Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Sphingomyelin phosphodiesterase 3

Gene

Smpd3

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Catalyzes the hydrolysis of sphingomyelin to form ceramide and phosphocholine. Ceramide mediates numerous cellular functions, such as apoptosis and growth arrest, and is capable of regulating these 2 cellular events independently. Also hydrolyzes sphingosylphosphocholine. Regulates the cell cycle by acting as a growth suppressor in confluent cells. Acts as a regulator of postnatal development and participates in bone and dentin mineralization. Overexpression enhances cell death, suggesting that it may be involved in apoptosis control.4 Publications

Catalytic activityi

Sphingomyelin + H2O = N-acylsphingosine + phosphocholine.1 Publication

Cofactori

Mg2+1 Publication

Enzyme regulationi

Inhibited by nSMase inhibitor GW4869.1 Publication

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 bindingi362 – 3621MagnesiumBy similarity
Sitei510 – 5101Important for substrate recognitionBy similarity
Active sitei639 – 6391Proton acceptorBy similarity

GO - Molecular functioni

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

GO - Biological processi

  • cell cycle Source: UniProtKB-KW
  • hematopoietic progenitor cell differentiation Source: MGI
  • peptide hormone secretion Source: MGI
  • signal transduction Source: MGI
  • sphingomyelin metabolic process Source: MGI
Complete GO annotation...

Keywords - Molecular functioni

Developmental protein, Hydrolase

Keywords - Biological processi

Cell cycle, Lipid metabolism, Sphingolipid metabolism

Keywords - Ligandi

Magnesium, Metal-binding

Enzyme and pathway databases

BRENDAi3.1.4.12. 3474.
ReactomeiR-MMU-1660662. Glycosphingolipid metabolism.
R-MMU-5626978. TNFR1-mediated ceramide production.
UniPathwayiUPA00222.

Chemistry

SwissLipidsiSLP:000000215.

Names & Taxonomyi

Protein namesi
Recommended name:
Sphingomyelin phosphodiesterase 3 (EC:3.1.4.12)
Alternative name(s):
Neutral sphingomyelinase 2
Short name:
nSMase-2
Short name:
nSMase2
Neutral sphingomyelinase II
Gene namesi
Name:Smpd3
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 8

Organism-specific databases

MGIiMGI:1927578. Smpd3.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 1010CytoplasmicSequence analysis
Intramembranei11 – 3121HelicalSequence analysisAdd
BLAST
Topological domaini32 – 6433CytoplasmicSequence analysisAdd
BLAST
Intramembranei65 – 8521HelicalSequence analysisAdd
BLAST
Topological domaini86 – 655570CytoplasmicSequence analysisAdd
BLAST

GO - Cellular componenti

  • Golgi apparatus Source: MGI
  • Golgi cis cisterna Source: MGI
  • Golgi membrane Source: UniProtKB-SubCell
  • plasma membrane Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Golgi apparatus, Membrane

Pathology & Biotechi

Disruption phenotypei

Defects in smpd3 are the cause of fragilitas ossium (fro) mutation characterized by severe osteogenesis and dentinogenesis imperfecta with no detectable collagen defect. Mice lacking Smpd2 and Smpd3 are completely devoid of neutral SMase activity but do not developed sphingomyelin storage abnormalities. Mice lacking Smpd3 develop a form of dwarfism and delayed puberty as part of a hypothalamus-induced combined pituitary hormone deficiency (CPHD). Growth retardation is probably due to delayed ossification of long bones.1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 655655Sphingomyelin phosphodiesterase 3PRO_0000075693Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Lipidationi53 – 531S-palmitoyl cysteine1 Publication
Lipidationi54 – 541S-palmitoyl cysteine1 Publication
Lipidationi59 – 591S-palmitoyl cysteine1 Publication
Modified residuei178 – 1781PhosphoserineCombined sources
Modified residuei289 – 2891PhosphoserineCombined sources
Lipidationi395 – 3951S-palmitoyl cysteine1 Publication
Lipidationi396 – 3961S-palmitoyl cysteine1 Publication

Post-translational modificationi

Palmitoylated, palmitoylation-deficient proteins are targeted for lysosomal degradation.1 Publication

Keywords - PTMi

Lipoprotein, Palmitate, Phosphoprotein

Proteomic databases

MaxQBiQ9JJY3.
PaxDbiQ9JJY3.
PeptideAtlasiQ9JJY3.
PRIDEiQ9JJY3.

PTM databases

iPTMnetiQ9JJY3.
PhosphoSiteiQ9JJY3.
SwissPalmiQ9JJY3.

Expressioni

Tissue specificityi

Predominantly expressed in brain (at protein level).1 Publication

Gene expression databases

BgeeiENSMUSG00000031906.
CleanExiMM_SMPD3.
GenevisibleiQ9JJY3. MM.

Interactioni

Binary interactionsi

WithEntry#Exp.IntActNotes
HSPD1P108093EBI-9817007,EBI-352528From a different organism.

Protein-protein interaction databases

DIPiDIP-60430N.
IntActiQ9JJY3. 1 interaction.
MINTiMINT-4998309.
STRINGi10090.ENSMUSP00000069255.

Structurei

3D structure databases

ProteinModelPortaliQ9JJY3.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the neutral sphingomyelinase family.Curated

Phylogenomic databases

eggNOGiENOG410IEKS. Eukaryota.
ENOG41104QW. LUCA.
GeneTreeiENSGT00400000022168.
HOGENOMiHOG000049296.
HOVERGENiHBG079416.
InParanoidiQ9JJY3.
KOiK12352.
OMAiPNSCLSA.
OrthoDBiEOG091G0RKM.
PhylomeDBiQ9JJY3.
TreeFamiTF328678.

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. 2 hits.

