Protein-S-isoprenylcysteine O-methyltransferase

ICMT
Identifiers
Symbol	ICMT
Pfam	PF04140
Pfam clan	CL0115
InterPro	IPR007269
OPM superfamily	159
OPM protein	4a2n
Available protein structures: Pfam   structures / ECOD   PDB RCSB PDB; PDBe; PDBj PDBsum structure summary

protein-S-isoprenylcysteine O-methyltransferase
Identifiers
EC no.	2.1.1.100
CAS no.	130731-20-3
Databases
IntEnz	IntEnz view
BRENDA	BRENDA entry
ExPASy	NiceZyme view
KEGG	KEGG entry
MetaCyc	metabolic pathway
PRIAM	profile
PDB structures	RCSB PDB PDBe PDBsum
Gene Ontology	AmiGO / QuickGO
Search PMC articles PubMed articles NCBI proteins

The isoprenylcysteine o-methyltransferase (EC 2.1.1.100) carries out carboxyl methylation of cleaved eukaryotic proteins that terminate in a CaaX motif. In Saccharomyces cerevisiae (Baker's yeast) this methylation is carried out by Ste14p, an integral endoplasmic reticulum membrane protein. Ste14p is the founding member of the isoprenylcysteine carboxyl methyltransferase (ICMT) family, whose members share significant sequence homology.^[1]

The enzyme catalyzes the chemical reaction

S-adenosyl-L-methionine + protein C-terminal S-farnesyl-L-cysteine ${\displaystyle \rightleftharpoons }$ S-adenosyl-L-homocysteine + protein C-terminal S-farnesyl-L-cysteine methyl ester

Thus, the two substrates of this enzyme are S-adenosyl methionine and protein C-terminal S-farnesyl-L-cysteine, whereas its two products are S-adenosylhomocysteine and protein C-terminal S-farnesyl-L-cysteine methyl ester.

References

1. Romano JD, Michaelis S (July 2001). "Topological and mutational analysis of Saccharomyces cerevisiae Ste14p, founding member of the isoprenylcysteine carboxyl methyltransferase family". Mol. Biol. Cell. 12 (7): 1957–71. doi:10.1091/mbc.12.7.1957. PMC 55642. PMID 11451995.

• Clarke S, Vogel JP, Deschenes RJ, Stock J (1988). "Posttranslational modification of the Ha-ras oncogene protein: evidence for a third class of protein carboxyl methyltransferases". Proc. Natl. Acad. Sci. U.S.A. 85 (13): 4643–7. Bibcode:1988PNAS...85.4643C. doi:10.1073/pnas.85.13.4643. PMC 280491. PMID 3290900.
• Ota IM, Clarke S (1989). "Enzymatic methylation of 23-29-kDa bovine retinal rod outer segment membrane proteins. Evidence for methyl ester formation at carboxyl-terminal cysteinyl residues". J. Biol. Chem. 264 (22): 12879–84. doi:10.1016/S0021-9258(18)51569-6. PMID 2753892.
• Stephenson RC, Clarke S (1990). "Identification of a C-terminal protein carboxyl methyltransferase in rat liver membranes utilizing a synthetic farnesyl cysteine-containing peptide substrate". J. Biol. Chem. 265 (27): 16248–54. doi:10.1016/S0021-9258(17)46215-6. PMID 2398053.

This article incorporates text from the public domain Pfam and InterPro: IPR007269