General Information of the m6A Target Gene (ID: M6ATAR00426)
Target Name Transcription factor EB (TFEB)
Synonyms
Class E basic helix-loop-helix protein 35; bHLHe35; BHLHE35
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Gene Name TFEB
Chromosomal Location 6p21.1
Family MiT/TFE family
Function
Transcription factor that acts as a master regulator of lysosomal biogenesis, autophagy, lysosomal exocytosis, lipid catabolism, energy metabolism and immune response. Specifically recognizes and binds E-box sequences (5'-CANNTG-3'); efficient DNA-binding requires dimerization with itself or with another MiT/TFE family member such as TFE3 or MITF. Involved in the cellular response to amino acid availability by acting downstream of MTOR: in the presence of nutrients, TFEB phosphorylation by MTOR promotes its cytosolic retention and subsequent inactivation. Upon starvation or lysosomal stress, inhibition of MTOR induces TFEB dephosphorylation, resulting in nuclear localization and transcription factor activity. Specifically recognizes and binds the CLEAR-box sequence (5'-GTCACGTGAC-3') present in the regulatory region of many lysosomal genes, leading to activate their expression, thereby playing a central role in expression of lysosomal genes. Regulates lysosomal positioning in response to nutrient deprivation by promoting the expression of PIP4P1. Acts as a positive regulator of autophagy by promoting expression of genes involved in autophagy. In association with TFE3, activates the expression of CD40L in T-cells, thereby playing a role in T-cell-dependent antibody responses in activated CD4(+) T-cells and thymus-dependent humoral immunity (By similarity). Specifically recognizes the gamma-E3 box, a subset of E-boxes, present in the heavy-chain immunoglobulin enhancer. Plays a role in the signal transduction processes required for normal vascularization of the placenta (By similarity). Involved in the immune response to infection by the bacteria S.aureus or S.enterica, acting downstream of protein kinase D (PKD), probably by regulating cytokine and chemokine expression (By similarity).
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Gene ID 7942
Uniprot ID
TFEB_HUMAN
HGNC ID
HGNC:11753
Ensembl Gene ID
ENSG00000112561
KEGG ID
hsa:7942
Full List of m6A Methylation Regulator of This Target Gene and Corresponding Disease/Drug Response(s)
TFEB 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
Methyltransferase-like 3 (METTL3) [WRITER]
Representative RNA-seq result indicating the expression of this target gene regulated by METTL3
Cell Line LNCaP cell line Homo sapiens
Treatment: shMETTL3 LNCaP cells
Control: shControl LNCaP cells
GSE147884
Regulation
logFC: -6.54E-01
p-value: 8.08E-07
More Results Click to View More RNA-seq Results
Representative RIP-seq result supporting the interaction between TFEB and the regulator
Cell Line MDA-MB-231 Homo sapiens
Regulation logFC: 8.22E+00 GSE60213
In total 1 item(s) under this regulator
Experiment 1 Reporting the m6A Methylation Regulator of This Target Gene [1]
Response Summary METTL3 methylates Transcription factor EB (TFEB), a master regulator of lysosomal biogenesis and autophagy genes, at two m6A residues in the 3'-UTR, which promotes the association of the RNA-binding protein HNRNPD with TFEB pre-mRNA and subsequently decreases the expression levels of TFEB. METTL3-ALKBH5 and autophagy, providing insight into the functional importance of the reversible mRNA m6A methylation and its modulators in ischemic heart disease.
Target Regulation Down regulation
Responsed Disease Ischemic heart disease ICD-11: BA40-BA6Z
Pathway Response Apoptosis hsa04210)
Cell Process Cell proliferation
In-vitro Model H9c2(2-1) Normal Rattus norvegicus CVCL_0286
HEK293T Normal Homo sapiens CVCL_0063
In-vivo Model To cause I/R injury, mice were subjected to 30 min of LAD ischemia followed by 60 min of reperfusion.
