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Version 2.5
Creation Date 2005-06-13 13:24:05
Update Date 2009-06-23 18:06:03
Primary Accession Number DB00302
Secondary Accession Number
  • APRD01270
  • EXPT00508
Name Tranexamic Acid
Drug Type
  • Approved
  • Small Molecule
Description Antifibrinolytic hemostatic used in severe hemorrhage. [PubChem]
Synonyms
  1. Tranexamsaeure
  2. Tranhexamic acid
  3. Trans AMCHA
  4. tranexmic acid
  5. trans-4-aminomethylcyclohexane-1-carboxylic acid
  6. trans-Amcha
  7. trans-Tranexamic acid
Brand Names
  1. Amcha
  2. Amikapron
  3. Amstat
  4. Anvitoff
  5. Carxamin
  6. Cyclocapron
  7. Cyklokapron
  8. Emorhalt
  9. Frenolyse
  10. Mastop
  11. Rikavarin
  12. Rikavarin-S
  13. Tamcha
  14. Tranexan
  15. Transamin
  16. Trasamlon
  17. Ugurol
Brand Mixtures Not Available
Chemical IUPAC Name 4-(aminomethyl)cyclohexane-1-carboxylic acid
Chemical Formula C8H15NO2
Chemical Structure Structure
CAS Registry Number 1197-18-8
InChI Identifier InChI=1/C8H15NO2/c9-5-6-1-3-7(4-2-6)8(10)11/h6-7H,1-5,9H2,(H,10,11)/f/h10H
InChI Key GYDJEQRTZSCIOI-KZFATGLACS
KEGG Drug D01136 Link Image
KEGG Compound Not Available
PubChem Compound 5526 Link Image
PubChem Substance 582925 Link Image
ChEBI ID Not Available
PharmGKB ID PA451738 Link Image
HET ID AMH Link Image
GenBank ID Not Available
Drug ID Number [DIN] 02064413 Link Image
RxList Link http://www.rxlist.com/cgi/generic3/cyclapron.htm Link Image
PDRhealth Link Not Available
Wikipedia Link http://en.wikipedia.org/wiki/Tranexamic_acid Link Image
FDA Label Not Available
Material Safety Data Sheet (MSDS)
Synthesis Reference Not Available
Average Molecular Weight 157.2102
Monoisotopic Molecular Weight 157.1103
State Solid
Melting Point >300 oC
Experimental Water Solubility 1.67E+005 mg/L Source: PhysProp
Predicted Water Solubility 1.82e+01 mg/mL Calculated using ALOGPS
Experimental LogP/Hydrophobicity 0.3 Source: PhysProp
Predicted LogP -1.42 Calculated using ALOGPS
Experimental LogS Not Available
Predicted LogS -0.94 Calculated using ALOGPS
Experimental Caco2 Permeability Not Available
pKa/Isoelectric Point Not Available
Mass Spectrum Not Available
MOL File Show Link Image | Download Link Image
SDF File Show Link Image | Download Link Image
PDB File Show Link Image | Download Link Image
2D Structure
3D Structure
Experimental PDB ID 1B2I Link Image
Experimental PDB File Show
Experimental PDB Structure
Isomeric SMILES NC[C@H]1CC[C@H](CC1)C(O)=O
Canonical SMILES NCC1CCC(CC1)C(O)=O
Drug Category
  • Antifibrinolytic Agents
ATC Codes
AHFS Codes
  • 20:28.16
Indication For use in patients with hemophilia for short term use (two to eight days) to reduce or prevent hemorrhage and reduce the need for replacement therapy during and following tooth extraction.
Pharmacology Tranexamic acid is an antifibrinolytic that competitively inhibits the activation of plasminogen to plasmin. Tranexamic acid is a competitive inhibitor of plasminogen activation, and at much higher concentrations, a noncompetitive inhibitor of plasmin, i.e., actions similar to aminocaproic acid. Tranexamic acid is about 10 times more potent in vitro than aminocaproic acid. Tranexamic acid binds more strongly than aminocaproic acid to both the strong and weak receptor sites of the plasminogen molecule in a ratio corresponding to the difference in potency between the compounds. Tranexamic acid in a concentration of 1 mg per mL does not aggregate platelets in vitro. In patients with hereditary angioedema, inhibition of the formation and activity of plasmin by tranexamic acid may prevent attacks of angioedema by decreasing plasmin-induced activation of the first complement protein (C1).
