USP31 Data Analysis

HGNC Gene Name
ubiquitin specific peptidase 31
HGNC Gene Symbol
USP31
Identifiers
hgnc:20060 NCBIGene:57478 uniprot:Q70CQ4
Orthologs
mgi:1923429 rgd:1308183
INDRA Statements
deubiquitinations all statements
Pathway Commons
Search for USP31
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 USP31using 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 USP31 using CRISPR-Cas9.

Knockout Differential Expression

Symbol Name log2-fold-change p-value p-value (adj.)
HSP90AB2P heat shock protein 90 alpha family class B member 2, pseudogene 1.07e+00 3.72e-06 2.06e-02
NSA2 NSA2 ribosome biogenesis factor 6.83e-01 2.11e-06 2.06e-02
RPL30 ribosomal protein L30 3.48e-01 3.29e-06 2.06e-02
SRPX sushi repeat containing protein X-linked 7.30e-01 3.73e-06 2.06e-02
HSP90AB1 heat shock protein 90 alpha family class B member 1 7.14e-01 7.14e-06 3.15e-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 USP31 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
USP31 affects NFkappaB
| 1 6
USP31 inhibits NFkappaB.
| 1 4
| 1 4

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USP31 and USP7 also inhibit NF-kappaB signaling by deubiquitinating K63 linked polyubiquitin chains [XREF_BIBR, XREF_BIBR].

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USP31 also inhibited NF-kappaB activation mediated by two TRAF proteins (TRAF2 and TRAF6), as well as by the IKKbeta kinase.

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YAP1 Mediated Suppression of USP31 Enhances NFkappaB Activity to Promote Sarcomagenesis.

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USP31 overexpression inhibited NF-kappaB activation mediated by TNFalpha and two members of the TNFR family, CD40 and LMP1, whereas it had no effect on the basal NF-kappaB activity.

eidos
USP31 and USP7 also inhibit NF-kappaB signaling by deubiquitinating K63-linked polyubiquitin chains [ 38,39 ] .
USP31 activates NFkappaB.
| 2
| 2

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These results reinforce the notion that USP31 has a specific role in NF-kappaB activation induced by TRAFs and members of the TNFR family.The nuclear localization of USP31 and its implication in NF-ka[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]

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The inhibition of NF-kappaB activation by USP31 was not due to a reduction of effector protein expression, since Western blot analysis revealed that the levels of all effector proteins were unaffected[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]
Silver(0) affects USP31
2 |
Silver(0) decreases the amount of USP31. 2 / 2
2 |

ctd
No evidence text available

ctd
No evidence text available
Paracetamol affects USP31
2 |
Paracetamol increases the amount of USP31. 2 / 2
2 |

ctd
No evidence text available

ctd
No evidence text available
2 |
Aflatoxin B1 increases the amount of USP31. 2 / 2
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ctd
No evidence text available

ctd
No evidence text available
YAP1 affects USP31
| 2
YAP1 inhibits USP31. 2 / 2
| 2

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It is worth noting that YAP1 was shown to inhibit the negative regulatory factor of NF-κB USP31 and induce excessive tumor cell proliferation.
| PMC

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YAP1 promoted sarcomagenesis by inhibiting expression of ubiquitin specific peptidase 31 (USP31), a newly identified upstream negative regulator of NFkappaB signaling.
USP31 affects TRAF6
| 1
USP31 inhibits TRAF6. 1 / 2
| 1

eidos
For example , USP11 negatively regulates TNFalpha-induced NF-kappaB activation associated with IkappaBalpha and attenuates IkappaBalpha degradation [ 34 ] ; USP20 deubiquitinates TRAF6 and suppresses interleukin 1beta ( IL-1beta ) - and Tax-induced NF-kappaB activation [ 40 ] ; Katrin et al. showed that USP15 regulates IkappaBalpha / NF-kappaB by deubiquitinylation IkappaBalpha [ 44 ] ; and USP31 inhibits TNFalpha , CD40 , TRAF2 , TRAF6 and IKKbeta-mediated NF-kappaB activation [ 45 ] .
USP31 affects TRAF2
| 1
USP31 inhibits TRAF2. 1 / 2
| 1

eidos
For example , USP11 negatively regulates TNFalpha-induced NF-kappaB activation associated with IkappaBalpha and attenuates IkappaBalpha degradation [ 34 ] ; USP20 deubiquitinates TRAF6 and suppresses interleukin 1beta ( IL-1beta ) - and Tax-induced NF-kappaB activation [ 40 ] ; Katrin et al. showed that USP15 regulates IkappaBalpha / NF-kappaB by deubiquitinylation IkappaBalpha [ 44 ] ; and USP31 inhibits TNFalpha , CD40 , TRAF2 , TRAF6 and IKKbeta-mediated NF-kappaB activation [ 45 ] .
USP31 affects CD40
| 1
USP31 inhibits CD40. 1 / 2
| 1

