General Information of the Ferroptosis Regulator (ID: REG10132)
Regulator Name Phosphatidylethanolamine-binding protein 1 (PEBP1)
Synonyms
PBP, PEBP; HCNPpp; Neuropolypeptide h3; Prostatic-binding protein; Raf kinase inhibitor protein
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Gene Name PEBP1
Gene ID 5037
Regulator Type Protein coding
Uniprot ID P30086
Sequence
MPVDLSKWSGPLSLQEVDEQPQHPLHVTYAGAAVDELGKVLTPTQVKNRPTSISWDGLDS
GKLYTLVLTDPDAPSRKDPKYREWHHFLVVNMKGNDISSGTVLSDYVGSGPPKGTGLHRY
VWLVYEQDRPLKCDEPILSNRSGDHRGKFKVASFRKKYELRAPVAGTCYQAEWDDYVPKL
YEQLSGK

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Family Phosphatidylethanolamine-binding protein family
Function
Binds ATP, opioids and phosphatidylethanolamine. Has lower affinity for phosphatidylinositol and phosphatidylcholine. Serine protease inhibitor which inhibits thrombin, neuropsin and chymotrypsin but not trypsin, tissue type plasminogen activator and elastase. Inhibits the kinase activity of RAF1 by inhibiting its activation and by dissociating the RAF1/MEK complex and acting as a competitive inhibitor of MEK phosphorylation.

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HGNC ID
HGNC:8630
KEGG ID hsa:5037
Full List of the Ferroptosis Target of This Regulator and Corresponding Disease/Drug Response(s)
PEBP1 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
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Phospholipid hydroperoxide glutathione peroxidase (GPX4) [Suppressor]
In total 1 item(s) under this target
Experiment 1 Reporting the Ferroptosis Target of This Regulator [1]
Target for Ferroptosis Suppressor
Responsed Disease Depressive disorder ICD-11: 6A70
Responsed Drug Xiaoyaosan Investigative
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
mHTs (Mouse hippocampus tissues)
In Vivo Model
The specific-pathogen free (SPF) male C57BL/6 mice (8-week-old, SCXK (Beijing) 2016-0006) were purchased from Beijing Vital River Laboratory Animal Technology Limited Company. A total of 48 mice were randomly assigned to 4 groups (n = 12): a control group (no stress + physiological saline), a CUMS group (CUMS + physiological saline), a Xiaoyaosan group (CUMS + Xiaoyaosan treatment) and a fluoxetine group (CUMS + fluoxetine treatment).

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Response regulation The activation of ferroptosis might exist in the hippocampi of CUMS-induced mice. The PEBP1-GPX4-mediated ferroptosis could be involved in the antidepressant mechanism of Xiaoyaosan. It also implied that ferroptosis could become a new target for research into the depression mechanism and antidepressant drugs.
Polyunsaturated fatty acid lipoxygenase ALOX15B (ALOX15B) [Driver]
In total 1 item(s) under this target
Experiment 1 Reporting the Ferroptosis Target of This Regulator [2]
Target for Ferroptosis Driver
Responsed Disease Health ICD-11: N.A.
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
hAECs (Human airway epithelial cells)
HT22 cells Normal Mus musculus CVCL_0321
HK-2 cells Normal Homo sapiens CVCL_0302
In Vivo Model
Male 20 weeks old CD-1 mice were obtained from Charles River Laboratories. The mice were randomly assigned (using random number generator in Excel) to receive 5 mg/kg Fer-1 (Abcam, cat #ab146169) or 1.5% DMSO (vehicle) 60 minutes before injection of folic acid (Sigma-Aldrich) of 250 mg/kg in 0.3 mol/L sodium bicarbonate intraperitoneally. Mice were euthanized 48 h later.

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Response regulation PEBP1, a scaffold protein inhibitor of protein kinase cascades, complexes with two 15LO isoforms, 15LO1 (ALOX15) and 15LO2 (ALOX15B) , and changes their substrate competence to generate hydroperoxy-PE. Inadequate reduction of hydroperoxy-PE due to insufficiency or dysfunction of a selenoperoxidase, GPX4, leads to ferroptosis.
Polyunsaturated fatty acid lipoxygenase ALOX15 (ALOX15) [Driver]
In total 1 item(s) under this target
Experiment 1 Reporting the Ferroptosis Target of This Regulator [2]
Target for Ferroptosis Driver
Responsed Disease Health ICD-11: N.A.
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
hAECs (Human airway epithelial cells)
HT22 cells Normal Mus musculus CVCL_0321
HK-2 cells Normal Homo sapiens CVCL_0302
In Vivo Model
Male 20 weeks old CD-1 mice were obtained from Charles River Laboratories. The mice were randomly assigned (using random number generator in Excel) to receive 5 mg/kg Fer-1 (Abcam, cat #ab146169) or 1.5% DMSO (vehicle) 60 minutes before injection of folic acid (Sigma-Aldrich) of 250 mg/kg in 0.3 mol/L sodium bicarbonate intraperitoneally. Mice were euthanized 48 h later.

