SMPD1
entrez
6609
canonical
uniprot
P17405
canonical
ensembl
ENSG00000166311
resolver
ensp
ENSP00000340409
resolver
ensp
ENSP00000435350
resolver
ensp
ENSP00000550970
resolver
ensp
ENSP00000659684
resolver
ensp
ENSP00000659686
resolver
genesymbol
SMPD1
resolver
genesymbol_syn
ASM
resolver
hgnc
HGNC:11120
resolver
uniprot
A8K8M3
resolver
uniprot
E9LUE8
resolver
uniprot
E9LUE9
resolver
uniprot
E9PKS3
resolver
uniprot
P17406
resolver
uniprot
Q13811
resolver
uniprot
Q16837
resolver
uniprot
Q16841
resolver
uniprot
Q59EN6
resolver
uniprot
Q8IUN0
resolver
uniprot_entry
ASM_HUMAN
resolver
uniprot_entry
E9LUE8_HUMAN
resolver
uniprot_entry
E9LUE9_HUMAN
resolver
uniprot_entry
Q59EN6_HUMAN
resolver
uniprot_entry
Q8IUN0_HUMAN
resolver
uniprot_sec
A8K8M3
resolver
uniprot_sec
E9PKS3
resolver
uniprot_sec
P17406
resolver
uniprot_sec
Q13811
resolver
uniprot_sec
Q16837
resolver
uniprot_sec
Q16841
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 (PubMed:25339683). Phosphatidylcholine hydrolysis is inhibited by incorporation of cholesterol, ceramide, DAG, monoacylglycerol and fatty acids (PubMed:25339683). Antidepressants, namely amitriptyline, imipramine, desipramine, fluoxetine, sertraline, escitalopram, and maprotiline inhibit sphingomyelin phosphodiesterase activity (PubMed:22573858, PubMed:33163980). {ECO:0000269|PubMed:22573858, ECO:0000269|PubMed:25339683, ECO:0000269|PubMed:33163980}.; ACTIVITY REGULATION: (Microbial infection) The secretory form is activated by P.aeruginosa, this activation results in the release of ceramide in the outer leaflet of the plasma membrane. {ECO:0000269|PubMed:12563314}.; ACTIVITY REGULATION: (Microbial infection) The secretory form is activated by human coronavirus SARS-CoV-2, this activation results in the release of ceramide in the outer leaflet of the plasma membrane. {ECO:0000269|PubMed:33163980}.
uniprot
proteins
amino_acid_sequence
MPRYGASLRQSCPRSGREQGQDGTAGAPGLLWMGLVLALALALALALALSDSRVLWAPAEAHPLSPQGHPARLHRIVPRLRDVFGWGNLTCPICKGLFTAINLGLKKEPNVARVGSVAIKLCNLLKIAPPAVCQSIVHLFEDDMVEVWRRSVLSPSEACGLLLGSTCGHWDIFSSWNISLPTVPKPPPKPPSPPAPGAPVSRILFLTDLHWDHDYLEGTDPDCADPLCCRRGSGLPPASRPGAGYWGEYSKCDLPLRTLESLLSGLGPAGPFDMVYWTGDIPAHDVWHQTRQDQLRALTTVTALVRKFLGPVPVYPAVGNHESTPVNSFPPPFIEGNHSSRWLYEAMAKAWEPWLPAEALRTLRIGGFYALSPYPGLRLISLNMNFCSRENFWLLINSTDPAGQLQWLVGELQAAEDRGDKVHIIGHIPPGHCLKSWSWNYYRIVARYENTLAAQFFGHTHVDEFEVFYDEETLSRPLAVAFLAPSATTYIGLNPGYRVYQIDGNYSGSSHVVLDHETYILNLTQANIPGAIPHWQLLYRARETYGLPNTLPTAWHNLVYRMRGDMQLFQTFWFLYHKGHPPSEPCGTPCRLATLCAQLSARADSPALCRHLMPDGSLPEAQSLWPRPLFC
uniprot
proteins
disease_involvement
DISEASE: Niemann-Pick disease A (NPDA) [MIM:257200]: An early-onset lysosomal storage disorder caused by failure to hydrolyze sphingomyelin to ceramide. It results in the accumulation of sphingomyelin and other metabolically related lipids in reticuloendothelial and other cell types throughout the body, leading to cell death. Niemann-Pick disease type A is a primarily neurodegenerative disorder characterized by onset within the first year of life, intellectual disability, digestive disorders, failure to thrive, major hepatosplenomegaly, and severe neurologic symptoms. The severe neurological disorders and pulmonary infections lead to an early death, often around the age of four. Clinical features are variable. A phenotypic continuum exists between type A (basic neurovisceral) and type B (purely visceral) forms of Niemann-Pick disease, and the intermediate types encompass a cluster of variants combining clinical features of both types A and B. {ECO:0000269|PubMed:12556236, ECO:0000269|PubMed:1391960, ECO:0000269|PubMed:15221801, ECO:0000269|PubMed:15877209, ECO:0000269|PubMed:1618760, ECO:0000269|PubMed:1718266, ECO:0000269|PubMed:18815062, ECO:0000269|PubMed:19405096, ECO:0000269|PubMed:2023926, ECO:0000269|PubMed:20386867, ECO:0000269|PubMed:22818240, ECO:0000269|PubMed:23252888, ECO:0000269|PubMed:23430884, ECO:0000269|PubMed:26499107, ECO:0000269|PubMed:27338287, ECO:0000269|PubMed:8680412, ECO:0000269|PubMed:8693491, ECO:0000269|PubMed:9266408, ECO:0000269|PubMed:9660788}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Niemann-Pick