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Protein

Sphingomyelin phosphodiesterase 2

Gene

SMPD2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Converts sphingomyelin to ceramide. Hydrolyze 1-acyl-2-lyso-sn-glycero-3-phosphocholine (lyso-PC) and 1-O-alkyl-2-lyso-sn-glycero-3-phosphocholine (lyso-platelet-activating factor). The physiological substrate seems to be Lyso-PAF.

Catalytic activityi

Sphingomyelin + H2O = N-acylsphingosine + phosphocholine.

Cofactori

pH dependencei

Optimum pH is 6.5-7.5.

Pathwayi

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi49 – 491MagnesiumBy similarity
Sitei180 – 1801Important for substrate recognitionBy similarity
Active sitei272 – 2721Proton acceptorBy similarity

GO - Molecular functioni

  1. metal ion binding Source: UniProtKB-KW
  2. sphingomyelin phosphodiesterase activity Source: ProtInc

GO - Biological processi

  1. apoptotic signaling pathway Source: Reactome
  2. ceramide biosynthetic process Source: Ensembl
  3. glycosphingolipid metabolic process Source: Reactome
  4. intracellular signal transduction Source: Ensembl
  5. neurotrophin TRK receptor signaling pathway Source: Reactome
  6. response to mechanical stimulus Source: Ensembl
  7. small molecule metabolic process Source: Reactome
  8. sphingolipid metabolic process Source: Reactome
  9. sphingomyelin metabolic process Source: ProtInc
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase

Keywords - Biological processi

Lipid metabolism, Sphingolipid metabolism

Keywords - Ligandi

Magnesium, Metal-binding

Enzyme and pathway databases

BRENDAi3.1.4.12. 2681.
ReactomeiREACT_116105. Glycosphingolipid metabolism.
REACT_13806. Ceramide signalling.
UniPathwayiUPA00222.

Names & Taxonomyi

Protein namesi
Recommended name:
Sphingomyelin phosphodiesterase 2 (EC:3.1.4.12)
Alternative name(s):
Lyso-platelet-activating factor-phospholipase C
Short name:
Lyso-PAF-PLC
Neutral sphingomyelinase
Short name:
N-SMase
Short name:
nSMase
Gene namesi
Name:SMPD2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 6

Organism-specific databases

HGNCiHGNC:11121. SMPD2.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Transmembranei330 – 35021HelicalSequence AnalysisAdd
BLAST
Transmembranei354 – 37421HelicalSequence AnalysisAdd
BLAST

GO - Cellular componenti

  1. caveola Source: Ensembl
  2. integral component of plasma membrane Source: ProtInc
  3. plasma membrane Source: Reactome
Complete GO annotation...

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA35970.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 423423Sphingomyelin phosphodiesterase 2PRO_0000075686Add
BLAST

Proteomic databases

MaxQBiO60906.
PaxDbiO60906.
PRIDEiO60906.

PTM databases

PhosphoSiteiO60906.

Expressioni

Gene expression databases

BgeeiO60906.
CleanExiHS_SMPD2.
GenevestigatoriO60906.

Organism-specific databases

HPAiHPA018110.
HPA018125.

Interactioni

Protein-protein interaction databases

BioGridi112494. 8 interactions.
STRINGi9606.ENSP00000258052.

Structurei

3D structure databases

ProteinModelPortaliO60906.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the neutral sphingomyelinase family.Curated

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG269293.
GeneTreeiENSGT00390000009166.
HOGENOMiHOG000044683.
HOVERGENiHBG019089.
InParanoidiO60906.
KOiK12351.
OMAiQARWWAT.
OrthoDBiEOG7SXW3M.
PhylomeDBiO60906.
TreeFamiTF313899.

Family and domain databases

Gene3Di3.60.10.10. 1 hit.
InterProiIPR005135. Endo/exonuclease/phosphatase.
[Graphical view]
PfamiPF03372. Exo_endo_phos. 1 hit.
[Graphical view]
SUPFAMiSSF56219. SSF56219. 1 hit.

Sequencei

Sequence statusi: Complete.

