Sphingomyelin phosphodiesterase

Details

Name
Sphingomyelin phosphodiesterase
Synonyms
  • 3.1.4.12
  • Acid sphingomyelinase
  • ASM
  • aSMase
Gene Name
SMPD1
Organism
Humans
Amino acid sequence
>lcl|BSEQ0037107|Sphingomyelin phosphodiesterase
MPRYGASLRQSCPRSGREQGQDGTAGAPGLLWMGLVLALALALALALSDSRVLWAPAEAH
PLSPQGHPARLHRIVPRLRDVFGWGNLTCPICKGLFTAINLGLKKEPNVARVGSVAIKLC
NLLKIAPPAVCQSIVHLFEDDMVEVWRRSVLSPSEACGLLLGSTCGHWDIFSSWNISLPT
VPKPPPKPPSPPAPGAPVSRILFLTDLHWDHDYLEGTDPDCADPLCCRRGSGLPPASRPG
AGYWGEYSKCDLPLRTLESLLSGLGPAGPFDMVYWTGDIPAHDVWHQTRQDQLRALTTVT
ALVRKFLGPVPVYPAVGNHESTPVNSFPPPFIEGNHSSRWLYEAMAKAWEPWLPAEALRT
LRIGGFYALSPYPGLRLISLNMNFCSRENFWLLINSTDPAGQLQWLVGELQAAEDRGDKV
HIIGHIPPGHCLKSWSWNYYRIVARYENTLAAQFFGHTHVDEFEVFYDEETLSRPLAVAF
LAPSATTYIGLNPGYRVYQIDGNYSGSSHVVLDHETYILNLTQANIPGAIPHWQLLYRAR
ETYGLPNTLPTAWHNLVYRMRGDMQLFQTFWFLYHKGHPPSEPCGTPCRLATLCAQLSAR
ADSPALCRHLMPDGSLPEAQSLWPRPLFC
Number of residues
629
Molecular Weight
69751.3
Theoretical pI
7.42
GO Classification
Functions
hydrolase activity, acting on glycosyl bonds / sphingomyelin phosphodiesterase activity
Processes
ceramide biosynthetic process / glycosphingolipid metabolic process / negative regulation of MAP kinase activity / nervous system development / positive regulation of apoptotic process / positive regulation of protein dephosphorylation / response to cocaine / response to drug / signal transduction / small molecule metabolic process / sphingolipid metabolic process / sphingomyelin catabolic process / sphingomyelin metabolic process / termination of signal transduction
Components
endosome / extracellular exosome / extracellular space / lamellar body / lysosomal lumen / lysosome / plasma membrane
General Function
Sphingomyelin phosphodiesterase activity
Specific Function
Converts 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 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-p15.1
External Identifiers
ResourceLink
UniProtKB IDP17405
UniProtKB Entry NameASM_HUMAN
GenBank Protein ID179095
GenBank Gene IDM59916
GenAtlas IDSMPD1
HGNC IDHGNC:11120
General 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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed:22613662]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB01151Desipramineapproved, investigationalunknowninhibitorDetails
DB00477Chlorpromazineapproved, investigational, vet_approvedunknowninhibitorDetails
DB00381AmlodipineapprovedunknowninhibitorDetails
DB09061Cannabidiolapproved, investigationalunknownDetails
DB14011NabiximolsinvestigationalunknownDetails
DB14009Medical Cannabisexperimental, investigationalunknownDetails