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Aliases for OTUB1 Gene

Aliases for OTUB1 Gene

  • OTU Deubiquitinase, Ubiquitin Aldehyde Binding 1 2 3 5
  • OTU Domain-Containing Ubiquitin Aldehyde-Binding Protein 1 3 4
  • Ubiquitin-Specific-Processing Protease OTUB1 3 4
  • OTU Domain, Ubiquitin Aldehyde Binding 1 2 3
  • Deubiquitinating Enzyme OTUB1 3 4
  • Otubain-1 3 4
  • OTB1 3 4
  • OTU1 3 4
  • Ubiquitin-Specific Protease Otubain 1 3
  • OTU-Domain Ubal-Binding 1 3
  • EC 3.4.19.12 4
  • EC 3.1.2 63
  • HSPC263 3
  • HOTU1 4

External Ids for OTUB1 Gene

Previous GeneCards Identifiers for OTUB1 Gene

  • GC11P063529
  • GC11P063510
  • GC11P063753
  • GC11P060082

Summaries for OTUB1 Gene

Entrez Gene Summary for OTUB1 Gene

  • 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]

GeneCards Summary for OTUB1 Gene

OTUB1 (OTU Deubiquitinase, Ubiquitin Aldehyde Binding 1) is a Protein Coding gene. Among its related pathways are Ubiquitination Cascade Pathway. GO annotations related to this gene include hydrolase activity and thiol-dependent ubiquitin-specific protease activity. An important paralog of this gene is OTUB2.

UniProtKB/Swiss-Prot for OTUB1 Gene

  • 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.

Gene Wiki entry for OTUB1 Gene

No data available for Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for OTUB1 Gene

Genomics for OTUB1 Gene

Regulatory Elements for OTUB1 Gene

Promoters for OTUB1 Gene
Ensembl Regulatory Elements (ENSRs) TSS Distance (bp) Size (bp) Binding Sites for Transcription Factors within promoters

ENSRs around OTUB1 on UCSC Golden Path with GeneCards custom track

Genomic Location for OTUB1 Gene

Chromosome:
11
Start:
63,985,853 bp from pter
End:
64,001,811 bp from pter
Size:
15,959 bases
Orientation:
Plus strand

Genomic View for OTUB1 Gene

Genes around OTUB1 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
OTUB1 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for OTUB1 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for OTUB1 Gene

Proteins for OTUB1 Gene

  • Protein details for OTUB1 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q96FW1-OTUB1_HUMAN
    Recommended name:
    Ubiquitin thioesterase OTUB1
    Protein Accession:
    Q96FW1
    Secondary Accessions:
    • Q32Q78
    • Q96II3
    • Q9NXQ4
    • Q9P0B8

    Protein attributes for OTUB1 Gene

    Size:
    271 amino acids
    Molecular mass:
    31284 Da
    Quaternary structure:
    • Isoform 1 and isoform 2 interact with RNF128. Isoform 1 forms a ternary complex with RNF128 and USP8. Isoform 1 interacts with the C-terminal UCH catalytic domain of USP8. Isoform 2 does not associate with USP8. Interacts with FUS, ESR1 and RACK1. Interacts with UBE2N/UBC13.
    Miscellaneous:
    • In the structure described by PubMed:18954305, the His-265 active site of the catalytic triad is located too far to interact directly with the active site Cys-91. A possible explanation is that OTUB1 is in inactive conformation in absence of ubiquitin and a conformation change may move His-265 in the proximity of Cys-91 in presence of ubiquitin substrate.
    SequenceCaution:
    • Sequence=AAF28941.1; Type=Erroneous initiation; Evidence={ECO:0000305};

    Three dimensional structures from OCA and Proteopedia for OTUB1 Gene

    Alternative splice isoforms for OTUB1 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for OTUB1 Gene

Proteomics data for OTUB1 Gene at MOPED

Selected DME Specific Peptides for OTUB1 Gene

Post-translational modifications for OTUB1 Gene

  • Ubiquitination at Lys 71, Lys 84, Lys 109, Lys 188, and Lys 201
  • Modification sites at PhosphoSitePlus

Antibody Products

  • Cell Signaling Technology (CST) Antibodies for OTUB1 (OTUB1)
  • Santa Cruz Biotechnology (SCBT) Antibodies for OTUB1

Protein Products

Domains & Families for OTUB1 Gene

Gene Families for OTUB1 Gene

Protein Domains for OTUB1 Gene

Suggested Antigen Peptide Sequences for OTUB1 Gene

GenScript: Design optimal peptide antigens:

Graphical View of Domain Structure for InterPro Entry

Q96FW1

UniProtKB/Swiss-Prot:

