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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
  • hydrolase activity, acting on glycosyl bonds
  • sphingomyelin phosphodiesterase activity
Processes
  • negative regulation of MAP kinase activity
  • signal transduction
  • ceramide biosynthetic process
  • 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
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
  1. Schuchman EH, Suchi M, Takahashi T, Sandhoff K, Desnick RJ: Human acid sphingomyelinase. Isolation, nucleotide sequence and expression of the full-length and alternatively spliced cDNAs. J Biol Chem. 1991 May 5;266(13):8531-9. 1840600
  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
  5. Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. 14702039
  6. Taylor TD, Noguchi H, Totoki Y, Toyoda A, Kuroki Y, Dewar K, Lloyd C, Itoh T, Takeda T, Kim DW, She X, Barlow KF, Bloom T, Bruford E, Chang JL, Cuomo CA, Eichler E, FitzGerald MG, Jaffe DB, LaButti K, Nicol R, Park HS, Seaman C, Sougnez C, Yang X, Zimmer AR, Zody MC, Birren BW, Nusbaum C, Fujiyama A, Hattori M, Rogers J, Lander ES, Sakaki Y: Human chromosome 11 DNA sequence and analysis including novel gene identification. Nature. 2006 Mar 23;440(7083):497-500. 16554811
  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
  9. Lansmann S, Schuette CG, Bartelsen O, Hoernschemeyer J, Linke T, Weisgerber J, Sandhoff K: Human acid sphingomyelinase. Eur J Biochem. 2003 Mar;270(6):1076-88. 12631268
  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
  12. 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. 2023926
  13. 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. 1885770
  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
  15. 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. 1301192
  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
  17. 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. 8051942
  18. 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. 8680412
  19. 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. 8693491
  20. Ida H, Rennert OM, Maekawa K, Eto Y: Identification of three novel mutations in the acid sphinogomyelinase gene of Japanese patients with Niemann-Pick disease type A and B. Hum Mutat. 1996;7(1):65-7. 8664904
  21. Pavlu H, Elleder M: Two novel mutations in patients with atypical phenotypes of acid sphingomyelinase deficiency. J Inherit Metab Dis. 1997 Aug;20(4):615-6. 9266408
  22. Simonaro CM, Desnick RJ, McGovern MM, Wasserstein MP, Schuchman EH: The demographics and distribution of type B Niemann-Pick disease: novel mutations lead to new genotype/phenotype correlations. Am J Hum Genet. 2002 Dec;71(6):1413-9. Epub 2002 Oct 4. 12369017
  23. Sikora J, Pavlu-Pereira H, Elleder M, Roelofs H, Wevers RA: Seven novel acid sphingomyelinase gene mutations in Niemann-Pick type A and B patients. Ann Hum Genet. 2003 Jan;67(Pt 1):63-70. 12556236
  24. Ricci V, Stroppiano M, Corsolini F, Di Rocco M, Parenti G, Regis S, Grossi S, Biancheri R, Mazzotti R, Filocamo M: Screening of 25 Italian patients with Niemann-Pick A reveals fourteen new mutations, one common and thirteen private, in SMPD1. Hum Mutat. 2004 Jul;24(1):105. 15221801
  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
  26. Dardis A, Zampieri S, Filocamo M, Burlina A, Bembi B, Pittis MG: Functional in vitro characterization of 14 SMPD1 mutations identified in Italian patients affected by Niemann Pick Type B disease. Hum Mutat. 2005 Aug;26(2):164. 16010684
  27. Pavlu-Pereira H, Asfaw B, Poupctova H, Ledvinova J, Sikora J, Vanier MT, Sandhoff K, Zeman J, Novotna Z, Chudoba D, Elleder M: Acid sphingomyelinase deficiency. Phenotype variability with prevalence of intermediate phenotype in a series of twenty-five Czech and Slovak patients. A multi-approach study. J Inherit Metab Dis. 2005;28(2):203-27. 15877209
  28. Mussig K, Harzer K, Mayrhofer H, Krageloh-Mann I, Haring HU, Machicao F: Clinical findings in Niemann-Pick disease type B. Intern Med J. 2006 Feb;36(2):135-6. 16472269
  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