UniProtKB - P11214 (TPA_MOUSE)
Tissue-type plasminogen activator
Plat
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. During oocyte activation, plays a role in cortical granule reaction in the zona reaction, which contributes to the block to polyspermy (By similarity).
By similarityCatalytic activityi
- Specific cleavage of Arg-|-Val bond in plasminogen to form plasmin. EC:3.4.21.68
Activity regulationi
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sitei | 99 | Important for binding to LRP1By similarity | 1 | |
Active sitei | 355 | Charge relay system | 1 | |
Active sitei | 404 | Charge relay system | 1 | |
Sitei | 462 | Important for single-chain activityBy similarity | 1 | |
Sitei | 509 | Important for single-chain activityBy similarity | 1 | |
Active sitei | 510 | Charge relay system | 1 |
GO - Molecular functioni
- phosphoprotein binding Source: MGI
- serine-type endopeptidase activity Source: MGI
- signaling receptor binding Source: MGI
GO - Biological processi
- cellular response to dexamethasone stimulus Source: Ensembl
- cellular response to follicle-stimulating hormone stimulus Source: Ensembl
- cellular response to luteinizing hormone stimulus Source: Ensembl
- negative regulation of proteolysis Source: MGI
- plasminogen activation Source: MGI
- platelet-derived growth factor receptor signaling pathway Source: MGI
- positive regulation of ovulation Source: MGI
- prevention of polyspermy Source: UniProtKB
- proteolysis Source: MGI
- regulation of synaptic plasticity Source: Ensembl
- response to cAMP Source: Ensembl
- response to fatty acid Source: Ensembl
- response to hypoxia Source: MGI
- smooth muscle cell migration Source: MGI
- synaptic transmission, glutamatergic Source: MGI
- trans-synaptic signaling by BDNF, modulating synaptic transmission Source: SynGO
- wound healing Source: Ensembl
Keywordsi
Molecular function | Hydrolase, Protease, Serine protease |
Biological process | Plasminogen activation |
Enzyme and pathway databases
BRENDAi | 3.4.21.68, 3474 |
Reactomei | R-MMU-186797, Signaling by PDGF R-MMU-75205, Dissolution of Fibrin Clot |
Protein family/group databases
MEROPSi | S01.232 |
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 |
Organismi | Mus musculus (Mouse) |
Taxonomic identifieri | 10090 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus |
Proteomesi |
|
Organism-specific databases
MGIi | MGI:97610, Plat |
VEuPathDBi | HostDB:ENSMUSG00000031538 |
Subcellular locationi
Extracellular region or secreted
Extracellular region or secreted
- extracellular space Source: MGI
- perisynaptic space Source: MGI
Other locations
- apical part of cell Source: MGI
- cell surface Source: MGI
- cytoplasm Source: MGI
- glutamatergic synapse Source: SynGO
- neuronal dense core vesicle Source: MGI
- postsynapse Source: MGI
- Schaffer collateral - CA1 synapse Source: SynGO
- secretory granule Source: MGI
- serine protease inhibitor complex Source: Ensembl
- synapse Source: MGI
Keywords - Cellular componenti
SecretedPTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Signal peptidei | 1 – 17 | Sequence analysisAdd BLAST | 17 | |
PropeptideiPRO_0000028353 | 18 – 29 | By similarityAdd BLAST | 12 | |
PropeptideiPRO_0000285906 | 30 – 32 | Removed by plasmin1 Publication | 3 | |
ChainiPRO_0000028354 | 33 – 559 | Tissue-type plasminogen activatorAdd BLAST | 527 | |
ChainiPRO_0000028355 | 33 – 308 | Tissue-type plasminogen activator chain AAdd BLAST | 276 | |
ChainiPRO_0000028356 | 309 – 559 | Tissue-type plasminogen activator chain BAdd BLAST | 251 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Disulfide bondi | 38 ↔ 68 | By similarity | ||
Disulfide bondi | 66 ↔ 75 | By similarity | ||
Disulfide bondi | 83 ↔ 94 | By similarity | ||
Disulfide bondi | 88 ↔ 105 | By similarity | ||
Disulfide bondi | 107 ↔ 116 | By similarity | ||
Disulfide bondi | 124 ↔ 205 | By similarity | ||
Disulfide bondi | 145 ↔ 187 | By similarity | ||
Glycosylationi | 149 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Disulfide bondi | 176 ↔ 200 | By similarity | ||
Disulfide bondi | 213 ↔ 294 | By similarity | ||
Disulfide bondi | 234 ↔ 276 | By similarity | ||
Disulfide bondi | 265 ↔ 289 | By similarity | ||
Disulfide bondi | 297 ↔ 428 | Interchain (between A and B chains)PROSITE-ProRule annotation | ||
Disulfide bondi | 340 ↔ 356 | By similarity | ||
Disulfide bondi | 348 ↔ 417 | By similarity | ||
Disulfide bondi | 442 ↔ 516 | By similarity | ||
Disulfide bondi | 474 ↔ 490 | By similarity | ||
Glycosylationi | 481 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Disulfide bondi | 506 ↔ 534 | By similarity |
Post-translational modificationi
Keywords - PTMi
Cleavage on pair of basic residues, Disulfide bond, Glycoprotein, ZymogenProteomic databases
MaxQBi | P11214 |
PaxDbi | P11214 |
PeptideAtlasi | P11214 |
PRIDEi | P11214 |
ProteomicsDBi | 258819 |
PTM databases
GlyGeni | P11214, 2 sites |
iPTMneti | P11214 |
PhosphoSitePlusi | P11214 |
Expressioni
Gene expression databases
Bgeei | ENSMUSG00000031538, Expressed in primary oocyte and 307 other tissues |
Genevisiblei | P11214, 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). In complex with SERPINE1, interacts with SORL1 (By similarity).
