OTUD6A Data Analysis

HGNC Gene Name
OTU deubiquitinase 6A
HGNC Gene Symbol
OTUD6A
Identifiers
hgnc:32312 NCBIGene:139562 uniprot:Q7L8S5
Orthologs
mgi:3644685 rgd:1560855
INDRA Statements
deubiquitinations all statements
Pathway Commons
Search for OTUD6A
Number of Papers
7 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
CCDC117 coiled-coil domain containing 117 0.252
ARMCX2 armadillo repeat containing X-linked 2 0.223
LXN latexin -0.223
SRCIN1 SRC kinase signaling inhibitor 1 0.216
ZNF214 zinc finger protein 214 -0.213
H2BW1 H2B.W histone 1 0.213
C10orf71 chromosome 10 open reading frame 71 0.21

Dependency GO Term Enrichment

Gene set enrichment analysis was done on the genes correlated with OTUD6Ausing 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 OTUD6A from literature and knowledge bases. The first section shows only DUB activity and the second shows all other results.

Deubiquitinase Activity

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
OTUD6A affects PLK1
| 1 1
OTUD6A activates PLK1. 2 / 2
| 1 1

reach
Consequently, our data suggest that Aurora-A, a critical mitotic regulator, is deubiquitinated, stabilized, and activated by OTUD6A, which in turn activates PLK1 to drive cells into mitosis.

eidos
Consequently , our data suggest that Aurora-A , a critical mitotic regulator , is deubiquitinated , stabilized , and activated by OTUD6A , which in turn activates PLK1 to drive cells into mitosis .
OTUD6A affects DNM1L
| 2
OTUD6A increases the amount of DNM1L.
| 1
Modified OTUD6A increases the amount of DNM1L. 1 / 1
| 1

reach
Conversely, overexpression of OTUD6A increases Drp1 levels and its protein half-life and enhances cancer cell growth.
OTUD6A decreases the amount of DNM1L.
| 1
OTUD6A decreases the amount of DNM1L. 1 / 1
| 1

reach
Depletion of OTUD6A leads to lower Drp1 levels and suppressed mitochondrial fission and the affected cells are consequently less prone to tumorigenesis.
OTUD6A affects CKS2
| 2
OTUD6A increases the amount of CKS2.
| 1
OTUD6A increases the amount of CKS2. 1 / 1
| 1

reach
OTUD6A Promotes CKS2 Gene Expression.
OTUD6A activates CKS2.
| 1
OTUD6A activates CKS2. 1 / 1
| 1

reach
We conducted an independent validation and found that CKS2 was significantly upregulated by OTUD6A overexpression (XREF_FIG b).

ctd
No evidence text available
Potassium dichromate decreases the amount of OTUD6A. 1 / 1
1 |

ctd
No evidence text available
1 |

ctd
No evidence text available
Ionomycin affects OTUD6A
1 |
Ionomycin decreases the amount of OTUD6A. 1 / 1
1 |

ctd
No evidence text available
1 |
Hsa-miR-92a-3p decreases the amount of OTUD6A. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-92a-2-5p decreases the amount of OTUD6A. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-6855-5p decreases the amount of OTUD6A. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-6832-5p decreases the amount of OTUD6A. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-6742-5p decreases the amount of OTUD6A. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-6134 decreases the amount of OTUD6A. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-588 decreases the amount of OTUD6A. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-548s decreases the amount of OTUD6A. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-5096 decreases the amount of OTUD6A. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-4781-3p decreases the amount of OTUD6A. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-4732-5p decreases the amount of OTUD6A. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-4716-5p decreases the amount of OTUD6A. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-4701-5p decreases the amount of OTUD6A. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-4435 decreases the amount of OTUD6A. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-3674 decreases the amount of OTUD6A. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-3187-3p decreases the amount of OTUD6A. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-3170 decreases the amount of OTUD6A. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-3149 decreases the amount of OTUD6A. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-197-3p decreases the amount of OTUD6A. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-193b-5p decreases the amount of OTUD6A. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-129-5p decreases the amount of OTUD6A. 1 / 1
1 |

biopax:mirtarbase
No evidence text available

reach
However, it has been demonstrated that OTUD6A enhances the protein levels of one of the crucial EMT inducers, Snail [XREF_BIBR], and promotes colorectal cancer by deubiquitinating and stabilizing DRP1 [XREF_BIBR].

reach
Deubiquitinase OTUD6A promotes proliferation of cancer cells via regulating Drp1 stability and mitochondrial fission.
| 1
Modified OTUD6A activates cell growth. 1 / 1
| 1

reach
Conversely, overexpression of OTUD6A increases Drp1 levels and its protein half-life and enhances cancer cell growth.
OTUD6A affects SNAI1
| 1
OTUD6A increases the amount of SNAI1. 1 / 1
| 1

reach
OTUD6A enhances the protein levels of Snail, an EMT (epithelial-mesenchymal transition) inducer [XREF_BIBR], and promotes tumorigenecity by deubiquitinating and stabilizing Drp1 [XREF_BIBR].

eidos
However , it has been demonstrated that OTUD6A enhances the protein levels of one of the crucial EMT inducers , Snail [ 22 ] , and promotes colorectal cancer by deubiquitinating and stabilizing DRP1 [ 23 ] .
OTUD1 affects OTUD6A
| 1
OTUD1 activates OTUD6A. 1 / 1
| 1

reach
Moreover, OTUD1 was not able to increase the enzymatic activity of Aurora-A as much as OTUD6A.
FOXO4 affects OTUD6A
1 |
FOXO4 decreases the amount of OTUD6A. 1 / 1
1 |

biopax:msigdb
No evidence text available
1 |
Dietary Sucrose increases the amount of OTUD6A. 1 / 1
1 |

ctd
No evidence text available
Cuprizone affects OTUD6A
1 |
Cuprizone decreases the amount of OTUD6A. 1 / 1
1 |

ctd
No evidence text available