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Protein

Ubiquitin thioesterase OTUB2

Gene

OTUB2

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 in vitro and may therefore play an important regulatory role at the level of protein turnover by preventing degradation. Mediates deubiquitination of 'Lys-11'-,'Lys-48'- and 'Lys-63'-linked polyubiquitin chains, with a preference for 'Lys-63'-linked polyubiquitin chains.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).1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei481 Publication1
Active sitei51Nucleophile2 Publications1
Active sitei2241 Publication1
Sitei226Required to orient and stabilize the active site H-2241 Publication1

GO - Molecular functioni

GO - Biological processi

  • protein deubiquitination Source: UniProtKB
  • protein K11-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

Enzyme and pathway databases

ReactomeiR-HSA-5689896. Ovarian tumor domain proteases.

Protein family/group databases

MEROPSiC65.002.

Names & Taxonomyi

Protein namesi
Recommended name:
Ubiquitin thioesterase OTUB2 (EC:3.4.19.121 Publication)
Alternative name(s):
Deubiquitinating enzyme OTUB2
OTU domain-containing ubiquitin aldehyde-binding protein 2
Otubain-2
Ubiquitin-specific-processing protease OTUB2
Gene namesi
Name:OTUB2
Synonyms:C14orf137, OTB2, OTU2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 14

Organism-specific databases

HGNCiHGNC:20351. OTUB2.

Subcellular locationi

GO - Cellular componenti

  • nucleus Source: UniProtKB
Complete GO annotation...

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi47G → P: Affects its ability to cleave 'K63'-linked ubiquitin. 1 Publication1
Mutagenesisi51C → S: Loss of function in vitro. 1 Publication1
Mutagenesisi226N → A: Abolishes deubiquitinase activity. 1 Publication1

Organism-specific databases

OpenTargetsiENSG00000089723.
ENSG00000277276.
PharmGKBiPA134861658.

Polymorphism and mutation databases

BioMutaiOTUB2.
DMDMi44888285.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002210101 – 234Ubiquitin thioesterase OTUB2Add BLAST234

Proteomic databases

EPDiQ96DC9.
MaxQBiQ96DC9.
PaxDbiQ96DC9.
PeptideAtlasiQ96DC9.
PRIDEiQ96DC9.

PTM databases

iPTMnetiQ96DC9.
PhosphoSitePlusiQ96DC9.

Expressioni

Tissue specificityi

Widely expressed. Expressed at higher level in brain.1 Publication

Gene expression databases

BgeeiENSG00000089723.
CleanExiHS_OTUB2.
GenevisibleiQ96DC9. HS.

Organism-specific databases

HPAiHPA002329.

Interactioni

Binary interactionsi

WithEntry#Exp.IntActNotes
ARRDC3Q96B673EBI-746259,EBI-2875665
CPSF6Q166303EBI-746259,EBI-358410
FAM168AQ925673EBI-746259,EBI-7957930
LZTS2Q9BRK43EBI-746259,EBI-741037
MID1O153443EBI-746259,EBI-2340316
MID2Q9UJV3-23EBI-746259,EBI-10172526
RELQ048643EBI-746259,EBI-307352
SIAH1Q8IUQ43EBI-746259,EBI-747107
TP53BP2Q13625-33EBI-746259,EBI-10175039
TRIM54Q9BYV23EBI-746259,EBI-2130429

GO - Molecular functioni

Protein-protein interaction databases

BioGridi122461. 41 interactors.
IntActiQ96DC9. 20 interactors.
STRINGi9606.ENSP00000203664.

