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 cata... See more...

Aliases for PLAU Gene

Aliases for PLAU Gene

  • Plasminogen Activator, Urokinase 2 3 5
  • Urokinase-Type Plasminogen Activator 3 4
  • U-Plasminogen Activator 3 4
  • EC 3.4.21.73 4 52
  • UPA 3 4
  • Plasminogen Activator, Urinary 3
  • EC 3.4.21 52
  • BDPLT5 3
  • U-PA 3
  • ATF 3
  • QPD 3
  • URK 3

External Ids for PLAU Gene

Previous GeneCards Identifiers for PLAU Gene

  • GC10P074625
  • GC10P074774
  • GC10P075561
  • GC10P075015
  • GC10P075340
  • GC10P075668
  • GC10P069666

Summaries for PLAU Gene

Entrez Gene Summary for PLAU Gene

  • 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]

GeneCards Summary for PLAU Gene

PLAU (Plasminogen Activator, Urokinase) is a Protein Coding gene. Diseases associated with PLAU include Quebec Platelet Disorder and Alzheimer Disease. Among its related pathways are Innate Immune System and Development HGF signaling pathway. Gene Ontology (GO) annotations related to this gene include serine-type endopeptidase activity. An important paralog of this gene is PRSS1.

UniProtKB/Swiss-Prot Summary for PLAU Gene

  • Specifically cleaves the zymogen plasminogen to form the active enzyme plasmin.

Tocris Summary for PLAU Gene

Gene Wiki entry for PLAU Gene

Additional gene information for PLAU Gene

No data available for CIViC Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for PLAU Gene

Genomics for PLAU Gene

GeneHancer (GH) Regulatory Elements for PLAU Gene

Promoters and enhancers for PLAU Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around PLAU on UCSC Golden Path with GeneCards custom track

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for PLAU

Top Transcription factor binding sites by QIAGEN in the PLAU gene promoter:
  • AML1a

Genomic Locations for PLAU Gene

Genomic Locations for PLAU Gene
chr10:73,909,177-73,917,501
(GRCh38/hg38)
Size:
8,325 bases
Orientation:
Plus strand
chr10:75,668,935-75,677,259
(GRCh37/hg19)
Size:
8,325 bases
Orientation:
Plus strand

Genomic View for PLAU Gene

Genes around PLAU on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
PLAU Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for PLAU Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for PLAU Gene

Proteins for PLAU Gene

  • Protein details for PLAU Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P00749-UROK_HUMAN
    Recommended name:
    Urokinase-type plasminogen activator
    Protein Accession:
    P00749
    Secondary Accessions:
    • B4DPZ2
    • Q15844
    • Q16618
    • Q53XS3
    • Q5SWW9
    • Q969W6

    Protein attributes for PLAU Gene

    Size:
    431 amino acids
    Molecular mass:
    48507 Da
    Quaternary structure:
    • Found in high and low molecular mass forms. Each consists of two chains, A and B. The high molecular mass form contains a long chain A which is cleaved to yield a short chain A. Forms heterodimer with SERPINA5. Binds LRP1B; binding is followed by internalization and degradation. Interacts with MRC2. Interacts with PLAUR. In complex with SERPINE1, interacts with PLAUR/uPAR (PubMed:15053742). Interacts with SORL1 and LRP1, either alone or in complex with SERPINE1; these interactions are abolished in the presence of LRPAP1/RAP (PubMed:15053742). The ternary complex composed of PLAUR-PLAU-PAI1 also interacts with SORLA (PubMed:15053742).

    Three dimensional structures from OCA and Proteopedia for PLAU Gene

    Alternative splice isoforms for PLAU Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for PLAU Gene

Selected DME Specific Peptides for PLAU Gene

P00749:
  • KEDYIVYLGR
  • CQQPHYYGSEVTTKMLCAADPQW
  • CEITGFG
  • GEMKFEVE
  • DSCQGDSGG
  • GIVSWGR
  • GDSGGPL
  • ENQPWFAAIY
  • CNCPKKF
  • CQGDSGGP
  • NYCRNPD
  • LGLGKHN
  • IQTICLP
  • SGGPLVC
  • TGIVSWG
  • CGGSLISPCWV
  • LRPRFKI

Post-translational modifications for PLAU Gene

  • Phosphorylation of Ser-158 and Ser-323 abolishes proadhesive ability but does not interfere with receptor binding.
  • Glycosylation at Thr38, Ser158, and Asn322
  • Modification sites at PhosphoSitePlus
  • Glycosylation from GlyConnect

