Ferroptosis Regulator Information

General Information of the Ferroptosis Regulator (ID: REG10489)
Regulator Name Cadherin-2 (CDH2)
Synonyms
CDHN; NCAD; CDw325; Neural cadherin; CD_antigen=CD325
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Gene Name CDH2
Gene ID 1000
Regulator Type Protein coding
Uniprot ID P19022
Sequence
MCRIAGALRTLLPLLAALLQASVEASGEIALCKTGFPEDVYSAVLSKDVHEGQPLLNVKF
SNCNGKRKVQYESSEPADFKVDEDGMVYAVRSFPLSSEHAKFLIYAQDKETQEKWQVAVK
LSLKPTLTEESVKESAEVEEIVFPRQFSKHSGHLQRQKRDWVIPPINLPENSRGPFPQEL
VRIRSDRDKNLSLRYSVTGPGADQPPTGIFIINPISGQLSVTKPLDREQIARFHLRAHAV
DINGNQVENPIDIVINVIDMNDNRPEFLHQVWNGTVPEGSKPGTYVMTVTAIDADDPNAL
NGMLRYRIVSQAPSTPSPNMFTINNETGDIITVAAGLDREKVQQYTLIIQATDMEGNPTY
GLSNTATAVITVTDVNDNPPEFTAMTFYGEVPENRVDIIVANLTVTDKDQPHTPAWNAVY
RISGGDPTGRFAIQTDPNSNDGLVTVVKPIDFETNRMFVLTVAAENQVPLAKGIQHPPQS
TATVSVTVIDVNENPYFAPNPKIIRQEEGLHAGTMLTTFTAQDPDRYMQQNIRYTKLSDP
ANWLKIDPVNGQITTIAVLDRESPNVKNNIYNATFLASDNGIPPMSGTGTLQIYLLDIND
NAPQVLPQEAETCETPDPNSINITALDYDIDPNAGPFAFDLPLSPVTIKRNWTITRLNGD
FAQLNLKIKFLEAGIYEVPIIITDSGNPPKSNISILRVKVCQCDSNGDCTDVDRIVGAGL
GTGAIIAILLCIIILLILVLMFVVWMKRRDKERQAKQLLIDPEDDVRDNILKYDEEGGGE
EDQDYDLSQLQQPDTVEPDAIKPVGIRRMDERPIHAEPQYPVRSAAPHPGDIGDFINEGL
KAADNDPTAPPYDSLLVFDYEGSGSTAGSLSSLNSSSSGGEQDYDYLNDWGPRFKKLADM
YGGGDD

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Function
Calcium-dependent cell adhesion protein; preferentially mediates homotypic cell-cell adhesion by dimerization with a CDH2 chain from another cell. Cadherins may thus contribute to the sorting of heterogeneous cell types. Acts as a regulator of neural stem cells quiescence by mediating anchorage of neural stem cells to ependymocytes in the adult subependymal zone: upon cleavage by MMP24, CDH2-mediated anchorage is affected, leading to modulate neural stem cell quiescence. Plays a role in cell-to-cell junction formation between pancreatic beta cells and neural crest stem (NCS) cells, promoting the formation of processes by NCS cells (By similarity). Required for proper neurite branching. Required for pre- and postsynaptic organization (By similarity). CDH2 may be involved in neuronal recognition mechanism. In hippocampal neurons, may regulate dendritic spine density.

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HGNC ID
HGNC:1759
KEGG ID hsa:1000
Full List of the Ferroptosis Target of This Regulator and Corresponding Disease/Drug Response(s)
CDH2 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 pancreatitis ICD-11: DC31
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Autophagy hsa04140
Cell Process Cell ferroptosis
Cell autophagy
In Vitro Model
 HT-1080 cells Fibrosarcoma Homo sapiens CVCL_0317
Calu-1 cells Lung squamous cell carcinoma Homo sapiens CVCL_0608
PANC-1 cells Pancreatic ductal adenocarcinoma Homo sapiens CVCL_0480
5637 cells Bladder carcinoma Homo sapiens CVCL_0126
SK-OV-3 cells Ovarian serous cystadenocarcinoma Homo sapiens CVCL_0532
PC-3 cells Prostate carcinoma Homo sapiens CVCL_0035
In Vivo Model
Pancreatic-specific gpx4 knockout mice were produced and identified in our laboratory by crossing floxed Gpx4 (a gift from Dr. Qitao Ran, UT Health San Antonio) and Pdx1-Cre (the Jackson Laboratory, 014647) transgenic mice (C57BL/6J background). For cerulein-induced acute pancreatitis, female mice (8-10 weeks) received seven hourly i.p. injections of 50 ug/kg cerulein in sterile saline. We repeatedly administered iHPCAL1 by i.p. at a dose of 10 mg/kg to mice at 3 and 12 h after the first cerulein injection, while controls were treated by administration with vehicle. The parameters of acute pancreatitis were assessed 12 h after the last cerulein treatment.

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Response regulation HPCAL1 as a specific autophagy receptor provides the first mechanistic understanding of how CDH2 is selectively delivered to phagophores, leading to CDH2 degradation for the induction of ferroptosis. The genetic or pharmacological inhibition of HPCAL1 prevented ferroptosis-induced tumor suppression and pancreatitis in suitable mouse models.
Acute pancreatitis [ICD-11: DC31]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response [1]
Target Regulator Cadherin-2 (CDH2) Protein coding
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Autophagy hsa04140
Cell Process Cell ferroptosis
Cell autophagy
In Vitro Model
 HT-1080 cells Fibrosarcoma Homo sapiens CVCL_0317
Calu-1 cells Lung squamous cell carcinoma Homo sapiens CVCL_0608
PANC-1 cells Pancreatic ductal adenocarcinoma Homo sapiens CVCL_0480
5637 cells Bladder carcinoma Homo sapiens CVCL_0126
SK-OV-3 cells Ovarian serous cystadenocarcinoma Homo sapiens CVCL_0532
PC-3 cells Prostate carcinoma Homo sapiens CVCL_0035
In Vivo Model
Pancreatic-specific gpx4 knockout mice were produced and identified in our laboratory by crossing floxed Gpx4 (a gift from Dr. Qitao Ran, UT Health San Antonio) and Pdx1-Cre (the Jackson Laboratory, 014647) transgenic mice (C57BL/6J background). For cerulein-induced acute pancreatitis, female mice (8-10 weeks) received seven hourly i.p. injections of 50 ug/kg cerulein in sterile saline. We repeatedly administered iHPCAL1 by i.p. at a dose of 10 mg/kg to mice at 3 and 12 h after the first cerulein injection, while controls were treated by administration with vehicle. The parameters of acute pancreatitis were assessed 12 h after the last cerulein treatment.

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Response regulation HPCAL1 as a specific autophagy receptor provides the first mechanistic understanding of how CDH2 is selectively delivered to phagophores, leading to CDH2 degradation for the induction of ferroptosis. The genetic or pharmacological inhibition of HPCAL1 prevented ferroptosis-induced tumor suppression and pancreatitis in suitable mouse models.
References
Ref 1 Identification of HPCAL1 as a specific autophagy receptor involved in ferroptosis. Autophagy. 2023 Jan;19(1):54-74. doi: 10.1080/15548627.2022.2059170. Epub 2022 Apr 10.