SIS2 phosphopantothenoylcysteine decarboxylase complex subunit SIS2 [Saccharomyces cerevisiae S288C] - Gene

Summary

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Official Symbol: SIS2
Official Full Name: phosphopantothenoylcysteine decarboxylase complex subunit SIS2
Primary source: SGD:S000001780
Locus tag: YKR072C
See related: AllianceGenome:SGD:S000001780; FungiDB:YKR072C; VEuPathDB:YKR072C
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Saccharomyces cerevisiae S288C (strain: S288C)
Lineage: Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes; Saccharomycetales; Saccharomycetaceae; Saccharomyces
Also known as: HAL3
Summary: Enables protein serine/threonine phosphatase inhibitor activity. Contributes to phosphopantothenoylcysteine decarboxylase activity. Involved in coenzyme A biosynthetic process; regulation of mitotic cell cycle; and response to salt stress. Located in chromatin and nucleus. Part of CoA-synthesizing protein complex and phosphopantothenoylcysteine decarboxylase complex. Used to study dilated cardiomyopathy. Orthologous to human PPCDC (phosphopantothenoylcysteine decarboxylase). [provided by Alliance of Genome Resources, Dec 2024]
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Genomic context

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See SIS2 in Genome Data Viewer

Location:: chromosome: XI

Exon count:: 1

Sequence:: Chromosome: XI; NC_001143.9 (576435..578123, complement)

Chromosome XI - NC_001143.9 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:: NC_001143.9

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Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Sis2 regulates yeast replicative lifespan in a dose-dependent manner.
Title: Sis2 regulates yeast replicative lifespan in a dose-dependent manner.
Functional mapping of the N-terminal region of the yeast moonlighting protein Sis2/Hal3 reveals crucial residues for Ppz1 regulation.
Title: Functional mapping of the N-terminal region of the yeast moonlighting protein Sis2/Hal3 reveals crucial residues for Ppz1 regulation.
The toxic effects of yeast Ppz1 phosphatase are counteracted by subcellular relocalization mediated by its regulatory subunit Hal3.
Title: The toxic effects of yeast Ppz1 phosphatase are counteracted by subcellular relocalization mediated by its regulatory subunit Hal3.
Site-directed mutagenesis results indicate mutation of ScHal3 L403 has no effect on trimerization and phosphopantothenoyl-cysteine decarboxylase function. ScHal3 L405E fails to form homotrimers, but retains the capacity to bind Cab3. Remarkably, the L405E mutation decreases Hal3's ability to interact with and to inhibit Ppz1, confirming the importance of the oligomer/monomer equilibrium in Hal3's Ppz1 regulating function.
Title: Mutations at the hydrophobic core affect Hal3 trimer stability, reducing its Ppz1 inhibitory capacity but not its PPCDC moonlighting function.
The Hal3 N-terminal domain is not functional by itself, although in vitro experiments indicate that when this domain is combined with the core it has a relevant function in Hal3's heteromeric phosphopantothenoylcysteine decarboxylase activity.
Title: Functional mapping of the disparate activities of the yeast moonlighting protein Hal3.
The aim of this work was to study mechanisms which relate the activity of Ppz1p/Hal3p complex to nonsense suppression efficiency.
Title: [The protein complex Ppz1p/Hal3p and nonsense suppression efficiency in the yeast Saccharomyces cerevisiae].
the Ppz1-Hal3 interaction is a sensor of intracellular pH that modulates H+ and K+ homeostasis through the regulation of Trk1p activity
Title: pH-Responsive, posttranslational regulation of the Trk1 potassium transporter by the type 1-related Ppz1 phosphatase.
Results demonstrate the participation of the Hal3-Ppz1 protein complex in regulation of read-through efficiency and manifestation of non-Mendelian anti-suppressor determinant [ISP(+)].
Title: The HAL3-PPZ1 dependent regulation of nonsense suppression efficiency in yeast and its influence on manifestation of the yeast prion-like determinant [ISP(+)].

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Pathways from PubChem

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Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Homology

Orthologs from OrthoDB

Gene Ontology Provided by SGD

Function	Evidence Code	Pubs
enables FMN binding	IBA Inferred from Biological aspect of Ancestor more info
enables catalytic activity	IEA Inferred from Electronic Annotation more info
contributes_to phosphopantothenoylcysteine decarboxylase activity	IDA Inferred from Direct Assay more info	PubMed
contributes_to phosphopantothenoylcysteine decarboxylase activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables protein phosphatase inhibitor activity	IEA Inferred from Electronic Annotation more info
enables protein serine/threonine phosphatase inhibitor activity	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
involved_in coenzyme A biosynthetic process	IBA Inferred from Biological aspect of Ancestor more info
involved_in coenzyme A biosynthetic process	IEA Inferred from Electronic Annotation more info
involved_in coenzyme A biosynthetic process	IGI Inferred from Genetic Interaction more info	PubMed
involved_in regulation of mitotic cell cycle	IGI Inferred from Genetic Interaction more info	PubMed
involved_in response to salt stress	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
part_of CoA-synthesizing protein complex	IDA Inferred from Direct Assay more info	PubMed
located_in chromatin	IDA Inferred from Direct Assay more info	PubMed
located_in cytoplasm	IEA Inferred from Electronic Annotation more info
located_in nucleus	IDA Inferred from Direct Assay more info	PubMed
located_in nucleus	IEA Inferred from Electronic Annotation more info
part_of phosphopantothenoylcysteine decarboxylase complex	IBA Inferred from Biological aspect of Ancestor more info
part_of phosphopantothenoylcysteine decarboxylase complex	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: phosphopantothenoylcysteine decarboxylase complex subunit SIS2

NP_012998.1

Negative regulatory subunit of protein phosphatase 1 (Ppz1p); involved in coenzyme A biosynthesis; subunit of the phosphopantothenoylcysteine decarboxylase (PPCDC: Cab3p, Sis2p, Vhs3p) complex and the CoA-Synthesizing Protein Complex (CoA-SPC: Cab2p, Cab3p, Cab4p, Cab5p, Sis2p and Vhs3p); dose-dependent regulator of replicative lifespan; SIS2 has a paralog, VHS3, that arose from the whole genome duplication

NCBI Reference Sequences (RefSeq)

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Genome Annotation

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference assembly

Genomic

NC_001143.9 Reference assembly

Range

576435..578123 complement

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001179862.1 → NP_012998.1 TPA: phosphopantothenoylcysteine decarboxylase complex subunit SIS2 [Saccharomyces cerevisiae S288C]

See identical proteins and their annotated locations for NP_012998.1

Status: REVIEWED

UniProtKB/Swiss-Prot

D6VXD3, P36024

UniProtKB/TrEMBL

C7GX68

Conserved Domains (2) summary

COG0452
Location:167 → 495

CoaBC; Phosphopantothenoylcysteine synthetase/decarboxylase [Coenzyme transport and metabolism]

cl19190
Location:353 → 474

Flavoprotein