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UniProtKB - P17405 (ASM_HUMAN)
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>sp|P17405|ASM_HUMAN Sphingomyelin phosphodiesterase OS=Homo sapiens OX=9606 GN=SMPD1 PE=1 SV=5 MPRYGASLRQSCPRSGREQGQDGTAGAPGLLWMGLVLALALALALALALSDSRVLWAPAE AHPLSPQGHPARLHRIVPRLRDVFGWGNLTCPICKGLFTAINLGLKKEPNVARVGSVAIK LCNLLKIAPPAVCQSIVHLFEDDMVEVWRRSVLSPSEACGLLLGSTCGHWDIFSSWNISL PTVPKPPPKPPSPPAPGAPVSRILFLTDLHWDHDYLEGTDPDCADPLCCRRGSGLPPASR PGAGYWGEYSKCDLPLRTLESLLSGLGPAGPFDMVYWTGDIPAHDVWHQTRQDQLRALTT VTALVRKFLGPVPVYPAVGNHESTPVNSFPPPFIEGNHSSRWLYEAMAKAWEPWLPAEAL RTLRIGGFYALSPYPGLRLISLNMNFCSRENFWLLINSTDPAGQLQWLVGELQAAEDRGD KVHIIGHIPPGHCLKSWSWNYYRIVARYENTLAAQFFGHTHVDEFEVFYDEETLSRPLAV AFLAPSATTYIGLNPGYRVYQIDGNYSGSSHVVLDHETYILNLTQANIPGAIPHWQLLYR ARETYGLPNTLPTAWHNLVYRMRGDMQLFQTFWFLYHKGHPPSEPCGTPCRLATLCAQLS ARADSPALCRHLMPDGSLPEAQSLWPRPLFCCommunity curation ()Add a publicationFeedback
Protein
Sphingomyelin phosphodiesterase
Gene
SMPD1
Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score:
Annotation score:5 out of 5
<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>-Experimental evidence at protein leveli <p>This indicates the type of evidence that supports the existence of the protein. Note that the 'protein existence' evidence does not give information on the accuracy or correctness of the sequence(s) displayed.<p><a href='/help/protein_existence' target='_top'>More...</a></p>Select a section on the left to see content.
<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni
Converts sphingomyelin to ceramide (PubMed:1840600, PubMed:18815062, PubMed:27659707, PubMed:25920558, PubMed:25339683, PubMed:33163980, PubMed:12563314).
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:21098024, PubMed:9660788, PubMed:20807762).
However, in response to various forms of stress, lysosomal exocytosis may represent a major source of the secretory form (PubMed:20530211, PubMed:12563314, PubMed:20807762, PubMed:9393854, PubMed:22573858).
Curated13 Publications<p>Manually curated information for which there is published experimental evidence.</p> <p><a href="/manual/evidences#ECO:0000269">More...</a></p> Manual assertion based on experiment ini
- Ref.1"Human acid sphingomyelinase. Isolation, nucleotide sequence and expression of the full-length and alternatively spliced cDNAs."
Schuchman E.H., Suchi M., Takahashi T., Sandhoff K., Desnick R.J.
J. Biol. Chem. 266:8531-8539(1991) [PubMed] [Europe PMC] [Abstract]Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY, ALTERNATIVE SPLICING, VARIANTS 48-ALA-LEU-49 DEL; ILE-324 AND ARG-508. - Ref.11"Acidic sphingomyelinase mediates entry of N. gonorrhoeae into nonphagocytic cells."
Grassme H., Gulbins E., Brenner B., Ferlinz K., Sandhoff K., Harzer K., Lang F., Meyer T.F.
Cell 91:605-615(1997) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, FUNCTION (MICROBIAL INFECTION). - Ref.13"Host defense against Pseudomonas aeruginosa requires ceramide-rich membrane rafts."
Grassme H., Jendrossek V., Riehle A., von Kuerthy G., Berger J., Schwarz H., Weller M., Kolesnick R., Gulbins E.
Nat. Med. 9:322-330(2003) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, SUBCELLULAR LOCATION, ACTIVITY REGULATION (MICROBIAL INFECTION), CATALYTIC ACTIVITY. - Ref.17"Regulated secretion of acid sphingomyelinase: implications for selectivity of ceramide formation."
Jenkins R.W., Canals D., Idkowiak-Baldys J., Simbari F., Roddy P., Perry D.M., Kitatani K., Luberto C., Hannun Y.A.
J. Biol. Chem. 285:35706-35718(2010) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, GLYCOSYLATION, MUTAGENESIS OF SER-510. - Ref.18"Exocytosis of acid sphingomyelinase by wounded cells promotes endocytosis and plasma membrane repair."
Tam C., Idone V., Devlin C., Fernandes M.C., Flannery A., He X., Schuchman E., Tabas I., Andrews N.W.
J. Cell Biol. 189:1027-1038(2010) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION. - Ref.19"Ebolavirus requires acid sphingomyelinase activity and plasma membrane sphingomyelin for infection."
Miller M.E., Adhikary S., Kolokoltsov A.A., Davey R.A.
J. Virol. 86:7473-7483(2012) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION (MICROBIAL INFECTION), SUBCELLULAR LOCATION, CATALYTIC ACTIVITY, ACTIVITY REGULATION. - Ref.20"Acid sphingomyelinase activity is regulated by membrane lipids and facilitates cholesterol transfer by NPC2."
Oninla V.O., Breiden B., Babalola J.O., Sandhoff K.
J. Lipid Res. 55:2606-2619(2014) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, SUBCELLULAR LOCATION. - Ref.22"Pharmacological Inhibition of Acid Sphingomyelinase Prevents Uptake of SARS-CoV-2 by Epithelial Cells."
Carpinteiro A., Edwards M.J., Hoffmann M., Kochs G., Gripp B., Weigang S., Adams C., Carpinteiro E., Gulbins A., Keitsch S., Sehl C., Soddemann M., Wilker B., Kamler M., Bertsch T., Lang K.S., Patel S., Wilson G.C. , Walter S., Hengel H., Poehlmann S., Lang P.A., Kornhuber J., Becker K.A., Ahmad S.A., Fassbender K., Gulbins E.
Cell Rep. 1:100142-100142(2020) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION (MICROBIAL INFECTION), ACTIVITY REGULATION, CATALYTIC ACTIVITY. - Ref.36"The cellular trafficking and zinc dependence of secretory and lysosomal sphingomyelinase, two products of the acid sphingomyelinase gene."
Schissel S.L., Keesler G.A., Schuchman E.H., Williams K.J., Tabas I.
J. Biol. Chem. 273:18250-18259(1998) [PubMed] [Europe PMC] [Abstract]Cited for: CHARACTERIZATION OF VARIANT NPDA LEU-498, FUNCTION, COFACTOR. - Ref.44"Characterization of common SMPD1 mutations causing types A and B Niemann-Pick disease and generation of mutation-specific mouse models."
Jones I., He X., Katouzian F., Darroch P.I., Schuchman E.H.
Mol. Genet. Metab. 95:152-162(2008) [PubMed] [Europe PMC] [Abstract]Cited for: CHARACTERIZATION OF VARIANTS NPDA PRO-304 AND LEU-498, CHARACTERIZATION OF VARIANTS NPDB TYR-423 AND ARG-610 DEL, FUNCTION, SUBCELLULAR LOCATION, CATALYTIC ACTIVITY. - Ref.48"A novel mechanism of lysosomal acid sphingomyelinase maturation: requirement for carboxyl-terminal proteolytic processing."
Jenkins R.W., Idkowiak-Baldys J., Simbari F., Canals D., Roddy P., Riner C.D., Clarke C.J., Hannun Y.A.
J. Biol. Chem. 286:3777-3788(2011) [PubMed] [Europe PMC] [Abstract]Cited for: CATALYTIC ACTIVITY, FUNCTION, SUBCELLULAR LOCATION, CHARACTERIZATION OF VARIANTS NPDB HIS-602; PRO-602 AND ARG-610 DEL. - Ref.58"Structural and functional analysis of the ASM p.Ala359Asp mutant that causes acid sphingomyelinase deficiency."
Acuna M., Castro-Fernandez V., Latorre M., Castro J., Schuchman E.H., Guixe V., Gonzalez M., Zanlungo S.
Biochem. Biophys. Res. Commun. 479:496-501(2016) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, CHARACTERIZATION OF VARIANT NPDB ASP-359. - Ref.59"Epidemiological, clinical and biochemical characterization of the p.(Ala359Asp) SMPD1 variant causing Niemann-Pick disease type B."
Acuna M., Martinez P., Moraga C., He X., Moraga M., Hunter B., Nuernberg P., Gutierrez R.A., Gonzalez M., Schuchman E.H., Santos J.L., Miquel J.F., Mabe P., Zanlungo S.
Eur. J. Hum. Genet. 24:208-213(2016) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, SUBCELLULAR LOCATION, VARIANT NPDB ASP-359, CHARACTERIZATION OF VARIANT NPDB ASP-359.
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).
4 PublicationsManual assertion based on experiment ini
- Ref.8"Acid sphingomyelinase-deficient human lymphoblasts and mice are defective in radiation-induced apoptosis."
Santana P., Pena L.A., Haimovitz-Friedman A., Martin S., Green D., McLoughlin M., Cordon-Cardo C., Schuchman E.H., Fuks Z., Kolesnick R.
Cell 86:189-199(1996) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, CATALYTIC ACTIVITY. - Ref.17"Regulated secretion of acid sphingomyelinase: implications for selectivity of ceramide formation."
Jenkins R.W., Canals D., Idkowiak-Baldys J., Simbari F., Roddy P., Perry D.M., Kitatani K., Luberto C., Hannun Y.A.
J. Biol. Chem. 285:35706-35718(2010) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, GLYCOSYLATION, MUTAGENESIS OF SER-510. - Ref.20"Acid sphingomyelinase activity is regulated by membrane lipids and facilitates cholesterol transfer by NPC2."
Oninla V.O., Breiden B., Babalola J.O., Sandhoff K.
J. Lipid Res. 55:2606-2619(2014) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, SUBCELLULAR LOCATION. - Ref.48"A novel mechanism of lysosomal acid sphingomyelinase maturation: requirement for carboxyl-terminal proteolytic processing."
Jenkins R.W., Idkowiak-Baldys J., Simbari F., Canals D., Roddy P., Riner C.D., Clarke C.J., Hannun Y.A.
J. Biol. Chem. 286:3777-3788(2011) [PubMed] [Europe PMC] [Abstract]Cited for: CATALYTIC ACTIVITY, FUNCTION, SUBCELLULAR LOCATION, CHARACTERIZATION OF VARIANTS NPDB HIS-602; PRO-602 AND ARG-610 DEL.
When secreted, modulates cell signaling with its ability to reorganize the plasma membrane by converting sphingomyelin to ceramide (PubMed:12563314, PubMed:20807762, PubMed:17303575).
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 (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 Ca2+ and promotes endocytosis and plasma membrane repair (PubMed:20530211).
5 PublicationsManual assertion based on experiment ini
- Ref.11"Acidic sphingomyelinase mediates entry of N. gonorrhoeae into nonphagocytic cells."
Grassme H., Gulbins E., Brenner B., Ferlinz K., Sandhoff K., Harzer K., Lang F., Meyer T.F.
Cell 91:605-615(1997) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, FUNCTION (MICROBIAL INFECTION). - Ref.13"Host defense against Pseudomonas aeruginosa requires ceramide-rich membrane rafts."
Grassme H., Jendrossek V., Riehle A., von Kuerthy G., Berger J., Schwarz H., Weller M., Kolesnick R., Gulbins E.
Nat. Med. 9:322-330(2003) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, SUBCELLULAR LOCATION, ACTIVITY REGULATION (MICROBIAL INFECTION), CATALYTIC ACTIVITY. - Ref.16"Activation of acid sphingomyelinase by protein kinase Cdelta-mediated phosphorylation."
Zeidan Y.H., Hannun Y.A.
J. Biol. Chem. 282:11549-11561(2007) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, PHOSPHORYLATION AT SER-510, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, MUTAGENESIS OF SER-151; SER-233; SER-250 AND SER-510. - Ref.17"Regulated secretion of acid sphingomyelinase: implications for selectivity of ceramide formation."
Jenkins R.W., Canals D., Idkowiak-Baldys J., Simbari F., Roddy P., Perry D.M., Kitatani K., Luberto C., Hannun Y.A.
J. Biol. Chem. 285:35706-35718(2010) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, GLYCOSYLATION, MUTAGENESIS OF SER-510. - Ref.18"Exocytosis of acid sphingomyelinase by wounded cells promotes endocytosis and plasma membrane repair."
Tam C., Idone V., Devlin C., Fernandes M.C., Flannery A., He X., Schuchman E., Tabas I., Andrews N.W.
J. Cell Biol. 189:1027-1038(2010) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION.
Lacks residues that bind the cofactor Zn2+ and has no enzyme activity.
Curated1 PublicationManual assertion based on experiment ini
- Ref.1"Human acid sphingomyelinase. Isolation, nucleotide sequence and expression of the full-length and alternatively spliced cDNAs."
Schuchman E.H., Suchi M., Takahashi T., Sandhoff K., Desnick R.J.
J. Biol. Chem. 266:8531-8539(1991) [PubMed] [Europe PMC] [Abstract]Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY, ALTERNATIVE SPLICING, VARIANTS 48-ALA-LEU-49 DEL; ILE-324 AND ARG-508.
Lacks residues that bind the cofactor Zn2+ and has no enzyme activity.
Curated1 PublicationManual assertion based on experiment ini
- Ref.1"Human acid sphingomyelinase. Isolation, nucleotide sequence and expression of the full-length and alternatively spliced cDNAs."
Schuchman E.H., Suchi M., Takahashi T., Sandhoff K., Desnick R.J.
J. Biol. Chem. 266:8531-8539(1991) [PubMed] [Europe PMC] [Abstract]Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY, ALTERNATIVE SPLICING, VARIANTS 48-ALA-LEU-49 DEL; ILE-324 AND ARG-508.
(Microbial infection) Secretion is activated by bacteria such as P. aeruginos, N. gonorrhoeae and others, this activation results in the release of ceramide in the outer leaflet of the plasma membrane which facilitates the infection.
1 Publication<p>Manually curated information which has been inferred by a curator based on his/her scientific knowledge or on the scientific content of an article.</p> <p><a href="/manual/evidences#ECO:0000305">More...</a></p> Manual assertion inferred by curator fromi
- Ref.21"Solving the secretory acid sphingomyelinase puzzle: Insights from lysosome-mediated parasite invasion and plasma membrane repair."
Andrews N.W.
Cell. Microbiol. 21:e13065-e13065(2019) [PubMed] [Europe PMC] [Abstract]Cited for: REVIEW OF FUNCTION AND SUBCELLULAR LOCATION.
Manual assertion based on experiment ini
- Ref.11"Acidic sphingomyelinase mediates entry of N. gonorrhoeae into nonphagocytic cells."
Grassme H., Gulbins E., Brenner B., Ferlinz K., Sandhoff K., Harzer K., Lang F., Meyer T.F.
Cell 91:605-615(1997) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, FUNCTION (MICROBIAL INFECTION). - Ref.13"Host defense against Pseudomonas aeruginosa requires ceramide-rich membrane rafts."
Grassme H., Jendrossek V., Riehle A., von Kuerthy G., Berger J., Schwarz H., Weller M., Kolesnick R., Gulbins E.
Nat. Med. 9:322-330(2003) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, SUBCELLULAR LOCATION, ACTIVITY REGULATION (MICROBIAL INFECTION), CATALYTIC ACTIVITY.
(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.
2 PublicationsManual assertion based on experiment ini
- Ref.19"Ebolavirus requires acid sphingomyelinase activity and plasma membrane sphingomyelin for infection."
Miller M.E., Adhikary S., Kolokoltsov A.A., Davey R.A.
J. Virol. 86:7473-7483(2012) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION (MICROBIAL INFECTION), SUBCELLULAR LOCATION, CATALYTIC ACTIVITY, ACTIVITY REGULATION. - Ref.22"Pharmacological Inhibition of Acid Sphingomyelinase Prevents Uptake of SARS-CoV-2 by Epithelial Cells."
Carpinteiro A., Edwards M.J., Hoffmann M., Kochs G., Gripp B., Weigang S., Adams C., Carpinteiro E., Gulbins A., Keitsch S., Sehl C., Soddemann M., Wilker B., Kamler M., Bertsch T., Lang K.S., Patel S., Wilson G.C. , Walter S., Hengel H., Poehlmann S., Lang P.A., Kornhuber J., Becker K.A., Ahmad S.A., Fassbender K., Gulbins E.
Cell Rep. 1:100142-100142(2020) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION (MICROBIAL INFECTION), ACTIVITY REGULATION, CATALYTIC ACTIVITY.
Miscellaneous
There are two types of sphingomyelinases: ASM (acid), and NSM (neutral).
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).3 Publications
Manual assertion based on experiment ini
- Ref.37"The demographics and distribution of type B Niemann-Pick disease: novel mutations lead to new genotype/phenotype correlations."
Simonaro C.M., Desnick R.J., McGovern M.M., Wasserstein M.P., Schuchman E.H.
Am. J. Hum. Genet. 71:1413-1419(2002) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANTS NPDB VAL-51; TRP-94; PRO-139; ARG-159; PRO-198; CYS-202; MET-227; CYS-230; ASP-234; SER-247; ARG-250; HIS-291; ALA-325; ARG-332; ASP-359; HIS-378; LEU-378; PRO-381; VAL-415; TYR-423; ARG-433; PRO-434; CYS-437; VAL-454; ASP-458; TRP-476; LEU-477; LEU-482; ASN-490; SER-496; CYS-498; GLN-516; VAL-517; ARG-535; PRO-551; ASN-578; HIS-602 AND PRO-602, VARIANT VAL-487. - Ref.39"Screening of 25 Italian patients with Niemann-Pick A reveals fourteen new mutations, one common and thirteen private, in SMPD1."
Ricci V., Stroppiano M., Corsolini F., Di Rocco M., Parenti G., Regis S., Grossi S., Biancheri R., Mazzotti R., Filocamo M.
Hum. Mutat. 24:105-105(2004) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANTS NPDA PRO-105; SER-247; LYS-248; HIS-315; PRO-452; LEU-477; LEU-498; HIS-498 AND CYS-519, VARIANT GLN-296. - Ref.54"The acid sphingomyelinase sequence variant p.A487V is not associated with decreased levels of enzymatic activity."
