Sphingomyelin phosphodiesterase
Details
- Name
- Sphingomyelin phosphodiesterase
- Synonyms
- 3.1.4.12
- 3.1.4.3
- Acid sphingomyelinase
- ASM
- aSMase
- Gene Name
- SMPD1
- UniProtKB Entry
- P17405Swiss-Prot
- Organism
- Humans
- NCBI Taxonomy ID
- 9606
- Amino acid sequence
>lcl|BSEQ0055867|Sphingomyelin phosphodiesterase MPRYGASLRQSCPRSGREQGQDGTAGAPGLLWMGLVLALALALALALALSDSRVLWAPAE AHPLSPQGHPARLHRIVPRLRDVFGWGNLTCPICKGLFTAINLGLKKEPNVARVGSVAIK LCNLLKIAPPAVCQSIVHLFEDDMVEVWRRSVLSPSEACGLLLGSTCGHWDIFSSWNISL PTVPKPPPKPPSPPAPGAPVSRILFLTDLHWDHDYLEGTDPDCADPLCCRRGSGLPPASR PGAGYWGEYSKCDLPLRTLESLLSGLGPAGPFDMVYWTGDIPAHDVWHQTRQDQLRALTT VTALVRKFLGPVPVYPAVGNHESTPVNSFPPPFIEGNHSSRWLYEAMAKAWEPWLPAEAL RTLRIGGFYALSPYPGLRLISLNMNFCSRENFWLLINSTDPAGQLQWLVGELQAAEDRGD KVHIIGHIPPGHCLKSWSWNYYRIVARYENTLAAQFFGHTHVDEFEVFYDEETLSRPLAV AFLAPSATTYIGLNPGYRVYQIDGNYSGSSHVVLDHETYILNLTQANIPGAIPHWQLLYR ARETYGLPNTLPTAWHNLVYRMRGDMQLFQTFWFLYHKGHPPSEPCGTPCRLATLCAQLS ARADSPALCRHLMPDGSLPEAQSLWPRPLFC
- Number of residues
- 631
- Molecular Weight
- 69935.53
- Theoretical pI
- 7.42
- GO Classification
- Functionsacid sphingomyelin phosphodiesterase activity / phosphatidylcholine phospholipase C activity / zinc ion bindingProcessescellular response to calcium ion / cellular response to UV / cholesterol metabolic process / glycosphingolipid catabolic process / plasma membrane repair / positive regulation of endocytosis / positive regulation of viral entry into host cell / response to interleukin-1 / response to ionizing radiation / response to tumor necrosis factor / response to type I interferon / response to virus / response to xenobiotic stimulus / symbiont entry into host cell / wound healingComponentsendolysosome / lipid droplet
- General Function
- Converts sphingomyelin to ceramide (PubMed:12563314, PubMed:1840600, PubMed:18815062, PubMed:25339683, PubMed:25920558, PubMed:27659707, PubMed:33163980). Exists as two enzymatic forms that arise from alternative trafficking of a single protein precursor, one that is targeted to the endolysosomal compartment, whereas the other is released extracellularly (PubMed:20807762, PubMed:21098024, PubMed:9660788). However, in response to various forms of stress, lysosomal exocytosis may represent a major source of the secretory form (PubMed:12563314, PubMed:20530211, PubMed:20807762, PubMed:22573858, PubMed:9393854)
- Specific Function
- acid sphingomyelin phosphodiesterase activity
- Pfam Domain Function
- Signal Regions
- 1-46
- Transmembrane Regions
- Not Available
- Cellular Location
- Lysosome
- Gene sequence
>lcl|BSEQ0019045|Sphingomyelin phosphodiesterase (SMPD1) ATGCCCCGCTACGGAGCGTCACTCCGCCAGAGCTGCCCCAGGTCCGGCCGGGAGCAGGGA CAAGACGGGACCGCCGGAGCCCCCGGACTCCTTTGGATGGGCCTGGTGCTGGCGCTGGCG CTGGCGCTGGCGCTGGCGCTGGCTCTGTCTGACTCTCGGGTTCTCTGGGCTCCGGCAGAG GCTCACCCTCTTTCTCCCCAAGGCCATCCTGCCAGGTTACATCGCATAGTGCCCCGGCTC CGAGATGTCTTTGGGTGGGGGAACCTCACCTGCCCAATCTGCAAAGGTCTATTCACCGCC ATCAACCTCGGGCTGAAGAAGGAACCCAATGTGGCTCGCGTGGGCTCCGTGGCCATCAAG CTGTGCAATCTGCTGAAGATAGCACCACCTGCCGTGTGCCAATCCATTGTCCACCTCTTT GAGGATGACATGGTGGAGGTGTGGAGACGCTCAGTGCTGAGCCCATCTGAGGCCTGTGGC CTGCTCCTGGGCTCCACCTGTGGGCACTGGGACATTTTCTCATCTTGGAACATCTCTTTG