Query author contributions in Reactome

Reactome depends on collaboration between our curation team and outside experts to assemble and peer-review its pathway modules. The integration of ORCID within Reactome enables us to meet a key challenge with authoring, curating and reviewing biological information by incentivizing and crediting the external experts that contribute their expertise and time to the Reactome curation process. More information is available at ORCID and Reactome.

If you have an ORCID ID that is not listed on this page, please forward this information to us and we will update your Reactome pathway records.

Details on Person UniProt:P17405 SMPD1

Class:Id	ReferenceGeneProduct:50397
_chainChangeLog	signal peptide:1-46 added on Fri February 6 2015;chain:47-629 added on Fri February 6 2015;chain:254-631 for 50397 added on Fri November 4 2022
_displayName	UniProt:P17405 SMPD1
_timestamp	2025-05-21 21:10:21
chain	signal peptide:1-46 chain:47-631 chain:254-631
checksum	F229709F6A9B0E9E
comment	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).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).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).FUNCTION 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).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.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.FUNCTION Lacks residues that bind the cofactor Zn(2+) and has no enzyme activity.FUNCTION Lacks residues that bind the cofactor Zn(2+) and has no enzyme activity.CATALYTIC ACTIVITY a sphingomyelin + H2O = phosphocholine + an N-acylsphing-4-enine + H(+)CATALYTIC ACTIVITY N-(octadecanoyl)-sphing-4-enine-1-phosphocholine + H2O = N-octadecanoylsphing-4-enine + phosphocholine + H(+)CATALYTIC ACTIVITY 1,2-dihexadecanoyl-sn-glycero-3-phosphocholine + H2O = 1,2-dihexadecanoyl-sn-glycerol + phosphocholine + H(+)CATALYTIC ACTIVITY a 1,2-diacyl-sn-glycero-3-phosphocholine + H2O = phosphocholine + a 1,2-diacyl-sn-glycerol + H(+)CATALYTIC ACTIVITY a sphingomyelin + H2O = phosphocholine + an N-acylsphing-4-enine + H(+)COFACTOR Binds 2 Zn(2+) ions per subunit (PubMed:27349982, PubMed:27725636).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).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.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.SUBUNIT Monomer. Interacts with SORT1; the interaction is required for SMPD1 targeting to lysosomes (PubMed:16787399).INTERACTION 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).SUBCELLULAR LOCATION This form is generated following cleavage by CASP7.ALTERNATIVE PRODUCTS Proteolytically processed (PubMed:21098024, PubMed:9030779). Mature lysosomal form arises from C-terminal proteolytic processing of pro-sphingomyelin phosphodiesterase (PubMed:21098024).PTM This form is generated following cleavage by CASP7 in the extracellular milieu (PubMed:21157428). It shows increased activity (By similarity).PTM Both lysosomal and secreted forms are glycosylated but they show a differential pattern of glycosylation.PTM Phosphorylated at Ser-510 by PRKCD upon stress stimuli. Phosphorylation is required for secretion.POLYMORPHISM A common polymorphism arises from a variable number of hexanucleotide repeat sequence within the signal peptide region.DISEASE The disease is caused by variants affecting the gene represented in this entry.DISEASE The disease is caused by variants affecting the gene represented in this entry.MISCELLANEOUS There are two types of sphingomyelinases: ASM (acid), and NSM (neutral).MISCELLANEOUS Most abundant (90%).MISCELLANEOUS Intermediate abundance (10%).MISCELLANEOUS Low abundance (<1%).SIMILARITY Belongs to the acid sphingomyelinase family.CAUTION Variants Gln-294 and Val-485 have been originally reported as disease-causing mutations in NPDA and NPDB (PubMed:12369017, PubMed:15221801). These variants have been reclassified as benign polymorphisms (PubMed:23430512).ONLINE INFORMATION Leiden Open Variation Database (LOVD)
description	recommendedName: fullName evidence="66"Sphingomyelin phosphodiesterase ecNumber evidence="14 19 23 24 41 44 56"3.1.4.12 ecNumber evidence="41"3.1.4.3 alternativeName: fullName evidence="63 64 65"Acid sphingomyelinase shortName: aSMase component recommendedName: fullName evidence="66"Sphingomyelin phosphodiesterase, processed form /component
geneName	SMPD1 ASM
identifier	P17405
isSequenceChanged	FALSE
keyword	3D-structure Alternative splicing Direct protein sequencing Disease variant Disulfide bond Glycoprotein Glycosidase Host-virus interaction Hydrolase Lipid droplet Lipid metabolism Lysosome Metal-binding Neurodegeneration Niemann-Pick disease Phosphoprotein Proteomics identification Reference proteome Secreted Signal Zinc
modified	[InstanceEdit:9836292] Weiser, Joel, 2023-05-25 [InstanceEdit:9852000] Weiser, Joel, 2023-11-03 [InstanceEdit:9917590] Weiser, Joel, 2024-08-09 [InstanceEdit:9926675] Weiser, Joel, 2024-11-03 [InstanceEdit:9939033] Weiser, Joel, 2025-02-21 [InstanceEdit:9948485] Weiser, Joel, 2025-05-21
name	SMPD1
referenceDatabase	[ReferenceDatabase:2] UniProt
referenceGene	[ReferenceDNASequence:9003390] ENSEMBL:ENSG00000166311 SMPD1 [Homo sapiens]
secondaryIdentifier	ASM_HUMAN A8K8M3 E9PKS3 P17406 Q13811 Q16837 Q16841
sequenceLength	631
species	[Species:48887] Homo sapiens
(isoformParent)	[ReferenceIsoform:144223] UniProt:P17405-2 SMPD1 [Homo sapiens] [ReferenceIsoform:144224] UniProt:P17405-3 SMPD1 [Homo sapiens] [ReferenceIsoform:403084] UniProt:P17405-1 SMPD1 [Homo sapiens] [ReferenceIsoform:8973182] UniProt:P17405-4 SMPD1 [Homo sapiens]
(referenceEntity)	[EntityWithAccessionedSequence:1605710] SMPD1 [lysosomal lumen] [Homo sapiens] [EntityWithAccessionedSequence:9769734] SMPD1 [plasma membrane] [Homo sapiens]
[Change default viewing format]

No pathways have been reviewed or authored by UniProt:P17405 SMPD1 (50397)