ICMT:Zn2+ transfers CH3 from AdoMet to isoprenylated proteins

Stable Identifier
Reaction [transition]
Homo sapiens
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Protein-S-isoprenylcysteine O-methyltransferase (ICMT) mediates the post-translational methyl esterification of C-terminal CAAX motifs in prenylated proteins such as the oncoprotein RAS and related GTPases, neutralising the negative charge of prenylcysteine species and thereby determining their subcellular localisation and correct biological function (Wright et al. 2009, Yang et al. 2011). ICMT may serve as a therapeutic target in cancer development (Lau et al. 2014, Diver et al. 2014).
Literature References
PubMed ID Title Journal Year
22195972 Mechanism of isoprenylcysteine carboxyl methylation from the crystal structure of the integral membrane methyltransferase ICMT

Zhang, Z, Yang, J, Kulkarni, K, Mas-Droux, C, Manolaridis, I, Barford, D, Dodd, RB

Mol. Cell 2011
24971579 An improved isoprenylcysteine carboxylmethyltransferase inhibitor induces cancer cell death and attenuates tumor growth in vivo

Guo, D, Yang, T, Wirawan, M, Casey, PJ, Lau, HY, Wang, M, Go, ML, Ramanujulu, PM

Cancer Biol. Ther. 2014
19158273 Topology of mammalian isoprenylcysteine carboxyl methyltransferase determined in live cells with a fluorescent probe

Court, H, Casey, PJ, Philips, MR, Wright, LP, Ahearn, IM, Mor, A

Mol. Cell. Biol. 2009
25059662 Mutational analysis of the integral membrane methyltransferase isoprenylcysteine carboxyl methyltransferase (ICMT) reveals potential substrate binding sites

Long, SB, Diver, MM

J. Biol. Chem. 2014
Catalyst Activity

protein C-terminal S-isoprenylcysteine carboxyl O-methyltransferase activity of ICMT:Zn2+ [endoplasmic reticulum membrane]

Orthologous Events
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