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Q9NY59 (NSMA2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified January 25, 2012. Version 73. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
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to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:SMPD3
OrganismHomo sapiens (Human)
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length655 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.1 Ref.3 Ref.4

Catalytic activity

Sphingomyelin + H2O = N-acylsphingosine + choline phosphate.

Cofactor

Magnesium. Ref.1 Ref.4

Enzyme regulation

Activated by unsaturated fatty acids and phosphatidylserine. Ref.1

Subcellular location

Golgi apparatus membrane; Lipid-anchor. Cell membrane; Lipid-anchor. Note: May localize to detergent-resistant subdomains of Golgi membranes of hypothalamic neurosecretory neurons. According to Ref.4, it localizes to plasma membrane in confluent contact-inhibited cells. Ref.1 Ref.4

Tissue specificity

Predominantly expressed in brain. Ref.1

Developmental stage

Up-regulated during G0/G1 phases.

Post-translational modification

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

Sequence similarities

Belongs to the neutral sphingomyelinase family.

Biophysicochemical properties

pH dependence:

Optimum pH is 7.5.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 655655Sphingomyelin phosphodiesterase 3
PRO_0000075692

Regions

Topological domain1 – 1010Cytoplasmic Potential
Intramembrane11 – 3121Helical; Potential
Topological domain32 – 6433Cytoplasmic Potential
Intramembrane65 – 8521Helical; Potential
Topological domain86 – 655570Cytoplasmic Potential

Sites

Active site6391Proton acceptor By similarity
Metal binding3641Magnesium By similarity
Site5121Important for substrate recognition By similarity

Amino acid modifications

Lipidation531S-palmitoyl cysteine By similarity
Lipidation541S-palmitoyl cysteine By similarity
Lipidation591S-palmitoyl cysteine By similarity
Lipidation3971S-palmitoyl cysteine By similarity
Lipidation3981S-palmitoyl cysteine By similarity

Sequences

Sequence LengthMass (Da)Tools
Q9NY59 [UniParc].

Last modified October 1, 2000. Version 1.
Checksum: C06401571633C48E

FASTA65571,081
        10         20         30         40         50         60 
MVLYTTPFPN SCLSALHCVS WALIFPCYWL VDRLAASFIP TTYEKRQRAD DPCCLQLLCT 

        70         80         90        100        110        120 
ALFTPIYLAL LVASLPFAFL GFLFWSPLQS ARRPYIYSRL EDKGLAGGAA LLSEWKGTGP 

       130        140        150        160        170        180 
GKSFCFATAN VCLLPDSLAR VNNLFNTQAR AKEIGQRIRN GAARPQIKIY IDSPTNTSIS 

       190        200        210        220        230        240 
AASFSSLVSP QGGDGVARAV PGSIKRTASV EYKGDGGRHP GDEAANGPAS GDPVDSSSPE 

       250        260        270        280        290        300 
DACIVRIGGE EGGRPPEADD PVPGGQARNG AGGGPRGQTP NHNQQDGDSG SLGSPSASRE 

       310        320        330        340        350        360 
SLVKGRAGPD TSASGEPGAN SKLLYKASVV KKAAARRRRH PDEAFDHEVS AFFPANLDFL 

       370        380        390        400        410        420 
CLQEVFDKRA ATKLKEQLHG YFEYILYDVG VYGCQGCCSF KCLNSGLLFA SRYPIMDVAY 

       430        440        450        460        470        480 
HCYPNKCNDD ALASKGALFL KVQVGSTPQD QRIVGYIACT HLHAPQEDSA IRCGQLDLLQ 

       490        500        510        520        530        540 
DWLADFRKST SSSSAANPEE LVAFDVVCGD FNFDNCSSDD KLEQQHSLFT HYRDPCRLGP 

       550        560        570        580        590        600 
GEEKPWAIGT LLDTNGLYDE DVCTPDNLQK VLESEEGRRE YLAFPTSKSS GQKGRKELLK 

       610        620        630        640        650 
GNGRRIDYML HAEEGLCPDW KAEVEEFSFI TQLSGLTDHL PVAMRLMVSS GEEEA

« Hide

References

« Hide 'large scale' references
[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: 10823942] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, COFACTOR, ENZYME REGULATION, SUBCELLULAR LOCATION, 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: 15489334] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Brain.
[3]"Hydrolysis of sphingosylphosphocholine by neutral sphingomyelinases."
Miura Y., Gotoh E., Nara F., Nishijima M., Hanada K.
FEBS Lett. 557:288-292(2004) [PubMed: 14741383] [Abstract]
Cited for: FUNCTION.
[4]"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: 15051724] [Abstract]
Cited for: FUNCTION, COFACTOR, SUBCELLULAR LOCATION.
[5]"Analysis of membrane topology of neutral sphingomyelinase 2."
Tani M., Hannun Y.A.
FEBS Lett. 581:1323-1328(2007) [PubMed: 17349629] [Abstract]
Cited for: TOPOLOGY.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ		AJ250460 mRNA. Translation: CAB92964.1.
BC112238 mRNA. Translation: AAI12239.1.
IPIIPI00032902.
RefSeqNP_061137.1. NM_018667.3.
UniGeneHs.368421.

3D structure databases

ProteinModelPortalQ9NY59.
SMRQ9NY59. Positions 354-520.
ModBaseSearch...

Protein-protein interaction databases

IntActQ9NY59. 10 interactions.
STRINGQ9NY59.

PTM databases

PhosphoSiteQ9NY59.

Polymorphism databases

DMDM73921262.

Proteomic databases

PRIDEQ9NY59.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000219334; ENSP00000219334; ENSG00000103056.
GeneID55512.
KEGGhsa:55512.
NMPDRfig|9606.3.peg.12457.
UCSCuc002ewa.1. human.

Organism-specific databases

CTD55512.
GeneCardsGC16M068392.
H-InvDBHIX0013176.
HGNCHGNC:14240. SMPD3.
HPACAB033885.
MIM605777. gene.
neXtProtNX_Q9NY59.
GenAtlasSearch...

Phylogenomic databases

GeneTreeENSGT00400000022168.
HOGENOMHBG444551.
HOVERGENHBG079416.
InParanoidQ9NY59.
OMARTASVEY.
OrthoDBEOG4PVNZ9.
PhylomeDBQ9NY59.

Enzyme and pathway databases

Pathway_Interaction_DBceramidepathway. Ceramide signaling pathway.

Gene expression databases

ArrayExpressQ9NY59.
BgeeQ9NY59.
CleanExHS_SMPD3.
GenevestigatorQ9NY59.
GermOnlineENSG00000103056. Homo sapiens.

Family and domain databases

InterProIPR005135. Endo/exonuclease/phosphatase.
[Graphical view]
KOK12352.
PfamPF03372. Exo_endo_phos. 1 hit.
[Graphical view]
SUPFAMSSF56219. Exo_endo_phos. 1 hit.
ProtoNetSearch...

Other

DrugBankDB00144. Phosphatidylserine.
NextBio59926.
SOURCESearch...

Entry information

Entry nameNSMA2_HUMAN
AccessionPrimary (citable) accession number: Q9NY59
Secondary accession number(s): Q2M1S8
Entry history
Integrated into UniProtKB/Swiss-Prot: August 30, 2005
Last sequence update: October 1, 2000
Last modified: January 25, 2012
This is version 73 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

Human chromosome 16

Human chromosome 16: entries, gene names and cross-references to MIM

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

SIMILARITY comments

Index of protein domains and families

to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents