Disease relevance of SPT14

• CWH6 was found to be identical to SPT14, a gene that is highly homologous to both human PIG-A and to RFAK from Salmonella typhimurium [1].
• Furthermore, Gpi3p-FLAG expressed in Escherichia coli is also cross-linked [2].

High impact information on SPT14

• The spt14 mutant causes several other abnormalities including transcriptional defects and a downregulation of inositolphosphoceramide synthesis [3].
• Temperature-sensitive yeast GPI anchoring mutants gpi2 and gpi3 are defective in the synthesis of N-acetylglucosaminyl phosphatidylinositol. Cloning of the GPI2 gene [4].
• We report the isolation of two more conditionally lethal mutants, gpi2 and gpi3, which, like gpi1, have a temperature-sensitive defect in the incorporation of [3H]inositol into protein and which lack in vitro GlcNAc-phosphatidylinositol synthetic activity [4].
• The gpi3 mutant is defective in the SPT14 gene, which encodes a yeast protein similar to the product of the mammalian PIG-A gene, which complements a GlcNAc-phosphatidylinositol synthesis-defective human cell line [4].
• These results indicate that Gpi3p is the UDP-GlcNAc-binding and probable catalytic subunit of the GlcNAc-PI synthetic complex [2].

Biological context of SPT14

• From the analysis of the effect of spt14 mutations on expression of various genes, we conclude that the SPT14 product has an important role in activation of Ty transcription as well as in the regulation of other genes including HIS4 and several of the a- and alpha-specific mating type genes [5].
• Haploid Saccharomyces cerevisiae strains containing any pairwise combination of the gpi1, gpi2, and gpi3 mutations are inviable [4].
• Physical analysis maps SAL6 to chromosome XVI between TPK2 and spt14 [6].
• Restrictive glycosylphosphatidylinositol anchor synthesis in cwh6/gpi3 yeast cells causes aberrant biogenesis of cell wall proteins [7].

Anatomical context of SPT14

• Depletion of Ynl038wp from membranes virtually abolished in vitro GlcNAc-PI synthetic activity, indicating that Ynl038wp is necessary for GlcNAc-PI synthesis in vitro [8].

Associations of SPT14 with chemical compounds

• To establish whether Gpi3p is the UDP-GlcNAc-binding subunit of the yeast GlcNAc-PI synthetic complex, we tested its ability to become cross-linked to the photoactivatable substrate analogue P(3)-(4-azidoanilido)-uridine 5'-triphosphate (AAUTP) [2].
• The mutation of the first Glu in the EX7E motif of Schizosaccharomyces pombe Gpi3p (Glu277) to Asp complemented the lethal null mutation in gpi3+ and supported growth at 37 degrees C, but the E285D mutant was nonviable [9].

Other interactions of SPT14

• Our current findings show that in contrast to SPT13/GAL11, which appears negatively to regulate Ty transcription, SPT14 plays a role in the activation of Ty transcription [5].
• The Saccharomyces cerevisiae SPT14 gene is essential for normal expression of the yeast transposon, Ty, as well as for expression of the HIS4 gene and several genes in the mating pathway [5].
• Identification of SPT14/CWH6 as the yeast homologue of hPIG-A, a gene involved in the biosynthesis of GPI anchors [1].

Analytical, diagnostic and therapeutic context of SPT14

• To test their importance for Gpi3p function in vivo, Glu289 and 297 in the EX7E motif of S. cerevisiae Gpi3p, as well as Cys301, were altered by site-specific mutagenesis, and the mutant proteins tested for their ability to complement nonviable GPI3-deleted haploids [9].

References