SAMD8 transfers phosphatidyl from PE onto C16DH CER

Stable Identifier
R-HSA-8959462
Type
Reaction [transition]
Species
Homo sapiens
Compartment
ReviewStatus
5/5
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Sphingolipids such as sphingomyelin (SM) are essential components of cellular membranes and dynamic regulators of many cellular processes in most organisms. Ceramides constitute the backbone of all sphingolipids and are synthesized on the cytosolic surface of the endoplasmic reticulum (ER) and then transported to the Golgi for conversion to SM. The ER-membrane resident protein sphingomyelin synthase-related protein 1 (SAMD8) catalyzes the synthesis of the SM analog ceramide phosphoethanolamine (CPE) in the ER lumen. SAMD8 only produces trace amounts of CPE, but blocking its catalytic activity causes a substantial rise in ER ceramide levels and a structural collapse of the early secretory pathway. SAMD8 is, therefore, a key regulator of ceramide homeostasis, functioning as a sensor rather than a converter of ceramides in the ER (Vacaru et al., 2009). SAMD8 self-associates into ER-resident trimers and hexamers (Cabukusta et al., 2017). The biological role of the produced CPE in humans needs to be better defined. However, it is the main sphingolipid in arthropods and some protozoa and bacteria (see review by Panewska et al., 2019).
Literature References
PubMed ID Title Journal Year
28120887 ER residency of the ceramide phosphoethanolamine synthase SMSr relies on homotypic oligomerization mediated by its SAM domain

Cabukusta, B, Bickert, A, Holthuis, JC, Mina, JG, Kol, M, Hilderink, A, Kneller, L, Korneev, S

Sci Rep 2017
19506037 Sphingomyelin synthase-related protein SMSr controls ceramide homeostasis in the ER

Rabouille, C, Kondylis, V, Holthuis, JC, Ternes, P, Vacaru, AM, Brouwers, JF, Hermansson, M, Somerharju, P, Tafesse, FG

J. Cell Biol. 2009
31067435 Ceramide phosphoethanolamine, an enigmatic cellular membrane sphingolipid

Sepčić, K, Maček, P, Skočaj, M, Panevska, A, Križaj, I

Biochim Biophys Acta Biomembr 2019
Participants
Participates
Catalyst Activity

ceramide phosphoethanolamine synthase activity of SAMD8 trimer [endoplasmic reticulum membrane]

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