Structurei

Secondary structure

1234
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi7 – 9Combined sources3
Helixi15 – 21Combined sources7
Helixi26 – 35Combined sources10
Turni36 – 38Combined sources3
Beta strandi39 – 43Combined sources5
Beta strandi47 – 49Combined sources3
Helixi51 – 64Combined sources14
Helixi68 – 87Combined sources20
Helixi92 – 110Combined sources19
Helixi115 – 122Combined sources8
Helixi125 – 144Combined sources20
Helixi147 – 150Combined sources4
Helixi151 – 153Combined sources3
Helixi160 – 167Combined sources8
Helixi177 – 187Combined sources11
Beta strandi191 – 196Combined sources6
Beta strandi198 – 200Combined sources3
Beta strandi204 – 209Combined sources6
Beta strandi215 – 223Combined sources9
Beta strandi225 – 230Combined sources6

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1TFFX-ray2.10A1-234[»]
4FJVX-ray2.05A/C1-234[»]
ProteinModelPortaliQ96DC9.
SMRiQ96DC9.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ96DC9.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini40 – 231OTUPROSITE-ProRule annotationAdd BLAST192

Sequence similaritiesi

Belongs to the peptidase C65 family.Curated
Contains 1 OTU domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG3991. Eukaryota.
ENOG410ZMN7. LUCA.
GeneTreeiENSGT00390000006979.
HOGENOMiHOG000019496.
HOVERGENiHBG053383.
InParanoidiQ96DC9.
KOiK09603.
OMAiATECDHV.
OrthoDBiEOG091G0GDO.
PhylomeDBiQ96DC9.
TreeFamiTF314145.

Family and domain databases

InterProiIPR003323. OTU_dom.
IPR030299. OTUB2.
IPR016615. Otubain.
IPR019400. Peptidase_C65_otubain.
[Graphical view]
PANTHERiPTHR12931:SF3. PTHR12931:SF3. 1 hit.
PfamiPF10275. Peptidase_C65. 1 hit.
[Graphical view]
PIRSFiPIRSF013503. Ubiquitin_thioesterase_Otubain. 1 hit.
PROSITEiPS50802. OTU. 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: Q96DC9-1) [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
MSETSFNLIS EKCDILSILR DHPENRIYRR KIEELSKRFT AIRKTKGDGN
60 70 80 90 100
CFYRALGYSY LESLLGKSRE IFKFKERVLQ TPNDLLAAGF EEHKFRNFFN
110 120 130 140 150
AFYSVVELVE KDGSVSSLLK VFNDQSASDH IVQFLRLLTS AFIRNRADFF
160 170 180 190 200
RHFIDEEMDI KDFCTHEVEP MATECDHIQI TALSQALSIA LQVEYVDEMD
210 220 230
TALNHHVFPE AATPSVYLLY KTSHYNILYA ADKH
Length:234
Mass (Da):27,213
Last modified:March 1, 2004 - v2
Checksum:iDF2DBD32A78F9929
GO
Isoform 2 (identifier: Q96DC9-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     74-234: Missing.

Note: No experimental confirmation available.
Show »
Length:73
Mass (Da):8,637
Checksum:iD3382B36FCD3C74A
GO

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_00946574 – 234Missing in isoform 2. 1 PublicationAdd BLAST161

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY177201 mRNA. Translation: AAO27703.1.
AK025569 mRNA. Translation: BAB15172.1.
CR457345 mRNA. Translation: CAG33626.1.
AL079302 Genomic DNA. No translation available.
BC009615 mRNA. Translation: AAH09615.1.
BC068058 mRNA. Translation: AAH68058.1.
CCDSiCCDS9917.1. [Q96DC9-1]
RefSeqiNP_075601.1. NM_023112.3. [Q96DC9-1]
UniGeneiHs.278815.

Genome annotation databases

EnsembliENST00000203664; ENSP00000203664; ENSG00000089723. [Q96DC9-1]
ENST00000553723; ENSP00000451283; ENSG00000089723. [Q96DC9-2]
ENST00000617748; ENSP00000478628; ENSG00000277276. [Q96DC9-1]
ENST00000628711; ENSP00000487491; ENSG00000277276. [Q96DC9-2]
GeneIDi78990.
KEGGihsa:78990.
UCSCiuc001ych.5. human. [Q96DC9-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY177201 mRNA. Translation: AAO27703.1.
AK025569 mRNA. Translation: BAB15172.1.
CR457345 mRNA. Translation: CAG33626.1.
AL079302 Genomic DNA. No translation available.
BC009615 mRNA. Translation: AAH09615.1.
BC068058 mRNA. Translation: AAH68058.1.
CCDSiCCDS9917.1. [Q96DC9-1]
RefSeqiNP_075601.1. NM_023112.3. [Q96DC9-1]
UniGeneiHs.278815.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1TFFX-ray2.10A1-234[»]
4FJVX-ray2.05A/C1-234[»]
ProteinModelPortaliQ96DC9.
SMRiQ96DC9.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi122461. 41 interactors.
IntActiQ96DC9. 20 interactors.
STRINGi9606.ENSP00000203664.

