USP53 Data Analysis

HGNC Gene Name
ubiquitin specific peptidase 53
HGNC Gene Symbol
USP53
Identifiers
hgnc:29255 NCBIGene:54532 uniprot:Q70EK8
Orthologs
mgi:2139607 rgd:1306615
INDRA Statements
deubiquitinations all statements
Pathway Commons
Search for USP53
Number of Papers
20 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
ADH5 alcohol dehydrogenase 5 (class III), chi polypeptide 0.278 0.10 0.49 3.48e-01
GNA14 G protein subunit alpha 14 -0.259
SMPDL3A sphingomyelin phosphodiesterase acid like 3A 0.255 0.00 -0.06 9.74e-01
WDFY4 WDFY family member 4 -0.24
GNAT3 G protein subunit alpha transducin 3 0.239
RUFY3 RUN and FYVE domain containing 3 0.23 -0.01 -0.13 9.56e-01
TMEM192 transmembrane protein 192 0.223 0.08 0.34 4.99e-01

Dependency GO Term Enrichment

Gene set enrichment analysis was done on the genes correlated with USP53using 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
GO:0031683 G-protein beta/gamma-subunit complex binding Molecular Function 1.58e-05 2.01e-03 9.31e-04
GO:0031234 extrinsic component of cytoplasmic side of plasma membrane Cellular Component 3.22e-04 4.09e-02 6.33e-03

Literature Mining

INDRA was used to automatically assemble known mechanisms related to USP53 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
USP53 deubiquitinates FKBP4. 1 / 1
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Mechanistically, USP53 deubiquitinates FKBP51, which in turn dephosphorylates AKT1, and ultimately inhibits tumor growth in lung adenocarcinoma.
USP53 leads to the deubiquitination of NFKBIA. 1 / 1
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As the expression of USP53 increases, the protein expression of IkappaBalpha was also gradually increased and USP53 reduced the ubiquitination of IkappaBalpha.

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
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Overexpression of USP53 promoted the osteogenic differentiation of hBMSCs in vitro.

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We hypothesized that USP53 may positively regulate the osteogenic differentiation of hBMSCs in vitro and that local delivery of AAV2-USP53 to calvarial defects would thus enhance bone formation.

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In addition, USP53 overexpression increased the level of active beta-catenin and enhanced the osteogenic differentiation of hBMSCs.

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Thus, USP53 positively regulated the osteogenic differentiation of hBMSCs.

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These results suggested that knockdown of USP53 decreased the osteogenic differentiation of hBMSCs.
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Knockdown of USP53 inhibited the osteogenic differentiation of hBMSCs in vitro.
USP53 affects CTNNB1
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USP53 activates CTNNB1.
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USP53 activates CTNNB1. 3 / 3
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Additionally, we confirmed that USP53 overexpression promoted osteogenesis in hBMSCs by activating the Wnt and beta-catenin signaling pathway in vitro and that USP53 bound with FBXO31 during the osteogenic differentiation of hBMSCs.

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In vitro ubiquitination assays showed that beta-catenin degradation was significantly reduced by USP53 overexpression in a concentration dependent manner, whereas downregulation of USP53 promoted the degradation of beta-catenin.

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Moreover, USP53 increased the half-life of active beta-catenin compared with that in the control group.
USP53 inhibits CTNNB1.
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USP53 bound to FBXO31 inhibits CTNNB1. 1 / 1
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Mass spectrometry showed that USP53 interacted with F-box only protein 31 (FBXO31) to promote proteasomal degradation of beta-catenin.
USP53 inhibits CTNNB1. 1 / 1
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In vitro ubiquitination assays showed that beta-catenin degradation was significantly reduced by USP53 overexpression in a concentration dependent manner, whereas downregulation of USP53 promoted the degradation of beta-catenin.
USP53 increases the amount of CTNNB1.
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USP53 increases the amount of CTNNB1. 1 / 1
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In addition, USP53 overexpression increased the level of active beta-catenin and enhanced the osteogenic differentiation of hBMSCs.
| 1 1 2
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USP53 also inhibits glycolysis, oxidative metabolism, and mitochondrial dynamics.

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USP53 promotes apoptosis and inhibits glycolysis in lung adenocarcinoma through FKBP51-AKT1 signaling.

