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neutral ceramidase (NCDase, N-CDase, acylsphingosine deacylase 2, N-acylsphingosine amidohydrolase 2, BCDase, LCDase, hCD, [Contains: Neutral ceramidase soluble form], ASAH2, HNAC1)
Function:
- hydrolyzes the sphingolipid ceramide into sphingosine & free fatty acid at an optimal pH of 6.5-8.5
- regulator of sphingolipid signaling metabolites by generating sphingosine at the cell surface
- repressor of apoptosis both by reducing C16-ceramide, thereby preventing ceramide-induced apoptosis, & generating sphingosine, a precursor of the antiapoptotic factor sphingosine 1-phosphate
- role in digestion of dietary sphingolipids in intestine by acting as a key enzyme for the catabolism of dietary sphingolipids & regulating the levels of bioactive sphingolipid metabolites in the intestinal tract
- phosphorylation may prevent ubiquitination & subsequent degradation (putative)
- ubiquitination leads to its degradation by the proteasome
- ubiquitination is triggered by nitric oxid (putative)
N-acylsphingosine + H2O a carboxylate + sphingosine
Cofactor:
- enhanced by Na+ & Ca+2, & at lower level Mg+2 & Mn+2
Inhibition:
- inhibited by dithiothreitol (DTT), 2-mercaptoethanol, Zn+2, Cu+2 & Fe+2
Kinetic parameters:
- KM=71.4 uM for octanoyl-sphingosine
- KM=66 uM for palmitoyl-sphingosine
- Vmax=160 umol/min/mg enzyme with octanoyl-sphingosine
- Vmax=16 umol/min/mg enzyme with palmitoyl-sphingosine
- Optimum pH is 7.5-9.5
Structure:
- belongs to the neutral ceramidase family
- N-glycosylated, required for enzyme activity (putative)
- O-glycosylated, required to retain it as a type 2 membrane protein at the cell surface
Compartment:
- cell membrane
- neutral ceramidase soluble form is a secreted protein
Alternative splicing: named isoforms=2
Expression:
- ubiquitously expressed
- higher levels in kidney, skeletal muscle & heart
General
ceramidase
glycoprotein
membrane protein
phosphoprotein
secreted protein
Properties
SIZE: MW = 86 kD
entity length = 780 aa
COMPARTMENT: cellular membrane
MOTIF: transmembrane domain {13-33}
Thr glycosylation site {T62}
Ser glycosylation site {S67}
Thr glycosylation site {T68}
Thr glycosylation site {T70}
Ser glycosylation site {S73}
Thr glycosylation site {T74}
Thr glycosylation site {T76}
Ser glycosylation site {S78}
Ser glycosylation site {S79}
Thr glycosylation site {T80}
Thr glycosylation site {T82}
Thr glycosylation site {T84}
N-glycosylation site {N98}
N-glycosylation site {N151}
N-glycosylation site {N217}
serine residue {S354}
N-glycosylation site {N468}
N-glycosylation site {N564}
N-glycosylation site {N730}
folding & localization {770-780}
MOTIF: Thr glycosylation site {T779}
Database Correlations
UniProt Q9NR71
Pfam PF04734
ENZYME 3.5.1.23
References
UniProt :accession Q9NR71