DB code: M00155

RLCP classification 1.13.30000.10 : Hydrolysis
CATH domain 2.10.70.10 : Complement Module; domain 1
2.10.25.10 : Laminin
2.40.20.10 : Plasminogen Kringle 4
2.40.10.10 : Thrombin, subunit H Catalytic domain
2.40.10.10 : Thrombin, subunit H Catalytic domain
E.C. 3.4.21.68
CSA 1rtf
M-CSA 1rtf
MACiE

CATH domain Related DB codes (homologues)
2.10.25.10 : Laminin M00139 M00133 M00212 M00152 M00315 M00316
2.10.70.10 : Complement Module; domain 1 M00139 M00315 M00316
2.40.10.10 : Thrombin, subunit H M00139 D00214 M00167 D00426 M00133 D00428 D00429 D00430 D00431 D00432 D00433 D00434 D00435 M00227 M00209 D00194 D00197 D00211 D00212 D00216 M00212 D00224 D00497 M00217 M00216 D00528 D00848 D00850 D00851 D00852 D00855 M00152 M00157 M00181 M00315 M00316 M00317 M00348 M00349 T00074 T00410 T00411
2.40.20.10 : Plasminogen Kringle 4 M00152 M00157

Uniprot Enzyme Name
UniprotKB Protein name Synonyms Contains RefSeq MEROPS Pfam
P00750 Tissue-type plasminogen activator (t-plasminogen activator) (t-PA) (tPA) (EC 3.4.21.68)AltName: INN=Alteplase;AltName: INN=Reteplase;
None Tissue-type plasminogen activator chain A
Tissue-type plasminogen activator chain B
NP_000921.1 (Protein)
NM_000930.3 (DNA/RNA sequence)
NP_127509.1 (Protein)
NM_033011.2 (DNA/RNA sequence)
S01.232 (Serine)
PF00008 (EGF)
PF00039 (fn1)
PF00051 (Kringle)
PF00089 (Trypsin)
[Graphical View]
P98119 Salivary plasminogen activator alpha 1
EC 3.4.21.68
DSPA alpha-1
None S01.239 (Serine)
PF00008 (EGF)
PF00039 (fn1)
PF00051 (Kringle)
PF00089 (Trypsin)
[Graphical View]

KEGG enzyme name
t-plasminogen activator
tissue plasminogen activator
plasminogen activator, tissue-type
tissue-type plasminogen activator
tPA
t-PA

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
P98119 URT1_DESRO Specific cleavage of Arg-|-Val bond in plasminogen to form plasmin. Monomer. Secreted.
P00750 TPA_HUMAN Specific cleavage of Arg-|-Val bond in plasminogen to form plasmin. 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 between 100-fold and 1000-fold, 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. Yet unidentified interactions on endothelial cells and vascular smooth muscle cells (VSMC) lead to a 100-fold stimulation of plasminogen activation. In addition, binding to VSMC reduces TPA inhibition by PAI-1 by 30-fold. Binds LRP1B, binding is followed by internalization and degradation. Secreted, extracellular space.

KEGG Pathways
Map code Pathways E.C.

Compound table
Substrates Products Intermediates
KEGG-id C00520 C00471 I00087 I00085 I00086
E.C.
Compound Plasminogen Plasmin Peptidyl-tetrahedral intermediate Acyl-enzyme Tetrahedral intermediate
Type peptide/protein peptide/protein
ChEBI
PubChem
1tpgA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1tpgA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1tpmA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1tpnA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1pk2A Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1pmlA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1pmlB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1pmlC Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1tpkA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1tpkB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1tpkC Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1a5hA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1a5hB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1a5iA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Transition-state-analogue:GLU-GLY-ARG-CH2
1bdaA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Transition-state-analogue:DSY-GLU-GLY-ARG-CH2
1bdaB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Transition-state-analogue:DSY-GLU-GLY-ARG-CH2
1rtfB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1a5hA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1a5hB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1a5iA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1bdaA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1bdaB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1rtfB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound

Reference for Active-site residues
resource references E.C.
Swoss-prot; P00750, P98119 & literature [21]

