element chr10.2662 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 2498 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 3587 Neighboring gene H3K27ac hESC enhancer GRCh37_chr10:75758175-75758826 Neighboring gene Sharpr-MPRA regulatory region 4496 Neighboring gene uncharacterized LOC124902455 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 3588 Neighboring gene vinculin Neighboring gene uncharacterized LOC124902458

    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
    • 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. PLAU contributes to the development of cholangiocarcinoma via activating NF-κB signaling pathway. Hu MD, et al. Cell Biol Int, 2023 Aug. PMID 37067236
    2. Metastatic phenotype and immunosuppressive tumour microenvironment in pancreatic ductal adenocarcinoma: Key role of the urokinase plasminogen activator (PLAU). Hosen SMZ, et al. Front Immunol, 2022. PMID 36591282, Free PMC Article
    3. In Vitro Study of the Fibrinolytic Activity via Single Chain Urokinase-Type Plasminogen Activator and Molecular Docking of FGFC1. Gao C, et al. Molecules, 2021 Mar 24. PMID 33804930, Free PMC Article
    4. Structure of an affinity-matured inhibitory recombinant fab against urokinase plasminogen activator reveals basis of potency and specificity. Sevillano N, et al. Biochim Biophys Acta Proteins Proteom, 2021 Feb. PMID 33221341, Free PMC Article
    5. Studies on the changes of uPA system in a co-culture model of bone marrow stromal cells-leukemia cells. Zhou L, et al. Biosci Rep, 2020 Nov 27. PMID 33146708, Free PMC Article

    See all (580) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Inflammatory cytokines and oral lichen planus: a Mendelian randomization study.
      Title: Inflammatory cytokines and oral lichen planus: a Mendelian randomization study.
    2. Pan-cancer analysis of PLAU indicates its potential prognostic value and correlation with neutrophil infiltration in BLCA.
      Title: Pan-cancer analysis of PLAU indicates its potential prognostic value and correlation with neutrophil infiltration in BLCA.
    3. Prognostic evaluation of oral squamous cell carcinoma based on pleiotrophin, urokinase plasminogen activator, and glycoprotein nonmetastatic melanoma protein B expression.
      Title: Prognostic evaluation of oral squamous cell carcinoma based on pleiotrophin, urokinase plasminogen activator, and glycoprotein nonmetastatic melanoma protein B expression.
    4. PLAU contributes to the development of cholangiocarcinoma via activating NF-kappaB signaling pathway.
      Title: PLAU contributes to the development of cholangiocarcinoma via activating NF-κB signaling pathway.
    5. Involvement of matrix metalloproteinase 1 and urokinase-type plasminogen activator in the PKCalpha-p38 MAPK pathway-mediated progression of human liver cancer cells.
      Title: Involvement of matrix metalloproteinase 1 and urokinase-type plasminogen activator in the PKCα-p38 MAPK pathway-mediated progression of human liver cancer cells.
    6. Recent Advances in Targeting the Urokinase Plasminogen Activator with Nanotherapeutics.
      Title: Recent Advances in Targeting the Urokinase Plasminogen Activator with Nanotherapeutics.
    7. m6A Methyltransferase, WTAP, Promotes Cancer Progression in Laryngeal Squamous Cell Carcinoma by Regulating PLAU Stability.
      Title: m6A Methyltransferase, WTAP, Promotes Cancer Progression in Laryngeal Squamous Cell Carcinoma by Regulating PLAU Stability.
    8. Metastatic phenotype and immunosuppressive tumour microenvironment in pancreatic ductal adenocarcinoma: Key role of the urokinase plasminogen activator (PLAU).
      Title: Metastatic phenotype and immunosuppressive tumour microenvironment in pancreatic ductal adenocarcinoma: Key role of the urokinase plasminogen activator (PLAU).
    9. PLAU is associated with cell migration and invasion and is regulated by transcription factor YY1 in cervical cancer.
      Title: PLAU is associated with cell migration and invasion and is regulated by transcription factor YY1 in cervical cancer.
    10. METTL3 promotes colorectal cancer metastasis by stabilizing PLAU mRNA in an m6A-dependent manner.
      Title: METTL3 promotes colorectal cancer metastasis by stabilizing PLAU mRNA in an m6A-dependent manner.
    Submit: New GeneRIF Correction See all GeneRIFs (447)

    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

    Associated conditions

    Description Tests
    Alzheimer disease type 1
    MedGen: C1863052 OMIM: 104300 GeneReviews: Alzheimer Disease Overview
    		Compare labs
    Quebec platelet disorder
    MedGen: C1866423 OMIM: 601709 GeneReviews: Not available
    		Compare labs

