Ferroptosis Regulator Information

General Information of the Ferroptosis Regulator (ID: REG10169)
Regulator Name Aldehyde dehydrogenase family 3 member A2 (ALDH3A2)
Synonyms
Aldehyde dehydrogenase 10; Fatty aldehyde dehydrogenase; Microsomal aldehyde dehydrogenase
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Gene Name ALDH3A2
Gene ID 224
Regulator Type Protein coding
Uniprot ID P51648
Sequence
MELEVRRVRQAFLSGRSRPLRFRLQQLEALRRMVQEREKDILTAIAADLCKSEFNVYSQE
VITVLGEIDFMLENLPEWVTAKPVKKNVLTMLDEAYIQPQPLGVVLIIGAWNYPFVLTIQ
PLIGAIAAGNAVIIKPSELSENTAKILAKLLPQYLDQDLYIVINGGVEETTELLKQRFDH
IFYTGNTAVGKIVMEAAAKHLTPVTLELGGKSPCYIDKDCDLDIVCRRITWGKYMNCGQT
CIAPDYILCEASLQNQIVWKIKETVKEFYGENIKESPDYERIINLRHFKRILSLLEGQKI
AFGGETDEATRYIAPTVLTDVDPKTKVMQEEIFGPILPIVPVKNVDEAINFINEREKPLA
LYVFSHNHKLIKRMIDETSSGGVTGNDVIMHFTLNSFPFGGVGSSGMGAYHGKHSFDTFS
HQRPCLLKSLKREGANKLRYPPNSQSKVDWGKFFLLKRFNKEKLGLLLLTFLGIVAAVLV
KAEYY

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Family Aldehyde dehydrogenase family
Function
Catalyzes the oxidation of medium and long chain aliphatic aldehydes to fatty acids. Active on a variety of saturated and unsaturated aliphatic aldehydes between 6 and 24 carbons in length. Responsible for conversion of the sphingosine 1-phosphate (S1P) degradation product hexadecenal to hexadecenoic acid.

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HGNC ID
HGNC:403
KEGG ID hsa:224
Full List of the Ferroptosis Target of This Regulator and Corresponding Disease/Drug Response(s)
ALDH3A2 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
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 myeloid leukaemia ICD-11: 2A60
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model
 HL-60 cells Adult acute myeloid leukemia Homo sapiens CVCL_0002
MOLM-14 cells Leukemia Homo sapiens CVCL_7916
Mono-Mac-6 cells Acute monocytic leukemia Homo sapiens CVCL_1426
NB4 cells Acute promyelocytic leukemia Homo sapiens CVCL_0005
NOMO-1 cells Acute monocytic leukemia Homo sapiens CVCL_1609
THP-1 cells Childhood acute monocytic leukemia Homo sapiens CVCL_0006
In Vivo Model
Six- to 12-week-old Aldh-mut and Aldh-Ctrl mice were used to generate MLL-AF9 leukemia through retroviral transduction. This was transplanted into lethally irradiated (9 Gy) primary leukemic C57BL/6J mice and then into sublethally irradiated (4.5 Gy) secondary leukemic C57BL/6J mice. Forty-eight hours after injection into secondary recipients, these mice received 3 doses of polyinosinic-polycytidylic acid (GE Healthcare) on alternate days.

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Response regulation Aldh3a2 inhibition was synthetically lethal with glutathione peroxidase-4 (GPX4) inhibition; GPX4 inhibition is a known trigger of ferroptosis that by itself minimally affects acute myeloid leukemia cells. Inhibiting Aldh3a2 provides a therapeutic opportunity and a unique synthetic lethality to exploit the distinctive metabolic state of malignant cells.
Acute myeloid leukaemia [ICD-11: 2A60]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response [1]
Target Regulator Aldehyde dehydrogenase family 3 member A2 (ALDH3A2) Protein coding
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model
 HL-60 cells Adult acute myeloid leukemia Homo sapiens CVCL_0002
MOLM-14 cells Leukemia Homo sapiens CVCL_7916
Mono-Mac-6 cells Acute monocytic leukemia Homo sapiens CVCL_1426
NB4 cells Acute promyelocytic leukemia Homo sapiens CVCL_0005
NOMO-1 cells Acute monocytic leukemia Homo sapiens CVCL_1609
THP-1 cells Childhood acute monocytic leukemia Homo sapiens CVCL_0006
In Vivo Model
Six- to 12-week-old Aldh-mut and Aldh-Ctrl mice were used to generate MLL-AF9 leukemia through retroviral transduction. This was transplanted into lethally irradiated (9 Gy) primary leukemic C57BL/6J mice and then into sublethally irradiated (4.5 Gy) secondary leukemic C57BL/6J mice. Forty-eight hours after injection into secondary recipients, these mice received 3 doses of polyinosinic-polycytidylic acid (GE Healthcare) on alternate days.

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Response regulation Aldh3a2 inhibition was synthetically lethal with glutathione peroxidase-4 (GPX4) inhibition; GPX4 inhibition is a known trigger of ferroptosis that by itself minimally affects acute myeloid leukemia cells. Inhibiting Aldh3a2 provides a therapeutic opportunity and a unique synthetic lethality to exploit the distinctive metabolic state of malignant cells.
References
Ref 1 Aldehyde dehydrogenase 3a2 protects AML cells from oxidative death and the synthetic lethality of ferroptosis inducers. Blood. 2020 Sep 10;136(11):1303-1316. doi: 10.1182/blood.2019001808.