Rhein C., Naumann J., Muehle C., Zill P., Adli M., Hegerl U., Hiemke C., Mergl R., Moeller H.J., Reichel M., Kornhuber J.
JIMD Rep. 8:1-6(2013) [PubMed] [Europe PMC] [Abstract]Cited for: CHARACTERIZATION OF VARIANT NPDB ALA-325, CHARACTERIZATION OF VARIANT VAL-487.
<p>This subsection of the <a href="http://www.uniprot.org/help/function_section">Function</a> section describes the catalytic activity of an enzyme, i.e. a chemical reaction that the enzyme catalyzes.<p><a href='/help/catalytic_activity' target='_top'>More...</a></p>Catalytic activityi
- a sphingomyelinEC:3.1.4.12
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- See the description of this molecule in ChEBI.
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- Search chemical reactions in Rhea for this molecule.
- See the description of this molecule in ChEBI.
- Search proteins in UniProtKB for this molecule.
- Search chemical reactions in Rhea for this molecule.
- See the description of this molecule in ChEBI.
- Search proteins in UniProtKB for this molecule.
- Search chemical reactions in Rhea for this molecule.
- See the description of this molecule in ChEBI.
- Search proteins in UniProtKB for this molecule.
- Search chemical reactions in Rhea for this molecule.
- See the description of this molecule in ChEBI.
Manual assertion based on experiment ini
- Ref.1"Human acid sphingomyelinase. Isolation, nucleotide sequence and expression of the full-length and alternatively spliced cDNAs."
Schuchman E.H., Suchi M., Takahashi T., Sandhoff K., Desnick R.J.
J. Biol. Chem. 266:8531-8539(1991) [PubMed] [Europe PMC] [Abstract]Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY, ALTERNATIVE SPLICING, VARIANTS 48-ALA-LEU-49 DEL; ILE-324 AND ARG-508. - Ref.8"Acid sphingomyelinase-deficient human lymphoblasts and mice are defective in radiation-induced apoptosis."
Santana P., Pena L.A., Haimovitz-Friedman A., Martin S., Green D., McLoughlin M., Cordon-Cardo C., Schuchman E.H., Fuks Z., Kolesnick R.
Cell 86:189-199(1996) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, CATALYTIC ACTIVITY. - Ref.9"Zn2+-stimulated sphingomyelinase is secreted by many cell types and is a product of the acid sphingomyelinase gene."
Schissel S.L., Schuchman E.H., Williams K.J., Tabas I.
J. Biol. Chem. 271:18431-18436(1996) [PubMed] [Europe PMC] [Abstract]Cited for: CATALYTIC ACTIVITY, COFACTOR, SUBCELLULAR LOCATION. - Ref.13"Host defense against Pseudomonas aeruginosa requires ceramide-rich membrane rafts."
Grassme H., Jendrossek V., Riehle A., von Kuerthy G., Berger J., Schwarz H., Weller M., Kolesnick R., Gulbins E.
Nat. Med. 9:322-330(2003) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, SUBCELLULAR LOCATION, ACTIVITY REGULATION (MICROBIAL INFECTION), CATALYTIC ACTIVITY. - Ref.19"Ebolavirus requires acid sphingomyelinase activity and plasma membrane sphingomyelin for infection."
Miller M.E., Adhikary S., Kolokoltsov A.A., Davey R.A.
J. Virol. 86:7473-7483(2012) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION (MICROBIAL INFECTION), SUBCELLULAR LOCATION, CATALYTIC ACTIVITY, ACTIVITY REGULATION. - Ref.22"Pharmacological Inhibition of Acid Sphingomyelinase Prevents Uptake of SARS-CoV-2 by Epithelial Cells."
Carpinteiro A., Edwards M.J., Hoffmann M., Kochs G., Gripp B., Weigang S., Adams C., Carpinteiro E., Gulbins A., Keitsch S., Sehl C., Soddemann M., Wilker B., Kamler M., Bertsch T., Lang K.S., Patel S., Wilson G.C. , Walter S., Hengel H., Poehlmann S., Lang P.A., Kornhuber J., Becker K.A., Ahmad S.A., Fassbender K., Gulbins E.
Cell Rep. 1:100142-100142(2020) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION (MICROBIAL INFECTION), ACTIVITY REGULATION, CATALYTIC ACTIVITY. - Ref.23"Structure of human acid sphingomyelinase reveals the role of the saposin domain in activating substrate hydrolysis."
Xiong Z.J., Huang J., Poda G., Pomes R., Prive G.G.
J. Mol. Biol. 428:3026-3042(2016) [PubMed] [Europe PMC] [Abstract]Cited for: X-RAY CRYSTALLOGRAPHY (2.80 ANGSTROMS) OF 47-629 OF MUTANT SER-631 IN COMPLEX WITH ZINC, CATALYTIC ACTIVITY, GLYCOSYLATION AT ASN-88; ASN-177; ASN-337; ASN-397; ASN-505 AND ASN-522, DISULFIDE BONDS, SUBUNIT. - Ref.25"Molecular basis of acid sphingomyelinase deficiency in a patient with Niemann-Pick disease type A."
Ferlinz K., Hurwitz R., Sandhoff K.
Biochem. Biophys. Res. Commun. 179:1187-1191(1991) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANT NPDA SER-579, CHARACTERIZATION OF VARIANT NPDA SER-579, CATALYTIC ACTIVITY. - Ref.42"Acid sphingomyelinase deficiency. Phenotype variability with prevalence of intermediate phenotype in a series of twenty-five Czech and Slovak patients. A multi-approach study."
Pavluu-Pereira H., Asfaw B., Poupctova H., Ledvinova J., Sikora J., Vanier M.T., Sandhoff K., Zeman J., Novotna Z., Chudoba D., Elleder M.
J. Inherit. Metab. Dis. 28:203-227(2005) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANTS NPDA ARG-168; LEU-186; HIS-230; VAL-243; ARG-250; GLU-253; ALA-280; HIS-291; LYS-294; PRO-343; HIS-378; TRP-476; ARG-535 AND SER-579, VARIANT ARG-508, CATALYTIC ACTIVITY, CHARACTERIZATION OF VARIANTS NPDA LEU-186; GLU-253; ALA-280; LYS-294; PRO-343 AND HIS-378. - Ref.44"Characterization of common SMPD1 mutations causing types A and B Niemann-Pick disease and generation of mutation-specific mouse models."
Jones I., He X., Katouzian F., Darroch P.I., Schuchman E.H.
Mol. Genet. Metab. 95:152-162(2008) [PubMed] [Europe PMC] [Abstract]Cited for: CHARACTERIZATION OF VARIANTS NPDA PRO-304 AND LEU-498, CHARACTERIZATION OF VARIANTS NPDB TYR-423 AND ARG-610 DEL, FUNCTION, SUBCELLULAR LOCATION, CATALYTIC ACTIVITY. - Ref.57"Alleged detrimental mutations in the SMPD1 gene in patients with Niemann-Pick disease."
Rhein C., Muehle C., Kornhuber J., Reichel M.
Int. J. Mol. Sci. 16:13649-13652(2015) [PubMed] [Europe PMC] [Abstract]Cited for: CHARACTERIZATION OF VARIANT NPDB ALA-325, CHARACTERIZATION OF VARIANTS ALA-36; VAL-487 AND ARG-508, CATALYTIC ACTIVITY.
- Search proteins in UniProtKB for this EC number.
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Manual assertion based on experiment ini
- Ref.1"Human acid sphingomyelinase. Isolation, nucleotide sequence and expression of the full-length and alternatively spliced cDNAs."
Schuchman E.H., Suchi M., Takahashi T., Sandhoff K., Desnick R.J.
J. Biol. Chem. 266:8531-8539(1991) [PubMed] [Europe PMC] [Abstract]Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY, ALTERNATIVE SPLICING, VARIANTS 48-ALA-LEU-49 DEL; ILE-324 AND ARG-508. - Ref.8"Acid sphingomyelinase-deficient human lymphoblasts and mice are defective in radiation-induced apoptosis."
Santana P., Pena L.A., Haimovitz-Friedman A., Martin S., Green D., McLoughlin M., Cordon-Cardo C., Schuchman E.H., Fuks Z., Kolesnick R.
Cell 86:189-199(1996) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, CATALYTIC ACTIVITY. - Ref.9"Zn2+-stimulated sphingomyelinase is secreted by many cell types and is a product of the acid sphingomyelinase gene."
Schissel S.L., Schuchman E.H., Williams K.J., Tabas I.
J. Biol. Chem. 271:18431-18436(1996) [PubMed] [Europe PMC] [Abstract]Cited for: CATALYTIC ACTIVITY, COFACTOR, SUBCELLULAR LOCATION. - Ref.13"Host defense against Pseudomonas aeruginosa requires ceramide-rich membrane rafts."
Grassme H., Jendrossek V., Riehle A., von Kuerthy G., Berger J., Schwarz H., Weller M., Kolesnick R., Gulbins E.
Nat. Med. 9:322-330(2003) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, SUBCELLULAR LOCATION, ACTIVITY REGULATION (MICROBIAL INFECTION), CATALYTIC ACTIVITY. - Ref.19"Ebolavirus requires acid sphingomyelinase activity and plasma membrane sphingomyelin for infection."
Miller M.E., Adhikary S., Kolokoltsov A.A., Davey R.A.
J. Virol. 86:7473-7483(2012) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION (MICROBIAL INFECTION), SUBCELLULAR LOCATION, CATALYTIC ACTIVITY, ACTIVITY REGULATION. - Ref.22"Pharmacological Inhibition of Acid Sphingomyelinase Prevents Uptake of SARS-CoV-2 by Epithelial Cells."
Carpinteiro A., Edwards M.J., Hoffmann M., Kochs G., Gripp B., Weigang S., Adams C., Carpinteiro E., Gulbins A., Keitsch S., Sehl C., Soddemann M., Wilker B., Kamler M., Bertsch T., Lang K.S., Patel S., Wilson G.C. , Walter S., Hengel H., Poehlmann S., Lang P.A., Kornhuber J., Becker K.A., Ahmad S.A., Fassbender K., Gulbins E.
Cell Rep. 1:100142-100142(2020) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION (MICROBIAL INFECTION), ACTIVITY REGULATION, CATALYTIC ACTIVITY. - Ref.23"Structure of human acid sphingomyelinase reveals the role of the saposin domain in activating substrate hydrolysis."
Xiong Z.J., Huang J., Poda G., Pomes R., Prive G.G.
J. Mol. Biol. 428:3026-3042(2016) [PubMed] [Europe PMC] [Abstract]Cited for: X-RAY CRYSTALLOGRAPHY (2.80 ANGSTROMS) OF 47-629 OF MUTANT SER-631 IN COMPLEX WITH ZINC, CATALYTIC ACTIVITY, GLYCOSYLATION AT ASN-88; ASN-177; ASN-337; ASN-397; ASN-505 AND ASN-522, DISULFIDE BONDS, SUBUNIT. - Ref.25"Molecular basis of acid sphingomyelinase deficiency in a patient with Niemann-Pick disease type A."
Ferlinz K., Hurwitz R., Sandhoff K.
Biochem. Biophys. Res. Commun. 179:1187-1191(1991) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANT NPDA SER-579, CHARACTERIZATION OF VARIANT NPDA SER-579, CATALYTIC ACTIVITY. - Ref.42"Acid sphingomyelinase deficiency. Phenotype variability with prevalence of intermediate phenotype in a series of twenty-five Czech and Slovak patients. A multi-approach study."
Pavluu-Pereira H., Asfaw B., Poupctova H., Ledvinova J., Sikora J., Vanier M.T., Sandhoff K., Zeman J., Novotna Z., Chudoba D., Elleder M.
J. Inherit. Metab. Dis. 28:203-227(2005) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANTS NPDA ARG-168; LEU-186; HIS-230; VAL-243; ARG-250; GLU-253; ALA-280; HIS-291; LYS-294; PRO-343; HIS-378; TRP-476; ARG-535 AND SER-579, VARIANT ARG-508, CATALYTIC ACTIVITY, CHARACTERIZATION OF VARIANTS NPDA LEU-186; GLU-253; ALA-280; LYS-294; PRO-343 AND HIS-378. - Ref.44"Characterization of common SMPD1 mutations causing types A and B Niemann-Pick disease and generation of mutation-specific mouse models."
Jones I., He X., Katouzian F., Darroch P.I., Schuchman E.H.
Mol. Genet. Metab. 95:152-162(2008) [PubMed] [Europe PMC] [Abstract]Cited for: CHARACTERIZATION OF VARIANTS NPDA PRO-304 AND LEU-498, CHARACTERIZATION OF VARIANTS NPDB TYR-423 AND ARG-610 DEL, FUNCTION, SUBCELLULAR LOCATION, CATALYTIC ACTIVITY. - Ref.57"Alleged detrimental mutations in the SMPD1 gene in patients with Niemann-Pick disease."
Rhein C., Muehle C., Kornhuber J., Reichel M.
Int. J. Mol. Sci. 16:13649-13652(2015) [PubMed] [Europe PMC] [Abstract]Cited for: CHARACTERIZATION OF VARIANT NPDB ALA-325, CHARACTERIZATION OF VARIANTS ALA-36; VAL-487 AND ARG-508, CATALYTIC ACTIVITY.
This reaction proceeds in the forward- Search for this reaction in UniProtKB.
- See the description of this reaction in Rhea.
Manual assertion inferred by curator fromi
- Ref.1"Human acid sphingomyelinase. Isolation, nucleotide sequence and expression of the full-length and alternatively spliced cDNAs."
Schuchman E.H., Suchi M., Takahashi T., Sandhoff K., Desnick R.J.
J. Biol. Chem. 266:8531-8539(1991) [PubMed] [Europe PMC] [Abstract]Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY, ALTERNATIVE SPLICING, VARIANTS 48-ALA-LEU-49 DEL; ILE-324 AND ARG-508. - Ref.8"Acid sphingomyelinase-deficient human lymphoblasts and mice are defective in radiation-induced apoptosis."
Santana P., Pena L.A., Haimovitz-Friedman A., Martin S., Green D., McLoughlin M., Cordon-Cardo C., Schuchman E.H., Fuks Z., Kolesnick R.
Cell 86:189-199(1996) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, CATALYTIC ACTIVITY. - Ref.13"Host defense against Pseudomonas aeruginosa requires ceramide-rich membrane rafts."
Grassme H., Jendrossek V., Riehle A., von Kuerthy G., Berger J., Schwarz H., Weller M., Kolesnick R., Gulbins E.
Nat. Med. 9:322-330(2003) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, SUBCELLULAR LOCATION, ACTIVITY REGULATION (MICROBIAL INFECTION), CATALYTIC ACTIVITY. - Ref.19"Ebolavirus requires acid sphingomyelinase activity and plasma membrane sphingomyelin for infection."
Miller M.E., Adhikary S., Kolokoltsov A.A., Davey R.A.
J. Virol. 86:7473-7483(2012) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION (MICROBIAL INFECTION), SUBCELLULAR LOCATION, CATALYTIC ACTIVITY, ACTIVITY REGULATION. - Ref.22"Pharmacological Inhibition of Acid Sphingomyelinase Prevents Uptake of SARS-CoV-2 by Epithelial Cells."
Carpinteiro A., Edwards M.J., Hoffmann M., Kochs G., Gripp B., Weigang S., Adams C., Carpinteiro E., Gulbins A., Keitsch S., Sehl C., Soddemann M., Wilker B., Kamler M., Bertsch T., Lang K.S., Patel S., Wilson G.C. , Walter S., Hengel H., Poehlmann S., Lang P.A., Kornhuber J., Becker K.A., Ahmad S.A., Fassbender K., Gulbins E.
Cell Rep. 1:100142-100142(2020) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION (MICROBIAL INFECTION), ACTIVITY REGULATION, CATALYTIC ACTIVITY.
Source: Rhea- Search for this reaction in UniProtKB.
- See the description of this reaction in Rhea.
a sphingomyelin- Search proteins in UniProtKB for this molecule.
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+H2O- Search proteins in UniProtKB for this molecule.
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=an N-acylsphing-4-enine- Search proteins in UniProtKB for this molecule.
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+phosphocholine- Search proteins in UniProtKB for this molecule.
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- H2O
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- Search proteins in UniProtKB for this molecule.
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Manual assertion based on experiment ini
- Ref.20"Acid sphingomyelinase activity is regulated by membrane lipids and facilitates cholesterol transfer by NPC2."
Oninla V.O., Breiden B., Babalola J.O., Sandhoff K.
J. Lipid Res. 55:2606-2619(2014) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, SUBCELLULAR LOCATION.
This reaction proceeds in the forward- Search for this reaction in UniProtKB.
- See the description of this reaction in Rhea.
Manual assertion based on experiment ini
- Ref.20"Acid sphingomyelinase activity is regulated by membrane lipids and facilitates cholesterol transfer by NPC2."
Oninla V.O., Breiden B., Babalola J.O., Sandhoff K.
J. Lipid Res. 55:2606-2619(2014) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, SUBCELLULAR LOCATION.
Source: Rhea- Search for this reaction in UniProtKB.
- See the description of this reaction in Rhea.
H2O- Search proteins in UniProtKB for this molecule.
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+N-(octadecanoyl)-sphing-4-enine-1-phosphocholine- Search proteins in UniProtKB for this molecule.
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+N-octadecanoylsphing-4-enine- Search proteins in UniProtKB for this molecule.
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+phosphocholine- Search proteins in UniProtKB for this molecule.
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- 1,2-dihexadecanoyl-sn-glycero-3-phosphocholine
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Manual assertion based on experiment ini
- Ref.20"Acid sphingomyelinase activity is regulated by membrane lipids and facilitates cholesterol transfer by NPC2."
Oninla V.O., Breiden B., Babalola J.O., Sandhoff K.
J. Lipid Res. 55:2606-2619(2014) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, SUBCELLULAR LOCATION.
This reaction proceeds in the forward- Search for this reaction in UniProtKB.
- See the description of this reaction in Rhea.
Source: Rhea- Search for this reaction in UniProtKB.
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1,2-dihexadecanoyl-sn-glycero-3-phosphocholine- Search proteins in UniProtKB for this molecule.
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=1,2-dihexadecanoyl-sn-glycerol- Search proteins in UniProtKB for this molecule.
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+phosphocholine- Search proteins in UniProtKB for this molecule.
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<p>This subsection of the 'Function' section provides information relevant to cofactors. A cofactor is any non-protein substance required for a protein to be catalytically active. Some cofactors are inorganic, such as the metal atoms zinc, iron, and copper in various oxidation states. Others, such as most vitamins, are organic.<p><a href='/help/cofactor' target='_top'>More...</a></p>Cofactori
Zn2+
- Search proteins in UniProtKB for this molecule.
