Gene Ontology annotation through association of InterPro records with GO terms
Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity
Annotation inferences using phylogenetic trees
Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara
Combined Automated Annotation using Multiple IEA Methods
Function of the cloned putative neutral sphingomyelinase as lyso-platelet activating factor-phospholipase C.
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In the tested unstimulated overexpression experiments, bulk sphingomyelin and ceramide metabolism were not apparently changed, whereas lyso-PAF metabolism increased; lyso-PC and lyso-PAF were good in vitro substrates. This supports context-dependent substrate use, not a universal absence of cellular nSMase activity.
"these results suggest that the protein acts as lyso-PAF-PLC rather than"
Hydrolysis of sphingosylphosphocholine by neutral sphingomyelinases.
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Human nSMase1 and nSMase2 hydrolyze sphingosylphosphocholine efficiently under detergent-free conditions; substrate specificity for sphingomyelin, sphingosylphosphocholine, and monoradyl glycerophosphocholine (but not diradyl species) indicates a required hydrogen-bond donor at the C-2/sn-2 position.
"efficiently under detergent-free conditions"
Architecture of the human interactome defines protein communities and disease networks.
A reference map of the human binary protein interactome.
Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins and Uncovers Widespread Protein Aggregation in Affected Brains.
Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.
SMPD2 and 3 hydrolyze sphingomyelin (plasma membrane)
TNF-α:TNFR1:NSMAF:GNB2L1 associates with SMPD2,3
Characterization and subcellular localization of murine and human magnesium-dependent neutral sphingomyelinase.
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Overexpressed human nSMase1 in HEK293 cells colocalized with ER and Golgi markers and needs its putative transmembrane domains for activity.
"The enzyme colocalized with marker proteins of the endoplasmic reticulum and the Golgi apparatus in immunocytochemistry."
Stress-induced ceramide generation and apoptosis via the phosphorylation and activation of nSMase1 by JNK signaling.
Transient mechanoactivation of neutral sphingomyelinase in caveolae to generate ceramide.
Purification and characterization of a magnesium-dependent neutral sphingomyelinase from bovine brain.
Novel tumor necrosis factor-responsive mammalian neutral sphingomyelinase-3 is a C-tail-anchored protein.
OpenScientist review of SMPD2 caveola and mechanosignaling attribution
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The report argues that the caveolar mechanosensitive neutral-SMase evidence most plausibly traces to SMPD4/nSMase3 or an unresolved antigen rather than SMPD2/nSMase1.
"Therefore the caveolar/mechanosensitive activity most plausibly belongs to **SMPD4 (nSMase3)** or an unresolved cross-reactive antigen"
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It recommends flagging both the caveola and mechanical-stimulus annotations for removal or NOT-qualification without disturbing SMPD2's independently supported core neutral-SMase function.
"Avoid a blanket "remove all non-core" that would collateralize the valid function."