Mechanism of Action Tranexamic acid competitively inhibits activation of plasminogen (via binding to the kringle domain), thereby reducing conversion of plasminogen to plasmin (fibrinolysin), an enzyme that degrades fibrin clots, fibrinogen, and other plasma proteins, including the procoagulant factors V and VIII. Tranexamic acid also directly inhibits plasmin activity, but higher doses are required than are needed to reduce plasmin formation.
Absorption Absorption of tranexamic acid after oral administration in humans represents approximately 30 to 50% of the ingested dose and bioavailability is not affected by food intake.
Toxicity Oral LD50 in mice is >10 gm/kg. Symptoms of overdosage may be nausea, vomiting, orthostatic symptoms and/or hypotension.
Protein Binding The plasma protein binding of tranexamic acid is about 3% at therapeutic plasma levels and seems to be fully accounted for by its binding to plasminogen (does not bind serum albumin).
Biotransformation Only a small fraction of the drug is metabolized (less than 5%).
Half Life Biological half-life in the joint fluid is about 3 hours.
Dosage Forms
Form Route
Solution Intravenous
Tablet Oral
Patient Information Not Available
Contraindications Show Link Image
Interactions Show Link Image
Drug Interactions Not Available
Food Interactions Not Available
Pathways
Name SMPDB Link KEGG Link
Tranexamic Acid Pathway SMP00287 Link Image
General References
  1. Wikipedia Link Image
  2. RxList Link Image
Organisms Affected
  • Humans and other mammals
Targets
  1. Plasminogen
  2. Tissue-type plasminogen activator
Drug Target 1 [top]
Target 1 ID 234
Target 1 Name Plasminogen
Target 1 Synonyms
  1. EC 3.4.21.7
  2. Plasminogen precursor
Target 1 Gene Name PLG
Target 1 Protein Sequence >Plasminogen precursor 
MEHKEVVLLLLLFLKSGQGEPLDDYVNTQGASLFSVTKKQLGAGSIEECAAKCEEDEEFT
CRAFQYHSKEQQCVIMAENRKSSIIIRMRDVVLFEKKVYLSECKTGNGKNYRGTMSKTKN
GITCQKWSSTSPHRPRFSPATHPSEGLEENYCRNPDNDPQGPWCYTTDPEKRYDYCDILE
CEEECMHCSGENYDGKISKTMSGLECQAWDSQSPHAHGYIPSKFPNKNLKKNYCRNPDRE
LRPWCFTTDPNKRWELCDIPRCTTPPPSSGPTYQCLKGTGENYRGNVAVTVSGHTCQHWS
AQTPHTHNRTPENFPCKNLDENYCRNPDGKRAPWCHTTNSQVRWEYCKIPSCDSSPVSTE
QLAPTAPPELTPVVQDCYHGDGQSYRGTSSTTTTGKKCQSWSSMTPHRHQKTPENYPNAG
LTMNYCRNPDADKGPWCFTTDPSVRWEYCNLKKCSGTEASVVAPPPVVLLPDVETPSEED
CMFGNGKGYRGKRATTVTGTPCQDWAAQEPHRHSIFTPETNPRAGLEKNYCRNPDGDVGG
PWCYTTNPRKLYDYCDVPQCAAPSFDCGKPQVEPKKCPGRVVGGCVAHPHSWPWQVSLRT
RFGMHFCGGTLISPEWVLTAAHCLEKSPRPSSYKVILGAHQEVNLEPHVQEIEVSRLFLE
PTRKDIALLKLSSPAVITDKVIPACLPSPNYVVADRTECFITGWGETQGTFGAGLLKEAQ
LPVIENKVCNRYEFLNGRVQSTELCAGHLAGGTDSCQGDSGGPLVCFEKDKYILQGVTSW
GLGCARPNKPGVYVRVSRFVTWIEGVMRNN
Target 1 Number of Residues 823
Target 1 Molecular Weight 90569
Target 1 Theoretical pI 7.25
Target 1 GO Classification
Function
binding
ion binding
cation binding
calcium ion binding
catalytic activity
hydrolase activity
peptidase activity
endopeptidase activity
serine-type endopeptidase activity
plasmin activity
Process
metabolism
macromolecule metabolism
protein metabolism
cellular protein metabolism
proteolysis
physiological process