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Manual assertion based on experiment ini
- Ref.9"Zn2+-stimulated sphingomyelinase is secreted by many cell types and is a product of the acid sphingomyelinase gene."
Schissel S.L., Schuchman E.H., Williams K.J., Tabas I.
J. Biol. Chem. 271:18431-18436(1996) [PubMed] [Europe PMC] [Abstract]Cited for: CATALYTIC ACTIVITY, COFACTOR, SUBCELLULAR LOCATION. - Ref.36"The cellular trafficking and zinc dependence of secretory and lysosomal sphingomyelinase, two products of the acid sphingomyelinase gene."
Schissel S.L., Keesler G.A., Schuchman E.H., Williams K.J., Tabas I.
J. Biol. Chem. 273:18250-18259(1998) [PubMed] [Europe PMC] [Abstract]Cited for: CHARACTERIZATION OF VARIANT NPDA LEU-498, FUNCTION, COFACTOR.
Manual assertion based on experiment ini
- Ref.9"Zn2+-stimulated sphingomyelinase is secreted by many cell types and is a product of the acid sphingomyelinase gene."
Schissel S.L., Schuchman E.H., Williams K.J., Tabas I.
J. Biol. Chem. 271:18431-18436(1996) [PubMed] [Europe PMC] [Abstract]Cited for: CATALYTIC ACTIVITY, COFACTOR, SUBCELLULAR LOCATION. - Ref.23"Structure of human acid sphingomyelinase reveals the role of the saposin domain in activating substrate hydrolysis."
Xiong Z.J., Huang J., Poda G., Pomes R., Prive G.G.
J. Mol. Biol. 428:3026-3042(2016) [PubMed] [Europe PMC] [Abstract]Cited for: X-RAY CRYSTALLOGRAPHY (2.80 ANGSTROMS) OF 47-629 OF MUTANT SER-631 IN COMPLEX WITH ZINC, CATALYTIC ACTIVITY, GLYCOSYLATION AT ASN-88; ASN-177; ASN-337; ASN-397; ASN-505 AND ASN-522, DISULFIDE BONDS, SUBUNIT. - Ref.24"Human acid sphingomyelinase structures provide insight to molecular basis of Niemann-Pick disease."
Zhou Y.F., Metcalf M.C., Garman S.C., Edmunds T., Qiu H., Wei R.R.
Nat. Commun. 7:13082-13082(2016) [PubMed] [Europe PMC] [Abstract]Cited for: X-RAY CRYSTALLOGRAPHY (2.25 ANGSTROMS) OF 47-629 OF APOENZYME AND IN COMPLEX WITH PHOSPHOCHOLINE AND ZINC, COFACTOR, GLYCOSYLATION AT ASN-88; ASN-177; ASN-337; ASN-397; ASN-505 AND ASN-522. - Ref.36"The cellular trafficking and zinc dependence of secretory and lysosomal sphingomyelinase, two products of the acid sphingomyelinase gene."
Schissel S.L., Keesler G.A., Schuchman E.H., Williams K.J., Tabas I.
J. Biol. Chem. 273:18250-18259(1998) [PubMed] [Europe PMC] [Abstract]Cited for: CHARACTERIZATION OF VARIANT NPDA LEU-498, FUNCTION, COFACTOR.
<p>This subsection of the <a href="http://www.uniprot.org/help/function_section">Function</a> section describes regulatory mechanisms for enzymes, transporters or microbial transcription factors, and reports the components which regulate (by activation or inhibition) the reaction.<p><a href='/help/activity_regulation' target='_top'>More...</a></p>Activity regulationi
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:33163980, PubMed:22573858).3 Publications
Manual assertion based on experiment ini
- Ref.19"Ebolavirus requires acid sphingomyelinase activity and plasma membrane sphingomyelin for infection."
Miller M.E., Adhikary S., Kolokoltsov A.A., Davey R.A.
J. Virol. 86:7473-7483(2012) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION (MICROBIAL INFECTION), SUBCELLULAR LOCATION, CATALYTIC ACTIVITY, ACTIVITY REGULATION. - Ref.20"Acid sphingomyelinase activity is regulated by membrane lipids and facilitates cholesterol transfer by NPC2."
Oninla V.O., Breiden B., Babalola J.O., Sandhoff K.
J. Lipid Res. 55:2606-2619(2014) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, SUBCELLULAR LOCATION. - Ref.22"Pharmacological Inhibition of Acid Sphingomyelinase Prevents Uptake of SARS-CoV-2 by Epithelial Cells."
Carpinteiro A., Edwards M.J., Hoffmann M., Kochs G., Gripp B., Weigang S., Adams C., Carpinteiro E., Gulbins A., Keitsch S., Sehl C., Soddemann M., Wilker B., Kamler M., Bertsch T., Lang K.S., Patel S., Wilson G.C. , Walter S., Hengel H., Poehlmann S., Lang P.A., Kornhuber J., Becker K.A., Ahmad S.A., Fassbender K., Gulbins E.
Cell Rep. 1:100142-100142(2020) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION (MICROBIAL INFECTION), ACTIVITY REGULATION, CATALYTIC ACTIVITY.
(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.1 Publication
Manual assertion based on experiment ini
- Ref.13"Host defense against Pseudomonas aeruginosa requires ceramide-rich membrane rafts."
Grassme H., Jendrossek V., Riehle A., von Kuerthy G., Berger J., Schwarz H., Weller M., Kolesnick R., Gulbins E.
Nat. Med. 9:322-330(2003) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, SUBCELLULAR LOCATION, ACTIVITY REGULATION (MICROBIAL INFECTION), CATALYTIC ACTIVITY.
(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.1 Publication
Manual assertion based on experiment ini
- Ref.22"Pharmacological Inhibition of Acid Sphingomyelinase Prevents Uptake of SARS-CoV-2 by Epithelial Cells."
Carpinteiro A., Edwards M.J., Hoffmann M., Kochs G., Gripp B., Weigang S., Adams C., Carpinteiro E., Gulbins A., Keitsch S., Sehl C., Soddemann M., Wilker B., Kamler M., Bertsch T., Lang K.S., Patel S., Wilson G.C. , Walter S., Hengel H., Poehlmann S., Lang P.A., Kornhuber J., Becker K.A., Ahmad S.A., Fassbender K., Gulbins E.
Cell Rep. 1:100142-100142(2020) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION (MICROBIAL INFECTION), ACTIVITY REGULATION, CATALYTIC ACTIVITY.
Sites
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| <p>This subsection of the <a href="http://www.uniprot.org/help/function_section">Function</a> section indicates at which position the protein binds a given metal ion. The nature of the metal is indicated in the 'Description' field.<p><a href='/help/metal' target='_top'>More...</a></p>Metal bindingi | 208 | Zinc 1Combined sources <p>Manually validated information inferred from a combination of experimental and computational evidence.</p> <p><a href="/manual/evidences#ECO:0007744">More...</a></p> Manual assertion inferred from combination of experimental and computational evidencei 1 PublicationManual assertion based on experiment ini
| 1 | |
| Metal bindingi | 210 | Zinc 1; via tele nitrogenCombined sources Manual assertion inferred from combination of experimental and computational evidencei 1 PublicationManual assertion based on experiment ini
| 1 | |
| Metal bindingi | 280 | Zinc 1Combined sources Manual assertion inferred from combination of experimental and computational evidencei 1 PublicationManual assertion based on experiment ini
| 1 | |
| Metal bindingi | 280 | Zinc 2Combined sources Manual assertion inferred from combination of experimental and computational evidencei 1 PublicationManual assertion based on experiment ini
| 1 | |
| Metal bindingi | 320 | Zinc 2Combined sources Manual assertion inferred from combination of experimental and computational evidencei 1 PublicationManual assertion based on experiment ini
| 1 | |
| Metal bindingi | 427 | Zinc 2; via tele nitrogenCombined sources Manual assertion inferred from combination of experimental and computational evidencei 1 PublicationManual assertion based on experiment ini
| 1 | |
| Metal bindingi | 459 | Zinc 2; via pros nitrogenCombined sources Manual assertion inferred from combination of experimental and computational evidencei 1 PublicationManual assertion based on experiment ini
| 1 | |
| Metal bindingi | 461 | Zinc 1; via tele nitrogenCombined sources Manual assertion inferred from combination of experimental and computational evidencei 1 PublicationManual assertion based on experiment ini
| 1 |
<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni
- acid sphingomyelin phosphodiesterase activity Source: UniProtKB
<p>Inferred from Direct Assay</p>
<p>Used to indicate a direct assay for the function, process or component indicated by the GO term.</p>
<p>More information in the <a href="http://geneontology.org/page/guide-go-evidence-codes#ida">GO evidence code guide</a></p>
Inferred from direct assayi
- Ref.16"Activation of acid sphingomyelinase by protein kinase Cdelta-mediated phosphorylation."
Zeidan Y.H., Hannun Y.A.
J. Biol. Chem. 282:11549-11561(2007) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, PHOSPHORYLATION AT SER-510, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, MUTAGENESIS OF SER-151; SER-233; SER-250 AND SER-510. - Ref.44"Characterization of common SMPD1 mutations causing types A and B Niemann-Pick disease and generation of mutation-specific mouse models."
Jones I., He X., Katouzian F., Darroch P.I., Schuchman E.H.
Mol. Genet. Metab. 95:152-162(2008) [PubMed] [Europe PMC] [Abstract]Cited for: CHARACTERIZATION OF VARIANTS NPDA PRO-304 AND LEU-498, CHARACTERIZATION OF VARIANTS NPDB TYR-423 AND ARG-610 DEL, FUNCTION, SUBCELLULAR LOCATION, CATALYTIC ACTIVITY. - Ref.17"Regulated secretion of acid sphingomyelinase: implications for selectivity of ceramide formation."
Jenkins R.W., Canals D., Idkowiak-Baldys J., Simbari F., Roddy P., Perry D.M., Kitatani K., Luberto C., Hannun Y.A.
J. Biol. Chem. 285:35706-35718(2010) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, GLYCOSYLATION, MUTAGENESIS OF SER-510. - Ref.9"Zn2+-stimulated sphingomyelinase is secreted by many cell types and is a product of the acid sphingomyelinase gene."
Schissel S.L., Schuchman E.H., Williams K.J., Tabas I.
J. Biol. Chem. 271:18431-18436(1996) [PubMed] [Europe PMC] [Abstract]Cited for: CATALYTIC ACTIVITY, COFACTOR, SUBCELLULAR LOCATION.
- hydrolase activity, acting on glycosyl bonds Source: UniProtKB-KW
- phosphoric diester hydrolase activity Source: GO_Central
<p>Inferred from Biological aspect of Ancestor</p>
<p>A type of phylogenetic evidence whereby an aspect of a descendent is inferred through the characterization of an aspect of a ancestral gene.</p>
<p>More information in the <a href="http://geneontology.org/page/guide-go-evidence-codes#iba">GO evidence code guide</a></p>
Inferred from biological aspect of ancestori
- "Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium."
Gaudet P., Livstone M.S., Lewis S.E., Thomas P.D.
Brief Bioinform 12:449-462(2011) [PubMed] [Europe PMC] [Abstract]
- sphingomyelin phosphodiesterase activity Source: UniProtKBInferred from direct assayi
- Ref.48"A novel mechanism of lysosomal acid sphingomyelinase maturation: requirement for carboxyl-terminal proteolytic processing."
Jenkins R.W., Idkowiak-Baldys J., Simbari F., Canals D., Roddy P., Riner C.D., Clarke C.J., Hannun Y.A.
J. Biol. Chem. 286:3777-3788(2011) [PubMed] [Europe PMC] [Abstract]Cited for: CATALYTIC ACTIVITY, FUNCTION, SUBCELLULAR LOCATION, CHARACTERIZATION OF VARIANTS NPDB HIS-602; PRO-602 AND ARG-610 DEL. - Ref.19"Ebolavirus requires acid sphingomyelinase activity and plasma membrane sphingomyelin for infection."
Miller M.E., Adhikary S., Kolokoltsov A.A., Davey R.A.
J. Virol. 86:7473-7483(2012) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION (MICROBIAL INFECTION), SUBCELLULAR LOCATION, CATALYTIC ACTIVITY, ACTIVITY REGULATION. - Ref.36"The cellular trafficking and zinc dependence of secretory and lysosomal sphingomyelinase, two products of the acid sphingomyelinase gene."
Schissel S.L., Keesler G.A., Schuchman E.H., Williams K.J., Tabas I.
J. Biol. Chem. 273:18250-18259(1998) [PubMed] [Europe PMC] [Abstract]Cited for: CHARACTERIZATION OF VARIANT NPDA LEU-498, FUNCTION, COFACTOR.
- zinc ion binding Source: UniProtKBInferred from direct assayi
- Ref.9"Zn2+-stimulated sphingomyelinase is secreted by many cell types and is a product of the acid sphingomyelinase gene."
Schissel S.L., Schuchman E.H., Williams K.J., Tabas I.
J. Biol. Chem. 271:18431-18436(1996) [PubMed] [Europe PMC] [Abstract]Cited for: CATALYTIC ACTIVITY, COFACTOR, SUBCELLULAR LOCATION. - Ref.36"The cellular trafficking and zinc dependence of secretory and lysosomal sphingomyelinase, two products of the acid sphingomyelinase gene."
Schissel S.L., Keesler G.A., Schuchman E.H., Williams K.J., Tabas I.
J. Biol. Chem. 273:18250-18259(1998) [PubMed] [Europe PMC] [Abstract]Cited for: CHARACTERIZATION OF VARIANT NPDA LEU-498, FUNCTION, COFACTOR.
GO - Biological processi
- cellular response to calcium ion Source: UniProtKBInferred from direct assayi
- Ref.18"Exocytosis of acid sphingomyelinase by wounded cells promotes endocytosis and plasma membrane repair."
Tam C., Idone V., Devlin C., Fernandes M.C., Flannery A., He X., Schuchman E., Tabas I., Andrews N.W.
J. Cell Biol. 189:1027-1038(2010) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION.
- cellular response to UV Source: UniProtKBInferred from direct assayi
- Ref.16"Activation of acid sphingomyelinase by protein kinase Cdelta-mediated phosphorylation."
Zeidan Y.H., Hannun Y.A.
J. Biol. Chem. 282:11549-11561(2007) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, PHOSPHORYLATION AT SER-510, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, MUTAGENESIS OF SER-151; SER-233; SER-250 AND SER-510.
- ceramide biosynthetic process Source: UniProtKBInferred from direct assayi
- Ref.16"Activation of acid sphingomyelinase by protein kinase Cdelta-mediated phosphorylation."
Zeidan Y.H., Hannun Y.A.
J. Biol. Chem. 282:11549-11561(2007) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, PHOSPHORYLATION AT SER-510, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, MUTAGENESIS OF SER-151; SER-233; SER-250 AND SER-510. - Ref.44"Characterization of common SMPD1 mutations causing types A and B Niemann-Pick disease and generation of mutation-specific mouse models."
Jones I., He X., Katouzian F., Darroch P.I., Schuchman E.H.
Mol. Genet. Metab. 95:152-162(2008) [PubMed] [Europe PMC] [Abstract]Cited for: CHARACTERIZATION OF VARIANTS NPDA PRO-304 AND LEU-498, CHARACTERIZATION OF VARIANTS NPDB TYR-423 AND ARG-610 DEL, FUNCTION, SUBCELLULAR LOCATION, CATALYTIC ACTIVITY. - Ref.17"Regulated secretion of acid sphingomyelinase: implications for selectivity of ceramide formation."
Jenkins R.W., Canals D., Idkowiak-Baldys J., Simbari F., Roddy P., Perry D.M., Kitatani K., Luberto C., Hannun Y.A.
J. Biol. Chem. 285:35706-35718(2010) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, GLYCOSYLATION, MUTAGENESIS OF SER-510.
- cholesterol metabolic process Source: Ensembl
- glycosphingolipid metabolic process Source: Reactome
- negative regulation of MAP kinase activity Source: BHF-UCL
<p>Inferred from Mutant Phenotype</p>
<p>Describes annotations that are concluded from looking at variations or changes in a gene product such as mutations or abnormal levels and includes techniques such as knockouts, overexpression, anti-sense experiments and use of specific protein inhibitors.</p>
<p>More information in the <a href="http://geneontology.org/page/guide-go-evidence-codes#imp">GO evidence code guide</a></p>
Inferred from mutant phenotypei
- "Acid beta-glucosidase 1 counteracts p38delta-dependent induction of interleukin-6: possible role for ceramide as an anti-inflammatory lipid."
Kitatani K., Sheldon K., Anelli V., Jenkins R.W., Sun Y., Grabowski G.A., Obeid L.M., Hannun Y.A.
J Biol Chem 284:12979-12988(2009) [PubMed] [Europe PMC] [Abstract]
- nervous system development Source: ProtInc
<p>Traceable Author Statement</p>
<p>Used for information from review articles where the original experiments are traceable through that article and also for information from text books or dictionaries.</p>
<p>More information in the <a href="http://geneontology.org/page/guide-go-evidence-codes#tas">GO evidence code guide</a></p>
Traceable author statementi
- "Acid sphingomyelinase deficient mice: a model of types A and B Niemann-Pick disease."
Horinouchi K., Erlich S., Perl D.P., Ferlinz K., Bisgaier C.L., Sandhoff K., Desnick R.J., Stewart C.L., Schuchman E.H.
Nat Genet 10:288-293(1995) [PubMed] [Europe PMC] [Abstract]
- plasma membrane repair Source: UniProtKBInferred from direct assayi
- Ref.18"Exocytosis of acid sphingomyelinase by wounded cells promotes endocytosis and plasma membrane repair."
Tam C., Idone V., Devlin C., Fernandes M.C., Flannery A., He X., Schuchman E., Tabas I., Andrews N.W.
J. Cell Biol. 189:1027-1038(2010) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION.
- positive regulation of apoptotic process Source: UniProtKBInferred from mutant phenotypei
- Ref.8"Acid sphingomyelinase-deficient human lymphoblasts and mice are defective in radiation-induced apoptosis."
Santana P., Pena L.A., Haimovitz-Friedman A., Martin S., Green D., McLoughlin M., Cordon-Cardo C., Schuchman E.H., Fuks Z., Kolesnick R.
Cell 86:189-199(1996) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, CATALYTIC ACTIVITY.
- positive regulation of endocytosis Source: UniProtKBInferred from direct assayi
- Ref.18"Exocytosis of acid sphingomyelinase by wounded cells promotes endocytosis and plasma membrane repair."
Tam C., Idone V., Devlin C., Fernandes M.C., Flannery A., He X., Schuchman E., Tabas I., Andrews N.W.
J. Cell Biol. 189:1027-1038(2010) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION.
- positive regulation of protein dephosphorylation Source: BHF-UCLInferred from mutant phenotypei
- "Acid beta-glucosidase 1 counteracts p38delta-dependent induction of interleukin-6: possible role for ceramide as an anti-inflammatory lipid."
Kitatani K., Sheldon K., Anelli V., Jenkins R.W., Sun Y., Grabowski G.A., Obeid L.M., Hannun Y.A.
J Biol Chem 284:12979-12988(2009) [PubMed] [Europe PMC] [Abstract]
- response to cocaine Source: Ensembl
- response to drug Source: Ensembl
- response to interleukin-1 Source: UniProtKBInferred from direct assayi
- Ref.17"Regulated secretion of acid sphingomyelinase: implications for selectivity of ceramide formation."
Jenkins R.W., Canals D., Idkowiak-Baldys J., Simbari F., Roddy P., Perry D.M., Kitatani K., Luberto C., Hannun Y.A.
J. Biol. Chem. 285:35706-35718(2010) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, GLYCOSYLATION, MUTAGENESIS OF SER-510.
- response to ionizing radiation Source: UniProtKBInferred from mutant phenotypei
- Ref.8"Acid sphingomyelinase-deficient human lymphoblasts and mice are defective in radiation-induced apoptosis."
Santana P., Pena L.A., Haimovitz-Friedman A., Martin S., Green D., McLoughlin M., Cordon-Cardo C., Schuchman E.H., Fuks Z., Kolesnick R.
Cell 86:189-199(1996) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, CATALYTIC ACTIVITY.
- response to tumor necrosis factor Source: UniProtKBInferred from direct assayi
- Ref.17"Regulated secretion of acid sphingomyelinase: implications for selectivity of ceramide formation."
Jenkins R.W., Canals D., Idkowiak-Baldys J., Simbari F., Roddy P., Perry D.M., Kitatani K., Luberto C., Hannun Y.A.
J. Biol. Chem. 285:35706-35718(2010) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, GLYCOSYLATION, MUTAGENESIS OF SER-510.
- response to type I interferon Source: UniProtKBInferred from direct assayi
- Ref.17"Regulated secretion of acid sphingomyelinase: implications for selectivity of ceramide formation."
Jenkins R.W., Canals D., Idkowiak-Baldys J., Simbari F., Roddy P., Perry D.M., Kitatani K., Luberto C., Hannun Y.A.
J. Biol. Chem. 285:35706-35718(2010) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, GLYCOSYLATION, MUTAGENESIS OF SER-510.
- response to virus Source: UniProtKBInferred from direct assayi
- Ref.19"Ebolavirus requires acid sphingomyelinase activity and plasma membrane sphingomyelin for infection."
Miller M.E., Adhikary S., Kolokoltsov A.A., Davey R.A.
J. Virol. 86:7473-7483(2012) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION (MICROBIAL INFECTION), SUBCELLULAR LOCATION, CATALYTIC ACTIVITY, ACTIVITY REGULATION.
- signal transduction Source: ProtIncTraceable author statementi
- "Acid sphingomyelinase deficient mice: a model of types A and B Niemann-Pick disease."
Horinouchi K., Erlich S., Perl D.P., Ferlinz K., Bisgaier C.L., Sandhoff K., Desnick R.J., Stewart C.L., Schuchman E.H.
Nat Genet 10:288-293(1995) [PubMed] [Europe PMC] [Abstract]
- sphingomyelin catabolic process Source: UniProtKBInferred from direct assayi
- Ref.44"Characterization of common SMPD1 mutations causing types A and B Niemann-Pick disease and generation of mutation-specific mouse models."
Jones I., He X., Katouzian F., Darroch P.I., Schuchman E.H.
Mol. Genet. Metab. 95:152-162(2008) [PubMed] [Europe PMC] [Abstract]Cited for: CHARACTERIZATION OF VARIANTS NPDA PRO-304 AND LEU-498, CHARACTERIZATION OF VARIANTS NPDB TYR-423 AND ARG-610 DEL, FUNCTION, SUBCELLULAR LOCATION, CATALYTIC ACTIVITY. - Ref.17"Regulated secretion of acid sphingomyelinase: implications for selectivity of ceramide formation."
Jenkins R.W., Canals D., Idkowiak-Baldys J., Simbari F., Roddy P., Perry D.M., Kitatani K., Luberto C., Hannun Y.A.
J. Biol. Chem. 285:35706-35718(2010) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, GLYCOSYLATION, MUTAGENESIS OF SER-510. - Ref.19"Ebolavirus requires acid sphingomyelinase activity and plasma membrane sphingomyelin for infection."
Miller M.E., Adhikary S., Kolokoltsov A.A., Davey R.A.
J. Virol. 86:7473-7483(2012) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION (MICROBIAL INFECTION), SUBCELLULAR LOCATION, CATALYTIC ACTIVITY, ACTIVITY REGULATION.
- sphingomyelin metabolic process Source: ProtIncTraceable author statementi
- "Acid sphingomyelinase deficient mice: a model of types A and B Niemann-Pick disease."
Horinouchi K., Erlich S., Perl D.P., Ferlinz K., Bisgaier C.L., Sandhoff K., Desnick R.J., Stewart C.L., Schuchman E.H.
Nat Genet 10:288-293(1995) [PubMed] [Europe PMC] [Abstract]
- termination of signal transduction Source: BHF-UCLInferred from mutant phenotypei
- "Acid beta-glucosidase 1 counteracts p38delta-dependent induction of interleukin-6: possible role for ceramide as an anti-inflammatory lipid."
Kitatani K., Sheldon K., Anelli V., Jenkins R.W., Sun Y., Grabowski G.A., Obeid L.M., Hannun Y.A.
J Biol Chem 284:12979-12988(2009) [PubMed] [Europe PMC] [Abstract]
- viral entry into host cell Source: UniProtKBInferred from direct assayi
- Ref.19"Ebolavirus requires acid sphingomyelinase activity and plasma membrane sphingomyelin for infection."
Miller M.E., Adhikary S., Kolokoltsov A.A., Davey R.A.
J. Virol. 86:7473-7483(2012) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION (MICROBIAL INFECTION), SUBCELLULAR LOCATION, CATALYTIC ACTIVITY, ACTIVITY REGULATION.
- wound healing Source: UniProtKBInferred from direct assayi
- Ref.18"Exocytosis of acid sphingomyelinase by wounded cells promotes endocytosis and plasma membrane repair."
Tam C., Idone V., Devlin C., Fernandes M.C., Flannery A., He X., Schuchman E., Tabas I., Andrews N.W.
J. Cell Biol. 189:1027-1038(2010) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION.
<p>UniProtKB Keywords constitute a <a href="http://www.uniprot.org/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='/help/keywords' target='_top'>More...</a></p>Keywordsi
| Molecular function | Glycosidase, Hydrolase |
| Biological process | Lipid metabolism |
| Ligand | Metal-binding, Zinc |
Enzyme and pathway databases
BRENDA Comprehensive Enzyme Information System More...BRENDAi | 3.1.4.12, 2681 |
Pathway Commons web resource for biological pathway data More...PathwayCommonsi | P17405 |
Reactome - a knowledgebase of biological pathways and processes More...Reactomei | R-HSA-1660662, Glycosphingolipid metabolism |
SIGNOR Signaling Network Open Resource More...SIGNORi | P17405 |
Chemistry databases
SwissLipids knowledge resource for lipid biology More...SwissLipidsi | SLP:000001748 |
<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi
| <p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section provides an exhaustive list of all names of the protein, from commonly used to obsolete, to allow unambiguous identification of a protein.<p><a href='/help/protein_names' target='_top'>More...</a></p>Protein namesi | Recommended name: Sphingomyelin phosphodiesteraseCurated (EC:3.1.4.12
Manual assertion based on experiment ini
Alternative name(s): Acid sphingomyelinase2 Publications <p>Manually curated information that is based on statements in scientific articles for which there is no experimental support.</p> <p><a href="/manual/evidences#ECO:0000303">More...</a></p> Manual assertion based on opinion ini
Short name: aSMase |
| <p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section indicates the name(s) of the gene(s) that code for the protein sequence(s) described in the entry. Four distinct tokens exist: 'Name', 'Synonyms', 'Ordered locus names' and 'ORF names'.<p><a href='/help/gene_name' target='_top'>More...</a></p>Gene namesi | Name:SMPD1Imported <p>Manually validated information which has been imported from another database.</p> <p><a href="/manual/evidences#ECO:0000312">More...</a></p> Manual assertion inferred from database entriesi Synonyms:ASM1 Publication Manual assertion based on opinion ini
|
| <p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section provides information on the name(s) of the organism that is the source of the protein sequence.<p><a href='/help/organism-name' target='_top'>More...</a></p>Organismi | Homo sapiens (Human) |
| <p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section shows the unique identifier assigned by the NCBI to the source organism of the protein. This is known as the 'taxonomic identifier' or 'taxid'.<p><a href='/help/taxonomic_identifier' target='_top'>More...</a></p>Taxonomic identifieri | 9606 [NCBI] |
| <p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section contains the taxonomic hierarchical classification lineage of the source organism. It lists the nodes as they appear top-down in the taxonomic tree, with the more general grouping listed first.<p><a href='/help/taxonomic_lineage' target='_top'>More...</a></p>Taxonomic lineagei | cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Dipnotetrapodomorpha › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Boreoeutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo |
| <p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section is present for entries that are part of a <a href="http://www.uniprot.org/proteomes">proteome</a>, i.e. of a set of proteins thought to be expressed by organisms whose genomes have been completely sequenced.<p><a href='/help/proteomes_manual' target='_top'>More...</a></p>Proteomesi |
|
Organism-specific databases
Human Gene Nomenclature Database More...HGNCi | HGNC:11120, SMPD1 |
Online Mendelian Inheritance in Man (OMIM) More...MIMi | 607608, gene |
neXtProt; the human protein knowledge platform More...neXtProti | NX_P17405 |
Eukaryotic Pathogen, Vector and Host Database Resources More...VEuPathDBi | HostDB:ENSG00000166311 |
<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi
Lysosome
- Lysosome 6 Publications
Manual assertion based on experiment ini
- Ref.14"The lysosomal trafficking of acid sphingomyelinase is mediated by sortilin and mannose 6-phosphate receptor."
Ni X., Morales C.R.
Traffic 7:889-902(2006) [PubMed] [Europe PMC] [Abstract]Cited for: SUBCELLULAR LOCATION, FUNCTION, INTERACTION WITH SORT1. - Ref.17"Regulated secretion of acid sphingomyelinase: implications for selectivity of ceramide formation."
Jenkins R.W., Canals D., Idkowiak-Baldys J., Simbari F., Roddy P., Perry D.M., Kitatani K., Luberto C., Hannun Y.A.
J. Biol. Chem. 285:35706-35718(2010) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, GLYCOSYLATION, MUTAGENESIS OF SER-510. - Ref.18"Exocytosis of acid sphingomyelinase by wounded cells promotes endocytosis and plasma membrane repair."
Tam C., Idone V., Devlin C., Fernandes M.C., Flannery A., He X., Schuchman E., Tabas I., Andrews N.W.
J. Cell Biol. 189:1027-1038(2010) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION. - Ref.36"The cellular trafficking and zinc dependence of secretory and lysosomal sphingomyelinase, two products of the acid sphingomyelinase gene."
Schissel S.L., Keesler G.A., Schuchman E.H., Williams K.J., Tabas I.
J. Biol. Chem. 273:18250-18259(1998) [PubMed] [Europe PMC] [Abstract]Cited for: CHARACTERIZATION OF VARIANT NPDA LEU-498, FUNCTION, COFACTOR. - Ref.44"Characterization of common SMPD1 mutations causing types A and B Niemann-Pick disease and generation of mutation-specific mouse models."
Jones I., He X., Katouzian F., Darroch P.I., Schuchman E.H.
Mol. Genet. Metab. 95:152-162(2008) [PubMed] [Europe PMC] [Abstract]Cited for: CHARACTERIZATION OF VARIANTS NPDA PRO-304 AND LEU-498, CHARACTERIZATION OF VARIANTS NPDB TYR-423 AND ARG-610 DEL, FUNCTION, SUBCELLULAR LOCATION, CATALYTIC ACTIVITY. - Ref.58"Structural and functional analysis of the ASM p.Ala359Asp mutant that causes acid sphingomyelinase deficiency."
Acuna M., Castro-Fernandez V., Latorre M., Castro J., Schuchman E.H., Guixe V., Gonzalez M., Zanlungo S.
Biochem. Biophys. Res. Commun. 479:496-501(2016) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, CHARACTERIZATION OF VARIANT NPDB ASP-359.
- Lysosome 6 Publications
Extracellular region or secreted
- Secreted 10 Publications
Manual assertion based on experiment ini
- Ref.9"Zn2+-stimulated sphingomyelinase is secreted by many cell types and is a product of the acid sphingomyelinase gene."
Schissel S.L., Schuchman E.H., Williams K.J., Tabas I.
J. Biol. Chem. 271:18431-18436(1996) [PubMed] [Europe PMC] [Abstract]Cited for: CATALYTIC ACTIVITY, COFACTOR, SUBCELLULAR LOCATION. - Ref.10"Functional characterization of the N-glycosylation sites of human acid sphingomyelinase by site-directed mutagenesis."
Ferlinz K., Hurwitz R., Moczall H., Lansmann S., Schuchman E.H., Sandhoff K.
Eur. J. Biochem. 243:511-517(1997) [PubMed] [Europe PMC] [Abstract]Cited for: GLYCOSYLATION AT ASN-88; ASN-177; ASN-337; ASN-397 AND ASN-522, MUTAGENESIS OF ASN-88; ASN-177; ASN-337; ASN-397; ASN-505 AND ASN-522, SUBCELLULAR LOCATION, PROTEOLYTIC CLEAVAGE, PHOSPHORYLATION. - Ref.13"Host defense against Pseudomonas aeruginosa requires ceramide-rich membrane rafts."
Grassme H., Jendrossek V., Riehle A., von Kuerthy G., Berger J., Schwarz H., Weller M., Kolesnick R., Gulbins E.
Nat. Med. 9:322-330(2003) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, SUBCELLULAR LOCATION, ACTIVITY REGULATION (MICROBIAL INFECTION), CATALYTIC ACTIVITY. - Ref.14"The lysosomal trafficking of acid sphingomyelinase is mediated by sortilin and mannose 6-phosphate receptor."
Ni X., Morales C.R.
Traffic 7:889-902(2006) [PubMed] [Europe PMC] [Abstract]Cited for: SUBCELLULAR LOCATION, FUNCTION, INTERACTION WITH SORT1. - Ref.16"Activation of acid sphingomyelinase by protein kinase Cdelta-mediated phosphorylation."
Zeidan Y.H., Hannun Y.A.
J. Biol. Chem. 282:11549-11561(2007) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, PHOSPHORYLATION AT SER-510, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, MUTAGENESIS OF SER-151; SER-233; SER-250 AND SER-510. - Ref.17"Regulated secretion of acid sphingomyelinase: implications for selectivity of ceramide formation."
Jenkins R.W., Canals D., Idkowiak-Baldys J., Simbari F., Roddy P., Perry D.M., Kitatani K., Luberto C., Hannun Y.A.
J. Biol. Chem. 285:35706-35718(2010) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, GLYCOSYLATION, MUTAGENESIS OF SER-510. - Ref.18"Exocytosis of acid sphingomyelinase by wounded cells promotes endocytosis and plasma membrane repair."
Tam C., Idone V., Devlin C., Fernandes M.C., Flannery A., He X., Schuchman E., Tabas I., Andrews N.W.
J. Cell Biol. 189:1027-1038(2010) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION. - Ref.19"Ebolavirus requires acid sphingomyelinase activity and plasma membrane sphingomyelin for infection."
Miller M.E., Adhikary S., Kolokoltsov A.A., Davey R.A.
J. Virol. 86:7473-7483(2012) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION (MICROBIAL INFECTION), SUBCELLULAR LOCATION, CATALYTIC ACTIVITY, ACTIVITY REGULATION. - Ref.36"The cellular trafficking and zinc dependence of secretory and lysosomal sphingomyelinase, two products of the acid sphingomyelinase gene."
Schissel S.L., Keesler G.A., Schuchman E.H., Williams K.J., Tabas I.
J. Biol. Chem. 273:18250-18259(1998) [PubMed] [Europe PMC] [Abstract]Cited for: CHARACTERIZATION OF VARIANT NPDA LEU-498, FUNCTION, COFACTOR. - Ref.58"Structural and functional analysis of the ASM p.Ala359Asp mutant that causes acid sphingomyelinase deficiency."
Acuna M., Castro-Fernandez V., Latorre M., Castro J., Schuchman E.H., Guixe V., Gonzalez M., Zanlungo S.
Biochem. Biophys. Res. Commun. 479:496-501(2016) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, CHARACTERIZATION OF VARIANT NPDB ASP-359.
- Secreted 10 Publications
Other locations
- Lipid droplet 1 Publication
Manual assertion based on experiment ini
- Ref.20"Acid sphingomyelinase activity is regulated by membrane lipids and facilitates cholesterol transfer by NPC2."
Oninla V.O., Breiden B., Babalola J.O., Sandhoff K.
J. Lipid Res. 55:2606-2619(2014) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, SUBCELLULAR LOCATION.
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 Ca2+-dependent (PubMed:20807762, PubMed:22573858, PubMed:20530211). 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).5 Publications- Lipid droplet 1 Publication
- Ref.13"Host defense against Pseudomonas aeruginosa requires ceramide-rich membrane rafts."
Grassme H., Jendrossek V., Riehle A., von Kuerthy G., Berger J., Schwarz H., Weller M., Kolesnick R., Gulbins E.
Nat. Med. 9:322-330(2003) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, SUBCELLULAR LOCATION, ACTIVITY REGULATION (MICROBIAL INFECTION), CATALYTIC ACTIVITY. - Ref.16"Activation of acid sphingomyelinase by protein kinase Cdelta-mediated phosphorylation."
Zeidan Y.H., Hannun Y.A.
J. Biol. Chem. 282:11549-11561(2007) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, PHOSPHORYLATION AT SER-510, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, MUTAGENESIS OF SER-151; SER-233; SER-250 AND SER-510. - Ref.17"Regulated secretion of acid sphingomyelinase: implications for selectivity of ceramide formation."
