Ferroptosis Regulator Information

General Information of the Ferroptosis Regulator (ID: REG10352)
Regulator Name Neutral ceramidase (ASAH2)
Synonyms
HNAC1; Acylsphingosine deacylase 2; BCDase; LCDase; N-acylsphingosine amidohydrolase 2; Non-lysosomal ceramidase
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Gene Name ASAH2
Gene ID 56624
Regulator Type Protein coding
Uniprot ID Q9NR71
Sequence
MAKRTFSNLETFLIFLLVMMSAITVALLSLLFITSGTIENHKDLGGHFFSTTQSPPATQG
STAAQRSTATQHSTATQSSTATQTSPVPLTPESPLFQNFSGYHIGVGRADCTGQVADINL
MGYGKSGQNAQGILTRLYSRAFIMAEPDGSNRTVFVSIDIGMVSQRLRLEVLNRLQSKYG
SLYRRDNVILSGTHTHSGPAGYFQYTVFVIASEGFSNQTFQHMVTGILKSIDIAHTNMKP
GKIFINKGNVDGVQINRSPYSYLQNPQSERARYSSNTDKEMIVLKMVDLNGDDLGLISWF
AIHPVSMNNSNHLVNSDNVGYASYLLEQEKNKGYLPGQGPFVAAFASSNLGDVSPNILGP
RCINTGESCDNANSTCPIGGPSMCIAKGPGQDMFDSTQIIGRAMYQRAKELYASASQEVT
GPLASAHQWVDMTDVTVWLNSTHASKTCKPALGYSFAAGTIDGVGGLNFTQGKTEGDPFW
DTIRDQILGKPSEEIKECHKPKPILLHTGELSKPHPWHPDIVDVQIITLGSLAITAIPGE
FTTMSGRRLREAVQAEFASHGMQNMTVVISGLCNVYTHYITTYEEYQAQRYEAASTIYGP
HTLSAYIQLFRNLAKAIATDTVANLSRGPEPPFFKQLIVPLIPSIVDRAPKGRTFGDVLQ
PAKPEYRVGEVAEVIFVGANPKNSVQNQTHQTFLTVEKYEATSTSWQIVCNDASWETRFY
WHKGLLGLSNATVEWHIPDTAQPGIYRIRYFGHNRKQDILKPAVILSFEGTSPAFEVVTI

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Family Neutral ceramidase family
Function
Plasma membrane ceramidase that hydrolyzes sphingolipid ceramides into sphingosine and free fatty acids at neutral pH. Ceramides, sphingosine, and its phosphorylated form sphingosine-1-phosphate are bioactive lipids that mediate cellular signaling pathways regulating several biological processes including cell proliferation, apoptosis and differentiation. Also catalyzes the reverse reaction allowing the synthesis of ceramides from fatty acids and sphingosine. Together with sphingomyelinase, participates in the production of sphingosine and sphingosine-1- phosphate from the degradation of sphingomyelin, a sphingolipid enriched in the plasma membrane of cells. Also participates in the hydrolysis of ceramides from the extracellular milieu allowing the production of sphingosine-1-phosphate inside and outside cells. This is the case for instance with the digestion of dietary sphingolipids in the intestinal tract.

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HGNC ID
HGNC:18860
KEGG ID hsa:56624
Full List of the Ferroptosis Target of This Regulator and Corresponding Disease/Drug Response(s)
ASAH2 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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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 Colon cancer ICD-11: 2B90
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
 CT26 cells Colon adenocarcinoma Mus musculus CVCL_7254
4T1 cells Mammary carcinoma Mus musculus CVCL_0125
In Vivo Model
BALB/c and C57BL/6 mice were obtained from the Jackson Laboratory (Bar Harbor, ME). To establish subcutaneous tumor models, CT26 cells (2 x 105 cells/mouse) were injected into the right flanks of BALB/c mice. For experimental lung metastasis models, colon carcinoma CT26, mesothelioma AB1 (2 x 105 cells/mouse) and mammary carcinoma 4T1 (2 x 104 cells/mouse) were injected into BALB/c mice. Tumor-bearing mice were treated with vehicle PEG300 (Sigma-Aldrich) and NC06 (dissolved in PEG300), respectively, every two days for 3-5 times by Intraperitoneal injection.

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Response regulation ASAH2 is overexpressed in MDSCs in human colon cancer patients. ASAH2 protects MDSCs from ferroptosis through destabilizing p53 protein to suppress the p53 pathway in MDSCs in the tumor microenvironment.
Colon cancer [ICD-11: 2B90]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response [1]
Target Regulator Neutral ceramidase (ASAH2) Protein coding
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
 CT26 cells Colon adenocarcinoma Mus musculus CVCL_7254
4T1 cells Mammary carcinoma Mus musculus CVCL_0125
In Vivo Model
BALB/c and C57BL/6 mice were obtained from the Jackson Laboratory (Bar Harbor, ME). To establish subcutaneous tumor models, CT26 cells (2 x 105 cells/mouse) were injected into the right flanks of BALB/c mice. For experimental lung metastasis models, colon carcinoma CT26, mesothelioma AB1 (2 x 105 cells/mouse) and mammary carcinoma 4T1 (2 x 104 cells/mouse) were injected into BALB/c mice. Tumor-bearing mice were treated with vehicle PEG300 (Sigma-Aldrich) and NC06 (dissolved in PEG300), respectively, every two days for 3-5 times by Intraperitoneal injection.

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Response regulation ASAH2 is overexpressed in MDSCs in human colon cancer patients. ASAH2 protects MDSCs from ferroptosis through destabilizing p53 protein to suppress the p53 pathway in MDSCs in the tumor microenvironment.
References
Ref 1 Asah2 Represses the p53-Hmox1 Axis to Protect Myeloid-Derived Suppressor Cells from Ferroptosis. J Immunol. 2021 Mar 15;206(6):1395-1404. doi: 10.4049/jimmunol.2000500. Epub 2021 Feb 5.