Details for: OTUD6B

Gene ID: 51633

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: OTUD6B

Ensembl ID: ENSG00000155100

Description: OTU deubiquitinase 6B

Cell Significance Landscape

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • VIP GABAergic cortical interneuron CL4023016
    CSI 4.54
    rCSI 5.42%
    PRS 90.22
  • pro-B cell CL0000826
    CSI 3.95
    rCSI 3.27%
    PRS 97.27
  • mature B cell CL0000785
    CSI 3.68
    rCSI 3.2%
    PRS 98.8
  • pancreatic D cell CL0000173
    CSI 3.37
    rCSI 3.31%
    PRS 96.81
  • melanocyte CL0000148
    CSI 3.17
    rCSI 2.35%
    PRS 94.64
  • neural crest cell CL0011012
    CSI 3.11
    rCSI 2.46%
    PRS 93.77
  • plasmacytoid dendritic cell, human CL0001058
    CSI 2.78
    rCSI 1.94%
    PRS 98.01
  • cerebral cortex endothelial cell CL1001602
    CSI 2.59
    rCSI 4.48%
    PRS 94.1
  • ciliated epithelial cell CL0000067
    CSI 2.46
    rCSI 2.17%
    PRS 91.36
  • myeloid leukocyte CL0000766
    CSI 2.44
    rCSI 2.26%
    PRS 97.52
  • extravillous trophoblast CL0008036
    CSI 2.37
    rCSI 2.94%
    PRS 95.37
  • vascular leptomeningeal cell CL4023051
    CSI 2.34
    rCSI 4.1%
    PRS 94.8
  • common lymphoid progenitor CL0000051
    CSI 2.26
    rCSI 3.02%
    PRS 99.14
  • astrocyte of the cerebral cortex CL0002605
    CSI 2.14
    rCSI 4.8%
    PRS 90.53
  • pvalb GABAergic cortical interneuron CL4023018
    CSI 2.03
    rCSI 2.53%
    PRS 88.64
  • pulmonary alveolar type 1 cell CL0002062
    CSI 2.02
    rCSI 11.63%
    PRS 94.8
  • cardiac muscle cell CL0000746
    CSI 1.86
    rCSI 2.66%
    PRS 91.78
  • sst GABAergic cortical interneuron CL4023017
    CSI 1.85
    rCSI 2.38%
    PRS 90.94
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 1.8
    rCSI 3.17%
    PRS 89.95
  • peripheral nervous system neuron CL2000032
    CSI 1.63
    rCSI 2.22%
    PRS 93.25
  • lamp5 GABAergic cortical interneuron CL4023011
    CSI 1.51
    rCSI 2.54%
    PRS 90.29
  • L6b glutamatergic cortical neuron CL4023038
    CSI 0.72
    rCSI 2.24%
    PRS 90.85

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

Explore relationships of the current gene. Select an Interaction Source: 'ONTOLOGY' for shared pathways (GO/Reactome) or 'STRING' for protein-protein interactions. Further refine by selecting context genes and comparing Cell Significance Index (CSI) scores between baseline and target cell types and their specific contexts.

