P00749 (UROK_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Urokinase-type plasminogen activator
Short name=U-plasminogen activator
Short name=uPA
EC=3.4.21.73

Cleaved into the following 3 chains:

1. Urokinase-type plasminogen activator long chain A
2. Urokinase-type plasminogen activator short chain A
3. Urokinase-type plasminogen activator chain B

Gene names

Name:

PLAU

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	431 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Specifically cleaves the zymogen plasminogen to form the active enzyme plasmin.
Catalytic activity	Specific cleavage of Arg-|-Val bond in plasminogen to form plasmin.
Enzyme regulation	Inhibited by SERPINA5. Ref.17 Ref.22
Subunit 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. Ref.20 Ref.21
Subcellular location	Secreted.
Tissue specificity	Expressed in the prostate gland and prostate cancers. Ref.23
Post-translational modification	Phosphorylation of Ser-158 and Ser-323 abolishes proadhesive ability but does not interfere with receptor binding.
Involvement in disease	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. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.24
Pharmaceutical use	Available under the name Abbokinase (Abbott). Used in Pulmonary Embolism (PE) to initiate fibrinolysis. Clinically used for therapy of thrombolytic disorders.
Sequence similarities	Belongs to the peptidase S1 family. Contains 1 EGF-like domain. Contains 1 kringle domain. Contains 1 peptidase S1 domain.

Ontologies

Keywords
Biological process	Blood coagulation Fibrinolysis Hemostasis Plasminogen activation
Cellular component	Secreted
Coding sequence diversity	Alternative splicing Polymorphism
Domain	EGF-like domain Kringle Signal
Molecular function	Hydrolase Protease Serine protease
PTM	Disulfide bond Glycoprotein Phosphoprotein Zymogen
Technical term	3D-structure Complete proteome Direct protein sequencing Pharmaceutical Reference proteome
Gene Ontology (GO)
Biological_process	blood coagulation Traceable author statement. Source: Reactome chemotaxis Traceable author statement PubMed 10749881. Source: ProtInc fibrinolysis Traceable author statement. Source: Reactome proteolysis Traceable author statement Ref.13. Source: ProtInc regulation of cell adhesion mediated by integrin Inferred from direct assay PubMed 8837777. Source: BHF-UCL regulation of cell proliferation Inferred from electronic annotation. Source: Compara regulation of receptor activity Inferred from direct assay PubMed 8837777. Source: BHF-UCL regulation of smooth muscle cell migration Inferred from direct assay PubMed 8837777. Source: BHF-UCL regulation of smooth muscle cell-matrix adhesion Inferred from direct assay PubMed 8837777. Source: BHF-UCL response to hypoxia Inferred from electronic annotation. Source: Compara signal transduction Traceable author statement PubMed 10749881. Source: ProtInc smooth muscle cell migration Inferred from electronic annotation. Source: Compara
Cellular_component	cell surface Inferred from direct assay PubMed 18835034. Source: BHF-UCL extracellular space Inferred from direct assay PubMed 18835034. Source: BHF-UCL plasma membrane Traceable author statement. Source: Reactome
Molecular_function	serine-type endopeptidase activity Traceable author statement. Source: Reactome
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P00749-1)

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.

Isoform 2 (identifier: P00749-2)

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

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 20

20

Ref.12 Ref.14

Chain

21 – 431

411

Urokinase-type plasminogen activator

PRO_0000028318

Chain

21 – 177

157

Urokinase-type plasminogen activator long chain A

PRO_0000028319

Chain

156 – 177

22

Urokinase-type plasminogen activator short chain A

PRO_0000028320

Chain

179 – 431

253

Urokinase-type plasminogen activator chain B

PRO_0000028321

Regions

Domain

27 – 63

37

EGF-like

Domain

70 – 151

82

Kringle

Domain

179 – 424

246

Peptidase S1

Region

34 – 57

24

Binds urokinase plasminogen activator surface receptor By similarity

Region

152 – 177

26

Connecting peptide

Sites

Active site

224

1

Charge relay system

Active site

275

1

Charge relay system

Active site

376

1

Charge relay system

Site

177 – 178

2

Cleavage; during zymogen activation

Amino acid modifications

Modified residue

158

1

Phosphoserine Ref.18

Modified residue

323

1

Phosphoserine Ref.18

Glycosylation

38

1

O-linked (Fuc) Ref.12

Glycosylation

322

1

N-linked (GlcNAc...)

