General Information of the m6A Target Gene (ID: M6ATAR00441)
Target Name Ubiquitin carboxyl-terminal hydrolase 7 (USP7)
Synonyms
Deubiquitinating enzyme 7; Herpesvirus-associated ubiquitin-specific protease; Ubiquitin thioesterase 7; Ubiquitin-specific-processing protease 7; HAUSP
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Gene Name USP7
Chromosomal Location 16p13.2
Family peptidase C19 family
Function
Hydrolase that deubiquitinates target proteins such as FOXO4, KAT5, p53/TP53, MDM2, ERCC6, DNMT1, UHRF1, PTEN, KMT2E/MLL5 and DAXX. Together with DAXX, prevents MDM2 self-ubiquitination and enhances the E3 ligase activity of MDM2 towards p53/TP53, thereby promoting p53/TP53 ubiquitination and proteasomal degradation. Deubiquitinates p53/TP53, preventing degradation of p53/TP53, and enhances p53/TP53-dependent transcription regulation, cell growth repression and apoptosis. Deubiquitinates p53/TP53 and MDM2 and strongly stabilizes p53/TP53 even in the presence of excess MDM2, and also induces p53/TP53-dependent cell growth repression and apoptosis. Deubiquitination of FOXO4 in presence of hydrogen peroxide is not dependent on p53/TP53 and inhibits FOXO4-induced transcriptional activity. In association with DAXX, is involved in the deubiquitination and translocation of PTEN from the nucleus to the cytoplasm, both processes that are counteracted by PML. Deubiquitinates KMT2E/MLL5 preventing KMT2E/MLL5 proteasomal-mediated degradation. Involved in cell proliferation during early embryonic development. Involved in transcription-coupled nucleotide excision repair (TC-NER) in response to UV damage: recruited to DNA damage sites following interaction with KIAA1530/UVSSA and promotes deubiquitination of ERCC6, preventing UV-induced degradation of ERCC6. Involved in maintenance of DNA methylation via its interaction with UHRF1 and DNMT1: acts by mediating deubiquitination of UHRF1 and DNMT1, preventing their degradation and promoting DNA methylation by DNMT1. Deubiquitinates alkylation repair enzyme ALKBH3. OTUD4 recruits USP7 and USP9X to stabilize ALKBH3, thereby promoting the repair of alkylated DNA lesions. Acts as a chromatin regulator via its association with the Polycomb group (PcG) multiprotein PRC1-like complex; may act by deubiquitinating components of the PRC1-like complex. Able to mediate deubiquitination of histone H2B; it is however unsure whether this activity takes place in vivo. Exhibits a preference towards 'Lys-48'-linked ubiquitin chains. Increases regulatory T-cells (Treg) suppressive capacity by deubiquitinating and stabilizing the transcription factor FOXP3 which is crucial for Treg cell function. Plays a role in the maintenance of the circadian clock periodicity via deubiquitination and stabilization of the CRY1 and CRY2 proteins. Deubiquitinates REST, thereby stabilizing REST and promoting the maintenance of neural progenitor cells. Deubiquitinates SIRT7, inhibiting SIRT7 histone deacetylase activity and regulating gluconeogenesis.; (Microbial infection) Contributes to the overall stabilization and trans-activation capability of the herpesvirus 1 trans-acting transcriptional protein ICP0/VMW110 during HSV-1 infection.
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Gene ID 7874
Uniprot ID
UBP7_HUMAN
HGNC ID
HGNC:12630
Ensembl Gene ID
ENSG00000187555
KEGG ID
hsa:7874
Full List of m6A Methylation Regulator of This Target Gene and Corresponding Disease/Drug Response(s)
USP7 can be regulated by the following regulator(s), and cause disease/drug response(s). You can browse detail information of regulator(s) or disease/drug response(s).
Browse Regulator
Browse Disease
Browse Drug
Methyltransferase-like 3 (METTL3) [WRITER]
Representative RNA-seq result indicating the expression of this target gene regulated by METTL3
Cell Line Liver Mus musculus
Treatment: Mettl3 knockout liver
Control: Wild type liver cells
GSE198513
Regulation
logFC: -7.46E-01
p-value: 2.02E-26
More Results Click to View More RNA-seq Results
In total 2 item(s) under this regulator
Experiment 1 Reporting the m6A Methylation Regulator of This Target Gene [1]
Response Summary METTL3 regulates the expression of Ubiquitin carboxyl-terminal hydrolase 7 (USP7) through m6A methylation and facilitate the invasion, migration and proliferation of HCC cells. Besides, the elevated METTL3 expression was related to worse overall survival.