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1tpgA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1tpgA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain mutant C83S
1tpmA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1tpnA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1pk2A Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1pmlA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASN 26;LYS 33;VAL 34;TYR 35;HIS 64(Chloride binding)
1pmlB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASN 26;LYS 33;VAL 34;TYR 35;HIS 64(Chloride binding)
1pmlC Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASN 26;LYS 33;VAL 34;TYR 35;HIS 64(Chloride binding)
1tpkA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASN 26;LYS 33;VAL 34;TYR 35;HIS 64(Chloride binding)
1tpkB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASN 26;LYS 33;VAL 34;TYR 35;HIS 64(Chloride binding)
1tpkC Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASN 26;LYS 33;VAL 34;TYR 35;HIS 64(Chloride binding)
1a5hA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 195 GLY 193;SER 195
1a5hB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 195 GLY 193;SER 195
1a5iA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 195 GLY 193;SER 195
1bdaA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 195 GLY 193;SER 195
1bdaB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 195 GLY 193;SER 195
1rtfB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 195 GLY 193;SER 195
1a5hA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 57;ASP 102
1a5hB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 57;ASP 102
1a5iA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 57;ASP 102
1bdaA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 57;ASP 102
1bdaB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 57;ASP 102
1rtfB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 57;ASP 102

