Tissue-type plasminogen activator precursor

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Reviewed, UniProtKB/Swiss-Prot P19637 (TPA_RAT)

Last modified June 16, 2009. Version 89. History...

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Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

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Names and origin

Protein names

Recommended name:
    Tissue-type plasminogen activator
      Short name=t-plasminogen activator
      Short name=t-PA
      Short name=tPA
    EC=3.4.21.68
Cleaved into the following 2 chains:
    1- Recommended name:
            Tissue-type plasminogen activator chain A
    2- Recommended name:
            Tissue-type plasminogen activator chain B

Gene names

Name:

Plat

Organism

Rattus norvegicus (Rat)

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

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

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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.

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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.
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 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.

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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
Gene Ontology (GO)
Biological process	blood vessel morphogenesis Inferred from expression pattern. Source: RGD regulation of synaptic plasticity Inferred from expression pattern. Source: RGD synaptic transmission, glutamatergic Inferred from mutant phenotype. Source: RGD
Cellular component	extracellular space Inferred from electronic annotation. Source: UniProtKB-SubCell synapse Inferred from direct assay. Source: RGD
Molecular function	serine-type endopeptidase activity Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

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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

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Sequences

Sequence

Length

Mass (Da)

Tools

P19637-1 [UniParc].

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

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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: 3148445] [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: 2105315] [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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Pituitary.

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Cross-references

Sequence databases
	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.
UniGene	Rn.107102
3D structure databases
HSSP	HSSP built from PDB template 1RTF based on UniProtKB P00750.
SMR	P19637. Positions 33-123, 212-296, 296-558.
ModBase	Search...
Protein family/group databases
MEROPS	S01.232.
Genome annotation databases
Ensembl	ENSRNOG00000019018. Rattus norvegicus. [Contig view]
GeneID	25692.
KEGG	rno:25692.
Organism-specific databases
RGD	3342. Plat.
Phylogenomic databases
HOVERGEN	P19637.
OMA	P19637. TCGLRQY.
Enzyme and pathway databases
BRENDA	3.4.21.68. 248.
Gene expression databases
ArrayExpress	P19637.
GermOnline	ENSRNOG00000019018. Rattus norvegicus.
Family and domain databases
InterPro	IPR016060. Complement_control_module. IPR006209. EGF. IPR006210. EGF-like. IPR013032. EGF-like_reg_CS. IPR000742. EGF_3. IPR000083. Fibrnctn1. IPR000001. Kringle. IPR018056. Kringle_CS. IPR018059. Kringle_sub. IPR018114. Peptidase_S1/S6_AS. IPR001254. Peptidase_S1_S6. IPR001314. Peptidase_S1A. [Graphical view]
Gene3D	G3DSA:2.10.70.10. Complement_control_module. 1 hit. G3DSA:2.40.20.10. Kringle. 2 hits.
Pfam	PF00008. EGF. 1 hit. PF00039. fn1. 1 hit. PF00051. Kringle. 2 hits. PF00089. Trypsin. 1 hit. [Graphical view]
PRINTS	PR00722. CHYMOTRYPSIN. PR00018. KRINGLE.
ProDom	PD000395. Kringle. 2 hits. [Graphical view] [Entries sharing at least one domain]
SMART	SM00181. EGF. 1 hit. SM00058. FN1. 1 hit. SM00130. KR. 2 hits. SM00020. Tryp_SPc. 1 hit. [Graphical view]
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 Resources
NextBio	607693.

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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:	June 16, 2009
This is version 89 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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Relevant documents

Peptidase families

Classification of peptidase families and list of entries

SIMILARITY comments

Index of protein domains and families

Names and origin

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 family/group databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Gene expression databases

Family and domain databases

Other Resources

Entry information

Relevant documents