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USP53 also inhibits glycolysis , oxidative metabolism , and mitochondrial dynamics .

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USP53 promotes apoptosis and inhibits glycolysis in lung adenocarcinoma through FKBP51-AKT1 signaling.
USP53 affects Cholestasis
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Previous studies identified a new type of normal-GGT cholestasis caused by autosomal recessive pathogenic variants in ubiquitin-specific peptidase 53 (USP53).
| PMC

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Here, we report a novel truncating mutation in the ubiquitin-specific peptidase gene ( USP53 ) causing low-γ-GT (GGT) cholestasis.

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Here, we report a novel truncating mutation in the ubiquitin-specific peptidase gene (USP53) causing low-gamma-GT (GGT) cholestasis.
| PMC

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However, we cannot be sure that hepatic hemangiomas are the specific symptom of cholestasis caused by mutations in USP53 gene because they are the most common benign liver tumor, the incidence of which ranges from 0.4% to 20% of the total population.
| PMC
Methylmercury chloride decreases the amount of USP53. 3 / 3
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CREB affects USP53
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CREB activates USP53. 3 / 3
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Our data (Fig.  xref C–E) have demonstrated the PTH-induced CREB activation of the Usp53 promoter.

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We then assessed the JUN-CREB activation of the Usp53 cloned fragment in Naca -knockdown cells.

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The transcriptional activation of the Usp53 promoter by CREB alone, CREB/JUN together or NACA/JUN/CREB combined was completely abolished following the overexpression of 100 ng of DN-PKA expression vector (Fig.  xref F).
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(+)-JQ1 compound increases the amount of USP53. 3 / 3
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Hsa-miR-16-5p decreases the amount of USP53. 2 / 2
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No evidence text available

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No evidence text available
Ethanol affects USP53
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Ethanol increases the amount of USP53. 2 / 2
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Dexamethasone increases the amount of USP53. 2 / 2
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No evidence text available
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USP53 also inhibits glycolysis, oxidative metabolism, and mitochondrial dynamics.

eidos
USP53 also inhibits glycolysis , oxidative metabolism , and mitochondrial dynamics .
| 1 1

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USP53 promotes apoptosis and inhibits glycolysis in lung adenocarcinoma through FKBP51-AKT1 signaling .

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USP53 promotes apoptosis and inhibits glycolysis in lung adenocarcinoma through FKBP51-AKT1 signaling.
USP53 affects SLPI
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USP53 activates SLPI. 2 / 2
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Additionally, knockdown of USP53 decreased ALP and Alizarin Red S staining intensity as well as ALP activity.

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Overexpression of USP53 enhanced ALP and Alizarin red S staining intensity as well as ALP activity.
| 1 1

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In addition , USP53 knockdown promoted ccRCC growth and metastasis .

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In addition, USP53 knockdown promoted ccRCC growth and metastasis.
USP53 affects GGT1
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USP53 activates GGT1. 2 / 2
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Here, we report a novel truncating mutation in the ubiquitin-specific peptidase gene ( USP53 ) causing low-γ-GT (GGT) cholestasis.

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Here, we report a novel truncating mutation in the ubiquitin-specific peptidase gene (USP53) causing low-gamma-GT (GGT) cholestasis.
| PMC
4,4'-sulfonyldiphenol increases the amount of USP53. 2 / 2
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No evidence text available

