USP21 Data Analysis

HGNC Gene Name
ubiquitin specific peptidase 21
HGNC Gene Symbol
USP21
Identifiers
hgnc:12620 NCBIGene:27005 uniprot:Q9UK80
Orthologs
mgi:1353665 rgd:1588822
INDRA Statements
deubiquitinations all statements
Pathway Commons
Search for USP21
Number of Papers
73 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
SLAMF1 signaling lymphocytic activation molecule family member 1 0.283
LHX9 LIM homeobox 9 0.267
TAGLN2 transgelin 2 0.264
DEDD death effector domain containing 0.244
RUSC1 RUN and SH3 domain containing 1 0.239
THEM4 thioesterase superfamily member 4 0.235 Reactome (1)
SLAMF8 SLAM family member 8 0.231

Dependency GO Term Enrichment

Gene set enrichment analysis was done on the genes correlated with USP21using 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 USP21 using CRISPR-Cas9.

Knockout Differential Expression

Symbol Name log2-fold-change p-value p-value (adj.)
RPS24 ribosomal protein S24 4.95e-01 1.55e-06 3.42e-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 USP21 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
USP21 deubiquitinates NANOG. 2 / 2
| 1

reach
For example, Oct4 and Sox2 protein levels are regulated by the E3 ligase WWP2, and ubiquitin-specific-processing protease 21 (Usp21) deubiquitinates and stabilizes Nanog, which maintains pluripotency, while FBXW8, an E3 ligase, ubiquitinates and destabilizes Nanog, thereby promoting ESC differentiation.

ubibrowser
Review
USP21 deubiquitinates BAZ2A. 2 / 2
|

ubibrowser
Deubiquitinates BAZ2A/TIP5 leading to its stabilization

ubibrowser
No evidence text available
USP21 deubiquitinates RIPK1. 1 / 1
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ubibrowser
The contrast in the phenotype of the Usp21-knockout line with the previously characterized GATA3 and RIPK1 knockout mice strongly indicates that USP21 is redundant for the regulation of GATA3 and RIPK1 activity during mouse development, in hematopoietic stem cells, and in lymphocyte differentiation.
USP21 deubiquitinates IL33. 1 / 1
|

ubibrowser
Furthermore, depletion of USP21 reduces IL-33 protein levels and IL-33-mediated NF-kappaB p65 promoter activity.
USP21 deubiquitinates RIPK1 on K377. 1 / 1
1 |

biopax:reactome
No evidence text available
USP21 deubiquitinates DDX58. 1 / 1
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ubibrowser
Another study demonstrated that USP21 deubiquitinates RIG‐1, an essential protein in antiviral immune defense.
USP21 deubiquitinates STING1. 1 / 1
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ubibrowser
In this study, we found that USP21 is an important deubiquitinating enzyme for STING and that it negatively regulates the DNA virus-induced production of type I interferons by hydrolyzing K27/63-linked polyubiquitin chain on STING.
USP21 deubiquitinates H2AC20. 1 / 1
|

ubibrowser
Deubiquitinates histone H2A, a specific tag for epigenetic transcriptional repression, thereby acting as a coactivator.
USP21 deubiquitinates H2AC17. 1 / 1
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ubibrowser
In this study, we report that H2Aub markedly decreases in hepatocellular carcinoma. Usp21, a H2A deubiquitinase, is probably responsible for decrease in H2Aub.
USP21 deubiquitinates BRCA2. 1 / 1
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ubibrowser
Together, our findings identify deubiquitination as a means to regulate BRCA2 function and point to USP21 as a potential therapeutic target in BRCA2-proficient tumors.
USP21 deubiquitinates FOXM1. 1 / 1
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ubibrowser
We identified USP21 in an RNAi-based screen for deubiquitinases that control FOXM1 abundance.
USP21 deubiquitinates MAP2K2. 1 / 1
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ubibrowser
The deubiquitinase USP21 stabilizes MEK2 to promote tumor growth
USP21 deubiquitinates FOXP3. 1 / 1
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ubibrowser
USP21 stabilizes FOXP3 protein by mediating its deubiquitination and maintains the expression of Treg signature genes.
USP21 deubiquitinates SLCO6A1. 1 / 1
| 1

reach
Ub-GST was also efficiently deubiquitinated by USP2-3 incrementSRM.
USP21 deubiquitinates GATA3. 1 / 1
|

ubibrowser
Review
USP21 deubiquitinates H2AW on K120. 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

eidos
Therefore , USP21 stimulates cell proliferation but cannot cause cell death .

eidos
We identify that knockdown of USP21 inhibits cell proliferation , and overexpression of USP21 promotes cell growth .

eidos
These data demonstrate that USP21 promotes cell proliferation via its deubiquitinating active site .

eidos
USP21 Regulates the Expression of MAPK1 Through GATA3 and Affects Cell Proliferation , Migration , Invasion , and Stemness of GC Since USP21 stimulated cell proliferation , migration , invasion , and stemness of GC , and could stabilize the expression of GATA3 by deubiquitinating GATA3 , while MAPK1 was the transcription target of GATA3 , it was further verified whether USP21 could play its oncogenic effect in GC through the GATA3 / MAPK1 axis .

