MPND Data Analysis

HGNC Gene Name
MPN domain containing
HGNC Gene Symbol
MPND
Identifiers
hgnc:25934 NCBIGene:84954 uniprot:Q8N594
Orthologs
mgi:1915297 rgd:1589335
INDRA Statements
deubiquitinations all statements
Pathway Commons
Search for MPND
Number of Papers
16 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
CATSPERD cation channel sperm associated auxiliary subunit delta 0.298
PLIN4 perilipin 4 0.268
ZNF446 zinc finger protein 446 0.253 0.20 0.99 5.29e-02
FUT5 fucosyltransferase 5 0.251
EBI3 Epstein-Barr virus induced 3 0.241
NMRK2 nicotinamide riboside kinase 2 0.239
S1PR4 sphingosine-1-phosphate receptor 4 0.235

Dependency GO Term Enrichment

Gene set enrichment analysis was done on the genes correlated with MPNDusing 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 MPND 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
| 3

reach
Interestingly, the indolactam specific TleC and MpnD both accepted different chain lengths (from C 5 to C 25) of prenyl pyrophosphate in vitro.

reach
In contrast to typical indole PTs that exhibit broad substrate specificities towards the prenyl acceptors but with strict specificities towards the prenyl donors XREF_BIBR XREF_BIBR XREF_BIBR XREF_BIBR, it is remarkable that the indolactam specific TleC and MpnD exhibited unusually relaxed substrate specificities towards the prenyl donors and accepted different chain lengths (from C 5 to C 25) of prenyl pyrophosphate in vitro.

reach
Interestingly, both TleC and MpnD also accepted farnesyl pyrophosphate (FPP) (C 15), geranylgeranyl pyrophosphate (GGPP) (C 20) and geranylfarnesyl pyrophosphate (GFPP) (C 25) as prenyl donors, to produce 5, 6 and 7, respectively (XREF_FIG and XREF_SUPPLEMENTARY).
| 2

reach
Thus, TleC and MpnD clearly prefer to accept GPP and DMAPP as the prenyl donors, respectively.

reach
First, the indolactam specific TleC and MpnD both accepted DMAPP (C 5) and GPP (C 10) as substrates to produce pendolmycin (3), and lyngbyatoxin A (2) and 5-geranylindolactam V (4) (2:4 = 26:1 for TleC; 2:4 = 1:3 for MpnD), respectively (XREF_FIG).
MPND affects DEG15
| 2
MPND activates DEG15. 2 / 2
| 2

reach
First, the indolactam specific TleC and MpnD both accepted DMAPP (C 5) and GPP (C 10) as substrates to produce pendolmycin (3), and lyngbyatoxin A (2) and 5-geranylindolactam V (4) (2:4 = 26:1 for TleC; 2:4 = 1:3 for MpnD), respectively (XREF_FIG).

reach
Thus, TleC and MpnD clearly prefer to accept GPP and DMAPP as the prenyl donors, respectively.
1 |
Valproic acid decreases the amount of MPND. 1 / 1
1 |

ctd
No evidence text available
1 |
Trichostatin A decreases the amount of MPND. 1 / 1
1 |

ctd
No evidence text available
1 |
Thioacetamide decreases the amount of MPND. 1 / 1
1 |

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

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

ctd
No evidence text available
1 |

ctd
No evidence text available
Methylmercury chloride decreases the amount of MPND. 1 / 1
1 |

ctd
No evidence text available
Jinfukang affects MPND
1 |
Jinfukang increases the amount of MPND. 1 / 1
1 |

ctd
No evidence text available
1 |
Hsa-miR-335-5p decreases the amount of MPND. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-let-7b-5p decreases the amount of MPND. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
Hexabromocyclododecane decreases the amount of MPND. 1 / 1
1 |

ctd
No evidence text available
Genistein affects MPND
1 |
Genistein increases the amount of MPND. 1 / 1
1 |

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

ctd
No evidence text available
1 |
Copper(II) sulfate decreases the amount of MPND. 1 / 1
1 |

ctd
No evidence text available
Copper atom affects MPND
1 |
Copper atom increases the amount of MPND. 1 / 1
1 |

ctd
No evidence text available
1 |
Cobalt dichloride decreases the amount of MPND. 1 / 1
1 |

ctd
No evidence text available
Clofibrate affects MPND
1 |
Clofibrate decreases the amount of MPND. 1 / 1
1 |

ctd
No evidence text available
1 |
Benzo[a]pyrene decreases the amount of MPND. 1 / 1
1 |

ctd
No evidence text available
Atrazine affects MPND
1 |
Atrazine decreases the amount of MPND. 1 / 1
1 |

ctd
No evidence text available
Aflatoxin B1 affects MPND
1 |
Aflatoxin B1 decreases the amount of MPND. 1 / 1
1 |

ctd
No evidence text available
Abrine affects MPND
1 |
Abrine decreases the amount of MPND. 1 / 1
1 |

ctd
No evidence text available
MPND affects C5
| 1
MPND activates C5. 1 / 1
| 1

reach
This would be the reason why MpnD produces not only the C-7 ' reverse ' prenylation product 2 but also the C-5 ' normal ' prenylation product 4.

reach
Interestingly, both TleC and MpnD also accepted farnesyl pyrophosphate (FPP) (C 15), geranylgeranyl pyrophosphate (GGPP) (C 20) and geranylfarnesyl pyrophosphate (GFPP) (C 25) as prenyl donors, to produce 5, 6 and 7, respectively (XREF_FIG and XREF_SUPPLEMENTARY).
GSK-J4 affects MPND
1 |
GSK-J4 decreases the amount of MPND. 1 / 1
1 |

ctd
No evidence text available
2-hydroxypropanoic acid decreases the amount of MPND. 1 / 1
1 |

ctd
No evidence text available
1 |

ctd
No evidence text available