References for Catalytic Mechanism
References Sections No. of steps in catalysis

References
[1]
Resource
Comments
Medline ID
PubMed ID 6685059
Journal FEBS Lett
Year 1983
Volume 163
Pages 37-41
Authors Banyai L, Varadi A, Patthy L
Title Common evolutionary origin of the fibrin-binding structures of fibronectin and tissue-type plasminogen activator.
Related PDB
Related UniProtKB
[2]
Resource
Comments
Medline ID
PubMed ID 3030730
Journal EMBO J
Year 1986
Volume 5
Pages 3525-30
Authors Verheijen JH, Caspers MP, Chang GT, de Munk GA, Pouwels PH, Enger-Valk BE
Title Involvement of finger domain and kringle 2 domain of tissue-type plasminogen activator in fibrin binding and stimulation of activity by fibrin.
Related PDB
Related UniProtKB
[3]
Resource
Comments
Medline ID
PubMed ID 3021732
Journal J Biol Chem
Year 1986
Volume 261
Pages 14214-8
Authors van Zonneveld AJ, Veerman H, Pannekoek H
Title On the interaction of the finger and the kringle-2 domain of tissue-type plasminogen activator with fibrin. Inhibition of kringle-2 binding to fibrin by epsilon-amino caproic acid.
Related PDB
Related UniProtKB
[4]
Resource
Comments
Medline ID
PubMed ID 3088564
Journal Proc Natl Acad Sci U S A
Year 1986
Volume 83
Pages 4670-4
Authors van Zonneveld AJ, Veerman H, Pannekoek H
Title Autonomous functions of structural domains on human tissue-type plasminogen activator.
Related PDB
Related UniProtKB
[5]
Resource
Comments
Medline ID
PubMed ID 2846282
Journal EMBO J
Year 1988
Volume 7
Pages 2731-40
Authors Gething MJ, Adler B, Boose JA, Gerard RD, Madison EL, McGookey D, Meidell RS, Roman LM, Sambrook J
Title Variants of human tissue-type plasminogen activator that lack specific structural domains of the heavy chain.
Related PDB
Related UniProtKB
[6]
Resource
Comments STRUCTURE BY NMR OF KRINGLE 2.
Medline ID 90122799
PubMed ID 2558718
Journal Biochemistry
Year 1989
Volume 28
Pages 9350-60
Authors Byeon IJ, Kelley RF, Llinas M
Title 1H NMR structural characterization of a recombinant kringle 2 domain from human tissue-type plasminogen activator.
Related PDB
Related UniProtKB P00750
[7]
Resource
Comments
Medline ID
PubMed ID 2497771
Journal Biochemistry
Year 1989
Volume 28
Pages 1884-91
Authors Cleary S, Mulkerrin MG, Kelley RF
Title Purification and characterization of tissue plasminogen activator kringle-2 domain expressed in Escherichia coli.
Related PDB
Related UniProtKB
[8]
Resource
Comments
Medline ID
PubMed ID 2502177
Journal Biochemistry
Year 1989
Volume 28
Pages 4047-54
Authors Kelley RF, Cleary S
Title Effect of residue 65 substitutions on thermal stability of tissue plasminogen activator kringle-2 domain.
Related PDB
Related UniProtKB
[9]
Resource
Comments
Medline ID
PubMed ID 2477307
Journal Gene
Year 1989
Volume 79
Pages 333-44
Authors Stern A, Mattes R, Buckel P, Weidle UH
Title Functional topology of human tissue-type plasminogen activator: characterization of two deletion derivatives and of a duplication derivative.
Related PDB
Related UniProtKB
[10]
Resource
Comments
Medline ID
PubMed ID 2556697
Journal Protein Eng
Year 1989
Volume 3
Pages 111-6
Authors Markland W, Pollock D, Livingston DJ
Title Tissue-type plasminogen activator variants with domain duplications and rearrangements.
Related PDB
Related UniProtKB
[11]
Resource
Comments
Medline ID
PubMed ID 2108143
Journal J Biol Chem
Year 1990
Volume 265
Pages 5540-5
Authors Ahern TJ, Morris GE, Barone KM, Horgan PG, Timony GA, Angus LB, Henson KS, Stoudemire JB, Langer-Safer PR, Larsen GR
Title Site-directed mutagenesis in human tissue-plasminogen activator. Distinguishing sites in the amino-terminal region required for full fibrinolytic activity and rapid clearance from the circulation.
Related PDB
Related UniProtKB
[12]
Resource
Comments
Medline ID
PubMed ID 2108167
Journal J Biol Chem
Year 1990
Volume 265
Pages 5170-7
