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. [PubMed:6337343]
  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. [PubMed:6089198]
  3. Degen SJ, Rajput B, Reich E: The human tissue plasminogen activator gene. J Biol Chem. 1986 May 25;261(15):6972-85. [PubMed:3009482]
  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. [PubMed:3090401]
  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. [PubMed:2824147]
  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. [PubMed:3133640]
  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. [PubMed:2107528]
  8. Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. [PubMed:14702039]
  9. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [PubMed:15489334]
  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. [PubMed:3161893]
  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. [PubMed:1368681]
  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. [PubMed:6682760]
  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. [PubMed:6433976]
  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. [PubMed:6572897]
  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. [PubMed:2513186]
  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. [PubMed:1900431]
  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. [PubMed:1645336]
  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. [PubMed:10340997]
  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. [PubMed:11384978]
  20. Hillman RT, Green RE, Brenner SE: An unappreciated role for RNA surveillance. Genome Biol. 2004;5(2):R8. Epub 2004 Feb 2. [PubMed:14759258]
  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. [PubMed:2558718]
  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. [PubMed:1901789]
  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. [PubMed:1762144]
  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. [PubMed:1310033]
  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. [PubMed:1602484]
  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. [PubMed:7582899]
  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. [PubMed:8613982]
  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. [PubMed:9305622]

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