CCTACTGTGCCGAAGCCGCCCCCCAAACCCCCTAGCCCCCCAGCCCCAGGTGCCCCTGTC AGCCGCATCCTCTTCCTCACTGACCTGCACTGGGATCATGACTACCTGGAGGGCACGGAC CCTGACTGTGCAGACCCACTGTGCTGCCGCCGGGGTTCTGGCCTGCCGCCCGCATCCCGG CCAGGTGCCGGATACTGGGGCGAATACAGCAAGTGTGACCTGCCCCTGAGGACCCTGGAG AGCCTGTTGAGTGGGCTGGGCCCAGCCGGCCCTTTTGATATGGTGTACTGGACAGGAGAC ATCCCCGCACATGATGTCTGGCACCAGACTCGTCAGGACCAACTGCGGGCCCTGACCACC GTCACAGCACTTGTGAGGAAGTTCCTGGGGCCAGTGCCAGTGTACCCTGCTGTGGGTAAC CATGAAAGCACACCTGTCAATAGCTTCCCTCCCCCCTTCATTGAGGGCAACCACTCCTCC CGCTGGCTCTATGAAGCGATGGCCAAGGCTTGGGAGCCCTGGCTGCCTGCCGAAGCCCTG CGCACCCTCAGAATTGGGGGGTTCTATGCTCTTTCCCCATACCCCGGTCTCCGCCTCATC TCTCTCAATATGAATTTTTGTTCCCGTGAGAACTTCTGGCTCTTGATCAACTCCACGGAT CCCGCAGGACAGCTCCAGTGGCTGGTGGGGGAGCTTCAGGCTGCTGAGGATCGAGGAGAC AAAGTGCATATAATTGGCCACATTCCCCCAGGGCACTGTCTGAAGAGCTGGAGCTGGAAT TATTACCGAATTGTAGCCAGGTATGAGAACACCCTGGCTGCTCAGTTCTTTGGCCACACT CATGTGGATGAATTTGAGGTCTTCTATGATGAAGAGACTCTGAGCCGGCCGCTGGCTGTA GCCTTCCTGGCACCCAGTGCAACTACCTACATCGGCCTTAATCCTGGTTACCGTGTGTAC CAAATAGATGGAAACTACTCCGGGAGCTCTCACGTGGTCCTGGACCATGAGACCTACATC CTGAATCTGACCCAGGCAAACATACCGGGAGCCATACCGCACTGGCAGCTTCTCTACAGG GCTCGAGAAACCTATGGGCTGCCCAACACACTGCCTACCGCCTGGCACAACCTGGTATAT CGCATGCGGGGCGACATGCAACTTTTCCAGACCTTCTGGTTTCTCTACCATAAGGGCCAC CCACCCTCGGAGCCCTGTGGCACGCCCTGCCGTCTGGCTACTCTTTGTGCCCAGCTCTCT GCCCGTGCTGACAGCCCTGCTCTGTGCCGCCACCTGATGCCAGATGGGAGCCTCCCAGAG GCCCAGAGCCTGTGGCCAAGGCCACTGTTTTGCTAG
- Chromosome Location
- 11
- Locus
- 11p15.4
- External Identifiers
Resource Link UniProtKB ID P17405 UniProtKB Entry Name ASM_HUMAN GenBank Protein ID 179095 GenBank Gene ID M59916 GeneCard ID SMPD1 GenAtlas ID SMPD1 HGNC ID HGNC:11120 PDB ID(s) 5I81, 5I85, 5I8R, 5JG8 KEGG ID hsa:6609 IUPHAR/Guide To Pharmacology ID 2514 NCBI Gene ID 6609 - General References
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- Schuchman EH, Levran O, Pereira LV, Desnick RJ: Structural organization and complete nucleotide sequence of the gene encoding human acid sphingomyelinase (SMPD1). Genomics. 1992 Feb;12(2):197-205. [Article]
- Ida H, Rennert OM, Eto Y, Chan WY: Cloning of a human acid sphingomyelinase cDNA with a new mutation that renders the enzyme inactive. J Biochem. 1993 Jul;114(1):15-20. [Article]
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- Quintern LE, Schuchman EH, Levran O, Suchi M, Ferlinz K, Reinke H, Sandhoff K, Desnick RJ: Isolation of cDNA clones encoding human acid sphingomyelinase: occurrence of alternatively processed transcripts. EMBO J. 1989 Sep;8(9):2469-73. [Article]
- Ferlinz K, Hurwitz R, Moczall H, Lansmann S, Schuchman EH, Sandhoff K: Functional characterization of the N-glycosylation sites of human acid sphingomyelinase by site-directed mutagenesis. Eur J Biochem. 1997 Jan 15;243(1-2):511-7. [Article]
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- Dastani Z, Ruel IL, Engert JC, Genest J Jr, Marcil M: Sphingomyelin phosphodiesterase-1 (SMPD1) coding variants do not contribute to low levels of high-density lipoprotein cholesterol. BMC Med Genet. 2007 Dec 18;8:79. [Article]
- Ferlinz K, Hurwitz R, Sandhoff K: Molecular basis of acid sphingomyelinase deficiency in a patient with Niemann-Pick disease type A. Biochem Biophys Res Commun. 1991 Sep 30;179(3):1187-91. [Article]
- Levran O, Desnick RJ, Schuchman EH: Niemann-Pick disease: a frequent missense mutation in the acid sphingomyelinase gene of Ashkenazi Jewish type A and B patients. Proc Natl Acad Sci U S A. 1991 May 1;88(9):3748-52. [Article]
- Levran O, Desnick RJ, Schuchman EH: 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. J Clin Invest. 1991 Sep;88(3):806-10. [Article]
- Levran O, Desnick RJ, Schuchman EH: Identification and expression of a common missense mutation (L302P) in the acid sphingomyelinase gene of Ashkenazi Jewish type A Niemann-Pick disease patients. Blood. 1992 Oct 15;80(8):2081-7. [Article]
- Takahashi T, Desnick RJ, Takada G, Schuchman EH: Identification of a missense mutation (S436R) in the acid sphingomyelinase gene from a Japanese patient with type B Niemann-Pick disease. Hum Mutat. 1992;1(1):70-1. [Article]
- Takahashi T, Suchi M, Desnick RJ, Takada G, Schuchman EH: 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. J Biol Chem. 1992 Jun 25;267(18):12552-8. [Article]
- Sperl W, Bart G, Vanier MT, Christomanou H, Baldissera I, Steichen-Gersdorf E, Paschke E: A family with visceral course of Niemann-Pick disease, macular halo syndrome and low sphingomyelin degradation rate. J Inherit Metab Dis. 1994;17(1):93-103. [Article]
- Schuchman EH: Two new mutations in the acid sphingomyelinase gene causing type a Niemann-pick disease: N389T and R441X. Hum Mutat. 1995;6(4):352-4. [Article]
- Takahashi T, Suchi M, Sato W, Ten SB, Sakuragawa N, Desnick RJ, Schuchman EH, Takada G: Identification and expression of a missense mutation (Y446C) in the acid sphingomyelinase gene from a Japanese patient with type A Niemann-Pick disease. Tohoku J Exp Med. 1995 Oct;177(2):117-23. [Article]
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- Lan MY, Lin SJ, Chen YF, Peng CH, Liu YF: A novel missense mutation of the SMPD1 gene in a Taiwanese patient with type B Niemann-Pick disease. Ann Hematol. 2009 Jul;88(7):695-7. doi: 10.1007/s00277-008-0648-8. Epub 2008 Dec 3. [Article]
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- Desnick JP, Kim J, He X, Wasserstein MP, Simonaro CM, Schuchman EH: Identification and characterization of eight novel SMPD1 mutations causing types A and B Niemann-Pick disease. Mol Med. 2010 Jul-Aug;16(7-8):316-21. doi: 10.2119/molmed.2010.00017. Epub 2010 Apr 6. [Article]
- Hua R, Wu H, Cui Z, Chen JX, Wang Z: A novel SMPD1 mutation in two Chinese sibling patients with type B Niemann-Pick disease. Chin Med J (Engl). 2012 Apr;125(8):1511-2. [Article]
Associated Data
- Bio-Entities
Bio-Entity Type Sphingomyelin phosphodiesterase (Humans) protein primary- Drug Relations
Drug Drug group Pharmacological action? Type Actions Details Desipramine approved, investigational unknown target inhibitor Details Chlorpromazine approved, investigational, vet_approved unknown target inhibitor Details Amlodipine approved unknown target inhibitor Details Medical Cannabis experimental, investigational unknown target inducer Details Brincidofovir approved, investigational no enzyme substrate Details