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Protein

Urokinase-type plasminogen activator

Gene

PLAU

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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

Catalytic activityi

Specific cleavage of Arg-|-Val bond in plasminogen to form plasmin.

Enzyme regulationi

Inhibited by SERPINA5.2 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei224Charge relay system1
Active sitei275Charge relay system1
Active sitei376Charge relay system1

GO - Molecular functioni

GO - Biological processi

  • blood coagulation Source: UniProtKB-KW
  • chemotaxis Source: ProtInc
  • fibrinolysis Source: Reactome
  • neutrophil degranulation Source: Reactome
  • plasminogen activation Source: AgBase
  • positive regulation of cell migration Source: MGI
  • proteolysis Source: ProtInc
  • regulation of cell adhesion mediated by integrin Source: BHF-UCL
  • regulation of cell proliferation Source: Ensembl
  • regulation of signaling receptor activity Source: BHF-UCL
  • regulation of smooth muscle cell-matrix adhesion Source: BHF-UCL
  • regulation of smooth muscle cell migration Source: BHF-UCL
  • regulation of wound healing Source: BHF-UCL
  • response to hypoxia Source: Ensembl
  • signal transduction Source: ProtInc
  • smooth muscle cell migration Source: Ensembl

Keywordsi

Molecular functionHydrolase, Protease, Serine protease
Biological processBlood coagulation, Fibrinolysis, Hemostasis, Plasminogen activation

Enzyme and pathway databases

BRENDAi3.4.21.73 2681
ReactomeiR-HSA-6798695 Neutrophil degranulation
R-HSA-75205 Dissolution of Fibrin Clot
SABIO-RKiP00749
SIGNORiP00749

Protein family/group databases

MEROPSiS01.231

Names & Taxonomyi

Protein namesi
Recommended name:
Urokinase-type plasminogen activator (EC:3.4.21.73)
Short name:
U-plasminogen activator
Short name:
uPA
Cleaved into the following 3 chains:
Gene namesi
Name:PLAU
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 10

Organism-specific databases

EuPathDBiHostDB:ENSG00000122861.15
HGNCiHGNC:9052 PLAU
MIMi191840 gene
neXtProtiNX_P00749

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Involvement in diseasei

Quebec platelet disorder (QPD)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn 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.
See also OMIM:601709

Pharmaceutical usei

Available under the name Abbokinase (Abbott). Used in Pulmonary Embolism (PE) to initiate fibrinolysis. Clinically used for therapy of thrombolytic disorders.

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi158S → E: Abolishes phosphorylation, proadhesive function and ability to induce chemotactic response; when associated with E-323. 1 Publication1
Mutagenesisi323S → E: Abolishes phosphorylation, proadhesive function and ability to induce chemotactic response; when associated with E-158. 1 Publication1

Organism-specific databases

DisGeNETi5328
MalaCardsiPLAU
MIMi601709 phenotype
Orphaneti220436 Quebec platelet disorder
PharmGKBiPA33382

Chemistry databases

ChEMBLiCHEMBL3286
DrugBankiDB07122 1-[4-(2-oxo-2-phenylethyl)phenyl]guanidine
DB01905 2-(2-Hydroxy-5-Methoxy-Phenyl)-1h-Benzoimidazole-5-Carboxamidine
DB06854 2-(2-HYDROXY-BIPHENYL)-1H-BENZOIMIDAZOLE-5-CARBOXAMIDINE
DB02193 2-(2-Hydroxy-Phenyl)-1h-Benzoimidazole-5-Carboxamidine
DB03729 2-Amino-5-Hydroxy-Benzimidazole
DB03136 4-Iodobenzo[B]Thiophene-2-Carboxamidine
DB01977 6-(N-Phenylcarbamyl)-2-Naphthalenecarboxamidine
DB07076 6-[(Z)-AMINO(IMINO)METHYL]-N-[3-(CYCLOPENTYLOXY)PHENYL]-2-NAPHTHAMIDE
DB03082 6-[(Z)-Amino(Imino)Methyl]-N-[4-(Aminomethyl)Phenyl]-4-(Pyrimidin-2-Ylamino)-2-Naphthamide
DB02398 6-[N-(4-(Aminomethyl)Phenyl)Carbamyl]-2-Naphthalenecarboxamidine
DB03865 6-Chloro-2-(2-Hydroxy-Biphenyl-3-Yl)-1h-Indole-5-Carboxamidine
DB06855 6-FLUORO-2-(2-HYDROXY-3-ISOBUTOXY-PHENYL)-1H-BENZOIMIDAZOLE-5-CARBOXAMIDINE
DB06856 6-FLUORO-2-[2-HYDROXY-3-(2-METHYL-CYCLOHEXYLOXY)-PHENYL]-1H-INDOLE-5-CARBOXAMIDINE
DB03046 7-Methoxy-8-[1-(Methylsulfonyl)-1h-Pyrazol-4-Yl]Naphthalene-2-Carboximidamide
DB04059 8-(Pyrimidin-2-Ylamino)Naphthalene-2-Carboximidamide
DB00594 Amiloride
DB03127 Benzamidine
DB02526 CRA_10655
DB03159 CRA_8696
DB03782 N-(1-Adamantyl)-N'-(4-Guanidinobenzyl)Urea
DB06857 N-(4-CARBAMIMIDOYL-3-CHORO-PHENYL)-2-HYDROXY-3-IODO-5-METHYL-BENZAMIDE
DB05254 Plasmin
DB03476 Trans-6-(2-Phenylcyclopropyl)-Naphthalene-2-Carboxamidine
DB00013 Urokinase
GuidetoPHARMACOLOGYi2393