Jenkins R.W., Canals D., Idkowiak-Baldys J., Simbari F., Roddy P., Perry D.M., Kitatani K., Luberto C., Hannun Y.A.
J. Biol. Chem. 285:35706-35718(2010) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, GLYCOSYLATION, MUTAGENESIS OF SER-510. - Ref.18"Exocytosis of acid sphingomyelinase by wounded cells promotes endocytosis and plasma membrane repair."
Tam C., Idone V., Devlin C., Fernandes M.C., Flannery A., He X., Schuchman E., Tabas I., Andrews N.W.
J. Cell Biol. 189:1027-1038(2010) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION. - Ref.19"Ebolavirus requires acid sphingomyelinase activity and plasma membrane sphingomyelin for infection."
Miller M.E., Adhikary S., Kolokoltsov A.A., Davey R.A.
J. Virol. 86:7473-7483(2012) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION (MICROBIAL INFECTION), SUBCELLULAR LOCATION, CATALYTIC ACTIVITY, ACTIVITY REGULATION.
Manual assertion based on experiment ini
Endosome
- endolysosome Source: UniProtKBInferred from direct assayi
- Ref.16"Activation of acid sphingomyelinase by protein kinase Cdelta-mediated phosphorylation."
Zeidan Y.H., Hannun Y.A.
J. Biol. Chem. 282:11549-11561(2007) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, PHOSPHORYLATION AT SER-510, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, MUTAGENESIS OF SER-151; SER-233; SER-250 AND SER-510.
- endosome Source: UniProtKBInferred from direct assayi
- "Syntaxin 4 is required for acid sphingomyelinase activity and apoptotic function."
Perrotta C., Bizzozero L., Cazzato D., Morlacchi S., Assi E., Simbari F., Zhang Y., Gulbins E., Bassi M.T., Rosa P., Clementi E.
J Biol Chem 285:40240-40251(2010) [PubMed] [Europe PMC] [Abstract]
- endolysosome Source: UniProtKBInferred from direct assayi
Extracellular region or secreted
- extracellular exosome Source: UniProtKBInferred from high throughput direct assayi
- "In-depth proteomic analyses of exosomes isolated from expressed prostatic secretions in urine."
Principe S., Jones E.E., Kim Y., Sinha A., Nyalwidhe J.O., Brooks J., Semmes O.J., Troyer D.A., Lance R.S., Kislinger T., Drake R.R.
Proteomics 13:1667-1671(2013) [PubMed] [Europe PMC] [Abstract]
- extracellular space Source: UniProtKBInferred from direct assayi
- Ref.14"The lysosomal trafficking of acid sphingomyelinase is mediated by sortilin and mannose 6-phosphate receptor."
Ni X., Morales C.R.
Traffic 7:889-902(2006) [PubMed] [Europe PMC] [Abstract]Cited for: SUBCELLULAR LOCATION, FUNCTION, INTERACTION WITH SORT1. - Ref.16"Activation of acid sphingomyelinase by protein kinase Cdelta-mediated phosphorylation."
Zeidan Y.H., Hannun Y.A.
J. Biol. Chem. 282:11549-11561(2007) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, PHOSPHORYLATION AT SER-510, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, MUTAGENESIS OF SER-151; SER-233; SER-250 AND SER-510. - Ref.18"Exocytosis of acid sphingomyelinase by wounded cells promotes endocytosis and plasma membrane repair."
Tam C., Idone V., Devlin C., Fernandes M.C., Flannery A., He X., Schuchman E., Tabas I., Andrews N.W.
J. Cell Biol. 189:1027-1038(2010) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION. - Ref.17"Regulated secretion of acid sphingomyelinase: implications for selectivity of ceramide formation."
Jenkins R.W., Canals D., Idkowiak-Baldys J., Simbari F., Roddy P., Perry D.M., Kitatani K., Luberto C., Hannun Y.A.
J. Biol. Chem. 285:35706-35718(2010) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, GLYCOSYLATION, MUTAGENESIS OF SER-510. - Ref.48"A novel mechanism of lysosomal acid sphingomyelinase maturation: requirement for carboxyl-terminal proteolytic processing."
Jenkins R.W., Idkowiak-Baldys J., Simbari F., Canals D., Roddy P., Riner C.D., Clarke C.J., Hannun Y.A.
J. Biol. Chem. 286:3777-3788(2011) [PubMed] [Europe PMC] [Abstract]Cited for: CATALYTIC ACTIVITY, FUNCTION, SUBCELLULAR LOCATION, CHARACTERIZATION OF VARIANTS NPDB HIS-602; PRO-602 AND ARG-610 DEL. - Ref.19"Ebolavirus requires acid sphingomyelinase activity and plasma membrane sphingomyelin for infection."
Miller M.E., Adhikary S., Kolokoltsov A.A., Davey R.A.
J. Virol. 86:7473-7483(2012) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION (MICROBIAL INFECTION), SUBCELLULAR LOCATION, CATALYTIC ACTIVITY, ACTIVITY REGULATION. - Ref.58"Structural and functional analysis of the ASM p.Ala359Asp mutant that causes acid sphingomyelinase deficiency."
Acuna M., Castro-Fernandez V., Latorre M., Castro J., Schuchman E.H., Guixe V., Gonzalez M., Zanlungo S.
Biochem. Biophys. Res. Commun. 479:496-501(2016) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, CHARACTERIZATION OF VARIANT NPDB ASP-359. - Ref.9"Zn2+-stimulated sphingomyelinase is secreted by many cell types and is a product of the acid sphingomyelinase gene."
Schissel S.L., Schuchman E.H., Williams K.J., Tabas I.
J. Biol. Chem. 271:18431-18436(1996) [PubMed] [Europe PMC] [Abstract]Cited for: CATALYTIC ACTIVITY, COFACTOR, SUBCELLULAR LOCATION. - Ref.36"The cellular trafficking and zinc dependence of secretory and lysosomal sphingomyelinase, two products of the acid sphingomyelinase gene."
Schissel S.L., Keesler G.A., Schuchman E.H., Williams K.J., Tabas I.
J. Biol. Chem. 273:18250-18259(1998) [PubMed] [Europe PMC] [Abstract]Cited for: CHARACTERIZATION OF VARIANT NPDA LEU-498, FUNCTION, COFACTOR.
- extracellular exosome Source: UniProtKBInferred from high throughput direct assayi
Lysosome
- endolysosome Source: UniProtKBInferred from direct assayi
- Ref.16"Activation of acid sphingomyelinase by protein kinase Cdelta-mediated phosphorylation."
Zeidan Y.H., Hannun Y.A.
J. Biol. Chem. 282:11549-11561(2007) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, PHOSPHORYLATION AT SER-510, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, MUTAGENESIS OF SER-151; SER-233; SER-250 AND SER-510.
- lysosomal lumen Source: Reactome
- lysosome Source: UniProtKBInferred from direct assayi
- Ref.14"The lysosomal trafficking of acid sphingomyelinase is mediated by sortilin and mannose 6-phosphate receptor."
Ni X., Morales C.R.
Traffic 7:889-902(2006) [PubMed] [Europe PMC] [Abstract]Cited for: SUBCELLULAR LOCATION, FUNCTION, INTERACTION WITH SORT1. - Ref.44"Characterization of common SMPD1 mutations causing types A and B Niemann-Pick disease and generation of mutation-specific mouse models."
Jones I., He X., Katouzian F., Darroch P.I., Schuchman E.H.
Mol. Genet. Metab. 95:152-162(2008) [PubMed] [Europe PMC] [Abstract]Cited for: CHARACTERIZATION OF VARIANTS NPDA PRO-304 AND LEU-498, CHARACTERIZATION OF VARIANTS NPDB TYR-423 AND ARG-610 DEL, FUNCTION, SUBCELLULAR LOCATION, CATALYTIC ACTIVITY. - Ref.18"Exocytosis of acid sphingomyelinase by wounded cells promotes endocytosis and plasma membrane repair."
Tam C., Idone V., Devlin C., Fernandes M.C., Flannery A., He X., Schuchman E., Tabas I., Andrews N.W.
J. Cell Biol. 189:1027-1038(2010) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION. - Ref.17"Regulated secretion of acid sphingomyelinase: implications for selectivity of ceramide formation."
Jenkins R.W., Canals D., Idkowiak-Baldys J., Simbari F., Roddy P., Perry D.M., Kitatani K., Luberto C., Hannun Y.A.
J. Biol. Chem. 285:35706-35718(2010) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, GLYCOSYLATION, MUTAGENESIS OF SER-510. - "Syntaxin 4 is required for acid sphingomyelinase activity and apoptotic function."
Perrotta C., Bizzozero L., Cazzato D., Morlacchi S., Assi E., Simbari F., Zhang Y., Gulbins E., Bassi M.T., Rosa P., Clementi E.
J Biol Chem 285:40240-40251(2010) [PubMed] [Europe PMC] [Abstract] - Ref.48"A novel mechanism of lysosomal acid sphingomyelinase maturation: requirement for carboxyl-terminal proteolytic processing."
Jenkins R.W., Idkowiak-Baldys J., Simbari F., Canals D., Roddy P., Riner C.D., Clarke C.J., Hannun Y.A.
J. Biol. Chem. 286:3777-3788(2011) [PubMed] [Europe PMC] [Abstract]Cited for: CATALYTIC ACTIVITY, FUNCTION, SUBCELLULAR LOCATION, CHARACTERIZATION OF VARIANTS NPDB HIS-602; PRO-602 AND ARG-610 DEL. - Ref.58"Structural and functional analysis of the ASM p.Ala359Asp mutant that causes acid sphingomyelinase deficiency."
Acuna M., Castro-Fernandez V., Latorre M., Castro J., Schuchman E.H., Guixe V., Gonzalez M., Zanlungo S.
Biochem. Biophys. Res. Commun. 479:496-501(2016) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, CHARACTERIZATION OF VARIANT NPDB ASP-359. - Ref.36"The cellular trafficking and zinc dependence of secretory and lysosomal sphingomyelinase, two products of the acid sphingomyelinase gene."
Schissel S.L., Keesler G.A., Schuchman E.H., Williams K.J., Tabas I.
J. Biol. Chem. 273:18250-18259(1998) [PubMed] [Europe PMC] [Abstract]Cited for: CHARACTERIZATION OF VARIANT NPDA LEU-498, FUNCTION, COFACTOR.
- endolysosome Source: UniProtKBInferred from direct assayi
Plasma Membrane
- plasma membrane Source: UniProtKBInferred from direct assayi
- "Syntaxin 4 is required for acid sphingomyelinase activity and apoptotic function."
Perrotta C., Bizzozero L., Cazzato D., Morlacchi S., Assi E., Simbari F., Zhang Y., Gulbins E., Bassi M.T., Rosa P., Clementi E.
J Biol Chem 285:40240-40251(2010) [PubMed] [Europe PMC] [Abstract]
- plasma membrane Source: UniProtKBInferred from direct assayi
Other locations
- lamellar body Source: Ensembl
- lipid droplet Source: UniProtKB-SubCell
Keywords - Cellular componenti
Lipid droplet, Lysosome, Secreted<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi
<p>This subsection of the 'Pathology and Biotech' section provides information on the disease(s) associated with genetic variations in a given protein. The information is extracted from the scientific literature and diseases that are also described in the <a href="http://www.ncbi.nlm.nih.gov/sites/entrez?db=omim">OMIM</a> database are represented with a <a href="http://www.uniprot.org/diseases">controlled vocabulary</a> in the following way:<p><a href='/help/involvement_in_disease' target='_top'>More...</a></p>Involvement in diseasei
Niemann-Pick disease A (NPDA)19 PublicationsManual assertion based on experiment ini
- Ref.25"Molecular basis of acid sphingomyelinase deficiency in a patient with Niemann-Pick disease type A."
Ferlinz K., Hurwitz R., Sandhoff K.
Biochem. Biophys. Res. Commun. 179:1187-1191(1991) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANT NPDA SER-579, CHARACTERIZATION OF VARIANT NPDA SER-579, CATALYTIC ACTIVITY. - Ref.26"Niemann-Pick disease: a frequent missense mutation in the acid sphingomyelinase gene of Ashkenazi Jewish type A and B patients."
Levran O., Desnick R.J., Schuchman E.H.
Proc. Natl. Acad. Sci. U.S.A. 88:3748-3752(1991) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANT NPDA LEU-498. - Ref.28"Identification and expression of a common missense mutation (L302P) in the acid sphingomyelinase gene of Ashkenazi Jewish type A Niemann-Pick disease patients."
Levran O., Desnick R.J., Schuchman E.H.
Blood 80:2081-2087(1992) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANT NPDA PRO-304. - Ref.30"Identification and expression of five mutations in the human acid sphingomyelinase gene causing types A and B Niemann-Pick disease. Molecular evidence for genetic heterogeneity in the neuronopathic and non-neuronopathic forms."
Takahashi T., Suchi M., Desnick R.J., Takada G., Schuchman E.H.
J. Biol. Chem. 267:12552-12558(1992) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANT NPDA ILE-384, VARIANTS NPDB ARG-244 AND SER-385. - Ref.32"Two new mutations in the acid sphingomyelinase gene causing type A Niemann-pick disease: N389T and R441X."
Schuchman E.H.
Hum. Mutat. 6:352-354(1995) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANT NPDA THR-391. - Ref.33"Identification and expression of a missense mutation (Y446C) in the acid sphingomyelinase gene from a Japanese patient with type A Niemann-Pick disease."
Takahashi T., Suchi M., Sato W., Ten S.B., Sakuragawa N., Desnick R.J., Schuchman E.H., Takada G.
Tohoku J. Exp. Med. 177:117-123(1995) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANT NPDA CYS-448. - Ref.35"Two novel mutations in patients with atypical phenotypes of acid sphingomyelinase deficiency."
Pavluu H., Elleder M.
J. Inherit. Metab. Dis. 20:615-616(1997) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANTS NPDA LYS-294 AND PRO-343. - Ref.36"The cellular trafficking and zinc dependence of secretory and lysosomal sphingomyelinase, two products of the acid sphingomyelinase gene."
Schissel S.L., Keesler G.A., Schuchman E.H., Williams K.J., Tabas I.
J. Biol. Chem. 273:18250-18259(1998) [PubMed] [Europe PMC] [Abstract]Cited for: CHARACTERIZATION OF VARIANT NPDA LEU-498, FUNCTION, COFACTOR. - Ref.38"Seven novel Acid sphingomyelinase gene mutations in Niemann-Pick type A and B patients."
Sikora J., Pavluu-Pereira H., Elleder M., Roelofs H., Wevers R.A.
Ann. Hum. Genet. 67:63-70(2003) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANTS NPDA ARG-250; TYR-321; SER-465; LEU-477 AND HIS-539, VARIANTS NPDB SER-373 AND ARG-610 DEL. - Ref.39"Screening of 25 Italian patients with Niemann-Pick A reveals fourteen new mutations, one common and thirteen private, in SMPD1."
Ricci V., Stroppiano M., Corsolini F., Di Rocco M., Parenti G., Regis S., Grossi S., Biancheri R., Mazzotti R., Filocamo M.
Hum. Mutat. 24:105-105(2004) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANTS NPDA PRO-105; SER-247; LYS-248; HIS-315; PRO-452; LEU-477; LEU-498; HIS-498 AND CYS-519, VARIANT GLN-296. - Ref.42"Acid sphingomyelinase deficiency. Phenotype variability with prevalence of intermediate phenotype in a series of twenty-five Czech and Slovak patients. A multi-approach study."
Pavluu-Pereira H., Asfaw B., Poupctova H., Ledvinova J., Sikora J., Vanier M.T., Sandhoff K., Zeman J., Novotna Z., Chudoba D., Elleder M.
J. Inherit. Metab. Dis. 28:203-227(2005) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANTS NPDA ARG-168; LEU-186; HIS-230; VAL-243; ARG-250; GLU-253; ALA-280; HIS-291; LYS-294; PRO-343; HIS-378; TRP-476; ARG-535 AND SER-579, VARIANT ARG-508, CATALYTIC ACTIVITY, CHARACTERIZATION OF VARIANTS NPDA LEU-186; GLU-253; ALA-280; LYS-294; PRO-343 AND HIS-378. - Ref.44"Characterization of common SMPD1 mutations causing types A and B Niemann-Pick disease and generation of mutation-specific mouse models."
Jones I., He X., Katouzian F., Darroch P.I., Schuchman E.H.
Mol. Genet. Metab. 95:152-162(2008) [PubMed] [Europe PMC] [Abstract]Cited for: CHARACTERIZATION OF VARIANTS NPDA PRO-304 AND LEU-498, CHARACTERIZATION OF VARIANTS NPDB TYR-423 AND ARG-610 DEL, FUNCTION, SUBCELLULAR LOCATION, CATALYTIC ACTIVITY. - Ref.46"Identification and characterization of SMPD1 mutations causing Niemann-Pick types A and B in Spanish patients."
Rodriguez-Pascau L., Gort L., Schuchman E.H., Vilageliu L., Grinberg D., Chabas A.
Hum. Mutat. 30:1117-1122(2009) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANTS NPDA SER-247; CYS-369; PHE-392 DEL; ARG-423; SER-469; GLU-484 AND THR-594 DEL, VARIANTS NPDB CYS-230; HIS-378; TRP-476; ALA-488 AND ARG-610 DEL. - Ref.47"Identification and characterization of eight novel SMPD1 mutations causing types A and B Niemann-Pick disease."
Desnick J.P., Kim J., He X., Wasserstein M.P., Simonaro C.M., Schuchman E.H.
Mol. Med. 16:316-321(2010) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANTS NPDA ARG-211 AND HIS-253, VARIANTS NPDB MET-314; ARG-427 AND HIS-525, CHARACTERIZATION OF VARIANTS NPDA ARG-211 AND HIS-253, CHARACTERIZATION OF VARIANTS NPDB MET-314; ARG-427 AND HIS-525. - Ref.51"Molecular genetic characterization of novel sphingomyelin phosphodiesterase 1 mutations causing niemann-pick disease."
Toth B., Erdos M., Szekely A., Ritli L., Bagossi P., Suemegi J., Marodi L.
JIMD Rep. 3:125-129(2012) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANTS NPDA ASP-247 AND LEU-572, CHARACTERIZATION OF VARIANTS NPDA ASP-247 AND LEU-572. - Ref.52"Acid sphingomyelinase (Asm) deficiency patients in The Netherlands and Belgium: disease spectrum and natural course in attenuated patients."