OTUB1_HUMAN :
  • In addition to ubiquitin-binding at the Cys-91 active site, a proximal ubiquitin-binding site is also present at Cys-23 Occupancy of the active site is needed to enable tight binding to the second site. Distinct binding sites for the ubiquitins may allow to discriminate among different isopeptide linkages (i.e. Lys-48-, Lys-63-linked polyubiquitin) in polyubiquitin substrates and achieve linkage-specific deubiquitination.
  • Belongs to the peptidase C65 family.
Domain:
  • In addition to ubiquitin-binding at the Cys-91 active site, a proximal ubiquitin-binding site is also present at Cys-23 Occupancy of the active site is needed to enable tight binding to the second site. Distinct binding sites for the ubiquitins may allow to discriminate among different isopeptide linkages (i.e. Lys-48-, Lys-63-linked polyubiquitin) in polyubiquitin substrates and achieve linkage-specific deubiquitination.
  • Contains 1 OTU domain.
Family:
  • Belongs to the peptidase C65 family.
genes like me logo Genes that share domains with OTUB1: view

Function for OTUB1 Gene

Molecular function for OTUB1 Gene

UniProtKB/Swiss-Prot CatalyticActivity:
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).
UniProtKB/Swiss-Prot EnzymeRegulation:
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.
UniProtKB/Swiss-Prot Function:
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.
UniProtKB/Swiss-Prot Function:
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.

Enzyme Numbers (IUBMB) for OTUB1 Gene

Gene Ontology (GO) - Molecular Function for OTUB1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0016787 hydrolase activity IEA --
genes like me logo Genes that share ontologies with OTUB1: view
genes like me logo Genes that share phenotypes with OTUB1: view

Animal Model Products

Inhibitory RNA Products

In Situ Assay Products

Flow Cytometry Products

No data available for Human Phenotype Ontology , Animal Models , Transcription Factor Targets and HOMER Transcription for OTUB1 Gene

Localization for OTUB1 Gene

Subcellular locations from UniProtKB/Swiss-Prot for OTUB1 Gene

Cytoplasm.

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for OTUB1 Gene COMPARTMENTS Subcellular localization image for OTUB1 gene
Compartment Confidence
extracellular 5
nucleus 5
cytosol 3
mitochondrion 2
cytoskeleton 1

No data available for Gene Ontology (GO) - Cellular Components for OTUB1 Gene

Pathways & Interactions for OTUB1 Gene

SuperPathways for OTUB1 Gene

genes like me logo Genes that share pathways with OTUB1: view

Pathways by source for OTUB1 Gene

1 R&D Systems pathway for OTUB1 Gene

SIGNOR curated interactions for OTUB1 Gene

Inactivates:

Gene Ontology (GO) - Biological Process for OTUB1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0002250 adaptive immune response IEA --
GO:0006281 DNA repair IEA --
genes like me logo Genes that share ontologies with OTUB1: view

Drugs & Compounds for OTUB1 Gene

No Compound Related Data Available

Transcripts for OTUB1 Gene

Unigene Clusters for OTUB1 Gene

OTU domain, ubiquitin aldehyde binding 1:
Representative Sequences:

Inhibitory RNA Products

Flow Cytometry Products

Alternative Splicing Database (ASD) splice patterns (SP) for OTUB1 Gene

ExUns: 1a · 1b · 1c · 1d ^ 2 ^ 3 ^ 4a · 4b ^ 5 ^ 6 ^ 7 ^ 8 ^ 9a · 9b ^ 10a · 10b
SP1: - - - - -
SP2: - - - -
SP3: - - -
SP4: - - -
SP5: - -
SP6: - -
SP7: -

Relevant External Links for OTUB1 Gene

GeneLoc Exon Structure for
OTUB1
ECgene alternative splicing isoforms for
OTUB1

Expression for OTUB1 Gene

mRNA expression in normal human tissues for OTUB1 Gene

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, and MOPED for OTUB1 Gene



SOURCE GeneReport for Unigene cluster for OTUB1 Gene Hs.473788

mRNA Expression by UniProt/SwissProt for OTUB1 Gene

Q96FW1-OTUB1_HUMAN
Tissue specificity: Isoform 1 is ubiquitous. Isoform 2 is expressed only in lymphoid tissues such as tonsils, lymph nodes and spleen, as well as peripheral blood mononuclear cells.
genes like me logo Genes that share expression patterns with OTUB1: view

Protein tissue co-expression partners for OTUB1 Gene

- Elite partner

Primer Products

In Situ Assay Products

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery , mRNA differential expression in normal tissues and Protein differential expression in normal tissues for OTUB1 Gene

Orthologs for OTUB1 Gene

This gene was present in the common ancestor of eukaryotes.

