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Reviewed, UniProtKB/Swiss-Prot P17405 (ASM_HUMAN)

Last modified June 16, 2009. Version 113. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Alternative products · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents

Names and origin

Protein namesRecommended name:
    Sphingomyelin phosphodiesterase
    EC=3.1.4.12
Alternative name(s):
    Acid sphingomyelinase
      Short name=aSMase
Gene names
Name: SMPD1
Synonyms: ASM
OrganismHomo sapiens (Human)
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length629 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level.

General annotation (Comments)

Function

Converts sphingomyelin to ceramide. Also has phospholipase C activities toward 1,2-diacylglycerolphosphocholine and 1,2-diacylglycerolphosphoglycerol.

Catalytic activity

Sphingomyelin + H2O = N-acylsphingosine + choline phosphate.

Subunit structure

Monomer.

Subcellular location

Lysosome.

Involvement in disease

Defects in SMPD1 are the cause of Niemann-Pick disease type A (NPA) [MIM:257200]; also referred to as the classical infantile form. Niemann-Pick disease is a clinically and genetically heterogeneous recessive disorder. It is caused by the accumulation of sphingomyelin and other metabolically related lipids in the lysosomes, resulting in neurodegeneration starting from early life. Patients may show xanthomas, pigmentation, hepatosplenomegaly, lymphadenopathy and mental retardation. Niemann-Pick disease occurs more frequently among individuals of Ashkenazi Jewish ancestry than in the general population. NPA is characterized by very early onset in infancy and a rapidly progressive course leading to death by three years. Ref.9 Ref.10 Ref.12 Ref.14 Ref.16 Ref.17 Ref.18 Ref.20

Defects in SMPD1 are the cause of Niemann-Pick disease type B (NPB) [MIM:607616]; also referred to as the visceral form. NPB has little if any neurologic involvement and patients may survive into adulthood.

Miscellaneous

There are two types of sphingomyelinases: ASM (acid), and NSM (neutral).

Isoform 1 is the most abundant (90%), isoforms 2 (10%) and 3 (<1%) are only found at lower levels. Only isoform 1 is a catalytic active enzyme.

Sequence similarities

Belongs to the acid sphingomyelinase family.

Contains 1 saposin B-type domain.

Ontologies

Keywords
   Cellular componentLysosome
   Coding sequence diversityAlternative splicing
   DiseaseDisease mutation
   DomainSignal
   Molecular functionGlycosidase
Hydrolase
   PTMDisulfide bond
Glycoprotein
   Technical termDirect protein sequencing
Gene Ontology (GO)
   Biological processnervous system development

Traceable author statement. Source: ProtInc

signal transduction

Traceable author statement. Source: ProtInc

sphingomyelin catabolic process

Inferred from electronic annotation. Source: InterPro

   Cellular componentlysosome

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular functionhydrolase activity, acting on glycosyl bonds

Inferred from electronic annotation. Source: UniProtKB-KW

sphingomyelin phosphodiesterase activity Ref.9

Traceable author statement. Source: ProtInc

Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P17405-1)

Also known as: ASM-1;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: P17405-2)

Also known as: ASM-2;

The sequence of this isoform differs from the canonical sequence as follows:
     363-374: IGGFYALSPYPG → YLSSVETQEGKR
     375-418: Missing.
Isoform 3 (identifier: P17405-3)

Also known as: ASM-3;

The sequence of this isoform differs from the canonical sequence as follows:
     363-418: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 4646
Chain47 – 629583Sphingomyelin phosphodiesterase
PRO_0000002323

