Ferroptosis Regulator Information

General Information of the Ferroptosis Regulator (ID: REG10044)
Regulator Name Serine/threonine-protein kinase ULK1 (ULK1)
Synonyms
Autophagy-related protein 1 homolog; Unc-51-like kinase 1
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Gene Name ULK1
Gene ID 8408
Regulator Type Protein coding
Uniprot ID O75385
Sequence
MEPGRGGTETVGKFEFSRKDLIGHGAFAVVFKGRHREKHDLEVAVKCINKKNLAKSQTLL
GKEIKILKELKHENIVALYDFQEMANSVYLVMEYCNGGDLADYLHAMRTLSEDTIRLFLQ
QIAGAMRLLHSKGIIHRDLKPQNILLSNPAGRRANPNSIRVKIADFGFARYLQSNMMAAT
LCGSPMYMAPEVIMSQHYDGKADLWSIGTIVYQCLTGKAPFQASSPQDLRLFYEKNKTLV
PTIPRETSAPLRQLLLALLQRNHKDRMDFDEFFHHPFLDASPSVRKSPPVPVPSYPSSGS
GSSSSSSSTSHLASPPSLGEMQQLQKTLASPADTAGFLHSSRDSGGSKDSSCDTDDFVMV
PAQFPGDLVAEAPSAKPPPDSLMCSGSSLVASAGLESHGRTPSPSPPCSSSPSPSGRAGP
FSSSRCGASVPIPVPTQVQNYQRIERNLQSPTQFQTPRSSAIRRSGSTSPLGFARASPSP
PAHAEHGGVLARKMSLGGGRPYTPSPQVGTIPERPGWSGTPSPQGAEMRGGRSPRPGSSA
PEHSPRTSGLGCRLHSAPNLSDLHVVRPKLPKPPTDPLGAVFSPPQASPPQPSHGLQSCR
NLRGSPKLPDFLQRNPLPPILGSPTKAVPSFDFPKTPSSQNLLALLARQGVVMTPPRNRT
LPDLSEVGPFHGQPLGPGLRPGEDPKGPFGRSFSTSRLTDLLLKAAFGTQAPDPGSTESL
QEKPMEIAPSAGFGGSLHPGARAGGTSSPSPVVFTVGSPPSGSTPPQGPRTRMFSAGPTG
SASSSARHLVPGPCSEAPAPELPAPGHGCSFADPITANLEGAVTFEAPDLPEETLMEQEH
TEILRGLRFTLLFVQHVLEIAALKGSASEAAGGPEYQLQESVVADQISLLSREWGFAEQL
VLYLKVAELLSSGLQSAIDQIRAGKLCLSSTVKQVVRRLNELYKASVVSCQGLSLRLQRF
FLDKQRLLDRIHSITAERLIFSHAVQMVQSAALDEMFQHREGCVPRYHKALLLLEGLQHM
LSDQADIENVTKCKLCIERRLSALLTGICA

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Family Ser/Thr protein kinase family
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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HGNC ID
HGNC:12558
KEGG ID hsa:8408
Full List of the Ferroptosis Target of This Regulator and Corresponding Disease/Drug Response(s)
ULK1 can regulate the following target(s), and cause disease/drug response(s). You can browse detail information of target(s) or disease/drug response(s).
Browse Target
Browse Disease
Browse Drug
Ferritin heavy chain (FTH1) [Suppressor; Marker]
 Target Info 
In total 1 item(s) under this target
Experiment 1 Reporting the Ferroptosis Target of This Regulator [1]
Target for Ferroptosis Marker/Suppressor
Responsed Disease Renal dysfunction ICD-11: GB6Z
 Disease Info 
Responsed Drug Bisphenol A Investigative
 Drug Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Autophagy hsa04140
Cell Process Cell ferroptosis
Cell autophagy
Cell proliferation
In Vitro Model
 TCMK-1 cells Normal Mus musculus CVCL_2772
In Vivo Model
Balb/c mice aged 6-8 weeks were purchased from Liaoning Changsheng biotechnology co., Ltd. (Benxi, China). All animal experiments comply with the requirements of the Institutional Animal Care and Use Committee (IACUC) of Jilin University. The mice were housed in separate cages and given enough food and drinking water during the conditions of a 12-h light and dark cycle. The establishment of animal models is as previously described.

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Response regulation Renal dysfunction and renal tubular epithelial damage induced by Bisphenol A (BPA) are linked to ferroptosis, which depends on the activation of ferritinophagy through AMPK-mTOR- ULK1 axis. These findings revealed that after BPA treatment, FTH was significantly reduced and iron was accumulated.
Renal dysfunction [ICD-11: GB6Z]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response [1]
Target Regulator Serine/threonine-protein kinase ULK1 (ULK1) Protein coding
 Regulator Info 
Responsed Drug Bisphenol A Investigative
 Drug Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Autophagy hsa04140
Cell Process Cell ferroptosis
Cell autophagy
Cell proliferation
In Vitro Model
 TCMK-1 cells Normal Mus musculus CVCL_2772
In Vivo Model
Balb/c mice aged 6-8 weeks were purchased from Liaoning Changsheng biotechnology co., Ltd. (Benxi, China). All animal experiments comply with the requirements of the Institutional Animal Care and Use Committee (IACUC) of Jilin University. The mice were housed in separate cages and given enough food and drinking water during the conditions of a 12-h light and dark cycle. The establishment of animal models is as previously described.

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Response regulation Renal dysfunction and renal tubular epithelial damage induced by Bisphenol A (BPA) are linked to ferroptosis, which depends on the activation of ferritinophagy through AMPK-mTOR- ULK1 axis. These findings revealed that after BPA treatment, FTH was significantly reduced and iron was accumulated.
Bisphenol A [Investigative]
 Drug Info 
In total 1 item(s) under this drug
Experiment 1 Reporting the Ferroptosis-centered Drug Response [1]
Drug for Ferroptosis Inducer
Response Target Ferritin heavy chain (FTH1) Suppressor; Marker
 Target Info 
Responsed Disease Renal dysfunction ICD-11: GB6Z
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Autophagy hsa04140
Cell Process Cell ferroptosis
Cell autophagy
Cell proliferation
In Vitro Model
 TCMK-1 cells Normal Mus musculus CVCL_2772
In Vivo Model
Balb/c mice aged 6-8 weeks were purchased from Liaoning Changsheng biotechnology co., Ltd. (Benxi, China). All animal experiments comply with the requirements of the Institutional Animal Care and Use Committee (IACUC) of Jilin University. The mice were housed in separate cages and given enough food and drinking water during the conditions of a 12-h light and dark cycle. The establishment of animal models is as previously described.

    Click to Show/Hide
Response regulation Renal dysfunction and renal tubular epithelial damage induced by Bisphenol A (BPA) are linked to ferroptosis, which depends on the activation of ferritinophagy through AMPK-mTOR- ULK1 axis. These findings revealed that after BPA treatment, FTH was significantly reduced and iron was accumulated.
References
Ref 1 Ferritinophagy is involved in Bisphenol A-induced ferroptosis of renal tubular epithelial cells through the activation of the AMPK-mTOR-ULK1 pathway. Food Chem Toxicol. 2022 May;163:112909. doi: 10.1016/j.fct.2022.112909. Epub 2022 Mar 12.