Sphingomyelin phosphodiesterase 1

SMPD1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 5JG8
Identifiers
Aliases	SMPD1, ASM, ASMASE, NPD, Sphingomyelin phosphodiesterase 1
External IDs	OMIM: 607608; MGI: 98325; HomoloGene: 457; GeneCards: SMPD1; OMA:SMPD1 - orthologs
Gene location (Human) Chr. Chromosome 11 (human)[1] Band 11p15.4 Start 6,390,440 bp[1] End 6,394,998 bp[1]
Gene location (Mouse) Chr. Chromosome 7 (mouse)[2] Band 7 E3|7 55.9 cM Start 105,203,567 bp[2] End 105,207,596 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in beta cell stromal cell of endometrium apex of heart right lobe of liver anterior pituitary tendon of biceps brachii right hemisphere of cerebellum right auricle of heart mucosa of transverse colon left ventricle Top expressed in choroid plexus of fourth ventricle gastrula interventricular septum CA3 field entorhinal cortex perirhinal cortex myocardium of ventricle cardiac muscle tissue of left ventricle Epithelium of choroid plexus decidua More reference expression data BioGPS More reference expression data
Gene ontology Molecular function sphingomyelin phosphodiesterase activity hydrolase activity, acting on glycosyl bonds protein binding hydrolase activity metal ion binding zinc ion binding acid sphingomyelin phosphodiesterase activity phosphoric diester hydrolase activity Cellular component endosome plasma membrane lamellar granule lysosomal lumen lysosome extracellular exosome extracellular region extracellular space Biological process termination of signal transduction glycosphingolipid metabolic process positive regulation of protein dephosphorylation ceramide biosynthetic process nervous system development sphingomyelin catabolic process negative regulation of MAP kinase activity positive regulation of apoptotic process metabolism signal transduction sphingomyelin metabolic process response to cocaine ceramide metabolic process cholesterol metabolic process Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 6609 20597 Ensembl ENSG00000166311 ENSMUSG00000037049 UniProt P17405 Q04519 RefSeq (mRNA) NM_000543 NM_001007593 NM_001318087 NM_001318088 NM_001365135 NM_011421 RefSeq (protein) NP_000534 NP_001007594 NP_001305016 NP_001305017 NP_001352064 NP_035551 Location (UCSC) Chr 11: 6.39 – 6.39 Mb Chr 7: 105.2 – 105.21 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Sphingomyelin phosphodiesterase 1 (SMPD1), also known as acid sphingomyelinase (ASM), is an enzyme that in humans is encoded by the SMPD1 gene.

Sphingomyelin phosphodiesterase 1 belongs to the sphingomyelin phosphodiesterase family.^[5]

Clinical significance

Defects in the SMPD1 gene cause Niemann–Pick disease, SMPD1-associated.^[5]

A mutation from leucine to proline at amino acid residue 302 encoded by the SMPD1 gene was identified by Gan-Or et al. (2013) as a risk factor for Parkinson disease.^[6]

References

1. GRCh38: Ensembl release 89: ENSG00000166311 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000037049 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. "Entrez Gene: SMPD1 sphingomyelin phosphodiesterase 1, acid lysosomal (acid sphingomyelinase)".
6. Gan-Or Z, Ozelius LJ, Bar-Shira A, Saunders-Pullman R, Mirelman A, Kornreich R, Gana-Weisz M, Raymond D, Rozenkrantz L, Deik A, Gurevich T, Gross SJ, Schreiber-Agus N, Giladi N, Bressman SB, Orr-Urtreger A (April 2013). "The p.L302P mutation in the lysosomal enzyme gene SMPD1 is a risk factor for Parkinson disease". Neurology. 80 (17): 1606–10. doi:10.1212/WNL.0b013e31828f180e. PMC 3662322. PMID 23535491.

