OTUD3 Data Analysis

HGNC Gene Name
OTU deubiquitinase 3
HGNC Gene Symbol
OTUD3
Identifiers
hgnc:29038 NCBIGene:23252 uniprot:Q5T2D3
Orthologs
mgi:1920412 rgd:1560468
INDRA Statements
deubiquitinations all statements
Pathway Commons
Search for OTUD3
Number of Papers
25 retrieved on 2022-05-22

DepMap Analysis

The Dependency Map (DepMap) is a genome-wide pooled CRISPR-Cas9 knockout proliferation screen conducted in more than 700 cancer cell lines spanning many different tumor lineages. Each cell line in the DepMap contains a unique barcode, and each gene knockout is assigned a “dependency score” on a per cell-line basis which quantifies the rate of CRISPR-Cas9 guide drop. It has been found that proteins with similar DepMap scores across cell lines, a phenomenon known as co-dependent genes, have closely related biological functions. This can include activity in the same or parallel pathways or membership in the same protein complex or the same pathway.

We identified the strongest seven co-dependent genes (“Symbol”) for DUBs and ran GO enrichment analysis. We used Biogrid, IntAct, and Pathway Commons PPIDs, and the NURSA protein-protein interaction databases (PPIDs) to determine whether co-dependent genes interact with one another. The “Evidence” column contains the PPIDs in which the interaction appears as well as whether there is support for the association by an INDRA statement. As another approach to identify potential interactors, we looked at proteomics data from the Broad Institute's Cancer Cell Line Encyclopedia (CCLE) for proteins whose expression across ~375 cell lines strongly correlated with the abundance of each DUB; it has previously been observed that proteins in the same complex are frequently significantly co-expressed. The correlations and associated p-values in the CCLE proteomics dataset are provided. And, we determined whether co-dependent genes yield similar transcriptomic signatures in the Broad Institute's Connectivity Map (CMap). A CMap score greater than 90 is considered significantly similar.

DepMap Correlations

Symbol Name DepMap Correlation Evidence CCLE Correlation CCLE Z-score CCLE p-value (adj) CCLE Significant CMAP Score CMAP Type
ASGR1 asialoglycoprotein receptor 1 0.244 Reactome (2)
MAP3K2 mitogen-activated protein kinase kinase kinase 2 0.237 -0.04 -0.32 6.35e-01
PRXL2C peroxiredoxin like 2C 0.234 -0.08 -0.53 5.41e-01
CAMK2N1 calcium/calmodulin dependent protein kinase II inhibitor 1 0.222
FBXO6 F-box protein 6 0.218 Reactome (2) -0.09 -0.59 2.84e-01
ABTB2 ankyrin repeat and BTB domain containing 2 0.215
KLHL21 kelch like family member 21 0.212 Reactome (2)

Dependency GO Term Enrichment

Gene set enrichment analysis was done on the genes correlated with OTUD3using the terms from Gene Ontology and gene sets derived from the Gene Ontology Annotations database via MSigDB.

Using the biological processes and other Gene Ontology terms from well characterized DUBs as a positive control, several gene set enrichment analyses were considered. Threshold-less methods like GSEA had relatively poor results. Over-representation analysis with a threshold of of the top 7 highest absolute value Dependency Map correlations yielded the best results and is reported below.

GO Identifier GO Name GO Type p-value p-value (adj.) q-value

Literature Mining

INDRA was used to automatically assemble known mechanisms related to OTUD3 from literature and knowledge bases. The first section shows only DUB activity and the second shows all other results.

Deubiquitinase Activity

psp cbn pc bel_lc signor biogrid lincs_drug tas hprd trrust ctd vhn pe drugbank omnipath conib crog dgi | rlimsp isi tees geneways eidos trips medscan sparser reach
OTUD3 deubiquitinates HSPA5. 1 / 1
| 1

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OTUD3 plays an oncogenic role in lung cancer cells and promotes the development of lung cancer by directly interacting with GRP78, where OTUD3 deubiquitylates GRP78 and maintains GRP78 stability in vitro and in vivo.
OTUD3 deubiquitinates ACTN4. 1 / 1
| 1

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Additionally, OTUD3 directly bound with ACTN4 and deubiquitinated ACTN4 to stabilize it.
OTUD3 leads to the deubiquitination of TOP2A. 1 / 1
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In the presence of PTEN, ubiquitination of TOP2A is inhibited by OTUD3.
OTUD3 deubiquitinates PTEN on lysine. 1 / 1
1 |

biopax:reactome
No evidence text available
OTUD3 deubiquitinates PTEN. 1 / 1
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ubibrowser
Here, we report OTUD3 as a deubiquitylase of PTEN. OTUD3 interacts with, de-polyubiquitylates and stabilizes PTEN.

Other Statements

psp cbn pc bel_lc signor biogrid lincs_drug tas hprd trrust ctd vhn pe drugbank omnipath conib crog dgi | rlimsp isi tees geneways eidos trips medscan sparser reach

reach
Furthermore, OTUD3 silence promoted proliferation and motility and decreased apoptosis for HCT116 cells and restored partly miR-32-mediated cell proliferation, migration, and antiapoptosis for colon cancer.

eidos
OTUD3 also inhibits cell proliferation and clone formation and increases the sensitivity of BC cells to apoptosis induced by chemotherapy drugs .

reach
Finally, ACTN4 was found to be essential for OTUD3 mediated HCC proliferation and metastasis in vitro and in vivo.
3 |
Pirinixic acid increases the amount of OTUD3.
1 |
Pirinixic acid increases the amount of OTUD3. 1 / 1
1 |

ctd
No evidence text available
Pirinixic acid decreases the amount of OTUD3.
1 |
Pirinixic acid decreases the amount of OTUD3. 1 / 1
1 |

ctd
No evidence text available
Pirinixic acid activates OTUD3.
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ctd
No evidence text available
OTUD3 affects MAVS
| 3
OTUD3 inhibits MAVS.
| 1
OTUD3 inhibits MAVS. 1 / 1
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For example, OTUD3 removes K63-linked ubiquitin chains from MAVS and thereby inhibits MAVS aggregation and IFN-I signaling activation (65).
OTUD3 increases the amount of MAVS.
| 1
OTUD3 increases the amount of MAVS. 1 / 1
| 1

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In addition, both OTUD3 and A20 negatively regulate the IFN-mediated antiviral response by modulating the polyubiquitination level of MAVS (125, 126).
OTUD3 decreases the amount of MAVS.
| 1
OTUD3 decreases the amount of MAVS. 1 / 1
| 1

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In addition, both OTUD3 and A20 negatively regulate the IFN-mediated antiviral response by modulating the polyubiquitination level of MAVS (125, 126).
Paracetamol affects OTUD3
2 |
Paracetamol increases the amount of OTUD3. 2 / 2
2 |

ctd
No evidence text available

ctd
No evidence text available
Nicotine affects OTUD3
| 1 1
| 1 1

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Nicotine-mediated OTUD3 downregulation inhibits VEGF-C mRNA decay to promote lymphatic metastasis of human esophageal cancer.

eidos
Here we show that OTU domain-containing protein 3 ( OTUD3 ) is downregulated by nicotine and correlates with poor prognosis in heavy-smoking esophageal cancer patients .
Methyl methanesulfonate increases the amount of OTUD3. 2 / 2
2 |

ctd
No evidence text available

ctd
No evidence text available
SIRT1 affects OTUD3
| 1 1
SIRT1 inhibits OTUD3. 2 / 2
| 1 1

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In response to virus infection, the acetylated Lys129 is removed by SIRT1, which promptly inactivates OTUD3 and thus allows timely induction of innate antiviral immunity.

