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    DOA4 ubiquitin-specific protease DOA4 [ Saccharomyces cerevisiae S288C ]

    Gene ID: 851641, updated on 2-Nov-2024

    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, Nov 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_001136.10Genomic Context describing neighboring genes Neighboring gene protein-tyrosine-phosphatase Neighboring gene Dos2p Neighboring gene Fmp16p Neighboring gene polyamine acetyltransferase

    Genomic regions, transcripts, and products

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    Genomic Sequence:
    NC_001136.10

    Go to nucleotide: Graphics FASTA GenBank

    Bibliography

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    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. 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
    3. 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
    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. Ubiquitin lys63 is involved in ubiquitination of a yeast plasma membrane protein. Galan JM, et al. EMBO J, 1997 Oct 1. PMID 9312043, Free PMC Article

    See all (143) 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

    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    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 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 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 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
    • 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

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

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