STE14/YDR410C Summary Help

Standard Name STE14 1
Systematic Name YDR410C
Feature Type ORF, Verified
Description Farnesyl cysteine-carboxyl methyltransferase; mediates the carboxyl methylation step during C-terminal CAAX motif processing of a-factor and RAS proteins in the endoplasmic reticulum, localizes to the ER membrane (2, 3, 4 and see Summary Paragraph)
Name Description STErile
Chromosomal Location
ChrIV:1293091 to 1292372 | ORF Map | GBrowse
Note: this feature is encoded on the Crick strand.
Gbrowse
Genetic position: 259.47 cM
Gene Ontology Annotations All STE14 GO evidence and references
  View Computational GO annotations for STE14
Molecular Function
Manually curated
Biological Process
Manually curated
Cellular Component
Manually curated
High-throughput
Regulators 4 genes
Resources
Classical genetics
null
overexpression
unspecified
Large-scale survey
null
overexpression
Resources
20 total interaction(s) for 15 unique genes/features.
Physical Interactions
  • Affinity Capture-MS: 1
  • Affinity Capture-Western: 1
  • PCA: 3
  • Reconstituted Complex: 2

Genetic Interactions
  • Negative Genetic: 4
  • Phenotypic Enhancement: 2
  • Positive Genetic: 4
  • Synthetic Growth Defect: 3

Resources
Expression Summary
histogram
Resources
Length (a.a.) 239
Molecular Weight (Da) 27,887
Isoelectric Point (pI) 8.03
Localization
Phosphorylation PhosphoGRID | PhosphoPep Database
Structure
Homologs
sequence information
ChrIV:1293091 to 1292372 | ORF Map | GBrowse
Note: this feature is encoded on the Crick strand.
SGD ORF map
Genetic position: 259.47 cM
Last Update Coordinates: 2011-02-03 | Sequence: 1996-07-31
Subfeature details
Relative
Coordinates
Chromosomal
Coordinates
Most Recent Updates
Coordinates Sequence
CDS 1..720 1293091..1292372 2011-02-03 1996-07-31
Retrieve sequences
Analyze Sequence
S288C only
S288C vs. other species
S288C vs. other strains
Resources
External Links All Associated Seq | E.C. | Entrez Gene | Entrez RefSeq Protein | MIPS | Search all NCBI (Entrez) | UniProtKB
Primary SGDIDS000002818
SUMMARY PARAGRAPH for STE14

STE14 encodes the founding member of a protein family of eukaryotic methyltransferases called the isoprenylcysteine carboxyl methyltransferase (ICMT) family (reviewed in 5). The Ste14p carboxymethyltransferase mediates methylation of the cysteine residue in the C-terminal CAAX motif that is present in some signal transduction proteins, such as Ras2p and a-factor pheromone (6, 7). The CAAX motif is the site of protein isoprenylation (farnesylation or geranylgeranylation) of the protein, and methylation by Ste14p occurs after attachment of the isoprenyl group to the cysteine and cleavage of the terminal AAX species (8). The net effect of these post-translational modifications is to increase the hydrophobicity of the prenylated proteins to direct them to membranes (reviewed in 9).

Ste14p localizes to the endoplasmic reticulum membrane (4). Topology studies have led to the proposal that Ste14p has six transmembrane spans, with two loops exposed to the ER lumen and the others present in the cytosol (5). A consensus sequence characteristic of ICMT proteins lies in the C terminus; it is comprised of a stretch of hydrophobic amino acids that form a helical hairpin and are flanked by two regions of amino acid conservation (5).

Null mutations in STE14 prevent mating because they block the carboxymethlyation step of a-factor pheromone maturation (7). The resulting unmethylated form remains a substrate for further N-terminal processing of a-factor, but the final form cannot be exported from the cell by the ABC transporter Ste6p to initiate the mating response (10).

STE14 homologs have been identified in a number of organisms, and the Schizosaccharomyces pombe, Arabidopsis thaliana, and human (OMIM) homologs have each been shown to complement the defects caused by a ste14 mutation in yeast (11, 4, 12, 13). Studies with small molecule inhibitors of ICMT proteins suggest that they are a good anticancer target for treatment of Ras-based cancers (9).

Last updated: 2008-03-02 Contact SGD

References cited on this page View Complete Literature Guide for STE14
1) Michaelis, S.  (1993) Personal Communication, Mortimer Map Edition 12
2) Hrycyna CA, et al.  (1991) The Saccharomyces cerevisiae STE14 gene encodes a methyltransferase that mediates C-terminal methylation of a-factor and RAS proteins. EMBO J 10(7):1699-709
3) Hrycyna CA and Clarke S  (1990) Farnesyl cysteine C-terminal methyltransferase activity is dependent upon the STE14 gene product in Saccharomyces cerevisiae. Mol Cell Biol 10(10):5071-6
4) Romano JD, et al.  (1998) The Saccharomyces cerevisiae prenylcysteine carboxyl methyltransferase Ste14p is in the endoplasmic reticulum membrane. Mol Biol Cell 9(8):2231-47
5) Romano JD and Michaelis S  (2001) Topological and mutational analysis of Saccharomyces cerevisiae Ste14p, founding member of the isoprenylcysteine carboxyl methyltransferase family. Mol Biol Cell 12(7):1957-71
6) Anderson JL, et al.  (2005) Purification, functional reconstitution, and characterization of the Saccharomyces cerevisiae isoprenylcysteine carboxylmethyltransferase Ste14p. J Biol Chem 280(8):7336-45
7) Marr RS, et al.  (1990) Saccharomyces cerevisiae STE14 gene is required for COOH-terminal methylation of a-factor mating pheromone. J Biol Chem 265(33):20057-60
8) Chen P, et al.  (1997) Biogenesis of the Saccharomyces cerevisiae mating pheromone a-factor. J Cell Biol 136(2):251-69
9) Anderson JL, et al.  (2005) The isoprenoid substrate specificity of isoprenylcysteine carboxylmethyltransferase: development of novel inhibitors. J Biol Chem 280(33):29454-61
10) Huyer G, et al.  (2006) Saccharomyces cerevisiae a-factor mutants reveal residues critical for processing, activity, and export. Eukaryot Cell 5(9):1560-70
11) Imai Y, et al.  (1997) Genes encoding farnesyl cysteine carboxyl methyltransferase in Schizosaccharomyces pombe and Xenopus laevis. Mol Cell Biol 17(3):1543-51
12) Dai Q, et al.  (1998) Mammalian prenylcysteine carboxyl methyltransferase is in the endoplasmic reticulum. J Biol Chem 273(24):15030-4
13) Crowell DN and Kennedy M  (2001) Identification and functional expression in yeast of a prenylcysteine alpha-carboxyl methyltransferase gene from Arabidopsis thaliana. Plant Mol Biol 45(4):469-76