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Protein

Sphingomyelin phosphodiesterase 2

Gene

Smpd2

Organism
Mus musculus (Mouse)
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 (By similarity).By similarity

Catalytic activityi

Sphingomyelin + H2O = N-acylsphingosine + phosphocholine.

Cofactori

pH dependencei

Optimum pH is 6.5-7.5.

Pathwayi: sphingolipid metabolism

This protein is involved in the pathway sphingolipid metabolism, which is part of Lipid metabolism.
View all proteins of this organism that are known to be involved in the pathway sphingolipid metabolism and in Lipid metabolism.

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

  • metal ion binding Source: UniProtKB-KW
  • sphingomyelin phosphodiesterase activity Source: MGI

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Hydrolase

Keywords - Biological processi

Lipid metabolism, Sphingolipid metabolism

Keywords - Ligandi

Magnesium, Metal-binding

Enzyme and pathway databases

ReactomeiR-MMU-1660662. Glycosphingolipid metabolism.
R-MMU-5626978. TNFR1-mediated ceramide production.
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
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 10

Organism-specific databases

MGIiMGI:1278330. Smpd2.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Transmembranei326 – 34621HelicalSequence analysisAdd
BLAST
Transmembranei354 – 37421HelicalSequence analysisAdd
BLAST

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Disruption phenotypei

Mice lacking Smpd2 and Smpd3 are completely devoid of neutral SMase activity but do not developed sphingomyelin storage abnormalities.1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 419419Sphingomyelin phosphodiesterase 2PRO_0000075687Add
BLAST

Proteomic databases

EPDiO70572.
MaxQBiO70572.
PaxDbiO70572.
PRIDEiO70572.

PTM databases

iPTMnetiO70572.
PhosphoSiteiO70572.

Expressioni

Tissue specificityi

Although widely expressed in all tissues examined, except the spleen, high enzymatic activity occurs only in the brain.1 Publication

Gene expression databases

BgeeiO70572.
CleanExiMM_SMPD2.
ExpressionAtlasiO70572. baseline and differential.
GenevisibleiO70572. MM.

Interactioni

Protein-protein interaction databases

MINTiMINT-1657649.
STRINGi10090.ENSMUSP00000019965.

Structurei

3D structure databases

ProteinModelPortaliO70572.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the neutral sphingomyelinase family.Curated

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG3873. Eukaryota.
ENOG410ZFPY. LUCA.
GeneTreeiENSGT00390000009166.
HOGENOMiHOG000044683.
HOVERGENiHBG019089.
InParanoidiO70572.
KOiK12351.
OMAiQARWWAT.
OrthoDBiEOG7SXW3M.
PhylomeDBiO70572.
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.

O70572-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MKLNFSLRLR VFNLNCWDIP YLSKHRADRM KRLGDFLNLE NFDLALLEEV
60 70 80 90 100
WSEQDFQYLR QRLSLTYPDA HYFRSGMIGS GLCVFSKHPI QEIFQHVYSL
110 120 130 140 150
NGYPYMFHHG DWFCGKSVGL LVLRLSGLVL NAYVTHLHAE YSRQKDIYFA
160 170 180 190 200
HRVAQAWELA QFIHHTSKNA DVVLLCGDLN MHPKDLGCCL LKEWTGLHDA
210 220 230 240 250
FVETEDFKGS DDGCTMVPKN CYVSQQDLGP FPSGIRIDYV LYKAVSEFHV
260 270 280 290 300
CCETLKTTTG CDPHSDKPFS DHEALMATLY VKHSPPQEDP CTACGPLERS
310 320 330 340 350
DLISVLREAR TELGLGIAKA RWWAAFSGYV IVWGLSLLVL LCVLAAGEEA
360 370 380 390 400
REVAIILCIP SVGLVLVAGA VYLFHKQEAK GLCRAQAEML HVLTRETETQ
410
DRGSEPHLAY CLQQEGDRA
Length:419
Mass (Da):47,467
Last modified:August 1, 1998 - v1
Checksum:i5812FC630A69C356
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ222800 mRNA. Translation: CAA10994.1.
BC010978 mRNA. Translation: AAH10978.1.
CCDSiCCDS23805.1.
RefSeqiNP_033239.1. NM_009213.2.
UniGeneiMm.953.

Genome annotation databases

EnsembliENSMUST00000019965; ENSMUSP00000019965; ENSMUSG00000019822.
GeneIDi20598.
KEGGimmu:20598.
UCSCiuc007exs.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ222800 mRNA. Translation: CAA10994.1.
BC010978 mRNA. Translation: AAH10978.1.
CCDSiCCDS23805.1.
RefSeqiNP_033239.1. NM_009213.2.
UniGeneiMm.953.

3D structure databases

ProteinModelPortaliO70572.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

MINTiMINT-1657649.
STRINGi10090.ENSMUSP00000019965.

PTM databases

iPTMnetiO70572.
PhosphoSiteiO70572.

Proteomic databases

EPDiO70572.
MaxQBiO70572.
PaxDbiO70572.
PRIDEiO70572.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000019965; ENSMUSP00000019965; ENSMUSG00000019822.
GeneIDi20598.
KEGGimmu:20598.
UCSCiuc007exs.1. mouse.

Organism-specific databases

CTDi6610.
MGIiMGI:1278330. Smpd2.

Phylogenomic databases

eggNOGiKOG3873. Eukaryota.
ENOG410ZFPY. LUCA.
GeneTreeiENSGT00390000009166.
HOGENOMiHOG000044683.
HOVERGENiHBG019089.
InParanoidiO70572.
KOiK12351.
OMAiQARWWAT.
OrthoDBiEOG7SXW3M.
PhylomeDBiO70572.
TreeFamiTF313899.

Enzyme and pathway databases

UniPathwayiUPA00222.
ReactomeiR-MMU-1660662. Glycosphingolipid metabolism.
R-MMU-5626978. TNFR1-mediated ceramide production.

Miscellaneous databases

ChiTaRSiSmpd2. mouse.
PROiO70572.
SOURCEiSearch...

Gene expression databases

BgeeiO70572.
CleanExiMM_SMPD2.
ExpressionAtlasiO70572. baseline and differential.
GenevisibleiO70572. MM.

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.
  2. "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].
    Tissue: Salivary gland.
  3. "Neutral sphingomyelinase 2 (smpd3) in the control of postnatal growth and development."
    Stoffel W., Jenke B., Bloeck B., Zumbansen M., Koebke J.
    Proc. Natl. Acad. Sci. U.S.A. 102:4554-4559(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: DISRUPTION PHENOTYPE.
  4. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Heart, Kidney, Liver, Lung and Pancreas.

Entry informationi

Entry nameiNSMA_MOUSE
AccessioniPrimary (citable) accession number: O70572
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 11, 2002
Last sequence update: August 1, 1998
Last modified: June 8, 2016
This is version 123 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  3. SIMILARITY comments
    Index of protein domains and families

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 one 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.