DOA4 ubiquitin-specific protease DOA4 [Saccharomyces cerevisiae S288C] - Gene

Summary

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Official Symbol: DOA4
Official Full Name: ubiquitin-specific protease DOA4
Primary source: SGD:S000002476
Locus tag: YDR069C
See related: AllianceGenome:SGD:S000002476; FungiDB:YDR069C; VEuPathDB:YDR069C
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: DOS1; MUT4; NPI2; SSV7; UBP4
Summary: Enables cysteine-type deubiquitinase activity. Involved in several processes, including ATP export; free ubiquitin chain depolymerization; and intralumenal vesicle formation. Located in endosome. Part of proteasome complex. Human ortholog(s) of this gene implicated in ACTH-secreting pituitary adenoma. Orthologous to human USP8 (ubiquitin specific peptidase 8). [provided by Alliance of Genome Resources, Dec 2024]
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Genomic context

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See DOA4 in Genome Data Viewer

Location:: chromosome: IV

Exon count:: 1

Sequence:: Chromosome: IV; NC_001136.10 (584939..587719, complement)

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?

Vacuolar H+-ATPase dysfunction rescues intralumenal vesicle cargo sorting in yeast lacking PI(3,5)P2 or Doa4.
Title: Vacuolar H+-ATPase dysfunction rescues intralumenal vesicle cargo sorting in yeast lacking PI(3,5)P2 or Doa4.
The ubiquitin hydrolase Doa4 directly binds Snf7 to inhibit recruitment of ESCRT-III remodeling factors in S. cerevisiae.
Title: The ubiquitin hydrolase Doa4 directly binds Snf7 to inhibit recruitment of ESCRT-III remodeling factors in S. cerevisiae.
Doa4 physically interacts with the ESCRT-III component Snf7 and preferentially cleaves Lys63-linked ubiquitin oligomers involved in membrane protein trafficking
Title: The N-terminal domains determine cellular localization and functions of the Doa4 and Ubp5 deubiquitinating enzymes.
Binding of Vps20 to the Doa4 N-terminus inhibits a non-catalytic function of Doa4 that promotes ILV formation.
Title: Doa4 function in ILV budding is restricted through its interaction with the Vps20 subunit of ESCRT-III.
identified a protein designated Rfu1 (regulator of free ubiquitin chains 1), which regulates intracellular concentrations of monomeric ubiquitins; functions as an inhibitor of Doa4
Title: An inhibitor of a deubiquitinating enzyme regulates ubiquitin homeostasis.
Deubiquitination by Doa4 of cargo proteins and/or some components of the multivesicular body (MVB) sorting machinery is essential to correct sorting of cargoes into the MVB pathway.
Title: Evidence for a direct role of the Doa4 deubiquitinating enzyme in protein sorting into the MVB pathway.
Dual mechanisms specify Doa4-mediated deubiquitination at multivesicular bodies.
Title: Dual mechanisms specify Doa4-mediated deubiquitination at multivesicular bodies.
This is the first demonstration of a physiologically important DUB (Doa4) subcellular localization signal and provides a striking example of the functional diversification of DUB paralogues by the evolution of alternative spatial signals.
Title: A conserved late endosome-targeting signal required for Doa4 deubiquitylating enzyme function.

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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 cysteine-type deubiquitinase activity	IDA Inferred from Direct Assay more info	PubMed
enables cysteine-type deubiquitinase activity	IEA Inferred from Electronic Annotation more info
enables cysteine-type deubiquitinase activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables cysteine-type peptidase activity	IEA Inferred from Electronic Annotation more info
enables zinc ion binding	RCA inferred from Reviewed Computational Analysis more info	PubMed

Process	Evidence Code	Pubs
involved_in ATP export	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in endocytosis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in free ubiquitin chain depolymerization	IDA Inferred from Direct Assay more info	PubMed
involved_in intralumenal vesicle formation	IGI Inferred from Genetic Interaction more info	PubMed
involved_in protein deubiquitination	IEA Inferred from Electronic Annotation more info
involved_in proteolysis	IEA Inferred from Electronic Annotation more info
involved_in regulation of DNA replication	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in ubiquitin recycling	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in ubiquitin-dependent protein catabolic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
located_in cytoplasm	IEA Inferred from Electronic Annotation more info
located_in cytosol	HDA more info	PubMed
located_in endosome	IDA Inferred from Direct Assay more info	PubMed
located_in endosome	IEA Inferred from Electronic Annotation more info
located_in late endosome membrane	IEA Inferred from Electronic Annotation more info
located_in membrane	IEA Inferred from Electronic Annotation more info
located_in mitochondrion	HDA more info	PubMed
part_of proteasome complex	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: ubiquitin-specific protease DOA4

NP_010354.3

EC 3.4.19.12

Ubiquitin hydrolase; deubiquitinates intralumenal vesicle (ILVs) cargo proteins; required for recycling ubiquitin from proteasome-bound ubiquitinated intermediates, acts at the late endosome/prevacuolar compartment to recover ubiquitin from ubiquitinated membrane proteins destined for the vacuole; DOA4 has a paralog, UBP5, 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_001136.10 Reference assembly

Range

584939..587719 complement

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001180377.3 → NP_010354.3 TPA: ubiquitin-specific protease DOA4 [Saccharomyces cerevisiae S288C]

See identical proteins and their annotated locations for NP_010354.3

Status: REVIEWED

UniProtKB/Swiss-Prot

B3LGK1, D6VS55, P32571

UniProtKB/TrEMBL

C7GVR7, C8Z4Y7

Conserved Domains (2) summary

smart00450
Location:208 → 324

RHOD; Rhodanese Homology Domain

COG5533
Location:495 → 924

COG5533; Ubiquitin C-terminal hydrolase [Posttranslational modification, protein turnover, chaperones]