High impact information on VAN1

• Anp1p, Van1p and Mnn9p constitute a family of membrane proteins required for proper Golgi function in Saccharomyces cerevisiae [1].
• These data suggest that the VAN1 gene product is involved in regulation of the phosphorylation of a number of proteins, some of which appear to be important in cell growth control [2].
• High copy suppressors of this synthetic lethality included three mannosyltransferases, VAN1, KTR4, and HOC1 [3].
• Both proteins contain a DXD motif found in the active site of many glycosyltransferases, and mutations in this motif in Mnn9p or Van1p reveal that both proteins contribute to mannose polymerization [4].
• A single mutation confers vanadate resistance to the plasma membrane H+-ATPase from the yeast Schizosaccharomyces pombe [5].

Biological context of VAN1

• Most mutants are defective in outer chain glycosylation of secreted invertase (van1, van2, van4, van5, van6, VAN7-116 and others), a phenotype found in some MNN or VRG mutants [6].
• Three type II membrane proteins Anp1, Van1 and Mnn9 of Saccharomyces cerevisiae share significant sequence homology [7].
• The H285Q and H285R mutants showed increased in vitro ATPase-specific activity, increased vanadate resistance, increased proton competition of vanadate sensitivity, accelerated ATP hydrolysis rates at a substrate concentration much lower than the Km, and slightly uncoupled proton pumping [8].
• In Saccharomyces cerevisiae, the pma1 mutations controlling the vanadate resistance of the H(+)-ATPase activity from the plasma membrane, map on chromosome VII in the vicinity of pdr1 mutations controlling multiple drug resistance [9].

Associations of VAN1 with chemical compounds

• Mutations selected at 3 nM sodium orthovanadate have different degrees of vanadate resistance, hygromycin sensitivity, detergent sensitivity and sporulation defects [6].
• Mutants in VAN1 were previously identified by their resistance to the drug orthovanadate [10].
• When solubilized by Triton X-100, it was recovered in two distinct complexes both having mannosyltransferase activity; one with Van1 protein (V-complex) and the other with Anp1, Hoc1, Mnn10, and Mnn11 proteins (A-complex) [11].
• Cloning and characterization of the Saccharomyces cerevisiae SVS1 gene which encodes a serine- and threonine-rich protein required for vanadate resistance [12].

Other interactions of VAN1

• The previously published VAN1 gene product has a 200 amino acid domain with 40% identity with the MNN9 gene product and 70% identity with the ANP1 gene product [6].
• In addition, van1 and ysl2 display actin cytoskeletal defects [10].
• In the yeast Saccharomyces cerevisiae, the pma1 mutations confers vanadate-resistance to H+-ATPase activity when measured in isolated plasma membranes [13].

References