Tissue-type plasminogen activator

Details

Name
Tissue-type plasminogen activator
Synonyms
  • 3.4.21.68
  • t-PA
Gene Name
PLAT
Organism
Humans
Amino acid sequence
>lcl|BSEQ0002165|Tissue-type plasminogen activator
MDAMKRGLCCVLLLCGAVFVSPSQEIHARFRRGARSYQVICRDEKTQMIYQQHQSWLRPV
LRSNRVEYCWCNSGRAQCHSVPVKSCSEPRCFNGGTCQQALYFSDFVCQCPEGFAGKCCE
IDTRATCYEDQGISYRGTWSTAESGAECTNWNSSALAQKPYSGRRPDAIRLGLGNHNYCR
NPDRDSKPWCYVFKAGKYSSEFCSTPACSEGNSDCYFGNGSAYRGTHSLTESGASCLPWN
SMILIGKVYTAQNPSAQALGLGKHNYCRNPDGDAKPWCHVLKNRRLTWEYCDVPSCSTCG
LRQYSQPQFRIKGGLFADIASHPWQAAIFAKHRRSPGERFLCGGILISSCWILSAAHCFQ
ERFPPHHLTVILGRTYRVVPGEEEQKFEVEKYIVHKEFDDDTYDNDIALLQLKSDSSRCA
QESSVVRTVCLPPADLQLPDWTECELSGYGKHEALSPFYSERLKEAHVRLYPSSRCTSQH
LLNRTVTDNMLCAGDTRSGGPQANLHDACQGDSGGPLVCLNDGRMTLVGIISWGLGCGQK
DVPGVYTKVTNYLDWIRDNMRP
Number of residues
562
Molecular Weight
62916.495
Theoretical pI
7.81
GO Classification
Functions
glycoprotein binding / phosphoprotein binding / receptor binding / serine-type endopeptidase activity
Processes
blood coagulation / cellular protein modification process / fibrinolysis / negative regulation of proteolysis / plasminogen activation / platelet-derived growth factor receptor signaling pathway / proteolysis / response to hypoxia / response to peptide hormone / smooth muscle cell migration
Components
apical part of cell / cell surface / cytoplasm / extracellular exosome / extracellular region / extracellular space / secretory granule
General Function
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. Plays a direct role in facilitating neuronal migration.
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Secreted
Gene sequence
>lcl|BSEQ0010763|Tissue-type plasminogen activator (PLAT)
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
Chromosome Location
8
Locus
8p12
External Identifiers
ResourceLink
UniProtKB IDP00750
UniProtKB Entry NameTPA_HUMAN
GenBank Protein ID339834
GenBank Gene IDL00153
GenAtlas IDPLAT
HGNC IDHGNC:9051
General References
  1. 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. [Article]
  2. 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. [Article]
  3. Degen SJ, Rajput B, Reich E: The human tissue plasminogen activator gene. J Biol Chem. 1986 May 25;261(15):6972-85. [Article]
  4. 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. [Article]
  5. 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. [Article]
  6. 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. [Article]
  7. 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. [Article]
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  10. 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. [Article]
  11. 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. [Article]
  12. 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. [Article]
  13. 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. [Article]
  14. 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. [Article]
  15. 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. [Article]
  16. 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. [Article]
  17. 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. [Article]
  18. He S, Lin YL, Liu YX: Functionally inactive protein C inhibitor in seminal plasma may be associated with infertility. Mol Hum Reprod. 1999 Jun;5(6):513-9. [Article]
  19. 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. [Article]
  20. Hillman RT, Green RE, Brenner SE: An unappreciated role for RNA surveillance. Genome Biol. 2004;5(2):R8. Epub 2004 Feb 2. [Article]
  21. 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. [Article]
  22. 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. [Article]
  23. 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. [Article]
  24. 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. [Article]
  25. 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. [Article]
  26. 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. [Article]
  27. 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. [Article]
  28. 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. [Article]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB00513Aminocaproic acidapproved, investigationalyesantagonistDetails
DB01088Iloprostapproved, investigationalunknownother/unknownDetails
DB076845-(DIMETHYLAMINO)-2-NAPHTHALENESULFONIC ACIDexperimentalunknownDetails
DB06404Human C1-esterase inhibitorapprovedyesinhibitorDetails
DB09228Conestat alfaapproved, investigationalyesinhibitorDetails
DB09213Dexibuprofenapproved, investigationalunknownmodulatorDetails
DB16701PlasminogenapprovedunknownsubstrateDetails