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DOA4 ubiquitin-specific protease DOA4 [ Saccharomyces cerevisiae S288C ]

Gene ID: 851641, updated on 15-Mar-2026
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. Orthologous to human USP2 (ubiquitin specific peptidase 2). [provided by Alliance of Genome Resources, Jul 2025]
Orthologs
all
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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_001136.10Genomic Context describing neighboring genes Neighboring gene protein-tyrosine-phosphatase Neighboring gene Dos2p Neighboring gene Fmp16p Neighboring gene polyamine acetyltransferase

Genomic Sequence:
NC_001136.10

Go to nucleotide: Graphics FASTA GenBank

Related articles in PubMed

  1. Inactivation-reactivation process and repression of permease formation regulate several ammonia-sensitive permeases in the yeast Saccharomyces cerevisiae. Grenson M. Eur J Biochem, 1983 Jun 1. PMID 6343083
  2. NH4+-induced down-regulation of the Saccharomyces cerevisiae Gap1p permease involves its ubiquitination with lysine-63-linked chains. Springael JY, et al. J Cell Sci, 1999 May. PMID 10194416
  3. Catabolite inactivation of the yeast maltose transporter requires ubiquitin-ligase npi1/rsp5 and ubiquitin-hydrolase npi2/doa4. Lucero P, et al. FEMS Microbiol Lett, 1997 Feb 15. PMID 9119204
  4. Evidence for a direct role of the Doa4 deubiquitinating enzyme in protein sorting into the MVB pathway. Nikko E, et al. Traffic, 2007 May. PMID 17376168
  5. The yeast DOA4 gene encodes a deubiquitinating enzyme related to a product of the human tre-2 oncogene. Papa FR, et al. Nature, 1993 Nov 25. PMID 8247125

See all (145) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. 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.
  2. 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.
  3. 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.
  4. 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.
  5. 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.
  6. 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.
  7. Dual mechanisms specify Doa4-mediated deubiquitination at multivesicular bodies.
    Title: Dual mechanisms specify Doa4-mediated deubiquitination at multivesicular bodies.
  8. 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
Products Interactant Other Gene Complex Source Pubs Description

Homology

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 hydrolase activity IEA
Inferred from Electronic Annotation
more info
  
enables peptidase activity IEA
Inferred from Electronic Annotation
more info
  
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
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 PubMed 
located_in endosome IDA
Inferred from Direct Assay
more info
 PubMed 
located_in late endosome membrane IEA
Inferred from Electronic Annotation
more info
  
located_in mitochondrion HDA PubMed 
part_of proteasome complex IDA
Inferred from Direct Assay
more info
 PubMed 
Preferred Names
ubiquitin-specific protease DOA4
NP_010354.3
  • 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

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Genome Annotation

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

Reference assembly

Genomic

  1. NC_001136.10 Reference assembly

    Range
    584939..587719 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001180377.3 → NP_010354.3  ubiquitin-specific protease DOA4

    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]
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
P32571.2

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