organismal physiological process
regulation of body fluids
hemostasis
blood coagulation
Component
Not Available
Target 1 General Function Involved in plasmin activity
Target 1 Specific Function Angiostatin is an angiogenesis inhibitor that blocks neovascularization and growth of experimental primary and metastatic tumors in vivo
Target 1 Pathways Not Available
Target 1 Reactions
  • Preferential cleavage: Lys! > Arg!; higher selectivity than trypsin. Converts fibrin into soluble products
Target 1 Pfam Domain Function
Target 1 Signals
  • 1-19
Target 1 Transmembrane Regions
  • None
Target 1 Essentiality Non-Essential
Target 1 GenBank ID Protein 387026 Link Image
Target 1 UniProtKB/Swiss-Prot ID P00747 Link Image
Target 1 UniProtKB/Swiss-Prot Entry Name PLMN_HUMAN Link Image
Target 1 PDB ID 1KI0 Link Image
Target 1 PDB File Show
Target 1 3D Structure
Target 1 Cellular Location
  • Secreted protein
Target 1 Gene Sequence >2433 bp 
ATGGAACATAAGGAAGTGGTTCTTCTACTTCTTTTATTTCTGAAATCAGGTCAAGGAGAG
CCTCTGGATGACTATGTGAATACCCAGGGGGCTTCACTGTTCAGTGTCACTAAGAAGCAG
CTGGGAGCAGGAAGTATAGAAGAATGTGCAGCAAAATGTGAGGAGGACGAAGAATTCACC
TGCAGGGCATTCCAATATCACAGTAAAGAGCAACAATGTGTGATAATGGCTGAAAACAGG
AAGTCCTCCATAATCATTAGGATGAGAGATGTAGTTTTATTTGAAAAGAAAGTGTATCTC
TCAGAGTGCAAGACTGGGAATGGAAAGAATTACAGAGGGACGATGTCCAAAACAAAAAAT
GGCATCACCTGTCAAAAATGGAGTTCCACTTCTCCCCACAGACCTAGATTCTCACCTGCT
ACACACCCCTCAGAGGGACTGGAGGAGAACTACTGCAGGAATCCAGACAACGATCCGCAG
GGGCCCTGGTGCTATACTACTGATCCAGAAAAGAGATATGACTACTGCGACATTCTTGAG
TGTGAAGAGGAATGTATGCATTGCAGTGGAGAAAACTATGACGGCAAAATTTCCAAGACC
ATGTCTGGACTGGAATGCCAGGCCTGGGACTCTCAGAGCCCACACGCTCATGGATACATT
CCTTCCAAATTTCCAAACAAGAACCTGAAGAAGAATTACTGTCGTAACCCCGATAGGGAG
CTGCGGCCTTGGTGTTTCACCACCGACCCCAACAAGCGCTGGGAACTTTGCGACATCCCC
CGCTGCACAACACCTCCACCATCTTCTGGTCCCACCTACCAGTGTCTGAAGGGAACAGGT
GAAAACTATCGCGGGAATGTGGCTGTTACCGTGTCCGGGCACACCTGTCAGCACTGGAGT
GCACAGACCCCTCACACACATAACAGGACACCAGAAAACTTTCCCTGCAAAAATTTGGAT
GAAAACTACTGCCGCAATCCTGACGGAAAAAGGGCCCCATGGTGCCATACAACCAACAGC
CAAGTGCGGTGGGAGTACTGTAAGATACCGTCCTGTGACTCCTCCCCAGTATCCACGGAA
CAATTGGCTCCCACAGCACCACCTGAGCTAACCCCTGTGGTCCAGGACTGCTACCATGGT
GATGGACAGAGCTACCGAGGCACATCCTCCACCACCACCACAGGAAAGAAGTGTCAGTCT
TGGTCATCTATGACACCACACCGGCACCAGAAGACCCCAGAAAACTACCCAAATGCTGGC
CTGACAATGAACTACTGCAGGAATCCAGATGCCGATAAAGGCCCCTGGTGTTTTACCACA
GACCCCAGCGTCAGGTGGGAGTACTGCAACCTGAAAAAATGCTCAGGAACAGAAGCGAGT
GTTGTAGCACCTCCGCCTGTTGTCCTGCTTCCAAATGTAGAGACTCCTTCCGAAGAAGAC
TGTATGTTTGGGAATGGGAAAGGATACCGAGGCAAGAGGGCGACCACTGTTACTGGGACG
CCATGCCAGGACTGGGCTGCCCAGGAGCCCCATAGACACAGCATTTTCACTCCAGAGACA
AATCCACGGGCGGGTCTGGAAAAAAATTACTGCCGTAACCCTGATGGTGATGTAGGTGGT
CCCTGGTGCTACACGACAAATCCAAGAAAACTTTACGACTACTGTGATGTCCCTCAGTGT
GCGGCCCCTTCATTTGATTGTGGGAAGCCTCAAGTGGAGCCGAAGAAATGTCCTGGAAGG
GTTGTAGGGGGGTGTGTGGCCCACCCACATTCCTGGCCCTGGCAAGTCAGTCTTAGAACA
AGGTTTGGAATGCACTTCTGTGGAGGCACCTTGATATCCCCAGAGTGGGTGTTGACTGCT
GCCCACTGCTTGGAGAAGTCCCCAAGGCCTTCATCCTACAAGGTCATCCTGGGTGCACAC
CAAGAAGTGAATCTCGAACCGCATGTTCAGGAAATAGAAGTGTCTAGGCTGTTCTTGGAG
CCCACACGAAAAGATATTGCCTTGCTAAAGCTAAGCAGTCCTGCCGTCATCACTGACAAA
GTAATCCCAGCTTGTCTGCCATCCCCAAATTATGTGGTCGCTGACCGGACCGAATGTTTC
