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Protein

Ubiquitin thioesterase OTU1

Gene

YOD1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

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.2 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

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei157By similarity1
Active sitei160Nucleophile1 Publication1
Binding sitei266Substrate; via carbonyl oxygenCombined sources1 Publication1
Active sitei2671 Publication1
Active sitei342By similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri318 – 342C2H2-typePROSITE-ProRule annotationAdd BLAST25

GO - Molecular functioni

  • 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
  • ubiquitin-specific protease activity involved in negative regulation of retrograde protein transport, ER to cytosol Source: ParkinsonsUK-UCL

GO - Biological processi

  • endoplasmic reticulum unfolded protein response Source: UniProtKB
  • ER-associated ubiquitin-dependent protein catabolic process Source: UniProtKB
  • 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
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Protease, Thiol protease

Keywords - Biological processi

Ubl conjugation pathway, Unfolded protein response

Keywords - Ligandi

Metal-binding, Zinc

Enzyme and pathway databases

BRENDAi3.4.19.12. 2681.
ReactomeiR-HSA-5689896. Ovarian tumor domain proteases.

Protein family/group databases

MEROPSiC85.007.

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
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

HGNCiHGNC:25035. YOD1.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi160C → 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. 1 Publication1
Mutagenesisi292I → Q: Does not affect activity or specificity. Impairs ability to cleave longer 'Lys-11'-linked ubiquitin chains; when associated with Q-295. 1 Publication1
Mutagenesisi295V → Q: Does not affect activity or specificity. Impairs ability to cleave longer 'Lys-11'-linked ubiquitin chains; when associated with Q-292. 1 Publication1
Mutagenesisi336H → 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 Publication1
Mutagenesisi342H → 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 Publication1

Organism-specific databases

DisGeNETi55432.
OpenTargetsiENSG00000180667.
PharmGKBiPA142670552.

Polymorphism and mutation databases

BioMutaiYOD1.
DMDMi74747276.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002823561 – 348Ubiquitin thioesterase OTU1Add BLAST348

Proteomic databases

EPDiQ5VVQ6.
MaxQBiQ5VVQ6.
PaxDbiQ5VVQ6.
PeptideAtlasiQ5VVQ6.
PRIDEiQ5VVQ6.

PTM databases

iPTMnetiQ5VVQ6.
PhosphoSitePlusiQ5VVQ6.

Expressioni

Gene expression databases

BgeeiENSG00000180667.
CleanExiHS_YOD1.
GenevisibleiQ5VVQ6. HS.

Organism-specific databases

HPAiHPA028400.
HPA028439.

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.2 Publications

GO - Molecular functioni

  • ubiquitin protein ligase binding Source: ParkinsonsUK-UCL

Protein-protein interaction databases

BioGridi120666. 27 interactors.
IntActiQ5VVQ6. 11 interactors.
STRINGi9606.ENSP00000326813.

Structurei

Secondary structure

1348
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi138 – 140Combined sources3
Beta strandi148 – 151Combined sources4
Helixi160 – 169Combined sources10
Helixi176 – 178Combined sources3
Helixi179 – 192Combined sources14
Turni194 – 196Combined sources3
Helixi199 – 202Combined sources4
Helixi206 – 213Combined sources8
Beta strandi215 – 217Combined sources3
Helixi222 – 232Combined sources11
Beta strandi234 – 240Combined sources7
Turni241 – 244Combined sources4
Beta strandi245 – 249Combined sources5
Turni250 – 252Combined sources3
Beta strandi256 – 263Combined sources8
Beta strandi268 – 274Combined sources7
Beta strandi276 – 280Combined sources5
Beta strandi285 – 287Combined sources3
Helixi292 – 308Combined sources17

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4BOQX-ray1.47A132-314[»]
4BOSX-ray2.35A/B147-314[»]
4BOZX-ray3.03A/D132-314[»]
ProteinModelPortaliQ5VVQ6.
SMRiQ5VVQ6.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini149 – 274OTUPROSITE-ProRule annotationAdd BLAST126

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni50 – 128UBX-like1 PublicationAdd BLAST79
Regioni154 – 160Cys-loop1 Publication7
Regioni213 – 223Variable-loop1 PublicationAdd BLAST11
Regioni263 – 267His-loop1 Publication5
Regioni291 – 296S2 site1 Publication6

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

Sequence similaritiesi

Contains 1 C2H2-type zinc finger.PROSITE-ProRule annotation
Contains 1 OTU domain.PROSITE-ProRule annotation

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri318 – 342C2H2-typePROSITE-ProRule annotationAdd BLAST25

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiKOG3288. Eukaryota.
COG5539. LUCA.
GeneTreeiENSGT00390000009989.
HOGENOMiHOG000193461.
HOVERGENiHBG097006.
InParanoidiQ5VVQ6.
KOiK13719.
OMAiGGHFGVP.
OrthoDBiEOG091G0CA6.
PhylomeDBiQ5VVQ6.
TreeFamiTF323700.