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No evidence text available
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Progesterone increases the amount of USP53.
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Progesterone increases the amount of USP53. 1 / 1
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No evidence text available
Progesterone decreases the amount of USP53.
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Progesterone decreases the amount of USP53. 1 / 1
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No evidence text available
Cisplatin affects USP53
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Cisplatin increases the amount of USP53.
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Cisplatin increases the amount of USP53. 1 / 1
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No evidence text available
Cisplatin decreases the amount of USP53.
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Cisplatin decreases the amount of USP53. 1 / 1
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No evidence text available
Bisphenol A affects USP53
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Bisphenol A increases the amount of USP53.
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Bisphenol A increases the amount of USP53. 1 / 1
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No evidence text available
Bisphenol A decreases the amount of USP53.
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Bisphenol A decreases the amount of USP53. 1 / 1
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No evidence text available
Abrine affects USP53
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Abrine increases the amount of USP53.
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Abrine increases the amount of USP53. 1 / 1
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Abrine decreases the amount of USP53.
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Abrine decreases the amount of USP53. 1 / 1
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USP53 affects Mice
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USP53 inhibits Mice.
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USP53 inhibits Mice. 1 / 1
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USP53 encodes a protein of uncertain function and USP53 deficiency causes deafness in mice.
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USP53 activates Mice.
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USP53 activates Mice. 1 / 1
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USP53 encodes a protein of uncertain function and USP53 deficiency causes deafness in mice.
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USP53 affects Deafness
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USP53 inhibits Deafness.
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USP53 encodes a protein of uncertain function and USP53 deficiency causes deafness in mice.
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USP53 activates Deafness.
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USP53 encodes a protein of uncertain function and USP53 deficiency causes deafness in mice.
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2,3,7,8-tetrachlorodibenzodioxine increases the amount of USP53.
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2,3,7,8-tetrachlorodibenzodioxine decreases the amount of USP53.
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No evidence text available
Vorinostat affects USP53
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Vorinostat increases the amount of USP53. 1 / 1
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No evidence text available
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Valproic acid increases the amount of USP53. 1 / 1
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Urethane affects USP53
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Urethane increases the amount of USP53. 1 / 1
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Trichostatin A increases the amount of USP53. 1 / 1
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Thioacetamide increases the amount of USP53. 1 / 1
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Silicon dioxide decreases the amount of USP53. 1 / 1
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AMP-activated protein kinase inhibitor reverses the effects of USP53 knockdown.
Peptidase affects USP53
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Retinol binding protein 1 (RBP1) mRNA was upregulated by 2.6-fold in OF, and ubiquitin specific peptidase 53 (USP53) was upregulated by 2.3-fold.
Paracetamol affects USP53
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Paracetamol increases the amount of USP53. 1 / 1
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No evidence text available
Pantogab affects USP53
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Pantogab increases the amount of USP53. 1 / 1
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No evidence text available
Mercury(0) affects USP53
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Mercury(0) decreases the amount of USP53. 1 / 1
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No evidence text available
Melphalan affects USP53
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Melphalan decreases the amount of USP53. 1 / 1
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No evidence text available
Jinfukang affects USP53
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Jinfukang decreases the amount of USP53. 1 / 1
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No evidence text available
Indometacin affects USP53
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Indometacin increases the amount of USP53. 1 / 1
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No evidence text available
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Hsa-miR-876-3p decreases the amount of USP53. 1 / 1
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No evidence text available
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Hsa-miR-6838-5p decreases the amount of USP53. 1 / 1
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No evidence text available
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Hsa-miR-6806-5p decreases the amount of USP53. 1 / 1
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No evidence text available
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Hsa-miR-6792-5p decreases the amount of USP53. 1 / 1
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No evidence text available
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Hsa-miR-6757-3p decreases the amount of USP53. 1 / 1
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No evidence text available
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Hsa-miR-6504-3p decreases the amount of USP53. 1 / 1
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No evidence text available
Hsa-miR-646 affects USP53
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Hsa-miR-646 decreases the amount of USP53. 1 / 1
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No evidence text available
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Hsa-miR-5685 decreases the amount of USP53. 1 / 1
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No evidence text available
Hsa-miR-559 affects USP53
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Hsa-miR-559 decreases the amount of USP53. 1 / 1
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No evidence text available
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Hsa-miR-548y decreases the amount of USP53. 1 / 1
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No evidence text available
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Hsa-miR-548w decreases the amount of USP53. 1 / 1
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No evidence text available
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Hsa-miR-548o-5p decreases the amount of USP53. 1 / 1
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No evidence text available
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Hsa-miR-548j-5p decreases the amount of USP53. 1 / 1
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No evidence text available
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Hsa-miR-548i decreases the amount of USP53. 1 / 1
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No evidence text available
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Hsa-miR-548h-5p decreases the amount of USP53. 1 / 1
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No evidence text available
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Hsa-miR-548d-5p decreases the amount of USP53. 1 / 1
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No evidence text available
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Hsa-miR-548c-5p decreases the amount of USP53. 1 / 1
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No evidence text available
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Hsa-miR-548bb-5p decreases the amount of USP53. 1 / 1
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No evidence text available
