Tissue-type plasminogen activator precursor

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P19637 (TPA_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified April 3, 2013. Version 123. History...

Clusters with 100%, 90%, 50% identity |

Documents (2) |

Third-party data

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Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents Customize order

Names and origin

Protein names

Recommended name:
Tissue-type plasminogen activator
Short name=t-PA
Short name=t-plasminogen activator
Short name=tPA
EC=3.4.21.68

Cleaved into the following 2 chains:

Tissue-type plasminogen activator chain A
Tissue-type plasminogen activator chain B

Gene names

Name:

Plat

Organism

Rattus norvegicus (Rat) [Reference proteome]

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	559 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at transcript level

General annotation (Comments)

Function	Converts the abundant, but inactive, zymogen plasminogen to plasmin by hydrolyzing a single Arg-Val bond in plasminogen. By controlling plasmin-mediated proteolysis, it plays an important role in tissue remodeling and degradation, in cell migration and many other physiopathological events.
Catalytic activity	Specific cleavage of Arg-\|-Val bond in plasminogen to form plasmin.
Enzyme regulation	Inhibited by SERPINA5 By similarity.
Subunit structure	Heterodimer of chain A and chain B held by a disulfide bond. Binds to fibrin with high affinity. This interaction leads to an increase in the catalytic efficiency of the enzyme due to an increase in affinity for plasminogen. Similarly, binding to heparin increases the activation of plasminogen. Binds to annexin A2, cytokeratin-8, fibronectin and laminin. Binds to mannose receptor and the low-density lipoprotein receptor-related protein (LRP1); these proteins are involved in TPA clearance. Binds LRP1B; binding is followed by internalization and degradation. Forms heterodimer with SERPINA5 By similarity.
Subcellular location	Secreted › extracellular space.
Domain	Both FN1 and one of the kringle domains are required for binding to fibrin By similarity. Both FN1 and EGF-like domains are important for binding to LRP1 By similarity. The FN1 domain mediates binding to annexin A2 By similarity. The second kringle domain is implicated in binding to cytokeratin-8 and to the endothelial cell surface binding site By similarity.
Post-translational modification	The single chain, almost fully active enzyme, can be further processed into a two-chain fully active form by a cleavage after Arg-308 catalyzed by plasmin, tissue kallikrein or factor Xa.
Sequence similarities	Belongs to the peptidase S1 family. Contains 1 EGF-like domain. Contains 1 fibronectin type-I domain. Contains 2 kringle domains. Contains 1 peptidase S1 domain.

Ontologies

Keywords
Biological process	Plasminogen activation
Cellular component	Secreted
Domain	EGF-like domain Kringle Repeat Signal
Molecular function	Hydrolase Protease Serine protease
PTM	Cleavage on pair of basic residues Disulfide bond Glycoprotein Zymogen
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	negative regulation of proteolysis Inferred from electronic annotation. Source: Compara plasminogen activation Inferred from electronic annotation. Source: Compara platelet-derived growth factor receptor signaling pathway Inferred from electronic annotation. Source: Compara positive regulation of ovulation Inferred from mutant phenotype PubMed 10727258. Source: RGD proteolysis Inferred from electronic annotation. Source: UniProtKB-KW regulation of synaptic plasticity Inferred from expression pattern PubMed 12070304. Source: RGD response to cAMP Inferred from expression pattern PubMed 3017447. Source: RGD response to glucocorticoid stimulus Inferred from expression pattern PubMed 3137452. Source: RGD response to hypoxia Inferred from electronic annotation. Source: Compara response to peptide hormone stimulus Inferred from expression pattern PubMed 3102470. Source: RGD smooth muscle cell migration Inferred from electronic annotation. Source: Compara synaptic transmission, glutamatergic Inferred from mutant phenotype PubMed 15496678. Source: RGD wound healing Inferred from expression pattern PubMed 12524078. Source: RGD
Cellular_component	apical part of cell Inferred from electronic annotation. Source: Compara cell surface Inferred from electronic annotation. Source: Compara cytoplasm Inferred from direct assay PubMed 3891762. Source: RGD extracellular space Inferred from direct assay PubMed 10727258 PubMed 3102470. Source: RGD secretory granule Inferred from electronic annotation. Source: Compara synapse Inferred from direct assay PubMed 15496678. Source: RGD
Molecular_function	serine-type endopeptidase activity Inferred from electronic annotation. Source: Compara
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 17