Regions

Domain85 – 16985Saposin B-type

Amino acid modifications

Glycosylation861N-linked (GlcNAc...) Ref.7
Glycosylation1751N-linked (GlcNAc...) Ref.7
Glycosylation3351N-linked (GlcNAc...) Ref.7
Glycosylation3951N-linked (GlcNAc...) Ref.7
Glycosylation5201N-linked (GlcNAc...) Ref.7
Disulfide bond89 ↔ 165 By similarity
Disulfide bond92 ↔ 157 By similarity
Disulfide bond120 ↔ 131 Ref.8
Disulfide bond221 ↔ 226 Ref.8
Disulfide bond227 ↔ 250 Ref.8
Disulfide bond385 ↔ 431 Ref.8
Disulfide bond584 ↔ 588 Ref.8
Disulfide bond594 ↔ 607 Ref.8

Natural variations

Alternative sequence363 – 41856Missing in isoform 3.
VSP_000333
Alternative sequence363 – 37412IGGFY…SPYPG → YLSSVETQEGKR in isoform 2.
VSP_000331
Alternative sequence375 – 41844Missing in isoform 2.
VSP_000332
Natural variant361V → A: dbSNP rs1050228. Ref.3
VAR_038191
Natural variant1571C → R Seems to be less active. Ref.4
VAR_011387
Natural variant2421G → R in NPB. Ref.14
VAR_005058
Natural variant2461E → Q in NPA; 30% residual activity. Ref.18
VAR_005059
Natural variant2481S → R in NPA. Ref.20
VAR_015287
Natural variant3021L → P in NPA; in 23% of NPA Ashkenazi Jewish patients. Ref.12
VAR_005060
Natural variant3161V → E: dbSNP rs12575136.
VAR_054642
Natural variant3191H → Y in NPA. Ref.20
VAR_015288
Natural variant3221T → I: dbSNP rs1050233. Ref.1 Ref.6
VAR_054643
Natural variant3711P → S in NPB. Ref.20
VAR_015289
Natural variant3821M → I in NPA. Ref.14
VAR_005061
Natural variant3831N → S in NPB. Ref.14
VAR_005062
Natural variant3891N → T in NPA. Ref.16
VAR_005063
Natural variant3911W → G in NPB; low sphingomyelin degradation rates. Ref.15
VAR_005064
Natural variant4211H → Y in NPB. Ref.19
VAR_015290
Natural variant4361S → R in NPB. Ref.13
VAR_005065
Natural variant4461Y → C in NPA. Ref.17
VAR_011388
Natural variant4631F → S in NPA. Ref.20
VAR_015291
Natural variant4751P → L in NPA. Ref.20
VAR_015292
Natural variant4961R → L in NPA; in 32% of NPA Ashkenazi Jewish patients. Ref.10
VAR_005066
Natural variant5061G → R: dbSNP rs1050239. Ref.1 Ref.6 Ref.2
VAR_054644
Natural variant5371Y → H in NPA. Ref.20
VAR_015293
Natural variant5771G → S in NPA. Ref.9
VAR_005067
Natural variant6081Missing in NPB; prevalent among NPB patients from the North African Maghreb region. Ref.20 Ref.11
VAR_005068

Experimental info

Sequence conflict35 – 362Missing in CAA42584. Ref.4

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (ASM-1) [UniParc].

Last modified March 3, 2009. Version 4.
Checksum: C9888CB8359C42AC

FASTA62969,752
        10         20         30         40         50         60 
MPRYGASLRQ SCPRSGREQG QDGTAGAPGL LWMGLVLALA LALALALSDS RVLWAPAEAH 

        70         80         90        100        110        120 
PLSPQGHPAR LHRIVPRLRD VFGWGNLTCP ICKGLFTAIN LGLKKEPNVA RVGSVAIKLC 

       130        140        150        160        170        180 
NLLKIAPPAV CQSIVHLFED DMVEVWRRSV LSPSEACGLL LGSTCGHWDI FSSWNISLPT 

       190        200        210        220        230        240 
VPKPPPKPPS PPAPGAPVSR ILFLTDLHWD HDYLEGTDPD CADPLCCRRG SGLPPASRPG 

       250        260        270        280        290        300 
AGYWGEYSKC DLPLRTLESL LSGLGPAGPF DMVYWTGDIP AHDVWHQTRQ DQLRALTTVT 