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Hsa-miR-548b-5p decreases the amount of USP53. 1 / 1
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No evidence text available
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Hsa-miR-548ay-5p decreases the amount of USP53. 1 / 1
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No evidence text available
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Hsa-miR-548au-5p decreases the amount of USP53. 1 / 1
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No evidence text available
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Hsa-miR-548as-5p decreases the amount of USP53. 1 / 1
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No evidence text available
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Hsa-miR-548ar-5p decreases the amount of USP53. 1 / 1
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No evidence text available
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Hsa-miR-548aq-5p decreases the amount of USP53. 1 / 1
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No evidence text available
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Hsa-miR-548ap-5p decreases the amount of USP53. 1 / 1
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No evidence text available
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Hsa-miR-548am-5p decreases the amount of USP53. 1 / 1
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No evidence text available
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Hsa-miR-548ak decreases the amount of USP53. 1 / 1
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No evidence text available
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Hsa-miR-548ae-5p decreases the amount of USP53. 1 / 1
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No evidence text available
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Hsa-miR-548ad-5p decreases the amount of USP53. 1 / 1
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No evidence text available
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Hsa-miR-548ab decreases the amount of USP53. 1 / 1
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No evidence text available
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Hsa-miR-548a-5p decreases the amount of USP53. 1 / 1
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No evidence text available
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Hsa-miR-545-3p decreases the amount of USP53. 1 / 1
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No evidence text available
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Hsa-miR-503-5p decreases the amount of USP53. 1 / 1
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No evidence text available
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Hsa-miR-497-5p decreases the amount of USP53. 1 / 1
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No evidence text available
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Hsa-miR-497-3p decreases the amount of USP53. 1 / 1
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No evidence text available
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Hsa-miR-4690-3p decreases the amount of USP53. 1 / 1
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No evidence text available
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Hsa-miR-4524b-5p decreases the amount of USP53. 1 / 1
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No evidence text available
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Hsa-miR-4524a-5p decreases the amount of USP53. 1 / 1
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No evidence text available
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Hsa-miR-4456 decreases the amount of USP53. 1 / 1
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No evidence text available
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Hsa-miR-424-5p decreases the amount of USP53. 1 / 1
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No evidence text available
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Hsa-miR-3973 decreases the amount of USP53. 1 / 1
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No evidence text available
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Hsa-miR-374b-3p decreases the amount of USP53. 1 / 1
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No evidence text available
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Hsa-miR-323a-5p decreases the amount of USP53. 1 / 1
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No evidence text available
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Hsa-miR-3120-3p decreases the amount of USP53. 1 / 1
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No evidence text available
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Hsa-miR-30b-5p decreases the amount of USP53. 1 / 1
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No evidence text available
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Hsa-miR-200a-3p decreases the amount of USP53. 1 / 1
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No evidence text available
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Hsa-miR-195-5p decreases the amount of USP53. 1 / 1
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No evidence text available
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Hsa-miR-186-3p decreases the amount of USP53. 1 / 1
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No evidence text available
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Hsa-miR-15b-5p decreases the amount of USP53. 1 / 1
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No evidence text available
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Hsa-miR-15a-5p decreases the amount of USP53. 1 / 1
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No evidence text available
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Hsa-miR-141-3p decreases the amount of USP53. 1 / 1
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No evidence text available
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Formaldehyde increases the amount of USP53. 1 / 1
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No evidence text available
Folic acid affects USP53
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Folic acid increases the amount of USP53. 1 / 1
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No evidence text available
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Fluoranthene increases the amount of USP53. 1 / 1
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No evidence text available
Dioxygen affects USP53
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Dioxygen increases the amount of USP53. 1 / 1
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No evidence text available
Dicrotophos affects USP53
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Dicrotophos decreases the amount of USP53. 1 / 1
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No evidence text available
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Dibutyl phthalate increases the amount of USP53. 1 / 1
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No evidence text available
Copper atom affects USP53
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Copper atom increases the amount of USP53. 1 / 1
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No evidence text available
Calcitriol affects USP53
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Calcitriol increases the amount of USP53. 1 / 1
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No evidence text available
Bortezomib affects USP53
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Bortezomib increases the amount of USP53. 1 / 1
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No evidence text available
Bisphenol F affects USP53
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Bisphenol F increases the amount of USP53. 1 / 1
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No evidence text available
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Aluminium atom decreases the amount of USP53. 1 / 1
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No evidence text available
All-trans-retinoic acid increases the amount of USP53. 1 / 1
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No evidence text available
Acrylamide affects USP53
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Acrylamide increases the amount of USP53. 1 / 1
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No evidence text available
Ubiquitin affects USP53
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Retinol binding protein 1 (RBP1) mRNA was upregulated by 2.6-fold in OF, and ubiquitin specific peptidase 53 (USP53) was upregulated by 2.3-fold.
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Our study reveals that USP53 is activated by H3K27 acetylation and suppresses ESCA progression by regulating cell growth and metabolism.
USP53 affects estrogen
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Furthermore, the roles of USP53 in osteoporosis were examined in an OVX mouse model to induce estrogen deficiency related osteoporosis.

