SUMMARY PARAGRAPH for SCS22
SCS22 encodes a VAP (VAMP/synaptobrevin-associated protein) family member that appears to play a minor role in the regulation of phospholipid biosynthesis (1). Scs22p has sequence similarity with Scs2p, a type II membrane protein (5, 6) that regulates intracellular lipid traffic and phospholipid biosynthesis (6). Strains deleted for SCS2 have a conditional inositol auxotrophy that can be suppressed by overexpression of the rate-limiting enzyme in inositol synthesis (INO1) (5), or by deletion of genes in the CDP-choline pathway (CKI1, PCT1, and CPT1) (7), while strains deleted for SCS22 alone do not exhibit an inositol auxotrophy (1). However, scs2 scs22 double mutants have a more severe phenotype than scs2 single mutants, suggesting a parallel function for SCS22 (1). Strains deleted for SCS2 also have a telomere silencing defect (8). However, strains deleted for SCS22 are not defective for silencing at the telomere, nor do they modify the silencing defect of an scs2 single mutant (8).
SCS22 has sequence similarity with three human VAP family members VAP-A (OMIM), VAP-B (OMIM) and VAP-C (OMIM) (a VAP-B splicing variant) (9) that are involved in recruiting FFAT (two phenylalanines (FF) in an Acidic Tract)-motif containing lipid-binding proteins to the ER similar to the SCS2 protein in yeast (10, 1, 6). Human VAP family members have also been implicated in both vesicular trafficking and organization of microtubule networks (references found within 11). The human VAP-A gene can partially complement the function of yeast VAPs by rescuing the inositol auxotrophy of an scs2 scs22 double mutant under less stringent conditions, and this rescue is dependent upon the integrity of the FFAT-binding region of VAP-A (1). Mutations in the human VAP-B gene cause atypical amyotrophic lateral sclerosis (ALS) type 8 (a neurodegenerative disease also known as Lou Gehrig's disease; OMIM), and late-onset spinal muscular atrophy (SMA) (OMIM) (12).
Last updated: 2007-06-01