CAR_000026

Disulfide bond

31 ↔ 39

Disulfide bond

33 ↔ 51

Disulfide bond

53 ↔ 62

Disulfide bond

70 ↔ 151

Disulfide bond

91 ↔ 133

Disulfide bond

122 ↔ 146

Disulfide bond

168 ↔ 299

Interchain (between A and B chains)

Disulfide bond

209 ↔ 225

Disulfide bond

217 ↔ 288

Disulfide bond

313 ↔ 382

Disulfide bond

345 ↔ 361

Disulfide bond

372 ↔ 400

Natural variations

Alternative sequence

1 – 29

29

MRALL…HQVPS → MVFHLRTRYEQA in isoform 2.

VSP_038368

Natural variant

15

1

V → L. Ref.7
Corresponds to variant rs2227580 [ dbSNP | Ensembl ].

VAR_038730

Natural variant

141

1

P → L. Ref.7 Ref.8 Ref.11 Ref.31 Ref.33 Ref.34
Corresponds to variant rs2227564 [ dbSNP | Ensembl ].

VAR_006722

Natural variant

214

1

I → M. Ref.4 Ref.13

VAR_013102

Natural variant

231

1

K → Q. Ref.7
Corresponds to variant rs2227567 [ dbSNP | Ensembl ].

VAR_038731

Experimental info

Mutagenesis

158

1

S → E: Abolishes phosphorylation, proadhesive function and ability to induce chemotactic response; when associated with E-323. Ref.18

Mutagenesis

323

1

S → E: Abolishes phosphorylation, proadhesive function and ability to induce chemotactic response; when associated with E-158. Ref.18

Sequence conflict

150

1

D → G in BAG60754. Ref.6

Sequence conflict

151

1

C → W in CAA26535. Ref.2

Sequence conflict

386

1

G → C in CAA26535. Ref.2

Sequence conflict

430

1

A → V in CAA26535. Ref.2

Secondary structure

1

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431

Helix Strand Turn

Details...

