m6A Target Gene Information

General Information of the m6A Target Gene (ID: M6ATAR00444)
Target Name Serine/threonine-protein kinase ULK1 (ULK1/ATG1)
Synonyms
Autophagy-related protein 1 homolog; ATG1; hATG1; Unc-51-like kinase 1; KIAA0722
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Gene Name ULK1
Chromosomal Location 12q24.33
Family protein kinase superfamily; Ser/Thr protein kinase family; APG1/unc-51/ULK1 subfamily
Function
Serine/threonine-protein kinase involved in autophagy in response to starvation. Acts upstream of phosphatidylinositol 3-kinase PIK3C3 to regulate the formation of autophagophores, the precursors of autophagosomes. Part of regulatory feedback loops in autophagy: acts both as a downstream effector and negative regulator of mammalian target of rapamycin complex 1 (mTORC1) via interaction with RPTOR. Activated via phosphorylation by AMPK and also acts as a regulator of AMPK by mediating phosphorylation of AMPK subunits PRKAA1, PRKAB2 and PRKAG1, leading to negatively regulate AMPK activity. May phosphorylate ATG13/KIAA0652 and RPTOR; however such data need additional evidences. Plays a role early in neuronal differentiation and is required for granule cell axon formation. May also phosphorylate SESN2 and SQSTM1 to regulate autophagy. Phosphorylates FLCN, promoting autophagy. Phosphorylates AMBRA1 in response to autophagy induction, releasing AMBRA1 from the cytoskeletal docking site to induce autophagosome nucleation. Phosphorylates ATG4B, leading to inhibit autophagy by decreasing both proteolytic activation and delipidation activities of ATG4B.
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Gene ID 8408
Uniprot ID
ULK1_HUMAN
HGNC ID
HGNC:12558
Ensembl Gene ID
ENSG00000177169
KEGG ID
hsa:8408
Full List of m6A Methylation Regulator of This Target Gene and Corresponding Disease/Drug Response(s)
ULK1 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
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Fat mass and obesity-associated protein (FTO) [ERASER]
 Regulator Info 
Representative RNA-seq result indicating the expression of this target gene regulated by FTO
Cell Line 253J cell line Homo sapiens
Treatment: siFTO 253J cells
Control: 253J cells
 GSE150239
Regulation
logFC: -6.13E-01
p-value: 1.25E-06
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 The m6A changes caused by FTO influence the stability of ULK1 transcripts, likely through a YTHDF2-dependent manner.Under both basal and rapamycin-induced autophagy conditions, depletion of FTO significantly reduced the formation of GFP-LC3B puncta. The level of p62/SQSTM1 (an autophagy substrate) was higher in FTO-knockdown cells than that in control cells. FTO specifically upregulates the Serine/threonine-protein kinase ULK1 (ULK1) protein abundance. ULK1 mRNA undergoes m6A modification in the 3'-UTR and the m6A-marked ULK1 transcripts can further be targeted for degradation by YTHDF2.
Target Regulation Up regulation
Pathway Response Autophagy hsa04140
Cell Process RNA stability
Cell autophagy
In-vitro Model HEK293T Normal Homo sapiens CVCL_0063
HeLa Endocervical adenocarcinoma Homo sapiens CVCL_0030
Experiment 2 Reporting the m6A Methylation Regulator of This Target Gene [2]
Response Summary Knockdown of FTO reversed cisplatin resistance of SGC-7901/DDP cells both in vitro and in vivo, which was attributed to the inhibition of Serine/threonine-protein kinase ULK1 (ULK1)-mediated autophagy. These findings indicate that the FTO/ULK1 axis exerts crucial roles in cisplatin resistance of gastric cancer.
Target Regulation Up regulation
Responsed Disease Gastric cancer ICD-11: 2B72
 Disease Info 
Responsed Drug Cisplatin Approved
 Drug Info 
In-vitro Model GES-1 Normal Homo sapiens CVCL_EQ22
SGC-7901 Gastric carcinoma Homo sapiens CVCL_0520
In-vivo Model A total of 5 × 106 cells in 200 ul PBS were injected subcutaneously into the flanks of nude mice. After injection, cisplatin treatment was initiated on day 5. Mice were injected with 5 mg/kg cisplatin or PBS solution in the abdominal cavity once a week for 3?weeks.
Methyltransferase-like 14 (METTL14) [WRITER]
 Regulator Info 
Representative RNA-seq result indicating the expression of this target gene regulated by METTL14
Cell Line BMDM Mus musculus
Treatment: METTL14 knockout mice BMDM
Control: Wild type mice BMDM
 GSE153512
Regulation
logFC: 9.25E-01
p-value: 4.64E-14
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 [3]
Response Summary Linking mTORC1 signaling with m6A RNA methylation and demonstrates their roles in suppressing autophagy. Double-stranded RNA (dsRNA)-mediated depletion of either METTL3 or METTL14 increased the half-life of luciferase mRNA with either Serine/threonine-protein kinase ULK1 (ULK1/ATG1) or Atg8a 3' UTRs. WTAP stabilizes the interaction between the two METTL proteins, and RBM15/RBM15B have been proposed to recruit the MTC to its target transcripts.
