UniProtKB - Q5VVQ6 (OTU1_HUMAN)
Protein
Ubiquitin thioesterase OTU1
Gene
YOD1
Organism
Homo sapiens (Human)
Status
Functioni
Hydrolase that can remove conjugated ubiquitin from proteins and participates in endoplasmic reticulum-associated degradation (ERAD) for misfolded lumenal proteins. May act by triming the ubiquitin chain on the associated substrate to facilitate their threading through the VCP/p97 pore. Ubiquitin moieties on substrates may present a steric impediment to the threading process when the substrate is transferred to the VCP pore and threaded through VCP's axial channel. Mediates deubiquitination of 'Lys-27'-, 'Lys-29'- and 'Lys-33'-linked polyubiquitin chains. Also able to hydrolyze 'Lys-11'-linked ubiquitin chains. Cleaves both polyubiquitin and di-ubiquitin. May play a role in macroautophagy, regulating for instance the clearance of damaged lysosomes. May recruit PLAA, UBXN6 and VCP to damaged lysosome membranes decorated with K48-linked ubiquitin chains and remove these chains allowing autophagosome formation (PubMed:27753622).3 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).2 Publications EC:3.4.19.12
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Active sitei | 157 | By similarity | 1 | |
Active sitei | 160 | Nucleophile1 Publication | 1 | |
Binding sitei | 266 | Substrate; via carbonyl oxygenCombined sources1 Publication | 1 | |
Active sitei | 267 | 1 Publication | 1 | |
Active sitei | 342 | By similarity | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Zinc fingeri | 318 – 342 | C2H2-typePROSITE-ProRule annotationAdd BLAST | 25 |
GO - Molecular functioni
- cysteine-type peptidase activity Source: UniProtKB-KW
- Lys48-specific deubiquitinase activity Source: ParkinsonsUK-UCL
- Lys63-specific deubiquitinase activity Source: ParkinsonsUK-UCL
- metal ion binding Source: UniProtKB-KW
- thiol-dependent ubiquitin-specific protease activity Source: UniProtKB
- ubiquitin protein ligase binding Source: ParkinsonsUK-UCL
- ubiquitinyl hydrolase activity Source: ParkinsonsUK-UCL
GO - Biological processi
- endoplasmic reticulum unfolded protein response Source: UniProtKB
- macroautophagy Source: UniProtKB
- negative regulation of retrograde protein transport, ER to cytosol Source: ParkinsonsUK-UCL
- protein deubiquitination Source: GO_Central
- protein K11-linked deubiquitination Source: UniProtKB
- protein K27-linked deubiquitination Source: UniProtKB
- protein K29-linked deubiquitination Source: UniProtKB
- protein K33-linked deubiquitination Source: UniProtKB
- protein K48-linked deubiquitination Source: UniProtKB
- protein K63-linked deubiquitination Source: UniProtKB
- ubiquitin-dependent ERAD pathway Source: UniProtKB
Keywordsi
Molecular function | Hydrolase, Protease, Thiol protease |
Biological process | Ubl conjugation pathway, Unfolded protein response |
Ligand | Metal-binding, Zinc |
Enzyme and pathway databases
BRENDAi | 3.4.19.12, 2681 |
PathwayCommonsi | Q5VVQ6 |
Reactomei | R-HSA-5689896, Ovarian tumor domain proteases |
Protein family/group databases
MEROPSi | C85.007 |
Names & Taxonomyi
Protein namesi | Recommended name: Ubiquitin thioesterase OTU1 (EC:3.4.19.122 Publications)Alternative name(s): DUBA-8 HIV-1-induced protease 7 Short name: HIN-7 Short name: HsHIN7 OTU domain-containing protein 2 |
Gene namesi | Name:YOD1 Synonyms:DUBA8, HIN7, OTUD2 ORF Names:PRO0907 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:25035, YOD1 |
MIMi | 612023, gene |
neXtProti | NX_Q5VVQ6 |
VEuPathDBi | HostDB:ENSG00000180667.10 |
Subcellular locationi
Cytoplasm and Cytosol
- Cytoplasm 1 Publication
Note: Recruited to damaged lysosomes decorated with K48-linked ubiquitin chains.1 Publication