Beta strand

34 – 36

3

Beta strand

38 – 41

4

Turn

43 – 47

5

Beta strand

49 – 52

4

Beta strand

57 – 59

3

Beta strand

64 – 67

4

Beta strand

70 – 72

3

Beta strand

73 – 77

5

Beta strand

86 – 89

4

Beta strand

94 – 96

3

Helix

99 – 101

3

Beta strand

102 – 104

3

Beta strand

106 – 108

3

Helix

111 – 114

4

Beta strand

117 – 119

3

Beta strand

128 – 130

3

Beta strand

132 – 137

6

Beta strand

140 – 147

8

Beta strand

180 – 184

5

Helix

187 – 189

3

Beta strand

193 – 197

5

Beta strand

201 – 203

3

Beta strand

207 – 215

9

Beta strand

218 – 221

4

Helix

223 – 225

3

Turn

226 – 228

3

Helix

232 – 234

3

Beta strand

236 – 240

5

Beta strand

243 – 246

4

Beta strand

252 – 261

10

Beta strand

269 – 271

3

Beta strand

272 – 274

3

Beta strand

277 – 282

6

Beta strand

312 – 318

7

Beta strand

329 – 331

3

Beta strand

333 – 340

8

Helix

342 – 345

4

Turn

348 – 351

4

Helix

352 – 354

3

Turn

356 – 358

3

Beta strand

359 – 363

5

Beta strand

365 – 367

3

Beta strand

379 – 383

5

Beta strand

385 – 396

12

Beta strand

398 – 402

5

Beta strand

407 – 411

5

Helix

412 – 414

3

Helix

416 – 422

7

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified July 28, 2009. Version 2. Checksum: 62C72400BC23115F	FASTA	431	48,507
	10 20 30 40 50 60 MRALLARLLL CVLVVSDSKG SNELHQVPSN CDCLNGGTCV SNKYFSNIHW CNCPKKFGGQ 70 80 90 100 110 120 HCEIDKSKTC YEGNGHFYRG KASTDTMGRP CLPWNSATVL QQTYHAHRSD ALQLGLGKHN 130 140 150 160 170 180 YCRNPDNRRR PWCYVQVGLK PLVQECMVHD CADGKKPSSP PEELKFQCGQ KTLRPRFKII 190 200 210 220 230 240 GGEFTTIENQ PWFAAIYRRH RGGSVTYVCG GSLISPCWVI SATHCFIDYP KKEDYIVYLG 250 260 270 280 290 300 RSRLNSNTQG EMKFEVENLI LHKDYSADTL AHHNDIALLK IRSKEGRCAQ PSRTIQTICL 310 320 330 340 350 360 PSMYNDPQFG TSCEITGFGK ENSTDYLYPE QLKMTVVKLI SHRECQQPHY YGSEVTTKML 370 380 390 400 410 420 CAADPQWKTD SCQGDSGGPL VCSLQGRMTL TGIVSWGRGC ALKDKPGVYT RVSHFLPWIR 430 SHTKEENGLA L
	Isoform 2 [UniParc]. Checksum: FB35DBE360D7E1CC	FASTA	414	46,908
	10 20 30 40 50 60 MVFHLRTRYE QANCDCLNGG TCVSNKYFSN IHWCNCPKKF GGQHCEIDKS KTCYEGNGHF 70 80 90 100 110 120 YRGKASTDTM GRPCLPWNSA TVLQQTYHAH RSDALQLGLG KHNYCRNPDN RRRPWCYVQV 130 140 150 160 170 180 GLKPLVQECM VHDCADGKKP SSPPEELKFQ CGQKTLRPRF KIIGGEFTTI ENQPWFAAIY 190 200 210 220 230 240 RRHRGGSVTY VCGGSLISPC WVISATHCFI DYPKKEDYIV YLGRSRLNSN TQGEMKFEVE 250 260 270 280 290 300 NLILHKDYSA DTLAHHNDIA LLKIRSKEGR CAQPSRTIQT ICLPSMYNDP QFGTSCEITG 310 320 330 340 350 360 FGKENSTDYL YPEQLKMTVV KLISHRECQQ PHYYGSEVTT KMLCAADPQW KTDSCQGDSG 370 380 390 400 410 GPLVCSLQGR MTLTGIVSWG RGCALKDKPG VYTRVSHFLP WIRSHTKEEN GLAL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning and expression of the gene for pro-urokinase in Escherichia coli." Holmes W.E., Pennica D., Blaber M., Rey M.W., Guenzler W.A., Steffens G.J., Heyneker H.L. Biotechnology (N.Y.) 3:923-929(1985) Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]	"Molecular cloning, sequencing, and expression in Escherichia coli of human preprourokinase cDNA." Jacobs P., Cravador A., Loriau R., Brockly F., Colau B., Chuchana P., van Elsen A., Herzog A., Bollen A. DNA 4:139-146(1985) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[3]	"Molecular cloning of cDNA coding for human preprourokinase." Nagai M., Hiramatsu R., Kaneda T., Hayasuke N., Arimura H., Nishida M., Suyama T. Gene 36:183-188(1985) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[4]	"The human urokinase-plasminogen activator gene and its promoter." Riccio A., Grimaldi G., Verde P., Sebastio G., Boast S., Blasi F. Nucleic Acids Res. 13:2759-2771(1985) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT MET-214.
[5]	"Cloning of human full-length CDSs in BD Creator(TM) System Donor vector." Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A. Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[6]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Mesangial cell.
