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

Summary

Go to the top of the page Help

Gene symbol: DOA4
Gene description: ubiquitin-specific protease DOA4
Primary source: FungiDB:YDR069C
Locus tag: YDR069C
See related: SGD:S000002476; AllianceGenome:SGD:S000002476; 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 thiol-dependent deubiquitinase. 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 several human genes including USP50 (ubiquitin specific peptidase 50) and USP8 (ubiquitin specific peptidase 8). [provided by Alliance of Genome Resources, Apr 2022]
NEW: Try the new Gene table
Try the new Transcript table

Genomic context

Go to the top of the page Help

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

Go to the top of the page Help

Go to reference sequence details

Genomic Sequence:: NC_001136.10

Go to nucleotide: Graphics FASTA GenBank

Bibliography

Go to the top of the page Help

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.

Submit: New GeneRIF Correction

Interactions

Go to the top of the page Help

Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

Go to the top of the page Help

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

Go to the top of the page Help

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)

Go to the top of the page Help

NEW Try the new Transcript table

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

Download

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]