Ferroptosis Regulator Information

General Information of the Ferroptosis Regulator (ID: REG10312)
Regulator Name Legumain (LGMN)
Synonyms
PRSC1; Asparaginyl endopeptidase; Protease, cysteine 1
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Gene Name LGMN
Gene ID 5641
Regulator Type Protein coding
Uniprot ID Q99538
Sequence
MVWKVAVFLSVALGIGAVPIDDPEDGGKHWVVIVAGSNGWYNYRHQADACHAYQIIHRNG
IPDEQIVVMMYDDIAYSEDNPTPGIVINRPNGTDVYQGVPKDYTGEDVTPQNFLAVLRGD
AEAVKGIGSGKVLKSGPQDHVFIYFTDHGSTGILVFPNEDLHVKDLNETIHYMYKHKMYR
KMVFYIEACESGSMMNHLPDNINVYATTAANPRESSYACYYDEKRSTYLGDWYSVNWMED
SDVEDLTKETLHKQYHLVKSHTNTSHVMQYGNKTISTMKVMQFQGMKRKASSPVPLPPVT
HLDLTPSPDVPLTIMKRKLMNTNDLEESRQLTEEIQRHLDARHLIEKSVRKIVSLLAASE
AEVEQLLSERAPLTGHSCYPEALLHFRTHCFNWHSPTYEYALRHLYVLVNLCEKPYPLHR
IKLSMDHVCLGHY

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Family Peptidase C13 family
Function
Has a strict specificity for hydrolysis of asparaginyl bonds. Can also cleave aspartyl bonds slowly, especially under acidic conditions. Required for normal lysosomal protein degradation in renal proximal tubules. Required for normal degradation of internalized EGFR. Plays a role in the regulation of cell proliferation via its role in EGFR degradation. May be involved in the processing of proteins for MHC class II antigen presentation in the lysosomal/endosomal system.

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HGNC ID
HGNC:9472
KEGG ID hsa:5641
Full List of the Ferroptosis Target of This Regulator and Corresponding Disease/Drug Response(s)
LGMN 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).
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Phospholipid hydroperoxide glutathione peroxidase (GPX4) [Suppressor]
 Target Info 
In total 1 item(s) under this target
Experiment 1 Reporting the Ferroptosis Target of This Regulator [1]
Target for Ferroptosis Suppressor
Responsed Disease Acute kidney failure ICD-11: GB60
 Disease Info 
Responsed Drug RR-11a Investigative
 Drug Info 
Pathway Response Fatty acid metabolism hsa01212
Autophagy hsa04140
Cell Process Cell ferroptosis
Cell autophagy
In Vitro Model
 HK-2 cells Normal Homo sapiens CVCL_0302
In Vivo Model
The genetic background of embryonic stem cells and the Flp mice used in this experiment was C57BL/6. Mice were randomly separated into experimental groups and control groups. (1) Bilateral IRI: mice (male, 8-10 weeks old) on the lgmnKO background or littermate control mice were anesthetized by an intraperitoneal (i.p.) injection of chloral hydrate and placed on a warm pad to retain their body temperature. A bilateral flank incision was made, both sides of the renal vessels were occluded with clamps for 40 min followed by removing the clamps to induce blood reperfusion. The same procedure was performed in the control group without vessel clamping. (2) Nephrotoxic folic acid-induced AKI: mice (female, 12-14 weeks old) received a single i.p. injection of folic acid at 250 mg/kg in 0.3 mol/L sodium bicarbonate or the vehicle. For therapeutic experiments, RR-11a was freshly dissolved in saline. Mice were administered an i.p. injection of 20 mg/kg RR-11a or the vehicle before ischemia.

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Response regulation Legumain promotes chaperone-mediated autophagy of GPX4 therefore facilitates tubular ferroptosis in acute kidney injury (AKI). Legumain inhibitor RR-11a attenuates ferroptosis and tubular injury induced by ischemia-reperfusion injury (IRI).
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 Legumain (LGMN) Protein coding
 Regulator Info 
Responsed Drug RR-11a Investigative
 Drug Info 
Pathway Response Fatty acid metabolism hsa01212
Autophagy hsa04140
Cell Process Cell ferroptosis
Cell autophagy
In Vitro Model
 HK-2 cells Normal Homo sapiens CVCL_0302
In Vivo Model
The genetic background of embryonic stem cells and the Flp mice used in this experiment was C57BL/6. Mice were randomly separated into experimental groups and control groups. (1) Bilateral IRI: mice (male, 8-10 weeks old) on the lgmnKO background or littermate control mice were anesthetized by an intraperitoneal (i.p.) injection of chloral hydrate and placed on a warm pad to retain their body temperature. A bilateral flank incision was made, both sides of the renal vessels were occluded with clamps for 40 min followed by removing the clamps to induce blood reperfusion. The same procedure was performed in the control group without vessel clamping. (2) Nephrotoxic folic acid-induced AKI: mice (female, 12-14 weeks old) received a single i.p. injection of folic acid at 250 mg/kg in 0.3 mol/L sodium bicarbonate or the vehicle. For therapeutic experiments, RR-11a was freshly dissolved in saline. Mice were administered an i.p. injection of 20 mg/kg RR-11a or the vehicle before ischemia.

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Response regulation Legumain promotes chaperone-mediated autophagy of GPX4 therefore facilitates tubular ferroptosis in acute kidney injury (AKI). Legumain inhibitor RR-11a attenuates ferroptosis and tubular injury induced by ischemia-reperfusion injury (IRI).
RR-11a [Investigative]
 Drug Info 
In total 1 item(s) under this drug
Experiment 1 Reporting the Ferroptosis-centered Drug Response [1]
Drug for Ferroptosis Suppressor
Response Target Phospholipid hydroperoxide glutathione peroxidase (GPX4) Suppressor
 Target Info 
Responsed Disease Acute kidney failure ICD-11: GB60
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Autophagy hsa04140
Cell Process Cell ferroptosis
Cell autophagy
In Vitro Model
 HK-2 cells Normal Homo sapiens CVCL_0302
In Vivo Model
The genetic background of embryonic stem cells and the Flp mice used in this experiment was C57BL/6. Mice were randomly separated into experimental groups and control groups. (1) Bilateral IRI: mice (male, 8-10 weeks old) on the lgmnKO background or littermate control mice were anesthetized by an intraperitoneal (i.p.) injection of chloral hydrate and placed on a warm pad to retain their body temperature. A bilateral flank incision was made, both sides of the renal vessels were occluded with clamps for 40 min followed by removing the clamps to induce blood reperfusion. The same procedure was performed in the control group without vessel clamping. (2) Nephrotoxic folic acid-induced AKI: mice (female, 12-14 weeks old) received a single i.p. injection of folic acid at 250 mg/kg in 0.3 mol/L sodium bicarbonate or the vehicle. For therapeutic experiments, RR-11a was freshly dissolved in saline. Mice were administered an i.p. injection of 20 mg/kg RR-11a or the vehicle before ischemia.

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Response regulation Legumain promotes chaperone-mediated autophagy of GPX4 therefore facilitates tubular ferroptosis in acute kidney injury (AKI). Legumain inhibitor RR-11a attenuates ferroptosis and tubular injury induced by ischemia-reperfusion injury (IRI).
References
Ref 1 Legumain promotes tubular ferroptosis by facilitating chaperone-mediated autophagy of GPX4 in AKI. Cell Death Dis. 2021 Jan 11;12(1):65. doi: 10.1038/s41419-020-03362-4.