Difference between revisions of "YGR157W"
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== Cho2 - domain structure and involvement in autophagy via Atg8p / LC3 ==
Cho2 - domain structure and involvement in autophagy via Atg8p / LC3 ==
Latest revision as of 09:17, 21 March 2013
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|Feature type||ORF, Verified|
Description of YGR157W: Phosphatidylethanolamine methyltransferase (PEMT), catalyzes the first step in the conversion of phosphatidylethanolamine to phosphatidylcholine during the methylation pathway of phosphatidylcholine biosynthesis
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Cho2 - domain structure and involvement in autophagy via Atg8p / LC3
Wlodarski et al  have identified a CoCoa_N domain at the carboxy-terminus of Cho2p. This is interesting, but not precisely for the reasons stated by Wlodarski et al., as explained below. Point (1) refers to the domain structure of Cho2p and points (2) and (3) provide an alternative likely function (and hence alternative binding partner) for a conserved motif in the carboxy-terminus of Cho2p to that suggested by Wlodarski et al.
(1) The enzymatic domain of Cho2p is repeated, as residues 35-321 are homologous to 344-577. This means that the whole amino-terminus 1-577 most likely contains an even number of transmembrane domains, despite automated prediction programmes suggesting an overall odd number. This is important because it sugests that the carboxy-terminus is in the cytoplasm (not in the lumen as might be assumed from Wlodarski et al.)
(2) the C-terminus of Cho2p contains WIGL. This motif is not only found in CoCoa_N, but also is found in the SKICH domains of phosphatidylinositol (4,5) bisphosphate 5-phosphatase (PIPP) and other proteins .
Critically the motif is of the form WxxL, which is the minimal requirement for motifs binding to Atg8/LC3 . WxxL motifs tend to have two other features also found in Cho2p: (A) they form beta-sheets, which is the structure for this portion of Cho2p predicted by PSI-PRED 3.0 (B) they are flanked by acidic residues (here in Cho2p: DDwiglYKVID). Together these factors create the strong suggestion that WIGL near the carboxy-terminus of Cho2p binds to Atg8p/LC3. Hence, it is predicted that Cho2p is directly involved in autophagy, possibly by methylating phosphatidylethanolamine, which is specifically required to activate Atg8p/LC3.
(3) Wlodarski et al. suggest that DWIGLYKV in Cho2p interacts with transcriptional activators related to p300, and so Cho2p is active in chromatic remodelling. However, there is little evidence to support this. Yang et al.  showed that the motif in CoCoa_N that binds to p300 is FLNVARTY, not DWIGLYKV which is >20 aa away. Also, Cho2p has no conserved sequence motif similar to FLNVARTY.
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- Kodaki T and Yamashita S (1987) Yeast phosphatidylethanolamine methylation pathway. Cloning and characterization of two distinct methyltransferase genes. J Biol Chem 262(32):15428-35 SGD PMID 2445736
- Paltauf F, et al. (1992) Regulation and compartmentalization of lipid synthesis in yeast. Pp. 415-500 in The Molecular and Cellular Biology of the Yeast Saccharomyces: Gene Expression, edited by Jones EW, Pringle JR and Broach JR. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory Press SGD PMID
- Summers EF, et al. (1988) Saccharomyces cerevisiae cho2 mutants are deficient in phospholipid methylation and cross-pathway regulation of inositol synthesis. Genetics 120(4):909-22 SGD PMID 3066687
- Wlodarski T, Kutner J, Towpik J, Knizewski L, Rychlewski L, Kudlicki A, Rowicka M, Dziembowski A and Ginalski K (2011) Comprehensive Structural and Substrate Specificity Classification of the Saccharomyces cerevisiae Methyltransferome. PLoS One. 2011;6(8):e23168. Epub 2011 Aug 9. PMID 21858014
- Ooms LM, Fedele CG, Astle MV, Ivetac I, Cheung V, Pearson RB, Layton MJ, Forrai A, Nandurkar HH, Mitchell CA (2006) The inositol polyphosphate 5-phosphatase, PIPP, Is a novel regulator of phosphoinositide 3-kinase-dependent neurite elongation. Mol Biol Cell. 17(2):607-22. PMID 16280363
- Noda NN, Ohsumi Y and Inagaki F (2010) Atg8-family interacting motif crucial for selective autophagy. FEBS Lett. 584(7):1379-85. PMID 20083108
- Yang CK, Kim JH and Stallcup MR (2006) Role of the N-terminal activation domain of the coiled-coil coactivator in mediating transcriptional activation by beta-catenin. Mol Endocrinol. 2006 Dec;20(12):3251-62. PMID 16931570
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See Help:References on how to add references
See Help:Categories on how to add the wiki page for this gene to a Category </protect>