Protein family/group databases

MEROPSiC65.002.

PTM databases

iPTMnetiQ96DC9.
PhosphoSitePlusiQ96DC9.

Polymorphism and mutation databases

BioMutaiOTUB2.
DMDMi44888285.

Proteomic databases

EPDiQ96DC9.
MaxQBiQ96DC9.
PaxDbiQ96DC9.
PeptideAtlasiQ96DC9.
PRIDEiQ96DC9.

Protocols and materials databases

DNASUi78990.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000203664; ENSP00000203664; ENSG00000089723. [Q96DC9-1]
ENST00000553723; ENSP00000451283; ENSG00000089723. [Q96DC9-2]
ENST00000617748; ENSP00000478628; ENSG00000277276. [Q96DC9-1]
ENST00000628711; ENSP00000487491; ENSG00000277276. [Q96DC9-2]
GeneIDi78990.
KEGGihsa:78990.
UCSCiuc001ych.5. human. [Q96DC9-1]

Organism-specific databases

CTDi78990.
GeneCardsiOTUB2.
HGNCiHGNC:20351. OTUB2.
HPAiHPA002329.
MIMi608338. gene.
neXtProtiNX_Q96DC9.
OpenTargetsiENSG00000089723.
ENSG00000277276.
PharmGKBiPA134861658.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3991. Eukaryota.
ENOG410ZMN7. LUCA.
GeneTreeiENSGT00390000006979.
HOGENOMiHOG000019496.
HOVERGENiHBG053383.
InParanoidiQ96DC9.
KOiK09603.
OMAiATECDHV.
OrthoDBiEOG091G0GDO.
PhylomeDBiQ96DC9.
TreeFamiTF314145.

Enzyme and pathway databases

ReactomeiR-HSA-5689896. Ovarian tumor domain proteases.

Miscellaneous databases

ChiTaRSiOTUB2. human.
EvolutionaryTraceiQ96DC9.
GeneWikiiOTUB2.
GenomeRNAii78990.
PROiQ96DC9.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000089723.
CleanExiHS_OTUB2.
GenevisibleiQ96DC9. HS.

Family and domain databases

InterProiIPR003323. OTU_dom.
IPR030299. OTUB2.
IPR016615. Otubain.
IPR019400. Peptidase_C65_otubain.
[Graphical view]
PANTHERiPTHR12931:SF3. PTHR12931:SF3. 1 hit.
PfamiPF10275. Peptidase_C65. 1 hit.
[Graphical view]
PIRSFiPIRSF013503. Ubiquitin_thioesterase_Otubain. 1 hit.
PROSITEiPS50802. OTU. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiOTUB2_HUMAN
AccessioniPrimary (citable) accession number: Q96DC9
Secondary accession number(s): Q6IA10, Q9H6T1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 1, 2004
Last sequence update: March 1, 2004
Last modified: November 30, 2016
This is version 132 of the entry and version 2 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

Miscellaneous

In the structure described by PubMed:15258613, the Asp-48 active site of the catalytic triad is located too far to interact directly with the active site His-224. A possible explanation is that OTUB2 is in inactive conformation in absence of ubiquitin and a conformation change may move Asp-48 in the proximity of His-224 in presence of ubiquitin substrate.1 Publication

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 14
    Human chromosome 14: 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. Peptidase families
    Classification of peptidase families and list of entries
  5. 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.