Tbio OTUB1 Ubiquitin thioesterase OTUB1

Protein Summary

Description

Hydrolase that can specifically remove '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, a crucial inductor of CD4 T-cell anergy. Isoform 1 destabilizes RNF128, leading to prevent anergy. In contrast, isoform 2 stabilizes RNF128 and promotes anergy. 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. 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. The product of this gene is a member of the OTU (ovarian tumor) superfamily of predicted cysteine proteases. The encoded protein is a highly specific ubiquitin iso-peptidase, and cleaves ubiquitin from branched poly-ubiquitin chains but not from ubiquitinated substrates. It interacts with another ubiquitin protease and an E3 ubiquitin ligase that inhibits cytokine gene transcription in the immune system. It is proposed to function in specific ubiquitin-dependent pathways, possibly by providing an editing function for polyubiquitin chain growth. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2008]

Uniprot Accession IDs

• Q96FW1
• Q32Q78
• Q96II3
• Q9NXQ4
• Q9P0B8

Gene Name

• OTUB1

Ensembl ID

• ENST00000428192
• ENSP00000402551
• ENSG00000167770
• ENST00000538426
• ENSP00000444357

Symbol

• OTB1
• OTU1
• OTB1
• OTU1
• HSPC263

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
hub protein	0.94
co-expressed gene	0.82
transcription factor binding site profile	0.77
biological process	0.68
transcription factor	0.68

Protein Classes

PANTHER Classes

Protein / Hydrolase / Ubiquitin Thioesterase Otub1

Protein / ... / Cysteine Protease / Ubiquitin Thioesterase Otub1

DTO Classes

Protein / Enzyme / Protease / Cysteine Protease / Ubiquitin Thioesterase Otub1

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 209.92   (req: < 5)

Gene RIFs: 27   (req: <= 3)

Antibodies: 415   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 209.92   (req: >= 5)

Gene RIFs: 27   (req: > 3)

Antibodies: 415   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 12

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligand: 0

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 0

Expression Data (0 Tissues)

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No expression data found

Protein Sequence and Structure

Residue Counts

Protein Sequence

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Related Tools (4)

Target Illumination GWAS Analytics (TIGA)

TIGA scores and ranks GWAS discovered associations according to the quantity and quality of the evidence supporting the association.

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GENEVA

GENEVA (GENe Expression Variance Analysis) allows you to identify RNA-sequencing datasets from the Gene Expression Omnibus (GEO) that contain conditions modulating a gene or a gene signature.

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GlyGen

GlyGen is a data integration and dissemination project for carbohydrate and glycoconjugate related data.

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ARCHS4

ARCHS4 provides access to gene-function predictions based on RNA-seq co-expression, and gene expression levels across cell and tissues.

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Approved Drugs (0)

No approved drugs found

Active Ligands (0)

No active ligands found

Protein-Protein Interactions (146)

Explore Interacting Targets

1 – 10 of 146

• See Interactions on String-DB

UBE2D2

Tbio

Novelty:  0.00603877

p_int:  0.999949844

p_ni:  0.000050156

Score:  0.783

Data Source:  BioPlex,STRINGDB

UBE2E3

Tbio

Novelty:  0.03477232

p_int:  0.99985218

p_ni:  0.00014782

Score:  0.567

Data Source:  BioPlex,STRINGDB

UBE2W

Tbio

Novelty:  0.07255713

p_int:  0.999418489

p_ni:  0.000581511

Score:  0.568

Data Source:  BioPlex,STRINGDB

UBE2D4

Tbio

Novelty:  0.40836104

p_int:  0.999345682

p_ni:  0.000654318

Score:  0.582

Data Source:  BioPlex,STRINGDB

UBE2E2

Tbio

Novelty:  0.02752227

p_int:  0.99867488

p_ni:  0.00132512

Score:  0.545

Data Source:  BioPlex,STRINGDB

HIF1AN

Tbio

Novelty:  0.00861018

p_int:  0.993905061

p_ni:  0.006094939

Score:  0.151

Data Source:  BioPlex,STRINGDB

USP47

Tchem

Family:  Enzyme

Novelty:  0.07579226

p_int:  0.972081773

p_ni:  0.027918227

Score:  0.522

Data Source:  BioPlex,STRINGDB

FGB

Tbio

Novelty:  0.00437751

p_int:  0.927531954

p_ni:  0.072468046

Score:  0.167

Data Source:  BioPlex,STRINGDB

UBE2D1

Tbio

Novelty:  0.00865867

p_int:  0.902285357

p_ni:  0.097714643

Score:  0.988

Data Source:  BioPlex,Reactome,STRINGDB

SNRNP27

Tbio

Novelty:  0.0175187

p_int:  0.890117887

p_ni:  0.109882113

Score:  0.166

Data Source:  BioPlex,STRINGDB

Nearest Tclin Targets

Nearest Tclin calculations are only available for targets with KEGG Pathway annotations.