Hollak C.E., de Sonnaville E.S., Cassiman D., Linthorst G.E., Groener J.E., Morava E., Wevers R.A., Mannens M., Aerts J.M., Meersseman W., Akkerman E., Niezen-Koning K.E., Mulder M.F., Visser G., Wijburg F.A., Lefeber D., Poorthuis B.J.
Mol. Genet. Metab. 107:526-533(2012) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANTS NPDB HIS-91; PRO-105; PRO-163; CYS-230; SER-373; PRO-551 AND ARG-610 DEL, VARIANTS NPDA ARG-250; SER-465; LEU-477 AND HIS-539. - Ref.53"Identification of seven novel SMPD1 mutations causing Niemann-Pick disease types A and B."
Irun P., Mallen M., Dominguez C., Rodriguez-Sureda V., Alvarez-Sala L.A., Arslan N., Bermejo N., Guerrero C., Perez de Soto I., Villalon L., Giraldo P., Pocovi M.
Clin. Genet. 84:356-361(2013) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANTS NPDA ARG-228 AND ARG-387, VARIANTS NPDB CYS-230; SER-247; HIS-378; TRP-476; SER-492; PHE-599 AND ARG-610 DEL. - Ref.55"Spectrum of SMPD1 mutations in Asian-Indian patients with acid sphingomyelinase (ASM)-deficient Niemann-Pick disease."
Ranganath P., Matta D., Bhavani G.S., Wangnekar S., Jain J.M., Verma I.C., Kabra M., Puri R.D., Danda S., Gupta N., Girisha K.M., Sankar V.H., Patil S.J., Ramadevi A.R., Bhat M., Gowrishankar K., Mandal K., Aggarwal S. , Tamhankar P.M., Tilak P., Phadke S.R., Dalal A.
Am. J. Med. Genet. A 170:2719-2730(2016) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANTS ALA-36; PHE-510 AND GLY-605, VARIANTS NPDA ARG-216; CYS-230; SER-255; ARG-319; PRO-324; ARG-343; ARG-363; HIS-391; ARG-393; SER-426; ILE-494; HIS-498; ARG-535 AND HIS-602, VARIANTS NPDB PRO-105; PHE-282; ASP-320; CYS-369; SER-465; LEU-520 AND LYS-549. - Ref.56"SMPD1 mutation update: database and comprehensive analysis of published and novel variants."
Zampieri S., Filocamo M., Pianta A., Lualdi S., Gort L., Coll M.J., Sinnott R., Geberhiwot T., Bembi B., Dardis A.
Hum. Mutat. 37:139-147(2016) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANTS NPDB ILE-258; GLN-476; ASP-577; ARG-598 AND CYS-610, VARIANT NPDA PHE-482 DEL, REVIEW ON VARIANTS.
Ref.25
"Molecular basis of acid sphingomyelinase deficiency in a patient with Niemann-Pick disease type A."
Ferlinz K., Hurwitz R., Sandhoff K.
Biochem. Biophys. Res. Commun. 179:1187-1191(1991) [PubMed] [Europe PMC] [Abstract]
Ferlinz K., Hurwitz R., Sandhoff K.
Biochem. Biophys. Res. Commun. 179:1187-1191(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT NPDA SER-579, CHARACTERIZATION OF VARIANT NPDA SER-579, CATALYTIC ACTIVITY.
Ref.26
"Niemann-Pick disease: a frequent missense mutation in the acid sphingomyelinase gene of Ashkenazi Jewish type A and B patients."
Levran O., Desnick R.J., Schuchman E.H.
Proc. Natl. Acad. Sci. U.S.A. 88:3748-3752(1991) [PubMed] [Europe PMC] [Abstract]
Levran O., Desnick R.J., Schuchman E.H.
Proc. Natl. Acad. Sci. U.S.A. 88:3748-3752(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT NPDA LEU-498.
Ref.28
"Identification and expression of a common missense mutation (L302P) in the acid sphingomyelinase gene of Ashkenazi Jewish type A Niemann-Pick disease patients."
Levran O., Desnick R.J., Schuchman E.H.
Blood 80:2081-2087(1992) [PubMed] [Europe PMC] [Abstract]
Levran O., Desnick R.J., Schuchman E.H.
Blood 80:2081-2087(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT NPDA PRO-304.
Ref.30
"Identification and expression of five mutations in the human acid sphingomyelinase gene causing types A and B Niemann-Pick disease. Molecular evidence for genetic heterogeneity in the neuronopathic and non-neuronopathic forms."
Takahashi T., Suchi M., Desnick R.J., Takada G., Schuchman E.H.
J. Biol. Chem. 267:12552-12558(1992) [PubMed] [Europe PMC] [Abstract]
Takahashi T., Suchi M., Desnick R.J., Takada G., Schuchman E.H.
J. Biol. Chem. 267:12552-12558(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT NPDA ILE-384, VARIANTS NPDB ARG-244 AND SER-385.
Ref.32
"Two new mutations in the acid sphingomyelinase gene causing type A Niemann-pick disease: N389T and R441X."
Schuchman E.H.
Hum. Mutat. 6:352-354(1995) [PubMed] [Europe PMC] [Abstract]
Schuchman E.H.
Hum. Mutat. 6:352-354(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT NPDA THR-391.
Ref.33
"Identification and expression of a missense mutation (Y446C) in the acid sphingomyelinase gene from a Japanese patient with type A Niemann-Pick disease."
Takahashi T., Suchi M., Sato W., Ten S.B., Sakuragawa N., Desnick R.J., Schuchman E.H., Takada G.
Tohoku J. Exp. Med. 177:117-123(1995) [PubMed] [Europe PMC] [Abstract]
Takahashi T., Suchi M., Sato W., Ten S.B., Sakuragawa N., Desnick R.J., Schuchman E.H., Takada G.
Tohoku J. Exp. Med. 177:117-123(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT NPDA CYS-448.
Ref.35
"Two novel mutations in patients with atypical phenotypes of acid sphingomyelinase deficiency."
Pavluu H., Elleder M.
J. Inherit. Metab. Dis. 20:615-616(1997) [PubMed] [Europe PMC] [Abstract]
Pavluu H., Elleder M.
J. Inherit. Metab. Dis. 20:615-616(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS NPDA LYS-294 AND PRO-343.
Ref.36
"The cellular trafficking and zinc dependence of secretory and lysosomal sphingomyelinase, two products of the acid sphingomyelinase gene."
Schissel S.L., Keesler G.A., Schuchman E.H., Williams K.J., Tabas I.
J. Biol. Chem. 273:18250-18259(1998) [PubMed] [Europe PMC] [Abstract]
Schissel S.L., Keesler G.A., Schuchman E.H., Williams K.J., Tabas I.
J. Biol. Chem. 273:18250-18259(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION OF VARIANT NPDA LEU-498, FUNCTION, COFACTOR.
Ref.38
"Seven novel Acid sphingomyelinase gene mutations in Niemann-Pick type A and B patients."
Sikora J., Pavluu-Pereira H., Elleder M., Roelofs H., Wevers R.A.
Ann. Hum. Genet. 67:63-70(2003) [PubMed] [Europe PMC] [Abstract]
Sikora J., Pavluu-Pereira H., Elleder M., Roelofs H., Wevers R.A.
Ann. Hum. Genet. 67:63-70(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS NPDA ARG-250; TYR-321; SER-465; LEU-477 AND HIS-539, VARIANTS NPDB SER-373 AND ARG-610 DEL.
Ref.39
"Screening of 25 Italian patients with Niemann-Pick A reveals fourteen new mutations, one common and thirteen private, in SMPD1."
Ricci V., Stroppiano M., Corsolini F., Di Rocco M., Parenti G., Regis S., Grossi S., Biancheri R., Mazzotti R., Filocamo M.
Hum. Mutat. 24:105-105(2004) [PubMed] [Europe PMC] [Abstract]
Ricci V., Stroppiano M., Corsolini F., Di Rocco M., Parenti G., Regis S., Grossi S., Biancheri R., Mazzotti R., Filocamo M.
Hum. Mutat. 24:105-105(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS NPDA PRO-105; SER-247; LYS-248; HIS-315; PRO-452; LEU-477; LEU-498; HIS-498 AND CYS-519, VARIANT GLN-296.
Ref.42
"Acid sphingomyelinase deficiency. Phenotype variability with prevalence of intermediate phenotype in a series of twenty-five Czech and Slovak patients. A multi-approach study."
Pavluu-Pereira H., Asfaw B., Poupctova H., Ledvinova J., Sikora J., Vanier M.T., Sandhoff K., Zeman J., Novotna Z., Chudoba D., Elleder M.
J. Inherit. Metab. Dis. 28:203-227(2005) [PubMed] [Europe PMC] [Abstract]
Pavluu-Pereira H., Asfaw B., Poupctova H., Ledvinova J., Sikora J., Vanier M.T., Sandhoff K., Zeman J., Novotna Z., Chudoba D., Elleder M.
J. Inherit. Metab. Dis. 28:203-227(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS NPDA ARG-168; LEU-186; HIS-230; VAL-243; ARG-250; GLU-253; ALA-280; HIS-291; LYS-294; PRO-343; HIS-378; TRP-476; ARG-535 AND SER-579, VARIANT ARG-508, CATALYTIC ACTIVITY, CHARACTERIZATION OF VARIANTS NPDA LEU-186; GLU-253; ALA-280; LYS-294; PRO-343 AND HIS-378.
Ref.44
"Characterization of common SMPD1 mutations causing types A and B Niemann-Pick disease and generation of mutation-specific mouse models."
Jones I., He X., Katouzian F., Darroch P.I., Schuchman E.H.
Mol. Genet. Metab. 95:152-162(2008) [PubMed] [Europe PMC] [Abstract]
Jones I., He X., Katouzian F., Darroch P.I., Schuchman E.H.
Mol. Genet. Metab. 95:152-162(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION OF VARIANTS NPDA PRO-304 AND LEU-498, CHARACTERIZATION OF VARIANTS NPDB TYR-423 AND ARG-610 DEL, FUNCTION, SUBCELLULAR LOCATION, CATALYTIC ACTIVITY.
Ref.46
"Identification and characterization of SMPD1 mutations causing Niemann-Pick types A and B in Spanish patients."
Rodriguez-Pascau L., Gort L., Schuchman E.H., Vilageliu L., Grinberg D., Chabas A.
Hum. Mutat. 30:1117-1122(2009) [PubMed] [Europe PMC] [Abstract]
Rodriguez-Pascau L., Gort L., Schuchman E.H., Vilageliu L., Grinberg D., Chabas A.
Hum. Mutat. 30:1117-1122(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS NPDA SER-247; CYS-369; PHE-392 DEL; ARG-423; SER-469; GLU-484 AND THR-594 DEL, VARIANTS NPDB CYS-230; HIS-378; TRP-476; ALA-488 AND ARG-610 DEL.
Ref.47
"Identification and characterization of eight novel SMPD1 mutations causing types A and B Niemann-Pick disease."
Desnick J.P., Kim J., He X., Wasserstein M.P., Simonaro C.M., Schuchman E.H.
Mol. Med. 16:316-321(2010) [PubMed] [Europe PMC] [Abstract]
Desnick J.P., Kim J., He X., Wasserstein M.P., Simonaro C.M., Schuchman E.H.
Mol. Med. 16:316-321(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS NPDA ARG-211 AND HIS-253, VARIANTS NPDB MET-314; ARG-427 AND HIS-525, CHARACTERIZATION OF VARIANTS NPDA ARG-211 AND HIS-253, CHARACTERIZATION OF VARIANTS NPDB MET-314; ARG-427 AND HIS-525.
Ref.51
"Molecular genetic characterization of novel sphingomyelin phosphodiesterase 1 mutations causing niemann-pick disease."
Toth B., Erdos M., Szekely A., Ritli L., Bagossi P., Suemegi J., Marodi L.
JIMD Rep. 3:125-129(2012) [PubMed] [Europe PMC] [Abstract]
Toth B., Erdos M., Szekely A., Ritli L., Bagossi P., Suemegi J., Marodi L.
JIMD Rep. 3:125-129(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS NPDA ASP-247 AND LEU-572, CHARACTERIZATION OF VARIANTS NPDA ASP-247 AND LEU-572.
Ref.52
"Acid sphingomyelinase (Asm) deficiency patients in The Netherlands and Belgium: disease spectrum and natural course in attenuated patients."
Hollak C.E., de Sonnaville E.S., Cassiman D., Linthorst G.E., Groener J.E., Morava E., Wevers R.A., Mannens M., Aerts J.M., Meersseman W., Akkerman E., Niezen-Koning K.E., Mulder M.F., Visser G., Wijburg F.A., Lefeber D., Poorthuis B.J.
Mol. Genet. Metab. 107:526-533(2012) [PubMed] [Europe PMC] [Abstract]
Hollak C.E., de Sonnaville E.S., Cassiman D., Linthorst G.E., Groener J.E., Morava E., Wevers R.A., Mannens M., Aerts J.M., Meersseman W., Akkerman E., Niezen-Koning K.E., Mulder M.F., Visser G., Wijburg F.A., Lefeber D., Poorthuis B.J.
Mol. Genet. Metab. 107:526-533(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS NPDB HIS-91; PRO-105; PRO-163; CYS-230; SER-373; PRO-551 AND ARG-610 DEL, VARIANTS NPDA ARG-250; SER-465; LEU-477 AND HIS-539.
Ref.53
"Identification of seven novel SMPD1 mutations causing Niemann-Pick disease types A and B."
Irun P., Mallen M., Dominguez C., Rodriguez-Sureda V., Alvarez-Sala L.A., Arslan N., Bermejo N., Guerrero C., Perez de Soto I., Villalon L., Giraldo P., Pocovi M.
Clin. Genet. 84:356-361(2013) [PubMed] [Europe PMC] [Abstract]
Irun P., Mallen M., Dominguez C., Rodriguez-Sureda V., Alvarez-Sala L.A., Arslan N., Bermejo N., Guerrero C., Perez de Soto I., Villalon L., Giraldo P., Pocovi M.
Clin. Genet. 84:356-361(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS NPDA ARG-228 AND ARG-387, VARIANTS NPDB CYS-230; SER-247; HIS-378; TRP-476; SER-492; PHE-599 AND ARG-610 DEL.
Ref.55
"Spectrum of SMPD1 mutations in Asian-Indian patients with acid sphingomyelinase (ASM)-deficient Niemann-Pick disease."
Ranganath P., Matta D., Bhavani G.S., Wangnekar S., Jain J.M., Verma I.C., Kabra M., Puri R.D., Danda S., Gupta N., Girisha K.M., Sankar V.H., Patil S.J., Ramadevi A.R., Bhat M., Gowrishankar K., Mandal K., Aggarwal S. , Tamhankar P.M., Tilak P., Phadke S.R., Dalal A.
Am. J. Med. Genet. A 170:2719-2730(2016) [PubMed] [Europe PMC] [Abstract]
Ranganath P., Matta D., Bhavani G.S., Wangnekar S., Jain J.M., Verma I.C., Kabra M., Puri R.D., Danda S., Gupta N., Girisha K.M., Sankar V.H., Patil S.J., Ramadevi A.R., Bhat M., Gowrishankar K., Mandal K., Aggarwal S. , Tamhankar P.M., Tilak P., Phadke S.R., Dalal A.
Am. J. Med. Genet. A 170:2719-2730(2016) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS ALA-36; PHE-510 AND GLY-605, VARIANTS NPDA ARG-216; CYS-230; SER-255; ARG-319; PRO-324; ARG-343; ARG-363; HIS-391; ARG-393; SER-426; ILE-494; HIS-498; ARG-535 AND HIS-602, VARIANTS NPDB PRO-105; PHE-282; ASP-320; CYS-369; SER-465; LEU-520 AND LYS-549.
Ref.56
"SMPD1 mutation update: database and comprehensive analysis of published and novel variants."
Zampieri S., Filocamo M., Pianta A., Lualdi S., Gort L., Coll M.J., Sinnott R., Geberhiwot T., Bembi B., Dardis A.
Hum. Mutat. 37:139-147(2016) [PubMed] [Europe PMC] [Abstract]
Zampieri S., Filocamo M., Pianta A., Lualdi S., Gort L., Coll M.J., Sinnott R., Geberhiwot T., Bembi B., Dardis A.
Hum. Mutat. 37:139-147(2016) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS NPDB ILE-258; GLN-476; ASP-577; ARG-598 AND CYS-610, VARIANT NPDA PHE-482 DEL, REVIEW ON VARIANTS.
The disease is caused by variants affecting the gene represented in this entry.
Disease descriptionAn 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, mental retardation, 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.