Sequencei

Sequence statusi: Complete.

Q9JJY3-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MVLYTTPFPN SCLSALHAVS WALIFPCYWL VDRLLASFIP TTYEKRQRAD
60 70 80 90 100
DPCCLQLFCT VLFTPVYLAL LVAALPFAFL GFIFWSPLQS ARRPYSYSRL
110 120 130 140 150
EDKNPAGGAA LLSEWKGTGA GKSFCFATAN VCLLPDSLAR LNNVFNTQAR
160 170 180 190 200
AKEIGQRIRN GAARPQIKIY IDSPTNTSIS AASFSSLVSP QGGDGSRAVP
210 220 230 240 250
GSIKRTASVE YKGDGGRHPS DEAANGPASG EQADGSLEDS CIVRIGGEEG
260 270 280 290 300
GRPQEADDPA AGSQARNGAG GTPKGQTPNH NQRDGDSGSL GSPSASRESL
310 320 330 340 350
VKARAGQDSG GSGEPGANSK LLYKTSVVKK AAARRRRHPD EAFDHEVSAF
360 370 380 390 400
FPANLDFLCL QEVFDKRAAA KLKEQLHGYF EYILYDVGVY GCHGCCNFKC
410 420 430 440 450
LNSGLFFASR YPVMDVAYHC YPNGCSFDAL ASKGALFLKV QVGSTPQDQR
460 470 480 490 500
IVGYIACTHL HAPPEDSAVR CEQLDLLQDW LADFRKSTSS TSTANPEELV
510 520 530 540 550
VFDVICGDLN FDNCSSDDKL EQQHSLFTRY KDPCRLGPGE EKPWAIGTLL
560 570 580 590 600
DTNGLYDEDV CTPDNLQKVL ESEEGRREYL AFPTSKSPGA GQKGRKDLLK
610 620 630 640 650
GNGRRIDYML HAEEGLCPDW KAEVEEFSFI TQLSGLTDHL PVAMRLMVSA

GEEEA
Length:655
Mass (Da):71,197
Last modified:October 1, 2000 - v1
Checksum:i6764769EEAB5A168
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ250461 mRNA. Translation: CAB92970.1.
AK019476 mRNA. Translation: BAB31745.1.
AK139226 mRNA. Translation: BAE23925.1.
BC043077 mRNA. Translation: AAH43077.1.
BC046980 mRNA. Translation: AAH46980.1.
CCDSiCCDS22634.1.
RefSeqiNP_067466.1. NM_021491.3.
XP_006531302.1. XM_006531239.2.
XP_006531304.1. XM_006531241.2.
XP_011246764.1. XM_011248462.1.
XP_011246765.1. XM_011248463.1.
XP_011246766.1. XM_011248464.1.
UniGeneiMm.23298.

Genome annotation databases

EnsembliENSMUST00000067512; ENSMUSP00000069255; ENSMUSG00000031906.
GeneIDi58994.
KEGGimmu:58994.
UCSCiuc009nfx.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ250461 mRNA. Translation: CAB92970.1.
AK019476 mRNA. Translation: BAB31745.1.
AK139226 mRNA. Translation: BAE23925.1.
BC043077 mRNA. Translation: AAH43077.1.
BC046980 mRNA. Translation: AAH46980.1.
CCDSiCCDS22634.1.
RefSeqiNP_067466.1. NM_021491.3.
XP_006531302.1. XM_006531239.2.
XP_006531304.1. XM_006531241.2.
XP_011246764.1. XM_011248462.1.
XP_011246765.1. XM_011248463.1.
XP_011246766.1. XM_011248464.1.
UniGeneiMm.23298.

3D structure databases

ProteinModelPortaliQ9JJY3.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

DIPiDIP-60430N.
IntActiQ9JJY3. 1 interaction.
MINTiMINT-4998309.
STRINGi10090.ENSMUSP00000069255.

Chemistry

SwissLipidsiSLP:000000215.

PTM databases

iPTMnetiQ9JJY3.
PhosphoSiteiQ9JJY3.
SwissPalmiQ9JJY3.

Proteomic databases

MaxQBiQ9JJY3.
PaxDbiQ9JJY3.
PeptideAtlasiQ9JJY3.
PRIDEiQ9JJY3.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000067512; ENSMUSP00000069255; ENSMUSG00000031906.
GeneIDi58994.
KEGGimmu:58994.
UCSCiuc009nfx.1. mouse.

Organism-specific databases

CTDi55512.
MGIiMGI:1927578. Smpd3.

Phylogenomic databases

eggNOGiENOG410IEKS. Eukaryota.
ENOG41104QW. LUCA.
GeneTreeiENSGT00400000022168.
HOGENOMiHOG000049296.
HOVERGENiHBG079416.
InParanoidiQ9JJY3.
KOiK12352.
OMAiPNSCLSA.
OrthoDBiEOG091G0RKM.
PhylomeDBiQ9JJY3.
TreeFamiTF328678.

Enzyme and pathway databases

UniPathwayiUPA00222.
BRENDAi3.1.4.12. 3474.
ReactomeiR-MMU-1660662. Glycosphingolipid metabolism.
R-MMU-5626978. TNFR1-mediated ceramide production.

Miscellaneous databases

ChiTaRSiSmpd3. mouse.
PROiQ9JJY3.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000031906.
CleanExiMM_SMPD3.
GenevisibleiQ9JJY3. 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. 2 hits.
ProtoNetiSearch...

Entry informationi

Entry nameiNSMA2_MOUSE
AccessioniPrimary (citable) accession number: Q9JJY3
Secondary accession number(s): Q3UTQ5
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 30, 2005
Last sequence update: October 1, 2000
Last modified: September 7, 2016
This is version 120 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.