       310        320        330        340        350        360 
ALVRKFLGPV PVYPAVGNHE STPVNSFPPP FIEGNHSSRW LYEAMAKAWE PWLPAEALRT 

       370        380        390        400        410        420 
LRIGGFYALS PYPGLRLISL NMNFCSRENF WLLINSTDPA GQLQWLVGEL QAAEDRGDKV 

       430        440        450        460        470        480 
HIIGHIPPGH CLKSWSWNYY RIVARYENTL AAQFFGHTHV DEFEVFYDEE TLSRPLAVAF 

       490        500        510        520        530        540 
LAPSATTYIG LNPGYRVYQI DGNYSGSSHV VLDHETYILN LTQANIPGAI PHWQLLYRAR 

       550        560        570        580        590        600 
ETYGLPNTLP TAWHNLVYRM RGDMQLFQTF WFLYHKGHPP SEPCGTPCRL ATLCAQLSAR 

       610        620 
ADSPALCRHL MPDGSLPEAQ SLWPRPLFC 

« Hide

Isoform 2 (ASM-2).

Checksum: A5FC9FE28C0D3E42
Show »

FASTA58564,889
Isoform 3 (ASM-3).

Checksum: 093B405E0C0AE061
Show »

FASTA57363,511

References

« Hide 'large scale' references
[1]"Human acid sphingomyelinase. Isolation, nucleotide sequence and expression of the full-length and alternatively spliced cDNAs."
Schuchman E.H., Suchi M., Takahashi T., Sandhoff K., Desnick R.J.
J. Biol. Chem. 266:8531-8539(1991) [PubMed: 1840600] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], ALTERNATIVE SPLICING, VARIANTS ILE-322 AND ARG-506.
[2]"Molecular cloning of the acid sphingomyelinase of the mouse and the organization and complete nucleotide sequence of the gene."
Newrzella D., Stoffel W.
Biol. Chem. Hoppe-Seyler 373:1233-1238(1992) [PubMed: 1292508] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT ARG-506.
[3]"Structural organization and complete nucleotide sequence of the gene encoding human acid sphingomyelinase (SMPD1)."
Schuchman E.H., Levran O., Pereira L.V., Desnick R.J.
Genomics 12:197-205(1992) [PubMed: 1740330] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT ALA-36.
[4]"Cloning of a human acid sphingomyelinase cDNA with a new mutation that renders the enzyme inactive."
Ida H., Rennert O.M., Eto Y., Chan W.Y.
J. Biochem. 114:15-20(1993) [PubMed: 8407868] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT ARG-157.
[5]"Human chromosome 11 DNA sequence and analysis including novel gene identification."
Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K., Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T., Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G. expand/collapse author list , Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C., Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A., Hattori M., Rogers J., Lander E.S., Sakaki Y.
Nature 440:497-500(2006) [PubMed: 16554811] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]"Isolation of cDNA clones encoding human acid sphingomyelinase: occurrence of alternatively processed transcripts."
Quintern L.E., Schuchman E.H., Levran O., Suchi M., Ferlinz K., Reinke H., Sandhoff K., Desnick R.J.
EMBO J. 8:2469-2473(1989) [PubMed: 2555181] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 128-629, PARTIAL PROTEIN SEQUENCE, ALTERNATIVE SPLICING, VARIANTS ILE-322 AND ARG-506.
Tissue: Fibroblast.
[7]"Functional characterization of the N-glycosylation sites of human acid sphingomyelinase by site-directed mutagenesis."
Ferlinz K., Hurwitz R., Moczall H., Lansmann S., Schuchman E.H., Sandhoff K.
Eur. J. Biochem. 243:511-517(1997) [PubMed: 9030779] [Abstract]
Cited for: GLYCOSYLATION AT ASN-86; ASN-175; ASN-335; ASN-395 AND ASN-520.
[8]"Human acid sphingomyelinase."
Lansmann S., Schuette C.G., Bartelsen O., Hoernschemeyer J., Linke T., Weisgerber J., Sandhoff K.