RNA demethylase ALKBH5 (ALKBH5) [ERASER]
Representative RNA-seq result indicating the expression of this target gene regulated by ALKBH5
Cell Line THP1 cell line Homo sapiens
Treatment: ALKBH5 knockdown THP1 cells
Control: Wild type THP1 cells
GSE128574
Regulation
logFC: -1.28E+00
p-value: 2.60E-04
More Results Click to View More RNA-seq Results
In total 1 item(s) under this regulator
Experiment 1 Reporting the m6A Methylation Regulator of This Target Gene [1]
Response Summary METTL3 methylates Transcription factor EB (TFEB), a master regulator of lysosomal biogenesis and autophagy genes, at two m6A residues in the 3'-UTR, which promotes the association of the RNA-binding protein HNRNPD with TFEB pre-mRNA and subsequently decreases the expression levels of TFEB. METTL3-ALKBH5 and autophagy, providing insight into the functional importance of the reversible mRNA m6A methylation and its modulators in ischemic heart disease.
Target Regulation Up regulation
Responsed Disease Ischemic heart disease ICD-11: BA40-BA6Z
Pathway Response Apoptosis hsa04210)
Cell Process Cell proliferation
In-vitro Model H9c2(2-1) Normal Rattus norvegicus CVCL_0286
HEK293T Normal Homo sapiens CVCL_0063
In-vivo Model To cause I/R injury, mice were subjected to 30 min of LAD ischemia followed by 60 min of reperfusion.
Ischemic heart disease [ICD-11: BA40-BA6Z]
In total 2 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [1]
Response Summary METTL3 methylates Transcription factor EB (TFEB), a master regulator of lysosomal biogenesis and autophagy genes, at two m6A residues in the 3'-UTR, which promotes the association of the RNA-binding protein HNRNPD with TFEB pre-mRNA and subsequently decreases the expression levels of TFEB. METTL3-ALKBH5 and autophagy, providing insight into the functional importance of the reversible mRNA m6A methylation and its modulators in ischemic heart disease.
Responsed Disease Ischemic heart disease [ICD-11: BA40-BA6Z]
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
Target Regulation Down regulation
Pathway Response Apoptosis hsa04210)
Cell Process Cell proliferation
In-vitro Model H9c2(2-1) Normal Rattus norvegicus CVCL_0286
HEK293T Normal Homo sapiens CVCL_0063
In-vivo Model To cause I/R injury, mice were subjected to 30 min of LAD ischemia followed by 60 min of reperfusion.
Experiment 2 Reporting the m6A-centered Disease Response [1]
Response Summary METTL3 methylates Transcription factor EB (TFEB), a master regulator of lysosomal biogenesis and autophagy genes, at two m6A residues in the 3'-UTR, which promotes the association of the RNA-binding protein HNRNPD with TFEB pre-mRNA and subsequently decreases the expression levels of TFEB. METTL3-ALKBH5 and autophagy, providing insight into the functional importance of the reversible mRNA m6A methylation and its modulators in ischemic heart disease.
Responsed Disease Ischemic heart disease [ICD-11: BA40-BA6Z]
Target Regulator RNA demethylase ALKBH5 (ALKBH5) ERASER
Target Regulation Up regulation
Pathway Response Apoptosis hsa04210)
Cell Process Cell proliferation
In-vitro Model H9c2(2-1) Normal Rattus norvegicus CVCL_0286
HEK293T Normal Homo sapiens CVCL_0063
In-vivo Model To cause I/R injury, mice were subjected to 30 min of LAD ischemia followed by 60 min of reperfusion.
References
Ref 1 METTL3 and ALKBH5 oppositely regulate m(6)A modification of TFEB mRNA, which dictates the fate of hypoxia/reoxygenation-treated cardiomyocytes. Autophagy. 2019 Aug;15(8):1419-1437. doi: 10.1080/15548627.2019.1586246. Epub 2019 Mar 17.