Molecule Information

General Information of the Molecule (ID: Mol04087)

• Name: N-acylsphingosine amidohydrolase 2 (ASAH2) ,Homo sapiens
• Synonyms: Acylsphingosine deacylase 2; BCDase; LCDase; N-acylsphingosine amidohydrolase 2; Non-lysosomal ceramidase
• Molecule Type: Protein
• Gene Name: ASAH2
• Gene ID: 56624
• Location: chr10:50182778-50279720[-]
• Sequence:
  MAKRTFSNLETFLIFLLVMMSAITVALLSLLFITSGTIENHKDLGGHFFSTTQSPPATQG
  STAAQRSTATQHSTATQSSTATQTSPVPLTPESPLFQNFSGYHIGVGRADCTGQVADINL
  MGYGKSGQNAQGILTRLYSRAFIMAEPDGSNRTVFVSIDIGMVSQRLRLEVLNRLQSKYG
  SLYRRDNVILSGTHTHSGPAGYFQYTVFVIASEGFSNQTFQHMVTGILKSIDIAHTNMKP
  GKIFINKGNVDGVQINRSPYSYLQNPQSERARYSSNTDKEMIVLKMVDLNGDDLGLISWF
  AIHPVSMNNSNHLVNSDNVGYASYLLEQEKNKGYLPGQGPFVAAFASSNLGDVSPNILGP
  RCINTGESCDNANSTCPIGGPSMCIAKGPGQDMFDSTQIIGRAMYQRAKELYASASQEVT
  GPLASAHQWVDMTDVTVWLNSTHASKTCKPALGYSFAAGTIDGVGGLNFTQGKTEGDPFW
  DTIRDQILGKPSEEIKECHKPKPILLHTGELSKPHPWHPDIVDVQIITLGSLAITAIPGE
  FTTMSGRRLREAVQAEFASHGMQNMTVVISGLCNVYTHYITTYEEYQAQRYEAASTIYGP
  HTLSAYIQLFRNLAKAIATDTVANLSRGPEPPFFKQLIVPLIPSIVDRAPKGRTFGDVLQ
  PAKPEYRVGEVAEVIFVGANPKNSVQNQTHQTFLTVEKYEATSTSWQIVCNDASWETRFY
  WHKGLLGLSNATVEWHIPDTAQPGIYRIRYFGHNRKQDILKPAVILSFEGTSPAFEVVTI
• 3D-structure: PDB ID: 4WGK; Classification: Hydrolase; Method: X-ray diffraction; Resolution: 2.58 Å
• Function: Plasma membrane ceramidase that hydrolyzes sphingolipid ceramides into sphingosine and free fatty acids at neutral pH (PubMed:10781606, PubMed:16229686, PubMed:26190575). 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 (PubMed:15946935, PubMed:19345744, PubMed:24798654). Also catalyzes the reverse reaction allowing the synthesis of ceramides from fatty acids and sphingosine (PubMed:11278489, PubMed:17475390). 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 (PubMed:16061940). Also participates in the hydrolysis of ceramides from the extracellular milieu allowing the production of sphingosine-1-phosphate inside and outside cells (By similarity). This is the case for instance with the digestion of dietary sphingolipids in the intestinal tract (By similarity). .
• Uniprot ID: ASAH2_HUMAN
• Ensembl ID: ENSG00000188611
• HGNC ID: HGNC:18860

Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Primates
Family: Hominidae
Genus: Homo
Species: Homo sapiens

Type(s) of Resistant Mechanism of This Molecule

  MRAP: Metabolic Reprogramming via Altered Pathways

Drug Resistance Data Categorized by Drug

Approved Drug(s) 2 drug(s) in total

Fluorouracil

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Metabolic Reprogramming via Altered Pathways (MRAP)

Disease Class: Pancreatic ductal adenocarcinoma [ICD-11: 2C10.0] [1]

