SIT4 type 2A-related serine/threonine-protein phosphatase SIT4 [Saccharomyces cerevisiae S288C] - Gene

Summary

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Gene symbol: SIT4
Gene description: type 2A-related serine/threonine-protein phosphatase SIT4
Primary source: FungiDB:YDL047W
Locus tag: YDL047W
See related: SGD:S000002205; AllianceGenome:SGD:S000002205; VEuPathDB:YDL047W
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: PPH1
Summary: Enables protein serine/threonine phosphatase activity. Involved in several processes, including nucleic acid metabolic process; peptidyl-serine dephosphorylation; and regulation of fungal-type cell wall organization. Acts upstream of or within regulation of TORC1 signaling. Located in cytoplasm. Part of protein phosphatase type 2A complex. Orthologous to human PPP6C (protein phosphatase 6 catalytic subunit). [provided by Alliance of Genome Resources, Apr 2022]
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Genomic context

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See SIT4 in Genome Data Viewer

Location:: chromosome: IV

Exon count:: 1

Sequence:: Chromosome: IV; NC_001136.10 (369771..370706)

Chromosome IV - NC_001136.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:: NC_001136.10

Go to nucleotide: Graphics FASTA GenBank

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Sit4 Genetically Interacts with Vps27 to Regulate Mitochondrial Function and Lifespan in Saccharomyces cerevisiae.
Title: Sit4 Genetically Interacts with Vps27 to Regulate Mitochondrial Function and Lifespan in Saccharomyces cerevisiae.
The Rpd3-Complex Regulates Expression of Multiple Cell Surface Recycling Factors in Yeast.
Title: The Rpd3-Complex Regulates Expression of Multiple Cell Surface Recycling Factors in Yeast.
Downregulation of Snf1p suppressed Deltasit4 mutant phenotypes, including mitochondrial derepression, resistance to oxidative stress and increased lifespan. Overall, this indicates a more prominent role of Snf1p downstream the Sit4p signalling pathway than previously suspected.
Title: Activation of SNF1/AMPK mediates the mitochondrial derepression, resistance to oxidative stress and increased lifespan of cells lacking the phosphatase Sit4p.
Results show that the multifunctional protein phosphatase Sit4 is required for tRNA modification and modification independent regulatory processes in S. cerevisiae. Absence of Sit4 lowers cellular lipid droplets (LD) levels and results in increased sensitivity to acetyl-CoA carboxylase (Acc1) inhibition by soraphen A.
Title: Protein Phosphatase Sit4 Affects Lipid Droplet Synthesis and Soraphen A Resistance Independent of Its Role in Regulating Elongator Dependent tRNA Modification.
suggest that Sit4p-mediated dephosphorylation of Atp2p-T124/T317 downregulates Atp2p alongside with ATP synthase and mitochondrial function
Title: Sit4p-mediated dephosphorylation of Atp2p regulates ATP synthase activity and mitochondrial function.
Phytoceramide accumulation and Sit4-dependent signaling mediate the mitochondrial dysfunction and shortened lifespan in the yeast model of Niemann-Pick type C1, in part through modulation of the Pkh1-Sch9 pathway.
Title: The ceramide activated protein phosphatase Sit4 impairs sphingolipid dynamics, mitochondrial function and lifespan in a yeast model of Niemann-Pick type C1.
This pathway is functionally relevant to TORC1 signaling since the stress sensitivity of a nonessential TORC1 mutant (tco89Delta) to hydroxyurea and arsenic can be reversed by combining tco89Delta with either hst3Delta, hst4Delta, or sit4Delta Surprisingly, while hst3Delta or hst4Delta rescues the sensitivity tco89Delta has to low concentrations of the TORC1 inhibitor rapamycin, sit4Delta fails to do so
Title: Saccharomyces cerevisiae TORC1 Controls Histone Acetylation by Signaling Through the Sit4/PP6 Phosphatase to Regulate Sirtuin Deacetylase Nuclear Accumulation.
The results suggest that the phosphorylated Hxk2 functions downstream of Sit4 in the control of cell cycle, mitochondrial function, oxidative stress resistance and chronological lifespan.
Title: The ceramide-activated protein phosphatase Sit4p controls lifespan, mitochondrial function and cell cycle progression by regulating hexokinase 2 phosphorylation.
Ceramide signalling impinges on Sit4p and Hog1p to promote mitochondrial fission and mitophagy in Isc1p-deficient cells.
Title: Ceramide signalling impinges on Sit4p and Hog1p to promote mitochondrial fission and mitophagy in Isc1p-deficient cells.
Results show that Sit4p and its mammalian orthologue, PP6, regulate traffic from the ER to the Golgi complex which is consistent with its role in coat recycling.
Title: Sit4p/PP6 regulates ER-to-Golgi traffic by controlling the dephosphorylation of COPII coat subunits.

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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 metal ion binding	IEA Inferred from Electronic Annotation more info
enables myosin phosphatase activity	IEA Inferred from Electronic Annotation more info
enables phosphoprotein phosphatase activity	IEA Inferred from Electronic Annotation more info
enables protein serine/threonine phosphatase activity	IBA Inferred from Biological aspect of Ancestor more info
enables protein serine/threonine phosphatase activity	IEA Inferred from Electronic Annotation more info
enables protein serine/threonine phosphatase activity	IMP Inferred from Mutant Phenotype more info	PubMed

Process	Evidence Code	Pubs
involved_in DNA repair	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in G1/S transition of mitotic cell cycle	IBA Inferred from Biological aspect of Ancestor more info
involved_in G1/S transition of mitotic cell cycle	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in cell division	IEA Inferred from Electronic Annotation more info
involved_in cellular response to oxidative stress	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in intracellular signal transduction	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within regulation of TORC1 signaling	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of actin cytoskeleton organization	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of fungal-type cell wall organization	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in tRNA wobble uridine modification	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
located_in cytoplasm	HDA more info	PubMed
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in cytoplasm	IEA Inferred from Electronic Annotation more info
located_in nucleus	HDA more info	PubMed
part_of protein phosphatase type 2A complex	IDA Inferred from Direct Assay more info	PubMed
part_of protein phosphatase type 2A complex	IMP Inferred from Mutant Phenotype more info	PubMed

General protein information

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Preferred Names: type 2A-related serine/threonine-protein phosphatase SIT4

NP_010236.1

EC 3.1.3.16

Ceramide-activated, type 2A-related serine-threonine phosphatase; functions in G1/S transition of mitotic cycle; controls lifespan, mitochondrial function, cell cycle progression by regulating HXK2 phosphorylation; regulator of COPII coat dephosphorylation; required for ER to Golgi traffic; interacts with Hrr25p kinase; cytoplasmic and nuclear protein that modulates functions mediated by Pkc1p including cell wall and actin cytoskeleton organization; similar to human PP6

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_001136.10 Reference assembly

Range

369771..370706

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001180106.1 → NP_010236.1 TPA: type 2A-related serine/threonine-protein phosphatase SIT4 [Saccharomyces cerevisiae S288C]

See identical proteins and their annotated locations for NP_010236.1

Status: REVIEWED

UniProtKB/Swiss-Prot

D6VRU8, P20604

UniProtKB/TrEMBL

A0A6A5PZ80, A6ZXS7, B3LGU6, C7GLI1, C8Z4M2, G2WCB3, N1P7S8

Conserved Domains (1) summary

cd07415
Location:7 → 291

MPP_PP2A_PP4_PP6; PP2A, PP4, and PP6 phosphoprotein phosphatases, metallophosphatase domain