[7]	SeattleSNPs variation discovery resource Submitted (JUN-2001) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS LEU-15; LEU-141 AND GLN-231.
[8]	"The DNA sequence and comparative analysis of human chromosome 10." Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., Taylor A., Battles J. , Bird C.P., Ainscough R., Almeida J.P., Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J. Nature 429:375-381(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANT LEU-141.
[9]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[10]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Lung.
[11]	"Characterization of single chain urokinase-type plasminogen activator with a novel amino-acid substitution in the kringle structure." Yoshimoto M., Ushiyama Y., Sakai M., Tamaki S., Hara H., Takahashi K., Sawasaki Y., Hanada K. Biochim. Biophys. Acta 1293:83-89(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 21-431, VARIANT LEU-141.
[12]	"Characterization of a posttranslational fucosylation in the growth factor domain of urinary plasminogen activator." Buko A.M., Kentzer E.J., Petros A., Menon G., Zuiderweg E.R., Sarin V.K. Proc. Natl. Acad. Sci. U.S.A. 88:3992-3996(1991) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 21-43, GLYCOSYLATION AT THR-38, MASS SPECTROMETRY.
[13]	"Identification and primary sequence of an unspliced human urokinase poly(A)+ RNA." Verde P., Stoppelli M.P., Galeffi P., di Nocera P., Blasi F. Proc. Natl. Acad. Sci. U.S.A. 81:4727-4731(1984) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] OF 66-431, VARIANT MET-214.
[14]	"The primary structure of high molecular mass urokinase from human urine. The complete amino acid sequence of the A chain." Gunzler W.A., Steffens G.J., Otting F., Kim S.-M.A., Frankus E., Flohe L. Hoppe-Seyler's Z. Physiol. Chem. 363:1155-1165(1982) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 21-177.
[15]	"Human low-molecular-weight urinary urokinase. Partial characterization and preliminary sequence data of the two polypeptide chains." Schaller J., Nick H., Rickli E.E., Gillessen D., Lergier W., Studer R.O. Eur. J. Biochem. 125:251-257(1982) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 156-176 AND 179-224.
[16]	"The complete amino acid sequence of low molecular mass urokinase from human urine." Steffens G.J., Gunzler W.A., Otting F., Frankus E., Flohe L. Hoppe-Seyler's Z. Physiol. Chem. 363:1043-1058(1982) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 158-410.
[17]	"Inhibition of urokinase by protein C-inhibitor (PCI). Evidence for identity of PCI and plasminogen activator inhibitor 3." Stief T.W., Radtke K.P., Heimburger N. Biol. Chem. Hoppe-Seyler 368:1427-1433(1987) [PubMed] [Europe PMC] [Abstract] Cited for: ENZYME REGULATION, HETERODIMER WITH SERPINA5.
[18]	"Phosphorylation of human pro-urokinase on Ser138/303 impairs its receptor-dependent ability to promote myelomonocytic adherence and motility." Franco P., Iaccarino C., Chiaradonna F., Brandazza A., Iavarone C., Mastronicola M.R., Nolli M.L., Stoppelli M.P. J. Cell Biol. 137:779-791(1997) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT SER-158 AND SER-323, MUTAGENESIS OF SER-158 AND SER-323.
[19]	"Functionally inactive protein C inhibitor in seminal plasma may be associated with infertility." He S., Lin Y.L., Liu Y.X. Mol. Hum. Reprod. 5:513-519(1999) [PubMed] [Europe PMC] [Abstract] Cited for: HETERODIMER WITH SERPINA5.
[20]	"A urokinase receptor-associated protein with specific collagen binding properties." Behrendt N., Jensen O.N., Engelholm L.H., Moertz E., Mann M., Danoe K. J. Biol. Chem. 275:1993-2002(2000) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH MRC2.
[21]	"The putative tumor suppressor LRP1B, a novel member of the low density lipoprotein (LDL) receptor family, exhibits both overlapping and distinct properties with the LDL receptor-related protein." Liu C.-X., Li Y., Obermoeller-McCormick L.M., Schwartz A.L., Bu G. J. Biol. Chem. 276:28889-28896(2001) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH LRP1B.
