General Information of the Ferroptosis Regulator (ID: REG10370)
Regulator Name NADH-cytochrome b5 reductase 1 (CYB5R1)
Synonyms
NQO3A2; Humb5R2; NAD(P)H:quinone oxidoreductase type 3 polypeptide A2
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Gene Name CYB5R1
Gene ID 51706
Regulator Type Protein coding
Uniprot ID Q9UHQ9
Sequence
MGIQTSPVLLASLGVGLVTLLGLAVGSYLVRRSRRPQVTLLDPNEKYLLRLLDKTTVSHN
TKRFRFALPTAHHTLGLPVGKHIYLSTRIDGSLVIRPYTPVTSDEDQGYVDLVIKVYLKG
VHPKFPEGGKMSQYLDSLKVGDVVEFRGPSGLLTYTGKGHFNIQPNKKSPPEPRVAKKLG
MIAGGTGITPMLQLIRAILKVPEDPTQCFLLFANQTEKDIILREDLEELQARYPNRFKLW
FTLDHPPKDWAYSKGFVTADMIREHLPAPGDDVLVLLCGPPPMVQLACHPNLDKLGYSQK
MRFTY

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Family Flavoprotein pyridine nucleotide cytochrome reductase family
Function
NADH-cytochrome b5 reductases are involved in desaturation and elongation of fatty acids, cholesterol biosynthesis, drug metabolism, and, in erythrocyte, methemoglobin reduction.

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HGNC ID
HGNC:13397
KEGG ID hsa:51706
Full List of the Ferroptosis Target of This Regulator and Corresponding Disease/Drug Response(s)
CYB5R1 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 Injury of intra-abdominal organs ICD-11: NB91
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
HCT 116 cells Colon carcinoma Homo sapiens CVCL_0291
HT-1080 cells Fibrosarcoma Homo sapiens CVCL_0317
HeLa cells Endocervical adenocarcinoma Homo sapiens CVCL_0030
mEFs (Mouse embryonic fibroblasts)
HEK-293T cells Normal Homo sapiens CVCL_0063
OVCAR-8 cells High grade ovarian serous adenocarcinoma Homo sapiens CVCL_1629
In Vivo Model
Female nu/nu mice aged 4-5 weeks were obtained from Charles River. Luciferase expresing-OVCAR-8 cells were harvested by trypsinization. Subsequently, cells were washed three times with cold PBS and suspended in a 1:1 mixture of PBS and Matrigel (Corning). Each mouse was inoculated subcutaneously with 5 x 106 cells. When tumor volume reached approximately 50 mm3, mice were randomly divided into indicated groups. 20 mg PACMA31 per kg body weight (10% DMSO, 30% PEG-4000, 60% Saline); 40 mg regorafenib per kg body weight (Saline); or 20 mg PACMA31 plus 40 mg regorafenib per kg body weight daily. PACMA31 was intraperitoneally injected and regorafenib was orally administered.

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Response regulation Genetic knockout of POR and CYB5R1 decreases cellular hydrogen peroxide generation, preventing lipid peroxidation and ferroptosis. Moreover, POR knockdown in mice confers protective effects during acute liver injury (ALI) caused from ferroptosis.
Injury of intra-abdominal organs [ICD-11: NB91]
In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response [1]
Target Regulator NADH-cytochrome b5 reductase 1 (CYB5R1) Protein coding
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
HCT 116 cells Colon carcinoma Homo sapiens CVCL_0291
HT-1080 cells Fibrosarcoma Homo sapiens CVCL_0317
HeLa cells Endocervical adenocarcinoma Homo sapiens CVCL_0030
mEFs (Mouse embryonic fibroblasts)
HEK-293T cells Normal Homo sapiens CVCL_0063
OVCAR-8 cells High grade ovarian serous adenocarcinoma Homo sapiens CVCL_1629
In Vivo Model
Female nu/nu mice aged 4-5 weeks were obtained from Charles River. Luciferase expresing-OVCAR-8 cells were harvested by trypsinization. Subsequently, cells were washed three times with cold PBS and suspended in a 1:1 mixture of PBS and Matrigel (Corning). Each mouse was inoculated subcutaneously with 5 x 106 cells. When tumor volume reached approximately 50 mm3, mice were randomly divided into indicated groups. 20 mg PACMA31 per kg body weight (10% DMSO, 30% PEG-4000, 60% Saline); 40 mg regorafenib per kg body weight (Saline); or 20 mg PACMA31 plus 40 mg regorafenib per kg body weight daily. PACMA31 was intraperitoneally injected and regorafenib was orally administered.

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Response regulation Genetic knockout of POR and CYB5R1 decreases cellular hydrogen peroxide generation, preventing lipid peroxidation and ferroptosis. Moreover, POR knockdown in mice confers protective effects during acute liver injury (ALI) caused from ferroptosis.
References
Ref 1 Membrane Damage during Ferroptosis Is Caused by Oxidation of Phospholipids Catalyzed by the Oxidoreductases POR and CYB5R1. Mol Cell. 2021 Jan 21;81(2):355-369.e10. doi: 10.1016/j.molcel.2020.11.024. Epub 2020 Dec 14.