ATCACTGGCTGGGGAGAAACCCAAGGTACTTTTGGAGCTGGCCTTCTCAAGGAAGCCCAG
CTCCCTGTGATTGAGAATAAAGTGTGCAATCGCTATGAGTTTCTGAATGGAAGAGTCCAA
TCCACCGAACTCTGTGCTGGGCATTTGGCCGGAGGCACTGACAGTTGCCAGGGTGACAGT
GGAGGGCCTCTGGTTTGCTTCGAGAAGGACAAATACATTTTACAAGGAGTCACTTCTTGG
GGTCTTGGCTGTGCACGCCCCAATAAGCCTGGTGTCTATGTTCGTGTTTCAAGGTTTGTT
ACTTGGATTGAGGGAGTGATGAGAAATAATTAA
Target 1 GenBank Gene ID
Target 1 GeneCard ID PLG Link Image
Target 1 GenAtlas ID PLG Link Image
Target 1 HGNC ID HGNC:9071 Link Image
Target 1 Chromosome Location 6
Target 1 Locus 6q26
Target 1 SNPs SNPJam Report Link Image
Target 1 General References
  1. Schuster V, Seidenspinner S, Zeitler P, Escher C, Pleyer U, Bernauer W, Stiehm ER, Isenberg S, Seregard S, Olsson T, Mingers AM, Schambeck C, Kreth HW: Compound-heterozygous mutations in the plasminogen gene predispose to the development of ligneous conjunctivitis. Blood. 1999 May 15;93(10):3457-66. [PubMed Link Image]
  2. Wiman B, Wallen P: Structural relationship between "glutamic acid" and "lysine" forms of human plasminogen and their interaction with the NH2-terminal activation peptide as studied by affinity chromatography. Eur J Biochem. 1975 Jan 15;50(3):489-94. [PubMed Link Image]
  3. Wiman B, Wallen P: Amino-acid sequence of the cyanogen-bromide fragment from human plasminogen that forms the linkage between the plasmin chains. Eur J Biochem. 1975 Oct 15;58(2):539-47. [PubMed Link Image]
  4. Wiman B: Primary structure of the B-chain of human plasmin. Eur J Biochem. 1977 Jun 1;76(1):129-37. [PubMed Link Image]
  5. Kikuchi S, Yamanouchi Y, Li L, Kobayashi K, Ijima H, Miyazaki R, Tsuchiya S, Hamaguchi H: Plasminogen with type-I mutation is polymorphic in the Japanese population. Hum Genet. 1992 Sep-Oct;90(1-2):7-11. [PubMed Link Image]
  6. Mulichak AM, Tulinsky A, Ravichandran KG: Crystal and molecular structure of human plasminogen kringle 4 refined at 1.9-A resolution. Biochemistry. 1991 Oct 29;30(43):10576-88. [PubMed Link Image]
  7. Wu TP, Padmanabhan K, Tulinsky A, Mulichak AM: The refined structure of the epsilon-aminocaproic acid complex of human plasminogen kringle 4. Biochemistry. 1991 Oct 29;30(43):10589-94. [PubMed Link Image]
  8. Ichinose A, Espling ES, Takamatsu J, Saito H, Shinmyozu K, Maruyama I, Petersen TE, Davie EW: Two types of abnormal genes for plasminogen in families with a predisposition for thrombosis. Proc Natl Acad Sci U S A. 1991 Jan 1;88(1):115-9. [PubMed Link Image]
  9. Atkinson RA, Williams RJ: Solution structure of the kringle 4 domain from human plasminogen by 1H nuclear magnetic resonance spectroscopy and distance geometry. J Mol Biol. 1990 Apr 5;212(3):541-52. [PubMed Link Image]
  10. Petersen TE, Martzen MR, Ichinose A, Davie EW: Characterization of the gene for human plasminogen, a key proenzyme in the fibrinolytic system. J Biol Chem. 1990 Apr 15;265(11):6104-11. [PubMed Link Image]
  11. 3030813 Forsgren M, Raden B, Israelsson M, Larsson K, Heden LO: Molecular cloning and characterization of a full-length cDNA clone for human plasminogen. FEBS Lett. 1987 Mar 23;213(2):254-60.
