Smpd1
entrez
20597
canonical
uniprot
Q04519
canonical
ensembl
ENSMUSG00000037049
resolver
ensp
ENSMUSP00000042187
resolver
enst
ENSMUST00000046983
resolver
genesymbol
Smpd1
resolver
genesymbol_syn
Asm
resolver
uniprot
Q3UL52
resolver
uniprot_entry
ASM_MOUSE
resolver
uniprot_sec
Q3UL52
resolver
activity_regulation
ACTIVITY REGULATION: Hydrolysis of liposomal sphingomyelin is stimulated by incorporation of diacylglycerol (DAG), ceramide and free fatty acids into the liposomal membranes. Phosphatidylcholine hydrolysis is inhibited by incorporation of cholesterol, ceramide, DAG, monoacylglycerol and fatty acids. {ECO:0000250|UniProtKB:P17405}.
uniprot
proteins
amino_acid_sequence
MPHHRASSGQDHLRAGWEQRLERSLPAPRVGLLWMGLGLALVLALFDSTVLWVPARAYPLPSEGHSVKFSAIAPPLQSAFGWQNLTCPACKVLFTALNHGLKKEPNVARVGSVAIKICKMLNIAPLDVCQSAVHLFEDDVVEVWTRSVLSPSEACGLLLGSSCGHWDIFSTWNISLPSVPKPPPKPPSPPAPGAPVSRVLFLTDLHWDHEYLEGTDPYCADPLCCRRGSGWPPNSQKGAGFWGEYSKCDLPLRTLESLLKGLGPAGPFEMVYWTGDIPAHDVWQQSRQDQLRALTTITDLVRKFLGPVPVYPAVGNHESTPVNGFPPPFIKGNQSSQWLYEAMAKAWEPWLPADALHTLRIGGFYALTPRPGLRLISLNMNFCSRENFWLLINSTDPAGQLQWLVEELQAAENRGDKVHIIGHIPPGHCLKSWSWNYYKIIARYENTLAGQFFGHTHVDEFEIFYDEETLSRPLAVAFLAPSATTFINLNPGYRVYQIDGNYPGSSHVVLDHETYILNLTQANAAGGTPSWKRLYRARETYGLPDAMPASWHNLVYRMRDDEQLFQTFWFLYHKGHPPSEPCGTPCRLATLCAQLSARADSPALCRHLMPNGSLPDANRLWSRPLLC
uniprot
proteins
ec_number
3.1.4.12
uniprot
proteins
ec_number
3.1.4.3
uniprot
proteins
function
FUNCTION: Converts sphingomyelin to ceramide (PubMed:8706124, PubMed:9660788). 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 extracellularly. However, in response to various forms of stress, lysosomal exocytosis may represent a major source of the secretory form (By similarity). {ECO:0000250|UniProtKB:P17405, ECO:0000269|PubMed:8706124, ECO:0000269|PubMed:9660788}.; FUNCTION: In the lysosomes, converts sphingomyelin to ceramide. Plays an important role in the export of cholesterol from the intraendolysosomal membranes. Also has phospholipase C activities toward 1,2-diacylglycerolphosphocholine and 1,2-diacylglycerolphosphoglycerol (PubMed:27435900). Modulates stress-induced apoptosis through the production of ceramide (PubMed:8706124). {ECO:0000269|PubMed:27435900, ECO:0000269|PubMed:8706124}.; FUNCTION: When secreted, modulates cell signaling with its ability to reorganize the plasma membrane by converting sphingomyelin to ceramide. 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 viruses. Produces the release of ceramide in the outer leaflet of the plasma membrane playing a central role in host defense. Ceramide reorganizes these rafts into larger signaling platforms that are required to internalize P.aeruginosa, induce apoptosis and regulate the cytokine response in infected cells. In wounded cells, the lysosomal form is released extracellularly in the presence of Ca(2+) and promotes endocytosis and plasma membrane repair. {ECO:0000250|UniProtKB:P17405}.; FUNCTION: [Sphingomyelin phosphodiesterase, processed form]: This form is generated following cleavage by CASP7 in the extracellular milieu in response to bacterial infection (PubMed:35705808). It shows increased ability to convert sphingomyelin to ceramide and promotes plasma membrane repair. Plasma membrane repair by ceramide counteracts the action of gasdermin-D (GSDMD) perforin (PRF1) pores that are formed in response to bacterial infection (PubMed:35705808). {ECO:0000269|PubMed:35705808}.; FUNCTION: (Microbial infection) Secretion is activated by bacteria such as P.aeruginosa, this activation results in the release of ceramide in the outer leaflet of the plasma membrane which facilitates the infection. {ECO:0000269|PubMed:12563314}.
