title: The Schizosaccharomyces pombe fusion gene hal3 encodes three distinct activities.
abstract: Saccharomyces cerevisiae Hal3 and Vhs3 are moonlighting proteins, forming an atypical heterotrimeric decarboxylase (PPCDC) required for CoA biosynthesis, and regulating cation homeostasis by inhibition of the Ppz1 phosphatase. The Schizosaccharomyces pombe ORF SPAC15E1.04 (renamed as Sp hal3) encodes a protein whose amino-terminal half is similar to Sc Hal3 whereas its carboxyl-terminal half is related to thymidylate synthase (TS). We show that Sp Hal3 and/or its N-terminal domain retain the ability to bind to and modestly inhibit in vitro S. cerevisiae Ppz1 as well as its S. pombe homolog Pzh1, and also exhibit PPCDC activity in vitro and provide PPCDC function in vivo, indicating that Sp Hal3 is a monogenic PPCDC in fission yeast. Whereas the Sp Hal3 N-terminal domain partially mimics Sc Hal3 functions, the entire protein and its carboxyl-terminal domain rescue the S. cerevisiae cdc21 mutant, thus proving TS function. Additionally, we show that the 70 kDa Sp Hal3 protein is not proteolytically processed under diverse forms of stress and that, as predicted, Sp hal3 is an essential gene. Therefore, Sp hal3 represents a fusion event that joined three different functional activities in the same gene. The possible advantage derived from this surprising combination of essential proteins is discussed.
authors: Institut de Biotecnologia i Biomedicina and Departament de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona, Cerdanyola del Vallès, Spain.
authors: Cristina
authors: C
authors: Molero
authors: Katalin
authors: K
authors: Petrényi
authors: Asier
authors: A
authors: González
authors: Mercè
authors: M
authors: Carmona
authors: Samuel
authors: S
authors: Gelis
authors: J Albert
authors: JA
authors: Abrie
authors: Erick
authors: E
authors: Strauss
authors: José
authors: J
authors: Ramos
authors: Viktor
authors: V
authors: Dombradi
authors: Elena
authors: E
authors: Hidalgo
authors: Joaquín
authors: J
authors: Ariño
mesh_terms: D002262:Carboxy-Lyases / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D050939:Gene Fusion; D020043:Genes, Essential; D005800:Genes, Fungal; D016366:Open Reading Frames; D010749:Phosphoprotein Phosphatases / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D012568:Schizosaccharomyces / Q000235:genetics* / Q000378:metabolism*; D029702:Schizosaccharomyces pombe Proteins / Q000235:genetics / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D013940:Thymidylate Synthase / Q000235:genetics / Q000378:metabolism*
chemical_list: D018797:Cell Cycle Proteins; D011994:Recombinant Proteins; C092936:SIS2 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D029702:Schizosaccharomyces pombe Proteins; D013940:Thymidylate Synthase; C075119:PPZ1 protein, S cerevisiae; D010749:Phosphoprotein Phosphatases; D002262:Carboxy-Lyases; C022373:Phosphopantothenoyl-cysteine decarboxylase