  12. 3356193 Marti T, Schaller J, Rickli EE, Schmid K, Kamerling JP, Gerwig GJ, van Halbeek H, Vliegenthart JF: The N- and O-linked carbohydrate chains of human, bovine and porcine plasminogen. Species specificity in relation to sialylation and fucosylation patterns. Eur J Biochem. 1988 Apr 5;173(1):57-63.
  13. 4240117 Groskopf WR, Summaria L, Robbins KC: Studies on the active center of human plasmin. Partial amino acid sequence of a peptide containing the active center serine residue. J Biol Chem. 1969 Jul 10;244(13):3590-7.
  14. 4694729 Robbins KC, Bernabe P, Arzadon L, Summaria L: The primary structure of human plasminogen. II. The histidine loop of human plasmin: light (B) chain active center histidine sequence. J Biol Chem. 1973 Mar 10;248(5):1631-3.
  15. 6094526 Vali Z, Patthy L: The fibrin-binding site of human plasminogen. Arginines 32 and 34 are essential for fibrin affinity of the kringle 1 domain. J Biol Chem. 1984 Nov 25;259(22):13690-4.
  16. 6148961 Malinowski DP, Sadler JE, Davie EW: Characterization of a complementary deoxyribonucleic acid coding for human and bovine plasminogen. Biochemistry. 1984 Aug 28;23(18):4243-50.
  17. 6216475 Miyata T, Iwanaga S, Sakata Y, Aoki N: Plasminogen Tochigi: inactive plasmin resulting from replacement of alanine-600 by threonine in the active site. Proc Natl Acad Sci U S A. 1982 Oct;79(20):6132-6.
  18. 6238949 Miyata T, Iwanaga S, Sakata Y, Aoki N, Takamatsu J, Kamiya T: Plasminogens Tochigi II and Nagoya: two additional molecular defects with Ala-600----Thr replacement found in plasmin light chain variants. J Biochem (Tokyo). 1984 Aug;96(2):277-87.
  19. 6919539 Trexler M, Vali Z, Patthy L: Structure of the omega-aminocarboxylic acid-binding sites of human plasminogen. Arginine 70 and aspartic acid 56 are essential for binding of ligand by kringle 4. J Biol Chem. 1982 Jul 10;257(13):7401-6.
  20. 7525077 O'Reilly MS, Holmgren L, Shing Y, Chen C, Rosenthal RA, Moses M, Lane WS, Cao Y, Sage EH, Folkman J: Angiostatin: a novel angiogenesis inhibitor that mediates the suppression of metastases by a Lewis lung carcinoma. Cell. 1994 Oct 21;79(2):315-28.
  21. 8181475 Rejante MR, Llinas M: 1H-NMR assignments and secondary structure of human plasminogen kringle 1. Eur J Biochem. 1994 May 1;221(3):927-37.
  22. 8181476 Rejante MR, Llinas M: Solution structure of the epsilon-aminohexanoic acid complex of human plasminogen kringle 1. Eur J Biochem. 1994 May 1;221(3):939-49.