Other Protein References for PLAU Gene

Antibody Products

Domains & Families for PLAU Gene

Gene Families for PLAU Gene

Human Protein Atlas (HPA):
  • Cancer-related genes
  • Disease related genes
  • Enzymes
  • FDA approved drug targets
  • Plasma proteins
  • Predicted intracellular proteins
  • Predicted secreted proteins

Protein Domains for PLAU Gene

Blocks:
  • Serine protease, trypsin family
  • Chymotrypsin serine protease family (S1) signature
  • Type I EGF
  • Kringle
InterPro:
ProtoNet:

Suggested Antigen Peptide Sequences for PLAU Gene

GenScript: Design optimal peptide antigens:
  • PLAU protein (Q9UEJ5_HUMAN)
  • Urokinase-type plasminogen activator (UROK_HUMAN)

Graphical View of Domain Structure for InterPro Entry

P00749

UniProtKB/Swiss-Prot:

UROK_HUMAN :
  • Belongs to the peptidase S1 family.
Family:
  • Belongs to the peptidase S1 family.
genes like me logo Genes that share domains with PLAU: view

Function for PLAU Gene

Molecular function for PLAU Gene

UniProtKB/Swiss-Prot Function:
Specifically cleaves the zymogen plasminogen to form the active enzyme plasmin.
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=Specific cleavage of Arg- -Val bond in plasminogen to form plasmin.; EC=3.4.21.73;.
UniProtKB/Swiss-Prot EnzymeRegulation:
Inhibited by SERPINA5.
GENATLAS Biochemistry:
plasminogen activator,urokinase serine protease,involved in plasminogen activation to plasmin

Enzyme Numbers (IUBMB) for PLAU Gene

Phenotypes From GWAS Catalog for PLAU Gene

Gene Ontology (GO) - Molecular Function for PLAU Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004252 serine-type endopeptidase activity TAS,IEA --
GO:0005515 protein binding IPI 3501295
GO:0008233 peptidase activity IEA --
GO:0008236 serine-type peptidase activity IEA --
GO:0016787 hydrolase activity IEA --
genes like me logo Genes that share ontologies with PLAU: view
genes like me logo Genes that share phenotypes with PLAU: view

Human Phenotype Ontology for PLAU Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for PLAU Gene

MGI Knock Outs for PLAU:
  • Plau Plau<tm1Mlg>
  • Plau Plau<tm1b(EUCOMM)Wtsi>

Animal Model Products

CRISPR Products

Transcription Factor Targets for PLAU Gene

Selected GeneGlobe predicted Target genes for PLAU

Clone Products

  • Addgene plasmids for PLAU

No data available for HOMER Transcription for PLAU Gene

Localization for PLAU Gene

Subcellular locations from UniProtKB/Swiss-Prot for PLAU Gene

Secreted.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for PLAU gene
Compartment Confidence
plasma membrane 5
extracellular 5
cytosol 3
cytoskeleton 2
mitochondrion 2
nucleus 2
endoplasmic reticulum 2
endosome 2
lysosome 2
peroxisome 1
golgi apparatus 1

Gene Ontology (GO) - Cellular Components for PLAU Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005576 extracellular region TAS,IEA --
GO:0005615 extracellular space IDA,IBA 18835034
GO:0005886 plasma membrane TAS --
GO:0005925 focal adhesion HDA 21423176
GO:0009986 cell surface IDA 18835034
genes like me logo Genes that share ontologies with PLAU: view

No data available for Subcellular locations from the Human Protein Atlas (HPA) for PLAU Gene

Pathways & Interactions for PLAU Gene

genes like me logo Genes that share pathways with PLAU: view

Pathways by source for PLAU Gene

5 GeneGo (Thomson Reuters) pathways for PLAU Gene
  • Cell adhesion PLAU signaling
  • Cell adhesion_ECM remodeling
  • Cell adhesion_Plasmin signaling
  • Development HGF signaling pathway
  • Development VEGF signaling via VEGFR2 - generic cascades
1 R&D Systems pathway for PLAU Gene
2 Qiagen pathways for PLAU Gene
  • Glioma Invasiveness
  • UPA-UPAR Pathway

SIGNOR curated interactions for PLAU Gene

Activates:
Is activated by:

Gene Ontology (GO) - Biological Process for PLAU Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001666 response to hypoxia IEA --
GO:0006508 proteolysis IEA,IBA 21873635
GO:0006935 chemotaxis TAS 10749881
GO:0007165 signal transduction TAS 10749881
GO:0007596 blood coagulation IEA --
genes like me logo Genes that share ontologies with PLAU: view