By similarityGO - Molecular functioni
- phosphoprotein binding Source: MGI
- signaling receptor binding Source: MGI
Protein-protein interaction databases
BioGRIDi | 202229, 4 interactors |
ComplexPortali | CPX-518, tPA-PAI-1 complex |
IntActi | P11214, 2 interactors |
MINTi | P11214 |
STRINGi | 10090.ENSMUSP00000033941 |
Chemistry databases
BindingDBi | P11214 |
Miscellaneous databases
RNActi | P11214, protein |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 36 – 78 | Fibronectin type-IPROSITE-ProRule annotationAdd BLAST | 43 | |
Domaini | 79 – 117 | EGF-likePROSITE-ProRule annotationAdd BLAST | 39 | |
Domaini | 124 – 205 | Kringle 1PROSITE-ProRule annotationAdd BLAST | 82 | |
Domaini | 213 – 294 | Kringle 2PROSITE-ProRule annotationAdd BLAST | 82 | |
Domaini | 309 – 558 | Peptidase S1PROSITE-ProRule annotationAdd BLAST | 250 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 39 – 49 | Important for binding to annexin A2By similarityAdd BLAST | 11 |
Domaini
Sequence similaritiesi
Keywords - Domaini
EGF-like domain, Kringle, Repeat, SignalPhylogenomic databases
eggNOGi | KOG3627, Eukaryota |
GeneTreei | ENSGT00940000158930 |
HOGENOMi | CLU_006842_18_4_1 |
InParanoidi | P11214 |
OMAi | TWEYCDI |
OrthoDBi | 1314811at2759 |
PhylomeDBi | P11214 |
TreeFami | TF329901 |
Family and domain databases
CDDi | cd00061, FN1, 1 hit cd00108, KR, 2 hits cd00190, Tryp_SPc, 1 hit |
Gene3Di | 2.40.10.10, 2 hits 2.40.20.10, 2 hits |
InterProi | View protein in InterPro IPR000742, EGF-like_dom IPR000083, Fibronectin_type1 IPR000001, Kringle IPR013806, Kringle-like IPR018056, Kringle_CS IPR038178, Kringle_sf IPR009003, Peptidase_S1_PA IPR043504, Peptidase_S1_PA_chymotrypsin IPR001314, Peptidase_S1A IPR026280, Tissue_plasm_act IPR034811, tPA IPR001254, Trypsin_dom IPR018114, TRYPSIN_HIS IPR033116, TRYPSIN_SER |
PANTHERi | PTHR24264:SF42, PTHR24264:SF42, 3 hits |
Pfami | View protein in Pfam PF00008, EGF, 1 hit PF00039, fn1, 1 hit PF00051, Kringle, 2 hits PF00089, Trypsin, 1 hit |
PIRSFi | PIRSF001145, Tissue_plasm_act, 1 hit |
PRINTSi | PR00722, CHYMOTRYPSIN |
SMARTi | View protein in SMART SM00181, EGF, 1 hit SM00058, FN1, 1 hit SM00130, KR, 2 hits SM00020, Tryp_SPc, 1 hit |
SUPFAMi | SSF50494, SSF50494, 1 hit SSF57440, SSF57440, 2 hits |
PROSITEi | View 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 |
i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
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
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 260 | G → A in AAA40470 (PubMed:2826484).Curated | 1 | |
Sequence conflicti | 325 | A → P in AAH11256 (PubMed:15489334).Curated | 1 |
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 |
CCDSi | CCDS22183.1 |
PIRi | A29941 |
RefSeqi | NP_032898.2, NM_008872.3 |
Genome annotation databases
Ensembli | ENSMUST00000033941; ENSMUSP00000033941; ENSMUSG00000031538 |
GeneIDi | 18791 |
KEGGi | mmu:18791 |
UCSCi | uc009ldx.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 |
CCDSi | CCDS22183.1 |
PIRi | A29941 |
RefSeqi | NP_032898.2, NM_008872.3 |
3D structure databases
SMRi | P11214 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 202229, 4 interactors |