Orthologs for OTUB1 Gene

Organism Taxonomy Gene Similarity Type Details
cow
(Bos Taurus)
Mammalia OTUB1 35
  • 93.97 (n)
  • 98.89 (a)
OTUB1 36
  • 99 (a)
OneToOne
dog
(Canis familiaris)
Mammalia OTUB1 35
  • 94.83 (n)
  • 99.63 (a)
OTUB1 36
  • 97 (a)
OneToOne
chimpanzee
(Pan troglodytes)
Mammalia OTUB1 35
  • 99.26 (n)
  • 100 (a)
OTUB1 36
  • 88 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia RGD1565010 35
  • 91.57 (n)
  • 95.91 (a)
oppossum
(Monodelphis domestica)
Mammalia OTUB1 36
  • 87 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Otub1 36
  • 100 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia OTUB1 36
  • 95 (a)
OneToOne
chicken
(Gallus gallus)
Aves OTUB1 35
  • 80 (n)
  • 81.85 (a)
OTUB1 36
  • 63 (a)
OneToOne
lizard
(Anolis carolinensis)
Reptilia OTUB1 36
  • 85 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia otub1 35
  • 71.04 (n)
  • 75.28 (a)
Str.10055 35
zebrafish
(Danio rerio)
Actinopterygii wufa19h07 35
otub1a 36
  • 79 (a)
OneToMany
otub1b 36
  • 83 (a)
OneToMany
fruit fly
(Drosophila melanogaster)
Insecta CG4968 36
  • 53 (a)
OneToMany
worm
(Caenorhabditis elegans)
Secernentea otub-1 36
  • 30 (a)
OneToMany
barley
(Hordeum vulgare)
Liliopsida Hv.12030 35
wheat
(Triticum aestivum)
Liliopsida Ta.10490 35
bread mold
(Neurospora crassa)
Ascomycetes NCU00595 35
  • 48.27 (n)
  • 33.48 (a)
sea squirt
(Ciona savignyi)
Ascidiacea CSA.5787 36
  • 45 (a)
OneToMany
Species with no ortholog for OTUB1:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • beta proteobacteria (Neisseria meningitidis)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)

Evolution for OTUB1 Gene

ENSEMBL:
Gene Tree for OTUB1 (if available)
TreeFam:
Gene Tree for OTUB1 (if available)

Paralogs for OTUB1 Gene

Paralogs for OTUB1 Gene

(2) SIMAP similar genes for OTUB1 Gene using alignment to 7 proteins:

genes like me logo Genes that share paralogs with OTUB1: view

Variants for OTUB1 Gene

Sequence variations from dbSNP and Humsavar for OTUB1 Gene

SNP ID Clin Chr 11 pos Sequence Context AA Info Type
rs14195 -- 63,997,369(-) CTCTC(C/T)TTGCA nc-transcript-variant, reference, synonymous-codon
rs320112 -- 63,990,589(-) TATTT(A/T)TTTAA intron-variant
rs320113 -- 63,987,743(-) TCCAT(C/G)ACCGC intron-variant
rs320114 -- 63,987,076(-) GGCAG(A/G)CGGAA intron-variant
rs320149 -- 63,996,485(+) CCCCC(A/G)TTCTG intron-variant

Structural Variations from Database of Genomic Variants (DGV) for OTUB1 Gene

Variant ID Type Subtype PubMed ID
dgv1155n71 CNV Loss 21882294
dgv1156n71 CNV Loss 21882294
nsv897639 CNV Loss 21882294
esv29993 CNV Loss 17803354
dgv1159n71 CNV Loss 21882294
nsv897642 CNV Loss 21882294
dgv1160n71 CNV Loss 21882294
nsv897648 CNV Loss 21882294

Variation tolerance for OTUB1 Gene

Residual Variation Intolerance Score: 29.3% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 2.06; 37.83% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for OTUB1 Gene

HapMap Linkage Disequilibrium report
OTUB1

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for OTUB1 Gene

Disorders for OTUB1 Gene

Relevant External Links for OTUB1

Atlas of Genetics and Cytogenetics in Oncology and Haematology:
OTUB1

No disorders were found for OTUB1 Gene.

No data available for MalaCards , UniProtKB/Swiss-Prot and Genatlas for OTUB1 Gene

Publications for OTUB1 Gene

  1. OTU Domain-containing ubiquitin aldehyde-binding protein 1 (OTUB1) deubiquitinates estrogen receptor (ER) alpha and affects ERalpha transcriptional activity. (PMID: 19383985) Stanisic V. … O'Malley B.W. (J. Biol. Chem. 2009) 2 3 4 23 67
  2. Structural basis and specificity of human otubain 1-mediated deubiquitination. (PMID: 18954305) Edelmann M.J. … Kessler B.M. (Biochem. J. 2009) 3 23
  3. Evidence for bidentate substrate binding as the basis for the K48 linkage specificity of otubain 1. (PMID: 19211026) Wang T. … Wolberger C. (J. Mol. Biol. 2009) 3 23
  4. Otubains: a new family of cysteine proteases in the ubiquitin pathway. (PMID: 12704427) Balakirev M.Y. … Chroboczek J. (EMBO Rep. 2003) 2 3
  5. Ubiquitin Ser65 phosphorylation affects ubiquitin structure, chain assembly and hydrolysis. (PMID: 25527291) Wauer T. … Komander D. (EMBO J. 2015) 3

Products for OTUB1 Gene

Sources for OTUB1 Gene

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