disease B (NPDB) [MIM:607616]: A late-onset lysosomal storage disorder caused by failure to hydrolyze sphingomyelin to ceramide. It results in the accumulation of sphingomyelin and other metabolically related lipids in reticuloendothelial and other cell types throughout the body, leading to cell death. Clinical signs involve only visceral organs. The most constant sign is hepatosplenomegaly which can be associated with pulmonary symptoms. Patients remain free of neurologic manifestations. However, a phenotypic continuum exists between type A (basic neurovisceral) and type B (purely visceral) forms of Niemann-Pick disease, and the intermediate types encompass a cluster of variants combining clinical features of both types A and B. In Niemann-Pick disease type B, onset of the first symptoms occurs in early childhood and patients can survive into adulthood. {ECO:0000269|PubMed:12369017, ECO:0000269|PubMed:12556236, ECO:0000269|PubMed:1301192, ECO:0000269|PubMed:15241805, ECO:0000269|PubMed:16010684, ECO:0000269|PubMed:1618760, ECO:0000269|PubMed:16472269, ECO:0000269|PubMed:18815062, ECO:0000269|PubMed:1885770, ECO:0000269|PubMed:19050888, ECO:0000269|PubMed:19405096, ECO:0000269|PubMed:20386867, ECO:0000269|PubMed:21098024, ECO:0000269|PubMed:21621718, ECO:0000269|PubMed:22613662, ECO:0000269|PubMed:22818240, ECO:0000269|PubMed:23252888, ECO:0000269|PubMed:23430512, ECO:0000269|PubMed:25920558, ECO:0000269|PubMed:26084044, ECO:0000269|PubMed:26499107, ECO:0000269|PubMed:27338287, ECO:0000269|PubMed:27659707, ECO:0000269|PubMed:8051942, ECO:0000269|PubMed:8664904}. Note=The disease is caused by variants affecting the gene represented in this entry.
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:12563314, PubMed:1840600, PubMed:18815062, PubMed:25339683, PubMed:25920558, PubMed:27659707, PubMed: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 extracellularly (PubMed:20807762, PubMed:21098024, PubMed:9660788). However, in response to various forms of stress, lysosomal exocytosis may represent a major source of the secretory form (PubMed:12563314, PubMed:20530211, PubMed:20807762, PubMed:22573858, PubMed:9393854). {ECO:0000269|PubMed:12563314, ECO:0000269|PubMed:1840600, ECO:0000269|PubMed:18815062, ECO:0000269|PubMed:20530211, ECO:0000269|PubMed:20807762, ECO:0000269|PubMed:21098024, ECO:0000269|PubMed:22573858, ECO:0000269|PubMed:25339683, ECO:0000269|PubMed:25920558, ECO:0000269|PubMed:27659707, ECO:0000269|PubMed:33163980, ECO:0000269|PubMed:9393854, ECO:0000269|PubMed:9660788, ECO:0000305}.; FUNCTION: In the lysosomes, converts sphingomyelin to ceramide (PubMed:20807762, PubMed:21098024). Plays an important role in the export of cholesterol from the intraendolysosomal membranes (PubMed:25339683). Also has phospholipase C activities toward 1,2-diacylglycerolphosphocholine and 1,2-diacylglycerolphosphoglycerol (PubMed:25339683). Modulates stress-induced apoptosis through the production of ceramide (PubMed:8706124). {ECO:0000269|PubMed:20807762, ECO:0000269|PubMed:21098024, ECO:0000269|PubMed:25339683, ECO:0000269|PubMed:8706124}.; FUNCTION: When secreted, modulates cell signaling with its ability to reorganize the plasma membrane by converting sphingomyelin to ceramide (PubMed:12563314, PubMed:17303575, PubMed: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 viruses (PubMed:12563314, PubMed:20807762, PubMed:9393854). Produces the release of ceramide in the outer leaflet of the plasma membrane playing a central role in host defense (PubMed:12563314, PubMed:20807762, PubMed: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 cells (PubMed:12563314). In wounded cells, the lysosomal form is released extracellularly in the presence of Ca(2+) and promotes endocytosis and plasma membrane repair (PubMed:20530211). {ECO:0000269|PubMed:12563314, ECO:0000269|PubMed:17303575, ECO:0000269|PubMed:20530211, ECO:0000269|PubMed:20807762, ECO:0000269|PubMed:9393854}.; FUNCTION: [Sphingomyelin phosphodiesterase, processed form]: This form is generated following cleavage by CASP7 in the extracellular milieu in response to bacterial infection (PubMed:21157428). 