Ferroptosis Regulator Information

General Information of the Ferroptosis Regulator (ID: REG10290)
Regulator Name Hamartin (TSC1)
Synonyms
KIAA0243, TSC; Tuberous sclerosis 1 protein
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Gene Name TSC1
Gene ID 7248
Regulator Type Protein coding
Uniprot ID Q92574
Sequence
MAQQANVGELLAMLDSPMLGVRDDVTAVFKENLNSDRGPMLVNTLVDYYLETSSQPALHI
LTTLQEPHDKHLLDRINEYVGKAATRLSILSLLGHVIRLQPSWKHKLSQAPLLPSLLKCL
KMDTDVVVLTTGVLVLITMLPMIPQSGKQHLLDFFDIFGRLSSWCLKKPGHVAEVYLVHL
HASVYALFHRLYGMYPCNFVSFLRSHYSMKENLETFEEVVKPMMEHVRIHPELVTGSKDH
ELDPRRWKRLETHDVVIECAKISLDPTEASYEDGYSVSHQISARFPHRSADVTTSPYADT
QNSYGCATSTPYSTSRLMLLNMPGQLPQTLSSPSTRLITEPPQATLWSPSMVCGMTTPPT
SPGNVPPDLSHPYSKVFGTTAGGKGTPLGTPATSPPPAPLCHSDDYVHISLPQATVTPPR
KEERMDSARPCLHRQHHLLNDRGSEEPPGSKGSVTLSDLPGFLGDLASEEDSIEKDKEEA
AISRELSEITTAEAEPVVPRGGFDSPFYRDSLPGSQRKTHSAASSSQGASVNPEPLHSSL
DKLGPDTPKQAFTPIDLPCGSADESPAGDRECQTSLETSIFTPSPCKIPPPTRVGFGSGQ
PPPYDHLFEVALPKTAHHFVIRKTEELLKKAKGNTEEDGVPSTSPMEVLDRLIQQGADAH
SKELNKLPLPSKSVDWTHFGGSPPSDEIRTLRDQLLLLHNQLLYERFKRQQHALRNRRLL
RKVIKAAALEEHNAAMKDQLKLQEKDIQMWKVSLQKEQARYNQLQEQRDTMVTKLHSQIR
QLQHDREEFYNQSQELQTKLEDCRNMIAELRIELKKANNKVCHTELLLSQVSQKLSNSES
VQQQMEFLNRQLLVLGEVNELYLEQLQNKHSDTTKEVEMMKAAYRKELEKNRSHVLQQTQ
RLDTSQKRILELESHLAKKDHLLLEQKKYLEDVKLQARGQLQAAESRYEAQKRITQVFEL
EILDLYGRLEKDGLLKKLEEEKAEAAEAAEERLDCCNDGCSDSMVGHNEEASGHNGETKT
PRPSSARGSSGSRGGGGSSSSSSELSTPEKPPHQRAGPFSSRWETTMGEASASIPTTVGS
LPSSKSFLGMKARELFRNKSESQCDEDGMTSSLSESLKTELGKDLGVEAKIPLNLDGPHP
SPPTPDSVGQLHIMDYNETHHEHS

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Function
In complex with TSC2, inhibits the nutrient-mediated or growth factor-stimulated phosphorylation of S6K1 and EIF4EBP1 by negatively regulating mTORC1 signaling. Seems not to be required for TSC2 GAP activity towards RHEB. Implicated as a tumor suppressor. Involved in microtubule-mediated protein transport, but this seems to be due to unregulated mTOR signaling. Acts as a co- chaperone for HSP90AA1 facilitating HSP90AA1 chaperoning of protein clients such as kinases, TSC2 and glucocorticoid receptor NR3C1. Increases ATP binding to HSP90AA1 and inhibits HSP90AA1 ATPase activity. Competes with the activating co-chaperone AHSA1 for binding to HSP90AA1, thereby providing a reciprocal regulatory mechanism for chaperoning of client proteins. Recruits TSC2 to HSP90AA1 and stabilizes TSC2 by preventing the interaction between TSC2 and ubiquitin ligase HERC1.

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HGNC ID
HGNC:12362
KEGG ID hsa:7248
Full List of the Ferroptosis Target of This Regulator and Corresponding Disease/Drug Response(s)
TSC1 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
Unspecific Target [Unspecific Target]
In total 1 item(s) under this target
Experiment 1 Reporting the Ferroptosis Target of This Regulator [1]
Responsed Disease Acute kidney failure ICD-11: GB60
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
 mTECs (Mouse tubular epithelial cells)
In Vivo Model
To induce AKI in mice, Tubule-Rheb1-/-, Tubule-Tsc1+/-and their control littermates aged between 8 and 10 weeks were injected with a single dose of 20 mg/kg cisplatin (cat: P4394, Sigma-Aldrich, St. Louis, MO) intraperitoneally. Mice were sacrificed at day 1, 2 and 3 after cisplatin administration, and mice in AKI models died before being sacrificed were excluded.

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Response regulation Haploinsufficiency for Tsc1 in tubular cells led to Rheb1 activation and mitigated cisplatin-induced cell death, mitochondrial defect and acute kidney injury (AKI).
Acute kidney failure [ICD-11: GB60]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response [1]
Target Regulator Hamartin (TSC1) Protein coding
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
 mTECs (Mouse tubular epithelial cells)
In Vivo Model
To induce AKI in mice, Tubule-Rheb1-/-, Tubule-Tsc1+/-and their control littermates aged between 8 and 10 weeks were injected with a single dose of 20 mg/kg cisplatin (cat: P4394, Sigma-Aldrich, St. Louis, MO) intraperitoneally. Mice were sacrificed at day 1, 2 and 3 after cisplatin administration, and mice in AKI models died before being sacrificed were excluded.

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Response regulation Haploinsufficiency for Tsc1 in tubular cells led to Rheb1 activation and mitigated cisplatin-induced cell death, mitochondrial defect and acute kidney injury (AKI).
References
Ref 1 Rheb1 protects against cisplatin-induced tubular cell death and acute kidney injury via maintaining mitochondrial homeostasis. Cell Death Dis. 2020 May 13;11(5):364. doi: 10.1038/s41419-020-2539-4.