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Protein

Sphingomyelin phosphodiesterase 3

Gene

SMPD3

Organism
Homo sapiens (Human)
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. Probably acts as a regulator of postnatal development and participates in bone and dentin mineralization.3 Publications

Catalytic activityi

Sphingomyelin + H2O = N-acylsphingosine + phosphocholine.

Cofactori

Mg2+2 Publications

Enzyme regulationi

Activated by unsaturated fatty acids and phosphatidylserine.1 Publication

pH dependencei

Optimum pH is 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 bindingi364MagnesiumBy similarity1
Sitei512Important for substrate recognitionBy similarity1
Active sitei639Proton acceptorBy similarity1

GO - Molecular functioni

GO - Biological processi

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

BioCyciZFISH:HS02449-MONOMER.
BRENDAi3.1.4.12. 2681.
ReactomeiR-HSA-1660662. Glycosphingolipid metabolism.
R-HSA-5626978. TNFR1-mediated ceramide production.
UniPathwayiUPA00222.

Chemistry databases

SwissLipidsiSLP:000001111.

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
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 16

Organism-specific databases

HGNCiHGNC:14240. SMPD3.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 10CytoplasmicSequence analysis10
Intramembranei11 – 31HelicalSequence analysisAdd BLAST21
Topological domaini32 – 64CytoplasmicSequence analysisAdd BLAST33
Intramembranei65 – 85HelicalSequence analysisAdd BLAST21
Topological domaini86 – 655CytoplasmicSequence analysisAdd BLAST570

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Golgi apparatus, Membrane

Pathology & Biotechi

Organism-specific databases

DisGeNETi55512.
OpenTargetsiENSG00000103056.
PharmGKBiPA37862.

Chemistry databases

DrugBankiDB00144. Phosphatidylserine.

Polymorphism and mutation databases

BioMutaiSMPD3.
DMDMi73921262.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000756921 – 655Sphingomyelin phosphodiesterase 3Add BLAST655

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Lipidationi53S-palmitoyl cysteineBy similarity1
Lipidationi54S-palmitoyl cysteineBy similarity1
Lipidationi59S-palmitoyl cysteineBy similarity1
Modified residuei178PhosphoserineBy similarity1
Modified residuei291PhosphoserineCombined sources1
Lipidationi397S-palmitoyl cysteineBy similarity1
Lipidationi398S-palmitoyl cysteineBy similarity1

Post-translational modificationi

Palmitoylated, palmitoylation-deficient proteins are targeted for lysosomal degradation.By similarity

Keywords - PTMi

Lipoprotein, Palmitate, Phosphoprotein

Proteomic databases

PaxDbiQ9NY59.
PeptideAtlasiQ9NY59.
PRIDEiQ9NY59.

PTM databases

iPTMnetiQ9NY59.
PhosphoSitePlusiQ9NY59.
SwissPalmiQ9NY59.

Expressioni

Tissue specificityi

Predominantly expressed in brain.1 Publication

Developmental stagei

Up-regulated during G0/G1 phases.

Gene expression databases

BgeeiENSG00000103056.
CleanExiHS_SMPD3.
ExpressionAtlasiQ9NY59. baseline and differential.
GenevisibleiQ9NY59. HS.

Organism-specific databases

HPAiCAB033885.

Interactioni

Protein-protein interaction databases

BioGridi120692. 9 interactors.
DIPiDIP-60431N.
IntActiQ9NY59. 10 interactors.
STRINGi9606.ENSP00000219334.

Structurei

3D structure databases

ProteinModelPortaliQ9NY59.
SMRiQ9NY59.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the neutral sphingomyelinase family.Curated

Phylogenomic databases

eggNOGiENOG410IEKS. Eukaryota.
ENOG41104QW. LUCA.
GeneTreeiENSGT00400000022168.
HOGENOMiHOG000049296.
HOVERGENiHBG079416.
InParanoidiQ9NY59.
KOiK12352.
OMAiPNSCLSA.
OrthoDBiEOG091G0RKM.
PhylomeDBiQ9NY59.
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.

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9NY59-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MVLYTTPFPN SCLSALHCVS WALIFPCYWL VDRLAASFIP TTYEKRQRAD
60 70 80 90 100
DPCCLQLLCT ALFTPIYLAL LVASLPFAFL GFLFWSPLQS ARRPYIYSRL
110 120 130 140 150
EDKGLAGGAA LLSEWKGTGP GKSFCFATAN VCLLPDSLAR VNNLFNTQAR
160 170 180 190 200
AKEIGQRIRN GAARPQIKIY IDSPTNTSIS AASFSSLVSP QGGDGVARAV
210 220 230 240 250
PGSIKRTASV EYKGDGGRHP GDEAANGPAS GDPVDSSSPE DACIVRIGGE
260 270 280 290 300
EGGRPPEADD PVPGGQARNG AGGGPRGQTP NHNQQDGDSG SLGSPSASRE
310 320 330 340 350
SLVKGRAGPD TSASGEPGAN SKLLYKASVV KKAAARRRRH PDEAFDHEVS
360 370 380 390 400
AFFPANLDFL CLQEVFDKRA ATKLKEQLHG YFEYILYDVG VYGCQGCCSF
410 420 430 440 450
KCLNSGLLFA SRYPIMDVAY HCYPNKCNDD ALASKGALFL KVQVGSTPQD
460 470 480 490 500
QRIVGYIACT HLHAPQEDSA IRCGQLDLLQ DWLADFRKST SSSSAANPEE
510 520 530 540 550
LVAFDVVCGD FNFDNCSSDD KLEQQHSLFT HYRDPCRLGP GEEKPWAIGT
560 570 580 590 600
LLDTNGLYDE DVCTPDNLQK VLESEEGRRE YLAFPTSKSS GQKGRKELLK
610 620 630 640 650
GNGRRIDYML HAEEGLCPDW KAEVEEFSFI TQLSGLTDHL PVAMRLMVSS

GEEEA
Length:655
Mass (Da):71,081
Last modified:October 1, 2000 - v1
Checksum:iC06401571633C48E
GO
Isoform 2 (identifier: Q9NY59-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     541-548: Missing.