O60906-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MKPNFSLRLR IFNLNCWGIP YLSKHRADRM RRLGDFLNQE SFDLALLEEV
60 70 80 90 100
WSEQDFQYLR QKLSPTYPAA HHFRSGIIGS GLCVFSKHPI QELTQHIYTL
110 120 130 140 150
NGYPYMIHHG DWFSGKAVGL LVLHLSGMVL NAYVTHLHAE YNRQKDIYLA
160 170 180 190 200
HRVAQAWELA QFIHHTSKKA DVVLLCGDLN MHPEDLGCCL LKEWTGLHDA
210 220 230 240 250
YLETRDFKGS EEGNTMVPKN CYVSQQELKP FPFGVRIDYV LYKAVSGFYI
260 270 280 290 300
SCKSFETTTG FDPHRGTPLS DHEALMATLF VRHSPPQQNP SSTHGPAERS
310 320 330 340 350
PLMCVLKEAW TELGLGMAQA RWWATFASYV IGLGLLLLAL LCVLAAGGGA
360 370 380 390 400
GEAAILLWTP SVGLVLWAGA FYLFHVQEVN GLYRAQAELQ HVLGRAREAQ
410 420
DLGPEPQPAL LLGQQEGDRT KEQ
Length:423
Mass (Da):47,646
Last modified:November 13, 2007 - v2
Checksum:i3C1514CE21560501
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti3 – 31P → L.1 Publication
Corresponds to variant rs1048197 [ dbSNP | Ensembl ].
VAR_050305
Natural varianti223 – 2231V → I.
Corresponds to variant rs9386806 [ dbSNP | Ensembl ].
VAR_050306
Natural varianti265 – 2651R → S.2 Publications
Corresponds to variant rs1476387 [ dbSNP | Ensembl ].
VAR_024181

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ222801 mRNA. Translation: CAA10995.1.
AL109947 Genomic DNA. Translation: CAI23338.1.
BC000038 mRNA. Translation: AAH00038.1.
CCDSiCCDS5075.1.
RefSeqiNP_003071.2. NM_003080.2.
UniGeneiHs.55235.

Genome annotation databases

EnsembliENST00000258052; ENSP00000258052; ENSG00000135587.
GeneIDi6610.
KEGGihsa:6610.
UCSCiuc003pti.3. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ222801 mRNA. Translation: CAA10995.1.
AL109947 Genomic DNA. Translation: CAI23338.1.
BC000038 mRNA. Translation: AAH00038.1.
CCDSiCCDS5075.1.
RefSeqiNP_003071.2. NM_003080.2.
UniGeneiHs.55235.

3D structure databases

ProteinModelPortaliO60906.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi112494. 8 interactions.
STRINGi9606.ENSP00000258052.

Chemistry

BindingDBiO60906.
ChEMBLiCHEMBL4712.

PTM databases

PhosphoSiteiO60906.

Proteomic databases

MaxQBiO60906.
PaxDbiO60906.
PRIDEiO60906.

Protocols and materials databases

DNASUi6610.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000258052; ENSP00000258052; ENSG00000135587.
GeneIDi6610.
KEGGihsa:6610.
UCSCiuc003pti.3. human.

Organism-specific databases

CTDi6610.
GeneCardsiGC06P109761.
H-InvDBHIX0006125.
HGNCiHGNC:11121. SMPD2.
HPAiHPA018110.
HPA018125.
MIMi603498. gene.
neXtProtiNX_O60906.
PharmGKBiPA35970.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG269293.
GeneTreeiENSGT00390000009166.
HOGENOMiHOG000044683.
HOVERGENiHBG019089.
InParanoidiO60906.
KOiK12351.
OMAiQARWWAT.
OrthoDBiEOG7SXW3M.
PhylomeDBiO60906.
TreeFamiTF313899.

Enzyme and pathway databases

UniPathwayiUPA00222.
BRENDAi3.1.4.12. 2681.
ReactomeiREACT_116105. Glycosphingolipid metabolism.
REACT_13806. Ceramide signalling.

Miscellaneous databases

GeneWikiiSMPD2.
GenomeRNAii6610.
NextBioi25735.
PROiO60906.
SOURCEiSearch...

Gene expression databases

BgeeiO60906.
CleanExiHS_SMPD2.
GenevestigatoriO60906.

Family and domain databases

Gene3Di3.60.10.10. 1 hit.
InterProiIPR005135. Endo/exonuclease/phosphatase.
[Graphical view]
PfamiPF03372. Exo_endo_phos. 1 hit.
[Graphical view]
SUPFAMiSSF56219. SSF56219. 1 hit.
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Cloned mammalian neutral sphingomyelinase: functions in sphingolipid signaling?"
    Tomiuk S., Hofmann K., Nix M., Zumbansen M., Stoffel W.
    Proc. Natl. Acad. Sci. U.S.A. 95:3638-3643(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], CHARACTERIZATION, TISSUE SPECIFICITY, VARIANTS LEU-3 AND SER-265.
  2. "The DNA sequence and analysis of human chromosome 6."
    Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., Andrews T.D.
    , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S.
    Nature 425:805-811(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  3. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT SER-265.
    Tissue: Brain.
  4. "Function of the cloned putative neutral sphingomyelinase as lyso-platelet activating factor-phospholipase C."
    Sawai H., Domae N., Nagan N., Hannun Y.A.
    J. Biol. Chem. 274:38131-38139(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: CHARACTERIZATION.

Entry informationi

Entry nameiNSMA_HUMAN
AccessioniPrimary (citable) accession number: O60906
Secondary accession number(s): Q5TED1, Q9BWR3
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 11, 2002
Last sequence update: November 13, 2007
Last modified: January 7, 2015
This is version 130 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 6
    Human chromosome 6: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  6. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.