eidos
For example , USP11 negatively regulates TNFalpha-induced NF-kappaB activation associated with IkappaBalpha and attenuates IkappaBalpha degradation [ 34 ] ; USP20 deubiquitinates TRAF6 and suppresses interleukin 1beta ( IL-1beta ) - and Tax-induced NF-kappaB activation [ 40 ] ; Katrin et al. showed that USP15 regulates IkappaBalpha / NF-kappaB by deubiquitinylation IkappaBalpha [ 44 ] ; and USP31 inhibits TNFalpha , CD40 , TRAF2 , TRAF6 and IKKbeta-mediated NF-kappaB activation [ 45 ] .
SREBF1 affects USP31
2 |
SREBF1 decreases the amount of USP31. 2 / 2
2 |

biopax:msigdb
No evidence text available

biopax:msigdb
No evidence text available
RELA affects USP31
| 2
RELA activates USP31. 2 / 2
| 2

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p65 and RelA is a possible target of USP31, since it is a major component of NF-kappaB and it is ubiquitinated and degraded by the proteasome in the nucleus [12].

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P65 and RelA is a possible target of USP31, since it is a major component of NF-kappaB and it is ubiquitinated and degraded by the proteasome in the nucleus [12].
Vinclozolin affects USP31
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Vinclozolin decreases the amount of USP31. 1 / 1
1 |

ctd
No evidence text available
1 |
Valproic acid increases the amount of USP31. 1 / 1
1 |

ctd
No evidence text available

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No evidence text available
1 |
Thioacetamide increases the amount of USP31. 1 / 1
1 |

ctd
No evidence text available
Tetrachloromethane increases the amount of USP31. 1 / 1
1 |

ctd
No evidence text available
Sunitinib affects USP31
1 |
Sunitinib increases the amount of USP31. 1 / 1
1 |

ctd
No evidence text available
1 |
Sodium arsenite increases the amount of USP31. 1 / 1
1 |

ctd
No evidence text available
1 |
Schizandrin B increases the amount of USP31. 1 / 1
1 |

ctd
No evidence text available
Leflunomide affects USP31
1 |
Leflunomide increases the amount of USP31. 1 / 1
1 |

ctd
No evidence text available
Lead atom affects USP31
1 |
Lead atom decreases the amount of USP31. 1 / 1
1 |

ctd
No evidence text available
1 |
Hsa-miR-92a-3p decreases the amount of USP31. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-7-5p decreases the amount of USP31. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-574-3p decreases the amount of USP31. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
Hsa-miR-375 affects USP31
1 |
Hsa-miR-375 decreases the amount of USP31. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-374a-5p decreases the amount of USP31. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-23b-3p decreases the amount of USP31. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-195-5p decreases the amount of USP31. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-16-5p decreases the amount of USP31. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-15b-5p decreases the amount of USP31. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-15a-5p decreases the amount of USP31. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Formaldehyde increases the amount of USP31. 1 / 1
1 |

ctd
No evidence text available
Ethyl methanesulfonate increases the amount of USP31. 1 / 1
1 |

ctd
No evidence text available
Endosulfan affects USP31
1 |
Endosulfan increases the amount of USP31. 1 / 1
1 |

ctd
No evidence text available
Doxorubicin affects USP31
1 |
Doxorubicin decreases the amount of USP31. 1 / 1
1 |

ctd
No evidence text available
1 |
Cyclosporin A increases the amount of USP31. 1 / 1
1 |

ctd
No evidence text available
1 |
Crotonaldehyde decreases the amount of USP31. 1 / 1
1 |

ctd
No evidence text available
Copper(II) sulfate increases the amount of USP31. 1 / 1
1 |

ctd
No evidence text available
1 |
Cobalt dichloride decreases the amount of USP31. 1 / 1
1 |

ctd
No evidence text available
Butanal affects USP31
1 |
Butanal decreases the amount of USP31. 1 / 1
1 |

ctd
No evidence text available
Bisphenol A affects USP31
1 |
Bisphenol A decreases the amount of USP31. 1 / 1
1 |

ctd
No evidence text available
1 |
Benzo[a]pyrene decreases the amount of USP31. 1 / 1
1 |

ctd
No evidence text available
1 |

ctd
No evidence text available
Acetamide affects USP31
1 |
Acetamide decreases the amount of USP31. 1 / 1
1 |

ctd
No evidence text available
Abrine affects USP31
1 |
Abrine increases the amount of USP31. 1 / 1
1 |