Target Regulation Up regulation
Responsed Disease Hepatocellular carcinoma ICD-11: 2C12.02
Cell Process Cell invasion
Cell migration
Cell proliferation
In-vitro Model MHCC97-L Adult hepatocellular carcinoma Homo sapiens CVCL_4973
L-02 Endocervical adenocarcinoma Homo sapiens CVCL_6926
Huh-7 Adult hepatocellular carcinoma Homo sapiens CVCL_0336
Hep 3B2.1-7 Childhood hepatocellular carcinoma Homo sapiens CVCL_0326
HCCLM3 Adult hepatocellular carcinoma Homo sapiens CVCL_6832
In-vivo Model Male nu/nu mice between 4 and 6 weeks of age received subcutaneous injections of equivalent Hep3B cells expressing either LV-shMETTL3 or LV-USP7 within 30 min of harvesting on the right and left flanks. The tumor was weighed after approximately 4 weeks, and the volume was measured every 5 days.
Experiment 2 Reporting the m6A Methylation Regulator of This Target Gene [2]
Response Summary Ubiquitin carboxyl-terminal hydrolase 7 (USP7) was upregulated in HCC and associated with METTL3 level positively. USP7 silencing decreased proliferation, migration, and invasion rates of HCC cells. METTL3 promotes HCC to proliferate, migrate, and invade by regulating m6A methylation of USP7.
Target Regulation Up regulation
Responsed Disease Hepatocellular carcinoma ICD-11: 2C12.02
Cell Process Cell proliferate
Cell migrate
Cell invade
In-vitro Model MHCC97-L Adult hepatocellular carcinoma Homo sapiens CVCL_4973
L-02 Endocervical adenocarcinoma Homo sapiens CVCL_6926
Huh-7 Adult hepatocellular carcinoma Homo sapiens CVCL_0336
Hep 3B2.1-7 Childhood hepatocellular carcinoma Homo sapiens CVCL_0326
HCCLM3 Adult hepatocellular carcinoma Homo sapiens CVCL_6832
Fat mass and obesity-associated protein (FTO) [ERASER]
In total 2 item(s) under this regulator
Experiment 1 Reporting the m6A Methylation Regulator of This Target Gene [3]
Response Summary The m6A demethylase FTO promotes the growth of Non-small cell lung cancer cells by increasing the expression of USP7.Genetic knockdown or pharmacological inhibition (P5091 or P22027) of Ubiquitin carboxyl-terminal hydrolase 7 (USP7) reduced the proliferation rate of lung cancer cells and decreased the capacity of colony formation of lung cancer cells in vitro, whereas lung cancer cells growth inhibition by FTO knockdown is restored by overexertion of USP7.
Target Regulation Up regulation
Responsed Disease Non-small-cell lung carcinoma ICD-11: 2C25.Y
Responsed Drug P22077 Investigative
Cell Process Ubiquitination degradation
In-vitro Model A-549 Lung adenocarcinoma Homo sapiens CVCL_0023
NCI-H522 Lung adenocarcinoma Homo sapiens CVCL_1567
HSAEC (Human small airway epithelial cells)
RERF-LC-A1 Lung squamous cell carcinoma Homo sapiens CVCL_4402
NCI-H1882 Lung small cell carcinoma Homo sapiens CVCL_1504
NCl-H466 (Human lung cancer cell line)
In-vivo Model Equal numbers of A549 cells expressing either control or shFTO were injected subcutaneously, within 30 min of harvesting, over the right and left flanks in male nu/nu mice between 4 and 6 weeks of age.
Experiment 2 Reporting the m6A Methylation Regulator of This Target Gene [3]
Response Summary The m6A demethylase FTO promotes the growth of Non-small cell lung cancer cells by increasing the expression of USP7.Genetic knockdown or pharmacological inhibition (P5091 or P22027) of Ubiquitin carboxyl-terminal hydrolase 7 (USP7) reduced the proliferation rate of lung cancer cells and decreased the capacity of colony formation of lung cancer cells in vitro, whereas lung cancer cells growth inhibition by FTO knockdown is restored by overexertion of USP7.
Target Regulation Up regulation
Responsed Disease Non-small-cell lung carcinoma ICD-11: 2C25.Y
Responsed Drug P5091 Investigative
Cell Process Ubiquitination degradation
In-vitro Model A-549 Lung adenocarcinoma Homo sapiens CVCL_0023
NCI-H522 Lung adenocarcinoma Homo sapiens CVCL_1567
HSAEC (Human small airway epithelial cells)
RERF-LC-A1 Lung squamous cell carcinoma Homo sapiens CVCL_4402
NCI-H1882 Lung small cell carcinoma Homo sapiens CVCL_1504
NCl-H466 (Human lung cancer cell line)
In-vivo Model Equal numbers of A549 cells expressing either control or shFTO were injected subcutaneously, within 30 min of harvesting, over the right and left flanks in male nu/nu mice between 4 and 6 weeks of age.