Comma-separated if multiple.
Comma-separated if multiple.
Legend:
  • Query Gene
  • Node Color (Target Cell CSI, relative to current network):
    • Very High
    • High
    • Medium
    • Low
    • Very Low
    • CSI N/A
  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary [OTUD6B](/details-gene/51633) (OTU deubiquitinase 6B) is a protein-coding gene located on chromosome 8q21.3 that encodes a cysteine-type deubiquitinating enzyme (DUB) belonging to the OTU (ovarian tumor) family. Its primary molecular function involves [protein deubiquitination](/details-go/GO:0016579), a key post-translational modification process that regulates protein stability and function. Functionally, [OTUD6B](/details-gene/51633) is implicated in fundamental cellular processes including the regulation of protein translation, [cell population proliferation](/details-go/GO:0008283), and proteasome assembly. Expression data indicates that **Overall**, [OTUD6B](/details-gene/51633) is a significant gene in a diverse array of cell types, with particularly high significance in specific neuronal populations like [VIP GABAergic cortical interneuron](/details-cell/CL4023016), developing and mature lymphocytes such as [pro-B cell](/details-cell/CL0000826) and [mature B cell](/details-cell/CL0000785), and endocrine cells like the [pancreatic D cell](/details-cell/CL0000173). Clinical research has linked biallelic loss-of-function variants in [OTUD6B](/details-gene/51633) to a syndromic form of intellectual disability, highlighting its critical role in human development ([Link](https://doi.org/10.1016/j.ajhg.2017.03.001)). ## Cellular Roles and Expression Landscape The expression profile of [OTUD6B](/details-gene/51633) suggests it plays important roles across multiple physiological systems rather than being restricted to a single lineage. **Overall**, its highest significance is observed in the [VIP GABAergic cortical interneuron](/details-cell/CL4023016) (CSI: 4.54), indicating a potentially crucial function in the regulation of cortical circuitry. Beyond the nervous system, [OTUD6B](/details-gene/51633) demonstrates a prominent role in the hematopoietic system. It is highly significant in both progenitor and mature B lymphocytes, including [pro-B cell](/details-cell/CL0000826) (CSI: 3.95), [mature B cell](/details-cell/CL0000785) (CSI: 3.68), and [common lymphoid progenitor](/details-cell/CL0000051) (CSI: 2.26). This expression pattern is consistent with previous findings that implicate [OTUD6B](/details-gene/51633) in the B lymphocyte cell cycle following cytokine stimulation ([Link](https://doi.org/10.1371/journal.pone.0014514)). Its significance also extends to other immune cells like the [plasmacytoid dendritic cell, human](/details-cell/CL0001058) (CSI: 2.78) and [myeloid leukocyte](/details-cell/CL0000766) (CSI: 2.44), suggesting a broader role in immune regulation. The gene also shows notable significance in other specialized cell types, including the [pancreatic D cell](/details-cell/CL0000173) (CSI: 3.37), which secretes somatostatin, and the pigment-producing [melanocyte](/details-cell/CL0000148) (CSI: 3.17). This widespread yet specific expression pattern underscores its role as a key enzymatic regulator in diverse cellular contexts. ## Pathways and Molecular Function [OTUD6B](/details-gene/51633) functions as a deubiquitinase, specializing in [cysteine-type deubiquitinase activity](/details-go/GO:0004843) ([Link](https://doi.org/10.1016/j.cell.2013.05.046)). This enzymatic activity is central to its involvement in [protein deubiquitination](/details-go/GO:0016579) and general [proteolysis](/details-go/GO:0006508), processes that are critical for maintaining protein homeostasis. A particularly notable aspect of its function is its dual role in protein synthesis, where it is annotated as participating in both [positive regulation of translation](/details-go/GO:0045727) and [negative regulation of translation](/details-go/GO:0017148). This suggests a sophisticated, context-dependent regulatory mechanism. Its physical association with the [eukaryotic translation initiation factor 4f complex](/details-go/GO:0016281) provides a direct mechanistic link to the translational machinery. By controlling the ubiquitination status of key translational components or regulatory factors, [OTUD6B](/details-gene/51633) can fine-tune protein production. This regulatory capacity is likely coupled to its role in governing [cell population proliferation](/details-go/GO:0008283) ([Link](https://doi.org/10.1158/1541-7786.mcr-16-0281-t)), a process that demands precise control over protein synthesis and degradation. ## Research Directions The diverse expression profile and multifaceted functions of [OTUD6B](/details-gene/51633) present several avenues for future investigation. Its critical, non-redundant role is underscored by the severe neurodevelopmental phenotype associated with its loss-of-function ([Link](https://doi.org/10.1016/j.ajhg.2017.03.001)). **Proposed Hypotheses:** 1. Given its high significance in [pro-B cell](/details-cell/CL0000826) and [mature B cell](/details-cell/CL0000785) and its documented role in the B cell cycle ([Link](https://doi.org/10.1371/journal.pone.0014514)), [OTUD6B](/details-gene/51633) likely deubiquitinates and stabilizes key proteins (e.g., cyclins, transcription factors) required for progression through specific checkpoints during B cell maturation and antigen-driven proliferation. 2. The high significance of [OTUD6B](/details-gene/51633) in specific neuronal subtypes, coupled with the intellectual disability syndrome caused by its deficiency, suggests that it is essential for neuronal proteostasis. We hypothesize that [OTUD6B](/details-gene/51633) regulates the turnover of synaptic proteins, and its absence leads to an accumulation of ubiquitinated, non-functional proteins, causing synaptic dysfunction and cognitive impairment. 3. The paradoxical involvement of [OTUD6B](/details-gene/51633) in both positive and negative regulation of translation suggests it may act as a molecular switch. It is hypothesized that post-translational modifications of [OTUD6B](/details-gene/51633) itself, or its association with different protein complexes, dictates its substrate specificity, allowing it to selectively stabilize or promote the degradation of factors that either enhance or repress the translation of specific mRNAs. **Proposed Experimental Approach:** To test the hypothesis regarding its role in B cell maturation (Hypothesis 1), a B-cell-specific conditional knockout of [OTUD6B](/details-gene/51633) could be generated in a mouse model (e.g., using a CD19-Cre driver). The developmental progression of B lymphocytes in the bone marrow and peripheral lymphoid organs would be quantified via multi-color flow cytometry. To identify its direct substrates, B cells from both knockout and wild-type mice could be stimulated *in vitro* and subjected to quantitative di-glycine remnant profiling (UbiScan) coupled with mass spectrometry to map changes in the ubiquitome. This would pinpoint the specific proteins whose ubiquitination status is directly regulated by [OTUD6B](/details-gene/51633) during B cell activation. **Therapeutic Potential:** The severe consequences of [OTUD6B](/details-gene/51633) loss-of-function suggest that it is a poor candidate for therapeutic inhibition, as this would likely mimic the pathogenic state and cause significant toxicity. Its role in promoting proliferation could make it a target in certain cancers, but its broad expression profile raises concerns about on-target, off-tumor side effects. Therefore, the most relevant therapeutic avenue may involve strategies for gene replacement or functional restoration in patients with [OTUD6B](/details-gene/51633)-deficiency syndrome, rather than its inhibition in diseases of over-proliferation.

