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Identification
HMDB Protein ID HMDBP01868
Secondary Accession Numbers
  • 7262
Name Tissue-type plasminogen activator
Synonyms
  1. Alteplase
  2. Reteplase
  3. Tissue-type plasminogen activator chain A
  4. Tissue-type plasminogen activator chain B
  5. t-PA
  6. t-plasminogen activator
  7. tPA
Gene Name PLAT
Protein Type Enzyme
Biological Properties
General Function Involved in serine-type endopeptidase activity
Specific Function 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. Play a direct role in facilitating neuronal migration
Pathways
  • Acenocoumarol Action Pathway
  • Alteplase Action Pathway
  • Aminocaproic Acid Action Pathway
  • Anistreplase Action Pathway
  • Aprotinin Action Pathway
  • Ardeparin Action Pathway
  • Argatroban Action Pathway
  • Bivalirudin Action Pathway
  • Coagulation
  • Dicoumarol Action Pathway
  • Dicumarol Action Pathway
  • Enoxaparin Action Pathway
  • Fondaparinux Action Pathway
  • Heparin Action Pathway
  • Lepirudin Action Pathway
  • Phenindione Action Pathway
  • Phenprocoumon Action Pathway
  • Reteplase Action Pathway
  • Streptokinase Action Pathway
  • Tenecteplase Action Pathway
  • Tranexamic Acid Action Pathway
  • Urokinase Action Pathway
  • Warfarin Action Pathway
  • Ximelagatran Action Pathway
Reactions Not Available
GO Classification
Component
extracellular region
Function
endopeptidase activity
serine-type endopeptidase activity
catalytic activity
hydrolase activity
peptidase activity
peptidase activity, acting on l-amino acid peptides
Process
metabolic process
macromolecule metabolic process
protein metabolic process
proteolysis
Cellular Location
  1. Secreted
  2. extracellular space
Gene Properties
Chromosome Location Chromosome:8
Locus 8p12
SNPs PLAT
Gene Sequence
>1689 bp
ATGGATGCAATGAAGAGAGGGCTCTGCTGTGTGCTGCTGCTGTGTGGAGCAGTCTTCGTT
TCGCCCAGCCAGGAAATCCATGCCCGATTCAGAAGAGGAGCCAGATCTTACCAAGTGATC
TGCAGAGATGAAAAAACGCAGATGATATACCAGCAACATCAGTCATGGCTGCGCCCTGTG
CTCAGAAGCAACCGGGTGGAATATTGCTGGTGCAACAGTGGCAGGGCACAGTGCCACTCA
GTGCCTGTCAAAAGTTGCAGCGAGCCAAGGTGTTTCAACGGGGGCACCTGCCAGCAGGCC
CTGTACTTCTCAGATTTCGTGTGCCAGTGCCCCGAAGGATTTGCTGGGAAGTGCTGTGAA
ATAGATACCAGGGCCACGTGCTACGAGGACCAGGGCATCAGCTACAGGGGCACGTGGAGC
ACAGCGGAGAGTGGCGCCGAGTGCACCAACTGGAACAGCAGCGCGTTGGCCCAGAAGCCC
TACAGCGGGCGGAGGCCAGACGCCATCAGGCTGGGCCTGGGGAACCACAACTACTGCAGA
AACCCAGATCGAGACTCAAAGCCCTGGTGCTACGTCTTTAAGGCGGGGAAGTACAGCTCA
GAGTTCTGCAGCACCCCTGCCTGCTCTGAGGGAAACAGTGACTGCTACTTTGGGAATGGG
TCAGCCTACCGTGGCACGCACAGCCTCACCGAGTCGGGTGCCTCCTGCCTCCCGTGGAAT
TCCATGATCCTGATAGGCAAGGTTTACACAGCACAGAACCCCAGTGCCCAGGCACTGGGC
CTGGGCAAACATAATTACTGCCGGAATCCTGATGGGGATGCCAAGCCCTGGTGCCACGTG
CTGAAGAACCGCAGGCTGACGTGGGAGTACTGTGATGTGCCCTCCTGCTCCACCTGCGGC
CTGAGACAGTACAGCCAGCCTCAGTTTCGCATCAAAGGAGGGCTCTTCGCCGACATCGCC
TCCCACCCCTGGCAGGCTGCCATCTTTGCCAAGCACAGGAGGTCGCCCGGAGAGCGGTTC
CTGTGCGGGGGCATACTCATCAGCTCCTGCTGGATTCTCTCTGCCGCCCACTGCTTCCAG
GAGAGGTTTCCGCCCCACCACCTGACGGTGATCTTGGGCAGAACATACCGGGTGGTCCCT
GGCGAGGAGGAGCAGAAATTTGAAGTCGAAAAATACATTGTCCATAAGGAATTCGATGAT
GACACTTACGACAATGACATTGCGCTGCTGCAGCTGAAATCGGATTCGTCCCGCTGTGCC
CAGGAGAGCAGCGTGGTCCGCACTGTGTGCCTTCCCCCGGCGGACCTGCAGCTGCCGGAC
TGGACGGAGTGTGAGCTCTCCGGCTACGGCAAGCATGAGGCCTTGTCTCCTTTCTATTCG
GAGCGGCTGAAGGAGGCTCATGTCAGACTGTACCCATCCAGCCGCTGCACATCACAACAT
TTACTTAACAGAACAGTCACCGACAACATGCTGTGTGCTGGAGACACTCGGAGCGGCGGG
CCCCAGGCAAACTTGCACGACGCCTGCCAGGGCGATTCGGGAGGCCCCCTGGTGTGTCTG
AACGATGGCCGCATGACTTTGGTGGGCATCATCAGCTGGGGCCTGGGCTGTGGACAGAAG
