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Protein

Tissue-type plasminogen activator

Gene

PLAT

Organism
Bos taurus (Bovine)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript leveli

Functioni

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 activityi

Specific cleavage of Arg-|-Val bond in plasminogen to form plasmin.

Enzyme regulationi

Inhibited by SERPINA5.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei103Important for binding to LRP1By similarity1
Active sitei361Charge relay system1
Active sitei410Charge relay system1
Sitei468Important for single-chain activityBy similarity1
Sitei516Important for single-chain activityBy similarity1
Active sitei517Charge relay system1

GO - Molecular functioni

  • phosphoprotein binding Source: AgBase
  • serine-type endopeptidase activity Source: AgBase
  • serpin family protein binding Source: AgBase

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Protease, Serine protease

Keywords - Biological processi

Plasminogen activation

Enzyme and pathway databases

ReactomeiR-BTA-186797. Signaling by PDGF.
R-BTA-75205. Dissolution of Fibrin Clot.

Protein family/group databases

MEROPSiS01.232.

Names & Taxonomyi

Protein namesi
Recommended name:
Tissue-type plasminogen activator (EC:3.4.21.68)
Short name:
t-PA
Short name:
t-plasminogen activator
Short name:
tPA
Cleaved into the following 2 chains:
Gene namesi
Name:PLAT
OrganismiBos taurus (Bovine)
Taxonomic identifieri9913 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaRuminantiaPecoraBovidaeBovinaeBos
Proteomesi
  • UP000009136 Componenti: Chromosome 27

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Secreted

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 21By similarityAdd BLAST21
PropeptideiPRO_000002834422 – 33By similarityAdd BLAST12
PropeptideiPRO_000028590534 – 36Removed by plasminBy similarity3
ChainiPRO_000002834537 – 566Tissue-type plasminogen activatorAdd BLAST530
ChainiPRO_000002834637 – 314Tissue-type plasminogen activator chain AAdd BLAST278
ChainiPRO_0000028347315 – 566Tissue-type plasminogen activator chain BAdd BLAST252

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi42 ↔ 72By similarity
Disulfide bondi70 ↔ 79By similarity
Disulfide bondi87 ↔ 98By similarity
Disulfide bondi92 ↔ 109By similarity
Disulfide bondi111 ↔ 120By similarity
Disulfide bondi128 ↔ 209By similarity
Disulfide bondi149 ↔ 191By similarity
Glycosylationi153N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi180 ↔ 204By similarity
Disulfide bondi219 ↔ 300By similarity
Disulfide bondi240 ↔ 282By similarity
Disulfide bondi271 ↔ 295By similarity
Disulfide bondi303 ↔ 434Interchain (between A and B chains)PROSITE-ProRule annotation
Disulfide bondi346 ↔ 362By similarity
Disulfide bondi354 ↔ 423By similarity
Disulfide bondi448 ↔ 523By similarity
Disulfide bondi480 ↔ 496By similarity
Glycosylationi487N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi513 ↔ 541By similarity

Post-translational modificationi

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.

Keywords - PTMi

Cleavage on pair of basic residues, Disulfide bond, Glycoprotein, Zymogen

Proteomic databases

PaxDbiQ28198.
PRIDEiQ28198.

Expressioni

Gene expression databases

BgeeiENSBTAG00000001244.

Interactioni

Subunit structurei

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).By similarity

GO - Molecular functioni

  • phosphoprotein binding Source: AgBase
  • serpin family protein binding Source: AgBase

Protein-protein interaction databases

STRINGi9913.ENSBTAP00000001642.

Structurei

3D structure databases

ProteinModelPortaliQ28198.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini40 – 82Fibronectin type-IPROSITE-ProRule annotationAdd BLAST43
Domaini83 – 121EGF-likePROSITE-ProRule annotationAdd BLAST39
Domaini128 – 209Kringle 1PROSITE-ProRule annotationAdd BLAST82
Domaini219 – 300Kringle 2PROSITE-ProRule annotationAdd BLAST82
Domaini315 – 565Peptidase S1PROSITE-ProRule annotationAdd BLAST251

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni43 – 53Important for binding to annexin A2By similarityAdd BLAST11

Domaini

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

Sequence similaritiesi

Belongs to the peptidase S1 family.PROSITE-ProRule annotation
Contains 1 EGF-like domain.PROSITE-ProRule annotation
Contains 1 fibronectin type-I domain.PROSITE-ProRule annotation
Contains 2 kringle domains.PROSITE-ProRule annotation
Contains 1 peptidase S1 domain.PROSITE-ProRule annotation

Keywords - Domaini

EGF-like domain, Kringle, Repeat, Signal

Phylogenomic databases

eggNOGiKOG3627. Eukaryota.
COG5640. LUCA.
GeneTreeiENSGT00760000119133.
HOGENOMiHOG000237314.
HOVERGENiHBG008633.
InParanoidiQ28198.
KOiK01343.
OMAiAHVRLYP.
OrthoDBiEOG091G0AH5.
TreeFamiTF329901.