Potential

Propeptide

18 – 29

By similarity

PRO_0000028357

Propeptide

30 – 32

Removed by plasmin

PRO_0000285917

Chain

33 – 559

527

Tissue-type plasminogen activator By similarity

PRO_0000028358

Chain

33 – 308

276

Tissue-type plasminogen activator chain A

PRO_0000028359

Chain

309 – 559

251

Tissue-type plasminogen activator chain B

PRO_0000028360

Regions

Domain

36 – 78

Fibronectin type-I

Domain

79 – 117

EGF-like

Domain

124 – 205

Kringle 1

Domain

213 – 294

Kringle 2

Domain

309 – 558

250

Peptidase S1

Region

39 – 49

Important for binding to annexin A2 By similarity

Sites

Active site

355

Charge relay system

Active site

404

Charge relay system

Active site

510

Charge relay system

Site

Important for binding to LRP1 By similarity

Site

462

Important for single-chain activity By similarity

Site

509

Important for single-chain activity By similarity

Amino acid modifications

Glycosylation

149

N-linked (GlcNAc...) Potential

Glycosylation

481

N-linked (GlcNAc...) Potential

Disulfide bond

38 ↔ 68

By similarity

Disulfide bond

66 ↔ 75

By similarity

Disulfide bond

83 ↔ 94

By similarity

Disulfide bond

88 ↔ 105

By similarity

Disulfide bond

107 ↔ 116

By similarity

Disulfide bond

124 ↔ 205

By similarity

Disulfide bond

145 ↔ 187

By similarity

Disulfide bond

176 ↔ 200

By similarity

Disulfide bond

213 ↔ 294

By similarity

Disulfide bond

234 ↔ 276

By similarity

Disulfide bond

265 ↔ 289

By similarity

Disulfide bond

297 ↔ 428

Interchain (between A and B chains) By similarity

Disulfide bond

340 ↔ 356

By similarity

Disulfide bond

348 ↔ 417

By similarity

Disulfide bond

442 ↔ 516

By similarity

Disulfide bond

474 ↔ 490

By similarity

Disulfide bond

506 ↔ 534

By similarity

Experimental info

Sequence conflict

380

E → K in AAA41812. Ref.1

Sequences

Sequence

Length

Mass (Da)

Tools

P19637 [UniParc].

Last modified November 1, 1991. Version 2.
Checksum: 7DBD3809C1D1C921
Show »

FASTA

559

62,903

        10         20         30         40         50         60 
MKGELLCVLL LCGVAFTLPD QGIHRRFRRG ARSYRATCRD EQTQTTYQQH QSWLRPMLRG 

        70         80         90        100        110        120 
NRVEYCRCNS GLAQCHSVPV RSCSEPRCFN GGTCQQALYF SDFVCQCPDG FVGKRCDIDT 

       130        140        150        160        170        180 
RATCFEGQGI TYRGTWSTAE NGAECINWNS SALSQKPYSA RRPNAIKLGL GNHNYCRNPD 

       190        200        210        220        230        240 
RDVKPWCYVF KAGKYTTEFC STPACPKGPT EDCYVGKGVT YRGTHSFTTS KASCLPWNSM 

       250        260        270        280        290        300 
ILIGKTYTAW RANSQALGLG RHNYCRNPDG DAKPWCHVMK DRKLTWEYCD MSPCSTCGLR 

       310        320        330        340        350        360 
QYKQPQFRIK GGLFTDITSH PWQAAIFVKN KRSPGERFLC GGVLISSCWV LSAAHCFVER 

       370        380        390        400        410        420 
FPPHHLKVVL GRTYRVVPGE EEQTFEIEKY IVHKEFDDDT YDNDIALLQL RSDSSQCAQE 

       430        440        450        460        470        480 
SSSVGTACLP DPDVQLPDWT ECELSGYGKH EASSPFFSDR LKEAHVRLYP SSRCTSQHLF 

       490        500        510        520        530        540 
NKTITSNMLC AGDTRTGGNQ DVHDACQGDS GGPLVCMIDK RMTLLGIISW GLGCGQKDVP 

