General Information of the m6A Target Gene (ID: M6ATAR00394)
Target Name NAD-dependent protein deacetylase sirtuin-6 (SIRT6)
Synonyms
Regulatory protein SIR2 homolog 6; SIR2-like protein 6; SIR2L6
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Gene Name SIRT6
Chromosomal Location 19p13.3
Family sirtuin family; Class IV subfamily
Function
NAD-dependent protein deacetylase involved in various processes including telomere maintenance and gene expression, and consequently has roles in genomic stability, cell senescence and apoptosis . Has very weak deacetylase activity and can bind NAD(+) in the absence of acetylated substrate. Has deacetylase activity towards histone H3K9Ac and H3K56Ac. Modulates acetylation of histone H3 in telomeric chromatin during the S-phase of the cell cycle. May also be required for the association of WRN with telomeres during S-phase and for normal telomere maintenance. Deacetylates histone H3K9Ac at NF-kappa-B target promoters and may down-regulate the expression of a subset of NF-kappa-B target genes. Deacetylation of nucleosomes interferes with RELA binding to target DNA. Acts as a corepressor of the transcription factor Hif1a to control the expression of multiple glycolytic genes to regulate glucose homeostasis (By similarity). Required for normal IGF1 serum levels and normal glucose homeostasis (By similarity). Regulates the production of TNF protein (By similarity). Has a role in the regulation of life span (By similarity).
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Gene ID 51548
Uniprot ID
SIR6_HUMAN
HGNC ID
HGNC:14934
Ensembl Gene ID
ENSG00000077463
KEGG ID
hsa:51548
Full List of m6A Methylation Regulator of This Target Gene and Corresponding Disease/Drug Response(s)
SIRT6 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).
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Methyltransferase-like 14 (METTL14) [WRITER]
In total 1 item(s) under this regulator
Experiment 1 Reporting the m6A Methylation Regulator of This Target Gene [1]
Response Summary Methyltransferase-like 14 (Mettl14)-induced m6A modification participated in the regulation of USP48 in hepatocellular carcinoma by maintaining USP48 mRNA stability. This work uncovers the tumor-suppressive function of the Mettl14-USP48-NAD-dependent protein deacetylase sirtuin-6 (SIRT6) axis via modulation of glycolysis, providing new insights into the critical roles of metabolic activities in HCC and identifying an attractive target for future treatment studies.
Target Regulation Up regulation
Responsed Disease Hepatocellular carcinoma ICD-11: 2C12.02
Pathway Response Ubiquitin mediated proteolysis hsa04120
Glycolysis / Gluconeogenesis hsa00010
Cell Process Ubiquitination degradation
Glycolysis
In-vitro Model BEL-7404 Endocervical adenocarcinoma Homo sapiens CVCL_6568
Huh-7 Adult hepatocellular carcinoma Homo sapiens CVCL_0336
SK-HEP-1 Liver and intrahepatic bile duct epithelial neoplasm Homo sapiens CVCL_0525
SK-HEP-1 Liver and intrahepatic bile duct epithelial neoplasm Homo sapiens CVCL_0525
In-vivo Model Hepatocyte-specific knockout USP48 was obtained by crossing Alb-Cre mice with USP48flox/flox mice.
Liver cancer [ICD-11: 2C12]
In total 1 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [1]
Response Summary Methyltransferase-like 14 (Mettl14)-induced m6A modification participated in the regulation of USP48 in hepatocellular carcinoma by maintaining USP48 mRNA stability. This work uncovers the tumor-suppressive function of the Mettl14-USP48-NAD-dependent protein deacetylase sirtuin-6 (SIRT6) axis via modulation of glycolysis, providing new insights into the critical roles of metabolic activities in HCC and identifying an attractive target for future treatment studies.
Responsed Disease Hepatocellular carcinoma [ICD-11: 2C12.02]
Target Regulator Methyltransferase-like 14 (METTL14) WRITER
Target Regulation Up regulation
Pathway Response Ubiquitin mediated proteolysis hsa04120
Glycolysis / Gluconeogenesis hsa00010
Cell Process Ubiquitination degradation
Glycolysis
In-vitro Model BEL-7404 Endocervical adenocarcinoma Homo sapiens CVCL_6568
Huh-7 Adult hepatocellular carcinoma Homo sapiens CVCL_0336
SK-HEP-1 Liver and intrahepatic bile duct epithelial neoplasm Homo sapiens CVCL_0525
SK-HEP-1 Liver and intrahepatic bile duct epithelial neoplasm Homo sapiens CVCL_0525
In-vivo Model Hepatocyte-specific knockout USP48 was obtained by crossing Alb-Cre mice with USP48flox/flox mice.
References
Ref 1 USP48 Is Upregulated by Mettl14 to Attenuate Hepatocellular Carcinoma via Regulating SIRT6 Stabilization. Cancer Res. 2021 Jul 15;81(14):3822-3834. doi: 10.1158/0008-5472.CAN-20-4163. Epub 2021 Apr 26.