Family and domain databases

CDDicd00190. Tryp_SPc. 1 hit.
InterProiIPR013032. EGF-like_CS.
IPR000742. EGF-like_dom.
IPR000083. Fibronectin_type1.
IPR000001. Kringle.
IPR013806. Kringle-like.
IPR018056. Kringle_CS.
IPR009003. Peptidase_S1_PA.
IPR001314. Peptidase_S1A.
IPR026280. Tissue_plasm_act.
IPR001254. Trypsin_dom.
IPR018114. TRYPSIN_HIS.
IPR033116. TRYPSIN_SER.
[Graphical view]
PfamiPF00008. EGF. 1 hit.
PF00039. fn1. 1 hit.
PF00051. Kringle. 2 hits.
PF00089. Trypsin. 1 hit.
[Graphical view]
PIRSFiPIRSF001145. Tissue_plasm_act. 1 hit.
PRINTSiPR00722. CHYMOTRYPSIN.
SMARTiSM00181. EGF. 1 hit.
SM00058. FN1. 1 hit.
SM00130. KR. 2 hits.
SM00020. Tryp_SPc. 1 hit.
[Graphical view]
SUPFAMiSSF50494. SSF50494. 1 hit.
SSF57440. SSF57440. 2 hits.
PROSITEiPS00022. 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]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q28198-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MMSAMKTEFL CVLLLCGAVF TSPSQETYRR LRRGARSYKV TCRDGKTQMT
60 70 80 90 100
YRQHDSWLRP LLRGNQVEHC WCDGGRAQCH SVPVRSCSEP WCFNGGTCRQ
110 120 130 140 150
ALYSSDFVCQ CPEGFMGKLC EIDATATCYK DQGVAYRGTW STAESGAECA
160 170 180 190 200
NWNSSGLAMK PYSGRRPNAI RLGLGNHNYC RNPDQDSKPW CYVFKAGKYI
210 220 230 240 250
SEFCSTPACA KVAEEDGDCY TGNGLAYRGT RSHTKSGASC LPWNSVFLTS
260 270 280 290 300
KIYTAWKSNA PALGLGKHNH CRNPDGDAQP WCHVWKDRQL TWEYCDVPQC
310 320 330 340 350
VTCGLRQYKR PQFRIKGGLF ADITSHPWQA AIFVKNRRSP GERFLCGGIL
360 370 380 390 400
ISSCWVLSAA HCFQERYPPH HLKVFLGRTY RLVPGEEEQT FEVEKYIIHK
410 420 430 440 450
EFDDDTYDND IALLHLKSDS LTCARESASV RTICLPDASL QLPDWTECEL
460 470 480 490 500
SGYGKHESSS PFFSERLKEA HVRLYPSSRC TSQHLFNRTV TNNMLCAGDT
510 520 530 540 550
RSGGDHTNLH DACQGDSGGP LVCMKDNHMT LVGIISWGLG CGRKDVPGVY
560
TKVTNYLDWI RDNTRP
Length:566
Mass (Da):63,701
Last modified:November 1, 1997 - v1
Checksum:i2EB6BEB4E32276C3
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti370H → L in AAI05349 (Ref. 2) Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X85800 mRNA. Translation: CAA59795.1.
BC105348 mRNA. Translation: AAI05349.1.
RefSeqiNP_776571.2. NM_174146.3.
UniGeneiBt.12302.

Genome annotation databases

EnsembliENSBTAT00000001642; ENSBTAP00000001642; ENSBTAG00000001244.
GeneIDi281407.
KEGGibta:281407.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X85800 mRNA. Translation: CAA59795.1.
BC105348 mRNA. Translation: AAI05349.1.
RefSeqiNP_776571.2. NM_174146.3.
UniGeneiBt.12302.

3D structure databases

ProteinModelPortaliQ28198.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9913.ENSBTAP00000001642.

Protein family/group databases

MEROPSiS01.232.

Proteomic databases

PaxDbiQ28198.
PRIDEiQ28198.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSBTAT00000001642; ENSBTAP00000001642; ENSBTAG00000001244.
GeneIDi281407.
KEGGibta:281407.

Organism-specific databases

CTDi5327.

Phylogenomic databases

eggNOGiKOG3627. Eukaryota.
COG5640. LUCA.
GeneTreeiENSGT00760000119133.
HOGENOMiHOG000237314.
HOVERGENiHBG008633.
InParanoidiQ28198.
KOiK01343.
OMAiAHVRLYP.
OrthoDBiEOG091G0AH5.
TreeFamiTF329901.

Enzyme and pathway databases

ReactomeiR-BTA-186797. Signaling by PDGF.
R-BTA-75205. Dissolution of Fibrin Clot.

Gene expression databases

BgeeiENSBTAG00000001244.

Family and domain databases

CDDicd00190. Tryp_SPc. 1 hit.
InterProiIPR013032. EGF-like_CS.
IPR000742. EGF-like_dom.
IPR000083. Fibronectin_type1.
IPR000001. Kringle.
IPR013806. Kringle-like.
IPR018056. Kringle_CS.
IPR009003. Peptidase_S1_PA.
IPR001314. Peptidase_S1A.
IPR026280. Tissue_plasm_act.
IPR001254. Trypsin_dom.
IPR018114. TRYPSIN_HIS.
IPR033116. TRYPSIN_SER.
[Graphical view]
PfamiPF00008. EGF. 1 hit.
PF00039. fn1. 1 hit.
PF00051. Kringle. 2 hits.
PF00089. Trypsin. 1 hit.
[Graphical view]
PIRSFiPIRSF001145. Tissue_plasm_act. 1 hit.
PRINTSiPR00722. CHYMOTRYPSIN.
SMARTiSM00181. EGF. 1 hit.
SM00058. FN1. 1 hit.
SM00130. KR. 2 hits.
SM00020. Tryp_SPc. 1 hit.
[Graphical view]
SUPFAMiSSF50494. SSF50494. 1 hit.
SSF57440. SSF57440. 2 hits.
PROSITEiPS00022. 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]
ProtoNetiSearch...

Entry informationi

Entry nameiTPA_BOVIN
AccessioniPrimary (citable) accession number: Q28198
Secondary accession number(s): Q2KJG9
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: November 1, 1997
Last modified: October 5, 2016
This is version 137 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Miscellaneous

Binds to the kringle structure of the fibrin A chain. Binding to fibrin enhances its catalytic activity.

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Peptidase families
    Classification of peptidase families and list of entries
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.