Pathways (5)

Reactome (5)

Deubiquitination (R-HSA-5688426)

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Data Source	Name	Explore in Pharos	Explore in Source
Reactome	Deubiquitination	278 targets	R-HSA-5688426
Reactome	Metabolism of proteins	2050 targets	R-HSA-392499
Reactome	Ovarian tumor domain proteases	38 targets	R-HSA-5689896
Reactome	Post-translational protein modification	1450 targets	R-HSA-597592
Reactome	Ub-specific processing proteases	205 targets	R-HSA-5689880

Name	Explore in Pharos	Explore in Source
Deubiquitination	278 targets	R-HSA-5688426
Metabolism of proteins	2050 targets	R-HSA-392499
Ovarian tumor domain proteases	38 targets	R-HSA-5689896
Post-translational protein modification	1450 targets	R-HSA-597592
Ub-specific processing proteases	205 targets	R-HSA-5689880

Viral Interactions (0)

No viral interactions found

Gene Ontology Terms (16)

Functions (4)

Components (4)

Processes (8)

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1 – 4 of 4

GO Term	Evidence	Assigned by
NEDD8-specific protease activity	Inferred from Direct Assay (IDA)	UniProtKB
thiol-dependent ubiquitin-specific protease activity	Inferred from Direct Assay (IDA)	UniProtKB
ubiquitin binding	Inferred from Direct Assay (IDA)	UniProtKB
ubiquitin protein ligase binding	Inferred from Physical Interaction (IPI)	UniProtKB

Disease Associations (null)

No disease associations found

GWAS Traits (17)

• Explore on Target Illumination GWAS Analytics (TIGA)

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1 – 5 of 17

GWAS Trait	EFO ID	Study Count	SNP Count	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
BMI-adjusted waist-hip ratio	EFO_0007788	3	8	10		96.1
uric acid measurement	EFO_0004761	1	2	2		95.5
waist-hip ratio	EFO_0004343	1	6	6		91.8
urate measurement	EFO_0004531	2	2	3		89.8
BMI-adjusted waist circumference	EFO_0007789	1	3	3		57.1

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1 – 5 of 17

GWAS Trait	EFO ID	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
BMI-adjusted waist-hip ratio	EFO_0007788	10		96.1
uric acid measurement	EFO_0004761	2		95.5
waist-hip ratio	EFO_0004343	6		91.8
urate measurement	EFO_0004531	3		89.8
BMI-adjusted waist circumference	EFO_0007789	3		57.1

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UniProt Keyword Find Similar Targets

No Header	No Header
3D-structure
Acetylation
Adaptive immunity
Alternative splicing
Complete proteome
Cytoplasm
Direct protein sequencing
DNA damage
DNA repair
Hydrolase

GWAS Trait Find Similar Targets

No Header	No Header
bipolar disorder
BMI-adjusted hip circumference
BMI-adjusted waist circumference
BMI-adjusted waist-hip ratio
cognitive function measurement
hip circumference
insulin measurement
intelligence
low density lipoprotein cholesterol measurement
pulse pressure measurement

MGI Phenotype Find Similar Targets

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behavior/neurological phenotype
growth/size/body region phenotype
mortality/aging

IDG Resources

No IDG generated resources found

Orthologs (11)

1 – 5 of 11

Species	Name	Source ID	Gene ID	OMA	EggNOG	Inparanoid
Chimp	OTU deubiquitinase, ubiquitin aldehyde binding 1	VGNC:6538	742797
Mouse	OTU domain, ubiquitin aldehyde binding 1	MGI:2147616	107260
Rat	OTU deubiquitinase, ubiquitin aldehyde binding 1	RGD:1311329	293705
Dog	OTU deubiquitinase, ubiquitin aldehyde binding 1	VGNC:49784	100855636
Horse	OTU deubiquitinase, ubiquitin aldehyde binding 1	VGNC:21086	100054829

Species	Name	OMA	EggNOG	Inparanoid
Chimp	OTU deubiquitinase, ubiquitin aldehyde binding 1
Mouse	OTU domain, ubiquitin aldehyde binding 1
Rat	OTU deubiquitinase, ubiquitin aldehyde binding 1
Dog	OTU deubiquitinase, ubiquitin aldehyde binding 1
Horse	OTU deubiquitinase, ubiquitin aldehyde binding 1

Publication Statistics

PubMed Score 209.92

PubMed score by year

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PubTator Score 31.70

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Related Publications

Text Mined References (46)

GeneRif Annotations (27)

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PMID	Year	Title