    Click to Show/Hide
Response regulation PEBP1, a scaffold protein inhibitor of protein kinase cascades, complexes with two 15LO isoforms, 15LO1 (ALOX15) and 15LO2 (ALOX15B) , and changes their substrate competence to generate hydroperoxy-PE. Inadequate reduction of hydroperoxy-PE due to insufficiency or dysfunction of a selenoperoxidase, GPX4, leads to ferroptosis.
Depressive disorder [ICD-11: 6A70]
In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response [1]
Target Regulator Phosphatidylethanolamine-binding protein 1 (PEBP1) Protein coding
Responsed Drug Xiaoyaosan Investigative
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
mHTs (Mouse hippocampus tissues)
In Vivo Model
The specific-pathogen free (SPF) male C57BL/6 mice (8-week-old, SCXK (Beijing) 2016-0006) were purchased from Beijing Vital River Laboratory Animal Technology Limited Company. A total of 48 mice were randomly assigned to 4 groups (n = 12): a control group (no stress + physiological saline), a CUMS group (CUMS + physiological saline), a Xiaoyaosan group (CUMS + Xiaoyaosan treatment) and a fluoxetine group (CUMS + fluoxetine treatment).

    Click to Show/Hide
Response regulation The activation of ferroptosis might exist in the hippocampi of CUMS-induced mice. The PEBP1-GPX4-mediated ferroptosis could be involved in the antidepressant mechanism of Xiaoyaosan. It also implied that ferroptosis could become a new target for research into the depression mechanism and antidepressant drugs.
Health [ICD-11: N.A.]
In total 2 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response [2]
Target Regulator Phosphatidylethanolamine-binding protein 1 (PEBP1) Protein coding
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
hAECs (Human airway epithelial cells)
HT22 cells Normal Mus musculus CVCL_0321
HK-2 cells Normal Homo sapiens CVCL_0302
In Vivo Model
Male 20 weeks old CD-1 mice were obtained from Charles River Laboratories. The mice were randomly assigned (using random number generator in Excel) to receive 5 mg/kg Fer-1 (Abcam, cat #ab146169) or 1.5% DMSO (vehicle) 60 minutes before injection of folic acid (Sigma-Aldrich) of 250 mg/kg in 0.3 mol/L sodium bicarbonate intraperitoneally. Mice were euthanized 48 h later.

    Click to Show/Hide
Response regulation PEBP1, a scaffold protein inhibitor of protein kinase cascades, complexes with two 15LO isoforms, 15LO1 (ALOX15) and 15LO2 (ALOX15B) , and changes their substrate competence to generate hydroperoxy-PE. Inadequate reduction of hydroperoxy-PE due to insufficiency or dysfunction of a selenoperoxidase, GPX4, leads to ferroptosis.
Experiment 2 Reporting the Ferroptosis-centered Disease Response [2]
Target Regulator Phosphatidylethanolamine-binding protein 1 (PEBP1) Protein coding
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
hAECs (Human airway epithelial cells)
HT22 cells Normal Mus musculus CVCL_0321
HK-2 cells Normal Homo sapiens CVCL_0302
In Vivo Model
Male 20 weeks old CD-1 mice were obtained from Charles River Laboratories. The mice were randomly assigned (using random number generator in Excel) to receive 5 mg/kg Fer-1 (Abcam, cat #ab146169) or 1.5% DMSO (vehicle) 60 minutes before injection of folic acid (Sigma-Aldrich) of 250 mg/kg in 0.3 mol/L sodium bicarbonate intraperitoneally. Mice were euthanized 48 h later.

    Click to Show/Hide
Response regulation PEBP1, a scaffold protein inhibitor of protein kinase cascades, complexes with two 15LO isoforms, 15LO1 (ALOX15) and 15LO2 (ALOX15B) , and changes their substrate competence to generate hydroperoxy-PE. Inadequate reduction of hydroperoxy-PE due to insufficiency or dysfunction of a selenoperoxidase, GPX4, leads to ferroptosis.
Xiaoyaosan [Investigative]
In total 1 item(s) under this drug
Experiment 1 Reporting the Ferroptosis-centered Drug Response [1]
Drug for Ferroptosis Inducer
Response Target Phospholipid hydroperoxide glutathione peroxidase (GPX4) Suppressor
Responsed Disease Depressive disorder ICD-11: 6A70
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
mHTs (Mouse hippocampus tissues)
In Vivo Model
The specific-pathogen free (SPF) male C57BL/6 mice (8-week-old, SCXK (Beijing) 2016-0006) were purchased from Beijing Vital River Laboratory Animal Technology Limited Company. A total of 48 mice were randomly assigned to 4 groups (n = 12): a control group (no stress + physiological saline), a CUMS group (CUMS + physiological saline), a Xiaoyaosan group (CUMS + Xiaoyaosan treatment) and a fluoxetine group (CUMS + fluoxetine treatment).

    Click to Show/Hide
Response regulation The activation of ferroptosis might exist in the hippocampi of CUMS-induced mice. The PEBP1-GPX4-mediated ferroptosis could be involved in the antidepressant mechanism of Xiaoyaosan. It also implied that ferroptosis could become a new target for research into the depression mechanism and antidepressant drugs.
References
Ref 1 Traditional Chinese Formula Xiaoyaosan Alleviates Depressive-Like Behavior in CUMS Mice by Regulating PEBP1-GPX4-Mediated Ferroptosis in the Hippocampus. Neuropsychiatr Dis Treat. 2021 Apr 6;17:1001-1019. doi: 10.2147/NDT.S302443. eCollection 2021.
Ref 2 PEBP1 Wardens Ferroptosis by Enabling Lipoxygenase Generation of Lipid Death Signals. Cell. 2017 Oct 19;171(3):628-641.e26. doi: 10.1016/j.cell.2017.09.044.