Liver cancer [ICD-11: 2C12]
In total 2 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [1]
Response Summary METTL3 regulates the expression of Ubiquitin carboxyl-terminal hydrolase 7 (USP7) through m6A methylation and facilitate the invasion, migration and proliferation of HCC cells. Besides, the elevated METTL3 expression was related to worse overall survival.
Responsed Disease Hepatocellular carcinoma [ICD-11: 2C12.02]
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
Target Regulation Up regulation
Cell Process Cell invasion
Cell migration
Cell proliferation
In-vitro Model MHCC97-L Adult hepatocellular carcinoma Homo sapiens CVCL_4973
L-02 Endocervical adenocarcinoma Homo sapiens CVCL_6926
Huh-7 Adult hepatocellular carcinoma Homo sapiens CVCL_0336
Hep 3B2.1-7 Childhood hepatocellular carcinoma Homo sapiens CVCL_0326
HCCLM3 Adult hepatocellular carcinoma Homo sapiens CVCL_6832
In-vivo Model Male nu/nu mice between 4 and 6 weeks of age received subcutaneous injections of equivalent Hep3B cells expressing either LV-shMETTL3 or LV-USP7 within 30 min of harvesting on the right and left flanks. The tumor was weighed after approximately 4 weeks, and the volume was measured every 5 days.
Experiment 2 Reporting the m6A-centered Disease Response [2]
Response Summary Ubiquitin carboxyl-terminal hydrolase 7 (USP7) was upregulated in HCC and associated with METTL3 level positively. USP7 silencing decreased proliferation, migration, and invasion rates of HCC cells. METTL3 promotes HCC to proliferate, migrate, and invade by regulating m6A methylation of USP7.
Responsed Disease Hepatocellular carcinoma [ICD-11: 2C12.02]
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
Target Regulation Up regulation
Cell Process Cell proliferate
Cell migrate
Cell invade
In-vitro Model MHCC97-L Adult hepatocellular carcinoma Homo sapiens CVCL_4973
L-02 Endocervical adenocarcinoma Homo sapiens CVCL_6926
Huh-7 Adult hepatocellular carcinoma Homo sapiens CVCL_0336
Hep 3B2.1-7 Childhood hepatocellular carcinoma Homo sapiens CVCL_0326
HCCLM3 Adult hepatocellular carcinoma Homo sapiens CVCL_6832
Lung cancer [ICD-11: 2C25]
In total 2 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [3]
Response Summary The m6A demethylase FTO promotes the growth of Non-small cell lung cancer cells by increasing the expression of USP7.Genetic knockdown or pharmacological inhibition (P5091 or P22027) of Ubiquitin carboxyl-terminal hydrolase 7 (USP7) reduced the proliferation rate of lung cancer cells and decreased the capacity of colony formation of lung cancer cells in vitro, whereas lung cancer cells growth inhibition by FTO knockdown is restored by overexertion of USP7.
Responsed Disease Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Target Regulator Fat mass and obesity-associated protein (FTO) ERASER
Target Regulation Up regulation
Responsed Drug P22077 Investigative
Cell Process Ubiquitination degradation
In-vitro Model A-549 Lung adenocarcinoma Homo sapiens CVCL_0023
NCI-H522 Lung adenocarcinoma Homo sapiens CVCL_1567
HSAEC (Human small airway epithelial cells)
RERF-LC-A1 Lung squamous cell carcinoma Homo sapiens CVCL_4402
NCI-H1882 Lung small cell carcinoma Homo sapiens CVCL_1504
NCl-H466 (Human lung cancer cell line)
In-vivo Model Equal numbers of A549 cells expressing either control or shFTO were injected subcutaneously, within 30 min of harvesting, over the right and left flanks in male nu/nu mice between 4 and 6 weeks of age.
Experiment 2 Reporting the m6A-centered Disease Response [3]
Response Summary The m6A demethylase FTO promotes the growth of Non-small cell lung cancer cells by increasing the expression of USP7.Genetic knockdown or pharmacological inhibition (P5091 or P22027) of Ubiquitin carboxyl-terminal hydrolase 7 (USP7) reduced the proliferation rate of lung cancer cells and decreased the capacity of colony formation of lung cancer cells in vitro, whereas lung cancer cells growth inhibition by FTO knockdown is restored by overexertion of USP7.