• Metabolic Type: Redox metabolism
• Resistant Disease: Pancreatic ductal adenocarcinoma [ICD-11: 2C10.0]
• Resistant Drug: Fluorouracil
• Molecule Alteration: Expression; Up-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Pancreatic cancer [ICD-11: 2C10]
• The Specified Disease: Pancreatic ductal adenocarcinoma
• The Studied Tissue: Pancreas
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 3.44E-01; Fold-change: 1.83E-01; Z-score: 9.68E-01
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Panc1 cells; Pancreas; Homo sapiens (Human); CVCL_0480
• In Vitro Model: TB32048 cells; N.A.; Homo sapiens (Human); N.A.
• Experiment for Molecule Alteration: qRT-PCR; Western blot analysis
• Experiment for Drug Resistance: IC50 assay
• Mechanism Description: Mechanistically, our proteomic analysis reveals a consistent up-regulation of sphingolipid metabolic enzyme ASAH2 and beta5-integrin expression in GemR pancreatic and lung cancer cells as well as stable beta5-integrin-expressing cells.

Disease Class: Lung adenocarcinoma [ICD-11: 2C25.0] [1]

• Metabolic Type: Redox metabolism
• Resistant Disease: Lung adenocarcinoma [ICD-11: 2C25.0]
• Resistant Drug: Fluorouracil
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: A5419 cells; Lung; Homo sapiens (Human); N.A.
• In Vitro Model: LLC cells; Lung; Homo sapiens (Human); CVCL_A9AW
• Experiment for Molecule Alteration: qRT-PCR; Western blot analysis
• Experiment for Drug Resistance: IC50 assay
• Mechanism Description: Mechanistically, our proteomic analysis reveals a consistent up-regulation of sphingolipid metabolic enzyme ASAH2 and beta5-integrin expression in GemR pancreatic and lung cancer cells as well as stable beta5-integrin-expressing cells.

Gemcitabine

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Metabolic Reprogramming via Altered Pathways (MRAP)

Disease Class: Pancreatic ductal adenocarcinoma [ICD-11: 2C10.0] [1]

• Metabolic Type: Redox metabolism
• Resistant Disease: Pancreatic ductal adenocarcinoma [ICD-11: 2C10.0]
• Resistant Drug: Gemcitabine
• Molecule Alteration: Expression; Up-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Pancreatic cancer [ICD-11: 2C10]
• The Specified Disease: Pancreatic ductal adenocarcinoma
• The Studied Tissue: Pancreas
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 3.44E-01; Fold-change: 1.83E-01; Z-score: 9.68E-01
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Panc1 cells; Pancreas; Homo sapiens (Human); CVCL_0480
• In Vitro Model: TB32048 cells; N.A.; Homo sapiens (Human); N.A.
• Experiment for Molecule Alteration: qRT-PCR; Western blot analysis
• Experiment for Drug Resistance: IC50 assay
• Mechanism Description: Mechanistically, our proteomic analysis reveals a consistent up-regulation of sphingolipid metabolic enzyme ASAH2 and beta5-integrin expression in GemR pancreatic and lung cancer cells as well as stable beta5-integrin-expressing cells.

Disease Class: Lung adenocarcinoma [ICD-11: 2C25.0] [1]

• Metabolic Type: Redox metabolism
• Resistant Disease: Lung adenocarcinoma [ICD-11: 2C25.0]
• Resistant Drug: Gemcitabine
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: A5419 cells; Lung; Homo sapiens (Human); N.A.
• In Vitro Model: LLC cells; Lung; Homo sapiens (Human); CVCL_A9AW
• Experiment for Molecule Alteration: qRT-PCR; Western blot analysis
• Experiment for Drug Resistance: IC50 assay
• Mechanism Description: Mechanistically, our proteomic analysis reveals a consistent up-regulation of sphingolipid metabolic enzyme ASAH2 and beta5-integrin expression in GemR pancreatic and lung cancer cells as well as stable beta5-integrin-expressing cells.

References

• Ref 1: Targeting Src reactivates pyroptosis to reverse chemoresistance in lung and pancreatic cancer models. Sci Transl Med. 2023 Jan 11;15(678):eabl7895.