Family and domain databases

InterProiIPR003323. OTU_dom.
IPR029071. Ubiquitin-rel_dom.
IPR007087. Znf_C2H2.
[Graphical view]
PfamiPF02338. OTU. 1 hit.
[Graphical view]
SUPFAMiSSF54236. SSF54236. 1 hit.
PROSITEiPS50802. OTU. 1 hit.
PS00028. ZINC_FINGER_C2H2_1. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q5VVQ6-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        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
Length:348
Mass (Da):38,322
Last modified:December 7, 2004 - v1
Checksum:i91DBD25BE85B1CCC
GO
Isoform 2 (identifier: Q5VVQ6-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-61: MFGPAKGRHF...KAKDGTHVLQ → METLHIIYSEAKSFTVE

Note: No experimental confirmation available.
Show »
Length:304
Mass (Da):33,979
Checksum:i8055467E0FD819CA
GO

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 keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti8R → G in CAD89975 (PubMed:17974005).Curated1
Sequence conflicti90L → F in BAC87233 (PubMed:14702039).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0241221 – 61MFGPA…THVLQ → METLHIIYSEAKSFTVE in isoform 2. 1 PublicationAdd BLAST61

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK128014 mRNA. Translation: BAC87233.1.
AL445493 Genomic DNA. Translation: CAH70775.1.
AL445493 Genomic DNA. Translation: CAH70776.1.
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.
CCDSiCCDS31002.1. [Q5VVQ6-1]
CCDS60402.1. [Q5VVQ6-2]
RefSeqiNP_001263249.1. NM_001276320.1. [Q5VVQ6-2]
NP_061036.3. NM_018566.3. [Q5VVQ6-1]
UniGeneiHs.567533.
Hs.745490.

Genome annotation databases

EnsembliENST00000315927; ENSP00000326813; ENSG00000180667. [Q5VVQ6-1]
ENST00000367084; ENSP00000356051; ENSG00000180667. [Q5VVQ6-2]
GeneIDi55432.
KEGGihsa:55432.
UCSCiuc001hfe.1. human. [Q5VVQ6-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK128014 mRNA. Translation: BAC87233.1.
AL445493 Genomic DNA. Translation: CAH70775.1.
AL445493 Genomic DNA. Translation: CAH70776.1.
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.
CCDSiCCDS31002.1. [Q5VVQ6-1]
CCDS60402.1. [Q5VVQ6-2]
RefSeqiNP_001263249.1. NM_001276320.1. [Q5VVQ6-2]
NP_061036.3. NM_018566.3. [Q5VVQ6-1]
UniGeneiHs.567533.
Hs.745490.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4BOQX-ray1.47A132-314[»]
4BOSX-ray2.35A/B147-314[»]
4BOZX-ray3.03A/D132-314[»]
ProteinModelPortaliQ5VVQ6.
SMRiQ5VVQ6.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi120666. 27 interactors.
IntActiQ5VVQ6. 11 interactors.
STRINGi9606.ENSP00000326813.

Protein family/group databases

MEROPSiC85.007.

PTM databases

iPTMnetiQ5VVQ6.
PhosphoSitePlusiQ5VVQ6.

Polymorphism and mutation databases

BioMutaiYOD1.
DMDMi74747276.

Proteomic databases

EPDiQ5VVQ6.
MaxQBiQ5VVQ6.
PaxDbiQ5VVQ6.
PeptideAtlasiQ5VVQ6.
PRIDEiQ5VVQ6.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000315927; ENSP00000326813; ENSG00000180667. [Q5VVQ6-1]
ENST00000367084; ENSP00000356051; ENSG00000180667. [Q5VVQ6-2]
GeneIDi55432.
KEGGihsa:55432.
UCSCiuc001hfe.1. human. [Q5VVQ6-1]

Organism-specific databases

CTDi55432.
DisGeNETi55432.
GeneCardsiYOD1.
HGNCiHGNC:25035. YOD1.
HPAiHPA028400.
HPA028439.
MIMi612023. gene.
neXtProtiNX_Q5VVQ6.
OpenTargetsiENSG00000180667.
PharmGKBiPA142670552.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3288. Eukaryota.
COG5539. LUCA.
GeneTreeiENSGT00390000009989.
HOGENOMiHOG000193461.
HOVERGENiHBG097006.
InParanoidiQ5VVQ6.
KOiK13719.
OMAiGGHFGVP.
OrthoDBiEOG091G0CA6.
PhylomeDBiQ5VVQ6.
TreeFamiTF323700.

Enzyme and pathway databases

BRENDAi3.4.19.12. 2681.
ReactomeiR-HSA-5689896. Ovarian tumor domain proteases.

Miscellaneous databases

GenomeRNAii55432.
PROiQ5VVQ6.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000180667.
CleanExiHS_YOD1.
GenevisibleiQ5VVQ6. HS.

Family and domain databases

InterProiIPR003323. OTU_dom.
IPR029071. Ubiquitin-rel_dom.
IPR007087. Znf_C2H2.
[Graphical view]
PfamiPF02338. OTU. 1 hit.
[Graphical view]
SUPFAMiSSF54236. SSF54236. 1 hit.
PROSITEiPS50802. OTU. 1 hit.
PS00028. ZINC_FINGER_C2H2_1. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiOTU1_HUMAN
AccessioniPrimary (citable) accession number: Q5VVQ6
Secondary accession number(s): B2RNX3
, Q5VVQ5, Q6ZRS6, Q86T63, Q9P1L8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 3, 2007
Last sequence update: December 7, 2004
Last modified: November 30, 2016
This is version 107 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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, Complete proteome, Reference proteome

Documents

  1. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. SIMILARITY comments
    Index of protein domains and families

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.