Note: No experimental confirmation available.
Show »
Length:647
Mass (Da):70,170
Checksum:i13D0B9A01922E639
GO

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_054334541 – 548Missing in isoform 2. 1 Publication8

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ250460 mRNA. Translation: CAB92964.1.
AC099521 Genomic DNA. No translation available.
BC112238 mRNA. Translation: AAI12239.1.
BC143631 mRNA. Translation: AAI43632.1.
CCDSiCCDS10867.1. [Q9NY59-1]
RefSeqiNP_061137.1. NM_018667.3. [Q9NY59-1]
XP_005256088.1. XM_005256031.3. [Q9NY59-1]
XP_005256089.1. XM_005256032.3. [Q9NY59-1]
XP_011521509.1. XM_011523207.1. [Q9NY59-1]
XP_011521510.1. XM_011523208.2. [Q9NY59-1]
XP_011521511.1. XM_011523209.2. [Q9NY59-1]
XP_016878894.1. XM_017023405.1. [Q9NY59-1]
XP_016878895.1. XM_017023406.1. [Q9NY59-1]
XP_016878896.1. XM_017023407.1. [Q9NY59-1]
XP_016878897.1. XM_017023408.1. [Q9NY59-1]
UniGeneiHs.368421.

Genome annotation databases

EnsembliENST00000219334; ENSP00000219334; ENSG00000103056. [Q9NY59-1]
ENST00000563226; ENSP00000455955; ENSG00000103056. [Q9NY59-2]
GeneIDi55512.
KEGGihsa:55512.
UCSCiuc002ewa.4. human. [Q9NY59-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ250460 mRNA. Translation: CAB92964.1.
AC099521 Genomic DNA. No translation available.
BC112238 mRNA. Translation: AAI12239.1.
BC143631 mRNA. Translation: AAI43632.1.
CCDSiCCDS10867.1. [Q9NY59-1]
RefSeqiNP_061137.1. NM_018667.3. [Q9NY59-1]
XP_005256088.1. XM_005256031.3. [Q9NY59-1]
XP_005256089.1. XM_005256032.3. [Q9NY59-1]
XP_011521509.1. XM_011523207.1. [Q9NY59-1]
XP_011521510.1. XM_011523208.2. [Q9NY59-1]
XP_011521511.1. XM_011523209.2. [Q9NY59-1]
XP_016878894.1. XM_017023405.1. [Q9NY59-1]
XP_016878895.1. XM_017023406.1. [Q9NY59-1]
XP_016878896.1. XM_017023407.1. [Q9NY59-1]
XP_016878897.1. XM_017023408.1. [Q9NY59-1]
UniGeneiHs.368421.

3D structure databases

ProteinModelPortaliQ9NY59.
SMRiQ9NY59.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi120692. 9 interactors.
DIPiDIP-60431N.
IntActiQ9NY59. 10 interactors.
STRINGi9606.ENSP00000219334.

Chemistry databases

DrugBankiDB00144. Phosphatidylserine.
SwissLipidsiSLP:000001111.

PTM databases

iPTMnetiQ9NY59.
PhosphoSitePlusiQ9NY59.
SwissPalmiQ9NY59.

Polymorphism and mutation databases

BioMutaiSMPD3.
DMDMi73921262.

Proteomic databases

PaxDbiQ9NY59.
PeptideAtlasiQ9NY59.
PRIDEiQ9NY59.

Protocols and materials databases

DNASUi55512.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000219334; ENSP00000219334; ENSG00000103056. [Q9NY59-1]
ENST00000563226; ENSP00000455955; ENSG00000103056. [Q9NY59-2]
GeneIDi55512.
KEGGihsa:55512.
UCSCiuc002ewa.4. human. [Q9NY59-1]

Organism-specific databases

CTDi55512.
DisGeNETi55512.
GeneCardsiSMPD3.
HGNCiHGNC:14240. SMPD3.
HPAiCAB033885.
MIMi605777. gene.
neXtProtiNX_Q9NY59.
OpenTargetsiENSG00000103056.
PharmGKBiPA37862.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IEKS. Eukaryota.
ENOG41104QW. LUCA.
GeneTreeiENSGT00400000022168.
HOGENOMiHOG000049296.
HOVERGENiHBG079416.
InParanoidiQ9NY59.
KOiK12352.
OMAiPNSCLSA.
OrthoDBiEOG091G0RKM.
PhylomeDBiQ9NY59.
TreeFamiTF328678.

Enzyme and pathway databases

UniPathwayiUPA00222.
BioCyciZFISH:HS02449-MONOMER.
BRENDAi3.1.4.12. 2681.
ReactomeiR-HSA-1660662. Glycosphingolipid metabolism.
R-HSA-5626978. TNFR1-mediated ceramide production.

Miscellaneous databases

GeneWikiiSMPD3.
GenomeRNAii55512.
PROiQ9NY59.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000103056.
CleanExiHS_SMPD3.
ExpressionAtlasiQ9NY59. baseline and differential.
GenevisibleiQ9NY59. HS.

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_HUMAN
AccessioniPrimary (citable) accession number: Q9NY59
Secondary accession number(s): B7ZL82, Q2M1S8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 30, 2005
Last sequence update: October 1, 2000
Last modified: November 2, 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
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 16
    Human chromosome 16: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  4. 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.