ASAH2

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).

Pathway

Lipid metabolism; sphingolipid metabolism.

Post-translational modifications

Proteolytic cleavage of the N-terminus removes the signal-anchor and produces a soluble form of the protein.

N-glycosylated. Required for enzyme activity.

O-glycosylated. Required to retain it as a type II membrane protein at the cell surface.

Phosphorylated. May prevent ubiquitination and subsequent degradation.

Ubiquitinated, leading to its degradation by the proteasome. Ubiquitination is triggered by nitric oxide.

Sequence Similarities

Belongs to the neutral ceramidase family.

Tissue Specificity

Primarily expressed in intestine (PubMed:17334805). Ubiquitously expressed with higher levels in kidney, skeletal muscle and heart (PubMed:10781606). The ubiquitous expression observed for ASAH2 might be an experimental artifact due to the paralog ASAH2B (PubMed:17334805).

Cellular localization

• Neutral ceramidase
• Cell membrane
• Single-pass type II membrane protein
• Membrane raft
• Single-pass type II membrane protein
• Membrane
• Caveola
• Single-pass type II membrane protein
• Golgi apparatus membrane
• Single-pass type II membrane protein
• Mitochondrion
• Secreted
• Extracellular exosome
• Enriched in exosomes upon stimulation by cytokine (PubMed:24798654). Enriched in caveolae and lipid rafts (By similarity). The localization to the mitochondrion could not be confirmed (PubMed:15845354).
• Neutral ceramidase soluble form
• Secreted

Alternative names

HNAC1, ASAH2, Neutral ceramidase, N-CDase, NCDase, Acylsphingosine deacylase 2, BCDase, LCDase, N-acylsphingosine amidohydrolase 2, Non-lysosomal ceramidase, hCD

Database links

swissprot:Q9NR71 entrezGene:653308 entrezGene:56624 omim:611202