eidos
USP21 promotes cell proliferation , tumor progression , and colony formation , and enhances cancer stem cell self-renewal .

eidos
USP21 promotes cell proliferation via Cys-221 .

eidos
These results demonstrated that USP21 stimulated cell proliferation , migration , invasion , and stemness of GC cells .

eidos
USP21 knockdown or overexpression in the DLBCL cell line shows that USP21 promotes cell proliferation .

eidos
USP21 promotes cell proliferation by maintaining the EZH2 level in diffuse large B-cell lymphoma MA et al. Abstract Background Diffuse large B-cell lymphoma ( DLBCL ) is the most common category of non-Hodgkin lymphoma ( NHL ) .

eidos
These results demonstrated that USP21 stimulated cell proliferation , migration , invasion , and stemness of GC cells .

eidos
We reported that USP21 promoted GC cell proliferation , migration , invasion , and stemness in vitro , and regulated GC tumor growth and cell stemness in mice in vivo .

eidos
USP21 amplification can increase proliferation , migration , and invasion [ 64 ] .

eidos
USP21 Regulates the Expression of MAPK1 Through GATA3 and Affects Cell Proliferation , Migration , Invasion , and Stemness of GC Since USP21 stimulated cell proliferation , migration , invasion , and stemness of GC , and could stabilize the expression of GATA3 by deubiquitinating GATA3 , while MAPK1 was the transcription target of GATA3 , it was further verified whether USP21 could play its oncogenic effect in GC through the GATA3 / MAPK1 axis .
3 |
Pirinixic acid increases the amount of USP21.
1 |
Pirinixic acid increases the amount of USP21. 1 / 1
1 |

ctd
No evidence text available
Pirinixic acid decreases the amount of USP21.
1 |
Pirinixic acid decreases the amount of USP21. 1 / 1
1 |

ctd
No evidence text available
Pirinixic acid activates USP21.
1 |

ctd
No evidence text available
USP21 affects cell growth
| 2
| 2

eidos
Mechanistically , USP21 promotes cell growth by maintaining the EZH2 protein level .

eidos
Mechanistically , USP21 promotes cell growth by maintaining EZH2 protein level .
USP21 affects Neoplasms
| 1
| 1

eidos
USP21 promotes cell proliferation , tumor progression , and colony formation , and enhances cancer stem cell self-renewal .
USP21 affects Interferon
| 1
| 1

eidos
USP21 can interact directly with STING and remove the K27 and K63 Ub chains on STING , thereby inhibiting the production of type I interferons .
USP21 affects HIV-1
| 2
USP21 inhibits HIV-1. 2 / 2
| 2

eidos
Here , we demonstrate that the deubiquitinase , USP21 , potently inhibits HIV-1 production by indirectly downregulating the expression of HIV-1 trans-activator of transcription ( Tat ) , which is essential for transcriptional elongation in HIV-1 .

eidos
Here , we screened a series of USP members and found that USP21 inhibits HIV-1 production by specifically targeting Tat , but not the other HIV-1 accessory proteins .
USP21 affects DDX58
| 1
USP21 activates DDX58. 1 / 2
| 1

eidos
Ubiquitylation events are reversible processes , and , accordingly , severaldeubiquitylating enzymes , in particular ubiquitin specific peptidase 3 ( USP3 ) , USP21 and CYLD lysine 63 deubiquitinase ( CYLD ) , modulate RIG-I signalling by removing K63-polyubiquitin chains , although with unique kinetics ( reviewed elsewhere112 ,118 ) .
2 |
Plant Extracts increases the amount of USP21.
1 |
Plant Extracts increases the amount of USP21. 1 / 1
1 |

ctd
No evidence text available
Plant Extracts decreases the amount of USP21.
1 |
Plant Extracts decreases the amount of USP21. 1 / 1
1 |

ctd
No evidence text available
2,3,7,8-tetrachlorodibenzodioxine increases the amount of USP21.
1 |
1 |

ctd
No evidence text available
2,3,7,8-tetrachlorodibenzodioxine decreases the amount of USP21.
1 |
1 |

ctd
No evidence text available
Vinclozolin affects USP21
1 |
Vinclozolin increases the amount of USP21. 1 / 1
1 |

ctd
No evidence text available
1 |
Valproic acid decreases the amount of USP21. 1 / 1
1 |

ctd
No evidence text available
Tert-butyl hydroperoxide decreases the amount of USP21. 1 / 1
1 |

ctd
No evidence text available
Rotenone affects USP21
1 |
Rotenone decreases the amount of USP21. 1 / 1
1 |

ctd
No evidence text available
1 |

ctd
No evidence text available
Pentabromodiphenyl ether decreases the amount of USP21. 1 / 1
1 |

ctd
No evidence text available
Paracetamol affects USP21
1 |
Paracetamol decreases the amount of USP21. 1 / 1
1 |