Polymorphism and mutation databases

BioMutaiPLAU
DMDMi254763341

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 202 PublicationsAdd BLAST20
ChainiPRO_000002831821 – 431Urokinase-type plasminogen activatorAdd BLAST411
ChainiPRO_000002831921 – 177Urokinase-type plasminogen activator long chain AAdd BLAST157
ChainiPRO_0000028320156 – 177Urokinase-type plasminogen activator short chain AAdd BLAST22
ChainiPRO_0000028321179 – 431Urokinase-type plasminogen activator chain BAdd BLAST253

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi31 ↔ 39
Disulfide bondi33 ↔ 51
Glycosylationi38O-linked (Fuc) threonine1 Publication1
Disulfide bondi53 ↔ 62
Disulfide bondi70 ↔ 151
Disulfide bondi91 ↔ 133
Disulfide bondi122 ↔ 146
Modified residuei158Phosphoserine1 Publication1
Disulfide bondi168 ↔ 299Interchain (between A and B chains)
Disulfide bondi209 ↔ 225
Disulfide bondi217 ↔ 288
Disulfide bondi313 ↔ 382
GlycosylationiCAR_000026322N-linked (GlcNAc...) asparagine1
Modified residuei323Phosphoserine1 Publication1
Disulfide bondi345 ↔ 361
Disulfide bondi372 ↔ 400

Post-translational modificationi

Phosphorylation of Ser-158 and Ser-323 abolishes proadhesive ability but does not interfere with receptor binding.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei177 – 178Cleavage; during zymogen activation2

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein, Zymogen

Proteomic databases

EPDiP00749
MaxQBiP00749
PaxDbiP00749
PeptideAtlasiP00749
PRIDEiP00749
ProteomicsDBi51279
51280 [P00749-2]

PTM databases

GlyConnecti503
519
612
iPTMnetiP00749
PhosphoSitePlusiP00749
UniCarbKBiP00749

Miscellaneous databases

PMAP-CutDBiQ53XS3

Expressioni

Tissue specificityi

Expressed in the prostate gland and prostate cancers.1 Publication

Gene expression databases

BgeeiENSG00000122861
CleanExiHS_PLAU
ExpressionAtlasiP00749 baseline and differential
GenevisibleiP00749 HS

Organism-specific databases

HPAiHPA008719

Interactioni

Subunit structurei

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.3 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
PLAURQ03405-12EBI-3905042,EBI-15695188

Protein-protein interaction databases

BioGridi111344, 21 interactors
ComplexPortaliCPX-483 uPA-PAI-1 complex
CPX-487 uPA-uPAR complex
CPX-501 uPA-uPAR-vitronectin complex
DIPiDIP-46387N
ELMiP00749
IntActiP00749, 9 interactors
MINTiP00749
STRINGi9606.ENSP00000361850