[22]	"Regulation of carcinoma cell invasion by protein C inhibitor whose expression is decreased in renal cell carcinoma." Wakita T., Hayashi T., Nishioka J., Tamaru H., Akita N., Asanuma K., Kamada H., Gabazza E.C., Ido M., Kawamura J., Suzuki K. Int. J. Cancer 108:516-523(2004) [PubMed] [Europe PMC] [Abstract] Cited for: ENZYME REGULATION, HETERODIMER WITH SERPINA5.
[23]	"Platelet-derived growth factor D is activated by urokinase plasminogen activator in prostate carcinoma cells." Ustach C.V., Kim H.-R.C. Mol. Cell. Biol. 25:6279-6288(2005) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY.
[24]	"Persons with Quebec platelet disorder have a tandem duplication of PLAU, the urokinase plasminogen activator gene." Paterson A.D., Rommens J.M., Bharaj B., Blavignac J., Wong I., Diamandis M., Waye J.S., Rivard G.E., Hayward C.P. Blood 115:1264-1266(2010) [PubMed] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN QPD.
[25]	"Dynamics of the multidomain fibrinolytic protein urokinase from two-dimensional NMR." Oswald R.E., Bogusky M.J., Bamberger M., Smith R.A.G., Dobson C.M. Nature 337:579-582(1989) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR.
[26]	"Sequential 1H NMR assignments and secondary structure of the kringle domain from urokinase." Li X., Smith R.A.G., Dobson C.M. Biochemistry 31:9562-9571(1992) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF 67-155.
[27]	"Solution structure of the kringle domain from urokinase-type plasminogen activator." Li X., Bokman A.M., Llinas M., Smith R.A.G., Dobson C.M. J. Mol. Biol. 235:1548-1559(1994) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF 67-155.
[28]	"The crystal structure of the catalytic domain of human urokinase-type plasminogen activator." Spraggon G., Phillips C., Nowak U.K., Ponting C.P., Saunders D., Dobson C.M., Stuart D.I., Jones E.Y. Structure 3:681-691(1995) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS).
[29]	"(4-aminomethyl)phenylguanidine derivatives as nonpeptidic highly selective inhibitors of human urokinase." Sperl S., Jacob U., Arroyo de Prada N., Sturzebecher J., Wilhelm O.G., Bode W., Magdolen V., Huber R., Moroder L. Proc. Natl. Acad. Sci. U.S.A. 97:5113-5118(2000) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 159-411.
[30]	"Structure of human urokinase plasminogen activator in complex with its receptor." Huai Q., Mazar A.P., Kuo A., Parry G.C., Shaw D.E., Callahan J., Li Y., Yuan C., Bian C., Chen L., Furie B., Furie B.C., Cines D.B., Huang M. Science 311:656-659(2006) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 31-152 IN COMPLEX WITH PLAUR.
[31]	"Detection of polymorphisms in the human urokinase-type plasminogen activator gene." Conne B., Berczy M., Belin D. Thromb. Haemost. 77:434-435(1997) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT LEU-141.
[32]	Erratum Conne B., Berczy M., Belin D. Thromb. Haemost. 78:973-973(1997)
[33]	"Mutational analysis of the genes encoding urokinase-type plasminogen activator (uPA) and its inhibitor PAI-1 in advanced ovarian cancer." Turkmen B., Schmitt M., Schmalfeldt B., Trommler P., Hell W., Creutzburg S., Graeff H., Magdolen V. Electrophoresis 18:686-689(1997) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT LEU-141.
[34]	"DNA sequencing of a cytogenetically normal acute myeloid leukaemia genome." Ley T.J., Mardis E.R., Ding L., Fulton B., McLellan M.D., Chen K., Dooling D., Dunford-Shore B.H., McGrath S., Hickenbotham M., Cook L., Abbott R., Larson D.E., Koboldt D.C., Pohl C., Smith S., Hawkins A., Abbott S. , Locke D., Hillier L.W., Miner T., Fulton L., Magrini V., Wylie T., Glasscock J., Conyers J., Sander N., Shi X., Osborne J.R., Minx P., Gordon D., Chinwalla A., Zhao Y., Ries R.E., Payton J.E., Westervelt P., Tomasson M.H., Watson M., Baty J., Ivanovich J., Heath S., Shannon W.D., Nagarajan R., Walter M.J., Link D.C., Graubert T.A., DiPersio J.F., Wilson R.K. Nature 456:66-72(2008) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT [LARGE SCALE ANALYSIS] LEU-141.
+	Additional computationally mapped references.