ctd
No evidence text available
1 |
Zoledronic Acid increases the amount of USP31. 1 / 1
1 |

ctd
No evidence text available

eidos
For example , USP11 negatively regulates TNFalpha-induced NF-kappaB activation associated with IkappaBalpha and attenuates IkappaBalpha degradation [ 34 ] ; USP20 deubiquitinates TRAF6 and suppresses interleukin 1beta ( IL-1beta ) - and Tax-induced NF-kappaB activation [ 40 ] ; Katrin et al. showed that USP15 regulates IkappaBalpha / NF-kappaB by deubiquitinylation IkappaBalpha [ 44 ] ; and USP31 inhibits TNFalpha , CD40 , TRAF2 , TRAF6 and IKKbeta-mediated NF-kappaB activation [ 45 ] .
USP31 affects cell cycle
| 1
| 1

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We also observed that mutated USP31 could promote apoptosis but not cell cycle by flow cytometer analysis.
| 1

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We also observed that mutated USP31 could promote apoptosis but not cell cycle by flow cytometer analysis.
USP31 affects USP31
| 1
USP31 inhibits USP31. 1 / 1
| 1

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Overexpression of mutated USP31 could reverse the effect in USP31 knockdown cell line.
USP31 affects TNF
| 1
USP31 inhibits TNF. 1 / 1
| 1

eidos
For example , USP11 negatively regulates TNFalpha-induced NF-kappaB activation associated with IkappaBalpha and attenuates IkappaBalpha degradation [ 34 ] ; USP20 deubiquitinates TRAF6 and suppresses interleukin 1beta ( IL-1beta ) - and Tax-induced NF-kappaB activation [ 40 ] ; Katrin et al. showed that USP15 regulates IkappaBalpha / NF-kappaB by deubiquitinylation IkappaBalpha [ 44 ] ; and USP31 inhibits TNFalpha , CD40 , TRAF2 , TRAF6 and IKKbeta-mediated NF-kappaB activation [ 45 ] .
Tobacco Smoke Pollution increases the amount of USP31. 1 / 1
1 |

ctd
No evidence text available
T-2 Toxin affects USP31
1 |
T-2 Toxin decreases the amount of USP31. 1 / 1
1 |

ctd
No evidence text available
Smoke affects USP31
1 |
Smoke decreases the amount of USP31. 1 / 1
1 |

ctd
No evidence text available
PCB 180 affects USP31
1 |
PCB 180 decreases the amount of USP31. 1 / 1
1 |

ctd
No evidence text available
PAX4 affects USP31
1 |
PAX4 decreases the amount of USP31. 1 / 1
1 |

biopax:msigdb
No evidence text available
MYC affects USP31
1 |
MYC decreases the amount of USP31. 1 / 1
1 |

biopax:msigdb
No evidence text available
LEF1 affects USP31
1 |
LEF1 decreases the amount of USP31. 1 / 1
1 |

biopax:msigdb
No evidence text available
K 7174 affects USP31
1 |
K 7174 increases the amount of USP31. 1 / 1
1 |

ctd
No evidence text available
ESRRA affects USP31
1 |
ESRRA decreases the amount of USP31. 1 / 1
1 |

biopax:msigdb
No evidence text available
1 |
Dietary Sucrose increases the amount of USP31. 1 / 1
1 |

ctd
No evidence text available
1 |
Dietary Fats decreases the amount of USP31. 1 / 1
1 |

ctd
No evidence text available
Cuprizone affects USP31
1 |
Cuprizone decreases the amount of USP31. 1 / 1
1 |

ctd
No evidence text available
Antirheumatic Agents increases the amount of USP31. 1 / 1
1 |

ctd
No evidence text available
Acetylation affects USP31
| 1
| 1

eidos
Therefore , acetylation at Lys1264 suppresses USP31 activity and plays a protective role in cancer cell growth .
ARNT affects USP31
1 |
ARNT decreases the amount of USP31. 1 / 1
1 |

biopax:msigdb
No evidence text available
6-propyl-2-thiouracil decreases the amount of USP31. 1 / 1
1 |

ctd
No evidence text available
1 |

ctd
No evidence text available
17alpha-ethynylestradiol increases the amount of USP31. 1 / 1
1 |

ctd
No evidence text available
1-phenylpropan-2-amine decreases the amount of USP31. 1 / 1
1 |

ctd
No evidence text available
1 |

ctd
No evidence text available
2,4,4'-trichlorobiphenyl decreases the amount of USP31. 1 / 1
1 |

ctd
No evidence text available
1 |

ctd
No evidence text available
1 |

ctd
No evidence text available
1 |

ctd
No evidence text available