  23. 8392398 Azuma H, Uno Y, Shigekiyo T, Saito S: Congenital plasminogen deficiency caused by a Ser572 to Pro mutation. Blood. 1993 Jul 15;82(2):475-80.
  24. 8611560 Mathews II, Vanderhoff-Hanaver P, Castellino FJ, Tulinsky A: Crystal structures of the recombinant kringle 1 domain of human plasminogen in complexes with the ligands epsilon-aminocaproic acid and trans-4-(aminomethyl)cyclohexane-1-carboxylic Acid. Biochemistry. 1996 Feb 27;35(8):2567-76.
  25. 8652577 Sohndel S, Hu CK, Marti D, Affolter M, Schaller J, Llinas M, Rickli EE: Recombinant gene expression and 1H NMR characteristics of the kringle (2 + 3) supermodule: spectroscopic/functional individuality of plasminogen kringle domains. Biochemistry. 1996 Feb 20;35(7):2357-64.
  26. 9054441 Pirie-Shepherd SR, Stevens RD, Andon NL, Enghild JJ, Pizzo SV: Evidence for a novel O-linked sialylated trisaccharide on Ser-248 of human plasminogen 2. J Biol Chem. 1997 Mar 14;272(11):7408-11.
  27. 9102221 Sim BK, O'Reilly MS, Liang H, Fortier AH, He W, Madsen JW, Lapcevich R, Nacy CA: A recombinant human angiostatin protein inhibits experimental primary and metastatic cancer. Cancer Res. 1997 Apr 1;57(7):1329-34.
  28. 9201958 Wang H, Prorok M, Bretthauer RK, Castellino FJ: Serine-578 is a major phosphorylation locus in human plasma plasminogen. Biochemistry. 1997 Jul 1;36(26):8100-6.
  29. 9242524 Schuster V, Mingers AM, Seidenspinner S, Nussgens Z, Pukrop T, Kreth HW: Homozygous mutations in the plasminogen gene of two unrelated girls with ligneous conjunctivitis. Blood. 1997 Aug 1;90(3):958-66.
  30. 9521645 Chang Y, Mochalkin I, McCance SG, Cheng B, Tulinsky A, Castellino FJ: Structure and ligand binding determinants of the recombinant kringle 5 domain of human plasminogen. Biochemistry. 1998 Mar 10;37(10):3258-71.
  31. 9858247 Higuchi Y, Furihata K, Ueno I, Ishikawa S, Okumura N, Tozuka M, Sakurai N: Plasminogen Kanagawa-I, a novel missense mutation, is caused by the amino acid substitution G732R. Br J Haematol. 1998 Dec;103(3):867-70.
Target 1 Drug References
  1. Dunn CJ, Goa KL: Tranexamic acid: a review of its use in surgery and other indications. Drugs. 1999 Jun;57(6):1005-32. [PubMed Link Image]
  2. Marti DN, Schaller J, Llinas M: Solution structure and dynamics of the plasminogen kringle 2-AMCHA complex: 3(1)-helix in homologous domains. Biochemistry. 1999 Nov 30;38(48):15741-55. [PubMed Link Image]
  3. Jansen AJ, Andreica S, Claeys M, D'Haese J, Camu F, Jochmans K: Use of tranexamic acid for an effective blood conservation strategy after total knee arthroplasty. Br J Anaesth. 1999 Oct;83(4):596-601. [PubMed Link Image]
  4. Bangert K, Thorsen S: Assay of functional plasminogen in rat plasma applicable to experimental studies of thrombolysis. Thromb Haemost. 2000 Aug;84(2):299-306. [PubMed Link Image]
  5. Hanson AJ, Quinn MT: Effect of fibrin sealant composition on human neutrophil chemotaxis. J Biomed Mater Res. 2002 Sep 5;61(3):474-81. [PubMed Link Image]
Drug Target 2 [top]
Target 2 ID 1792
Target 2 Name Tissue-type plasminogen activator
Target 2 Synonyms
  1. Alteplase
  2. EC 3.4.21.68
  3. Reteplase
  4. Tissue-type plasminogen activator precursor
  5. t- PA
  6. t-plasminogen activator
  7. tPA
Target 2 Gene Name PLAT