Web resources

Wikipedia

Urokinase entry

SeattleSNPs

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

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. Translation: CAI13969.1.
CH471083 Genomic DNA. Translation: EAW54544.1.
BC013575 mRNA. Translation: AAH13575.1.
D11143 mRNA. Translation: BAA01919.1.
K02286 Genomic DNA. Translation: AAA61252.1.

IPI

IPI00296180.
IPI00645018.

PIR

UKHU. A00931.

RefSeq

NP_001138503.1. NM_001145031.1.
NP_002649.1. NM_002658.3.

UniGene

Hs.77274.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1C5W	X-ray	1.94	A	156-178	[»]
			B	179-431	[»]
1C5X	X-ray	1.75	A	156-178	[»]
			B	179-431	[»]
1C5Y	X-ray	1.65	A	156-178	[»]
			B	179-431	[»]
1C5Z	X-ray	1.85	A	156-178	[»]
			B	179-431	[»]
1EJN	X-ray	1.80	A	179-431	[»]
1F5K	X-ray	1.80	U	179-431	[»]
1F5L	X-ray	2.10	A	179-431	[»]
1F92	X-ray	2.60	A	179-431	[»]
1FV9	X-ray	3.00	A	179-423	[»]
1GI7	X-ray	1.79	A	156-178	[»]
			B	179-423	[»]
1GI8	X-ray	1.75	A	156-178	[»]
			B	179-423	[»]
1GI9	X-ray	1.80	A	156-178	[»]
			B	179-423	[»]
1GJ7	X-ray	1.50	A	156-178	[»]
			B	179-431	[»]
1GJ8	X-ray	1.64	A	156-178	[»]
			B	179-431	[»]
1GJ9	X-ray	1.80	A	156-178	[»]
			B	179-431	[»]
1GJA	X-ray	1.56	A	156-178	[»]
			B	179-431	[»]
1GJB	X-ray	1.90	A	156-178	[»]
			B	179-431	[»]
1GJC	X-ray	1.73	A	156-178	[»]
			B	179-431	[»]
1GJD	X-ray	1.75	A	156-178	[»]
			B	179-431	[»]
1KDU	NMR	-	A	69-153	[»]
1LMW	X-ray	2.50	A/C	156-178	[»]
			B/D	179-431	[»]
1O3P	X-ray	1.81	A	156-178	[»]
			B	179-431	[»]
1O5A	X-ray	1.68	A	156-178	[»]
			B	179-431	[»]
1O5B	X-ray	1.85	A	156-178	[»]
			B	179-431	[»]
1O5C	X-ray	1.63	A	156-178	[»]
			B	179-431	[»]
1OWD	X-ray	2.32	A	179-423	[»]
1OWE	X-ray	1.60	A	179-423	[»]
1OWH	X-ray	1.61	A	179-423	[»]
1OWI	X-ray	2.93	A	179-423	[»]
1OWJ	X-ray	3.10	A	179-423	[»]
1OWK	X-ray	2.80	A	179-423	[»]
1SC8	X-ray	2.40	U	164-425	[»]
1SQA	X-ray	2.00	A	179-423	[»]
1SQO	X-ray	1.84	A	179-423	[»]
1SQT	X-ray	1.90	A	179-423	[»]
1U6Q	X-ray	2.02	A	179-423	[»]
1URK	NMR	-	A	26-155	[»]
1VJ9	X-ray	2.40	U	164-425	[»]
1VJA	X-ray	2.00	U	164-425	[»]
1W0Z	X-ray	1.90	U	179-425	[»]
1W10	X-ray	2.00	U	179-425	[»]
1W11	X-ray	2.00	U	179-425	[»]
1W12	X-ray	2.40	U	179-425	[»]
1W13	X-ray	2.00	U	179-425	[»]
1W14	X-ray	2.20	U	179-425	[»]
2FD6	X-ray	1.90	A	31-152	[»]
2I9A	X-ray	1.90	A/B/C/D	21-163	[»]
2I9B	X-ray	2.80	A/B/C/D	21-163	[»]
2NWN	X-ray	2.15	A	179-431	[»]
2O8T	X-ray	1.45	A	179-431	[»]
2O8U	X-ray	1.70	A	179-431	[»]
2O8W	X-ray	1.86	A	179-431	[»]
2R2W	X-ray	2.01	U	179-431	[»]
2VIN	X-ray	1.90	A	179-431	[»]
2VIO	X-ray	1.80	A	179-431	[»]
2VIP	X-ray	1.72	A	179-431	[»]
2VIQ	X-ray	2.00	A	179-431	[»]
2VIV	X-ray	1.72	A	179-431	[»]
2VIW	X-ray	2.05	A	179-431	[»]
2VNT	X-ray	2.20	A/B/C/D/E/F	156-428	[»]
3BT1	X-ray	2.80	A	21-153	[»]
3BT2	X-ray	2.50	A	21-153	[»]
3IG6	X-ray	1.83	A/C	156-178	[»]
			B/D	179-431	[»]
3KGP	X-ray	2.35	A	179-431	[»]
3KHV	X-ray	2.35	A	179-431	[»]
3KID	X-ray	2.71	U	179-431	[»]
3M61	X-ray	1.68	U	179-431	[»]
3MHW	X-ray	1.45	U	179-425	[»]
3MWI	X-ray	2.03	U	179-424	[»]
3OX7	X-ray	1.58	U	179-431	[»]
3OY5	X-ray	2.31	U	179-431	[»]
3OY6	X-ray	2.31	U	179-431	[»]
3PB1	X-ray	2.30	E	179-431	[»]
3QN7	X-ray	1.90	A	179-431	[»]
3U73	X-ray	3.19	A	21-152	[»]
4DVA	X-ray	1.94	U	179-424	[»]
4DW2	X-ray	2.97	U	179-424	[»]
4FU7	X-ray	2.00	A	179-424	[»]
4FU8	X-ray	2.20	A	179-424	[»]
4FU9	X-ray	1.60	A	179-424	[»]
4FUB	X-ray	1.90	A	179-424	[»]
4FUC	X-ray	1.72	A	179-424	[»]
4FUD	X-ray	2.00	A	179-424	[»]
4FUE	X-ray	2.00	A	179-424	[»]
4FUF	X-ray	2.00	A	179-424	[»]
4FUG	X-ray	1.80	A	179-424	[»]
4FUH	X-ray	1.60	A	179-424	[»]
4FUI	X-ray	2.00	A	179-424	[»]
4FUJ	X-ray	2.05	A	179-424	[»]

