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Protein

Ubiquitin carboxyl-terminal hydrolase 4

Gene

DOA4

Organism
Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Ubiquitin thioesterase that acts at the late endosome/prevacuolar compartment to recover ubiquitin from ubiquitinated membrane proteins en route to the vacuole. Removes also ubiquitin from soluble proteins targeted to proteasomes. Is essential to maintain a normal level of free ubiquitin. Involved in the ammonium-induced down-regulation of the GAP1 permease and the UME3 destruction in response to oxidative stress. Has a role in the RAD9 checkpoint response to TOP1 poisons. Required for promoting coordination of DNA replication and avoids DNA overreplication.19 Publications

Catalytic activityi

Thiol-dependent hydrolysis of ester, thioester, amide, peptide and isopeptide bonds formed by the C-terminal Gly of ubiquitin (a 76-residue protein attached to proteins as an intracellular targeting signal).

Enzyme regulationi

RFU1 is an inhibitor of deubiquitination activity.1 Publication

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Active sitei571 – 5711Nucleophile
Active sitei880 – 8801Proton acceptorPROSITE-ProRule annotation

GO - Molecular functioni

  • thiol-dependent ubiquitin-specific protease activity Source: SGD

GO - Biological processi

  • endocytosis Source: SGD
  • free ubiquitin chain depolymerization Source: SGD
  • intralumenal vesicle formation Source: SGD
  • protein deubiquitination Source: InterPro
  • regulation of DNA replication Source: SGD
  • ubiquitin-dependent protein catabolic process Source: SGD
  • ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway Source: SGD
  • ubiquitin homeostasis Source: SGD
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Protease, Thiol protease

Keywords - Biological processi

Ubl conjugation pathway

Enzyme and pathway databases

BioCyciYEAST:G3O-29676-MONOMER.
ReactomeiR-SCE-1169408. ISG15 antiviral mechanism.
R-SCE-1358803. Downregulation of ERBB2:ERBB3 signaling.

Protein family/group databases

MEROPSiC19.005.

Names & Taxonomyi

Protein namesi
Recommended name:
Ubiquitin carboxyl-terminal hydrolase 4 (EC:3.4.19.12)
Alternative name(s):
Deubiquitinating enzyme 4
Ubiquitin thioesterase 4
Ubiquitin-specific-processing protease 4
Vacuole biogenesis protein SSV7
Gene namesi
Name:DOA4
Synonyms:DOS1, MUT4, NPI2, SSV7, UBP4
Ordered Locus Names:YDR069C
ORF Names:D4270, YD8554.02C, YD9609.23C
OrganismiSaccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)
Taxonomic identifieri559292 [NCBI]
Taxonomic lineageiEukaryotaFungiDikaryaAscomycotaSaccharomycotinaSaccharomycetesSaccharomycetalesSaccharomycetaceaeSaccharomyces
Proteomesi
  • UP000002311 Componenti: Chromosome IV

Organism-specific databases

EuPathDBiFungiDB:YDR069C.
SGDiS000002476. DOA4.

Subcellular locationi

GO - Cellular componenti

  • endosome Source: SGD
  • late endosome membrane Source: UniProtKB-SubCell
  • proteasome complex Source: SGD
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Endosome, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi571 – 5711C → S or A: Impairs deubiquitination activity and protein sorting into the MVB pathway. 2 Publications
Mutagenesisi826 – 8261Y → A: Impairs deubiquitination activity and binding to BRO1; when associated with A-827 and A-829. 1 Publication
Mutagenesisi827 – 8271P → A: Impairs deubiquitination activity and binding to BRO1; when associated with A-826 and A-829. 1 Publication
Mutagenesisi829 – 8291L → A: Impairs deubiquitination activity and binding to BRO1; when associated with A-826 and A-827. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 926926Ubiquitin carboxyl-terminal hydrolase 4PRO_0000080589Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei443 – 4431PhosphoserineCombined sources

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiP32571.

PTM databases

iPTMnetiP32571.

Interactioni

Subunit structurei

Interacts with BRO1, RFU1 and VPS32. Associates with the 26S proteasome.5 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
BRO1P4858215EBI-19840,EBI-3768
RFU1Q080032EBI-19840,EBI-2353109

Protein-protein interaction databases

BioGridi32124. 129 interactions.
DIPiDIP-5298N.
IntActiP32571. 27 interactions.
MINTiMINT-550253.