Genular Protein ID: 4177647740

Symbol: OTU6B_HUMAN

Name: DUBA-5

UniProtKB Accession Codes:

Q8N6M0 A8K6I1 B4DEY0 Q9NTA4 Q9Y387

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BindingDB 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 2 CDD 1 CTD 1 ChEMBL 1 DMDM 1 DNASU 1 DisGeNET 1 EC 1 EMBL 6 Ensembl 2 ExpressionAtlas 1 GO 7 Gene3D 1 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 4 KEGG 1 MANE-Select 1 MEROPS 1 MIM 3 MINT 1 MalaCards 1 MassIVE 1 NCBI Taxonomy 1 OpenTargets 1 Orphanet 1 OrthoDB 1 PANTHER 2 PIR 1 PRO 1 PROSITE 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 Pumba 1 RNAct 1 RefSeq 3 SIGNOR 1 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 10810093

Title: Identification of novel human genes evolutionarily conserved in Caenorhabditis elegans by comparative proteomics.

PubMed ID: 10810093

DOI: 10.1101/gr.10.5.703

PubMed ID: 14702039

Title: Complete sequencing and characterization of 21,243 full-length human cDNAs.

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 16421571

Title: DNA sequence and analysis of human chromosome 8.

PubMed ID: 16421571

DOI: 10.1038/nature04406

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 17974005

Title: The full-ORF clone resource of the German cDNA consortium.

PubMed ID: 17974005

DOI: 10.1186/1471-2164-8-399

PubMed ID: 23827681

Title: OTU deubiquitinases reveal mechanisms of linkage specificity and enable ubiquitin chain restriction analysis.

PubMed ID: 23827681

DOI: 10.1016/j.cell.2013.05.046

PubMed ID: 19413330

Title: Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach.

PubMed ID: 19413330

DOI: 10.1021/ac9004309

PubMed ID: 21269460

Title: Initial characterization of the human central proteome.

PubMed ID: 21269460

DOI: 10.1186/1752-0509-5-17

PubMed ID: 21267069

Title: Evidence for OTUD-6B participation in B lymphocytes cell cycle after cytokine stimulation.

