PEP4 proteinase A [Saccharomyces cerevisiae S288C] - Gene

Summary

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Official Symbol: PEP4
Official Full Name: proteinase A
Primary source: SGD:S000006075
Locus tag: YPL154C
See related: AllianceGenome:SGD:S000006075; FungiDB:YPL154C; VEuPathDB:YPL154C
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: PHO9; PRA1; yscA
Summary: Enables peptidase activity. Involved in several processes, including cytoplasm to vacuole targeting by the Cvt pathway; microautophagy; and pexophagy. Located in fungal-type vacuole. Human ortholog(s) of this gene implicated in several diseases, including autosomal dominant tubulointerstitial kidney disease; hand, foot and mouth disease; hypertension (multiple); neuronal ceroid lipofuscinosis 10; and portal hypertension. Orthologous to several human genes including NAPSA (napsin A aspartic peptidase). [provided by Alliance of Genome Resources, Apr 2025]
Orthologs: all
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Genomic context

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See PEP4 in Genome Data Viewer

Location:: chromosome: XVI

Exon count:: 1

Sequence:: Chromosome: XVI; NC_001148.4 (259714..260931, complement)

Chromosome XVI - NC_001148.4 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:: NC_001148.4

Go to nucleotide: Graphics FASTA GenBank

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Vps10-mediated targeting of Pep4 determines the activity of the vacuole in a substrate-dependent manner.
Title: Vps10-mediated targeting of Pep4 determines the activity of the vacuole in a substrate-dependent manner.
regulating the Golgi apparatus sorting of PrA facilitates the delivery of more PrA to the vacuoles in the yeast cells; this has implications for beverage production as well as understanding the role of PrA
Title: Regulating the Golgi apparatus sorting of proteinase A to decrease its excretion in Saccharomyces cerevisiae.
Pep4 mutant cells are highly sensitive to oxidative and apoptotic stress induced by hydrogen peroxide and acetic acid.
Title: Quercetin Protects Yeast Saccharomyces cerevisiae pep4 Mutant from Oxidative and Apoptotic Stress and Extends Chronological Lifespan.
Study discuss the structure and physiological function of PEP4, and its transport routes: the Golgi-to-vacuole pathway and the constitutive Golgi-to-plasma membrane pathway. In addition, it is briefly discussed that calcium homeostasis plays an important role in the secretory pathway of proteins, implying that the regulation of PrA delivery to the plasma membrane requires the involvement of calcium ion. [review]
Title: Saccharomyces cerevisiae proteinase A excretion and wine making.
The propeptide of yeast cathepsin D inhibits programmed necrosis.
Title: The propeptide of yeast cathepsin D inhibits programmed necrosis.
The finding that both mitochondrial AAC proteins and the vacuolar Pep4p interfere with mitochondrial degradation suggests a complex regulation and interplay between mitochondria and the vacuole in yeast programmed cell death.[Pep4 & AAC]
Title: Mitochondrial degradation in acetic acid-induced yeast apoptosis: the role of Pep4 and the ADP/ATP carrier.
the lag phase of cell growth of partial PrA (PEP4) gene deletion mutant (36 h) and PrA-negative mutant (48 h) was significantly extended, compared with the wild type strain (24 h) (P<0.05), but PrA had no effect on glucose metabolism
Title: Effects of proteinase A on cultivation and viability characteristics of industrial Saccharomyces cerevisiae WZ65.
Rck2 degradation upon exposure of cells to high levels of zinc is dependent on Pep4
Title: Degradation of Saccharomyces cervisiae Rck2 upon exposure of cells to high levels of zinc is dependent on Pep4.
results indicate that Pep4p is important for protein turnover after oxidative damage; however, increased removal of oxidized proteins is not sufficient to enhance lifespan
Title: The Pep4p vacuolar proteinase contributes to the turnover of oxidized proteins but PEP4 overexpression is not sufficient to increase chronological lifespan in Saccharomyces cerevisiae.
concluded that increases in reactive-oxygen species and nuclear pore complex permeability occur relatively early during H2O2-induced cell death; later, Pep4p migrates out of vacuoles and degrades nucleoporins after the cells are effectively dead
Title: Increased nuclear envelope permeability and Pep4p-dependent degradation of nucleoporins during hydrogen peroxide-induced cell death.

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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

NCBI Orthologs

Orthologs from OrthoDB

Gene Ontology Provided by SGD

Function	Evidence Code	Pubs
enables aspartic-type endopeptidase activity	IBA Inferred from Biological aspect of Ancestor more info
enables aspartic-type endopeptidase activity	IDA Inferred from Direct Assay more info	PubMed
enables aspartic-type endopeptidase activity	IEA Inferred from Electronic Annotation more info
enables disordered domain specific binding	IPI Inferred from Physical Interaction more info	PubMed
enables hydrolase activity	IEA Inferred from Electronic Annotation more info
enables oligosaccharide binding	IDA Inferred from Direct Assay more info	PubMed
enables peptidase activity	IDA Inferred from Direct Assay more info	PubMed
enables peptidase activity	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
involved_in autophagy	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in cytoplasm to vacuole targeting by the Cvt pathway	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in macroautophagy	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in microautophagy	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in pexophagy	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in proteolysis	IEA Inferred from Electronic Annotation more info
involved_in proteolysis involved in protein catabolic process	IBA Inferred from Biological aspect of Ancestor more info
involved_in proteolysis involved in protein catabolic process	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
located_in endoplasmic reticulum	HDA more info	PubMed
located_in fungal-type vacuole	HDA more info	PubMed
is_active_in fungal-type vacuole	IBA Inferred from Biological aspect of Ancestor more info
located_in fungal-type vacuole	IDA Inferred from Direct Assay more info	PubMed
located_in fungal-type vacuole	IEA Inferred from Electronic Annotation more info
located_in mitochondrion	HDA more info	PubMed
part_of protein-containing complex	IDA Inferred from Direct Assay more info	PubMed
located_in vacuole	IEA Inferred from Electronic Annotation more info

General protein information

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Preferred Names: proteinase A

NP_015171.1

EC 3.4.23.25

Vacuolar aspartyl protease (proteinase A); required for post-translational precursor maturation of vacuolar proteinases; important for protein turnover after oxidative damage; plays a protective role in acetic acid induced apoptosis; synthesized as a zymogen, self-activates; targeted to vacuole via Vps10p-dependent endosomal vacuolar protein sorting pathway