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Protein

Tissue-type plasminogen activator

Gene

Plat

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -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.

Activity 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

GO - Biological processi

Keywordsi

Molecular functionHydrolase, Protease, Serine protease
Biological processPlasminogen 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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 8

Organism-specific databases

MGIiMGI:97610 Plat

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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...) asparagineSequence 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...) asparagineSequence 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

iPTMnetiP11214
PhosphoSitePlusiP11214

Expressioni

Gene expression databases

BgeeiENSMUSG00000031538 Expressed in 287 organ(s), highest expression level in primary oocyte
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

ComplexPortaliCPX-518 tPA-PAI-1 complex
IntActiP11214, 2 interactors
MINTiP11214
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

Keywords - Domaini

EGF-like domain, Kringle, Repeat, Signal

Phylogenomic databases

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

Family and domain databases

CDDicd00061 FN1, 1 hit
cd00108 KR, 2 hits
cd00190 Tryp_SPc, 1 hit
Gene3Di2.40.20.10, 2 hits
InterProiView protein in InterPro
IPR013032 EGF-like_CS
IPR000742 EGF-like_dom
IPR000083 Fibronectin_type1
IPR000001 Kringle
IPR013806 Kringle-like
IPR018056 Kringle_CS
IPR038178 Kringle_sf
IPR009003 Peptidase_S1_PA
IPR001314 Peptidase_S1A
IPR026280 Tissue_plasm_act
IPR034811 tPA
IPR001254 Trypsin_dom
IPR018114 TRYPSIN_HIS
IPR033116 TRYPSIN_SER
PANTHERiPTHR44617 PTHR44617, 1 hit
PfamiView protein in Pfam
PF00008 EGF, 1 hit
PF00039 fn1, 1 hit
PF00051 Kringle, 2 hits
PF00089 Trypsin, 1 hit
PIRSFiPIRSF001145 Tissue_plasm_act, 1 hit
PRINTSiPR00722 CHYMOTRYPSIN
SMARTiView protein in SMART
SM00181 EGF, 1 hit
SM00058 FN1, 1 hit
SM00130 KR, 2 hits
SM00020 Tryp_SPc, 1 hit
SUPFAMiSSF50494 SSF50494, 1 hit
SSF57440 SSF57440, 2 hits
PROSITEiView protein in 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

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

Similar proteinsi

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

ComplexPortaliCPX-518 tPA-PAI-1 complex
IntActiP11214, 2 interactors
MINTiP11214
STRINGi10090.ENSMUSP00000033941

Chemistry databases

ChEMBLiCHEMBL3259492

Protein family/group databases

MEROPSiS01.232

PTM databases

iPTMnetiP11214
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
OMAiPLVCMKD
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

PROiPR:P11214
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000031538 Expressed in 287 organ(s), highest expression level in primary oocyte
CleanExiMM_PLAT
GenevisibleiP11214 MM

Family and domain databases

CDDicd00061 FN1, 1 hit
cd00108 KR, 2 hits
cd00190 Tryp_SPc, 1 hit
Gene3Di2.40.20.10, 2 hits
InterProiView protein in InterPro
IPR013032 EGF-like_CS
IPR000742 EGF-like_dom
IPR000083 Fibronectin_type1
IPR000001 Kringle
IPR013806 Kringle-like
IPR018056 Kringle_CS
IPR038178 Kringle_sf
IPR009003 Peptidase_S1_PA
IPR001314 Peptidase_S1A
IPR026280 Tissue_plasm_act
IPR034811 tPA
IPR001254 Trypsin_dom
IPR018114 TRYPSIN_HIS
IPR033116 TRYPSIN_SER
PANTHERiPTHR44617 PTHR44617, 1 hit
PfamiView protein in Pfam
PF00008 EGF, 1 hit
PF00039 fn1, 1 hit
PF00051 Kringle, 2 hits
PF00089 Trypsin, 1 hit
PIRSFiPIRSF001145 Tissue_plasm_act, 1 hit
PRINTSiPR00722 CHYMOTRYPSIN
SMARTiView protein in SMART
SM00181 EGF, 1 hit
SM00058 FN1, 1 hit
SM00130 KR, 2 hits
SM00020 Tryp_SPc, 1 hit
SUPFAMiSSF50494 SSF50494, 1 hit
SSF57440 SSF57440, 2 hits
PROSITEiView protein in 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
ProtoNetiSearch...

Entry informationi

Entry nameiTPA_MOUSE
AccessioniPrimary (citable) accession number: P11214
Secondary accession number(s): Q6P7U0, Q91VP2
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 1, 1989
Last sequence update: October 2, 2007
Last modified: November 7, 2018
This is version 182 of the entry and version 3 of the sequence. See 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. SIMILARITY comments
    Index of protein domains and families
  2. Peptidase families
    Classification of peptidase families and list of entries
  3. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
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