ComplexPortali | CPX-518, tPA-PAI-1 complex |
IntActi | P11214, 2 interactors |
MINTi | P11214 |
STRINGi | 10090.ENSMUSP00000033941 |
Chemistry databases
BindingDBi | P11214 |
ChEMBLi | CHEMBL3259492 |
Protein family/group databases
MEROPSi | S01.232 |
PTM databases
GlyGeni | P11214, 2 sites |
iPTMneti | P11214 |
PhosphoSitePlusi | P11214 |
Proteomic databases
MaxQBi | P11214 |
PaxDbi | P11214 |
PeptideAtlasi | P11214 |
PRIDEi | P11214 |
ProteomicsDBi | 258819 |
Protocols and materials databases
ABCDi | P11214, 5 sequenced antibodies |
Antibodypediai | 998, 801 antibodies from 39 providers |
DNASUi | 18791 |
Genome annotation databases
Ensembli | ENSMUST00000033941; ENSMUSP00000033941; ENSMUSG00000031538 |
GeneIDi | 18791 |
KEGGi | mmu:18791 |
UCSCi | uc009ldx.2, mouse |
Organism-specific databases
CTDi | 5327 |
MGIi | MGI:97610, Plat |
VEuPathDBi | HostDB:ENSMUSG00000031538 |
Phylogenomic databases
eggNOGi | KOG3627, Eukaryota |
GeneTreei | ENSGT00940000158930 |
HOGENOMi | CLU_006842_18_4_1 |
InParanoidi | P11214 |
OMAi | TWEYCDI |
OrthoDBi | 1314811at2759 |
PhylomeDBi | P11214 |
TreeFami | TF329901 |
Enzyme and pathway databases
BRENDAi | 3.4.21.68, 3474 |
Reactomei | R-MMU-186797, Signaling by PDGF R-MMU-75205, Dissolution of Fibrin Clot |
Miscellaneous databases
BioGRID-ORCSi | 18791, 1 hit in 64 CRISPR screens |
PROi | PR:P11214 |
RNActi | P11214, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSMUSG00000031538, Expressed in primary oocyte and 307 other tissues |
Genevisiblei | P11214, MM |
Family and domain databases
CDDi | cd00061, FN1, 1 hit cd00108, KR, 2 hits cd00190, Tryp_SPc, 1 hit |
Gene3Di | 2.40.10.10, 2 hits 2.40.20.10, 2 hits |
InterProi | View protein in InterPro IPR000742, EGF-like_dom IPR000083, Fibronectin_type1 IPR000001, Kringle IPR013806, Kringle-like IPR018056, Kringle_CS IPR038178, Kringle_sf IPR009003, Peptidase_S1_PA IPR043504, Peptidase_S1_PA_chymotrypsin IPR001314, Peptidase_S1A IPR026280, Tissue_plasm_act IPR034811, tPA IPR001254, Trypsin_dom IPR018114, TRYPSIN_HIS IPR033116, TRYPSIN_SER |
PANTHERi | PTHR24264:SF42, PTHR24264:SF42, 3 hits |
Pfami | View protein in Pfam PF00008, EGF, 1 hit PF00039, fn1, 1 hit PF00051, Kringle, 2 hits PF00089, Trypsin, 1 hit |
PIRSFi | PIRSF001145, Tissue_plasm_act, 1 hit |
PRINTSi | PR00722, CHYMOTRYPSIN |
SMARTi | View protein in SMART SM00181, EGF, 1 hit SM00058, FN1, 1 hit SM00130, KR, 2 hits SM00020, Tryp_SPc, 1 hit |
SUPFAMi | SSF50494, SSF50494, 1 hit SSF57440, SSF57440, 2 hits |
PROSITEi | View 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 |
MobiDBi | Search... |
Entry informationi
Entry namei | TPA_MOUSE | |
Accessioni | P11214Primary (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: | February 23, 2022 | |
This is version 201 of the entry and version 3 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
Direct protein sequencing, Reference proteomeDocuments
- Peptidase families
Classification of peptidase families and list of entries - MGD cross-references
Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot - SIMILARITY comments
Index of protein domains and families