Gene Symbol: SIS2
Description: phosphopantothenoylcysteine decarboxylase complex subunit SIS2
Alias: HAL3, phosphopantothenoylcysteine decarboxylase complex subunit SIS2
Species: Saccharomyces cerevisiae S288c

Top Publications

  1. Abrie J, González A, Strauss E, Arino J. Functional mapping of the disparate activities of the yeast moonlighting protein Hal3. Biochem J. 2012;442:357-68 pubmed publisher
    The Saccharomyces cerevisiae Hal3 protein is a moonlighting protein, able to function both as an inhibitory subunit of the Ppz1 protein phosphatase and as a constituent protomer of an unprecedented heterotrimeric PPCDC (..
  2. Merchan S, Pedelini L, Hueso G, Calzada A, Serrano R, Yenush L. Genetic alterations leading to increases in internal potassium concentrations are detrimental for DNA integrity in Saccharomyces cerevisiae. Genes Cells. 2011;16:152-65 pubmed publisher
  3. Makanae K, Kintaka R, Makino T, Kitano H, Moriya H. Identification of dosage-sensitive genes in Saccharomyces cerevisiae using the genetic tug-of-war method. Genome Res. 2013;23:300-11 pubmed publisher
    ..The results obtained in this study will provide basic knowledge about the physiology of chromosomal abnormalities and the evolution of chromosomal composition. ..
  4. Yenush L, Mulet J, Arino J, Serrano R. The Ppz protein phosphatases are key regulators of K+ and pH homeostasis: implications for salt tolerance, cell wall integrity and cell cycle progression. EMBO J. 2002;21:920-9 pubmed
    ..In addition to providing a coherent explanation for all Ppz-dependent phenotypes, our results provide evidence for a causal relationship between intracellular cation homeostasis and a potential cell cycle checkpoint. ..
  5. Rios G, Ferrando A, Serrano R. Mechanisms of salt tolerance conferred by overexpression of the HAL1 gene in Saccharomyces cerevisiae. Yeast. 1997;13:515-28 pubmed
    ..As a consequence, osmotic adjustment through glycerolsynthesis, a process not affected by HAL1, is the limiting factor for growth on galactose under NaCl stressed. ..
  6. Masson J, Ramotar D. The transcriptional activator Imp2p maintains ion homeostasis in Saccharomyces cerevisiae. Genetics. 1998;149:893-901 pubmed
    ..Two genes that independently restored normal salt-resistance to the imp2Delta mutant, ENA1 and HAL3, were isolated...
  7. Ivanov M, Radchenko E, Mironova L. [The protein complex Ppz1p/Hal3p and nonsense suppression efficiency in the yeast Saccharomyces cerevisiae]. Mol Biol (Mosk). 2010;44:1018-26 pubmed
    ..we used a genetic approach consisting of the analysis of nonsense suppression phenotype of strains over-expressing HAL3 or PPZ1 genes and also bearing deletions or mutant alleles of genes which presumably could participate in the ..
  8. Ruiz A, González A, García Salcedo R, Ramos J, Arino J. Role of protein phosphatases 2C on tolerance to lithium toxicity in the yeast Saccharomyces cerevisiae. Mol Microbiol. 2006;62:263-77 pubmed
    ..cerevisiae, overexpression of the Ptc3p isoform resulted in increased lithium tolerance in the hypersensitive hal3 background...
  9. Olzhausen J, Moritz T, Neetz T, Schüller H. Molecular characterization of the heteromeric coenzyme A-synthesizing protein complex (CoA-SPC) in the yeast Saccharomyces cerevisiae. FEMS Yeast Res. 2013;13:565-73 pubmed publisher
    ..In addition, nonessential genes SIS2 and VHS3 similar to CAB3 are also involved...