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). {ECO:0000250|UniProtKB:Q04519, ECO:0000269|PubMed:21157428}.; FUNCTION: (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. {ECO:0000269|PubMed:12563314, ECO:0000269|PubMed:9393854, ECO:0000305|PubMed:31155842}.; FUNCTION: (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. {ECO:0000269|PubMed:22573858, ECO:0000269|PubMed:33163980}.; FUNCTION: [Isoform 2]: Lacks residues that bind the cofactor Zn(2+) and has no enzyme activity. {ECO:0000269|PubMed:1840600, ECO:0000305}.; FUNCTION: [Isoform 3]: Lacks residues that bind the cofactor Zn(2+) and has no enzyme activity. {ECO:0000269|PubMed:1840600, ECO:0000305}.
uniprot
proteins
mass_dalton
69936
uniprot
proteins
mutagenesis
MUTAGEN 88; /note="N->G: No effect on sphingomyelin phosphodiesterase activity. No effect on secretion."; /evidence="ECO:0000269|PubMed:9030779"; MUTAGEN 151; /note="S->A: No effect on sphingomyelin phosphodiesterase activity. No effect on subcellular location. No effect on phosphorylation by PRKCD."; /evidence="ECO:0000269|PubMed:17303575"; MUTAGEN 177; /note="N->G: Reduces protein levels. Reduces sphingomyelin phosphodiesterase activity. No effect on secretion."; /evidence="ECO:0000269|PubMed:9030779"; MUTAGEN 225; /note="D->A: Does not affect cleavage by CASP7."; /evidence="ECO:0000269|PubMed:21157428"; MUTAGEN 233; /note="S->A: No effect on sphingomyelin phosphodiesterase activity. No effect on endolysosome location. No effect on phosphorylation by PRKCD."; /evidence="ECO:0000269|PubMed:17303575"; MUTAGEN 250; /note="S->A: No effect on sphingomyelin phosphodiesterase activity. No effect on endolysosome location. No effect on phosphorylation by PRKCD."; /evidence="ECO:0000269|PubMed:17303575"; MUTAGEN 253; /note="D->A: Abolished cleavage by CASP7."; /evidence="ECO:0000269|PubMed:21157428"; MUTAGEN 337; /note="N->G: No effect on sphingomyelin phosphodiesterase activity. No effect on secretion."; /evidence="ECO:0000269|PubMed:9030779"; MUTAGEN 397; /note="N->G: Reduces sphingomyelin phosphodiesterase activity. No effect on secretion."; /evidence="ECO:0000269|PubMed:9030779"; MUTAGEN 505; /note="N->G: Loss of sphingomyelin phosphodiesterase activity. Loss of secretion."; /evidence="ECO:0000269|PubMed:9030779"; MUTAGEN 510; /note="S->A: Abolishes constitutive secretion and decreases secretion in response to IL1B. No effect on lysosomal targeting. No effect on sphingomyelin phosphodiesterase activity. No effect on endolysosome location. Abolishes phosphorylation by PRKCD."; /evidence="ECO:0000269|PubMed:17303575, ECO:0000269|PubMed:20807762"; MUTAGEN 522; /note="N->G: Loss of sphingomyelin phosphodiesterase activity. Loss of secretion."; /evidence="ECO:0000269|PubMed:9030779
uniprot
proteins
post_translational_modification
PTM: Proteolytically processed (PubMed:21098024, PubMed:9030779). Mature lysosomal form arises from C-terminal proteolytic processing of pro-sphingomyelin phosphodiesterase (PubMed:21098024). {ECO:0000269|PubMed:21098024, ECO:0000269|PubMed:9030779}.; PTM: [Sphingomyelin phosphodiesterase, processed form]: This form is generated following cleavage by CASP7 in the extracellular milieu (PubMed:21157428). It shows increased activity (By similarity). {ECO:0000250|UniProtKB:Q04519, ECO:0000269|PubMed:21157428}.; PTM: Both lysosomal and secreted forms are glycosylated but they show a differential pattern of glycosylation. {ECO:0000269|PubMed:20807762, ECO:0000269|PubMed:9030779}.; PTM: Phosphorylated at Ser-510 by PRKCD upon stress stimuli. Phosphorylation is required for secretion. {ECO:0000269|PubMed:17303575, ECO:0000269|PubMed:20807762, ECO:0000269|PubMed:9030779}.