Authors Burck PJ, Berg DH, Warrick MW, Berg DT, Walls JD, Jaskunas SR, Crisel RM, Weigel B, Vlahos CJ, McClure DB, et al
Title Characterization of a modified human tissue plasminogen activator comprising a kringle-2 and a protease domain.
Related PDB
Related UniProtKB
[13]
Resource
Comments
Medline ID
PubMed ID 2115513
Journal J Biol Chem
Year 1990
Volume 265
Pages 12184-91
Authors Collen D, Lijnen HR, Bulens F, Vandamme AM, Tulinsky A, Nelles L
Title Biochemical and functional characterization of human tissue-type plasminogen activator variants with mutagenized kringle domains.
Related PDB
Related UniProtKB
[14]
Resource
Comments
Medline ID
PubMed ID 2117612
Journal J Biol Chem
Year 1990
Volume 265
Pages 14606-11
Authors Wilhelm OG, Jaskunas SR, Vlahos CJ, Bang NU
Title Functional properties of the recombinant kringle-2 domain of tissue plasminogen activator produced in Escherichia coli.
Related PDB
Related UniProtKB
[15]
Resource
Comments STRUCTURE BY NMR OF KRINGLE 2.
Medline ID 91200042
PubMed ID 1901789
Journal Eur J Biochem
Year 1991
Volume 197
Pages 155-65
Authors Byeon IJ, Kelley RF, Llinas M
Title Kringle-2 domain of the tissue-type plasminogen activator. 1H-NMR assignments and secondary structure.
Related PDB
Related UniProtKB P00750
[16]
Resource
Comments
Medline ID
PubMed ID 1900516
Journal J Biol Chem
Year 1991
Volume 266
Pages 5191-201
Authors Bennett WF, Paoni NF, Keyt BA, Botstein D, Jones AJ, Presta L, Wurm FM, Zoller MJ
Title High resolution analysis of functional determinants on human tissue-type plasminogen activator.
Related PDB
Related UniProtKB
[17]
Resource
Comments DISULFIDE BONDS IN KRINGLE 2.
Medline ID 91244765
PubMed ID 1645336
Journal J Biol Chem
Year 1991
Volume 266
Pages 10070-2
Authors Vlahos CJ, Wilhelm OG, Hassell T, Jaskunas SR, Bang NU
Title Disulfide pairing of the recombinant kringle-2 domain of tissue plasminogen activator produced in Escherichia coli.
Related PDB
Related UniProtKB P00750
[18]
Resource
Comments STRUCTURE BY NMR OF KRINGLE 2.
Medline ID 92106329
PubMed ID 1762144
Journal J Mol Biol
Year 1991
Volume 222
Pages 1035-51
Authors Byeon IJ, Llinas M
Title Solution structure of the tissue-type plasminogen activator kringle 2 domain complexed to 6-aminohexanoic acid an antifibrinolytic drug.
Related PDB 1pk2
Related UniProtKB P00750
[19]
Resource
Comments
Medline ID
PubMed ID 1309292
Journal Arch Biochem Biophys
Year 1992
Volume 292
Pages 206-12
Authors De Serrano VS, Sehl LC, Castellino FJ
Title Direct identification of lysine-33 as the principal cationic center of the omega-amino acid binding site of the recombinant kringle 2 domain of tissue-type plasminogen activator.
Related PDB
Related UniProtKB
[20]
Resource
Comments
Medline ID
PubMed ID 1554717
Journal Biochemistry
Year 1992
Volume 31
Pages 3326-35
Authors De Serrano VS, Castellino FJ
Title Role of tryptophan-74 of the recombinant kringle 2 domain of tissue-type plasminogen activator in its omega-amino acid binding properties.
Related PDB
Related UniProtKB
[21]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF KRINGLE 2.
Medline ID 92118803
PubMed ID 1310033
Journal Biochemistry
Year 1992
Volume 31
Pages 270-9
Authors de Vos AM, Ultsch MH, Kelley RF, Padmanabhan K, Tulinsky A, Westbrook ML, Kossiakoff AA
Title Crystal structure of the kringle 2 domain of tissue plasminogen activator at 2.4-A resolution.
Related PDB 1tpk
Related UniProtKB P00750
[22]
Resource
Comments
Medline ID
PubMed ID 1731899
Journal Biochemistry
Year 1992
Volume 31
Pages 419-22
Authors Eastman D, Wurm FM, van Reis R, Higgins DL
Title A region of tissue plasminogen activator that affects plasminogen activation differentially with various fibrin(ogen)-related stimulators.
Related PDB
Related UniProtKB
[23]
Resource
Comments
Medline ID
PubMed ID 1315765
Journal J Biol Chem
Year 1992
Volume 267
Pages 9668-77
Authors Bassel-Duby R, Jiang NY, Bittick T, Madison E, McGookey D, Orth K, Shohet R, Sambrook J, Gething MJ
