m6A Target Gene Information

General Information of the m6A Target Gene (ID: M6ATAR00347)
Target Name E3 ubiquitin-protein ligase NEDD4-like (NEDD4L)
Synonyms
HECT-type E3 ubiquitin transferase NED4L; NEDD4.2; Nedd4-2; KIAA0439; NEDL3
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Gene Name NEDD4L
Chromosomal Location 18q21.31
Function
E3 ubiquitin-protein ligase which accepts ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfers the ubiquitin to targeted substrates. Inhibits TGF-beta signaling by triggering SMAD2 and TGFBR1 ubiquitination and proteasome-dependent degradation. Promotes ubiquitination and internalization of various plasma membrane channels such as ENaC, SCN2A/Nav1.2, SCN3A/Nav1.3, SCN5A/Nav1.5, SCN9A/Nav1.7, SCN10A/Nav1.8, KCNA3/Kv1.3, KCNH2, EAAT1, KCNQ2/Kv7.2, KCNQ3/Kv7.3 or CLC. Promotes ubiquitination and degradation of SGK1 and TNK2. Ubiquitinates BRAT1 and this ubiquitination is enhanced in the presence of NDFIP1. Plays a role in dendrite formation by melanocytes .
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Gene ID 23327
Uniprot ID
NED4L_HUMAN
HGNC ID
HGNC:7728
Ensembl Gene ID
ENSG00000049759
KEGG ID
hsa:23327
Full List of m6A Methylation Regulator of This Target Gene and Corresponding Disease/Drug Response(s)
NEDD4L 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
Fat mass and obesity-associated protein (FTO) [ERASER]
 Regulator Info 
In total 2 item(s) under this regulator
Experiment 1 Reporting the m6A Methylation Regulator of This Target Gene [1]
Response Summary FTO deletion inhibited arsenic-induced tumorigenesis. Epidermis-specific FTO deletion prevented skin tumorigenesis induced by arsenic and UVB irradiation. E3 ubiquitin-protein ligase NEDD4-like (NEDD4L) was identified as the m6A-modified gene target of FTO. Arsenic stabilizes FTO protein through inhibiting p62-mediated selective autophagy. FTO-mediated dysregulation of mRNA m6A methylation as an epitranscriptomic mechanism to promote arsenic tumorigenicity. Arsenic suppresses p62 expression by downregulating the NF-Kappa-B pathway to upregulate FTO.
Responsed Disease Solid tumour/cancer ICD-11: 2A00-2F9Z
 Disease Info 
Pathway Response Autophagy hsa04140
Cell Process Cellular Processes, Transport and catabolism
Cell autophagy
In-vitro Model HaCaT Normal Homo sapiens CVCL_0038
HEK293T Normal Homo sapiens CVCL_0063
HeLa Endocervical adenocarcinoma Homo sapiens CVCL_0030
MEF (Mouse embryonic fibroblasts)
In-vivo Model As cells (5 million) in Matrigel or As-T (1 million) cells in PBS with or without gene manipulations were injected subcutaneously into the right flanks of female mice (6-8 weeks of age). For treatment with CS1 or CS2, As-T cells (1 million) in PBS were injected subcutaneously into the right flanks of 6-week-old female nude mice.
Experiment 2 Reporting the m6A Methylation Regulator of This Target Gene [1]
Response Summary FTO deletion inhibited arsenic-induced tumorigenesis. Epidermis-specific FTO deletion prevented skin tumorigenesis induced by arsenic and UVB irradiation. E3 ubiquitin-protein ligase NEDD4-like (NEDD4L) was identified as the m6A-modified gene target of FTO. Arsenic stabilizes FTO protein through inhibiting p62-mediated selective autophagy. FTO-mediated dysregulation of mRNA m6A methylation as an epitranscriptomic mechanism to promote arsenic tumorigenicity. Arsenic suppresses p62 expression by downregulating the NF-Kappa-B pathway to upregulate FTO.