Related information in OMIM| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| <p>This subsection of the 'Sequence' section describes natural variant(s) of the protein sequence.<p><a href='/help/variant' target='_top'>More...</a></p>Natural variantiVAR_060872 | 105 | L → P in NPDA and NPDB; expresses protein level comparable to wild-type SMPD1 expressing cells; retains very low enzyme activity. 5 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_060877 | 186 | P → L in NPDA; reduces enzyme activity; intermediate form with clinical features of both Niemann-Pick disease types A and B. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_068435 | 211 | W → R in NPDA; results in less than 0.5% of wild-type activity. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_077311 | 216 | L → R in NPDA. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_075324 | 228 | C → R in NPDA. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_060882 | 230 | R → C in NPDB and NPDA; some patients have a NPDA/NPDB intermediate phenotype. 5 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_060883 | 230 | R → H in NPDA; intermediate form with clinical features of both Niemann-Pick disease types A and B. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_060885 | 243 | A → V in NPDA; intermediate form with clinical features of both Niemann-Pick disease types A and B. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_075325 | 247 | G → D in NPDA; severe decrease in activity; the mutant is highly unstable. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_060887 | 247 | G → S in NPDA and NPDB. 4 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_060888 | 248 | E → K in NPDA. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_015287 | 250 | S → R in NPDA and NPDB; also found in patients with an intermediate form. 4 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_060889 | 253 | D → E in NPDA; strongly reduces enzyme activity; intermediate form with clinical features of both Niemann-Pick disease types A and B. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_068436 | 253 | D → H in NPDA; results in loss of activity. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_077312 | 255 | P → S in NPDA. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_060890 | 280 | D → A in NPDA; strongly reduces enzyme activity; intermediate form with clinical features of both Niemann-Pick disease types A and B. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_060893 | 294 | Q → K in NPDA; strongly reduces enzyme activity; intermediate form with clinical features of both Niemann-Pick disease types A and B. 3 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_005060 | 304 | L → P in NPDA; in 23% of NPDA Ashkenazi Jewish patients; abolishes enzyme activity. 2 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_060895 | 315 | Y → H in NPDA. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_077314 | 319 | G → R in NPDA. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_015288 | 321 | H → Y in NPDA. 2 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_077316 | 324 | T → P in NPDA; unknown pathological significance. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_060898 | 343 | L → P in NPDA; strongly reduces enzyme activity; intermediate form with clinical features of both Niemann-Pick disease types A and B. 2 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_077317 | 343 | L → R in NPDA. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_077318 | 363 | L → R in NPDA; unknown pathological significance. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_060900 | 369 | Y → C in NPDA. 2 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_005061 | 384 | M → I in NPDA and NPDB. 2 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_075327 | 387 | C → R in NPDA. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_077319 | 391 | N → H in NPDA. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_005063 | 391 | N → T in NPDA. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_060904 | 392 | Missing in NPDA. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_077320 | 393 | W → R in NPDA; intermediate form. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_060906 | 423 | H → R in NPDA. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_077321 | 426 | G → S in NPDA. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_011388 | 448 | Y → C in NPDA. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_060910 | 452 | L → P in NPDA. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_015291 | 465 | F → S in NPDA. 2 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_060913 | 469 | Y → S in NPDA. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_015292 | 477 | P → L in NPDA and NPDB. 4 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_075329 | 482 | Missing in NPDA; unknown pathological significance. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_060916 | 484 | A → E in NPDA. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_077322 | 494 | N → I in NPDA; intermediate form. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_060922 | 498 | R → H in NPDA. 2 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_005066 | 498 | R → L in NPDA; in 32% of NPDA Ashkenazi Jewish patients; nearly abolishes enzyme activity. 4 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_060926 | 519 | Y → C in NPDA. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_060927 | 535 | W → R in NPDB and NPDA; also in patients with an intermediate form. 3 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_015293 | 539 | Y → H in NPDA. 2 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_075331 | 572 | F → L in NPDA; results in decreased activity; decreased stability. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_005067 | 579 | G → S in NPDA; impairs enzyme activity; also in patients with an intermediate form. 2 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_060931 | 594 | Missing in NPDA. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_060932 | 602 | R → H in NPDB and NPDA; expresses protein level comparable to wild-type SMPD1 expressing cells; retains about 10% residual enzyme activity; loss of location to lysosome. 4 Publications Manual assertion based on experiment ini
| 1 |
Niemann-Pick disease B (NPDB)25 PublicationsManual assertion based on experiment ini
- Ref.27"Niemann-Pick type B disease. Identification of a single codon deletion in the acid sphingomyelinase gene and genotype/phenotype correlations in type A and B patients."
Levran O., Desnick R.J., Schuchman E.H.
J. Clin. Invest. 88:806-810(1991) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANT NPDB ARG-610 DEL. - Ref.29"Identification of a missense mutation (S436R) in the acid sphingomyelinase gene from a Japanese patient with type B Niemann-Pick disease."
Takahashi T., Desnick R.J., Takada G., Schuchman E.H.
Hum. Mutat. 1:70-71(1992) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANT NPDB ARG-438. - Ref.30"Identification and expression of five mutations in the human acid sphingomyelinase gene causing types A and B Niemann-Pick disease. Molecular evidence for genetic heterogeneity in the neuronopathic and non-neuronopathic forms."
Takahashi T., Suchi M., Desnick R.J., Takada G., Schuchman E.H.
J. Biol. Chem. 267:12552-12558(1992) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANT NPDA ILE-384, VARIANTS NPDB ARG-244 AND SER-385. - Ref.31"A family with visceral course of Niemann-Pick disease, macular halo syndrome and low sphingomyelin degradation rate."
Sperl W., Bart G., Vanier M.T., Christomanou H., Baldissera I., Steichensdorf E., Paschke E.
J. Inherit. Metab. Dis. 17:93-103(1994) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANT NPDB GLY-393. - Ref.34"Identification of three novel mutations in the acid sphingomyelinase gene of Japanese patients with Niemann-Pick disease type A and B."
Ida H., Rennert O.M., Maekawa K., Eto Y.
Hum. Mutat. 7:65-67(1996) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANT NPDB GLN-248. - Ref.37"The demographics and distribution of type B Niemann-Pick disease: novel mutations lead to new genotype/phenotype correlations."
Simonaro C.M., Desnick R.J., McGovern M.M., Wasserstein M.P., Schuchman E.H.
Am. J. Hum. Genet. 71:1413-1419(2002) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANTS NPDB VAL-51; TRP-94; PRO-139; ARG-159; PRO-198; CYS-202; MET-227; CYS-230; ASP-234; SER-247; ARG-250; HIS-291; ALA-325; ARG-332; ASP-359; HIS-378; LEU-378; PRO-381; VAL-415; TYR-423; ARG-433; PRO-434; CYS-437; VAL-454; ASP-458; TRP-476; LEU-477; LEU-482; ASN-490; SER-496; CYS-498; GLN-516; VAL-517; ARG-535; PRO-551; ASN-578; HIS-602 AND PRO-602, VARIANT VAL-487. - Ref.38"Seven novel Acid sphingomyelinase gene mutations in Niemann-Pick type A and B patients."
Sikora J., Pavluu-Pereira H., Elleder M., Roelofs H., Wevers R.A.
Ann. Hum. Genet. 67:63-70(2003) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANTS NPDA ARG-250; TYR-321; SER-465; LEU-477 AND HIS-539, VARIANTS NPDB SER-373 AND ARG-610 DEL. - Ref.40"Acid sphingomyelinase: identification of nine novel mutations among Italian Niemann Pick type B patients and characterization of in vivo functional in-frame start codon."
Pittis M.G., Ricci V., Guerci V.I., Marcais C., Ciana G., Dardis A., Gerin F., Stroppiano M., Vanier M.T., Filocamo M., Bembi B.
Hum. Mutat. 24:186-187(2004) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANTS NPDB PRO-105; PRO-227; CYS-246; THR-283; LYS-294 AND ILE-384. - Ref.41"Functional in vitro characterization of 14 SMPD1 mutations identified in Italian patients affected by Niemann Pick type B disease."
Dardis A., Zampieri S., Filocamo M., Burlina A., Bembi B., Pittis M.G.
Hum. Mutat. 26:164-164(2005) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANTS NPDB ALA-132 AND TYR-565, CHARACTERIZATION OF VARIANTS NPDB PRO-105; ALA-132; PRO-227; CYS-246; THR-283; TYR-565; HIS-602 AND PRO-602. - Ref.43"Clinical findings in Niemann-Pick disease type B."
Muessig K., Harzer K., Mayrhofer H., Kraegeloh-Mann I., Haering H.-U., Machicao F.
Intern. Med. J. 36:135-136(2006) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANTS NPDB ARG-168 AND ASN-178, VARIANT GLY-507. - Ref.44"Characterization of common SMPD1 mutations causing types A and B Niemann-Pick disease and generation of mutation-specific mouse models."
Jones I., He X., Katouzian F., Darroch P.I., Schuchman E.H.
Mol. Genet. Metab. 95:152-162(2008) [PubMed] [Europe PMC] [Abstract]Cited for: CHARACTERIZATION OF VARIANTS NPDA PRO-304 AND LEU-498, CHARACTERIZATION OF VARIANTS NPDB TYR-423 AND ARG-610 DEL, FUNCTION, SUBCELLULAR LOCATION, CATALYTIC ACTIVITY. - Ref.45"A novel missense mutation of the SMPD1 gene in a Taiwanese patient with type B Niemann-Pick disease."
Lan M.Y., Lin S.J., Chen Y.F., Peng C.H., Liu Y.F.
Ann. Hematol. 88:695-697(2009) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANTS NPDB ARG-332 AND ASP-453. - Ref.46"Identification and characterization of SMPD1 mutations causing Niemann-Pick types A and B in Spanish patients."
Rodriguez-Pascau L., Gort L., Schuchman E.H., Vilageliu L., Grinberg D., Chabas A.
Hum. Mutat. 30:1117-1122(2009) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANTS NPDA SER-247; CYS-369; PHE-392 DEL; ARG-423; SER-469; GLU-484 AND THR-594 DEL, VARIANTS NPDB CYS-230; HIS-378; TRP-476; ALA-488 AND ARG-610 DEL. - Ref.47"Identification and characterization of eight novel SMPD1 mutations causing types A and B Niemann-Pick disease."
Desnick J.P., Kim J., He X., Wasserstein M.P., Simonaro C.M., Schuchman E.H.
Mol. Med. 16:316-321(2010) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANTS NPDA ARG-211 AND HIS-253, VARIANTS NPDB MET-314; ARG-427 AND HIS-525, CHARACTERIZATION OF VARIANTS NPDA ARG-211 AND HIS-253, CHARACTERIZATION OF VARIANTS NPDB MET-314; ARG-427 AND HIS-525. - Ref.48"A novel mechanism of lysosomal acid sphingomyelinase maturation: requirement for carboxyl-terminal proteolytic processing."
Jenkins R.W., Idkowiak-Baldys J., Simbari F., Canals D., Roddy P., Riner C.D., Clarke C.J., Hannun Y.A.
J. Biol. Chem. 286:3777-3788(2011) [PubMed] [Europe PMC] [Abstract]Cited for: CATALYTIC ACTIVITY, FUNCTION, SUBCELLULAR LOCATION, CHARACTERIZATION OF VARIANTS NPDB HIS-602; PRO-602 AND ARG-610 DEL. - Ref.49"PAS-positive macrophages--not always infection."
Meersseman W., Verschueren P., Tousseyn T., De Vos R., Cassiman D.
Lancet 377:1890-1890(2011) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANT NPDB PRO-163. - Ref.52"Acid sphingomyelinase (Asm) deficiency patients in The Netherlands and Belgium: disease spectrum and natural course in attenuated patients."
Hollak C.E., de Sonnaville E.S., Cassiman D., Linthorst G.E., Groener J.E., Morava E., Wevers R.A., Mannens M., Aerts J.M., Meersseman W., Akkerman E., Niezen-Koning K.E., Mulder M.F., Visser G., Wijburg F.A., Lefeber D., Poorthuis B.J.
Mol. Genet. Metab. 107:526-533(2012) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANTS NPDB HIS-91; PRO-105; PRO-163; CYS-230; SER-373; PRO-551 AND ARG-610 DEL, VARIANTS NPDA ARG-250; SER-465; LEU-477 AND HIS-539. - Ref.53"Identification of seven novel SMPD1 mutations causing Niemann-Pick disease types A and B."
Irun P., Mallen M., Dominguez C., Rodriguez-Sureda V., Alvarez-Sala L.A., Arslan N., Bermejo N., Guerrero C., Perez de Soto I., Villalon L., Giraldo P., Pocovi M.
Clin. Genet. 84:356-361(2013) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANTS NPDA ARG-228 AND ARG-387, VARIANTS NPDB CYS-230; SER-247; HIS-378; TRP-476; SER-492; PHE-599 AND ARG-610 DEL. - Ref.54"The acid sphingomyelinase sequence variant p.A487V is not associated with decreased levels of enzymatic activity."
Rhein C., Naumann J., Muehle C., Zill P., Adli M., Hegerl U., Hiemke C., Mergl R., Moeller H.J., Reichel M., Kornhuber J.
JIMD Rep. 8:1-6(2013) [PubMed] [Europe PMC] [Abstract]Cited for: CHARACTERIZATION OF VARIANT NPDB ALA-325, CHARACTERIZATION OF VARIANT VAL-487. - Ref.55"Spectrum of SMPD1 mutations in Asian-Indian patients with acid sphingomyelinase (ASM)-deficient Niemann-Pick disease."
Ranganath P., Matta D., Bhavani G.S., Wangnekar S., Jain J.M., Verma I.C., Kabra M., Puri R.D., Danda S., Gupta N., Girisha K.M., Sankar V.H., Patil S.J., Ramadevi A.R., Bhat M., Gowrishankar K., Mandal K., Aggarwal S. , Tamhankar P.M., Tilak P., Phadke S.R., Dalal A.
Am. J. Med. Genet. A 170:2719-2730(2016) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANTS ALA-36; PHE-510 AND GLY-605, VARIANTS NPDA ARG-216; CYS-230; SER-255; ARG-319; PRO-324; ARG-343; ARG-363; HIS-391; ARG-393; SER-426; ILE-494; HIS-498; ARG-535 AND HIS-602, VARIANTS NPDB PRO-105; PHE-282; ASP-320; CYS-369; SER-465; LEU-520 AND LYS-549. - Ref.56"SMPD1 mutation update: database and comprehensive analysis of published and novel variants."
Zampieri S., Filocamo M., Pianta A., Lualdi S., Gort L., Coll M.J., Sinnott R., Geberhiwot T., Bembi B., Dardis A.
Hum. Mutat. 37:139-147(2016) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANTS NPDB ILE-258; GLN-476; ASP-577; ARG-598 AND CYS-610, VARIANT NPDA PHE-482 DEL, REVIEW ON VARIANTS. - Ref.57"Alleged detrimental mutations in the SMPD1 gene in patients with Niemann-Pick disease."
Rhein C., Muehle C., Kornhuber J., Reichel M.
Int. J. Mol. Sci. 16:13649-13652(2015) [PubMed] [Europe PMC] [Abstract]Cited for: CHARACTERIZATION OF VARIANT NPDB ALA-325, CHARACTERIZATION OF VARIANTS ALA-36; VAL-487 AND ARG-508, CATALYTIC ACTIVITY. - Ref.58"Structural and functional analysis of the ASM p.Ala359Asp mutant that causes acid sphingomyelinase deficiency."
Acuna M., Castro-Fernandez V., Latorre M., Castro J., Schuchman E.H., Guixe V., Gonzalez M., Zanlungo S.
Biochem. Biophys. Res. Commun. 479:496-501(2016) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, CHARACTERIZATION OF VARIANT NPDB ASP-359. - Ref.59"Epidemiological, clinical and biochemical characterization of the p.(Ala359Asp) SMPD1 variant causing Niemann-Pick disease type B."
Acuna M., Martinez P., Moraga C., He X., Moraga M., Hunter B., Nuernberg P., Gutierrez R.A., Gonzalez M., Schuchman E.H., Santos J.L., Miquel J.F., Mabe P., Zanlungo S.
Eur. J. Hum. Genet. 24:208-213(2016) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, SUBCELLULAR LOCATION, VARIANT NPDB ASP-359, CHARACTERIZATION OF VARIANT NPDB ASP-359.
Ref.27
"Niemann-Pick type B disease. Identification of a single codon deletion in the acid sphingomyelinase gene and genotype/phenotype correlations in type A and B patients."
Levran O., Desnick R.J., Schuchman E.H.
J. Clin. Invest. 88:806-810(1991) [PubMed] [Europe PMC] [Abstract]
Levran O., Desnick R.J., Schuchman E.H.
J. Clin. Invest. 88:806-810(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT NPDB ARG-610 DEL.
Ref.29
"Identification of a missense mutation (S436R) in the acid sphingomyelinase gene from a Japanese patient with type B Niemann-Pick disease."
Takahashi T., Desnick R.J., Takada G., Schuchman E.H.
Hum. Mutat. 1:70-71(1992) [PubMed] [Europe PMC] [Abstract]
Takahashi T., Desnick R.J., Takada G., Schuchman E.H.
Hum. Mutat. 1:70-71(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT NPDB ARG-438.
Ref.30
"Identification and expression of five mutations in the human acid sphingomyelinase gene causing types A and B Niemann-Pick disease. Molecular evidence for genetic heterogeneity in the neuronopathic and non-neuronopathic forms."
Takahashi T., Suchi M., Desnick R.J., Takada G., Schuchman E.H.
J. Biol. Chem. 267:12552-12558(1992) [PubMed] [Europe PMC] [Abstract]
Takahashi T., Suchi M., Desnick R.J., Takada G., Schuchman E.H.
J. Biol. Chem. 267:12552-12558(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT NPDA ILE-384, VARIANTS NPDB ARG-244 AND SER-385.
Ref.31
"A family with visceral course of Niemann-Pick disease, macular halo syndrome and low sphingomyelin degradation rate."
Sperl W., Bart G., Vanier M.T., Christomanou H., Baldissera I., Steichensdorf E., Paschke E.
J. Inherit. Metab. Dis. 17:93-103(1994) [PubMed] [Europe PMC] [Abstract]
Sperl W., Bart G., Vanier M.T., Christomanou H., Baldissera I., Steichensdorf E., Paschke E.
J. Inherit. Metab. Dis. 17:93-103(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT NPDB GLY-393.
Ref.34
"Identification of three novel mutations in the acid sphingomyelinase gene of Japanese patients with Niemann-Pick disease type A and B."
Ida H., Rennert O.M., Maekawa K., Eto Y.
Hum. Mutat. 7:65-67(1996) [PubMed] [Europe PMC] [Abstract]
Ida H., Rennert O.M., Maekawa K., Eto Y.
Hum. Mutat. 7:65-67(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT NPDB GLN-248.
Ref.37
"The demographics and distribution of type B Niemann-Pick disease: novel mutations lead to new genotype/phenotype correlations."
Simonaro C.M., Desnick R.J., McGovern M.M., Wasserstein M.P., Schuchman E.H.
Am. J. Hum. Genet. 71:1413-1419(2002) [PubMed] [Europe PMC] [Abstract]
Simonaro C.M., Desnick R.J., McGovern M.M., Wasserstein M.P., Schuchman E.H.
Am. J. Hum. Genet. 71:1413-1419(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS NPDB VAL-51; TRP-94; PRO-139; ARG-159; PRO-198; CYS-202; MET-227; CYS-230; ASP-234; SER-247; ARG-250; HIS-291; ALA-325; ARG-332; ASP-359; HIS-378; LEU-378; PRO-381; VAL-415; TYR-423; ARG-433; PRO-434; CYS-437; VAL-454; ASP-458; TRP-476; LEU-477; LEU-482; ASN-490; SER-496; CYS-498; GLN-516; VAL-517; ARG-535; PRO-551; ASN-578; HIS-602 AND PRO-602, VARIANT VAL-487.
Ref.38
"Seven novel Acid sphingomyelinase gene mutations in Niemann-Pick type A and B patients."
Sikora J., Pavluu-Pereira H., Elleder M., Roelofs H., Wevers R.A.
Ann. Hum. Genet. 67:63-70(2003) [PubMed] [Europe PMC] [Abstract]
Sikora J., Pavluu-Pereira H., Elleder M., Roelofs H., Wevers R.A.