Title Tyrosine 67 in the epidermal growth factor-like domain of tissue-type plasminogen activator is important for clearance by a specific hepatic receptor.
Related PDB
Related UniProtKB
[24]
Resource
Comments STRUCTURE BY NMR OF 38-85.
Medline ID 92292163
PubMed ID 1602484
Journal J Mol Biol
Year 1992
Volume 225
Pages 821-33
Authors Downing AK, Driscoll PC, Harvey TS, Dudgeon TJ, Smith BO, Baron M, Campbell ID
Title Solution structure of the fibrin binding finger domain of tissue-type plasminogen activator determined by 1H nuclear magnetic resonance.
Related PDB 1tpm 1tpn
Related UniProtKB P00750
[25]
Resource
Comments
Medline ID
PubMed ID 1321420
Journal Protein Eng
Year 1992
Volume 5
Pages 93-100
Authors Kohnert U, Rudolph R, Verheijen JH, Weening-Verhoeff EJ, Stern A, Opitz U, Martin U, Lill H, Prinz H, Lechner M, et al
Title Biochemical properties of the kringle 2 and protease domains are maintained in the refolded t-PA deletion variant BM 06.022.
Related PDB
Related UniProtKB
[26]
Resource
Comments
Medline ID
PubMed ID 1287881
Journal Thromb Haemost
Year 1992
Volume 68
Pages 672-7
Authors Yahara H, Matsumoto K, Maruyama H, Nagaoka T, Ikenaka Y, Yajima K, Fukao H, Ueshima S, Matsuo O
Title Recombinant variants of tissue-type plasminogen activator containing amino acid substitutions in the finger domain.
Related PDB
Related UniProtKB
[27]
Resource
Comments
Medline ID
PubMed ID 8424682
Journal Arch Biochem Biophys
Year 1993
Volume 300
Pages 472-82
Authors Rydzewski A, Castellino FJ
Title The effector roles of kringle 1 and kringle 2 in the enzymatic properties of recombinant tissue-type plasminogen activator as revealed by generation of recombinant molecules containing each kringle linked to the protease domain.
Related PDB
Related UniProtKB
[28]
Resource
Comments
Medline ID
PubMed ID 8385482
Journal Biochemistry
Year 1993
Volume 32
Pages 3540-8
Authors De Serrano VS, Castellino FJ
Title Specific anionic residues of the recombinant kringle 2 domain of tissue-type plasminogen activator that are responsible for stabilization of its interaction with omega-amino acid ligands.
Related PDB
Related UniProtKB
[29]
Resource
Comments
Medline ID
PubMed ID 8449917
Journal J Biol Chem
Year 1993
Volume 268
Pages 5550-6
Authors Lubin IM, Caban R, Runge MS
Title The tissue plasminogen activator finger domain confers fibrin-dependent enhancement of catalytic activity to single-chain urokinase-type plasminogen activator.
Related PDB
Related UniProtKB
[30]
Resource
Comments
Medline ID
PubMed ID 8030371
Journal Acta Biochim Pol
Year 1994
Volume 41
Pages 25-34
Authors Pietrucha T, Stec WJ, Okruszek A, Uznanski B, Koziolkiewicz M, Wilk A, Plucienniczak A, Swiatkowska M, Cierniewski CS
Title The epidermal growth factor-like domain from tissue plasminogen activator. Cloning in E. coli, purification and ESR studies of its interaction with human blood platelets.
Related PDB
Related UniProtKB
[31]
Resource
Comments
Medline ID
PubMed ID 8142348
Journal Biochemistry
Year 1994
Volume 33
Pages 3509-14
Authors De Serrano VS, Castellino FJ
Title Involvement of tyrosine-76 of the kringle 2 domain of tissue-type plasminogen activator in its thermal stability and its omega-amino acid ligand binding site.
Related PDB
Related UniProtKB
[32]
Resource
Comments
Medline ID
PubMed ID 8312251
Journal Biochemistry
Year 1994
Volume 33
Pages 1340-4
Authors De Serrano VS, Castellino FJ
Title Role of the strictly conserved tryptophan-25 residue in the stabilization of the structure and in the ligand binding properties of the kringle 2 domain of tissue-type plasminogen activator.
Related PDB
Related UniProtKB
[33]
Resource
Comments
Medline ID
PubMed ID 8175674
Journal J Biol Chem
Year 1994
Volume 269
Pages 12639-44
Authors Horrevoets AJ, Smilde A, de Vries C, Pannekoek H
Title The specific roles of finger and kringle 2 domains of tissue-type plasminogen activator during in vitro fibrinolysis.
