title: A conserved family of enzymes that phosphorylate inositol hexakisphosphate.
abstract: Inositol pyrophosphates are a diverse group of high-energy signaling molecules whose cellular roles remain an active area of study. We report a previously uncharacterized class of inositol pyrophosphate synthase and find it is identical to yeast Vip1 and Asp1 proteins, regulators of actin-related protein-2/3 (ARP 2/3) complexes. Vip1 and Asp1 acted as enzymes that encode inositol hexakisphosphate (IP6) and inositol heptakisphosphate (IP7) kinase activities. Alterations in kinase activity led to defects in cell growth, morphology, and interactions with ARP complex members. The functionality of Asp1 and Vip1 may provide cells with increased signaling capacity through metabolism of IP6.
authors.affiliation: Howard Hughes Medical Institute, Department of Pharmacology and Cancer Biology, Duke University Medical Center, DUMC 3813, Durham, NC 27710, USA.
authors.forename: Sashidhar
authors.initials: S
authors.lastname: Mulugu
authors.forename: Wenli
authors.initials: W
authors.lastname: Bai
authors.forename: Peter C
authors.initials: PC
authors.lastname: Fridy
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Bastidas
authors.forename: James C
authors.initials: JC
authors.lastname: Otto
authors.forename: D Eric
authors.initials: DE
authors.lastname: Dollins
authors.forename: Timothy A
authors.initials: TA
authors.lastname: Haystead
authors.forename: Anthony A
authors.initials: AA
authors.lastname: Ribeiro
authors.forename: John D
authors.initials: JD
authors.lastname: York
mesh_terms: D051378:Actin-Related Protein 3 / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D020134:Catalytic Domain; D002851:Chromatography, High Pressure Liquid; D017124:Conserved Sequence; D003598:Cytoskeletal Proteins / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D006801:Humans; D007295:Inositol Phosphates / Q000378:metabolism; D008969:Molecular Sequence Data; D064251:Multifunctional Enzymes; D010766:Phosphorylation; D017856:Phosphotransferases (Phosphate Group Acceptor) / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D010833:Phytic Acid / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D011755:Pyrophosphatases; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000201:enzymology* / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D012568:Schizosaccharomyces / Q000166:cytology / Q000201:enzymology* / Q000235:genetics / Q000254:growth & development; D029702:Schizosaccharomyces pombe Proteins / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D016415:Sequence Alignment; D013379:Substrate Specificity; D013696:Temperature
chemical_list: D051378:Actin-Related Protein 3; C121265:Asp1 protein, S pombe; D003598:Cytoskeletal Proteins; D007295:Inositol Phosphates; D064251:Multifunctional Enzymes; D011993:Recombinant Fusion Proteins; D029701:Saccharomyces cerevisiae Proteins; D029702:Schizosaccharomyces pombe Proteins; C402123:inositol heptakisphosphate; D010833:Phytic Acid; D017856:Phosphotransferases (Phosphate Group Acceptor); C098863:KCS1 protein, S cerevisiae; C099438:inositol hexakisphosphate kinase; D011755:Pyrophosphatases