Keywords - Cellular componenti
CytoplasmPathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 160 | C → S: Abolishes deubiquitinase activity without affecting interaction with VCP. Specifically blocks a step in the course of dislocation and/or degradation of endoplasmic reticulum-resident proteins destined for proteasomal degradation. Prevents the macroautophagy of damaged lysosome membranes decorated with K48-linked ubiquitin chains. 2 Publications | 1 | |
Mutagenesisi | 292 | I → Q: Does not affect activity or specificity. Impairs ability to cleave longer 'Lys-11'-linked ubiquitin chains; when associated with Q-295. 1 Publication | 1 | |
Mutagenesisi | 295 | V → Q: Does not affect activity or specificity. Impairs ability to cleave longer 'Lys-11'-linked ubiquitin chains; when associated with Q-292. 1 Publication | 1 | |
Mutagenesisi | 336 | H → A: Reduced activity toward 'Lys-27'-, 'Lys-29'- and 'Lys-33'-linked ubiquitin without affecting activity toward 'Lys-11'-linked ubiquitin; when associated with A-342. 1 Publication | 1 | |
Mutagenesisi | 342 | H → A: Reduced activity toward 'Lys-27'-, 'Lys-29'- and 'Lys-33'-linked ubiquitin without affecting activity toward 'Lys-11'-linked ubiquitin; when associated with A-336. 1 Publication | 1 |
Organism-specific databases
DisGeNETi | 55432 |
NIAGADSi | ENSG00000180667 |
OpenTargetsi | ENSG00000180667 |
PharmGKBi | PA142670552 |
Miscellaneous databases
Pharosi | Q5VVQ6, Tbio |
Genetic variation databases
BioMutai | YOD1 |
DMDMi | 74747276 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000282356 | 1 – 348 | Ubiquitin thioesterase OTU1Add BLAST | 348 |
Proteomic databases
EPDi | Q5VVQ6 |
jPOSTi | Q5VVQ6 |
MassIVEi | Q5VVQ6 |
MaxQBi | Q5VVQ6 |
PaxDbi | Q5VVQ6 |
PeptideAtlasi | Q5VVQ6 |
PRIDEi | Q5VVQ6 |
ProteomicsDBi | 65481 [Q5VVQ6-1] 65482 [Q5VVQ6-2] |
PTM databases
iPTMneti | Q5VVQ6 |
PhosphoSitePlusi | Q5VVQ6 |
Expressioni
Gene expression databases
Bgeei | ENSG00000180667, Expressed in amniotic fluid and 221 other tissues |
Genevisiblei | Q5VVQ6, HS |
Organism-specific databases
HPAi | ENSG00000180667, Tissue enhanced (bone) |
Interactioni
Subunit structurei
Interacts with VCP; the interaction is direct.
Interacts with FAF2/UBXD8.
Interacts with DERL1; however interaction is dependent on the UBAX-like region, suggesting that it may be indirect.
Interacts with PLAA, UBXN6 and VCP; may form a complex involved in macroautophagy (PubMed:27753622).
3 PublicationsBinary interactionsi
Hide detailsQ5VVQ6
GO - Molecular functioni
- ubiquitin protein ligase binding Source: ParkinsonsUK-UCL
Protein-protein interaction databases
BioGRIDi | 120666, 58 interactors |
IntActi | Q5VVQ6, 31 interactors |
STRINGi | 9606.ENSP00000326813 |
Miscellaneous databases
RNActi | Q5VVQ6, protein |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details3D structure databases
SMRi | Q5VVQ6 |
ModBasei | Search... |
PDBe-KBi | Search... |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 149 – 274 | OTUPROSITE-ProRule annotationAdd BLAST | 126 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 50 – 128 | UBX-like1 PublicationAdd BLAST | 79 | |
Regioni | 154 – 160 | Cys-loop1 Publication | 7 | |
Regioni | 213 – 223 | Variable-loop1 PublicationAdd BLAST | 11 | |
Regioni | 263 – 267 | His-loop1 Publication | 5 | |
Regioni | 291 – 296 | S2 site1 Publication | 6 |
Domaini
The UBAX-like region mediates the interaction with VCP. According to PubMed:19818707, it corresponds to a UBX domain, which is a hallmark for VCP-associated proteins. However, no canonical UBX is detected by prediction tools such as Pfam or PROSITE.
