USP40 Data Analysis

HGNC Gene Name
ubiquitin specific peptidase 40
HGNC Gene Symbol
USP40
Identifiers
hgnc:20069 NCBIGene:55230 uniprot:Q9NVE5
Orthologs
mgi:2443184 rgd:1309613
INDRA Statements
deubiquitinations all statements
Pathway Commons
Search for USP40
Number of Papers
15 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 USP40using 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 USP40 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
2 |
Pirinixic acid increases the amount of USP40. 2 / 2
2 |

ctd
No evidence text available

ctd
No evidence text available
Bisphenol A affects USP40
2 |
Bisphenol A increases the amount of USP40.
1 |
Bisphenol A increases the amount of USP40. 1 / 1
1 |

ctd
No evidence text available
Bisphenol A decreases the amount of USP40.
1 |
Bisphenol A decreases the amount of USP40. 1 / 1
1 |

ctd
No evidence text available
USP40 affects CFLAR
| 2
USP40 decreases the amount of CFLAR.
| 1
USP40 decreases the amount of CFLAR. 1 / 1
| 1

reach
USP40 knockdown did not increase CFLAR L protein level despite GMEB1 overexpression, suggesting GMEB1 promotes CFLAR L stability via USP40.
USP40 activates CFLAR.
| 1
USP40 activates CFLAR. 1 / 1
| 1

reach
USP40 targeted CFLAR L for K48 linked de-ubiquitination.
Vinclozolin affects USP40
1 |
Vinclozolin increases the amount of USP40. 1 / 1
1 |

ctd
No evidence text available
1 |
Valproic acid increases the amount of USP40. 1 / 1
1 |

ctd
No evidence text available
Urethane affects USP40
1 |
Urethane decreases the amount of USP40. 1 / 1
1 |

ctd
No evidence text available
Tetrachloromethane decreases the amount of USP40. 1 / 1
1 |

ctd
No evidence text available
Sunitinib affects USP40
1 |
Sunitinib increases the amount of USP40. 1 / 1
1 |

ctd
No evidence text available
1 |
Schizandrin B decreases the amount of USP40. 1 / 1
1 |

ctd
No evidence text available
1 |

ctd
No evidence text available
Pentabromodiphenyl ether decreases the amount of USP40. 1 / 1
1 |

ctd
No evidence text available
Paracetamol affects USP40
1 |
Paracetamol decreases the amount of USP40. 1 / 1
1 |

ctd
No evidence text available
Leflunomide affects USP40
1 |
Leflunomide decreases the amount of USP40. 1 / 1
1 |

ctd
No evidence text available
1 |
Lead diacetate increases the amount of USP40. 1 / 1
1 |

ctd
No evidence text available
Lead atom affects USP40
1 |
Lead atom decreases the amount of USP40. 1 / 1
1 |

ctd
No evidence text available
Ionomycin affects USP40
1 |
Ionomycin decreases the amount of USP40. 1 / 1
1 |

ctd
No evidence text available
Indometacin affects USP40
1 |
Indometacin decreases the amount of USP40. 1 / 1
1 |

ctd
No evidence text available
Hydralazine affects USP40
1 |
Hydralazine increases the amount of USP40. 1 / 1
1 |

ctd
No evidence text available
Hsa-miR-484 affects USP40
1 |
Hsa-miR-484 decreases the amount of USP40. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
Hexabromocyclododecane increases the amount of USP40. 1 / 1
1 |

ctd
No evidence text available
Glycidamide affects USP40
1 |
Glycidamide increases the amount of USP40. 1 / 1
1 |

ctd
No evidence text available
Dioxygen affects USP40
1 |
Dioxygen increases the amount of USP40. 1 / 1
1 |

ctd
No evidence text available
1 |
Dibutyl phthalate decreases the amount of USP40. 1 / 1
1 |

ctd
No evidence text available
1 |
Dexamethasone decreases the amount of USP40. 1 / 1
1 |

ctd
No evidence text available
1 |
Cyclosporin A decreases the amount of USP40. 1 / 1
1 |

ctd
No evidence text available
Coumestrol affects USP40
1 |
Coumestrol decreases the amount of USP40. 1 / 1
1 |

ctd
No evidence text available
Calcitriol affects USP40
1 |
Calcitriol increases the amount of USP40. 1 / 1
1 |

ctd
No evidence text available
Butanal affects USP40
1 |
Butanal decreases the amount of USP40. 1 / 1
1 |

ctd
No evidence text available
Bisphenol F affects USP40
1 |
Bisphenol F decreases the amount of USP40. 1 / 1
1 |

ctd
No evidence text available
1 |
Aflatoxin B1 increases the amount of USP40. 1 / 1
1 |

ctd
No evidence text available
| 1

reach
Interestingly, it has been reported that some polymorphisms of USP24 and USP40 significantly decrease the risk of developing PD [22,23].
USP40 affects IL10
| 1
USP40 activates IL10. 1 / 1
| 1

reach
Knockdown of USP40 significantly decreased ManLAM and Pam3CSK4 induced IL-10 production by WT B cells, whereas IL-10 production by USP40 silenced TLR2 -/- B cells was not reduced compared with scramble RNA treated TLR2 -/- B cells upon stimulation with ManLAM (XREF_FIG C, 5D, and XREF_SUPPLEMENTARY F).
STAT6 affects USP40
1 |
STAT6 decreases the amount of USP40. 1 / 1
1 |

biopax:msigdb
No evidence text available
STAT5A affects USP40
1 |
STAT5A decreases the amount of USP40. 1 / 1
1 |

biopax:msigdb
No evidence text available
1 |
Phthalic Acids decreases the amount of USP40. 1 / 1
1 |

ctd
No evidence text available
GSK-J4 affects USP40
1 |
GSK-J4 decreases the amount of USP40. 1 / 1
1 |

ctd
No evidence text available
Antirheumatic Agents increases the amount of USP40. 1 / 1
1 |

ctd
No evidence text available
4-hydroxyphenyl retinamide increases the amount of USP40. 1 / 1
1 |

ctd
No evidence text available
1 |

ctd
No evidence text available
1-phenylpropan-2-amine decreases the amount of USP40. 1 / 1
1 |

ctd
No evidence text available
1,3-dinitrobenzene increases the amount of USP40. 1 / 1
1 |

ctd
No evidence text available