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Protein

Tissue-type plasminogen activator

Gene

Plat

Organism
Rattus norvegicus (Rat)
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)LengthDescriptionGraphical viewFeature identifierActions
Sitei99 – 991Important for binding to LRP1By similarity
Active sitei355 – 3551Charge relay system
Active sitei404 – 4041Charge relay system
Sitei462 – 4621Important for single-chain activityBy similarity
Sitei509 – 5091Important for single-chain activityBy similarity
Active sitei510 – 5101Charge relay system

GO - Molecular functioni

GO - Biological processi

  • cellular response to dexamethasone stimulus Source: RGD
  • plasminogen activation Source: InterPro
  • positive regulation of ovulation Source: RGD
  • regulation of synaptic plasticity Source: RGD
  • response to cAMP Source: RGD
  • response to peptide hormone Source: RGD
  • synaptic transmission, glutamatergic Source: RGD
  • wound healing Source: RGD
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Protease, Serine protease

Keywords - Biological processi

Plasminogen 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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 16

Organism-specific databases

RGDi3342. Plat.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: RGD
  • extracellular space Source: RGD
  • synapse Source: RGD
Complete GO annotation...

Keywords - Cellular componenti

Secreted

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 1717Sequence analysisAdd
BLAST
Propeptidei18 – 2912By similarityPRO_0000028357Add
BLAST
Propeptidei30 – 323Removed by plasminPRO_0000285917
Chaini33 – 559527Tissue-type plasminogen activatorBy similarityPRO_0000028358Add
BLAST
Chaini33 – 308276Tissue-type plasminogen activator chain APRO_0000028359Add
BLAST
Chaini309 – 559251Tissue-type plasminogen activator chain BPRO_0000028360Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
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
Glycosylationi149 – 1491N-linked (GlcNAc...)Sequence analysis
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
Glycosylationi481 – 4811N-linked (GlcNAc...)Sequence analysis
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

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 interaction.
MINTiMINT-7138910.
STRINGi10116.ENSRNOP00000025764.

Structurei

3D structure databases

ProteinModelPortaliP19637.
SMRiP19637. Positions 33-123, 212-558.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini36 – 7843Fibronectin type-IPROSITE-ProRule annotationAdd
BLAST
Domaini79 – 11739EGF-likePROSITE-ProRule annotationAdd
BLAST
Domaini124 – 20582Kringle 1PROSITE-ProRule annotationAdd
BLAST
Domaini213 – 29482Kringle 2PROSITE-ProRule annotationAdd
BLAST
Domaini309 – 558250Peptidase S1PROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni39 – 4911Important for binding to annexin A2By similarityAdd
BLAST

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.
InParanoidiP19637.
KOiK01343.
OMAiAHVRLYP.
OrthoDBiEOG75B84T.
PhylomeDBiP19637.
TreeFamiTF329901.

Family and domain databases

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.

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)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti380 – 3801E → K in AAA41812 (PubMed:3148445).Curated

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.

Cross-referencesi

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.

3D structure databases

ProteinModelPortaliP19637.
SMRiP19637. Positions 33-123, 212-558.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiP19637. 1 interaction.
MINTiMINT-7138910.
STRINGi10116.ENSRNOP00000025764.

Protein family/group databases

MEROPSiS01.232.

Proteomic databases

PaxDbiP19637.
PRIDEiP19637.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi5327.
RGDi3342. Plat.

Phylogenomic databases

eggNOGiKOG3627. Eukaryota.
COG5640. LUCA.
GeneTreeiENSGT00760000119133.
HOGENOMiHOG000237314.
HOVERGENiHBG008633.
InParanoidiP19637.
KOiK01343.
OMAiAHVRLYP.
OrthoDBiEOG75B84T.
PhylomeDBiP19637.
TreeFamiTF329901.

Enzyme and pathway databases

BRENDAi3.4.21.68. 5301.
ReactomeiR-RNO-186797. Signaling by PDGF.
R-RNO-75205. Dissolution of Fibrin Clot.

Miscellaneous databases

NextBioi607693.
PROiP19637.

Gene expression databases

GenevisibleiP19637. RN.

Family and domain databases

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...

Publicationsi

« Hide 'large scale' publications
  1. "Cloning and characterization of a cDNA for rat tissue-type plasminogen activator."
    Ny T., Leonardsson G., Hsueh A.J.W.
    DNA 7:671-677(1988) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  2. "The structure of the TATA-less rat tissue-type plasminogen activator gene. Species-specific sequence divergences in the promoter predict differences in regulation of gene expression."
    Feng P., Ohlsson M., Ny T.
    J. Biol. Chem. 265:2022-2027(1990) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
  3. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Pituitary.

Entry informationi

Entry nameiTPA_RAT
AccessioniPrimary (citable) accession number: P19637
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 1, 1991
Last sequence update: November 1, 1991
Last modified: May 11, 2016
This is version 148 of the entry and version 2 of the sequence. [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

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.