Sphingomyelin phosphodiesterase

Sphingomyelin phosphodiesterase

Converts sphingomyelin to ceramide12563314,1840600,18815062,25339683,25920558,27659707,33163980. Exists as two enzymatic forms that arise from alternative trafficking of a single protein precursor, one that is targeted to the endolysosomal compartment, whereas the other is released extracellularly20807762,21098024,9660788. However, in response to various forms of stress, lysosomal exocytosis may represent a major source of the secretory form12563314,20530211,20807762,22573858,9393854

In the lysosomes, converts sphingomyelin to ceramide20807762,21098024. Plays an important role in the export of cholesterol from the intraendolysosomal membranes25339683. Also has phospholipase C activities toward 1,2-diacylglycerolphosphocholine and 1,2-diacylglycerolphosphoglycerol25339683. Modulates stress-induced apoptosis through the production of ceramide8706124

When secreted, modulates cell signaling with its ability to reorganize the plasma membrane by converting sphingomyelin to ceramide12563314,17303575,20807762. Secreted form is increased in response to stress and inflammatory mediators such as IL1B, IFNG or TNF as well as upon infection with bacteria and viruses12563314,20807762,9393854. Produces the release of ceramide in the outer leaflet of the plasma membrane playing a central role in host defense12563314,20807762,9393854. Ceramide reorganizes these rafts into larger signaling platforms that are required to internalize P.aeruginosa, induce apoptosis and regulate the cytokine response in infected cells12563314. In wounded cells, the lysosomal form is released extracellularly in the presence of Ca(2+) and promotes endocytosis and plasma membrane repair20530211

This form is generated following cleavage by CASP7 in the extracellular milieu in response to bacterial infection21157428. It shows increased ability to convert sphingomyelin to ceramide and promotes plasma membrane repair (By similarity). Plasma membrane repair by ceramide counteracts the action of gasdermin-D (GSDMD) perforin (PRF1) pores that are formed in response to bacterial infection (By similarity)

(Microbial infection) Secretion is activated by bacteria such as P.aeruginosa, N.gonorrhoeae and others, this activation results in the release of ceramide in the outer leaflet of the plasma membrane which facilitates the infection

(Microbial infection) Secretion is activated by human coronaviruses SARS-CoV and SARS-CoV-2 as well as Zaire ebolavirus, this activation results in the release of ceramide in the outer leaflet of the plasma membrane which facilitates the infection

Lacks residues that bind the cofactor Zn(2+) and has no enzyme activity

Lacks residues that bind the cofactor Zn(2+) and has no enzyme activity

Quoted from UniProt’s FUNCTION annotation for P17405 (reviewed). The superscript numbers are UniProt’s own PubMed citations, kept in the sentence and in order, each linking to the paper it names.

What it acts with

STRING’s highest-confidence human functional partners. The combined score mixes several kinds of evidence, so each channel is shown separately — a partner supported by experiment is a different claim from one supported only by text mining, and for a receptor this is where its coupling appears as evidence rather than as assertion.

Where it sits in the cell

UniProt, curated Lysosome · Lipid droplet · Secreted · Secreted, extracellular space

Expression by cell type

Single cell type RNA, the 5 highest of those the Human Protein Atlas reports for this gene. Transcript, not protein, and a cell type rather than a tissue.

• Late spermatids365.5 nCPM
• Platelets132.6 nCPM
• Esophageal apical cells126.8 nCPM
• Hepatocytes83.9 nCPM
• Colonocytes78.8 nCPM