Responsed Disease Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Target Regulator Fat mass and obesity-associated protein (FTO) ERASER
Target Regulation Up regulation
Responsed Drug P5091 Investigative
Cell Process Ubiquitination degradation
In-vitro Model A-549 Lung adenocarcinoma Homo sapiens CVCL_0023
NCI-H522 Lung adenocarcinoma Homo sapiens CVCL_1567
HSAEC (Human small airway epithelial cells)
RERF-LC-A1 Lung squamous cell carcinoma Homo sapiens CVCL_4402
NCI-H1882 Lung small cell carcinoma Homo sapiens CVCL_1504
NCl-H466 (Human lung cancer cell line)
In-vivo Model Equal numbers of A549 cells expressing either control or shFTO were injected subcutaneously, within 30 min of harvesting, over the right and left flanks in male nu/nu mice between 4 and 6 weeks of age.
P22077 [Investigative]
In total 1 item(s) under this drug
Experiment 1 Reporting the m6A-centered Drug Response [3]
Response Summary The m6A demethylase FTO promotes the growth of Non-small cell lung cancer cells by increasing the expression of USP7.Genetic knockdown or pharmacological inhibition (P5091 or P22027) of Ubiquitin carboxyl-terminal hydrolase 7 (USP7) reduced the proliferation rate of lung cancer cells and decreased the capacity of colony formation of lung cancer cells in vitro, whereas lung cancer cells growth inhibition by FTO knockdown is restored by overexertion of USP7.
Target Regulator Fat mass and obesity-associated protein (FTO) ERASER
Target Regulation Up regulation
Responsed Disease Non-small-cell lung carcinoma ICD-11: 2C25.Y
Cell Process Ubiquitination degradation
In-vitro Model A-549 Lung adenocarcinoma Homo sapiens CVCL_0023
NCI-H522 Lung adenocarcinoma Homo sapiens CVCL_1567
HSAEC (Human small airway epithelial cells)
RERF-LC-A1 Lung squamous cell carcinoma Homo sapiens CVCL_4402
NCI-H1882 Lung small cell carcinoma Homo sapiens CVCL_1504
NCl-H466 (Human lung cancer cell line)
In-vivo Model Equal numbers of A549 cells expressing either control or shFTO were injected subcutaneously, within 30 min of harvesting, over the right and left flanks in male nu/nu mice between 4 and 6 weeks of age.
P5091 [Investigative]
In total 1 item(s) under this drug
Experiment 1 Reporting the m6A-centered Drug Response [3]
Response Summary The m6A demethylase FTO promotes the growth of Non-small cell lung cancer cells by increasing the expression of USP7.Genetic knockdown or pharmacological inhibition (P5091 or P22027) of Ubiquitin carboxyl-terminal hydrolase 7 (USP7) reduced the proliferation rate of lung cancer cells and decreased the capacity of colony formation of lung cancer cells in vitro, whereas lung cancer cells growth inhibition by FTO knockdown is restored by overexertion of USP7.
Target Regulator Fat mass and obesity-associated protein (FTO) ERASER
Target Regulation Up regulation
Responsed Disease Non-small-cell lung carcinoma ICD-11: 2C25.Y
Cell Process Ubiquitination degradation
In-vitro Model A-549 Lung adenocarcinoma Homo sapiens CVCL_0023
NCI-H522 Lung adenocarcinoma Homo sapiens CVCL_1567
HSAEC (Human small airway epithelial cells)
RERF-LC-A1 Lung squamous cell carcinoma Homo sapiens CVCL_4402
NCI-H1882 Lung small cell carcinoma Homo sapiens CVCL_1504
NCl-H466 (Human lung cancer cell line)
In-vivo Model Equal numbers of A549 cells expressing either control or shFTO were injected subcutaneously, within 30 min of harvesting, over the right and left flanks in male nu/nu mice between 4 and 6 weeks of age.
References
Ref 1 METTL3 facilitates the progression of hepatocellular carcinoma by modulating the m6A level of USP7. Am J Transl Res. 2021 Dec 15;13(12):13423-13437. eCollection 2021.
Ref 2 Methyltransferase-like 3 Aggravates HCC Development via Mediating N6-Methyladenosine of Ubiquitin-Specific Protease 7. J Oncol. 2022 May 5;2022:6167832. doi: 10.1155/2022/6167832. eCollection 2022.
Ref 3 The m6A demethylase FTO promotes the growth of lung cancer cells by regulating the m6A level of USP7 mRNA. Biochem Biophys Res Commun. 2019 May 7;512(3):479-485. doi: 10.1016/j.bbrc.2019.03.093. Epub 2019 Mar 21.