uniprot
proteins
mass_dalton
69927
uniprot
proteins
mutagenesis
MUTAGEN 128; /note="V->E: Retains 20% of wild-type activity with sphingomyelin as substrate; retains 70% of wild-type activity with bis(p-nitrophenyl) phosphate as substrate."; /evidence="ECO:0000269|PubMed:27435900"; MUTAGEN 143; /note="V->R: Retains 10% of wild-type activity with sphingomyelin as substrate; retains 70% of wild-type activity with bis(p-nitrophenyl) phosphate as substrate."; /evidence="ECO:0000269|PubMed:27435900"; MUTAGEN 249; /note="D->A: Knockin mice are fertile and healthy but show increased burdens in response to bacterial infection. Cleavage by Casp7 is abolished, ceramide synthesis is decreased, leading to increased burdens in response to bacterial infection."; /evidence="ECO:0000269|PubMed:35705808"; MUTAGEN 280; /note="H->A: Complete loss of activity."; /evidence="ECO:0000269|PubMed:27435900"; MUTAGEN 283; /note="W->N: Retains 10% of wild-type activity."; /evidence="ECO:0000269|PubMed:27435900"; MUTAGEN 317; /note="H->A: No activity with sphingomyelin as substrate; retains 70% of wild-type activity with bis(p-nitrophenyl) phosphate as substrate."; /evidence="ECO:0000269|PubMed:27435900"; MUTAGEN 321; /note="P->E: Retains 10% of wild-type activity."; /evidence="ECO:0000269|PubMed:27435900"; MUTAGEN 388; /note="F->R: Retains 10% of wild-type activity."; /evidence="ECO:0000269|PubMed:27435900"; MUTAGEN 391; /note="L->R: Retains 20% of wild-type activity with sphingomyelin as substrate; retains 50% of wild-type activity with bis(p-nitrophenyl) phosphate as substrate."; /evidence="ECO:0000269|PubMed:27435900
uniprot
proteins
post_translational_modification
PTM: Proteolytically processed. Mature lysosomal form arises from C-terminal proteolytic processing of pro-sphingomyelin phosphodiesterase. {ECO:0000250|UniProtKB:P17405}.; PTM: Both lysosomal and secreted forms are glycosylated but they show a differential pattern of glycosylation. {ECO:0000250|UniProtKB:P17405}.; PTM: Phosphorylated at Ser-506 by PRKCD upon stress stimuli. Phosphorylation is required for secretion. {ECO:0000250|UniProtKB:P17405}.; PTM: [Sphingomyelin phosphodiesterase, processed form]: This form is generated following cleavage by CASP7 in the extracellular milieu (PubMed:35705808). It shows increased activity (PubMed:35705808). {ECO:0000269|PubMed:35705808}.
uniprot
proteins
protein_family
Acid sphingomyelinase family
uniprot
proteins
pubmed
12563314
uniprot
proteins
pubmed
1292508
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16141072
uniprot
proteins
pubmed
27435900
uniprot
proteins
pubmed
35705808
uniprot
proteins
pubmed
8702487
uniprot
proteins
pubmed
8706124
uniprot
proteins
pubmed
9660788
uniprot
proteins
sequence_length
627
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Lysosome {ECO:0000250|UniProtKB:P17405}. Lipid droplet {ECO:0000250|UniProtKB:P17405}. Secreted {ECO:0000269|PubMed:8702487}. Note=The secreted form is induced in a time- and dose-dependent by IL1B and TNF as well as stress and viral infection. This increase of the secreted form seems to be due to exocytosis of the lysosomal form and is Ca(2+)-dependent. Secretion is dependent of phosphorylation at Ser-506. Secretion is induced by inflammatory mediators such as IL1B, IFNG or TNF as well as infection with bacteria and viruses. {ECO:0000250|UniProtKB:P17405}.; SUBCELLULAR LOCATION: [Sphingomyelin phosphodiesterase, processed form]: Secreted, extracellular space {ECO:0000269|PubMed:35705808}. Note=This form is generated following cleavage by CASP7. {ECO:0000269|PubMed:35705808}.
uniprot
proteins