ctd
No evidence text available
Methylazoxymethanol increases the amount of USP21. 1 / 1
1 |

ctd
No evidence text available
Ionomycin affects USP21
1 |
Ionomycin decreases the amount of USP21. 1 / 1
1 |

ctd
No evidence text available
1 |
Hsa-miR-93-5p decreases the amount of USP21. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-744-5p decreases the amount of USP21. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-671-5p decreases the amount of USP21. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-331-3p decreases the amount of USP21. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-32-5p decreases the amount of USP21. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
Hexabromocyclododecane increases the amount of USP21. 1 / 1
1 |

ctd
No evidence text available
Doxorubicin affects USP21
1 |
Doxorubicin decreases the amount of USP21. 1 / 1
1 |

ctd
No evidence text available
1 |
Dibutyl phthalate decreases the amount of USP21. 1 / 1
1 |

ctd
No evidence text available
Butanal affects USP21
1 |
Butanal decreases the amount of USP21. 1 / 1
1 |

ctd
No evidence text available
Bisphenol A affects USP21
1 |
Bisphenol A decreases the amount of USP21. 1 / 1
1 |

ctd
No evidence text available
Atrazine affects USP21
1 |
Atrazine increases the amount of USP21. 1 / 1
1 |

ctd
No evidence text available
Abrine affects USP21
1 |
Abrine increases the amount of USP21. 1 / 1
1 |

ctd
No evidence text available
ZIC1 affects USP21
1 |
ZIC1 decreases the amount of USP21. 1 / 1
1 |

biopax:msigdb
No evidence text available

eidos
Besides , USP21 could promote transcription by deubiquitylating ubH2A in vitro [ 46 ] .

eidos
We noted the upregulation of usp21 , which modulates the innate immune responses through inhibition of the NF-kappaB-signaling cascade , which leads to down-regulation of TNFalpha ( 69 ) .
USP21 affects cell cycle
| 1
| 1

eidos
18 , 19 USP21 can modulate cell cycle progression by deubiquitinating Forkhead box M1 ( FOXM1 ) in basal-like breast cancer .
| 1

eidos
Given the proapoptotic properties of p53 , it can be concluded that USP2-1 abates apoptosis by stabilizing MDM2 , MDMX , MDM4 , and FASN .
| 1

eidos
USP3 , USP21 and CYLD inhibit RIG-I K63-linked ubiquitination and activation .
USP21 affects SNHG16
| 1
USP21 activates SNHG16. 1 / 1
| 1

eidos
USP21 can further increase expression of SNHG16 ( Xu P. et al ., 2020 ) .
| PMC
USP21 affects NFkappaB
| 1
| 1

eidos
In addition , the ubiquitin-specific peptidase 21 ( USP21 ) inhibits NF-kappaB in the TNF pathway by deubiquitination of RIP1 [ 37 ] .
USP21 affects NFAT
| 1
USP21 increases the amount of NFAT. 1 / 1
| 1

reach
Mechanistically, they found that Usp16-mediated de-ubiquitination of calcineurin A, which is a calcium-activated phosphatase that dephosphorylates members of the nuclear factor of activated T cells (NFAT) family, leads to transcription of NFAT-targeted genes, which helps in the maintenance and proliferation of peripheral T cells [105].
| PMC
USP21 affects FOXP3
| 1
USP21 inhibits FOXP3. 1 / 1
| 1

eidos
USP21 prevents FOXP3 degradation through deubiquination , thus stabilizing Treg phenotype and antagonizing the development of Th1-like Tregs [ 65 ] .

eidos
Cell counting and 5-ethynyl-2 ' - deoxyuridine incorporation assays reveal that USP21 promotes the proliferation of cholangiocarcinoma .
SP1 affects USP21
1 |
SP1 decreases the amount of USP21. 1 / 1
1 |

biopax:msigdb
No evidence text available
PCBP1 affects USP21
1 |
PCBP1 decreases the amount of USP21. 1 / 1
1 |

biopax:msigdb
No evidence text available
USP21 is modified
| 1
USP21 is deubiquitinated. 1 / 1
| 1

trips
Deubiquitinating enzyme USP21 inhibits HIV-1 replication by downregulating Tat expression.
FOXP3 affects USP21
1 |
FOXP3 increases the amount of USP21. 1 / 1
1 |

trrust
No evidence text available
Cuprizone affects USP21
1 |
Cuprizone increases the amount of USP21. 1 / 1
1 |

ctd
No evidence text available
Antirheumatic Agents increases the amount of USP21. 1 / 1
1 |

ctd
No evidence text available
AZM551248 affects USP21
1 |
AZM551248 decreases the amount of USP21. 1 / 1
1 |

ctd
No evidence text available
1 |

ctd
No evidence text available
17alpha-ethynylestradiol increases the amount of USP21. 1 / 1
1 |

ctd
No evidence text available
1 |
(+)-JQ1 compound decreases the amount of USP21. 1 / 1
1 |

ctd
No evidence text available