USP9Y Data Analysis

HGNC Gene Name
ubiquitin specific peptidase 9 Y-linked
HGNC Gene Symbol
USP9Y
Identifiers
hgnc:12633 NCBIGene:8287 uniprot:O00507
Orthologs
mgi:1313274 rgd:9087771
INDRA Statements
deubiquitinations all statements
Pathway Commons
Search for USP9Y
Number of Papers
90 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 USP9Yusing 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 USP9Y using CRISPR-Cas9.

Knockout Differential Expression

Symbol Name log2-fold-change p-value p-value (adj.)
CCNB1IP1 cyclin B1 interacting protein 1 8.42e-01 1.56e-06 3.45e-02
PTK7 protein tyrosine kinase 7 (inactive) 9.78e-01 3.13e-06 3.45e-02

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 USP9Y 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
USP9Y deubiquitinates SMAD4. 1 / 1
|

ubibrowser
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 |
Benzo[a]pyrene decreases the amount of USP9Y. 2 / 2
2 |

ctd
No evidence text available

ctd
No evidence text available
USP9Y affects DDX3Y
| 2
USP9Y activates DDX3Y. 2 / 2
| 2

reach
In addition to overexpression of Y-chromosome-related transcripts (n = 18), such as USP9Y (FC> 13.1), DDX3Y (FC> 11.3), RPS4Y1 (FC> 9.9), and EIF1AY (FC> 11.8) in males, there was overexpression of CD24 (FC> 5.6) and KCNK1 (FC> 1.5).

reach
The AZFa sub-region comprises three candidate genes- DDX3Y (former name DBY), USP9Y and UTY and mutation in these genes leads to absence of spermatogenic cells.
1 |
Vanadium oxoanion increases the amount of USP9Y. 1 / 1
1 |

ctd
No evidence text available
1 |
Tetrachloroethene decreases the amount of USP9Y. 1 / 1
1 |

ctd
No evidence text available
Potassium chromate decreases the amount of USP9Y. 1 / 1
1 |

ctd
No evidence text available
IncobotulinumtoxinA decreases the amount of USP9Y. 1 / 1
1 |

ctd
No evidence text available
1 |
Formaldehyde decreases the amount of USP9Y. 1 / 1
1 |

ctd
No evidence text available
Doxorubicin affects USP9Y
1 |
Doxorubicin decreases the amount of USP9Y. 1 / 1
1 |

ctd
No evidence text available
1 |
Cyclosporin A decreases the amount of USP9Y. 1 / 1
1 |

ctd
No evidence text available
1 |
Chromium atom decreases the amount of USP9Y. 1 / 1
1 |

ctd
No evidence text available
Butanal affects USP9Y
1 |
Butanal decreases the amount of USP9Y. 1 / 1
1 |

ctd
No evidence text available
1 |
Arsenite(3-) increases the amount of USP9Y. 1 / 1
1 |

ctd
No evidence text available
1 |
Aflatoxin B1 increases the amount of USP9Y. 1 / 1
1 |

ctd
No evidence text available
USP9Y affects USP9X
| 1
USP9Y activates USP9X. 1 / 1
| 1

reach
USP9Y expression therefore completely restores the USP9X dosage imbalance between males and females.
USP9Y affects RPS4Y1
| 1
USP9Y activates RPS4Y1. 1 / 1
| 1

reach
In addition to overexpression of Y-chromosome-related transcripts (n = 18), such as USP9Y (FC> 13.1), DDX3Y (FC> 11.3), RPS4Y1 (FC> 9.9), and EIF1AY (FC> 11.8) in males, there was overexpression of CD24 (FC> 5.6) and KCNK1 (FC> 1.5).
USP9Y affects EIF1AY
| 1
USP9Y activates EIF1AY. 1 / 1
| 1

reach
In addition to overexpression of Y-chromosome-related transcripts (n = 18), such as USP9Y (FC> 13.1), DDX3Y (FC> 11.3), RPS4Y1 (FC> 9.9), and EIF1AY (FC> 11.8) in males, there was overexpression of CD24 (FC> 5.6) and KCNK1 (FC> 1.5).
USP9Y affects DEGs
| 1
USP9Y activates DEGs. 1 / 1
| 1

reach
Ubiquitin specific peptidase 9 Y linked (USP9Y), ribosomal protein S4 Y linked 1 (RPS4Y1) and eukaryotic translation initiation factor 1A Y linked (EIF1AY) were significantly upregulated DEGs in the present study.