Sphingomyelin phosphodiesterase

NameSphingomyelin phosphodiesterase
Synonyms
  • 3.1.4.12
  • Acid sphingomyelinase
  • ASM
  • aSMase
Gene NameSMPD1
OrganismHuman
Amino acid sequence
>lcl|BSEQ0037107|Sphingomyelin phosphodiesterase
MPRYGASLRQSCPRSGREQGQDGTAGAPGLLWMGLVLALALALALALSDSRVLWAPAEAH
PLSPQGHPARLHRIVPRLRDVFGWGNLTCPICKGLFTAINLGLKKEPNVARVGSVAIKLC
NLLKIAPPAVCQSIVHLFEDDMVEVWRRSVLSPSEACGLLLGSTCGHWDIFSSWNISLPT
VPKPPPKPPSPPAPGAPVSRILFLTDLHWDHDYLEGTDPDCADPLCCRRGSGLPPASRPG
AGYWGEYSKCDLPLRTLESLLSGLGPAGPFDMVYWTGDIPAHDVWHQTRQDQLRALTTVT
ALVRKFLGPVPVYPAVGNHESTPVNSFPPPFIEGNHSSRWLYEAMAKAWEPWLPAEALRT
LRIGGFYALSPYPGLRLISLNMNFCSRENFWLLINSTDPAGQLQWLVGELQAAEDRGDKV
HIIGHIPPGHCLKSWSWNYYRIVARYENTLAAQFFGHTHVDEFEVFYDEETLSRPLAVAF
LAPSATTYIGLNPGYRVYQIDGNYSGSSHVVLDHETYILNLTQANIPGAIPHWQLLYRAR
ETYGLPNTLPTAWHNLVYRMRGDMQLFQTFWFLYHKGHPPSEPCGTPCRLATLCAQLSAR
ADSPALCRHLMPDGSLPEAQSLWPRPLFC
Number of residues629
Molecular Weight69751.3
Theoretical pI7.42
GO Classification
Functions
  • sphingomyelin phosphodiesterase activity
  • hydrolase activity, acting on glycosyl bonds
Processes
  • glycosphingolipid metabolic process
  • response to drug
  • sphingomyelin catabolic process
  • termination of signal transduction
  • sphingomyelin metabolic process
  • small molecule metabolic process
  • positive regulation of apoptotic process
  • nervous system development
  • response to cocaine
  • positive regulation of protein dephosphorylation
  • sphingolipid metabolic process
  • negative regulation of MAP kinase activity
  • signal transduction
  • ceramide biosynthetic process
Components
  • plasma membrane
  • extracellular space
  • lamellar body
  • lysosome
  • extracellular exosome
  • endosome
  • lysosomal lumen
General FunctionSphingomyelin phosphodiesterase activity
Specific FunctionConverts sphingomyelin to ceramide. Also has phospholipase C activities toward 1,2-diacylglycerolphosphocholine and 1,2-diacylglycerolphosphoglycerol. Isoform 2 and isoform 3 have lost catalytic activity.
Pfam Domain Function
Transmembrane RegionsNot Available
GenBank Protein ID179095
UniProtKB IDP17405
UniProtKB Entry NameASM_HUMAN
Cellular LocationLysosome
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
GenBank Gene IDM59916
GeneCard IDNot Available
GenAtlas IDSMPD1
HGNC IDHGNC:11120
Chromosome Location11
Locus11p15.4-p15.1
References
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  2. Newrzella D, Stoffel W: Molecular cloning of the acid sphingomyelinase of the mouse and the organization and complete nucleotide sequence of the gene. Biol Chem Hoppe Seyler. 1992 Dec;373(12):1233-8. 1292508
  3. 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. 1740330
  4. 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. 8407868
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  7. 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. 2555181
  8. 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. 9030779
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  10. 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. 18088425
  11. 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. 1718266
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  14. 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. 1391960
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  16. 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. 1618760
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  25. Pittis MG, Ricci V, Guerci VI, Marcais C, Ciana G, Dardis A, Gerin F, Stroppiano M, Vanier MT, Filocamo M, Bembi B: Acid sphingomyelinase: identification of nine novel mutations among Italian Niemann Pick type B patients and characterization of in vivo functional in-frame start codon. Hum Mutat. 2004 Aug;24(2):186-7. 15241805
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  29. 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. 19050888
  30. Rodriguez-Pascau L, Gort L, Schuchman EH, Vilageliu L, Grinberg D, Chabas A: Identification and characterization of SMPD1 mutations causing Niemann-Pick types A and B in Spanish patients. Hum Mutat. 2009 Jul;30(7):1117-22. doi: 10.1002/humu.21018. 19405096
  31. 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. 20386867
  32. 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. 22613662