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Protein

Tissue-type plasminogen activator

Gene

Plat

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: -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
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

  • cellular response to dexamethasone stimulus Source: RGD
  • cellular response to follicle-stimulating hormone stimulus Source: RGD
  • cellular response to luteinizing hormone stimulus Source: RGD
  • plasminogen activation Source: RGD
  • positive regulation of ovulation Source: RGD
  • regulation of synaptic plasticity Source: RGD
  • response to cAMP Source: RGD
  • response to fatty acid Source: RGD
  • synaptic transmission, glutamatergic Source: RGD
  • wound healing Source: RGD

Keywordsi

Molecular functionHydrolase, Protease, Serine protease
Biological processPlasminogen activation

Enzyme and pathway databases

BRENDAi3.4.21.68 5301
ReactomeiR-RNO-186797 Signaling by PDGF
R-RNO-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
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeRattus
Proteomesi

Organism-specific databases

RGDi3342 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

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 17Sequence analysisAdd BLAST17
PropeptideiPRO_000002835718 – 29By similarityAdd BLAST12
PropeptideiPRO_000028591730 – 32Removed by plasmin3
ChainiPRO_000002835833 – 559Tissue-type plasminogen activatorBy similarityAdd BLAST527
ChainiPRO_000002835933 – 308Tissue-type plasminogen activator chain AAdd BLAST276
ChainiPRO_0000028360309 – 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

PaxDbiP19637
PRIDEiP19637

Expressioni

Gene expression databases

BgeeiENSRNOG00000019018
GenevisibleiP19637 RN

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

Protein-protein interaction databases

IntActiP19637, 1 interactor
MINTiP19637
STRINGi10116.ENSRNOP00000025764

Structurei

3D structure databases

ProteinModelPortaliP19637
SMRiP19637
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
InParanoidiP19637
KOiK01343
OMAiAHVRLYP
OrthoDBiEOG091G0AH5
PhylomeDBiP19637
TreeFamiTF329901

Family and domain databases

CDDicd00190 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.

P19637-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MKGELLCVLL LCGVAFTLPD QGIHRRFRRG ARSYRATCRD EQTQTTYQQH
60 70 80 90 100
QSWLRPMLRG NRVEYCRCNS GLAQCHSVPV RSCSEPRCFN GGTCQQALYF
110 120 130 140 150
SDFVCQCPDG FVGKRCDIDT RATCFEGQGI TYRGTWSTAE NGAECINWNS
160 170 180 190 200
SALSQKPYSA RRPNAIKLGL GNHNYCRNPD RDVKPWCYVF KAGKYTTEFC
210 220 230 240 250
STPACPKGPT EDCYVGKGVT YRGTHSFTTS KASCLPWNSM ILIGKTYTAW
260 270 280 290 300
RANSQALGLG RHNYCRNPDG DAKPWCHVMK DRKLTWEYCD MSPCSTCGLR
310 320 330 340 350
QYKQPQFRIK GGLFTDITSH PWQAAIFVKN KRSPGERFLC GGVLISSCWV
360 370 380 390 400
LSAAHCFVER FPPHHLKVVL GRTYRVVPGE EEQTFEIEKY IVHKEFDDDT
410 420 430 440 450
YDNDIALLQL RSDSSQCAQE SSSVGTACLP DPDVQLPDWT ECELSGYGKH
460 470 480 490 500
EASSPFFSDR LKEAHVRLYP SSRCTSQHLF NKTITSNMLC AGDTRTGGNQ
510 520 530 540 550
DVHDACQGDS GGPLVCMIDK RMTLLGIISW GLGCGQKDVP GIYTKVTNYL

NWIQDNMKQ
Length:559
Mass (Da):62,903
Last modified:November 1, 1991 - v2
Checksum:i7DBD3809C1D1C921
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti380E → K in AAA41812 (PubMed:3148445).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M23697 mRNA Translation: AAA41812.1
M31197
, M31185, M31186, M31187, M31188, M31189, M31190, M31191, M31192, M31193, M31194, M31195, M31196 Genomic DNA Translation: AAA42261.1
BC061565 mRNA Translation: AAH61565.1
PIRiA35029
RefSeqiNP_037283.2, NM_013151.2
XP_008769570.1, XM_008771348.1
UniGeneiRn.107102

Genome annotation databases

EnsembliENSRNOT00000025763; ENSRNOP00000025764; ENSRNOG00000019018
GeneIDi25692
KEGGirno:25692
UCSCiRGD:3342 rat

Entry informationi

Entry nameiTPA_RAT
AccessioniPrimary (citable) accession number: P19637
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 1, 1991
Last sequence update: November 1, 1991
Last modified: May 23, 2018
This is version 161 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

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

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