uniprot
proteins
protein_family
Acid sphingomyelinase family
uniprot
proteins
pubmed
12369017
uniprot
proteins
pubmed
12556236
uniprot
proteins
pubmed
12563314
uniprot
proteins
pubmed
12631268
uniprot
proteins
pubmed
1292508
uniprot
proteins
pubmed
1301192
uniprot
proteins
pubmed
1391960
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15221801
uniprot
proteins
pubmed
15241805
uniprot
proteins
pubmed
15877209
uniprot
proteins
pubmed
16010684
uniprot
proteins
pubmed
1618760
uniprot
proteins
pubmed
16472269
uniprot
proteins
pubmed
16554811
uniprot
proteins
pubmed
16787399
uniprot
proteins
pubmed
1718266
uniprot
proteins
pubmed
17303575
uniprot
proteins
pubmed
1740330
uniprot
proteins
pubmed
18088425
uniprot
proteins
pubmed
1840600
uniprot
proteins
pubmed
18815062
uniprot
proteins
pubmed
1885770
uniprot
proteins
pubmed
19050888
uniprot
proteins
pubmed
19405096
uniprot
proteins
pubmed
2023926
uniprot
proteins
pubmed
20386867
uniprot
proteins
pubmed
20530211
uniprot
proteins
pubmed
20807762
uniprot
proteins
pubmed
21098024
uniprot
proteins
pubmed
21157428
uniprot
proteins
pubmed
21621718
uniprot
proteins
pubmed
22573858
uniprot
proteins
pubmed
22613662
uniprot
proteins
pubmed
22818240
uniprot
proteins
pubmed
23252888
uniprot
proteins
pubmed
23430512
uniprot
proteins
pubmed
23430884
uniprot
proteins
pubmed
25339683
uniprot
proteins
pubmed
2555181
uniprot
proteins
pubmed
25920558
uniprot
proteins
pubmed
26084044
uniprot
proteins
pubmed
26499107
uniprot
proteins
pubmed
27338287
uniprot
proteins
pubmed
27349982
uniprot
proteins
pubmed
27659707
uniprot
proteins
pubmed
27725636
uniprot
proteins
pubmed
31155842
uniprot
proteins
pubmed
33163980
uniprot
proteins
pubmed
8051942
uniprot
proteins
pubmed
8407868
uniprot
proteins
pubmed
8664904
uniprot
proteins
pubmed
8680412
uniprot
proteins
pubmed
8693491
uniprot
proteins
pubmed
8702487
uniprot
proteins
pubmed
8706124
uniprot
proteins
pubmed
9030779
uniprot
proteins
pubmed
9266408
uniprot
proteins
pubmed
9393854
uniprot
proteins
pubmed
9660788
uniprot
proteins
sequence_length
631
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Lysosome {ECO:0000269|PubMed:16787399, ECO:0000269|PubMed:18815062, ECO:0000269|PubMed:20530211, ECO:0000269|PubMed:20807762, ECO:0000269|PubMed:27659707, ECO:0000269|PubMed:9660788}. Lipid droplet {ECO:0000269|PubMed:25339683}. Secreted {ECO:0000269|PubMed:12563314, ECO:0000269|PubMed:16787399, ECO:0000269|PubMed:17303575, ECO:0000269|PubMed:20530211, ECO:0000269|PubMed:20807762, ECO:0000269|PubMed:22573858, ECO:0000269|PubMed:27659707, ECO:0000269|PubMed:8702487, ECO:0000269|PubMed:9030779, ECO:0000269|PubMed:9660788}. 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 (PubMed:20530211, PubMed:20807762, PubMed:22573858). Secretion is dependent of phosphorylation at Ser-510 (PubMed:17303575). Secretion is induced by inflammatory mediators such as IL1B, IFNG or TNF as well as infection with bacteria and viruses (PubMed:12563314, PubMed:20807762). {ECO:0000269|PubMed:12563314, ECO:0000269|PubMed:17303575, ECO:0000269|PubMed:20530211, ECO:0000269|PubMed:20807762, ECO:0000269|PubMed:22573858}.; SUBCELLULAR LOCATION: [Sphingomyelin phosphodiesterase, processed form]: Secreted, extracellular space {ECO:0000250|UniProtKB:Q04519}. Note=This form is generated following cleavage by CASP7. {ECO:0000250|UniProtKB:Q04519}.
uniprot
proteins