Ann. Hum. Genet. 67:63-70(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS NPDA ARG-250; TYR-321; SER-465; LEU-477 AND HIS-539, VARIANTS NPDB SER-373 AND ARG-610 DEL.
Ref.40
"Acid sphingomyelinase: identification of nine novel mutations among Italian Niemann Pick type B patients and characterization of in vivo functional in-frame start codon."
Pittis M.G., Ricci V., Guerci V.I., Marcais C., Ciana G., Dardis A., Gerin F., Stroppiano M., Vanier M.T., Filocamo M., Bembi B.
Hum. Mutat. 24:186-187(2004) [PubMed] [Europe PMC] [Abstract]
Pittis M.G., Ricci V., Guerci V.I., Marcais C., Ciana G., Dardis A., Gerin F., Stroppiano M., Vanier M.T., Filocamo M., Bembi B.
Hum. Mutat. 24:186-187(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS NPDB PRO-105; PRO-227; CYS-246; THR-283; LYS-294 AND ILE-384.
Ref.41
"Functional in vitro characterization of 14 SMPD1 mutations identified in Italian patients affected by Niemann Pick type B disease."
Dardis A., Zampieri S., Filocamo M., Burlina A., Bembi B., Pittis M.G.
Hum. Mutat. 26:164-164(2005) [PubMed] [Europe PMC] [Abstract]
Dardis A., Zampieri S., Filocamo M., Burlina A., Bembi B., Pittis M.G.
Hum. Mutat. 26:164-164(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS NPDB ALA-132 AND TYR-565, CHARACTERIZATION OF VARIANTS NPDB PRO-105; ALA-132; PRO-227; CYS-246; THR-283; TYR-565; HIS-602 AND PRO-602.
Ref.43
"Clinical findings in Niemann-Pick disease type B."
Muessig K., Harzer K., Mayrhofer H., Kraegeloh-Mann I., Haering H.-U., Machicao F.
Intern. Med. J. 36:135-136(2006) [PubMed] [Europe PMC] [Abstract]
Muessig K., Harzer K., Mayrhofer H., Kraegeloh-Mann I., Haering H.-U., Machicao F.
Intern. Med. J. 36:135-136(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS NPDB ARG-168 AND ASN-178, VARIANT GLY-507.
Ref.44
"Characterization of common SMPD1 mutations causing types A and B Niemann-Pick disease and generation of mutation-specific mouse models."
Jones I., He X., Katouzian F., Darroch P.I., Schuchman E.H.
Mol. Genet. Metab. 95:152-162(2008) [PubMed] [Europe PMC] [Abstract]
Jones I., He X., Katouzian F., Darroch P.I., Schuchman E.H.
Mol. Genet. Metab. 95:152-162(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION OF VARIANTS NPDA PRO-304 AND LEU-498, CHARACTERIZATION OF VARIANTS NPDB TYR-423 AND ARG-610 DEL, FUNCTION, SUBCELLULAR LOCATION, CATALYTIC ACTIVITY.
Ref.45
"A novel missense mutation of the SMPD1 gene in a Taiwanese patient with type B Niemann-Pick disease."
Lan M.Y., Lin S.J., Chen Y.F., Peng C.H., Liu Y.F.
Ann. Hematol. 88:695-697(2009) [PubMed] [Europe PMC] [Abstract]
Lan M.Y., Lin S.J., Chen Y.F., Peng C.H., Liu Y.F.
Ann. Hematol. 88:695-697(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS NPDB ARG-332 AND ASP-453.
Ref.46
"Identification and characterization of SMPD1 mutations causing Niemann-Pick types A and B in Spanish patients."
Rodriguez-Pascau L., Gort L., Schuchman E.H., Vilageliu L., Grinberg D., Chabas A.
Hum. Mutat. 30:1117-1122(2009) [PubMed] [Europe PMC] [Abstract]
Rodriguez-Pascau L., Gort L., Schuchman E.H., Vilageliu L., Grinberg D., Chabas A.
Hum. Mutat. 30:1117-1122(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS NPDA SER-247; CYS-369; PHE-392 DEL; ARG-423; SER-469; GLU-484 AND THR-594 DEL, VARIANTS NPDB CYS-230; HIS-378; TRP-476; ALA-488 AND ARG-610 DEL.
Ref.47
"Identification and characterization of eight novel SMPD1 mutations causing types A and B Niemann-Pick disease."
Desnick J.P., Kim J., He X., Wasserstein M.P., Simonaro C.M., Schuchman E.H.
Mol. Med. 16:316-321(2010) [PubMed] [Europe PMC] [Abstract]
Desnick J.P., Kim J., He X., Wasserstein M.P., Simonaro C.M., Schuchman E.H.
Mol. Med. 16:316-321(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS NPDA ARG-211 AND HIS-253, VARIANTS NPDB MET-314; ARG-427 AND HIS-525, CHARACTERIZATION OF VARIANTS NPDA ARG-211 AND HIS-253, CHARACTERIZATION OF VARIANTS NPDB MET-314; ARG-427 AND HIS-525.
Ref.48
"A novel mechanism of lysosomal acid sphingomyelinase maturation: requirement for carboxyl-terminal proteolytic processing."
Jenkins R.W., Idkowiak-Baldys J., Simbari F., Canals D., Roddy P., Riner C.D., Clarke C.J., Hannun Y.A.
J. Biol. Chem. 286:3777-3788(2011) [PubMed] [Europe PMC] [Abstract]
Jenkins R.W., Idkowiak-Baldys J., Simbari F., Canals D., Roddy P., Riner C.D., Clarke C.J., Hannun Y.A.
J. Biol. Chem. 286:3777-3788(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: CATALYTIC ACTIVITY, FUNCTION, SUBCELLULAR LOCATION, CHARACTERIZATION OF VARIANTS NPDB HIS-602; PRO-602 AND ARG-610 DEL.
Ref.49
"PAS-positive macrophages--not always infection."
Meersseman W., Verschueren P., Tousseyn T., De Vos R., Cassiman D.
Lancet 377:1890-1890(2011) [PubMed] [Europe PMC] [Abstract]
Meersseman W., Verschueren P., Tousseyn T., De Vos R., Cassiman D.
Lancet 377:1890-1890(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT NPDB PRO-163.
Ref.52
"Acid sphingomyelinase (Asm) deficiency patients in The Netherlands and Belgium: disease spectrum and natural course in attenuated patients."
Hollak C.E., de Sonnaville E.S., Cassiman D., Linthorst G.E., Groener J.E., Morava E., Wevers R.A., Mannens M., Aerts J.M., Meersseman W., Akkerman E., Niezen-Koning K.E., Mulder M.F., Visser G., Wijburg F.A., Lefeber D., Poorthuis B.J.
Mol. Genet. Metab. 107:526-533(2012) [PubMed] [Europe PMC] [Abstract]
Hollak C.E., de Sonnaville E.S., Cassiman D., Linthorst G.E., Groener J.E., Morava E., Wevers R.A., Mannens M., Aerts J.M., Meersseman W., Akkerman E., Niezen-Koning K.E., Mulder M.F., Visser G., Wijburg F.A., Lefeber D., Poorthuis B.J.
Mol. Genet. Metab. 107:526-533(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS NPDB HIS-91; PRO-105; PRO-163; CYS-230; SER-373; PRO-551 AND ARG-610 DEL, VARIANTS NPDA ARG-250; SER-465; LEU-477 AND HIS-539.
Ref.53
"Identification of seven novel SMPD1 mutations causing Niemann-Pick disease types A and B."
Irun P., Mallen M., Dominguez C., Rodriguez-Sureda V., Alvarez-Sala L.A., Arslan N., Bermejo N., Guerrero C., Perez de Soto I., Villalon L., Giraldo P., Pocovi M.
Clin. Genet. 84:356-361(2013) [PubMed] [Europe PMC] [Abstract]
Irun P., Mallen M., Dominguez C., Rodriguez-Sureda V., Alvarez-Sala L.A., Arslan N., Bermejo N., Guerrero C., Perez de Soto I., Villalon L., Giraldo P., Pocovi M.
Clin. Genet. 84:356-361(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS NPDA ARG-228 AND ARG-387, VARIANTS NPDB CYS-230; SER-247; HIS-378; TRP-476; SER-492; PHE-599 AND ARG-610 DEL.
Ref.54
"The acid sphingomyelinase sequence variant p.A487V is not associated with decreased levels of enzymatic activity."
Rhein C., Naumann J., Muehle C., Zill P., Adli M., Hegerl U., Hiemke C., Mergl R., Moeller H.J., Reichel M., Kornhuber J.
JIMD Rep. 8:1-6(2013) [PubMed] [Europe PMC] [Abstract]
Rhein C., Naumann J., Muehle C., Zill P., Adli M., Hegerl U., Hiemke C., Mergl R., Moeller H.J., Reichel M., Kornhuber J.
JIMD Rep. 8:1-6(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION OF VARIANT NPDB ALA-325, CHARACTERIZATION OF VARIANT VAL-487.
Ref.55
"Spectrum of SMPD1 mutations in Asian-Indian patients with acid sphingomyelinase (ASM)-deficient Niemann-Pick disease."
Ranganath P., Matta D., Bhavani G.S., Wangnekar S., Jain J.M., Verma I.C., Kabra M., Puri R.D., Danda S., Gupta N., Girisha K.M., Sankar V.H., Patil S.J., Ramadevi A.R., Bhat M., Gowrishankar K., Mandal K., Aggarwal S. , Tamhankar P.M., Tilak P., Phadke S.R., Dalal A.
Am. J. Med. Genet. A 170:2719-2730(2016) [PubMed] [Europe PMC] [Abstract]
Ranganath P., Matta D., Bhavani G.S., Wangnekar S., Jain J.M., Verma I.C., Kabra M., Puri R.D., Danda S., Gupta N., Girisha K.M., Sankar V.H., Patil S.J., Ramadevi A.R., Bhat M., Gowrishankar K., Mandal K., Aggarwal S. , Tamhankar P.M., Tilak P., Phadke S.R., Dalal A.
Am. J. Med. Genet. A 170:2719-2730(2016) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS ALA-36; PHE-510 AND GLY-605, VARIANTS NPDA ARG-216; CYS-230; SER-255; ARG-319; PRO-324; ARG-343; ARG-363; HIS-391; ARG-393; SER-426; ILE-494; HIS-498; ARG-535 AND HIS-602, VARIANTS NPDB PRO-105; PHE-282; ASP-320; CYS-369; SER-465; LEU-520 AND LYS-549.
Ref.56
"SMPD1 mutation update: database and comprehensive analysis of published and novel variants."
Zampieri S., Filocamo M., Pianta A., Lualdi S., Gort L., Coll M.J., Sinnott R., Geberhiwot T., Bembi B., Dardis A.
Hum. Mutat. 37:139-147(2016) [PubMed] [Europe PMC] [Abstract]
Zampieri S., Filocamo M., Pianta A., Lualdi S., Gort L., Coll M.J., Sinnott R., Geberhiwot T., Bembi B., Dardis A.
Hum. Mutat. 37:139-147(2016) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS NPDB ILE-258; GLN-476; ASP-577; ARG-598 AND CYS-610, VARIANT NPDA PHE-482 DEL, REVIEW ON VARIANTS.
Ref.57
"Alleged detrimental mutations in the SMPD1 gene in patients with Niemann-Pick disease."
Rhein C., Muehle C., Kornhuber J., Reichel M.
Int. J. Mol. Sci. 16:13649-13652(2015) [PubMed] [Europe PMC] [Abstract]
Rhein C., Muehle C., Kornhuber J., Reichel M.
Int. J. Mol. Sci. 16:13649-13652(2015) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION OF VARIANT NPDB ALA-325, CHARACTERIZATION OF VARIANTS ALA-36; VAL-487 AND ARG-508, CATALYTIC ACTIVITY.
Ref.58
"Structural and functional analysis of the ASM p.Ala359Asp mutant that causes acid sphingomyelinase deficiency."
Acuna M., Castro-Fernandez V., Latorre M., Castro J., Schuchman E.H., Guixe V., Gonzalez M., Zanlungo S.
Biochem. Biophys. Res. Commun. 479:496-501(2016) [PubMed] [Europe PMC] [Abstract]
Acuna M., Castro-Fernandez V., Latorre M., Castro J., Schuchman E.H., Guixe V., Gonzalez M., Zanlungo S.
Biochem. Biophys. Res. Commun. 479:496-501(2016) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, CHARACTERIZATION OF VARIANT NPDB ASP-359.
Ref.59
"Epidemiological, clinical and biochemical characterization of the p.(Ala359Asp) SMPD1 variant causing Niemann-Pick disease type B."
Acuna M., Martinez P., Moraga C., He X., Moraga M., Hunter B., Nuernberg P., Gutierrez R.A., Gonzalez M., Schuchman E.H., Santos J.L., Miquel J.F., Mabe P., Zanlungo S.
Eur. J. Hum. Genet. 24:208-213(2016) [PubMed] [Europe PMC] [Abstract]
Acuna M., Martinez P., Moraga C., He X., Moraga M., Hunter B., Nuernberg P., Gutierrez R.A., Gonzalez M., Schuchman E.H., Santos J.L., Miquel J.F., Mabe P., Zanlungo S.
Eur. J. Hum. Genet. 24:208-213(2016) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, VARIANT NPDB ASP-359, CHARACTERIZATION OF VARIANT NPDB ASP-359.
The disease is caused by variants affecting the gene represented in this entry.
Disease descriptionA 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.
Related information in OMIM| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Natural variantiVAR_060870 | 51 | D → V in NPDB; unknown pathological significance. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_075322 | 91 | C → H in NPDB; requires 2 nucleotide substitutions. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_060871 | 94 | C → W in NPDB. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_060872 | 105 | L → P in NPDA and NPDB; expresses protein level comparable to wild-type SMPD1 expressing cells; retains very low enzyme activity. 5 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_060873 | 132 | V → A in NPDB; expresses protein level comparable to wild-type SMPD1 expressing cells; retains 13% residual enzyme activity. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_060874 | 139 | L → P in NPDB. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_011387 | 159 | C → R in NPDB. 2 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_075323 | 163 | L → P in NPDB. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_060875 | 168 | G → R in NPDB; also in patients with an intermediate form. 2 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_060876 | 178 | I → N in NPDB. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_060878 | 198 | A → P in NPDB. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_060879 | 202 | R → C in NPDB. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_060880 | 227 | L → M in NPDB. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_060881 | 227 | L → P in NPDB; expresses protein level comparable to wild-type SMPD1 expressing cells; retains no enzyme activity. 2 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_060882 | 230 | R → C in NPDB and NPDA; some patients have a NPDA/NPDB intermediate phenotype. 5 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_060884 | 234 | G → D in NPDB. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_005058 | 244 | G → R in NPDB. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_060886 | 246 | W → C in NPDB; expresses protein level comparable to wild-type SMPD1 expressing cells; retains no enzyme activity. 2 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_060887 | 247 | G → S in NPDA and NPDB. 4 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_005059 | 248 | E → Q in NPDB; 30% residual activity. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_015287 | 250 | S → R in NPDA and NPDB; also found in patients with an intermediate form. 4 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_075326 | 258 | T → I in NPDB. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_077313 | 282 | P → F in NPDB; requires 2 nucleotide substitutions. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_060891 | 283 | A → T in NPDB; expresses protein level comparable to wild-type SMPD1 expressing cells; retains no enzyme activity. 2 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_060892 | 291 | R → H in NPDB; also in patients with an intermediate form; unknown pathological significance. 2 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_068437 | 314 | V → M in NPDB; results in 20% of wild-type activity. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_077315 | 320 | N → D in NPDB; unknown pathological significance. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_060896 | 325 | P → A in NPDB; results in 1-4% of wild type activity. 3 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_060897 | 332 | P → R in NPDB. 2 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_060899 | 359 | A → D in NPDB; sphingomyelinase activity is decreased to 4% of wild-type activity; no effect on protein abundance; no effect on protein localization to lysosome; no effect on protein localization to extracellular space. 3 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_015289 | 373 | P → S in NPDB. 2 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_060901 | 378 | R → H in NPDB; reduces enzyme activity; some patients have a NPDA/NPDB intermediate phenotype. 4 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_060902 | 378 | R → L in NPDB. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_060903 | 381 | S → P in NPDB. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_005061 | 384 | M → I in NPDA and NPDB. 2 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_005062 | 385 | N → S in NPDB. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_005064 | 393 | W → G in NPDB; low sphingomyelin degradation rates. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_060905 | 415 | A → V in NPDB. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_015290 | 423 | H → Y in NPDB; abolishes enzyme activity. 2 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_068438 | 427 | H → R in NPDB; results in loss of activity; the patient also carries mutation H-228 that has sufficient activity to account for the Niemann-Pick disease type B phenotype. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_060907 | 433 | C → R in NPDB. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_060908 | 434 | L → P in NPDB. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_060909 | 437 | W → C in NPDB. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_005065 | 438 | S → R in NPDB. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_068439 | 453 | A → D in NPDB. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_060911 | 454 | A → V in NPDB. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_060912 | 458 | G → D in NPDB. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_075328 | 476 | R → Q in NPDB; unknown pathological significance. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_060914 | 476 | R → W in NPDB; some patients have a NPDA/NPDB intermediate phenotype. 4 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_015292 | 477 | P → L in NPDA and NPDB. 4 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_060915 | 482 | F → L in NPDB. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_060918 | 488 | T → A in NPDB. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_060919 | 490 | Y → N in NPDB. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_075330 | 492 | G → S in NPDB. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_060920 | 496 | G → S in NPDB. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_060921 | 498 | R → C in NPDB. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_060924 | 516 | H → Q in NPDB. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_060925 | 517 | E → V in NPDB. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_077324 | 520 | I → L in NPDB. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_068440 | 522 | N → S in NPDB. 1 Publication Manual assertion based on experiment ini | 1 | |
| Natural variantiVAR_068441 | 525 | Q → H in NPDB; results in 64% of wild-type activity. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_060927 | 535 | W → R in NPDB and NPDA; also in patients with an intermediate form. 3 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_077325 | 549 | N → K in NPDB. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_060928 | 551 | L → P in NPDB. 2 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_060929 | 565 | D → Y in NPDB; expresses protein level comparable to wild-type SMPD1 expressing cells; retains 6.8% residual enzyme activity. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_075332 | 577 | H → D in NPDB; unknown pathological significance. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_060930 | 578 | K → N in NPDB. 1 Publication Manual assertion based on experiment ini
| 1 |