The C2H2-type zinc finger mediates specificity for 'Lys-27'-, 'Lys-29'- and 'Lys-33'-linked polyubiquitin chains but not for 'Lys-11'-linked ubiquitin chains. Selectivity for 'Lys-11'-linked ubiquitin chains is provided by recognition of the sequence surrounding 'Lys-11' in ubiquitin. The S2 site region provides specificity for longer 'Lys-11'-linked ubiquitin chains (PubMed:23827681).1 Publication
Zinc finger
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Zinc fingeri | 318 – 342 | C2H2-typePROSITE-ProRule annotationAdd BLAST | 25 |
Keywords - Domaini
Zinc-fingerPhylogenomic databases
eggNOGi | KOG3288, Eukaryota |
GeneTreei | ENSGT00390000009989 |
HOGENOMi | CLU_049327_1_0_1 |
InParanoidi | Q5VVQ6 |
OMAi | SCMFRAL |
OrthoDBi | 1327072at2759 |
PhylomeDBi | Q5VVQ6 |
TreeFami | TF323700 |
Family and domain databases
InterProi | View protein in InterPro IPR039138, OTU1_2_3 IPR003323, OTU_dom IPR038765, Papain-like_cys_pep_sf IPR029071, Ubiquitin-like_domsf IPR013087, Znf_C2H2_type |
PANTHERi | PTHR13312, PTHR13312, 1 hit |
Pfami | View protein in Pfam PF02338, OTU, 1 hit |
SUPFAMi | SSF54001, SSF54001, 1 hit SSF54236, SSF54236, 1 hit |
PROSITEi | View protein in PROSITE PS50802, OTU, 1 hit PS00028, ZINC_FINGER_C2H2_1, 1 hit |
s (2)i Sequence
Sequence statusi: Complete.
This entry describes 2 produced by isoformsialternative splicing. AlignAdd to basketIsoform 1 (identifier: Q5VVQ6-1) [UniParc]FASTAAdd to basket
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MFGPAKGRHF GVHPAPGFPG GVSQQAAGTK AGPAGAWPVG SRTDTMWRLR
60 70 80 90 100
CKAKDGTHVL QGLSSRTRVR ELQGQIAAIT GIAPGGQRIL VGYPPECLDL
110 120 130 140 150
SNGDTILEDL PIQSGDMLII EEDQTRPRSS PAFTKRGASS YVRETLPVLT
160 170 180 190 200
RTVVPADNSC LFTSVYYVVE GGVLNPACAP EMRRLIAQIV ASDPDFYSEA
210 220 230 240 250
ILGKTNQEYC DWIKRDDTWG GAIEISILSK FYQCEICVVD TQTVRIDRFG
260 270 280 290 300
EDAGYTKRVL LIYDGIHYDP LQRNFPDPDT PPLTIFSSND DIVLVQALEL
310 320 330 340
ADEARRRRQF TDVNRFTLRC MVCQKGLTGQ AEAREHAKET GHTNFGEV
Sequence cautioni
The sequence AAF71033 differs from that shown. Reason: Erroneous translation. Wrong choice of frame.Curated
The sequence EAW93510 differs from that shown. Reason: Erroneous gene model prediction.Curated
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 8 | R → G in CAD89975 (PubMed:17974005).Curated | 1 | |
Sequence conflicti | 90 | L → F in BAC87233 (PubMed:14702039).Curated | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_024122 | 1 – 61 | MFGPA…THVLQ → METLHIIYSEAKSFTVE in isoform 2. 1 PublicationAdd BLAST | 61 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AK128014 mRNA Translation: BAC87233.1 AL445493 Genomic DNA No translation available. CH471100 Genomic DNA Translation: EAW93509.1 CH471100 Genomic DNA Translation: EAW93510.1 Sequence problems. BC137166 mRNA Translation: AAI37167.1 BC137167 mRNA Translation: AAI37168.1 AL833081 mRNA Translation: CAD89975.1 AF116608 mRNA Translation: AAF71033.1 Sequence problems. |
CCDSi | CCDS31002.1 [Q5VVQ6-1] CCDS60402.1 [Q5VVQ6-2] |
RefSeqi | NP_001263249.1, NM_001276320.1 [Q5VVQ6-2] NP_061036.3, NM_018566.3 [Q5VVQ6-1] |
Genome annotation databases
Ensembli | ENST00000315927; ENSP00000326813; ENSG00000180667 [Q5VVQ6-1] ENST00000367084; ENSP00000356051; ENSG00000180667 [Q5VVQ6-2] |
GeneIDi | 55432 |
KEGGi | hsa:55432 |
UCSCi | uc001hfe.1, human [Q5VVQ6-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AK128014 mRNA Translation: BAC87233.1 AL445493 Genomic DNA No translation available. CH471100 Genomic DNA Translation: EAW93509.1 CH471100 Genomic DNA Translation: EAW93510.1 Sequence problems. BC137166 mRNA Translation: AAI37167.1 BC137167 mRNA Translation: AAI37168.1 AL833081 mRNA Translation: CAD89975.1 AF116608 mRNA Translation: AAF71033.1 Sequence problems. |
