InterPro domain: IPR038445

This superfamily represents the C-terminal domain of a group of neutral ceramidases found in both bacteria and eukaryotes [ 1 , 2 , 3 ]. The EC classification is 3.5.1.23 . The enzyme hydrolyses ceramide to generate sphingosine and fatty acid. The enzyme plays a regulatory role in a variety of physiological events in eukaryotes and also functions as an exotoxin in particular bacteria. This C-terminal tail of the enzyme is highly conserved across all species and may play a role in the interaction of the enzyme with the plasma membranes. The tail is also vital for the stabilisation of the enzyme as a whole [ 4 , 5 ].

Ceramidases play a key role in sphingolipid metabolism by converting the apoptosis-associated lipid ceramide to Sph, a precursor for the proliferative factor S1P. Three families of CDases (acid, neutral, and alkaline) have been identified that are distinguished by their pH optima, subcellular localisation, primary structure, mechanism, and function [ 6 ].

1. Molecular cloning of the full-length cDNA encoding mouse neutral ceramidase. A novel but highly conserved gene family of neutral/alkaline ceramidases. J. Biol. Chem. 275, 11229-34
2. Molecular cloning and characterization of a human mitochondrial ceramidase. J. Biol. Chem. 275, 21508-13
3. Molecular cloning, sequencing, and expression of the gene encoding alkaline ceramidase from Pseudomonas aeruginosa. Cloning of a ceramidase homologue from Mycobacterium tuberculosis. J. Biol. Chem. 274, 36616-22
4. Conserved amino acid residues in the COOH-terminal tail are indispensable for the correct folding and localization and enzyme activity of neutral ceramidase. J Biol Chem 279, 29351-8
5. Mechanistic insights into the hydrolysis and synthesis of ceramide by neutral ceramidase. J. Biol. Chem. 284, 9566-77
6. Structural Basis for Ceramide Recognition and Hydrolysis by Human Neutral Ceramidase. Structure 23, 1482-1491