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Protein

Ubiquitin thioesterase OTUB2

Gene

OTUB2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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

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

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

Keywordsi

Molecular functionHydrolase, Protease, Thiol protease
Biological processUbl 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

EuPathDBiHostDB:ENSG00000089723.9
HGNCiHGNC:20351 OTUB2
MIMi608338 gene
neXtProtiNX_Q96DC9

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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

DisGeNETi78990
OpenTargetsiENSG00000089723
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
HPA075090

Interactioni

Binary interactionsi

Show more details

GO - Molecular functioni

Protein-protein interaction databases

BioGridi122461, 42 interactors
IntActiQ96DC9, 24 interactors
MINTiQ96DC9
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

Phylogenomic databases

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

Family and domain databases

InterProiView protein in InterPro
IPR003323 OTU_dom
IPR030299 OTUB2
IPR016615 Otubain
IPR019400 Peptidase_C65_otubain
PANTHERiPTHR12931 PTHR12931, 1 hit
PTHR12931:SF3 PTHR12931:SF3, 1 hit
PfamiView protein in Pfam
PF10275 Peptidase_C65, 1 hit
PIRSFiPIRSF013503 Ubiquitin_thioesterase_Otubain, 1 hit
PROSITEiView protein in PROSITE
PS50802 OTU, 1 hit

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

Similar proteinsi

Entry informationi

Entry nameiOTUB2_HUMAN
AccessioniPrimary (citable) accession number: Q96DC9
Secondary accession number(s): Q6IA10, Q9H6T1
Entry historyiIntegrated into UniProtKB/Swiss-Prot: March 1, 2004
Last sequence update: March 1, 2004
Last modified: February 28, 2018
This is version 139 of the entry and version 2 of the sequence. See 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
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Main funding by: National Institutes of Health