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Protein

Tissue-type plasminogen activator

Gene

Plat

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein 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
Sitei99Important for binding to LRP1By similarity1
Active sitei355Charge relay system1
Active sitei404Charge relay system1
Sitei462Important for single-chain activityBy similarity1
Sitei509Important for single-chain activityBy similarity1
Active sitei510Charge relay system1

GO - Molecular functioni

  • phosphoprotein binding Source: MGI
  • receptor binding Source: MGI
  • serine-type endopeptidase activity Source: MGI

GO - Biological processi

  • negative regulation of proteolysis Source: MGI
  • plasminogen activation Source: MGI
  • platelet-derived growth factor receptor signaling pathway Source: MGI
  • proteolysis Source: MGI
  • response to hypoxia Source: MGI
  • smooth muscle cell migration Source: MGI
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Protease, Serine protease

Keywords - Biological processi

Plasminogen activation

Enzyme and pathway databases

BRENDAi3.4.21.68. 3474.
ReactomeiR-MMU-186797. Signaling by PDGF.
R-MMU-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
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 8

Organism-specific databases

MGIiMGI:97610. Plat.

Subcellular locationi

GO - Cellular componenti

  • apical part of cell Source: MGI
  • cell surface Source: MGI
  • cytoplasm Source: MGI
  • extracellular exosome Source: MGI
  • extracellular space Source: MGI
  • secretory granule Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Chemistry databases

ChEMBLiCHEMBL3259492.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 17Sequence analysisAdd BLAST17
PropeptideiPRO_000002835318 – 29By similarityAdd BLAST12
PropeptideiPRO_000028590630 – 32Removed by plasmin1 Publication3
ChainiPRO_000002835433 – 559Tissue-type plasminogen activatorAdd BLAST527
ChainiPRO_000002835533 – 308Tissue-type plasminogen activator chain AAdd BLAST276
ChainiPRO_0000028356309 – 559Tissue-type plasminogen activator chain BAdd BLAST251

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi38 ↔ 68By similarity
Disulfide bondi66 ↔ 75By similarity
Disulfide bondi83 ↔ 94By similarity
Disulfide bondi88 ↔ 105By similarity
Disulfide bondi107 ↔ 116By similarity
Disulfide bondi124 ↔ 205By similarity
Disulfide bondi145 ↔ 187By similarity
Glycosylationi149N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi176 ↔ 200By similarity
Disulfide bondi213 ↔ 294By similarity
Disulfide bondi234 ↔ 276By similarity
Disulfide bondi265 ↔ 289By similarity
Disulfide bondi297 ↔ 428Interchain (between A and B chains)PROSITE-ProRule annotation
Disulfide bondi340 ↔ 356By similarity
Disulfide bondi348 ↔ 417By similarity
Disulfide bondi442 ↔ 516By similarity
Disulfide bondi474 ↔ 490By similarity
Glycosylationi481N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi506 ↔ 534By 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-308 catalyzed by plasmin, tissue kallikrein or factor Xa.

Keywords - PTMi

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

Proteomic databases

MaxQBiP11214.
PaxDbiP11214.
PeptideAtlasiP11214.
PRIDEiP11214.

PTM databases

PhosphoSitePlusiP11214.

Expressioni

Gene expression databases

BgeeiENSMUSG00000031538.
CleanExiMM_PLAT.
GenevisibleiP11214. MM.

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

Protein-protein interaction databases

IntActiP11214. 2 interactors.
MINTiMINT-8178492.
STRINGi10090.ENSMUSP00000033941.

Structurei

3D structure databases

ProteinModelPortaliP11214.
SMRiP11214.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini36 – 78Fibronectin type-IPROSITE-ProRule annotationAdd BLAST43
Domaini79 – 117EGF-likePROSITE-ProRule annotationAdd BLAST39
Domaini124 – 205Kringle 1PROSITE-ProRule annotationAdd BLAST82
Domaini213 – 294Kringle 2PROSITE-ProRule annotationAdd BLAST82
Domaini309 – 558Peptidase S1PROSITE-ProRule annotationAdd BLAST250

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni39 – 49Important 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.
InParanoidiP11214.
KOiK01343.
OMAiAHVRLYP.
OrthoDBiEOG091G0AH5.
PhylomeDBiP11214.
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. 2 hits.
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.

