Tissue-type plasminogen activator precursor

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Q28198 (TPA_BOVIN) Reviewed, UniProtKB/Swiss-Prot

Last modified December 14, 2011. Version 99. 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

Bos taurus (Bovine)

Taxonomic identifier

9913 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Laurasiatheria › Cetartiodactyla › Ruminantia › Pecora › Bovidae › Bovinae › Bos

Protein attributes

Sequence length	566 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-314 catalyzed by plasmin, tissue kallikrein or factor Xa.
Miscellaneous	Binds to the kringle structure of the fibrin A chain. Binding to fibrin enhances its catalytic activity.
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	proteolysis Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	extracellular space Inferred from electronic annotation. Source: UniProtKB-SubCell
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 21

By similarity

Propeptide

22 – 33

By similarity

PRO_0000028344

Propeptide

34 – 36

Removed by plasmin By similarity

PRO_0000285905

Chain

37 – 566

530

Tissue-type plasminogen activator

PRO_0000028345

Chain

37 – 314

278

Tissue-type plasminogen activator chain A

PRO_0000028346

Chain

315 – 566

252

Tissue-type plasminogen activator chain B

PRO_0000028347

Regions

Domain

40 – 82

Fibronectin type-I

Domain

83 – 121

EGF-like

Domain

128 – 209

Kringle 1

Domain

219 – 300

Kringle 2

Domain

315 – 565

251

Peptidase S1

Region

43 – 53

Important for binding to annexin A2 By similarity

Sites

Active site

361

Charge relay system

Active site

410

Charge relay system

Active site

517

Charge relay system

Site

103

Important for binding to LRP1 By similarity

Site

468

Important for single-chain activity By similarity

Site

516

Important for single-chain activity By similarity

Amino acid modifications

Glycosylation

153

N-linked (GlcNAc...) Potential

Glycosylation

487

N-linked (GlcNAc...) Potential

Disulfide bond

42 ↔ 72

By similarity

Disulfide bond

70 ↔ 79

By similarity

Disulfide bond

87 ↔ 98

By similarity

Disulfide bond

92 ↔ 109

By similarity

Disulfide bond

111 ↔ 120

By similarity

Disulfide bond

128 ↔ 209

By similarity

Disulfide bond

149 ↔ 191

By similarity

Disulfide bond

180 ↔ 204

By similarity

Disulfide bond

219 ↔ 300

By similarity

Disulfide bond

240 ↔ 282

By similarity

Disulfide bond

271 ↔ 295

By similarity

Disulfide bond

303 ↔ 434

Interchain (between A and B chains) By similarity

Disulfide bond

346 ↔ 362

By similarity

Disulfide bond

354 ↔ 423

By similarity

Disulfide bond

448 ↔ 523

By similarity

Disulfide bond

480 ↔ 496

By similarity

Disulfide bond

513 ↔ 541

By similarity

Experimental info

Sequence conflict

370

H → L in AAI05349. Ref.2

Sequences

Sequence

Length

Mass (Da)

Tools

Q28198 [UniParc].

Last modified November 1, 1997. Version 1.
Checksum: 2EB6BEB4E32276C3
Show »

FASTA

566

63,701

        10         20         30         40         50         60 
MMSAMKTEFL CVLLLCGAVF TSPSQETYRR LRRGARSYKV TCRDGKTQMT YRQHDSWLRP 

        70         80         90        100        110        120 
LLRGNQVEHC WCDGGRAQCH SVPVRSCSEP WCFNGGTCRQ ALYSSDFVCQ CPEGFMGKLC 

       130        140        150        160        170        180 
EIDATATCYK DQGVAYRGTW STAESGAECA NWNSSGLAMK PYSGRRPNAI RLGLGNHNYC 

       190        200        210        220        230        240 
RNPDQDSKPW CYVFKAGKYI SEFCSTPACA KVAEEDGDCY TGNGLAYRGT RSHTKSGASC 

       250        260        270        280        290        300 
LPWNSVFLTS KIYTAWKSNA PALGLGKHNH CRNPDGDAQP WCHVWKDRQL TWEYCDVPQC 

       310        320        330        340        350        360 
VTCGLRQYKR PQFRIKGGLF ADITSHPWQA AIFVKNRRSP GERFLCGGIL ISSCWVLSAA 

       370        380        390        400        410        420 
HCFQERYPPH HLKVFLGRTY RLVPGEEEQT FEVEKYIIHK EFDDDTYDND IALLHLKSDS 

       430        440        450        460        470        480 
LTCARESASV RTICLPDASL QLPDWTECEL SGYGKHESSS PFFSERLKEA HVRLYPSSRC 

       490        500        510        520        530        540 
TSQHLFNRTV TNNMLCAGDT RSGGDHTNLH DACQGDSGGP LVCMKDNHMT LVGIISWGLG 

       550        560 
CGRKDVPGVY TKVTNYLDWI RDNTRP

« Hide

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning and characterization of the bovine plasminogen activators uPA and tPA." Ravn P., Berglund L., Petersen T.E. Int. Dairy J. 5:605-617(1995) [Agricola: IND20546782] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Kidney.
[2]	NIH - Mammalian Gene Collection (MGC) project Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: Crossbred X Angus. Tissue: Ileum.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	X85800 mRNA. Translation: CAA59795.1. BC105348 mRNA. Translation: AAI05349.1.
IPI	IPI00694104.
RefSeq	NP_776571.2. NM_174146.3.
UniGene	Bt.12302.
3D structure databases
ProteinModelPortal	Q28198.
SMR	Q28198. Positions 37-127, 213-566.
ModBase	Search...
Protein-protein interaction databases
STRING	Q28198.
Protein family/group databases
MEROPS	S01.232.
Proteomic databases
PRIDE	Q28198.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSBTAT00000001642; ENSBTAP00000001642; ENSBTAG00000001244.
GeneID	281407.
KEGG	bta:281407.
Organism-specific databases
CTD	5327.
Phylogenomic databases
eggNOG	maNOG04276.
HOVERGEN	HBG008633.
InParanoid	Q28198.
OMA	TCGLRQY.
OrthoDB	EOG4BVRTC.
Family and domain databases
InterPro	IPR016060. Complement_control_module. IPR006209. EGF. IPR006210. EGF-like. IPR013032. EGF-like_reg_CS. IPR000742. EGF_3. IPR000083. Fibronectin_type1. IPR000001. Kringle. IPR013806. Kringle-like. IPR018056. Kringle_CS. IPR009003. Pept_cys/ser_Trypsin-like. 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.
KO	K01343.
Pfam	PF00008. EGF. 1 hit. PF00039. fn1. 1 hit. PF00051. Kringle. 2 hits. PF00089. Trypsin. 1 hit. [Graphical view]
PRINTS	PR00722. CHYMOTRYPSIN. PR00018. KRINGLE.
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. 1 hit. PS50070. KRINGLE_2. 2 hits. PS50240. TRYPSIN_DOM. 1 hit. PS00134. TRYPSIN_HIS. 1 hit. PS00135. TRYPSIN_SER. 1 hit. [Graphical view]
ProtoNet	Search...

Entry information

Entry name

TPA_BOVIN

Accession

Primary (citable) accession number: Q28198
Secondary accession number(s): Q2KJG9

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	November 1, 1997
Last modified:	December 14, 2011
This is version 99 of the entry and version 1 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

Family and domain databases

Entry information

Relevant documents