P29598 (UROK_RAT) 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

Rattus norvegicus (Rat) [Reference proteome]

Taxonomic identifier

10116 [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 › Rattus

Protein attributes

Sequence length	432 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 By similarity.
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	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	angiogenesis Inferred from mutant phenotype PubMed 15854129. Source: RGD cellular response to fluid shear stress Inferred from expression pattern PubMed 19166201. Source: RGD cellular response to glucose stimulus Inferred from expression pattern PubMed 17953365. Source: RGD cellular response to hepatocyte growth factor stimulus Inferred from expression pattern PubMed 19834131. Source: RGD cellular response to hypoxia Inferred from expression pattern PubMed 19490965. Source: RGD cellular response to lipopolysaccharide Inferred from expression pattern PubMed 19184369. Source: RGD cellular response to staurosporine Inferred from expression pattern PubMed 19137075. Source: RGD embryo implantation Inferred from expression pattern PubMed 15019809. Source: RGD neuron death Inferred from mutant phenotype PubMed 17939964. Source: RGD positive regulation of cell proliferation Inferred from mutant phenotype PubMed 16899994. Source: RGD positive regulation of ovulation Inferred from mutant phenotype PubMed 10727258. Source: RGD positive regulation of reactive oxygen species metabolic process Inferred from direct assay PubMed 16456094. Source: RGD positive regulation of smooth muscle cell migration Inferred from mutant phenotype PubMed 9315743. Source: RGD proteolysis Inferred from electronic annotation. Source: UniProtKB-KW regulation of hepatocyte proliferation Inferred from mutant phenotype PubMed 17587687. Source: RGD response to activity Inferred from expression pattern PubMed 22592543. Source: RGD response to hyperoxia Inferred from expression pattern PubMed 19099788. Source: RGD skeletal muscle tissue regeneration Inferred from mutant phenotype PubMed 12919869. Source: RGD spermatogenesis Inferred from expression pattern PubMed 17712486. Source: RGD
Cellular_component	extracellular space Inferred from direct assay PubMed 10727258. Source: RGD membrane Inferred from direct assay PubMed 17939964. Source: RGD
Molecular_function	peptidase activity Inferred from direct assay PubMed 2509088. Source: RGD 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 – 19	19	Potential
	Chain	20 – 432	413	Urokinase-type plasminogen activator		PRO_0000028333
	Chain	20 – 177	158	Urokinase-type plasminogen activator long chain A By similarity		PRO_0000028334
	Chain	156 – 177	22	Urokinase-type plasminogen activator short chain A By similarity		PRO_0000028335
	Chain	179 – 432	254	Urokinase-type plasminogen activator chain B By similarity		PRO_0000028336
Regions
	Domain	27 – 63	37	EGF-like
	Domain	70 – 151	82	Kringle
	Domain	179 – 425	247	Peptidase S1
	Region	34 – 57	24	Binds urokinase plasminogen activator surface receptor
	Region	152 – 178	27	Connecting peptide
Sites
	Active site	225	1	Charge relay system
	Active site	276	1	Charge relay system
	Active site	377	1	Charge relay system
Amino acid modifications
	Modified residue	158	1	Phosphoserine By similarity
	Disulfide bond	31 ↔ 39		By similarity
	Disulfide bond	33 ↔ 51		By similarity
	Disulfide bond	53 ↔ 62		By similarity
	Disulfide bond	70 ↔ 151		By similarity
	Disulfide bond	91 ↔ 133		By similarity
	Disulfide bond	122 ↔ 146		By similarity
	Disulfide bond	168 ↔ 300		Interchain (between A and B chains) By similarity
	Disulfide bond	210 ↔ 226		By similarity
	Disulfide bond	218 ↔ 289		By similarity
	Disulfide bond	314 ↔ 383		By similarity
	Disulfide bond	346 ↔ 362		By similarity
	Disulfide bond	373 ↔ 401		By similarity
Experimental info
	Sequence conflict	16	1	N → H in CAA46601. Ref.2
	Sequence conflict	24	1	E → G in CAA46601. Ref.2
	Sequence conflict	332	1	D → N in CAA46601. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	P29598 [UniParc]. Last modified April 1, 1993. Version 1. Checksum: 4EB1B96C716244C8	FASTA	432	47,957
	10 20 30 40 50 60 MRVWLASLFL CALVANSEGG SELEASDESN CGCQNGGVCV SYKYFSSIRR CSCPKKFKGE 70 80 90 100 110 120 HCEIDTSKTC YHGNGQSYRG KANTDTKGRP CLAWNSPAVL QQTYNAHRSD ALSLGLGKHN 130 140 150 160 170 180 YCRNPDNQRR PWCYVQIGLK QFVQECMVQD CSLSKKPSST VDQQGFQCGQ KALRPRFKIV 190 200 210 220 230 240 GGEFTVVENQ PWFAAIYLKN KGGSPPSFKC GGSLISPCWV ASATHCFVNQ PKKEEYVVYL 250 260 270 280 290 300 GQSKRNSYNP GEMKFEVEQL ILHEDFSDET LAFHNDIALL KIRTSTGQCA QPSRTIQTIC 310 320 330 340 350 360 LPPRFGDAPF GSDCEITGFG QESATDYFYP KDLKMSVVKI ISHEQCKQPH YYGSEINYKM 370 380 390 400 410 420 LCAADPEWKT DSCSGDSGGP LICNIDGRPT LSGIVSWGSG CAEKNKPGVY TRVSYFLNWI 430 QSHIGEENGL AF

References

[1]	"Transcriptional and posttranscriptional activation of urokinase plasminogen activator gene expression in metastatic tumor cells." Henderson B.R., Tansey W.P., Phillips S.M., Ramshaw I.A., Kefford R.F. Cancer Res. 52:2489-2496(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Strain: Fischer 344.
[2]	Rabbani S.A. Submitted (APR-1992) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Kidney.
[3]	"The receptor for the plasminogen activator of urokinase type is up-regulated in transformed rat thyroid cells." Ragno P., Cassano S., Degen J., Kessler C., Blasi F., Rossi G. FEBS Lett. 306:193-198(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 31-62, IDENTIFICATION OF UROKINASE PLASMINOGEN ACTIVATOR SURFACE RECEPTOR BINDING DOMAIN.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	X63434 mRNA. Translation: CAA45028.1. X65651 mRNA. Translation: CAA46601.1. X66907 Genomic DNA. Translation: CAA47356.1.
IPI	IPI00205838.
PIR	S18932. S24604.
UniGene	Rn.6064.
3D structure databases
ProteinModelPortal	P29598.
SMR	P29598. Positions 29-155, 166-427.
ModBase	Search...
Protein family/group databases
MEROPS	S01.231.
PTM databases
PhosphoSite	P29598.
Proteomic databases
PaxDb	P29598.
PRIDE	P29598.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
UCSC	RGD:3343. rat.
Organism-specific databases
RGD	3343. Plau.
Phylogenomic databases
eggNOG	COG5640.
HOGENOM	HOG000237314.
HOVERGEN	HBG008633.
InParanoid	P29598.
OrthoDB	EOG4229K6.
Gene expression databases
ArrayExpress	P29598.
Genevestigator	P29598.
GermOnline	ENSRNOG00000010516. Rattus norvegicus.
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	CHEMBL1075245.

Entry information

Entry name

UROK_RAT

Accession

Primary (citable) accession number: P29598
Secondary accession number(s): Q6LBK5

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 1, 1993
Last sequence update:	April 1, 1993
Last modified:	May 1, 2013
This is version 120 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program