Related PDB
Related UniProtKB
[34]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 8069221
Journal Protein Sci
Year 1994
Volume 3
Pages 898-910
Authors Padmanabhan K, Wu TP, Ravichandran KG, Tulinsky A
Title Kringle-kringle interactions in multimer kringle structures.
Related PDB 1pmk 1pml
Related UniProtKB
[35]
Resource
Comments
Medline ID
PubMed ID 7740461
Journal Thromb Haemost
Year 1994
Volume 72
Pages 900-5
Authors Stringer HA, van Swieten P, Horrevoets AJ, Smilde A, Pannekoek H
Title The role of the finger domain of tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor 1 (PAI-1) in initiation and progression of thrombolysis.
Related PDB
Related UniProtKB
[36]
Resource
Comments
Medline ID
PubMed ID 7893685
Journal Biochemistry
Year 1995
Volume 34
Pages 2739-50
Authors Byeon IJ, Kelley RF, Mulkerrin MG, An SS, Llinas M
Title Ligand binding to the tissue-type plasminogen activator kringle 2 domain: structural characterization by 1H-NMR.
Related PDB
Related UniProtKB
[37]
Resource
Comments
Medline ID
PubMed ID 7711052
Journal Biochim Biophys Acta
Year 1995
Volume 1248
Pages 1-10
Authors Rudd PM, Woods RJ, Wormald MR, Opdenakker G, Downing AK, Campbell ID, Dwek RA
Title The effects of variable glycosylation on the functional activities of ribonuclease, plasminogen and tissue plasminogen activator.
Related PDB
Related UniProtKB
[38]
Resource
Comments
Medline ID
PubMed ID 8530479
Journal J Biol Chem
Year 1995
Volume 270
Pages 30486-90
Authors Smith JW, Tachias K, Madison EL
Title Protein loop grafting to construct a variant of tissue-type plasminogen activator that binds platelet integrin alpha IIb beta 3.
Related PDB
Related UniProtKB
[39]
Resource
Comments
Medline ID
PubMed ID 7479691
Journal Protein Eng
Year 1995
Volume 8
Pages 293-300
Authors Bakker AH, Rehberg EF, Marotti KR, Verheijen JH
Title The position of the structurally autonomous kringle 2 domain influences the functional features of tissue-type plasminogen activator.
Related PDB
Related UniProtKB
[40]
Resource
Comments STRUCTURE BY NMR OF 36-126.
Medline ID 96027104
PubMed ID 7582899
Journal Structure
Year 1995
Volume 3
Pages 823-33
Authors Smith BO, Downing AK, Driscoll PC, Dudgeon TJ, Campbell ID
Title The solution structure and backbone dynamics of the fibronectin type I and epidermal growth factor-like pair of modules of tissue-type plasminogen activator.
Related PDB 1tpg
Related UniProtKB P00750
[41]
Resource
Comments
Medline ID
PubMed ID 8605163
Journal Biochemistry
Year 1996
Volume 35
Pages 3270-6
Authors Hu CK, Kohnert U, Sturzebecher J, Fischer S, Llinas M
Title Complexation of the tissue plasminogen activator protease with benzamidine-type inhibitors: interference by the kringle 2 module.
Related PDB
Related UniProtKB
[42]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF CATALYTIC DOMAIN.
Medline ID 96200985
PubMed ID 8613982
Journal J Mol Biol
Year 1996
Volume 258
Pages 117-35
Authors Lamba D, Bauer M, Huber R, Fischer S, Rudolph R, Kohnert U, Bode W
Title The 2.3 A crystal structure of the catalytic domain of recombinant two-chain human tissue-type plasminogen activator.
Related PDB 1rtf
Related UniProtKB P00750
[43]
Resource
Comments
Medline ID
PubMed ID 8736495
Journal Protein Eng
Year 1996
Volume 9
Pages 283-90
Authors Sehl LC, Nguyen HV, Berleau LT, Arcila P, Bennett WF, Keyt BA
Title Locating the unpaired cysteine of tissue-type plasminogen activator.
Related PDB
Related UniProtKB
[44]
Resource
Comments
Medline ID
PubMed ID 9201906
Journal Biochemistry
Year 1997
Volume 36
Pages 7652-63
Authors Chang Y, Zajicek J, Castellino FJ
Title Role of tryptophan-63 of the kringle 2 domain of tissue-type plasminogen activator in its thermal stability, folding, and ligand binding properties.
Related PDB
Related UniProtKB
[45]
Resource
Comments TISSUE=Salivary gland;
Medline ID 98022741