GATGTCCCGGGTGTGTACACCAAGGTTACCAACTACCTAGACTGGATTCGTGACAACATG
CGACCGTGA
Protein Properties
Number of Residues 562
Molecular Weight 62916.5
Theoretical pI 7.81
Pfam Domain Function
Signals
  • 1-22
Transmembrane Regions
  • None
Protein Sequence
>Tissue-type plasminogen activator
MDAMKRGLCCVLLLCGAVFVSPSQEIHARFRRGARSYQVICRDEKTQMIYQQHQSWLRPV
LRSNRVEYCWCNSGRAQCHSVPVKSCSEPRCFNGGTCQQALYFSDFVCQCPEGFAGKCCE
IDTRATCYEDQGISYRGTWSTAESGAECTNWNSSALAQKPYSGRRPDAIRLGLGNHNYCR
NPDRDSKPWCYVFKAGKYSSEFCSTPACSEGNSDCYFGNGSAYRGTHSLTESGASCLPWN
SMILIGKVYTAQNPSAQALGLGKHNYCRNPDGDAKPWCHVLKNRRLTWEYCDVPSCSTCG
LRQYSQPQFRIKGGLFADIASHPWQAAIFAKHRRSPGERFLCGGILISSCWILSAAHCFQ
ERFPPHHLTVILGRTYRVVPGEEEQKFEVEKYIVHKEFDDDTYDNDIALLQLKSDSSRCA
QESSVVRTVCLPPADLQLPDWTECELSGYGKHEALSPFYSERLKEAHVRLYPSSRCTSQH
LLNRTVTDNMLCAGDTRSGGPQANLHDACQGDSGGPLVCLNDGRMTLVGIISWGLGCGQK
DVPGVYTKVTNYLDWIRDNMRP
GenBank ID Protein 190032
UniProtKB/Swiss-Prot ID P00750
UniProtKB/Swiss-Prot Entry Name TPA_HUMAN
PDB IDs
GenBank Gene ID M15518
GeneCard ID PLAT
GenAtlas ID PLAT
HGNC ID HGNC:9051
References
General References
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  3. Hillman RT, Green RE, Brenner SE: An unappreciated role for RNA surveillance. Genome Biol. 2004;5(2):R8. Epub 2004 Feb 2. [PubMed:14759258 ]
  4. Liu CX, Li Y, Obermoeller-McCormick LM, Schwartz AL, Bu G: The putative tumor suppressor LRP1B, a novel member of the low density lipoprotein (LDL) receptor family, exhibits both overlapping and distinct properties with the LDL receptor-related protein. J Biol Chem. 2001 Aug 3;276(31):28889-96. Epub 2001 May 30. [PubMed:11384978 ]
  5. Pennica D, Holmes WE, Kohr WJ, Harkins RN, Vehar GA, Ward CA, Bennett WF, Yelverton E, Seeburg PH, Heyneker HL, Goeddel DV, Collen D: Cloning and expression of human tissue-type plasminogen activator cDNA in E. coli. Nature. 1983 Jan 20;301(5897):214-21. [PubMed:6337343 ]
  6. Ny T, Elgh F, Lund B: The structure of the human tissue-type plasminogen activator gene: correlation of intron and exon structures to functional and structural domains. Proc Natl Acad Sci U S A. 1984 Sep;81(17):5355-9. [PubMed:6089198 ]
  7. Degen SJ, Rajput B, Reich E: The human tissue plasminogen activator gene. J Biol Chem. 1986 May 25;261(15):6972-85. [PubMed:3009482 ]
  8. Harris TJ, Patel T, Marston FA, Little S, Emtage JS, Opdenakker G, Volckaert G, Rombauts W, Billiau A, De Somer P: Cloning of cDNA coding for human tissue-type plasminogen activator and its expression in Escherichia coli. Mol Biol Med. 1986 Jun;3(3):279-92. [PubMed:3090401 ]
  9. Reddy VB, Garramone AJ, Sasak H, Wei CM, Watkins P, Galli J, Hsiung N: Expression of human uterine tissue-type plasminogen activator in mouse cells using BPV vectors. DNA. 1987 Oct;6(5):461-72. [PubMed:2824147 ]
  10. Sasaki H, Saito Y, Hayashi M, Otsuka K, Niwa M: Nucleotide sequence of the tissue-type plasminogen activator cDNA from human fetal lung cells. Nucleic Acids Res. 1988 Jun 24;16(12):5695. [PubMed:3133640 ]
  11. Siebert PD, Fong K: Variant tissue-type plasminogen activator (PLAT) cDNA obtained from human endothelial cells. Nucleic Acids Res. 1990 Feb 25;18(4):1086. [PubMed:2107528 ]
  12. Fisher R, Waller EK, Grossi G, Thompson D, Tizard R, Schleuning WD: Isolation and characterization of the human tissue-type plasminogen activator structural gene including its 5' flanking region. J Biol Chem. 1985 Sep 15;260(20):11223-30. [PubMed:3161893 ]