Chemistry databases

BindingDBiP00749

Structurei

Secondary structure

1431
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi34 – 36Combined sources3
Beta strandi38 – 41Combined sources4
Turni43 – 47Combined sources5
Beta strandi49 – 52Combined sources4
Beta strandi57 – 59Combined sources3
Beta strandi64 – 67Combined sources4
Beta strandi70 – 72Combined sources3
Beta strandi73 – 77Combined sources5
Beta strandi86 – 89Combined sources4
Beta strandi94 – 96Combined sources3
Helixi99 – 101Combined sources3
Beta strandi102 – 104Combined sources3
Beta strandi106 – 108Combined sources3
Helixi111 – 114Combined sources4
Beta strandi117 – 119Combined sources3
Beta strandi128 – 130Combined sources3
Beta strandi132 – 137Combined sources6
Beta strandi140 – 147Combined sources8
Helixi162 – 165Combined sources4
Beta strandi180 – 184Combined sources5
Helixi187 – 189Combined sources3
Beta strandi193 – 199Combined sources7
Beta strandi201 – 203Combined sources3
Beta strandi205 – 215Combined sources11
Beta strandi218 – 221Combined sources4
Helixi223 – 225Combined sources3
Turni226 – 228Combined sources3
Helixi232 – 234Combined sources3
Beta strandi235 – 240Combined sources6
Beta strandi243 – 246Combined sources4
Beta strandi252 – 261Combined sources10
Beta strandi268 – 271Combined sources4
Beta strandi272 – 274Combined sources3
Beta strandi277 – 282Combined sources6
Beta strandi293 – 295Combined sources3
Beta strandi312 – 318Combined sources7
Beta strandi329 – 331Combined sources3
Beta strandi333 – 340Combined sources8
Helixi342 – 345Combined sources4
Turni348 – 351Combined sources4
Helixi352 – 354Combined sources3
Turni356 – 358Combined sources3
Beta strandi359 – 363Combined sources5
Beta strandi365 – 367Combined sources3
Beta strandi379 – 384Combined sources6
Beta strandi387 – 396Combined sources10
Beta strandi398 – 402Combined sources5
Beta strandi407 – 411Combined sources5
Helixi412 – 414Combined sources3
Helixi416 – 422Combined sources7

3D structure databases

ProteinModelPortaliP00749
SMRiP00749
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP00749

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini27 – 63EGF-likePROSITE-ProRule annotationAdd BLAST37
Domaini70 – 151KringlePROSITE-ProRule annotationAdd BLAST82
Domaini179 – 424Peptidase S1PROSITE-ProRule annotationAdd BLAST246

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni34 – 57Binds urokinase plasminogen activator surface receptorBy similarityAdd BLAST24
Regioni152 – 177Connecting peptideAdd BLAST26

Sequence similaritiesi

Belongs to the peptidase S1 family.PROSITE-ProRule annotation

Keywords - Domaini

EGF-like domain, Kringle, Signal

Phylogenomic databases

eggNOGiENOG410IGFI Eukaryota
COG5640 LUCA
HOVERGENiHBG008633
InParanoidiP00749
KOiK01348
OrthoDBiEOG091G0AH5
PhylomeDBiP00749
TreeFamiTF329901

Family and domain databases

CDDicd00190 Tryp_SPc, 1 hit
Gene3Di2.40.20.10, 1 hit
InterProiView protein in InterPro
IPR013032 EGF-like_CS
IPR000742 EGF-like_dom
IPR000001 Kringle
IPR013806 Kringle-like
IPR018056 Kringle_CS
IPR038178 Kringle_sf
IPR009003 Peptidase_S1_PA
IPR001314 Peptidase_S1A
IPR001254 Trypsin_dom
IPR018114 TRYPSIN_HIS
IPR033116 TRYPSIN_SER
IPR034814 Urokinase
PANTHERiPTHR24264:SF38 PTHR24264:SF38, 1 hit
PfamiView protein in Pfam
PF00051 Kringle, 1 hit
PF00089 Trypsin, 1 hit
PRINTSiPR00722 CHYMOTRYPSIN
SMARTiView protein in SMART
SM00130 KR, 1 hit
SM00020 Tryp_SPc, 1 hit
SUPFAMiSSF50494 SSF50494, 1 hit
SSF57440 SSF57440, 1 hit
PROSITEiView protein in PROSITE
PS00022 EGF_1, 1 hit
PS50026 EGF_3, 1 hit
PS00021 KRINGLE_1, 1 hit
PS50070 KRINGLE_2, 1 hit
PS50240 TRYPSIN_DOM, 1 hit
PS00134 TRYPSIN_HIS, 1 hit
PS00135 TRYPSIN_SER, 1 hit

