Disease relevance of ALG2

• A cell-membrane fraction isolated from Escherichia coli overexpressing thioredoxin-tagged Alg2 was used to demonstrate that this enzyme actually carries out an alpha1,3-mannosylation, followed by an alpha1,6-mannosylation, to form the first branched pentasaccharide intermediate of the pathway [1].

High impact information on ALG2

• There was virtually no outer chain addition in the alg2 and alg4 mutants. alg4 was the only mutant that failed to secrete invertase [2].
• Here we have used ALG-2 as bait in a yeast two hybrid screen of a mouse brain cDNA library [3].
• Vito et al have shown that ALG-2 expression is required for apoptosis following a number of death stimuli,1 although nothing is known about the effectors which underlie ALG-2 function [3].
• The Ca2+-binding Protein ALG-2 Is Recruited to Endoplasmic Reticulum Exit Sites by Sec31A and Stabilizes the Localization of Sec31A [4].
• In addition to these Alg11-related proteins, Alg11p is also similar to Alg2p, a protein that regulates the addition of the third mannose to the core oligosaccharide [5].

Biological context of ALG2

• The genomic DNA and cDNA encoding an ALG2 homologue were cloned from the zygomycete fungus, Rhizomucor pusillus, and their nucleotide sequences were determined [6].
• Here, we show that expression of the ALG7, ALG1 and ALG2 genes is coordinately regulated at the G0/G1 transition point in the yeast life cycle [7].
• A gene having the function and genomic location of ALG2 was cloned from libraries based on the multicopy plasmid YEp24 and on the centromere plasmid YCp50 [8].
• ALG2 was essential for viability in haploid and diploid yeast [8].
• Site-directed mutagenesis of the fungal Alg2 and determination of their phenotypes in the yeast alg2-1 mutant showed that a mutation at 368Gly (equivalent to 377Gly of yeast Alg2) to Arg resulted in generation of a ts enzyme [6].

Anatomical context of ALG2

• Thermosensitive mutants of Saccharomyces cerevisiae, affected in the endoplasmic reticulum (ER) located glycosylation, i.e. in Dol-P-Man synthase (dpm1), in beta-1,4 mannosyl transferase (alg1) and in alpha-1,3 mannosyltransferase (alg2), were used to assess the role of GDP-Man availability for the synthesis of dolichol-linked saccharides [9].

Associations of ALG2 with chemical compounds

• ALG2 of Saccharomyces cerevisiae encodes the glycosyltransferase that mannosylates Man2GlcNAc2-dolichol diphosphate (PP-Dol) and Man1GlcNAc2-PP-Dol to form Man3GlcNAc2-PP-Dol [6].
• Consistent with this, rapid degradation of ALG7, ALG1 and ALG2 mRNAs was completely abolished in the presence of cycloheximide [7].
• In addition, labeling of the wild-type yeast cells with [3H]palmitate in the presence of tunicamycin revealed the incorporation of [3H]palmitate into the same five bands as found in the alg1 and alg2 mutants at the non-permissive temperature without tunicamycin [10].
• We present evidence indicating that, in H. polymorpha, neither isocitrate lyase activity nor the ALG2 gene product are necessary for C(1)-peroxisome degradation triggered by ethanol [11].
• To set the basis for molecular and cellular studies of the glyoxylate cycle in methylotrophic yeasts, we isolated and characterized ALG2, the Hansenula polymorpha isocitrate lyase gene [11].

Physical interactions of ALG2

• The two Alg1-containing complexes differ from one another in that one complex contains Alg2 and the other contains Alg11 [12].

Other interactions of ALG2

• The cloned cDNA under the control of the yeast GAL1 promoter complemented the temperature-sensitive (ts) growth of the alg2-1 mutant of S. cerevisiae, indicating that it represented a functional ALG2 homologue of R. pusillus [6].
• In the alg1 and alg2 mutants, complemented with MPG1 gene, N-glycosylation of invertase was in part restored, to a degree comparable to that of the wild-type control [9].
• The second fragment covers the 72.6 kb region between the chromosomal markers CYH2 and ALG2 [13].
• ALG2, the Hansenula polymorpha isocitrate lyase gene [11].

Analytical, diagnostic and therapeutic context of ALG2

• Using co-immunoprecipitation experiments, we confirmed ALG-2/ALG-2 binding and demonstrated that this interaction is calcium independent [3].

References