PubMed ID: 21267069

DOI: 10.1371/journal.pone.0014514

PubMed ID: 22814378

Title: N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB.

PubMed ID: 22814378

DOI: 10.1073/pnas.1210303109

PubMed ID: 28343629

Title: Biallelic variants in OTUD6B cause an intellectual disability syndrome associated with seizures and dysmorphic features.

PubMed ID: 28343629

DOI: 10.1016/j.ajhg.2017.03.001

PubMed ID: 27864334

Title: Deubiquitinase OTUD6B isoforms are important regulators of growth and proliferation.

PubMed ID: 27864334

DOI: 10.1158/1541-7786.mcr-16-0281-t

Sequence Information:

  • Length: 293
  • Mass: 33813
  • Checksum: 468DB88E2637D869
  • Sequence:
    • MEAVLTEELD EEEQLLRRHR KEKKELQAKI QGMKNAVPKN DKKRRKQLTE DVAKLEKEME 
QKHREELEQL KLTTKENKID SVAVNISNLV LENQPPRISK AQKRREKKAA LEKEREERIA 
EAEIENLTGA RHMESEKLAQ ILAARQLEIK QIPSDGHCMY KAIEDQLKEK DCALTVVALR 
SQTAEYMQSH VEDFLPFLTN PNTGDMYTPE EFQKYCEDIV NTAAWGGQLE LRALSHILQT 
PIEIIQADSP PIIVGEEYSK KPLILVYMRH AYGLGEHYNS VTRLVNIVTE NCS

Genular Protein ID: 1865110023

Symbol: A0A087X0W9_HUMAN

Name: N/A

UniProtKB Accession Codes:

A0A087X0W9

Database IDs:

ARBA 2 Antibodypedia 1 Bgee 1 BioGRID-ORCS 1 CDD 1 CTD 1 DNASU 1 DisGeNET 1 EC 1 EMBL 3 Ensembl 3 GO 2 Gene3D 1 GeneTree 1 HGNC 1 InterPro 4 KEGG 1 NCBI Taxonomy 1 OrthoDB 1 PANTHER 2 PROSITE 2 PeptideAtlas 1 Pfam 1 Proteomes 2 ProteomicsDB 1 RefSeq 1 SAM 1 SUPFAM 1 UCSC 1 VEuPathDB 1

Citations:

PubMed ID: 11237011

Title: Initial sequencing and analysis of the human genome.

PubMed ID: 11237011

DOI: 10.1038/35057062

PubMed ID: 11181995

Title: The sequence of the human genome.

PubMed ID: 11181995

DOI: 10.1126/science.1058040

PubMed ID: 15496913

Title: Finishing the euchromatic sequence of the human genome.

PubMed ID: 15496913

DOI: 10.1038/nature03001

PubMed ID: 16421571

Title: DNA sequence and analysis of human chromosome 8.

PubMed ID: 16421571

DOI: 10.1038/nature04406

PubMed ID: 19413330

Title: Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach.

PubMed ID: 19413330

DOI: 10.1021/ac9004309

PubMed ID: 21269460

Title: Initial characterization of the human central proteome.

PubMed ID: 21269460

DOI: 10.1186/1752-0509-5-17

PubMed ID: 22814378

Title: N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB.

PubMed ID: 22814378

DOI: 10.1073/pnas.1210303109

Sequence Information:

  • Length: 323
  • Mass: 37326
  • Checksum: BAD169986EC47B6F
  • Sequence:
    • MEPRVRVEGW KVPTSRCRFL LARVLGYLVV MEAVLTEELD EEEQLLRRHR KEKKELQAKI 
QGMKNAVPKN DKKRRKQLTE DVAKLEKEME QKHREELEQL KLTTKENKID SVAVNISNLV 
LENQPPRISK AQKRREKKAA LEKEREERIA EAEIENLTGA RHMESEKLAQ ILAARQLEIK 
QIPSDGHCMY KAIEDQLKEK DCALTVVALR SQTAEYMQSH VEDFLPFLTN PNTGDMYTPE 
EFQKYCEDIV NTAAWGGQLE LRALSHILQT PIEIIQADSP PIIVGEEYSK KPLILVYMRH 
AYGLGEHYNS VTRLVNIVTE NCS