OTUD7A Data Analysis

HGNC Gene Name
OTU deubiquitinase 7A
HGNC Gene Symbol
OTUD7A
Identifiers
hgnc:20718 NCBIGene:161725 uniprot:Q8TE49
Orthologs
mgi:2158505 rgd:1563721
INDRA Statements
deubiquitinations all statements
Pathway Commons
Search for OTUD7A
Number of Papers
20 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

Dependency GO Term Enrichment

Gene set enrichment analysis was done on the genes correlated with OTUD7Ausing 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

Transcriptomics

The following table shows the significantly differentially expressed genes after knocking out OTUD7A using CRISPR-Cas9.

Knockout Differential Expression

Symbol Name log2-fold-change p-value p-value (adj.)
ANKRD1 ankyrin repeat domain 1 4.05e-01 6.71e-07 7.40e-03
SERPINB1 serpin family B member 1 -8.06e-01 6.01e-07 7.40e-03

Gene Set Enrichment Analysis

There were too few differentially expressed genes to run a meaningful GSEA.

Literature Mining

INDRA was used to automatically assemble known mechanisms related to OTUD7A 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
OTUD7A deubiquitinates UBC on K239. 1 / 1
1 |

biopax:reactome
No evidence text available
OTUD7A deubiquitinates UBC on K391. 1 / 1
1 |

biopax:reactome
No evidence text available
OTUD7A deubiquitinates UBC on K543. 1 / 1
1 |

biopax:reactome
No evidence text available
OTUD7A deubiquitinates UBA52 on K11. 1 / 1
1 |

biopax:reactome
No evidence text available
OTUD7A deubiquitinates UBB on K11. 1 / 1
1 |

biopax:reactome
No evidence text available
OTUD7A deubiquitinates UBB on K163. 1 / 1
1 |

biopax:reactome
No evidence text available
OTUD7A deubiquitinates UBC on K11. 1 / 1
1 |

biopax:reactome
No evidence text available
OTUD7A deubiquitinates UBC on K163. 1 / 1
1 |

biopax:reactome
No evidence text available
OTUD7A deubiquitinates RPS27A on K11. 1 / 1
1 |

biopax:reactome
No evidence text available
OTUD7A deubiquitinates UBC on K87. 1 / 1
1 |

biopax:reactome
No evidence text available
OTUD7A deubiquitinates UBC on K619. 1 / 1
1 |

biopax:reactome
No evidence text available
OTUD7A deubiquitinates UBC on K315. 1 / 1
1 |

biopax:reactome
No evidence text available
OTUD7A deubiquitinates UBB on K87. 1 / 1
1 |

biopax:reactome
No evidence text available
OTUD7A deubiquitinates UBC on K467. 1 / 1
1 |

biopax:reactome
No evidence text available

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
2 |
Bisphenol A decreases the amount of OTUD7A. 2 / 2
2 |

ctd
No evidence text available

ctd
No evidence text available
2 |
Paracetamol increases the amount of OTUD7A.
1 |
Paracetamol increases the amount of OTUD7A. 1 / 1
1 |

ctd
No evidence text available
Paracetamol decreases the amount of OTUD7A.
1 |
Paracetamol decreases the amount of OTUD7A. 1 / 1
1 |

ctd
No evidence text available
Triclosan affects OTUD7A
1 |
Triclosan increases the amount of OTUD7A. 1 / 1
1 |

ctd
No evidence text available
1 |
Titanium dioxide decreases the amount of OTUD7A. 1 / 1
1 |

ctd
No evidence text available
1 |
Sulforaphane decreases the amount of OTUD7A. 1 / 1
1 |

ctd
No evidence text available
Methyltestosterone decreases the amount of OTUD7A. 1 / 1
1 |

ctd
No evidence text available
1 |
Hsa-miR-8080 decreases the amount of OTUD7A. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-7-2-3p decreases the amount of OTUD7A. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-7-1-3p decreases the amount of OTUD7A. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-670-3p decreases the amount of OTUD7A. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-642b-3p decreases the amount of OTUD7A. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-642a-3p decreases the amount of OTUD7A. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-5582-3p decreases the amount of OTUD7A. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-548x-5p decreases the amount of OTUD7A. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-548o-3p decreases the amount of OTUD7A. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-548g-5p decreases the amount of OTUD7A. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-548f-5p decreases the amount of OTUD7A. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-548aw decreases the amount of OTUD7A. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-548aj-5p decreases the amount of OTUD7A. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-491-3p decreases the amount of OTUD7A. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-30c-5p decreases the amount of OTUD7A. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-153-5p decreases the amount of OTUD7A. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-1468-3p decreases the amount of OTUD7A. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-1323 decreases the amount of OTUD7A. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
Hsa-miR-1255b-2-3p decreases the amount of OTUD7A. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-1238-3p decreases the amount of OTUD7A. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-1197 decreases the amount of OTUD7A. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
Gentamycin affects OTUD7A
1 |
Gentamycin decreases the amount of OTUD7A. 1 / 1
1 |

ctd
No evidence text available
Acrylamide affects OTUD7A
1 |
Acrylamide increases the amount of OTUD7A. 1 / 1
1 |

ctd
No evidence text available
Sesame Oil affects OTUD7A
1 |
Sesame Oil increases the amount of OTUD7A. 1 / 1
1 |

ctd
No evidence text available
REPIN1 affects OTUD7A
1 |
REPIN1 decreases the amount of OTUD7A. 1 / 1
1 |

biopax:msigdb
No evidence text available
OTUD7A affects Mice
| 1
OTUD7A activates Mice. 1 / 1
| 1

reach
Uddin and colleagues combined whole-genome sequencing, human brain gene expression analysis, and study of a mouse model with a syntenic heterozygous deletion of 15q13; they found reduced expression of OTUD7A in the dendritic spine of the cortical neurons that contributed to the dendrite outgrowth abnormalities in the heterozygous 15q13 deletion mice.
| PMC
OTUD7A affects EGFR
| 1
OTUD7A activates EGFR. 1 / 1
| 1

reach
Accordingly, simultaneous knockdown of Cezanne-1 and Cezanne-2 by using two pools of four oligonucleotides (approximately 70% and 50%, respectively) moderately enhanced both basal and inducible degradation of EGFR, whereas the reciprocal silencing of c-CBL and CBL-b showed the expected opposite effect (XREF_FIG).