Responsed Disease Human skin lesions ICD-11: ME60
 Disease Info 
Pathway Response Autophagy hsa04140
Cell Process Cellular Processes, Transport and catabolism
Cell autophagy
In-vitro Model HaCaT Normal Homo sapiens CVCL_0038
HEK293T Normal Homo sapiens CVCL_0063
HeLa Endocervical adenocarcinoma Homo sapiens CVCL_0030
MEF (Mouse embryonic fibroblasts)
In-vivo Model As cells (5 million) in Matrigel or As-T (1 million) cells in PBS with or without gene manipulations were injected subcutaneously into the right flanks of female mice (6-8 weeks of age). For treatment with CS1 or CS2, As-T cells (1 million) in PBS were injected subcutaneously into the right flanks of 6-week-old female nude mice.
Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [1]
Response Summary FTO deletion inhibited arsenic-induced tumorigenesis. Epidermis-specific FTO deletion prevented skin tumorigenesis induced by arsenic and UVB irradiation. E3 ubiquitin-protein ligase NEDD4-like (NEDD4L) was identified as the m6A-modified gene target of FTO. Arsenic stabilizes FTO protein through inhibiting p62-mediated selective autophagy. FTO-mediated dysregulation of mRNA m6A methylation as an epitranscriptomic mechanism to promote arsenic tumorigenicity. Arsenic suppresses p62 expression by downregulating the NF-Kappa-B pathway to upregulate FTO.
Responsed Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
Target Regulator Fat mass and obesity-associated protein (FTO) ERASER
 Regulator Info 
Pathway Response Autophagy hsa04140
Cell Process Cellular Processes, Transport and catabolism
Cell autophagy
In-vitro Model HaCaT Normal Homo sapiens CVCL_0038
HEK293T Normal Homo sapiens CVCL_0063
HeLa Endocervical adenocarcinoma Homo sapiens CVCL_0030
MEF (Mouse embryonic fibroblasts)
In-vivo Model As cells (5 million) in Matrigel or As-T (1 million) cells in PBS with or without gene manipulations were injected subcutaneously into the right flanks of female mice (6-8 weeks of age). For treatment with CS1 or CS2, As-T cells (1 million) in PBS were injected subcutaneously into the right flanks of 6-week-old female nude mice.
Human skin lesions [ICD-11: ME60]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [1]
Response Summary FTO deletion inhibited arsenic-induced tumorigenesis. Epidermis-specific FTO deletion prevented skin tumorigenesis induced by arsenic and UVB irradiation. E3 ubiquitin-protein ligase NEDD4-like (NEDD4L) was identified as the m6A-modified gene target of FTO. Arsenic stabilizes FTO protein through inhibiting p62-mediated selective autophagy. FTO-mediated dysregulation of mRNA m6A methylation as an epitranscriptomic mechanism to promote arsenic tumorigenicity. Arsenic suppresses p62 expression by downregulating the NF-Kappa-B pathway to upregulate FTO.
Responsed Disease Human skin lesions [ICD-11: ME60]
Target Regulator Fat mass and obesity-associated protein (FTO) ERASER
 Regulator Info 
Pathway Response Autophagy hsa04140
Cell Process Cellular Processes, Transport and catabolism
Cell autophagy
In-vitro Model HaCaT Normal Homo sapiens CVCL_0038
HEK293T Normal Homo sapiens CVCL_0063
HeLa Endocervical adenocarcinoma Homo sapiens CVCL_0030
MEF (Mouse embryonic fibroblasts)
In-vivo Model As cells (5 million) in Matrigel or As-T (1 million) cells in PBS with or without gene manipulations were injected subcutaneously into the right flanks of female mice (6-8 weeks of age). For treatment with CS1 or CS2, As-T cells (1 million) in PBS were injected subcutaneously into the right flanks of 6-week-old female nude mice.
References
Ref 1 Autophagy of the m(6)A mRNA demethylase FTO is impaired by low-level arsenic exposure to promote tumorigenesis. Nat Commun. 2021 Apr 12;12(1):2183. doi: 10.1038/s41467-021-22469-6.