sparser
In response to virus infection, the acetylated Lys129 is removed by SIRT1, which promptly inactivates OTUD3 and thus allows timely induction of innate antiviral immunity.
STUB1 affects OTUD3
| 1 1
STUB1 bound to OTUD3 inhibits OTUD3. 1 / 1
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CHIP interacts with, polyubiquitylates OTUD3 and promotes OTUD3 degradation.
STUB1 inhibits OTUD3. 1 / 1
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eidos
CHIP interacts with , polyubiquitylates OTUD3 and promotes OTUD3 degradation .
OTUD3 affects TOP2A
| 2
OTUD3 increases the amount of TOP2A.
| 1
Modified OTUD3 increases the amount of TOP2A. 1 / 1
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A finding of particular interest is that overexpression of OTUD3 in PTEN +/+ cells but not in PTEN -/- cells upregulates TOP2A protein levels, indicating PTEN is required for OTUD3 function.
OTUD3 activates TOP2A.
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OTUD3 activates TOP2A. 1 / 1
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Overexpression of OTUD3 leads to upregulation of TOP2A in PTEN +/+ cells, but not in PTEN -/- cells (XREF_FIG lane 1 vs lane 2, lane 3 vs lane 4).
1 |
Valproic acid increases the amount of OTUD3. 1 / 1
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ctd
No evidence text available
Urethane affects OTUD3
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Urethane increases the amount of OTUD3. 1 / 1
1 |

ctd
No evidence text available
1 |
Titanium dioxide decreases the amount of OTUD3. 1 / 1
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ctd
No evidence text available
1 |
Thioacetamide increases the amount of OTUD3. 1 / 1
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ctd
No evidence text available
1 |
Sodium arsenite increases the amount of OTUD3. 1 / 1
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ctd
No evidence text available
1 |
Sodium arsenate decreases the amount of OTUD3. 1 / 1
1 |

ctd
No evidence text available
1 |
Methylparaben increases the amount of OTUD3. 1 / 1
1 |

ctd
No evidence text available
Indometacin affects OTUD3
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Indometacin increases the amount of OTUD3. 1 / 1
1 |

ctd
No evidence text available
1 |
Hydroperoxide increases the amount of OTUD3. 1 / 1
1 |

ctd
No evidence text available
1 |
Hsa-miR-92b-3p decreases the amount of OTUD3. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-92a-3p decreases the amount of OTUD3. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-769-5p decreases the amount of OTUD3. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-6864-3p decreases the amount of OTUD3. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-6849-3p decreases the amount of OTUD3. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-6771-3p decreases the amount of OTUD3. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-6770-5p decreases the amount of OTUD3. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-664a-5p decreases the amount of OTUD3. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-6516-3p decreases the amount of OTUD3. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-624-3p decreases the amount of OTUD3. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-513b-5p decreases the amount of OTUD3. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-4803 decreases the amount of OTUD3. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-4794 decreases the amount of OTUD3. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-4786-5p decreases the amount of OTUD3. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-4773 decreases the amount of OTUD3. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-4768-3p decreases the amount of OTUD3. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-4749-3p decreases the amount of OTUD3. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-4729 decreases the amount of OTUD3. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-4671-3p decreases the amount of OTUD3. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-4650-5p decreases the amount of OTUD3. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-454-3p decreases the amount of OTUD3. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-4493 decreases the amount of OTUD3. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-4459 decreases the amount of OTUD3. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-4457 decreases the amount of OTUD3. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-4433a-3p decreases the amount of OTUD3. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-4311 decreases the amount of OTUD3. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-4295 decreases the amount of OTUD3. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-411-3p decreases the amount of OTUD3. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-3974 decreases the amount of OTUD3. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-379-3p decreases the amount of OTUD3. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-3672 decreases the amount of OTUD3. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-3666 decreases the amount of OTUD3. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-32-5p decreases the amount of OTUD3. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-301b-3p decreases the amount of OTUD3. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-301a-3p decreases the amount of OTUD3. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-216a-5p decreases the amount of OTUD3. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-212-3p decreases the amount of OTUD3. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-20a-3p decreases the amount of OTUD3. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-194-5p decreases the amount of OTUD3. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-192-5p decreases the amount of OTUD3. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-132-3p decreases the amount of OTUD3. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-130b-3p decreases the amount of OTUD3. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-130a-3p decreases the amount of OTUD3. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-125b-2-3p decreases the amount of OTUD3. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-1207-3p decreases the amount of OTUD3. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
Endosulfan affects OTUD3
1 |
Endosulfan increases the amount of OTUD3. 1 / 1
1 |