PubMed ID 9354616
Journal Biochemistry
Year 1997
Volume 36
Pages 13483-93
Authors Renatus M, Stubbs MT, Huber R, Bringmann P, Donner P, Schleuning WD, Bode W
Title Catalytic domain structure of vampire bat plasminogen activator: a molecular paradigm for proteolysis without activation cleavage.
Related PDB 1a5i
Related UniProtKB P98119
[46]
Resource
Comments
Medline ID
PubMed ID 9434908
Journal Curr Opin Struct Biol
Year 1997
Volume 7
Pages 865-72
Authors Bode W, Renatus M
Title Tissue-type plasminogen activator: variants and crystal/solution structures demarcate structural determinants of function.
Related PDB
Related UniProtKB
[47]
Resource
Comments X-RAY CRYSTALLOGRAPHY (3.1 ANGSTROMS) OF CATALYTIC DOMAIN.
Medline ID 97449126
PubMed ID 9305622
Journal EMBO J
Year 1997
Volume 16
Pages 4797-805
Authors Renatus M, Engh RA, Stubbs MT, Huber R, Fischer S, Kohnert U, Bode W
Title Lysine 156 promotes the anomalous proenzyme activity of tPA: X-ray crystal structure of single-chain human tPA.
Related PDB 1bda
Related UniProtKB P00750
[48]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 9268299
Journal J Biol Chem
Year 1997
Volume 272
Pages 21713-9
Authors Renatus M, Bode W, Huber R, Sturzebecher J, Prasa D, Fischer S, Kohnert U, Stubbs MT
Title Structural mapping of the active site specificity determinants of human tissue-type plasminogen activator. Implications for the design of low molecular weight substrates and inhibitors.
Related PDB 1a5h
Related UniProtKB
[49]
Resource
Comments
Medline ID
PubMed ID 10543954
Journal J Mol Biol
Year 1999
Volume 293
Pages 613-27
Authors Dekker RJ, Eichinger A, Stoop AA, Bode W, Pannekoek H, Horrevoets AJ
Title The variable region-1 from tissue-type plasminogen activator confers specificity for plasminogen activator inhibitor-1 to thrombin by facilitating catalysis: release of a kinetic block by a heterologous protein surface loop.
Related PDB
Related UniProtKB
[50]
Resource
Comments
Medline ID
PubMed ID 10408340
Journal J Pept Res
Year 1999
Volume 53
Pages 656-64
Authors Chang Y, Nilsen SL, Castellino FJ
Title Functional and structural consequences of aromatic residue substitutions within the kringle-2 domain of tissue-type plasminogen activator.
Related PDB
Related UniProtKB
[51]
Resource
Comments
Medline ID
PubMed ID 10744692
Journal J Biol Chem
Year 2000
Volume 275
Pages 10112-20
Authors Stewart RJ, Fredenburgh JC, Leslie BA, Keyt BA, Rischke JA, Weitz JI
Title Identification of the mechanism responsible for the increased fibrin specificity of TNK-tissue plasminogen activator relative to tissue plasminogen activator.
Related PDB
Related UniProtKB
[52]
Resource
Comments
Medline ID
PubMed ID 12696753
Journal Curr Top Dev Biol
Year 2003
Volume 54
Pages 263-312
Authors Ellis V
Title Plasminogen activation at the cell surface.
Related PDB
Related UniProtKB
[53]
Resource
Comments
Medline ID
PubMed ID 14500731
Journal J Biol Chem
Year 2003
Volume 278
Pages 48197-203
Authors Perron MJ, Blouse GE, Shore JD
Title Distortion of the catalytic domain of tissue-type plasminogen activator by plasminogen activator inhibitor-1 coincides with the formation of stable serpin-proteinase complexes.
Related PDB
Related UniProtKB

Comments
This enzyme belongs to the peptidase family-S1.
This enzyme is composed of six domains; fibronectin type-I domain, EGF-like domain, Kringle1 domain, Kringle2 domain and catalytic domains of serine protease.
The PDB structures correspond to the following domains.
(PDB;1tpg, Swiss-prot;P00750, residues 36-126 [EGF-like/Kringle1 domain],
PDB;1pk2, Swiss-prot;P00750, residues 209-297 [klingle2 domain],
PDB;1a5hA, Swiss-prot;P00750, residues 311-562 [Catalytic domain]).
As this enzyme has got a classical catalytic triad composed of Ser/His/Asp, which is the same as that of trypsin (D00197 in EzCatDB), it should have a similar mechanism.

Created Updated
2004-08-13 2011-02-21