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Transient depletion of USP12, USP46, and USP53 did not induce a senescence arrest.

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USP53 suppresses the proliferation and growth of ESCA cells in vitro and in vivo, whereas its knockdown exerts opposite effects.
USP53 affects cell growth
| 1
| 1

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Our study reveals that USP53 is activated by H3K27 acetylation and suppresses ESCA progression by regulating cell growth and metabolism.
USP53 affects Wnt
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USP53 activates Wnt. 1 / 1
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Additionally, we confirmed that USP53 overexpression promoted osteogenesis in hBMSCs by activating the Wnt and beta-catenin signaling pathway in vitro and that USP53 bound with FBXO31 during the osteogenic differentiation of hBMSCs.
USP53 affects NACA
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USP53 activates NACA. 1 / 1
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Using ChIP-Seq against NACA in parallel with RNA sequencing, we report the identification of Ubiquitin Specific Peptidase 53 (Usp53) as a target gene of PTH activated NACA in osteoblasts.

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USP53 also inhibits glycolysis , oxidative metabolism , and mitochondrial dynamics .
USP53 affects Bglap2
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USP53 decreases the amount of Bglap2. 1 / 1
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Usp53 knockdown in ST2 stromal cells stimulated expression of the osteoblastic markers Bglap2 (Osteocalcin) and Alpl (Alkaline phosphatase) and inhibited expression of the adipogenic markers Pparg and Cebpa.
USP53 affects ALPL
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USP53 decreases the amount of ALPL. 1 / 1
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Usp53 knockdown in ST2 stromal cells stimulated expression of the osteoblastic markers Bglap2 (Osteocalcin) and Alpl (Alkaline phosphatase) and inhibited expression of the adipogenic markers Pparg and Cebpa.

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Additionally, knockdown of USP53 decreased ALP and Alizarin Red S staining intensity as well as ALP activity.
Tobacco Smoke Pollution increases the amount of USP53. 1 / 1
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No evidence text available
PTH affects USP53
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PTH activates USP53. 1 / 1
| 1

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The mutation abrogated the PTH-induced activation of the cloned Usp53 fragment, resulting in > 50% reduction in the promoter activity (Fig.  xref A, grey bars ).
NSC 689534 affects USP53
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NSC 689534 increases the amount of USP53. 1 / 1
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No evidence text available
JUN_family affects USP53
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We then assessed the JUN-CREB activation of the Usp53 cloned fragment in Naca -knockdown cells.
GSK-J4 affects USP53
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GSK-J4 increases the amount of USP53. 1 / 1
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No evidence text available

eidos
AMP-activated protein kinase inhibitor reverses the effects of USP53 knockdown .
Cuprizone affects USP53
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Cuprizone increases the amount of USP53. 1 / 1
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No evidence text available
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Air Pollutants decreases the amount of USP53. 1 / 1
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No evidence text available
AMPK affects USP53
| 1
AMPK inhibits USP53. 1 / 1
| 1

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AMP-activated protein kinase inhibitor reverses the effects of USP53 knockdown.
4-hydroxyphenyl retinamide increases the amount of USP53. 1 / 1
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No evidence text available
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No evidence text available
1 |

ctd
No evidence text available
1-methylanthracene increases the amount of USP53. 1 / 1
1 |

ctd
No evidence text available
4,4'-diaminodiphenylmethane decreases the amount of USP53. 1 / 1
1 |

ctd
No evidence text available
1 |

ctd
No evidence text available