Target 2 Protein Sequence >Tissue-type plasminogen activator precursor 
MDAMKRGLCCVLLLCGAVFVSPSQEIHARFRRGARSYQVICRDEKTQMIYQQHQSWLRPV
LRSNRVEYCWCNSGRAQCHSVPVKSCSEPRCFNGGTCQQALYFSDFVCQCPEGFAGKCCE
IDTRATCYEDQGISYRGTWSTAESGAECTNWNSSALAQKPYSGRRPDAIRLGLGNHNYCR
NPDRDSKPWCYVFKAGKYSSEFCSTPACSEGNSDCYFGNGSAYRGTHSLTESGASCLPWN
SMILIGKVYTAQNPSAQALGLGKHNYCRNPDGDAKPWCHVLKNRRLTWEYCDVPSCSTCG
LRQYSQPQFRIKGGLFADIASHPWQAAIFAKHRRSPGERFLCGGILISSCWILSAAHCFQ
ERFPPHHLTVILGRTYRVVPGEEEQKFEVEKYIVHKEFDDDTYDNDIALLQLKSDSSRCA
QESSVVRTVCLPPADLQLPDWTECELSGYGKHEALSPFYSERLKEAHVRLYPSSRCTSQH
LLNRTVTDNMLCAGDTRSGGPQANLHDACQGDSGGPLVCLNDGRMTLVGIISWGLGCGQK
DVPGVYTKVTNYLDWIRDNMRP
Target 2 Number of Residues 571
Target 2 Molecular Weight 62917
Target 2 Theoretical pI 7.81
Target 2 GO Classification
Function
catalytic activity
hydrolase activity
peptidase activity
endopeptidase activity
serine-type endopeptidase activity
plasminogen activator activity
Process
physiological process
metabolism
macromolecule metabolism
protein metabolism
cellular protein metabolism
proteolysis
Component
extracellular region
Target 2 General Function Involved in plasminogen activator activity
Target 2 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
Target 2 Pathways Not Available
Target 2 Reactions
  • Specific cleavage of Arg!Val bond in plasminogen to form plasmin EFFECTOR Fibrin
Target 2 Pfam Domain Function
Target 2 Signals
  • 1-23
Target 2 Transmembrane Regions
  • None
Target 2 Essentiality Non-Essential
Target 2 GenBank ID Protein 339834 Link Image
Target 2 UniProtKB/Swiss-Prot ID P00750 Link Image
Target 2 UniProtKB/Swiss-Prot Entry Name TPA_HUMAN Link Image
Target 2 PDB ID 1BDA Link Image
Target 2 PDB File Show
Target 2 3D Structure
Target 2 Cellular Location
  • Secreted protein
  • extracellular space
Target 2 Gene Sequence >1689 bp 
ATGGATGCAATGAAGAGAGGGCTCTGCTGTGTGCTGCTGCTGTGTGGAGCAGTCTTCGTT
TCGCCCAGCCAGGAAATCCATGCCCGATTCAGAAGAGGAGCCAGATCTTACCAAGTGATC
TGCAGAGATGAAAAAACGCAGATGATATACCAGCAACATCAGTCATGGCTGCGCCCTGTG
CTCAGAAGCAACCGGGTGGAATATTGCTGGTGCAACAGTGGCAGGGCACAGTGCCACTCA
GTGCCTGTCAAAAGTTGCAGCGAGCCAAGGTGTTTCACCGGGGGCACCTGCCAGCAGGCC
CTGTACTTCTCAGATTTCGTGTGCCAGTGCCCCGAAGGATTTGCTGGGAAGTGCTGTGAA
ATAGATACCAGGGCCACGTGCTACGAGGACCAGGGCATCAGCTACAGGGGCACGTGGAGC
ACAGCGGAGAGTGGCGCCGAGTGCACCAACTGGAACAGCAGCGCGTTGGCCCAGAAGCCC
TACAGCGGGCGGAGGCCAGATGCCATCAGGCTGGGCCTGGGGAACCACAACTACTGCAGA
AACCCAGATCGAGACTCAAAGCCCTGGTGCTACGTCTTTAAGGCGGGGAAGTACAGCTCA
GAGTTCTGCAGCACCCCTGCCTGCTCTGAGGGAAACAGTGACTGCTACTTTGGGAATGGG
TCAGCCTACCGTGGCACGCACAGCCTCACCGAGTCGGGTGCCTCCTGCCTCCCGTGGAAT
TCCATGATCCTGATAGGCAAGGTTTACACAGCACAGAACCCCAGTGCCCAGGCACTGGGC
CTGGGCAAACATAATTACTGCCGGAATCCTGATGGGGATGCCAAGCCCTGGTGCCACGTG
CTGAAGAACCGCAGGCTGACGTGGGAGTACTGTGATGTGCCCTCCTGCTCCACCTGCGGC
CTGAGACAGTACAGCCAGCCTCAGTTTCGCATCAAAGGAGGGCTCTTCGCCGACATCGCC
TCCCACCCCTGGCAGGCTGCCATCTTTGCCAAGCACAGGAGGTCGCCCGGAGAGCGGTTC
CTGTGCGGGGGCATACTCATCAGCTCCTGCTGGATTCTCTCTGCCGCCCACTGCTTCCAG
GAGAGGTTTCCGCCCCACCACCTGACGGTGATCTTGGGCAGAACATACCGGGTGGTCCCT
GGCGAGGAGGAGCAGAAATTTGAAGTCGAAAAATACATTGTCCATAAGGAATTCGATGAT
GACACTTACGACAATGACATTGCGCTGCTGCAGCTGAAATCGGATTCGTCCCGCTGTGCC
CAGGAGAGCAGCGTGGTCCGCACTGTGTGCCTTCCCCCGGCGGACCTGCAGCTGCCGGAC
TGGACGGAGTGTGAGCTCTCCGGCTACGGCAAGCATGAGGCCTTGTCTCCTTTCTATTCG
GAGCGGCTGAAGGAGGCTCATGTCAGACTGTACCCATCCAGCCGCTGCACATCACAACAT