More Information


  1. Aksenova A, Munoz I, Volkov K, Arino J, Mironova L. The HAL3-PPZ1 dependent regulation of nonsense suppression efficiency in yeast and its influence on manifestation of the yeast prion-like determinant [ISP(+)]. Genes Cells. 2007;12:435-45 pubmed
    ..In this study, we demonstrate the participation of the Hal3-Ppz1 protein complex in regulation of read-through efficiency and manifestation of non-Mendelian anti-suppressor ..
  2. Munoz I, Ruiz A, Marquina M, Barceló A, Albert A, Arino J. Functional characterization of the yeast Ppz1 phosphatase inhibitory subunit Hal3: a mutagenesis study. J Biol Chem. 2004;279:42619-27 pubmed
    Saccharomyces cerevisiae Hal3 is a conserved protein that binds the carboxyl-terminal catalytic domain of the PP1c (protein phosphatase 1)-related phosphatase Ppz1 and potently inhibits its activity, thus modulating all of the ..
  3. Abrie J, Molero C, Ariño J, Strauss E. Complex stability and dynamic subunit interchange modulates the disparate activities of the yeast moonlighting proteins Hal3 and Vhs3. Sci Rep. 2015;5:15774 pubmed publisher
    Saccharomyces cerevisiae Hal3 and Vhs3 are moonlighting proteins, acting both as inhibitors of the serine/threonine protein phosphatase Ppz1 and as subunits (together with Cab3) of the unique heterotrimeric phosphopantothenoylcysteine ..
  4. Di Como C, Bose R, Arndt K. Overexpression of SIS2, which contains an extremely acidic region, increases the expression of SWI4, CLN1 and CLN2 in sit4 mutants. Genetics. 1995;139:95-107 pubmed
    The Saccharomyces cerevisiae SIS2 gene was identified by its ability, when present on a high copy number plasmid, to increase dramatically the growth rate of sit4 mutants...
  5. Hemenway C, Heitman J. Lic4, a nuclear phosphoprotein that cooperates with calcineurin to regulate cation homeostasis in Saccharomyces cerevisiae. Mol Gen Genet. 1999;261:388-401 pubmed
    ..lic4 mutations also exacerbate the Li+-sensitive phenotype of hal3 mutant strains, and overexpression of either Lic4 or Hal3 suppresses the salt sensitivity of mutant strains lacking ..
  6. Clotet J, Gari E, Aldea M, Arino J. The yeast ser/thr phosphatases sit4 and ppz1 play opposite roles in regulation of the cell cycle. Mol Cell Biol. 1999;19:2408-15 pubmed
    ..The growth defect is rescued by overexpression of the HAL3/SIS2 gene, encoding a negative regulator of Ppz1...
  7. Luke M, Della Seta F, Di Como C, Sugimoto H, Kobayashi R, Arndt K. The SAP, a new family of proteins, associate and function positively with the SIT4 phosphatase. Mol Cell Biol. 1996;16:2744-55 pubmed
    ..Overexpression of a SAP from one group does not suppress the defects due to the loss of the other group. These findings and others indicate that the SAPs have distinct functions. ..
  8. Yenush L, Merchan S, Holmes J, Serrano R. pH-Responsive, posttranslational regulation of the Trk1 potassium transporter by the type 1-related Ppz1 phosphatase. Mol Cell Biol. 2005;25:8683-92 pubmed
    ..These results are consistent with a model in which the Ppz1-Hal3 interaction is a sensor of intracellular pH that modulates H+ and K+ homeostasis through the regulation of Trk1p ..
  9. Munoz I, Simon E, Casals N, Clotet J, Arino J. Identification of multicopy suppressors of cell cycle arrest at the G1-S transition in Saccharomyces cerevisiae. Yeast. 2003;20:157-69 pubmed
    Inactivation of HAL3 in the absence of SIT4 function leads to cell cycle arrest at the G(1)-S transition...
  10. Tatusov R, Galperin M, Natale D, Koonin E. The COG database: a tool for genome-scale analysis of protein functions and evolution. Nucleic Acids Res. 2000;28:33-6 pubmed
    ..The COG database is accompanied by the COGNITOR program that is used to fit new proteins into the COGs and can be applied to functional and phylogenetic annotation of newly sequenced genomes. ..
  11. Molero C, Petrényi K, González A, Carmona M, Gelis S, Abrie J, et al. The Schizosaccharomyces pombe fusion gene hal3 encodes three distinct activities. Mol Microbiol. 2013;90:367-82 pubmed publisher
    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...
  12. Ruiz A, Munoz I, Serrano R, González A, Simon E, Arino J. Functional characterization of the Saccharomyces cerevisiae VHS3 gene: a regulatory subunit of the Ppz1 protein phosphatase with novel, phosphatase-unrelated functions. J Biol Chem. 2004;279:34421-30 pubmed
    ..has been recently identified as a multicopy suppressor of the G(1)/S cell cycle blockade of a conditional sit4 and hal3 mutant...
  13. Simon E, Barceló A, Arino J. Mutagenesis analysis of the yeast Nha1 Na+/H+ antiporter carboxy-terminal tail reveals residues required for function in cell cycle. FEBS Lett. 2003;545:239-45 pubmed
    ..the NHA1 gene is able to rescue the blockage at the G(1)/S transition of cells lacking Sit4 protein phosphatase and Hal3 activities...
  14. Stirling P, Srayko M, Takhar K, Pozniakovsky A, Hyman A, Leroux M. Functional interaction between phosducin-like protein 2 and cytosolic chaperonin is essential for cytoskeletal protein function and cell cycle progression. Mol Biol Cell. 2007;18:2336-45 pubmed
    ..Our data support a model in which Plp2p modulates the biogenesis of several CCT substrates relating to cell cycle and cytoskeletal function, which together contribute to the essential function of PLP2. ..
  15. Ruiz A, González A, Munoz I, Serrano R, Abrie J, Strauss E, et al. Moonlighting proteins Hal3 and Vhs3 form a heteromeric PPCDC with Ykl088w in yeast CoA biosynthesis. Nat Chem Biol. 2009;5:920-8 pubmed publisher
    ..Sequence homology analyses suggest three candidates-Ykl088w, Hal3 and Vhs3-as putative PPCDC enzymes in Saccharomyces cerevisiae...
  16. Simon E, Clotet J, Calero F, Ramos J, Arino J. A screening for high copy suppressors of the sit4 hal3 synthetically lethal phenotype reveals a role for the yeast Nha1 antiporter in cell cycle regulation. J Biol Chem. 2001;276:29740-7 pubmed
    A screening for multicopy suppressors of the G(1)/S blockage of a conditional sit4 hal3 mutant yielded the NHA1 gene, encoding a Na(+),K(+)/H(+) antiporter, composed of a transmembrane domain and a large carboxyl-terminal tail, which has ..
  17. González A, Casado C, Petrezselyova S, Ruiz A, Arino J. Molecular analysis of a conditional hal3 vhs3 yeast mutant links potassium homeostasis with flocculation and invasiveness. Fungal Genet Biol. 2013;53:1-9 pubmed publisher
    ..b>Hal3 and Vhs3 are moonlighting proteins acting in Saccharomyces cerevisiae both as inhibitors of the Ppz protein ..
  18. de Nadal E, Clotet J, Posas F, Serrano R, Gomez N, Arino J. The yeast halotolerance determinant Hal3p is an inhibitory subunit of the Ppz1p Ser/Thr protein phosphatase. Proc Natl Acad Sci U S A. 1998;95:7357-62 pubmed
    ..Disruption or overexpression of HAL3 (also known as SIS2) has no effect on salt tolerance in the absence of PPZ1, suggesting that Hal3p might function ..