  13. Itagaki Y, Yasuda H, Morinaga T, Mitsuda S, Higashio K: Purification and characterization of tissue plasminogen activator secreted by human embryonic lung diploid fibroblasts, IMR-90 cells. Agric Biol Chem. 1991 May;55(5):1225-32. [PubMed:1368681 ]
  14. Wallen P, Pohl G, Bergsdorf N, Ranby M, Ny T, Jornvall H: Purification and characterization of a melanoma cell plasminogen activator. Eur J Biochem. 1983 May 16;132(3):681-6. [PubMed:6682760 ]
  15. Pohl G, Kallstrom M, Bergsdorf N, Wallen P, Jornvall H: Tissue plasminogen activator: peptide analyses confirm an indirectly derived amino acid sequence, identify the active site serine residue, establish glycosylation sites, and localize variant differences. Biochemistry. 1984 Jul 31;23(16):3701-7. [PubMed:6433976 ]
  16. Edlund T, Ny T, Ranby M, Heden LO, Palm G, Holmgren E, Josephson S: Isolation of cDNA sequences coding for a part of human tissue plasminogen activator. Proc Natl Acad Sci U S A. 1983 Jan;80(2):349-52. [PubMed:6572897 ]
  17. Pfeiffer G, Schmidt M, Strube KH, Geyer R: Carbohydrate structure of recombinant human uterine tissue plasminogen activator expressed in mouse epithelial cells. Eur J Biochem. 1989 Dec 8;186(1-2):273-86. [PubMed:2513186 ]
  18. Harris RJ, Leonard CK, Guzzetta AW, Spellman MW: Tissue plasminogen activator has an O-linked fucose attached to threonine-61 in the epidermal growth factor domain. Biochemistry. 1991 Mar 5;30(9):2311-4. [PubMed:1900431 ]
  19. Vlahos CJ, Wilhelm OG, Hassell T, Jaskunas SR, Bang NU: Disulfide pairing of the recombinant kringle-2 domain of tissue plasminogen activator produced in Escherichia coli. J Biol Chem. 1991 Jun 5;266(16):10070-2. [PubMed:1645336 ]
  20. Byeon IJ, Kelley RF, Llinas M: 1H NMR structural characterization of a recombinant kringle 2 domain from human tissue-type plasminogen activator. Biochemistry. 1989 Nov 28;28(24):9350-60. [PubMed:2558718 ]
  21. Byeon IJ, Kelley RF, Llinas M: Kringle-2 domain of the tissue-type plasminogen activator. 1H-NMR assignments and secondary structure. Eur J Biochem. 1991 Apr 10;197(1):155-65. [PubMed:1901789 ]
  22. Byeon IJ, Llinas M: Solution structure of the tissue-type plasminogen activator kringle 2 domain complexed to 6-aminohexanoic acid an antifibrinolytic drug. J Mol Biol. 1991 Dec 20;222(4):1035-51. [PubMed:1762144 ]
  23. de Vos AM, Ultsch MH, Kelley RF, Padmanabhan K, Tulinsky A, Westbrook ML, Kossiakoff AA: Crystal structure of the kringle 2 domain of tissue plasminogen activator at 2.4-A resolution. Biochemistry. 1992 Jan 14;31(1):270-9. [PubMed:1310033 ]
  24. Downing AK, Driscoll PC, Harvey TS, Dudgeon TJ, Smith BO, Baron M, Campbell ID: Solution structure of the fibrin binding finger domain of tissue-type plasminogen activator determined by 1H nuclear magnetic resonance. J Mol Biol. 1992 Jun 5;225(3):821-33. [PubMed:1602484 ]
  25. Smith BO, Downing AK, Driscoll PC, Dudgeon TJ, Campbell ID: The solution structure and backbone dynamics of the fibronectin type I and epidermal growth factor-like pair of modules of tissue-type plasminogen activator. Structure. 1995 Aug 15;3(8):823-33. [PubMed:7582899 ]
  26. Lamba D, Bauer M, Huber R, Fischer S, Rudolph R, Kohnert U, Bode W: The 2.3 A crystal structure of the catalytic domain of recombinant two-chain human tissue-type plasminogen activator. J Mol Biol. 1996 Apr 26;258(1):117-35. [PubMed:8613982 ]
  27. Renatus M, Engh RA, Stubbs MT, Huber R, Fischer S, Kohnert U, Bode W: Lysine 156 promotes the anomalous proenzyme activity of tPA: X-ray crystal structure of single-chain human tPA. EMBO J. 1997 Aug 15;16(16):4797-805. [PubMed:9305622 ]