CCDSi | CCDS31002.1 [Q5VVQ6-1] CCDS60402.1 [Q5VVQ6-2] |
RefSeqi | NP_001263249.1, NM_001276320.1 [Q5VVQ6-2] NP_061036.3, NM_018566.3 [Q5VVQ6-1] |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
4BOQ | X-ray | 1.47 | A | 132-314 | [»] | |
4BOS | X-ray | 2.35 | A/B | 147-314 | [»] | |
4BOZ | X-ray | 3.03 | A/D | 132-314 | [»] | |
SMRi | Q5VVQ6 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 120666, 58 interactors |
IntActi | Q5VVQ6, 31 interactors |
STRINGi | 9606.ENSP00000326813 |
Protein family/group databases
MEROPSi | C85.007 |
PTM databases
iPTMneti | Q5VVQ6 |
PhosphoSitePlusi | Q5VVQ6 |
Genetic variation databases
BioMutai | YOD1 |
DMDMi | 74747276 |
Proteomic databases
EPDi | Q5VVQ6 |
jPOSTi | Q5VVQ6 |
MassIVEi | Q5VVQ6 |
MaxQBi | Q5VVQ6 |
PaxDbi | Q5VVQ6 |
PeptideAtlasi | Q5VVQ6 |
PRIDEi | Q5VVQ6 |
ProteomicsDBi | 65481 [Q5VVQ6-1] 65482 [Q5VVQ6-2] |
Protocols and materials databases
Antibodypediai | 34591, 155 antibodies |
Genome annotation databases
Ensembli | ENST00000315927; ENSP00000326813; ENSG00000180667 [Q5VVQ6-1] ENST00000367084; ENSP00000356051; ENSG00000180667 [Q5VVQ6-2] |
GeneIDi | 55432 |
KEGGi | hsa:55432 |
UCSCi | uc001hfe.1, human [Q5VVQ6-1] |
Organism-specific databases
CTDi | 55432 |
DisGeNETi | 55432 |
GeneCardsi | YOD1 |
HGNCi | HGNC:25035, YOD1 |
HPAi | ENSG00000180667, Tissue enhanced (bone) |
MIMi | 612023, gene |
neXtProti | NX_Q5VVQ6 |
NIAGADSi | ENSG00000180667 |
OpenTargetsi | ENSG00000180667 |
PharmGKBi | PA142670552 |
VEuPathDBi | HostDB:ENSG00000180667.10 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG3288, Eukaryota |
GeneTreei | ENSGT00390000009989 |
HOGENOMi | CLU_049327_1_0_1 |
InParanoidi | Q5VVQ6 |
OMAi | SCMFRAL |
OrthoDBi | 1327072at2759 |
PhylomeDBi | Q5VVQ6 |
TreeFami | TF323700 |
Enzyme and pathway databases
BRENDAi | 3.4.19.12, 2681 |
PathwayCommonsi | Q5VVQ6 |
Reactomei | R-HSA-5689896, Ovarian tumor domain proteases |
Miscellaneous databases
BioGRID-ORCSi | 55432, 2 hits in 994 CRISPR screens |
ChiTaRSi | YOD1, human |
GenomeRNAii | 55432 |
Pharosi | Q5VVQ6, Tbio |
PROi | PR:Q5VVQ6 |
RNActi | Q5VVQ6, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000180667, Expressed in amniotic fluid and 221 other tissues |
Genevisiblei | Q5VVQ6, HS |
Family and domain databases
InterProi | View protein in InterPro IPR039138, OTU1_2_3 IPR003323, OTU_dom IPR038765, Papain-like_cys_pep_sf IPR029071, Ubiquitin-like_domsf IPR013087, Znf_C2H2_type |
PANTHERi | PTHR13312, PTHR13312, 1 hit |
Pfami | View protein in Pfam PF02338, OTU, 1 hit |
SUPFAMi | SSF54001, SSF54001, 1 hit SSF54236, SSF54236, 1 hit |
PROSITEi | View protein in PROSITE PS50802, OTU, 1 hit PS00028, ZINC_FINGER_C2H2_1, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | OTU1_HUMAN | |
Accessioni | Q5VVQ6Primary (citable) accession number: Q5VVQ6 Secondary accession number(s): B2RNX3 Q9P1L8 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | April 3, 2007 |
Last sequence update: | December 7, 2004 | |
Last modified: | April 7, 2021 | |
This is version 138 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. |
Miscellaneousi
Keywords - Technical termi
3D-structure, Reference proteomeDocuments
- Human chromosome 1
Human chromosome 1: entries, gene names and cross-references to MIM - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references