ASAH2

Ceramidases (EC 3.5.1.23), such as ASAH2, catalyze hydrolysis of the N-acyl linkage of ceramide, a second messenger in a variety of cellular events, to produce sphingosine. Sphingosine exerts both mitogenic and apoptosis-inducing activities, and its phosp

Full Name

N-Acylsphingosine Amidohydrolase 2

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).

Biological Process

Apoptotic process Source: UniProtKB-KW
Cellular response to cytokine stimulus Source: UniProtKB
Ceramide biosynthetic process Source: UniProtKB
Ceramide catabolic process Source: UniProtKB
Ceramide metabolic process Source: UniProtKB
Lipid digestion Source: UniProtKB
Long-chain fatty acid biosynthetic process Source: GO_Central
Negative regulation of apoptotic signaling pathway Source: UniProtKB
Regulation of mitotic cell cycle Source: UniProtKB
Sphingosine biosynthetic process Source: UniProtKB
Sphingosine metabolic process Source: UniProtKB

Cellular Location

Neutral ceramidase: Cell membrane; Extracellular exosome; Golgi apparatus membrane; Mitochondrion; Membrane raft; Caveola. 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

Topology

Cytoplasmic: 1-12 aa
Helical: 13-33 aa
Lumenal: 34-780 aa

PTM

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.