P06869 (UROK_MOUSE) 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

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	433 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 By similarity.
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 By similarity.
Subcellular location	Secreted.
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	Plasminogen activation
Cellular component	Secreted
Domain	EGF-like domain Kringle Signal
Molecular function	Hydrolase Protease Serine protease
PTM	Disulfide bond Phosphoprotein Zymogen
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	fibrinolysis Inferred from mutant phenotype PubMed 9733098. Source: MGI proteolysis Inferred from electronic annotation. Source: UniProtKB-KW regulation of cell adhesion mediated by integrin Inferred from electronic annotation. Source: Compara regulation of cell proliferation Inferred from genetic interaction PubMed 17893885. Source: MGI regulation of receptor activity Inferred from electronic annotation. Source: Compara regulation of smooth muscle cell migration Inferred from electronic annotation. Source: Compara regulation of smooth muscle cell-matrix adhesion Inferred from electronic annotation. Source: Compara response to hypoxia Inferred from mutant phenotype PubMed 17382917. Source: MGI smooth muscle cell migration Inferred from mutant phenotype PubMed 17382917. Source: MGI
Cellular_component	cell surface Inferred from electronic annotation. Source: Compara extracellular space Inferred from electronic annotation. Source: Compara
Molecular_function	serine-type endopeptidase activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 20

20

Potential

Chain

21 – 433

413

Urokinase-type plasminogen activator

PRO_0000028322

Chain

21 – 178

158

Urokinase-type plasminogen activator long chain A By similarity

PRO_0000028323

Chain

157 – 178

22

Urokinase-type plasminogen activator short chain A By similarity

PRO_0000028324

Chain

180 – 433

254

Urokinase-type plasminogen activator chain B By similarity

PRO_0000028325

Regions

Domain

28 – 64

37

EGF-like

Domain

71 – 152

82

Kringle

Domain

180 – 426

247

Peptidase S1

Region

35 – 58

24

Binds urokinase plasminogen activator surface receptor By similarity

Region

153 – 179

27

Connecting peptide

Sites

Active site

226

1

Charge relay system

Active site

277

1

Charge relay system

Active site

378

1

Charge relay system

Amino acid modifications

Modified residue

159

1

Phosphoserine By similarity

Disulfide bond

32 ↔ 40

Ref.3

Disulfide bond

34 ↔ 52

Ref.3

Disulfide bond

54 ↔ 63

Ref.3

Disulfide bond

71 ↔ 152

Ref.3

Disulfide bond

92 ↔ 134

Ref.3

Disulfide bond

123 ↔ 147

Ref.3

Disulfide bond

169 ↔ 301

Interchain (between A and B chains) By similarity

Disulfide bond

211 ↔ 227

By similarity

Disulfide bond

219 ↔ 290

By similarity

Disulfide bond

315 ↔ 384

By similarity

Disulfide bond

347 ↔ 363

By similarity

Disulfide bond

374 ↔ 402

By similarity

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

433

Helix Strand Turn

Details...

Beta strand

40 – 42

3

Helix

44 – 46

3

Beta strand

50 – 52

3

Turn

60 – 63

4

Beta strand

65 – 68

4

Helix

100 – 102

3

Beta strand

103 – 106

4

Turn

110 – 116

7

Beta strand

118 – 120

3

Beta strand

133 – 138

6

Beta strand

141 – 147

7

Sequences

	Sequence		Length	Mass (Da)
	P06869 [UniParc]. Last modified January 1, 1988. Version 1. Checksum: A99C35F6250443F9	FASTA	433	48,268
	10 20 30 40 50 60 MKVWLASLFL CALVVKNSEG GSVLGAPDES NCGCQNGGVC VSYKYFSRIR RCSCPRKFQG 70 80 90 100 110 120 EHCEIDASKT CYHGNGDSYR GKANTDTKGR PCLAWNAPAV LQKPYNAHRP DAISLGLGKH 130 140 150 160 170 180 NYCRNPDNQK RPWCYVQIGL RQFVQECMVH DCSLSKKPSS SVDQQGFQCG QKALRPRFKI 190 200 210 220 230 240 VGGEFTEVEN QPWFAAIYQK NKGGSPPSFK CGGSLISPCW VASAAHCFIQ LPKKENYVVY 250 260 270 280 290 300 LGQSKESSYN PGEMKFEVEQ LILHEYYRED SLAYHNDIAL LKIRTSTGQC AQPSRSIQTI 310 320 330 340 350 360 CLPPRFTDAP FGSDCEITGF GKESESDYLY PKNLKMSVVK LVSHEQCMQP HYYGSEINYK 370 380 390 400 410 420 MLCAADPEWK TDSCKGDSGG PLICNIEGRP TLSGIVSWGR GCAEKNKPGV YTRVSHFLDW 430 IQSHIGEEKG LAF

References

[1]	"Cloning, nucleotide sequencing and expression of cDNAs encoding mouse urokinase-type plasminogen activator." Belin D., Vassalli J.-D., Combepine C., Godeau F., Nagamine Y., Reich E., Kocher H.P., Duvoisin R.M. Eur. J. Biochem. 148:225-232(1985) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"The murine urokinase-type plasminogen activator gene." Degen S.J.F., Heckel J.L., Reich E., Degen J.L. Biochemistry 26:8270-8279(1987) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	"Structure-based engineering of species selectivity in the interaction between urokinase and its receptor: implication for preclinical cancer therapy." Lin L., Gardsvoll H., Huai Q., Huang M., Ploug M. J. Biol. Chem. 285:10982-10992(2010) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (3.2 ANGSTROMS) OF 21-154 IN COMPLEX WITH PLAUR, DISULFIDE BONDS.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

X02389 mRNA. Translation: CAA26231.1.
M17922 Genomic DNA. Translation: AAA40539.1.

IPI

IPI00129102.

PIR

UKMS. A29420.

RefSeq

NP_032899.1. NM_008873.3.

UniGene

Mm.4183.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3LAQ	X-ray	3.20	A/B	21-154	[»]

ProteinModelPortal

P06869.

SMR

P06869. Positions 28-152, 180-424.

ModBase

Search...

Protein-protein interaction databases

STRING

10090.ENSMUSP00000022368.

Protein family/group databases

MEROPS

S01.231.

PTM databases

PhosphoSite

P06869.

Proteomic databases

PaxDb

P06869.

PRIDE

P06869.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENSMUST00000022368; ENSMUSP00000022368; ENSMUSG00000021822.

GeneID

18792.

KEGG

mmu:18792.

Organism-specific databases

CTD

5328.

MGI

MGI:97611. Plau.

Phylogenomic databases

eggNOG

COG5640.

HOGENOM

HOG000237314.

HOVERGEN

HBG008633.

InParanoid

P06869.

KO

K01348.

OMA

CQQPHYY.

OrthoDB

EOG4229K6.

Gene expression databases

ArrayExpress

P06869.

Bgee

P06869.

CleanEx

MM_PLAU.

Genevestigator

P06869.

GermOnline

ENSMUSG00000021822. Mus musculus.

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. False negative.
PS00135. TRYPSIN_SER. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

ChEMBL

CHEMBL1075311.

EvolutionaryTrace

P06869.

NextBio

295072.

SOURCE

Search...

Entry information

Entry name

UROK_MOUSE

Accession

Primary (citable) accession number: P06869

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 1, 1988
Last sequence update:	January 1, 1988
Last modified:	April 3, 2013
This is version 132 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program