Further reading

• Stoffel W (November 1999). "Functional analysis of acid and neutral sphingomyelinases in vitro and in vivo". Chemistry and Physics of Lipids. 102 (1–2): 107–21. doi:10.1016/S0009-3084(99)00079-1. PMID 11001565.
• Newrzella D, Stoffel W (December 1992). "Molecular cloning of the acid sphingomyelinase of the mouse and the organization and complete nucleotide sequence of the gene". Biological Chemistry Hoppe-Seyler. 373 (12): 1233–8. doi:10.1515/bchm3.1992.373.2.1233. PMID 1292508.
• Takahashi T, Desnick RJ, Takada G, Schuchman EH (1993). "Identification of a missense mutation (S436R) in the acid sphingomyelinase gene from a Japanese patient with type B Niemann-Pick disease". Human Mutation. 1 (1): 70–1. doi:10.1002/humu.1380010111. PMID 1301192. S2CID 31754300.
• Levran O, Desnick RJ, Schuchman EH (October 1992). "Identification and expression of a common missense mutation (L302P) in the acid sphingomyelinase gene of Ashkenazi Jewish type A Niemann-Pick disease patients". Blood. 80 (8): 2081–7. doi:10.1182/blood.V80.8.2081.2081. PMID 1391960.
• Takahashi T, Suchi M, Desnick RJ, Takada G, Schuchman EH (June 1992). "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". The Journal of Biological Chemistry. 267 (18): 12552–8. doi:10.1016/S0021-9258(18)42312-5. PMID 1618760.
• Schuchman EH, Levran O, Suchi M, Desnick RJ (June 1991). "An MspI polymorphism in the human acid sphingomyelinase gene (SMPD1)". Nucleic Acids Research. 19 (11): 3160. doi:10.1093/nar/19.11.3160. PMC 328296. PMID 1711683.
• Ferlinz K, Hurwitz R, Sandhoff K (September 1991). "Molecular basis of acid sphingomyelinase deficiency in a patient with Niemann-Pick disease type A". Biochemical and Biophysical Research Communications. 179 (3): 1187–91. doi:10.1016/0006-291X(91)91697-B. PMID 1718266.
• Schuchman EH, Levran O, Pereira LV, Desnick RJ (February 1992). "Structural organization and complete nucleotide sequence of the gene encoding human acid sphingomyelinase (SMPD1)". Genomics. 12 (2): 197–205. doi:10.1016/0888-7543(92)90366-Z. PMID 1740330.
• Schuchman EH, Suchi M, Takahashi T, Sandhoff K, Desnick RJ (May 1991). "Human acid sphingomyelinase. Isolation, nucleotide sequence and expression of the full-length and alternatively spliced cDNAs". The Journal of Biological Chemistry. 266 (13): 8531–9. doi:10.1016/S0021-9258(18)93007-3. PMID 1840600.
• Levran O, Desnick RJ, Schuchman EH (September 1991). "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". The Journal of Clinical Investigation. 88 (3): 806–10. doi:10.1172/JCI115380. PMC 295465. PMID 1885770.
• da Veiga Pereira L, Desnick RJ, Adler DA, Disteche CM, Schuchman EH (February 1991). "Regional assignment of the human acid sphingomyelinase gene (SMPD1) by PCR analysis of somatic cell hybrids and in situ hybridization to 11p15.1----p15.4". Genomics. 9 (2): 229–34. doi:10.1016/0888-7543(91)90246-B. PMID 2004772.
• Levran O, Desnick RJ, Schuchman EH (May 1991). "Niemann-Pick disease: a frequent missense mutation in the acid sphingomyelinase gene of Ashkenazi Jewish type A and B patients". Proceedings of the National Academy of Sciences of the United States of America. 88 (9): 3748–52. Bibcode:1991PNAS...88.3748L. doi:10.1073/pnas.88.9.3748. PMC 51530. PMID 2023926.
• Quintern LE, Schuchman EH, Levran O, Suchi M, Ferlinz K, Reinke H, Sandhoff K, Desnick RJ (September 1989). "Isolation of cDNA clones encoding human acid sphingomyelinase: occurrence of alternatively processed transcripts". The EMBO Journal. 8 (9): 2469–73. doi:10.1002/j.1460-2075.1989.tb08382.x. PMC 401234. PMID 2555181.
• Horinouchi K, Erlich S, Perl DP, Ferlinz K, Bisgaier CL, Sandhoff K, Desnick RJ, Stewart CL, Schuchman EH (July 1995). "Acid sphingomyelinase deficient mice: a model of types A and B Niemann-Pick disease". Nature Genetics. 10 (3): 288–93. doi:10.1038/ng0795-288. PMID 7670466. S2CID 37065681.
• Sperl W, Bart G, Vanier MT, Christomanou H, Baldissera I, Steichen-Gersdorf E, Paschke E (1994). "A family with visceral course of Niemann-Pick disease, macular halo syndrome and low sphingomyelin degradation rate". Journal of Inherited Metabolic Disease. 17 (1): 93–103. doi:10.1007/BF00735404. PMID 8051942. S2CID 12743175.
• Ida H, Rennert OM, Eto Y, Chan WY (July 1993). "Cloning of a human acid sphingomyelinase cDNA with a new mutation that renders the enzyme inactive". Journal of Biochemistry. 114 (1): 15–20. doi:10.1093/oxfordjournals.jbchem.a124131. PMID 8407868.
• Ida H, Rennert OM, Maekawa K, Eto Y (1996). "Identification of three novel mutations in the acid sphinogomyelinase gene of Japanese patients with Niemann-Pick disease type A and B". Human Mutation. 7 (1): 65–7. doi:10.1002/(SICI)1098-1004(1996)7:1<65::AID-HUMU10>3.0.CO;2-Q. PMID 8664904. S2CID 6033746.
• Schuchman EH (1996). "Two new mutations in the acid sphingomyelinase gene causing type a Niemann-pick disease: N389T and R441X". Human Mutation. 6 (4): 352–4. doi:10.1002/humu.1380060412. PMID 8680412. S2CID 44787586.
• Takahashi T, Suchi M, Sato W, Ten SB, Sakuragawa N, Desnick RJ, Schuchman EH, Takada G (October 1995). "Identification and expression of a missense mutation (Y446C) in the acid sphingomyelinase gene from a Japanese patient with type A Niemann-Pick disease". The Tohoku Journal of Experimental Medicine. 177 (2): 117–23. doi:10.1620/tjem.177.117. PMID 8693491.
• Ferlinz K, Hurwitz R, Moczall H, Lansmann S, Schuchman EH, Sandhoff K (January 1997). "Functional characterization of the N-glycosylation sites of human acid sphingomyelinase by site-directed mutagenesis". European Journal of Biochemistry. 243 (1–2): 511–7. doi:10.1111/j.1432-1033.1997.511_1a.x. PMID 9030779.

External links

• GeneReviews/NCBI/NIH/UW entry on Acid Sphingomyelinase Deficiency Includes: Niemann-Pick Disease Type A, Niemann-Pick Disease Type B
• OMIM entries on Acid Sphingomyelinase Deficiency
• Overview of all the structural information available in the PDB for UniProt: P17405 (Human Sphingomyelin phosphodiesterase) at the PDBe-KB.