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Unless otherwise stated all data on this page refer to the human proteins. Gene information is provided for human (Hs), mouse (Mm) and rat (Rn).
Farnesyltransferase is a member of the prenyltransferases family which also includes geranylgeranyltransferase types I (EC 126.96.36.199) and II (EC 188.8.131.52) . Protein farnesyltransferase catalyses the post-translational formation of a thioether linkage between the C-1 of an isoprenyl group and a cysteine residue fourth from the C-terminus of a protein (ie to the CaaX motif, where 'a' is an aliphatic amino acid and 'X' is usually serine, methionine, alanine or glutamine; leucine for EC 184.108.40.206) . Farnesyltransferase is a dimer, composed of an alpha and beta subunit and requires Mg2+ and Zn2+ ions as cofactors. The active site is located between the subunits. Prenylation creates a hydrophobic domain on protein tails which acts as a membrane anchor.
Substrates of the prenyltransferases include Ras, Rho, Rab, other Ras-related small GTP-binding proteins, G-protein γ-subunits, nuclear lamins, centromeric proteins and many proteins involved in visual signal transduction.
In relation to the causative association between oncogenic Ras proteins and cancer, farnesyltransferase has become an important mechanistic drug discovery target.
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2. Casey PJ, Seabra MC. (1996) Protein prenyltransferases. J. Biol. Chem., 271 (10): 5289-92. [PMID:8621375]
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4. Furfine ES, Leban JJ, Landavazo A, Moomaw JF, Casey PJ. (1995) Protein farnesyltransferase: kinetics of farnesyl pyrophosphate binding and product release. Biochemistry, 34 (20): 6857-62. [PMID:7756316]
5. Hunt JT, Ding CZ, Batorsky R, Bednarz M, Bhide R, Cho Y, Chong S, Chao S, Gullo-Brown J, Guo P et al.. (2000) Discovery of (R)-7-cyano-2,3,4, 5-tetrahydro-1-(1H-imidazol-4-ylmethyl)-3- (phenylmethyl)-4-(2-thienylsulfonyl)-1H-1,4-benzodiazepine (BMS-214662), a farnesyltransferase inhibitor with potent preclinical antitumor activity. J. Med. Chem., 43 (20): 3587-95. [PMID:11020273]
6. Kohl NE, Wilson FR, Mosser SD, Giuliani E, deSolms SJ, Conner MW, Anthony NJ, Holtz WJ, Gomez RP, Lee TJ et al.. (1994) Protein farnesyltransferase inhibitors block the growth of ras-dependent tumors in nude mice. Proc. Natl. Acad. Sci. U.S.A., 91 (19): 9141-5. [PMID:8090782]
7. Lee H, Lee J, Lee S, Shin Y, Jung W, Kim JH, Park K, Kim K, Cho HS, Ro S et al.. (2001) A novel class of highly potent, selective, and non-peptidic inhibitor of Ras farnesyltransferase (FTase). Bioorg. Med. Chem. Lett., 11 (23): 3069-72. [PMID:11714612]
8. Lerner EC, Qian Y, Blaskovich MA, Fossum RD, Vogt A, Sun J, Cox AD, Der CJ, Hamilton AD, Sebti SM. (1995) Ras CAAX peptidomimetic FTI-277 selectively blocks oncogenic Ras signaling by inducing cytoplasmic accumulation of inactive Ras-Raf complexes. J. Biol. Chem., 270 (45): 26802-6. [PMID:7592920]
Database page citation:
220.127.116.11 Protein farnesyltransferase. Accessed on 28/03/2017. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=898.
Concise Guide to PHARMACOLOGY citation:
Alexander SPH, Fabbro D, Kelly E, Marrion N, Peters JA, Benson HE, Faccenda E, Pawson AJ, Sharman JL, Southan C, Davies JA and CGTP Collaborators (2015) The Concise Guide to PHARMACOLOGY 2015/16: Enzymes. Br J Pharmacol. 172: 6024-6109.