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MT001193

UniProt Annotations

Entry Information

Gene Name	N-acylsphingosine amidohydrolase (non-lysosomal ceramidase) 2
Protein Entry	ASAH2_HUMAN
UniProt ID	Q9NR71
Species	Human

Comments

Comment type	Description
Alternative Products	Event=Alternative splicing; Named isoforms=2; Name=1; IsoId=Q9NR71-1; Sequence=Displayed; Name=2; IsoId=Q9NR71-2; Sequence=VSP_019928; Note=No experimental confirmation available.;
Biophysicochemical Properties	Kinetic parameters: KM=71.4 uM for octanoyl-sphingosine {ECO:0000269\|PubMed:10781606, ECO:0000269\|PubMed:16229686}; KM=66 uM for palmitoyl-sphingosine {ECO:0000269\|PubMed:10781606, ECO:0000269\|PubMed:16229686}; KM=60.1 uM for D-erythro-C12-NBD-ceramide {ECO:0000269\|PubMed:10781606, ECO:0000269\|PubMed:16229686}; Vmax=160 umol/min/mg enzyme with octanoyl-sphingosine as substrate {ECO:0000269\|PubMed:10781606, ECO:0000269\|PubMed:16229686}; Vmax=16 umol/min/mg enzyme with palmitoyl-sphingosine as substrate {ECO:0000269\|PubMed:10781606, ECO:0000269\|PubMed:16229686}; Vmax=0.68 nmol/min/mg enzyme with D-erythro-C12-NBD-ceramide as substrate {ECO:0000269\|PubMed:10781606, ECO:0000269\|PubMed:16229686}; pH dependence: Optimum pH is 7.5-9.5. {ECO:0000269\|PubMed:10781606, ECO:0000269\|PubMed:16229686};
Catalytic Activity	N-acylsphingosine + H(2)O = a carboxylate + sphingosine. {ECO:0000269\|PubMed:10781606, ECO:0000269\|PubMed:16229686}.
Enzyme Regulation	Inhibited by dithiothreitol (DTT), 2- mercaptoethanol, Zn(2+), Cu(2+) and Fe(2+). Enhanced by Na(+) and Ca(2+), and at lower level Mg(2+) and Mn(2+).
Function	Hydrolyzes the sphingolipid ceramide into sphingosine and free fatty acid at an optimal pH of 6.5-8.5. Acts as a key regulator of sphingolipid signaling metabolites by generating sphingosine at the cell surface. Acts as a repressor of apoptosis both by reducing C16-ceramide, thereby preventing ceramide-induced apoptosis, and generating sphingosine, a precursor of the antiapoptotic factor sphingosine 1-phosphate. Probably involved in the digestion of dietary sphingolipids in intestine by acting as a key enzyme for the catabolism of dietary sphingolipids and regulating the levels of bioactive sphingolipid metabolites in the intestinal tract. {ECO:0000269\|PubMed:15946935, ECO:0000269\|PubMed:16061940}.
Ptm	N-glycosylated. Required for enzyme activity (By similarity). {ECO:0000250}.
Ptm	O-glycosylated. Required to retain it as a type II membrane protein at the cell surface. {ECO:0000269\|PubMed:15845354}.
Ptm	Phosphorylated. May prevent ubiquitination and subsequent degradation (By similarity). {ECO:0000250}.
Ptm	Ubiquitinated, leading to its degradation by the proteasome. Ubiquitination is triggered by nitric oxid (By similarity). {ECO:0000250}.
Sequence Caution	Sequence=AAL06061.1; Type=Erroneous initiation; Evidence={ECO:0000305}; Sequence=CAI15870.1; Type=Erroneous initiation; Evidence={ECO:0000305};
Similarity	Belongs to the neutral ceramidase family. {ECO:0000305}.
Subcellular Location	Cell membrane {ECO:0000269\|PubMed:15845354}; Single-pass type II membrane protein {ECO:0000269\|PubMed:15845354}. Note=The neutral ceramidase soluble form is a secreted protein. According to PubMed:10781606, it is mitochondrial. However, they used a shorter form in its N- terminus, which may explain this localization which probably does not exist in vivo.
Tissue Specificity	Primarily expressed in the intestine (PubMed:17334805). Ubiquitously expressed with higher levels in kidney, skeletal muscle and heart (PubMed:10781606). According to PubMed:17334805, ubiquitous expression attributed to ASAH2 may be actually that of the paralog ASAH2B. {ECO:0000269\|PubMed:10781606, ECO:0000269\|PubMed:17334805}.