Drugs & Compounds for PLAU Gene

(118) Drugs for PLAU Gene - From: DrugBank, ApexBio, DGIdb, HMDB, Tocris, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Amiloride Approved Pharma Channel blocker, Target, inhibitor 59
Urokinase Approved, Investigational, Withdrawn Pharma Target, activator 0
4-Iodobenzo[B]Thiophene-2-Carboxamidine Experimental Pharma Target 0
benzamidine Experimental Pharma Target 0
(2R)-1-(2,6-dimethylphenoxy)propan-2-amine Experimental Pharma Target 0

(71) Additional Compounds for PLAU Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs

(2) Tocris Compounds for PLAU Gene

Compound Action Cas Number
4-Chlorophenylguanidine hydrochloride Urokinase inhibitor 14279-91-5
BC 11 hydrobromide Selective urokinase (uPA) inhibitor 443776-49-6

(4) ApexBio Compounds for PLAU Gene

Compound Action Cas Number
4-Chlorophenylguanidine hydrochloride Urokinase inhibitor, potent and specific 14279-91-5
BC 11 hydrobromide Selective urokinase inhibitor 443776-49-6
GGACK Dihydrochloride Urokinase/VIIa/Ixa/Xa/trypsin inhibitor
Tiplaxtinin(PAI-039) Orally efficacious inhibitor of PAI-1 393105-53-8
genes like me logo Genes that share compounds with PLAU: view

Transcripts for PLAU Gene

mRNA/cDNA for PLAU Gene

3 REFSEQ mRNAs :
23 NCBI additional mRNA sequence :
5 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Clone Products

  • Addgene plasmids for PLAU

Alternative Splicing Database (ASD) splice patterns (SP) for PLAU Gene

No ASD Table

Relevant External Links for PLAU Gene

GeneLoc Exon Structure for
PLAU

Expression for PLAU Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for PLAU Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for PLAU Gene

This gene is overexpressed in Adipose - Visceral (Omentum) (x4.7).

Protein differential expression in normal tissues from HIPED for PLAU Gene

This gene is overexpressed in Urine (59.7) and Amniocyte (6.9).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for PLAU Gene



Protein tissue co-expression partners for PLAU Gene

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for PLAU

SOURCE GeneReport for Unigene cluster for PLAU Gene:

Hs.77274

mRNA Expression by UniProt/SwissProt for PLAU Gene:

P00749-UROK_HUMAN
Tissue specificity: Expressed in the prostate gland and prostate cancers.

Evidence on tissue expression from TISSUES for PLAU Gene

  • Lung(4.8)
  • Kidney(4.6)
  • Nervous system(3.8)
  • Pancreas(3.4)
  • Skin(2.9)
  • Heart(2.6)
  • Intestine(2.6)
  • Liver(2.6)
  • Blood(2.4)
  • Lymph node(2.4)
  • Muscle(2.1)
  • Bone marrow(2)
  • Stomach(2)

Phenotype-based relationships between genes and organs from Gene ORGANizer for PLAU Gene

Germ Layers:
  • ectoderm
  • mesoderm
Systems:
  • cardiovascular
  • integumentary
  • reproductive
  • skeleton
  • urinary
Regions:
Head and neck:
  • face
  • head
  • nose
Abdomen:
  • kidney
Pelvis:
  • uterus
Limb:
  • ankle
  • digit
  • elbow
  • finger
  • foot
  • hand
  • hip
  • knee
  • lower limb
  • shoulder
  • toe
  • upper limb
  • wrist
General:
  • blood
  • blood vessel
  • coagulation system
  • skin
genes like me logo Genes that share expression patterns with PLAU: view

Orthologs for PLAU Gene

This gene was present in the common ancestor of animals.

Orthologs for PLAU Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia PLAU 31 30
  • 99.15 (n)
OneToOne
dog
(Canis familiaris)
Mammalia PLAU 31 30
  • 84.66 (n)
OneToOne
cow
(Bos Taurus)
Mammalia PLAU 31 30
  • 82.93 (n)
OneToOne
rat
(Rattus norvegicus)
Mammalia Plau 30
  • 78.26 (n)
mouse
(Mus musculus)
Mammalia Plau 17 31 30
  • 77.75 (n)
oppossum
(Monodelphis domestica)
Mammalia PLAU 31
  • 56 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia PLAU 31
  • 52 (a)
OneToOne
chicken
(Gallus gallus)
Aves PLAU 31 30
  • 56.8 (n)
OneToOne
lizard
(Anolis carolinensis)
Reptilia PLAU 31
  • 44 (a)
OneToOne
zebrafish
(Danio rerio)
Actinopterygii plaua 31 30
  • 51.2 (n)
OneToMany
plaub 31
  • 36 (a)
OneToMany
fruit fly
(Drosophila melanogaster)
Insecta CG6041 32
  • 37 (a)
CG11836 32
  • 37 (a)
Species where no ortholog for PLAU was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea squirt (Ciona intestinalis)
  • sea squirt (Ciona savignyi)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • tropical clawed frog (Silurana tropicalis)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)