Eur. J. Biochem. 270:1076-1088(2003) [PubMed: 12631268] [Abstract]
Cited for: DISULFIDE BONDS.
[9]"Molecular basis of acid sphingomyelinase deficiency in a patient with Niemann-Pick disease type A."
Ferlinz K., Hurwitz R., Sandhoff K.
Biochem. Biophys. Res. Commun. 179:1187-1191(1991) [PubMed: 1718266] [Abstract]
Cited for: VARIANT NPA SER-577.
[10]"Niemann-Pick disease: a frequent missense mutation in the acid sphingomyelinase gene of Ashkenazi Jewish type A and B patients."
Levran O., Desnick R.J., Schuchman E.H.
Proc. Natl. Acad. Sci. U.S.A. 88:3748-3752(1991) [PubMed: 2023926] [Abstract]
Cited for: VARIANT NPA LEU-496.
[11]"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."
Levran O., Desnick R.J., Schuchman E.H.
J. Clin. Invest. 88:806-810(1991) [PubMed: 1885770] [Abstract]
Cited for: VARIANT NPB ARG-608 DEL.
[12]"Identification and expression of a common missense mutation (L302P) in the acid sphingomyelinase gene of Ashkenazi Jewish type A Niemann-Pick disease patients."
Levran O., Desnick R.J., Schuchman E.H.
Blood 80:2081-2087(1992) [PubMed: 1391960] [Abstract]
Cited for: VARIANT NPA PRO-302.
[13]"Identification of a missense mutation (S436R) in the acid sphingomyelinase gene from a Japanese patient with type B Niemann-Pick disease."
Takahashi T., Desnick R.J., Takada G., Schuchman E.H.
Hum. Mutat. 1:70-71(1992) [PubMed: 1301192] [Abstract]
Cited for: VARIANT NPB ARG-436.
[14]"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."
Takahashi T., Suchi M., Desnick R.J., Takada G., Schuchman E.H.
J. Biol. Chem. 267:12552-12558(1992) [PubMed: 1618760] [Abstract]
Cited for: VARIANT NPA ILE-382, VARIANTS NPB ARG-242 AND SER-383.
[15]"A family with visceral course of Niemann-Pick disease, macular halo syndrome and low sphingomyelin degradation rate."
Sperl W., Bart G., Vanier M.T., Christomanou H., Baldissera I., Steichensdorf E., Paschke E.
J. Inherit. Metab. Dis. 17:93-103(1994) [PubMed: 8051942] [Abstract]
Cited for: VARIANT NPB GLY-391.
[16]"Two new mutations in the acid sphingomyelinase gene causing type A Niemann-pick disease: N389T and R441X."
Schuchman E.H.
Hum. Mutat. 6:352-354(1995) [PubMed: 8680412] [Abstract]
Cited for: VARIANT NPA THR-389.
[17]"Identification and expression of a missense mutation (Y446C) in the acid sphingomyelinase gene from a Japanese patient with type A Niemann-Pick disease."
Takahashi T., Suchi M., Sato W., Ten S.B., Sakuragawa N., Desnick R.J., Schuchman E.H., Takada G.
Tohoku J. Exp. Med. 177:117-123(1995) [PubMed: 8693491] [Abstract]
Cited for: VARIANT NPA CYS-446.
[18]"Identification of three novel mutations in the acid sphingomyelinase gene of Japanese patients with Niemann-Pick disease type A and B."
Ida H., Rennert O.M., Maekawa K., Eto Y.
Hum. Mutat. 7:65-67(1996) [PubMed: 8664904] [Abstract]
Cited for: VARIANT NPA GLN-246.
[19]"The demographics and distribution of type B Niemann-Pick disease: novel mutations lead to new genotype/phenotype correlations."
Simonaro C.M., Desnick R.J., McGovern M.M., Wasserstein M.P., Schuchman E.H.
Am. J. Hum. Genet. 71:1413-1419(2002) [PubMed: 12369017] [Abstract]
Cited for: VARIANT NPB TYR-421.
[20]"Seven novel Acid sphingomyelinase gene mutations in Niemann-Pick type A and B patients."
Sikora J., Pavlu-Pereira H., Elleder M., Roelofs H., Wevers R.A.
Ann. Hum. Genet. 67:63-70(2003) [PubMed: 12556236] [Abstract]
Cited for: VARIANTS NPA ARG-248; TYR-319; SER-463; LEU-475 AND HIS-537, VARIANTS NPB SER-371 AND ARG-608 DEL.
+Additional computationally mapped references.