Structurei

3D structure databases

ProteinModelPortaliP32571.
SMRiP32571. Positions 563-922.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini205 – 328124RhodanesePROSITE-ProRule annotationAdd
BLAST
Domaini562 – 923362USPAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi386 – 3927Poly-Gln

Domaini

Residues 1-208 are essential for the localization to the late endosome and constitute a late endosome localization (LEL) domain.1 Publication

Sequence similaritiesi

Belongs to the peptidase C19 family.Curated
Contains 1 rhodanese domain.PROSITE-ProRule annotation
Contains 1 USP domain.Curated

Phylogenomic databases

GeneTreeiENSGT00790000122967.
HOGENOMiHOG000248489.
InParanoidiP32571.
KOiK11839.
OMAiGQYASQL.
OrthoDBiEOG092C5R71.

Family and domain databases

Gene3Di3.40.250.10. 1 hit.
InterProiIPR001394. Peptidase_C19_UCH.
IPR001763. Rhodanese-like_dom.
IPR018200. USP_CS.
IPR028889. USP_dom.
[Graphical view]
PfamiPF00581. Rhodanese. 1 hit.
PF00443. UCH. 1 hit.
[Graphical view]
SMARTiSM00450. RHOD. 1 hit.
[Graphical view]
SUPFAMiSSF52821. SSF52821. 1 hit.
PROSITEiPS50206. RHODANESE_3. 1 hit.
PS00972. USP_1. 1 hit.
PS00973. USP_2. 1 hit.
PS50235. USP_3. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

P32571-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MEQNIISTIR DECIRHRSKY LTIAQLTAIA EAKINEFIIT GKAKDQDLSS
60 70 80 90 100
LLDKCIDILS IYKKNSKDIK NIISCKNKGA MISSNSVMII QLNYVYYKVI
110 120 130 140 150
HIIVTTNIPH LSEFAKIKLH KSTSDEGNGN NNNNEFQLMN IYNTLLETLL
160 170 180 190 200
KDENIAKIKS FIKSSIKQTK LNHEQEECNL MRTGSYITSN QLNSLISSSA
210 220 230 240 250
NSASSQMEIL LIDIRSRLEF NKSHIDTKNI ICLEPISFKM SYSDHDLEKK
260 270 280 290 300
SLITSPNSEI KMFQSRNLFK FIILYTDANE YNVKQQSVLL DILVNHSFEK
310 320 330 340 350
PISDDFTKIF ILESGFPGWL KSNYGRQVSS SFPSNNNIKD DSVYINGNTS
360 370 380 390 400
GLSLQHLPKM SPSIRHSMDD SMKEMLVAPT PLNHLQQQQQ QQSDNDHVLK
410 420 430 440 450
RSSSFKKLFS NYTSPNPKNS NSNLYSISSL SISSSPSPLP LHSPDPVKGN
460 470 480 490 500
SLPINYPETP HLWKNSETDF MTNQREQLNH NSFAHIAPIN TKAITSPSRT
510 520 530 540 550
ATPKLQRFPQ TISMNLNMNS NGHSSATSTI QPSCLSLSNN DSLDHTDVTP
560 570 580 590 600
TSSHNYDLDF AVGLENLGNS CYMNCIIQCI LGTHELTQIF LDDSYAKHIN
610 620 630 640 650
INSKLGSKGI LAKYFARLVH MMYKEQVDGS KKISISPIKF KLACGSVNSL
660 670 680 690 700
FKTASQQDCQ EFCQFLLDGL HEDLNQCGSN PPLKELSQEA EARREKLSLR
710 720 730 740 750
IASSIEWERF LTTDFSVIVD LFQGQYASRL KCKVCSHTST TYQPFTVLSI
760 770 780 790 800
PIPKKNSRNN ITIEDCFREF TKCENLEVDE QWLCPHCEKR QPSTKQLTIT
810 820 830 840 850
RLPRNLIVHL KRFDNLLNKN NDFVIYPFLL DLTPFWANDF DGVFPPGVND
860 870 880 890 900
DELPIRGQIP PFKYELYGVA CHFGTLYGGH YTAYVKKGLK KGWLYFDDTK
910 920
YKPVKNKADA INSNAYVLFY HRVYGV
Length:926
Mass (Da):105,192
Last modified:February 1, 1994 - v2
Checksum:iB863FE6062510F3C
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti327 – 3271Q → K in AAA35105 (Ref. 2) Curated
Sequence conflicti345 – 3451I → F in AAA35105 (Ref. 2) Curated
Sequence conflicti375 – 3784MLVA → TASW in AAA35105 (Ref. 2) Curated
Sequence conflicti383 – 3831N → I in AAA35105 (Ref. 2) Curated
Sequence conflicti407 – 4071K → T in AAA35105 (Ref. 2) Curated
Sequence conflicti543 – 57028LDHTD…NLGNS → FRSYEMLHQLLLIIMTLISR LVWENLEIP in AAA35105 (Ref. 2) CuratedAdd
BLAST
Sequence conflicti580 – 5801I → T in AAA35105 (Ref. 2) Curated
Sequence conflicti836 – 8361W → G in AAA35105 (Ref. 2) Curated
Sequence conflicti897 – 8971D → N in AAA35105 (Ref. 2) Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U02518 Genomic DNA. Translation: AAC48915.1.
L08070 Genomic DNA. Translation: AAA35105.1.
Z49209 Genomic DNA. Translation: CAA89098.1.
Z46796 Genomic DNA. Translation: CAA86791.1.
Z74365 Genomic DNA. Translation: CAA98887.1.
X84162 Genomic DNA. Translation: CAA58985.1.
BK006938 Genomic DNA. Translation: DAA11915.1.
PIRiS39344.
RefSeqiNP_010354.3. NM_001180377.3.