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P00749-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MRALLARLLL CVLVVSDSKG SNELHQVPSN CDCLNGGTCV SNKYFSNIHW
60 70 80 90 100
CNCPKKFGGQ HCEIDKSKTC YEGNGHFYRG KASTDTMGRP CLPWNSATVL
110 120 130 140 150
QQTYHAHRSD ALQLGLGKHN YCRNPDNRRR PWCYVQVGLK PLVQECMVHD
160 170 180 190 200
CADGKKPSSP PEELKFQCGQ KTLRPRFKII GGEFTTIENQ PWFAAIYRRH
210 220 230 240 250
RGGSVTYVCG GSLISPCWVI SATHCFIDYP KKEDYIVYLG RSRLNSNTQG
260 270 280 290 300
EMKFEVENLI LHKDYSADTL AHHNDIALLK IRSKEGRCAQ PSRTIQTICL
310 320 330 340 350
PSMYNDPQFG TSCEITGFGK ENSTDYLYPE QLKMTVVKLI SHRECQQPHY
360 370 380 390 400
YGSEVTTKML CAADPQWKTD SCQGDSGGPL VCSLQGRMTL TGIVSWGRGC
410 420 430
ALKDKPGVYT RVSHFLPWIR SHTKEENGLA L
Length:431
Mass (Da):48,507
Last modified:July 28, 2009 - v2
Checksum:i62C72400BC23115F
GO
Isoform 2 (identifier: P00749-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-29: MRALLARLLLCVLVVSDSKGSNELHQVPS → MVFHLRTRYEQA

Show »
Length:414
Mass (Da):46,908
Checksum:iFB35DBE360D7E1CC
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti150D → G in BAG60754 (PubMed:14702039).Curated1
Sequence conflicti151C → W in CAA26535 (PubMed:3888571).Curated1
Sequence conflicti386G → C in CAA26535 (PubMed:3888571).Curated1
Sequence conflicti430A → V in CAA26535 (PubMed:3888571).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_03873015V → L1 PublicationCorresponds to variant dbSNP:rs2227580EnsemblClinVar.1
Natural variantiVAR_006722141P → L6 PublicationsCorresponds to variant dbSNP:rs2227564Ensembl.1
Natural variantiVAR_013102214I → M2 Publications1
Natural variantiVAR_038731231K → Q1 PublicationCorresponds to variant dbSNP:rs2227567EnsemblClinVar.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0383681 – 29MRALL…HQVPS → MVFHLRTRYEQA in isoform 2. 1 PublicationAdd BLAST29

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M15476 mRNA Translation: AAA61253.1
X02760 mRNA Translation: CAA26535.1
D00244 mRNA Translation: BAA00175.1
K03226 mRNA Translation: AAC97138.1
X02419 Genomic DNA Translation: CAA26268.1
AF377330 Genomic DNA Translation: AAK53822.1
BT007391 mRNA Translation: AAP36055.1
AK298560 mRNA Translation: BAG60754.1
AL596247 Genomic DNA No translation available.
CH471083 Genomic DNA Translation: EAW54544.1
BC013575 mRNA Translation: AAH13575.1
D11143 mRNA Translation: BAA01919.1
K02286 Genomic DNA Translation: AAA61252.1
CCDSiCCDS44442.1 [P00749-2]
CCDS7339.1 [P00749-1]
PIRiA00931 UKHU
RefSeqiNP_001138503.1, NM_001145031.2 [P00749-2]
NP_001306120.1, NM_001319191.1
NP_002649.1, NM_002658.4 [P00749-1]
UniGeneiHs.77274

Genome annotation databases

EnsembliENST00000372764; ENSP00000361850; ENSG00000122861
ENST00000496777; ENSP00000431795; ENSG00000122861
GeneIDi5328
KEGGihsa:5328
UCSCiuc001jwa.4 human [P00749-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiUROK_HUMAN
AccessioniPrimary (citable) accession number: P00749
Secondary accession number(s): B4DPZ2
, Q15844, Q16618, Q53XS3, Q5SWW9, Q969W6
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: July 28, 2009
Last modified: June 20, 2018
This is version 232 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Pharmaceutical, Reference proteome

Documents

  1. Human chromosome 10
    Human chromosome 10: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Peptidase families
    Classification of peptidase families and list of entries
  7. SIMILARITY comments
    Index of protein domains and families

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