P11214-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MKRELLCVLL LCGLAFPLPD QGIHGRFRRG ARSYRATCRD EPTQTTYQQH
60 70 80 90 100
QSWLRPMLRS SRVEYCRCNS GLVQCHSVPV RSCSEPRCFN GGTCQQALYF
110 120 130 140 150
SDFVCQCPDG FVGKRCDIDT RATCFEEQGI TYRGTWSTAE SGAECINWNS
160 170 180 190 200
SVLSLKPYNA RRPNAIKLGL GNHNYCRNPD RDLKPWCYVF KAGKYTTEFC
210 220 230 240 250
STPACPKGKS EDCYVGKGVT YRGTHSLTTS QASCLPWNSI VLMGKSYTAW
260 270 280 290 300
RTNSQALGLG RHNYCRNPDG DARPWCHVMK DRKLTWEYCD MSPCSTCGLR
310 320 330 340 350
QYKRPQFRIK GGLYTDITSH PWQAAIFVKN KRSPGERFLC GGVLISSCWV
360 370 380 390 400
LSAAHCFLER FPPNHLKVVL GRTYRVVPGE EEQTFEIEKY IVHEEFDDDT
410 420 430 440 450
YDNDIALLQL RSQSKQCAQE SSSVGTACLP DPNLQLPDWT ECELSGYGKH
460 470 480 490 500
EASSPFFSDR LKEAHVRLYP SSRCTSQHLF NKTVTNNMLC AGDTRSGGNQ
510 520 530 540 550
DLHDACQGDS GGPLVCMINK QMTLTGIISW GLGCGQKDVP GVYTKVTNYL

DWIHDNMKQ
Length:559
Mass (Da):63,097
Last modified:October 2, 2007 - v3
Checksum:i0A158A5A273CFAA0
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti260G → A in AAA40470 (PubMed:2826484).Curated1
Sequence conflicti325A → P in AAH11256 (PubMed:15489334).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
J03520 mRNA. Translation: AAA40470.1.
AK135857 mRNA. Translation: BAE22698.1.
AK135965 mRNA. Translation: BAE22749.1.
BC011256 mRNA. Translation: AAH11256.1.
BC057967 mRNA. Translation: AAH57967.1.
BC061508 mRNA. Translation: AAH61508.1.
CCDSiCCDS22183.1.
PIRiA29941.
RefSeqiNP_032898.2. NM_008872.3.
UniGeneiMm.154660.

Genome annotation databases

EnsembliENSMUST00000033941; ENSMUSP00000033941; ENSMUSG00000031538.
GeneIDi18791.
KEGGimmu:18791.
UCSCiuc009ldx.2. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
J03520 mRNA. Translation: AAA40470.1.
AK135857 mRNA. Translation: BAE22698.1.
AK135965 mRNA. Translation: BAE22749.1.
BC011256 mRNA. Translation: AAH11256.1.
BC057967 mRNA. Translation: AAH57967.1.
BC061508 mRNA. Translation: AAH61508.1.
CCDSiCCDS22183.1.
PIRiA29941.
RefSeqiNP_032898.2. NM_008872.3.
UniGeneiMm.154660.

3D structure databases

ProteinModelPortaliP11214.
SMRiP11214.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiP11214. 2 interactors.
MINTiMINT-8178492.
STRINGi10090.ENSMUSP00000033941.

Chemistry databases

ChEMBLiCHEMBL3259492.

Protein family/group databases

MEROPSiS01.232.

PTM databases

PhosphoSitePlusiP11214.

Proteomic databases

MaxQBiP11214.
PaxDbiP11214.
PeptideAtlasiP11214.
PRIDEiP11214.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000033941; ENSMUSP00000033941; ENSMUSG00000031538.
GeneIDi18791.
KEGGimmu:18791.
UCSCiuc009ldx.2. mouse.

Organism-specific databases

CTDi5327.
MGIiMGI:97610. Plat.

Phylogenomic databases

eggNOGiKOG3627. Eukaryota.
COG5640. LUCA.
GeneTreeiENSGT00760000119133.
HOGENOMiHOG000237314.
HOVERGENiHBG008633.
InParanoidiP11214.
KOiK01343.
OMAiAHVRLYP.
OrthoDBiEOG091G0AH5.
PhylomeDBiP11214.
TreeFamiTF329901.

Enzyme and pathway databases

BRENDAi3.4.21.68. 3474.
ReactomeiR-MMU-186797. Signaling by PDGF.
R-MMU-75205. Dissolution of Fibrin Clot.

Miscellaneous databases

PROiP11214.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000031538.
CleanExiMM_PLAT.
GenevisibleiP11214. MM.

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. 2 hits.
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_MOUSE
AccessioniPrimary (citable) accession number: P11214
Secondary accession number(s): Q6P7U0, Q91VP2
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 1, 1989
Last sequence update: October 2, 2007
Last modified: November 2, 2016
This is version 170 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. Peptidase families
    Classification of peptidase families and list of entries
  3. 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.