Genome annotation databases

EnsemblFungiiYDR069C; YDR069C; YDR069C.
GeneIDi851641.
KEGGisce:YDR069C.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U02518 Genomic DNA. Translation: AAC48915.1.
L08070 Genomic DNA. Translation: AAA35105.1.
Z49209 Genomic DNA. Translation: CAA89098.1.
Z46796 Genomic DNA. Translation: CAA86791.1.
Z74365 Genomic DNA. Translation: CAA98887.1.
X84162 Genomic DNA. Translation: CAA58985.1.
BK006938 Genomic DNA. Translation: DAA11915.1.
PIRiS39344.
RefSeqiNP_010354.3. NM_001180377.3.

3D structure databases

ProteinModelPortaliP32571.
SMRiP32571. Positions 563-922.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi32124. 129 interactions.
DIPiDIP-5298N.
IntActiP32571. 27 interactions.
MINTiMINT-550253.

Protein family/group databases

MEROPSiC19.005.

PTM databases

iPTMnetiP32571.

Proteomic databases

MaxQBiP32571.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsemblFungiiYDR069C; YDR069C; YDR069C.
GeneIDi851641.
KEGGisce:YDR069C.

Organism-specific databases

EuPathDBiFungiDB:YDR069C.
SGDiS000002476. DOA4.

Phylogenomic databases

GeneTreeiENSGT00790000122967.
HOGENOMiHOG000248489.
InParanoidiP32571.
KOiK11839.
OMAiGQYASQL.
OrthoDBiEOG092C5R71.

Enzyme and pathway databases

BioCyciYEAST:G3O-29676-MONOMER.
ReactomeiR-SCE-1169408. ISG15 antiviral mechanism.
R-SCE-1358803. Downregulation of ERBB2:ERBB3 signaling.

Miscellaneous databases

PROiP32571.

Family and domain databases

Gene3Di3.40.250.10. 1 hit.
InterProiIPR001394. Peptidase_C19_UCH.
IPR001763. Rhodanese-like_dom.
IPR018200. USP_CS.
IPR028889. USP_dom.
[Graphical view]
PfamiPF00581. Rhodanese. 1 hit.
PF00443. UCH. 1 hit.
[Graphical view]
SMARTiSM00450. RHOD. 1 hit.
[Graphical view]
SUPFAMiSSF52821. SSF52821. 1 hit.
PROSITEiPS50206. RHODANESE_3. 1 hit.
PS00972. USP_1. 1 hit.
PS00973. USP_2. 1 hit.
PS50235. USP_3. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiUBP4_YEAST
AccessioniPrimary (citable) accession number: P32571
Secondary accession number(s): D6VS55
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1993
Last sequence update: February 1, 1994
Last modified: September 7, 2016
This is version 168 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programFungal Protein Annotation Program

Miscellaneousi

Miscellaneous

Present with 428 molecules/cell in log phase SD medium.1 Publication

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Peptidase families
    Classification of peptidase families and list of entries
  2. SIMILARITY comments
    Index of protein domains and families
  3. Yeast
    Yeast (Saccharomyces cerevisiae): entries, gene names and cross-references to SGD
  4. Yeast chromosome IV
    Yeast (Saccharomyces cerevisiae) chromosome IV: entries and gene names

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.