ctd
No evidence text available
Cisplatin affects OTUD3
1 |
Cisplatin decreases the amount of OTUD3. 1 / 1
1 |

ctd
No evidence text available
1 |
Carbon nanotube increases the amount of OTUD3. 1 / 1
1 |

ctd
No evidence text available
Bisphenol A affects OTUD3
1 |
Bisphenol A increases the amount of OTUD3. 1 / 1
1 |

ctd
No evidence text available
1 |
Plant Extracts increases the amount of OTUD3. 1 / 1
1 |

ctd
No evidence text available

reach
Nicotine-mediated OTUD3 downregulation inhibits VEGF-C mRNA decay to promote lymphatic metastasis of human esophageal cancer.
| 1

reach
Acetylation Dependent Deubiquitinase OTUD3 Controls MAVS Activation in Innate Antiviral Immunity.
| 1

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Furthermore, OTUD3 silence promoted proliferation and motility and decreased apoptosis for HCT116 cells and restored partly miR-32-mediated cell proliferation, migration, and antiapoptosis for colon cancer.
OTUD3 affects VEGFC
| 1
OTUD3 inhibits VEGFC. 1 / 1
| 1

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Nicotine-mediated OTUD3 downregulation inhibits VEGF-C mRNA decay to promote lymphatic metastasis of human esophageal cancer.
OTUD3 affects OTUD3
| 1
OTUD3 inhibits OTUD3. 1 / 1
| 1

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CHIP interacts with, polyubiquitylates OTUD3 and promotes OTUD3 degradation.
OTUD3 affects Neoplasms
| 1
| 1

eidos
OTU domain-containing protein 3 ( OTUD3 ) , as a deubiquitinase ( DUB ) belonging to the ovarian tumor protease ( OTU ) family , has been reported to suppress tumor via OTUD3-PTEN signaling axis .

reach
Finally, ACTN4 was found to be essential for OTUD3 mediated HCC proliferation and metastasis in vitro and in vivo.

reach
Nicotine-mediated OTUD3 downregulation inhibits VEGF-C mRNA decay to promote lymphatic metastasis of human esophageal cancer.
OTUD3 affects Interferon
| 1
| 1

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As an acetylation-dependent deubiquitinase, OTUD3 can restrict IFN signaling by directly hydrolyzing the K63-linked poly-ubiquitinated MAVS at K129 residue (Zhang et al., 2020c).
OTUD3 affects HSPA5
| 1
OTUD3 increases the amount of HSPA5. 1 / 1
| 1

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Knockdown of CHIP stabilizes OTUD3 which leads to elevated GRP78 levels in lung cancer cells.
OTUD3 affects Clone Cells
| 1
| 1

eidos
OTUD3 also inhibits cell proliferation and clone formation and increases the sensitivity of BC cells to apoptosis induced by chemotherapy drugs .
OTUD3 affects C4B_2
| 1
OTUD3 activates C4B_2. 1 / 1
| 1

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Association analysis of genome-wide genetic variants identified dozens of genetic loci associated with CH mutations, including a candidate SNP rs2298110, which may promote CH by increasing expression of a potential leukemia promoter gene OTUD3.
MAX affects OTUD3
| 1
MAX activates OTUD3. 1 / 1
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For OTUD2, the main determinant for S1-S2 site specificity appears to be affinity, whereas for OTUD3 specificity appears to be driven by an increase in V max of the reaction.
GSK-J4 affects OTUD3
1 |
GSK-J4 increases the amount of OTUD3. 1 / 1
1 |

ctd
No evidence text available
6-propyl-2-thiouracil decreases the amount of OTUD3. 1 / 1
1 |

ctd
No evidence text available
1 |

ctd
No evidence text available
17alpha-ethynylestradiol increases the amount of OTUD3. 1 / 1
1 |

ctd
No evidence text available