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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: 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)DescriptionActionsGraphical viewLength
Metal bindingi49MagnesiumBy similarity1
Sitei180Important for substrate recognitionBy similarity1
Active sitei272Proton acceptorBy similarity1

GO - Molecular functioni

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

GO - Biological processi

Keywordsi

Molecular functionHydrolase
Biological processLipid metabolism, Sphingolipid metabolism
LigandMagnesium, Metal-binding

Enzyme and pathway databases

BRENDAi3.1.4.12. 2681.
ReactomeiR-HSA-1660662. Glycosphingolipid metabolism.
R-HSA-193681. Ceramide signalling.
R-HSA-5626978. TNFR1-mediated ceramide production.
UniPathwayiUPA00222.

Chemistry databases

SwissLipidsiSLP:000000174.

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
Proteomesi
  • UP000005640 Componenti: Chromosome 6

Organism-specific databases

EuPathDBiHostDB:ENSG00000135587.8.
HGNCiHGNC:11121. SMPD2.

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Transmembranei330 – 350HelicalSequence analysisAdd BLAST21
Transmembranei354 – 374HelicalSequence analysisAdd BLAST21

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Organism-specific databases

DisGeNETi6610.
OpenTargetsiENSG00000135587.
PharmGKBiPA35970.

Chemistry databases

ChEMBLiCHEMBL4712.

Polymorphism and mutation databases

BioMutaiSMPD2.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000756861 – 423Sphingomyelin phosphodiesterase 2Add BLAST423

Proteomic databases

EPDiO60906.
MaxQBiO60906.
PaxDbiO60906.
PeptideAtlasiO60906.
PRIDEiO60906.

PTM databases

iPTMnetiO60906.
PhosphoSitePlusiO60906.

Expressioni

Gene expression databases

BgeeiENSG00000135587.
CleanExiHS_SMPD2.
ExpressionAtlasiO60906. baseline and differential.
GenevisibleiO60906. HS.

Organism-specific databases

HPAiHPA018110.
HPA018125.

Interactioni

Protein-protein interaction databases

BioGridi112494. 30 interactors.
IntActiO60906. 8 interactors.
STRINGi9606.ENSP00000258052.

Chemistry databases

BindingDBiO60906.

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

eggNOGiKOG3873. Eukaryota.
ENOG410ZFPY. LUCA.
GeneTreeiENSGT00390000009166.
HOGENOMiHOG000044683.
HOVERGENiHBG019089.
InParanoidiO60906.
KOiK12351.
OMAiRIQHADW.
OrthoDBiEOG091G0EZ8.
PhylomeDBiO60906.
TreeFamiTF313899.

Family and domain databases

Gene3Di3.60.10.10. 1 hit.
InterProiView protein in InterPro
IPR036691. Endo/exonu/phosph_ase_sf.
IPR005135. Endo/exonuclease/phosphatase.
PfamiView protein in Pfam
PF03372. Exo_endo_phos. 1 hit.
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)DescriptionActionsGraphical viewLength
Natural variantiVAR_0503053P → L1 PublicationCorresponds to variant dbSNP:rs1048197Ensembl.1
Natural variantiVAR_050306223V → I. Corresponds to variant dbSNP:rs9386806Ensembl.1
Natural variantiVAR_024181265R → S2 PublicationsCorresponds to variant dbSNP:rs1476387Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ222801 mRNA. Translation: CAA10995.1.
AL109947 Genomic DNA. No translation available.
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.4. human.

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Entry informationi

Entry nameiNSMA_HUMAN
AccessioniPrimary (citable) accession number: O60906
Secondary accession number(s): Q5TED1, Q9BWR3
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 11, 2002
Last sequence update: November 13, 2007
Last modified: October 25, 2017
This is version 153 of the entry and version 2 of the sequence. See 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