    EBI GWAS Catalog

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

    HIV-1 interactions

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    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 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

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables serine-type endopeptidase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables serine-type endopeptidase activity TAS
    Traceable Author Statement
    more info
    		  
    Process Evidence Code Pubs
    involved_in blood coagulation IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in chemotaxis TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in fibrinolysis IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    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 plasminogen activation IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in plasminogen activation IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    acts_upstream_of_or_within positive regulation of cell migration IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in proteolysis TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in regulation of cell adhesion IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in regulation of cell adhesion mediated by integrin IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in regulation of cell adhesion mediated by integrin IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in regulation of cell population proliferation IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in regulation of fibrinolysis NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    involved_in regulation of plasminogen activation NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    involved_in regulation of signaling receptor activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in regulation of smooth muscle cell migration IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in regulation of smooth muscle cell-matrix adhesion IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in regulation of wound healing IC
    Inferred by Curator
    more info
    		 PubMed 
    involved_in response to hypoxia IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in signal transduction TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in smooth muscle cell migration IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in urokinase plasminogen activator signaling pathway NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    Component Evidence Code Pubs
    located_in cell surface IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in external side of plasma membrane NAS
    Non-traceable Author Statement
    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 extracellular space IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in focal adhesion HDA PubMed 
    located_in plasma membrane TAS
    Traceable Author Statement
    more info
    		  
    part_of protein complex involved in cell-matrix adhesion IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    part_of serine protease inhibitor complex IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    part_of serine-type endopeptidase complex IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    located_in specific granule membrane TAS
    Traceable Author Statement
    more info
    		  
    located_in tertiary granule membrane TAS
    Traceable Author Statement
    more info
    		  

    General protein information

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    Preferred Names
    urokinase-type plasminogen activator
    Names
    U-plasminogen activator
    plasminogen activator, urinary
    NP_001138503.2
    NP_001306120.2
    NP_002649.2
    XP_011538168.1
    XP_047281309.1
    XP_054222066.1
    XP_054222067.1

    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_011904.1 RefSeqGene

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

    mRNA and Protein(s)

    1. NM_001145031.3 → NP_001138503.2  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, AL596247, BC013575, DC349055
      Consensus CDS
      CCDS44442.1
      UniProtKB/TrEMBL
      E7ET40, Q5PY49
      Related
      ENSP00000388474.1, ENST00000446342.5

    2. NM_001319191.2 → NP_001306120.2  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, AL596247, BC013575
      UniProtKB/TrEMBL
      B4DNJ4
      Conserved Domains (2) summary
      cd00108
      Location:1 → 66
      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:93 → 336
      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_002658.6 → NP_002649.2  urokinase-type plasminogen activator isoform 1 preproprotein

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) encodes the longest isoform (1).
      Source sequence(s)
      AB208961, AL596247, BC013575, DC349055
      Consensus CDS
      CCDS7339.1
      UniProtKB/Swiss-Prot
      B4DPZ2, P00749, Q15844, Q16618, Q53XS3, Q5SWW9, Q969W6
      UniProtKB/TrEMBL
      B2R7F2
      Related
      ENSP00000361850.3, ENST00000372764.4
      Conserved Domains (2) summary
      cd00108
      Location:67 → 152
      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:179 → 422
      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: GCF_000001405.40-RS_2023_10

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

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000010.11 Reference GRCh38.p14 Primary Assembly

      Range
      73909164..73917494
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_011539866.3 → XP_011538168.1  urokinase-type plasminogen activator isoform X1

      See identical proteins and their annotated locations for XP_011538168.1

      UniProtKB/Swiss-Prot
      B4DPZ2, P00749, Q15844, Q16618, Q53XS3, Q5SWW9, Q969W6
      UniProtKB/TrEMBL
      B2R7F2
      Conserved Domains (2) summary
      cd00108
      Location:67 → 152
      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:179 → 422
      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. XM_047425353.1 → XP_047281309.1  urokinase-type plasminogen activator isoform X1

      UniProtKB/Swiss-Prot
      B4DPZ2, P00749, Q15844, Q16618, Q53XS3, Q5SWW9, Q969W6

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060934.1 Alternate T2T-CHM13v2.0

      Range
      74779718..74788885
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054366092.1 → XP_054222067.1  urokinase-type plasminogen activator isoform X1

    2. XM_054366091.1 → XP_054222066.1  urokinase-type plasminogen activator isoform X1

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    P00749.3 GenPept UniProtKB/Swiss-Prot:P00749

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