Target Regulation Down regulation
Pathway Response mTOR signaling pathway hsa04150
Autophagy hsa04140
Cell Process Cell growth
Cell metabolism
In-vitro Model MCF-7 Invasive breast carcinoma Homo sapiens CVCL_0031
Methyltransferase-like 3 (METTL3) [WRITER]
 Regulator Info 
Representative RNA-seq result indicating the expression of this target gene regulated by METTL3
Cell Line LX2 cell line Homo sapiens
Treatment: shMETTL3 LX2 cells
Control: shLuc LX2 cells
 GSE207909
Regulation
logFC: 1.21E+00
p-value: 7.24E-41
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 [3]
Response Summary Linking mTORC1 signaling with m6A RNA methylation and demonstrates their roles in suppressing autophagy. Double-stranded RNA (dsRNA)-mediated depletion of either METTL3 or METTL14 increased the half-life of luciferase mRNA with either Serine/threonine-protein kinase ULK1 (ULK1/ATG1) or Atg8a 3' UTRs. WTAP stabilizes the interaction between the two METTL proteins, and RBM15/RBM15B have been proposed to recruit the MTC to its target transcripts.
Target Regulation Down regulation
Pathway Response mTOR signaling pathway hsa04150
Autophagy hsa04140
Cell Process Cell growth
Cell metabolism
In-vitro Model MCF-7 Invasive breast carcinoma Homo sapiens CVCL_0031
YTH domain-containing family protein 2 (YTHDF2) [READER]
 Regulator Info 
In total 1 item(s) under this regulator
Experiment 1 Reporting the m6A Methylation Regulator of This Target Gene [1]
Response Summary The m6A changes caused by FTO influence the stability of ULK1 transcripts, likely through a YTHDF2-dependent manner.Under both basal and rapamycin-induced autophagy conditions, depletion of FTO significantly reduced the formation of GFP-LC3B puncta. The level of p62/SQSTM1 (an autophagy substrate) was higher in FTO-knockdown cells than that in control cells. FTO specifically upregulates the Serine/threonine-protein kinase ULK1 (ULK1) protein abundance. ULK1 mRNA undergoes m6A modification in the 3'-UTR and the m6A-marked ULK1 transcripts can further be targeted for degradation by YTHDF2.
Target Regulation Up regulation
Pathway Response Autophagy hsa04140
Cell Process RNA stability
Cell autophagy
In-vitro Model HEK293T Normal Homo sapiens CVCL_0063
HeLa Endocervical adenocarcinoma Homo sapiens CVCL_0030
Gastric cancer [ICD-11: 2B72]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [2]
Response Summary Knockdown of FTO reversed cisplatin resistance of SGC-7901/DDP cells both in vitro and in vivo, which was attributed to the inhibition of Serine/threonine-protein kinase ULK1 (ULK1)-mediated autophagy. These findings indicate that the FTO/ULK1 axis exerts crucial roles in cisplatin resistance of gastric cancer.
Responsed Disease Gastric cancer [ICD-11: 2B72]
Target Regulator Fat mass and obesity-associated protein (FTO) ERASER
 Regulator Info 
Target Regulation Up regulation
Responsed Drug Cisplatin Approved
 Drug Info 
In-vitro Model GES-1 Normal Homo sapiens CVCL_EQ22
SGC-7901 Gastric carcinoma Homo sapiens CVCL_0520
In-vivo Model A total of 5 × 106 cells in 200 ul PBS were injected subcutaneously into the flanks of nude mice. After injection, cisplatin treatment was initiated on day 5. Mice were injected with 5 mg/kg cisplatin or PBS solution in the abdominal cavity once a week for 3?weeks.
Cisplatin [Approved]
 Drug Info 
In total 1 item(s) under this drug
Experiment 1 Reporting the m6A-centered Drug Response [2]
Response Summary Knockdown of FTO reversed cisplatin resistance of SGC-7901/DDP cells both in vitro and in vivo, which was attributed to the inhibition of Serine/threonine-protein kinase ULK1 (ULK1)-mediated autophagy. These findings indicate that the FTO/ULK1 axis exerts crucial roles in cisplatin resistance of gastric cancer.
Target Regulator Fat mass and obesity-associated protein (FTO) ERASER
 Regulator Info 
Target Regulation Up regulation
Responsed Disease Gastric cancer ICD-11: 2B72
 Disease Info 
In-vitro Model GES-1 Normal Homo sapiens CVCL_EQ22
SGC-7901 Gastric carcinoma Homo sapiens CVCL_0520
In-vivo Model A total of 5 × 106 cells in 200 ul PBS were injected subcutaneously into the flanks of nude mice. After injection, cisplatin treatment was initiated on day 5. Mice were injected with 5 mg/kg cisplatin or PBS solution in the abdominal cavity once a week for 3?weeks.
References
Ref 1 m(6)A RNA modification controls autophagy through upregulating ULK1 protein abundance. Cell Res. 2018 Sep;28(9):955-957. doi: 10.1038/s41422-018-0069-8. Epub 2018 Jul 25.
Ref 2 M(6) A demethylase fat mass and obesity-associated protein regulates cisplatin resistance of gastric cancer by modulating autophagy activation through ULK1. Cancer Sci. 2022 Jun 22. doi: 10.1111/cas.15469. Online ahead of print.
Ref 3 mTORC1-chaperonin CCT signaling regulates m(6)A RNA methylation to suppress autophagy. Proc Natl Acad Sci U S A. 2021 Mar 9;118(10):e2021945118. doi: 10.1073/pnas.2021945118.