TTACTTAACAGAACAGTCACCGACAACATGCTGTGTGCTGGAGACACTCGGAGCGGCGGG
CCCCAGGCAAACTTGCACGACGCCTGCCAGGGCGATTCGGGAGGCCCCCTGGTGTGTCTG
AACGATGGCCGCATGACTTTGGTGGGCATCATCAGCTGGGGCCTGGGCTGTGGACAGAAG
GATGTCCCGGGTGTGTACACCAAGGTTACCAACTACCTAGACTGGATTCGTGACAACATG
CGACCGTGA
Target 2 GenBank Gene ID
Target 2 GeneCard ID PLAT Link Image
Target 2 GenAtlas ID PLAT Link Image
Target 2 HGNC ID HGNC:9051 Link Image
Target 2 Chromosome Location 8
Target 2 Locus 8p12
Target 2 SNPs SNPJam Report Link Image
Target 2 General References
  1. 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 Link Image]
  2. 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 Link Image]
  3. 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 Link Image]
  4. 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 Link Image]
  5. 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 Link Image]
  6. 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 Link Image]
  7. 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 Link Image]
  8. 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 Link Image]
  9. 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 Link Image]
  10. 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 Link Image]
  11. 2558718 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.
  12. 2824147 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.
  13. 3009482 Degen SJ, Rajput B, Reich E: The human tissue plasminogen activator gene. J Biol Chem. 1986 May 25;261(15):6972-85.
  14. 3090401 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.
  15. 3133640 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.
  16. 3161893 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.
  17. 6089198 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.
  18. 6337343 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.
  19. 6433976 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.
  20. 6572897 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.
  21. 6682760 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.
  22. 7582899 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.
  23. 8613982 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.
  24. 9305622 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.
Target 2 Drug References
  1. Kojima T, Gando S, Morimoto Y, Mashio H, Goda Y, Kawahigashi H, Kemmotsu O: Systematic elucidation of effects of tranexamic acid on fibrinolysis and bleeding during and after cardiopulmonary bypass surgery. Thromb Res. 2001 Dec 1;104(5):301-7. [PubMed Link Image]
  2. Leroux P, Hennebert O, Legros H, Laudenbach V, Carmeliet P, Marret S: Role of tissue-plasminogen activator (t-PA) in a mouse model of neonatal white matter lesions: interaction with plasmin inhibitors and anti-inflammatory drugs. Neuroscience. 2007 May 11;146(2):670-8. Epub 2007 Feb 22. [PubMed Link Image]
  3. Takada A, Takada Y: Inhibition by tranexamic acid of the conversion of single-chain tissue plasminogen activator to its two chain form by plasmin: the presence on tissue plasminogen activator of a site to bind with lysine binding sites of plasmin. Thromb Res. 1989 Sep 15;55(6):717-25. [PubMed Link Image]

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.