Evolution for PLAU Gene

ENSEMBL:
Gene Tree for PLAU (if available)
TreeFam:
Gene Tree for PLAU (if available)
Aminode:
Evolutionary constrained regions (ECRs) for PLAU: view image

Paralogs for PLAU Gene

Paralogs for PLAU Gene

genes like me logo Genes that share paralogs with PLAU: view

Variants for PLAU Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for PLAU Gene

SNP ID Clinical significance and condition Chr 10 pos Variation AA Info Type
752927 Likely Benign: not provided 73,916,490(+) C/T SYNONYMOUS_VARIANT
793048 Likely Benign: not provided 73,914,043(+) G/A SYNONYMOUS_VARIANT
rs117134857 Benign: Quebec platelet disorder 73,917,085(+) G/T THREE_PRIME_UTR_VARIANT
rs140559980 Likely Benign: Quebec platelet disorder 73,916,920(+) C/T THREE_PRIME_UTR_VARIANT
rs142059320 Likely Benign: Quebec platelet disorder; not provided 73,912,291(+) A/G SYNONYMOUS_VARIANT,FIVE_PRIME_UTR_VARIANT

Additional dbSNP identifiers (rs#s) for PLAU Gene

Structural Variations from Database of Genomic Variants (DGV) for PLAU Gene

Variant ID Type Subtype PubMed ID
dgv46n21 CNV loss 19592680
nsv1035390 CNV loss 25217958
nsv521018 CNV gain 19592680
nsv825468 CNV gain 20364138

Variation tolerance for PLAU Gene

Residual Variation Intolerance Score: 91.4% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 2.53; 44.14% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for PLAU Gene

Human Gene Mutation Database (HGMD)
PLAU
SNPedia medical, phenotypic, and genealogical associations of SNPs for
PLAU

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for PLAU Gene

Disorders for PLAU Gene

MalaCards: The human disease database

(46) MalaCards diseases for PLAU Gene - From: OMIM, ClinVar, GTR, Orphanet, DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
quebec platelet disorder
  • qpd
alzheimer disease
  • ad
ureter, cancer of
  • ureter cancer
fibrosarcoma
  • fibrocytic tumor
angiostrongyliasis
- elite association - COSMIC cancer census association via MalaCards
Search PLAU in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

UROK_HUMAN
  • Quebec platelet disorder (QPD) [MIM:601709]: An autosomal dominant bleeding disorder due to a gain-of-function defect in fibrinolysis. Although affected individuals do not exhibit systemic fibrinolysis, they show delayed onset bleeding after challenge, such as surgery. The hallmark of the disorder is markedly increased PLAU levels within platelets, which causes intraplatelet plasmin generation and secondary degradation of alpha-granule proteins. {ECO:0000269 PubMed:20007542}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Additional Disease Information for PLAU

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
genes like me logo Genes that share disorders with PLAU: view

No data available for Genatlas for PLAU Gene

Publications for PLAU Gene

  1. Persons with Quebec platelet disorder have a tandem duplication of PLAU, the urokinase plasminogen activator gene. (PMID: 20007542) Paterson AD … Hayward CP (Blood 2010) 3 4 41 54
  2. Gene polymorphisms of fibrinolytic enzymes in coal workers' pneumoconiosis. (PMID: 17649957) Chang LC … Wu HP (Archives of environmental & occupational health 2006) 3 23 41 54
  3. A functional polymorphism within plasminogen activator urokinase (PLAU) is associated with Alzheimer's disease. (PMID: 16825285) Riemenschneider M … Kurz A (Human molecular genetics 2006) 3 23 41 54
  4. (4-aminomethyl)phenylguanidine derivatives as nonpeptidic highly selective inhibitors of human urokinase. (PMID: 10805774) Sperl S … Moroder L (Proceedings of the National Academy of Sciences of the United States of America 2000) 3 4 23 54
  5. Molecular cloning of cDNA coding for human preprourokinase. (PMID: 2415429) Nagai M … Suyama T (Gene 1985) 2 3 4 54

Products for PLAU Gene