ProteinModelPortal

P00749.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-46387N.

IntAct

P00749. 3 interactions.

STRING

9606.ENSP00000361850.

Protein family/group databases

MEROPS

S01.231.

PTM databases

GlycoSuiteDB

P00749.

PhosphoSite

P00749.

Polymorphism databases

DMDM

254763341.

Proteomic databases

PaxDb

P00749.

PRIDE

P00749.

Protocols and materials databases

DNASU

5328.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000372764; ENSP00000361850; ENSG00000122861.
ENST00000496777; ENSP00000431795; ENSG00000122861.

GeneID

5328.

KEGG

hsa:5328.

UCSC

uc001jwa.3. human.
uc010qkw.2. human.

Organism-specific databases

CTD

5328.

GeneCards

GC10P075668.

HGNC

HGNC:9052. PLAU.

HPA

HPA008719.

MIM

191840. gene.
601709. phenotype.

neXtProt

NX_P00749.

Orphanet

220436. Quebec platelet disorder.

PharmGKB

PA33382.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG5640.

HOVERGEN

HBG008633.

InParanoid

P00749.

KO

K01348.

OrthoDB

EOG4229K6.

Enzyme and pathway databases

Pathway_Interaction_DB

amb2_neutrophils_pathway. amb2 Integrin signaling.
fgf_pathway. FGF signaling pathway.
avb3_opn_pathway. Osteopontin-mediated events.

Reactome

REACT_604. Hemostasis.

SABIO-RK

P00749.

Gene expression databases

ArrayExpress

P00749.

Bgee

P00749.

CleanEx

HS_PLAU.

Genevestigator

P00749.

GermOnline

ENSG00000122861. Homo sapiens.

Family and domain databases

Gene3D

2.40.20.10. 1 hit.

InterPro

IPR000742. EG-like_dom.
IPR013032. EGF-like_CS.
IPR000001. Kringle.
IPR013806. Kringle-like.
IPR018056. Kringle_CS.
IPR001254. Peptidase_S1.
IPR018114. Peptidase_S1_AS.
IPR001314. Peptidase_S1A.
IPR009003. Trypsin-like_Pept_dom.
[Graphical view]

Pfam

PF00051. Kringle. 1 hit.
PF00089. Trypsin. 1 hit.
[Graphical view]

PRINTS

PR00722. CHYMOTRYPSIN.

SMART

SM00181. EGF. 1 hit.
SM00130. KR. 1 hit.
SM00020. Tryp_SPc. 1 hit.
[Graphical view]

SUPFAM

SSF57440. Kringle-like. 1 hit.
SSF50494. Pept_Ser_Cys. 1 hit.

PROSITE

PS00022. EGF_1. 1 hit.
PS01186. EGF_2. False negative.
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.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

P00749.

ChEMBL

CHEMBL3286.

DrugBank

DB00594. Amiloride.
DB00013. Urokinase.

EvolutionaryTrace

P00749.

GenomeRNAi

5328.

NextBio

20628.

PMAP-CutDB

Q53XS3.

SOURCE

Search...

Entry information

Entry name

UROK_HUMAN

Accession

Primary (citable) accession number: P00749
Secondary accession number(s): B4DPZ2 , Q15844, Q16618, Q53XS3, Q5SWW9, Q969W6

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 21, 1986
Last sequence update:	July 28, 2009
Last modified:	May 1, 2013
This is version 179 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.