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Protein

Ubiquitin thioesterase OTUB1

Gene

Otub1

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Hydrolase that can specifically remove compared to 'Lys-48'-linked conjugated ubiquitin from proteins and plays an important regulatory role at the level of protein turnover by preventing degradation. Regulator of T-cell anergy, a phenomenon that occurs when T-cells are rendered unresponsive to antigen rechallenge and no longer respond to their cognate antigen. Acts via its interaction with RNF128/GRAIL. Surprisingly, it regulates RNF128-mediated ubiquitination, but does not deubiquitinate polyubiquitinated RNF128. Deubiquitinates estrogen receptor alpha (ESR1). Mediates deubiquitination of 'Lys-48'-linked polyubiquitin chains, but not 'Lys-63'-linked polyubiquitin chains. Not able to cleave di-ubiquitin. Also capable of removing NEDD8 from NEDD8 conjugates, but with a much lower preference compared to 'Lys-48'-linked ubiquitin (By similarity).By similarity
Plays a key non-catalytic role in DNA repair regulation by inhibiting activity of RNF168, an E3 ubiquitin-protein ligase that promotes accumulation of 'Lys-63'-linked histone H2A and H2AX at DNA damage sites. Inhibits RNF168 independently of ubiquitin thioesterase activity by binding and inhibiting UBE2N/UBC13, the E2 partner of RNF168, thereby limiting spreading of 'Lys-63'-linked histone H2A and H2AX marks. Inhibition occurs by binding to free ubiquitin: free ubiquitin acts as an allosteric regulator that increases affinity for UBE2N/UBC13 and disrupts interaction with UBE2V1. The OTUB1-UBE2N/UBC13-free ubiquitin complex adopts a configuration that mimics a cleaved 'Lys48'-linked di-ubiquitin chain (By similarity).By similarity

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).By similarity

Enzyme regulationi

By free ubiquitin: binding of free ubiquitin triggers conformational changes in the OTU domain and formation of a ubiquitin-binding helix in the N-terminus, promoting binding of the conjugated donor ubiquitin in UBE2N/UBC13 to OTUB1.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei23Required for proximal ubiquitin-bindingBy similarity1
Active sitei88By similarity1
Active sitei91NucleophileBy similarity1
Binding sitei221Free ubiquitinBy similarity1
Binding sitei235Free ubiquitinBy similarity1
Binding sitei237Free ubiquitinBy similarity1
Binding sitei261Free ubiquitinBy similarity1
Active sitei265By similarity1
Binding sitei266Free ubiquitinBy similarity1

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionHydrolase, Protease, Thiol protease
Biological processAdaptive immunity, DNA damage, DNA repair, Immunity, Ubl conjugation pathway

Enzyme and pathway databases

ReactomeiR-RNO-5689880 Ub-specific processing proteases
R-RNO-5689896 Ovarian tumor domain proteases

Names & Taxonomyi

Protein namesi
Recommended name:
Ubiquitin thioesterase OTUB1By similarity (EC:3.4.19.12By similarity)
Alternative name(s):
Deubiquitinating enzyme OTUB1By similarity
OTU domain-containing ubiquitin aldehyde-binding protein 1By similarity
Otubain-1By similarity
Ubiquitin-specific-processing protease OTUB1By similarity
Gene namesi
Name:Otub1Imported
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 1

Organism-specific databases

RGDi1311329 Otub1

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

Keywords - Cellular componenti

Cytoplasm

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedBy similarity
ChainiPRO_00003491252 – 271Ubiquitin thioesterase OTUB1Add BLAST270

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanineBy similarity1
Modified residuei16PhosphoserineBy similarity1

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

PaxDbiB2RYG6
PeptideAtlasiB2RYG6
PRIDEiB2RYG6

2D gel databases

World-2DPAGE0004:B2RYG6

PTM databases

iPTMnetiB2RYG6
PhosphoSitePlusiB2RYG6
SwissPalmiB2RYG6

Expressioni

Gene expression databases

BgeeiENSRNOG00000021175
GenevisibleiB2RYG6 RN

Interactioni

Subunit structurei

Interacts with RNF128. Forms a ternary complex with RNF128 and USP8. Interacts with FUS, ESR1 and RACK1. Interacts with UBE2N/UBC13 (By similarity).By similarity

GO - Molecular functioni

Protein-protein interaction databases

BioGridi254414, 2 interactors
STRINGi10116.ENSRNOP00000028752

Structurei

3D structure databases

ProteinModelPortaliB2RYG6
SMRiB2RYG6
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini80 – 271OTUPROSITE-ProRule annotationAdd BLAST192

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni130 – 138Ubiquitin-conjugating enzyme E2 bindingBy similarity9
Regioni169 – 177Ubiquitin-conjugating enzyme E2 bindingBy similarity9
Regioni189 – 195Free ubiquitin bindingBy similarity7
Regioni206 – 213Ubiquitin-conjugating enzyme E2 bindingBy similarity8
Regioni214 – 221Free ubiquitin bindingBy similarity8
Regioni245 – 251Free ubiquitin bindingBy similarity7

Sequence similaritiesi

Belongs to the peptidase C65 family.Sequence analysis

Phylogenomic databases

eggNOGiKOG3991 Eukaryota
ENOG410ZMN7 LUCA
GeneTreeiENSGT00390000006979
HOGENOMiHOG000019496
HOVERGENiHBG053383
InParanoidiB2RYG6
KOiK09602
OMAiEDFHETF
OrthoDBiEOG091G0GDO
PhylomeDBiB2RYG6
TreeFamiTF314145

Family and domain databases

InterProiView protein in InterPro
IPR003323 OTU_dom
IPR030298 OTUB1
IPR016615 Otubain
IPR019400 Peptidase_C65_otubain
PANTHERiPTHR12931 PTHR12931, 1 hit
PTHR12931:SF19 PTHR12931:SF19, 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

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

B2RYG6-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAAEEPQQQK QEPLGSDSEG VNCLAYDEAI MAQQDRIQQE IAVQNPLVSE
60 70 80 90 100
RLELSVLYKE YAEDDNIYQQ KIKDLHKKYS YIRKTRPDGN CFYRAFGFSH
110 120 130 140 150
LEALLDDSKE LQRFKAVSAK SKEDLVSQGF TEFTIEDFHN TFMDLIEQVE
160 170 180 190 200
KQTSVADLLA SFNDQSTSDY LVVYLRLLTS GYLQRESKFF EHFIEGGRTV
210 220 230 240 250
KEFCQQEVEP MCKESDHIHI IALAQALSVS IQVEYMDRGE GGTTNPHVFP
260 270
EGSEPKVYLL YRPGHYDILY K
Length:271
Mass (Da):31,270
Last modified:July 1, 2008 - v1
Checksum:i32F78EE1DC5FD679
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
CH473953 Genomic DNA Translation: EDM12666.1
BC166771 mRNA Translation: AAI66771.1
RefSeqiNP_001099802.1, NM_001106332.1
UniGeneiRn.9218

Genome annotation databases

EnsembliENSRNOT00000028752; ENSRNOP00000028752; ENSRNOG00000021175
GeneIDi293705
KEGGirno:293705
UCSCiRGD:1311329 rat

Similar proteinsi

Entry informationi

Entry nameiOTUB1_RAT
AccessioniPrimary (citable) accession number: B2RYG6
Entry historyiIntegrated into UniProtKB/Swiss-Prot: September 2, 2008
Last sequence update: July 1, 2008
Last modified: May 23, 2018
This is version 77 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

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