       550 
GIYTKVTNYL NWIQDNMKQ

« Hide

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning and characterization of a cDNA for rat tissue-type plasminogen activator." Ny T., Leonardsson G., Hsueh A.J.W. DNA 7:671-677(1988) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"The structure of the TATA-less rat tissue-type plasminogen activator gene. Species-specific sequence divergences in the promoter predict differences in regulation of gene expression." Feng P., Ohlsson M., Ny T. J. Biol. Chem. 265:2022-2027(1990) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	"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]. Tissue: Pituitary.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	M23697 mRNA. Translation: AAA41812.1. M31197 M31196 Genomic DNA. Translation: AAA42261.1. BC061565 mRNA. Translation: AAH61565.1.
IPI	IPI00332012.
PIR	A35029.
RefSeq	NP_037283.2. NM_013151.2.
UniGene	Rn.107102.
3D structure databases
ProteinModelPortal	P19637.
SMR	P19637. Positions 33-123, 212-558.
ModBase	Search...
Protein-protein interaction databases
MINT	MINT-7138910.
STRING	10116.ENSRNOP00000025764.
Protein family/group databases
MEROPS	S01.232.
Proteomic databases
PRIDE	P19637.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSRNOT00000025763; ENSRNOP00000025764; ENSRNOG00000019018.
GeneID	25692.
KEGG	rno:25692.
UCSC	RGD:3342. rat.
Organism-specific databases
CTD	5327.
RGD	3342. Plat.
Phylogenomic databases
eggNOG	COG5640.
GeneTree	ENSGT00570000078945.
HOGENOM	HOG000237314.
HOVERGEN	HBG008633.
InParanoid	P19637.
KO	K01343.
OMA	AHVRLYP.
OrthoDB	EOG4BVRTC.
Enzyme and pathway databases
BRENDA	3.4.21.68. 5301.
Gene expression databases
Genevestigator	P19637.
GermOnline	ENSRNOG00000019018. Rattus norvegicus.
Family and domain databases
Gene3D	2.40.20.10. 2 hits.
InterPro	IPR000742. EG-like_dom. IPR013032. EGF-like_CS. IPR000083. Fibronectin_type1. IPR000001. Kringle. IPR013806. Kringle-like. IPR018056. Kringle_CS. IPR001254. Peptidase_S1. IPR018114. Peptidase_S1_AS. IPR001314. Peptidase_S1A. IPR026280. Tissue_plasm_act. IPR009003. Trypsin-like_Pept_dom. [Graphical view]
Pfam	PF00008. EGF. 1 hit. PF00039. fn1. 1 hit. PF00051. Kringle. 2 hits. PF00089. Trypsin. 1 hit. [Graphical view]
PIRSF	PIRSF001145. Tissue_plasm_act. 1 hit.
PRINTS	PR00722. CHYMOTRYPSIN.
SMART	SM00181. EGF. 1 hit. SM00058. FN1. 1 hit. SM00130. KR. 2 hits. SM00020. Tryp_SPc. 1 hit. [Graphical view]
SUPFAM	SSF57440. Kringle-like. 2 hits. SSF50494. Pept_Ser_Cys. 1 hit.
PROSITE	PS00022. EGF_1. 1 hit. PS01186. EGF_2. 1 hit. PS50026. EGF_3. 1 hit. PS01253. FN1_1. 1 hit. PS51091. FN1_2. 1 hit. PS00021. KRINGLE_1. 2 hits. PS50070. KRINGLE_2. 2 hits. PS50240. TRYPSIN_DOM. 1 hit. PS00134. TRYPSIN_HIS. 1 hit. PS00135. TRYPSIN_SER. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	607693.

Entry information

Entry name

TPA_RAT

Accession

Primary (citable) accession number: P19637

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1991
Last sequence update:	November 1, 1991
Last modified:	April 3, 2013
This is version 123 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Relevant documents

Peptidase families

Classification of peptidase families and list of entries

SIMILARITY comments

Index of protein domains and families

Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents

Preferred order of sections

Names and origin

Cleaved into the following 2 chains:

Protein attributes

General annotation (Comments)

Ontologies

Sequence annotation (Features)

Molecule processing

Regions

Sites

Amino acid modifications

Experimental info

Sequences

References

Cross-references

Sequence databases

3D structure databases

Protein-protein interaction databases

Protein family/group databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Gene expression databases

Family and domain databases

Other

Entry information

Relevant documents