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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)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi364 – 3641MagnesiumBy similarity
Sitei512 – 5121Important for substrate recognitionBy similarity
Active sitei639 – 6391Proton acceptorBy similarity

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

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

Chemistry

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)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

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Golgi apparatus, Membrane

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA37862.

Chemistry

DrugBankiDB00144. Phosphatidylserine.

Polymorphism and mutation databases

BioMutaiSMPD3.
DMDMi73921262.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 655655Sphingomyelin phosphodiesterase 3PRO_0000075692Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Lipidationi53 – 531S-palmitoyl cysteineBy similarity
Lipidationi54 – 541S-palmitoyl cysteineBy similarity
Lipidationi59 – 591S-palmitoyl cysteineBy similarity
Modified residuei178 – 1781PhosphoserineBy similarity
Modified residuei291 – 2911PhosphoserineCombined sources
Lipidationi397 – 3971S-palmitoyl cysteineBy similarity
Lipidationi398 – 3981S-palmitoyl cysteineBy similarity

Post-translational modificationi

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

Keywords - PTMi

Lipoprotein, Palmitate, Phosphoprotein

Proteomic databases

PaxDbiQ9NY59.
PRIDEiQ9NY59.

PTM databases

iPTMnetiQ9NY59.
PhosphoSiteiQ9NY59.
SwissPalmiQ9NY59.

Expressioni

Tissue specificityi

Predominantly expressed in brain.1 Publication

Developmental stagei

Up-regulated during G0/G1 phases.

Gene expression databases

BgeeiQ9NY59.
CleanExiHS_SMPD3.
ExpressionAtlasiQ9NY59. baseline and differential.
GenevisibleiQ9NY59. HS.

Organism-specific databases

HPAiCAB033885.

Interactioni

Protein-protein interaction databases

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

Structurei

3D structure databases

ProteinModelPortaliQ9NY59.
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.
OrthoDBiEOG7BZVRT.
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)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei541 – 5488Missing in isoform 2. 1 PublicationVSP_054334

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_005256031.2. [Q9NY59-1]
XP_005256089.1. XM_005256032.2. [Q9NY59-1]
XP_011521509.1. XM_011523207.1. [Q9NY59-1]
XP_011521510.1. XM_011523208.1. [Q9NY59-1]
XP_011521511.1. XM_011523209.1. [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_005256031.2. [Q9NY59-1]
XP_005256089.1. XM_005256032.2. [Q9NY59-1]
XP_011521509.1. XM_011523207.1. [Q9NY59-1]
XP_011521510.1. XM_011523208.1. [Q9NY59-1]
XP_011521511.1. XM_011523209.1. [Q9NY59-1]
UniGeneiHs.368421.

3D structure databases

ProteinModelPortaliQ9NY59.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

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

Chemistry

DrugBankiDB00144. Phosphatidylserine.
SwissLipidsiSLP:000001111.

PTM databases

iPTMnetiQ9NY59.
PhosphoSiteiQ9NY59.
SwissPalmiQ9NY59.

Polymorphism and mutation databases

BioMutaiSMPD3.
DMDMi73921262.

Proteomic databases

PaxDbiQ9NY59.
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.
GeneCardsiSMPD3.
HGNCiHGNC:14240. SMPD3.
HPAiCAB033885.
MIMi605777. gene.
neXtProtiNX_Q9NY59.
PharmGKBiPA37862.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IEKS. Eukaryota.
ENOG41104QW. LUCA.
GeneTreeiENSGT00400000022168.
HOGENOMiHOG000049296.
HOVERGENiHBG079416.
InParanoidiQ9NY59.
KOiK12352.
OMAiPNSCLSA.
OrthoDBiEOG7BZVRT.
PhylomeDBiQ9NY59.
TreeFamiTF328678.

Enzyme and pathway databases

UniPathwayiUPA00222.
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

BgeeiQ9NY59.
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...

Publicationsi

« Hide 'large scale' publications
  1. "Cloning and characterization of the mammalian brain-specific, Mg2+-dependent neutral sphingomyelinase."
    Hofmann K., Tomiuk S., Wolff G., Stoffel W.
    Proc. Natl. Acad. Sci. U.S.A. 97:5895-5900(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, COFACTOR, ENZYME REGULATION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
  2. "The sequence and analysis of duplication-rich human chromosome 16."
    Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G., Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E., Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J.
    , Buckingham J.M., Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C., Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M., Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M., Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D., Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L., Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E., Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H., Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y., Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J., Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D., Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S., Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A., Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M., Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H., Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A., Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J., DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J., Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M., Myers R.M., Rubin E.M., Pennacchio L.A.
    Nature 432:988-994(2004) [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] (ISOFORMS 1 AND 2).
    Tissue: Brain.
  4. "Hydrolysis of sphingosylphosphocholine by neutral sphingomyelinases."
    Miura Y., Gotoh E., Nara F., Nishijima M., Hanada K.
    FEBS Lett. 557:288-292(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  5. "Role for mammalian neutral sphingomyelinase 2 in confluence-induced growth arrest of MCF7 cells."
    Marchesini N., Osta W., Bielawski J., Luberto C., Obeid L.M., Hannun Y.A.
    J. Biol. Chem. 279:25101-25111(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, COFACTOR, SUBCELLULAR LOCATION.
  6. "Analysis of membrane topology of neutral sphingomyelinase 2."
    Tani M., Hannun Y.A.
    FEBS Lett. 581:1323-1328(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: TOPOLOGY.
  7. "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome."
    Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., Ye M., Zou H.
    J. Proteomics 96:253-262(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-291, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Liver.

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: June 8, 2016
This is version 116 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.