Web resources

Cross-references

Sequence databases

M59916 mRNA. Translation: AAA58377.1.
M59917 Genomic DNA. Translation: AAA58378.1.
X63600 Genomic DNA. Translation: CAA45145.1.
M81780 Genomic DNA. Translation: AAA75008.1.
M81780 Genomic DNA. Translation: AAA75009.1.
X59960 mRNA. Translation: CAA42584.1.
AC068733 Genomic DNA. No translation available.
X52678 mRNA. Translation: CAA36901.1.
X52679 mRNA. Translation: CAA36902.1.
IPIIPI00218784.
IPI00218785.
IPI00296461.
PIRS06958.
A39825. S27009.
RefSeqNP_000534.3.
UniGeneHs.498173

3D structure databases

ModBaseSearch...

PTM databases

PhosphoSiteP17405.

Proteomic databases

PRIDEP17405.

Genome annotation databases

EnsemblENSG00000166311. Homo sapiens. [Contig view]
GeneID6609.
KEGGhsa:6609.

Organism-specific databases

GeneCardsGC11P006368.
HGNCHGNC:11120. SMPD1.
HPAHPA001823.
MIM257200. phenotype.
607608. gene.
607616. phenotype.
Orphanet645. Niemann-Pick disease.
77292. Niemann-Pick disease, type A.
77293. Niemann-Pick disease, type B.
PharmGKBPA35969.
GenAtlasSearch...

Phylogenomic databases

HOVERGENP17405.

Enzyme and pathway databases

BRENDA3.1.4.12. 247.
Pathway_Interaction_DBceramidepathway. Ceramide signaling pathway.
il2_pi3kpathway. IL2 signaling events mediated by PI3K.
tnfpathway. TNF receptor signaling pathway.
trail_pathway. TRAIL signaling pathway.

Gene expression databases

ArrayExpressP17405.
BgeeP17405.
CleanExHS_SMPD1.
GermOnlineENSG00000166311. Homo sapiens.

Family and domain databases

InterProIPR004843. M-pesterase.
IPR008139. SaposinB.
IPR011160. Sphingomy_PDE.
[Graphical view]
PfamPF00149. Metallophos. 1 hit.
[Graphical view]
PIRSFPIRSF000948. Sphingomy_PDE. 1 hit.
SMARTSM00741. SapB. 1 hit.
[Graphical view]
PROSITEPS50015. SAP_B. 1 hit.
[Graphical view]
ProtoNetSearch...

Other Resources

DrugBankDB01151. Desipramine.
NextBio25729.
SOURCESearch...

Entry information

Entry nameASM_HUMAN
AccessionPrimary (citable) accession number: P17405
Secondary accession number(s): P17406 expand/collapse secondary AC list , Q13811, Q16837, Q16841
Entry history
Integrated into UniProtKB/Swiss-Prot: August 1, 1990
Last sequence update: March 3, 2009
Last modified: June 16, 2009
This is version 113 of the entry and version 4 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)

Relevant documents

Human chromosome 11

Human chromosome 11: entries, gene names and cross-references to MIM

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Alternative products · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents