Reviewed, UniProtKB/Swiss-Prot Q9NY59 (NSMA2_HUMAN)

Names and origin

Protein names

Recommended name:
    Sphingomyelin phosphodiesterase 3
    EC=3.1.4.12
Alternative name(s):
    Neutral sphingomyelinase II
    Neutral sphingomyelinase 2
      Short name=nSMase-2
      Short name=nSMase2

Gene names

Name:

SMPD3

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	655 AA.
Sequence status	Complete.
Protein existence	Evidence 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; Multi-pass membrane protein. Cell membrane; Multi-pass membrane protein. 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.
Sequence similarities	Belongs to the neutral sphingomyelinase family.
Biophysicochemical properties	pH dependence: Optimum pH is 7.5.

Ontologies

Keywords
Biological process	Cell cycle
Cellular component	Cell membrane Golgi apparatus Membrane
Domain	Transmembrane
Ligand	Magnesium Metal-binding
Molecular function	Developmental protein Hydrolase
Technical term	Complete proteome
Gene Ontology (GO)
Biological process	cell cycle Inferred from electronic annotation. Source: UniProtKB-KW multicellular organismal development Inferred from electronic annotation. Source: UniProtKB-KW sphingomyelin catabolic process Ref.1 Traceable author statement. Source: ProtInc
Cellular component	integral to membrane Inferred from electronic annotation. Source: UniProtKB-SubCell plasma membrane Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	magnesium ion binding Inferred from electronic annotation. Source: UniProtKB-KW sphingomyelin phosphodiesterase activity Inferred from electronic annotation. Source: EC
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 655	655	Sphingomyelin phosphodiesterase 3		PRO_0000075692
Regions
	Topological domain	1 – 10	10	Lumenal Potential
	Transmembrane	11 – 31	21	Potential
	Topological domain	32 – 64	33	Cytoplasmic Potential
	Transmembrane	65 – 85	21	Potential
	Topological domain	86 – 655	570	Lumenal Potential
Sites
	Active site	639	1	Proton acceptor By similarity
	Metal binding	364	1	Magnesium By similarity
	Site	512	1	Important for substrate recognition By similarity

Sequences

	Sequence		Length	Mass (Da)
	Q9NY59-1 [UniParc]. Last modified October 1, 2000. Version 1. Checksum: C06401571633C48E	FASTA	655	71,081
	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

References

	« Hide 'large scale' referencesShow '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.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AJ250460 mRNA. Translation: CAB92964.1. BC112238 mRNA. Translation: AAI12239.1.
IPI	IPI00032902.
RefSeq	NP_061137.1.
UniGene	Hs.368421
3D structure databases
SMR	Q9NY59. Positions 351-519, 354-647.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9NY59. 10 interactions.
STRING	Q9NY59.
Proteomic databases
PRIDE	Q9NY59.
Genome annotation databases
Ensembl	ENST00000219334; ENSP00000219334; ENSG00000103056; Homo sapiens. [Genome view]
GeneID	55512.
KEGG	hsa:55512.
NMPDR	fig|9606.3.peg.12457.
UCSC	uc002ewa.1. human.
Organism-specific databases
CTD	55512.
GeneCards	GC16M066949.
H-InvDB	HIX0013176.
HGNC	HGNC:14240. SMPD3.
MIM	605777. gene.
PharmGKB	PA37862.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	HBG444551.
HOVERGEN	Q9NY59.
InParanoid	Q9NY59.
OMA	RTASVEY.
OrthoDB	EOG95XBGN.
PhylomeDB	Q9NY59.
Enzyme and pathway databases
Pathway_Interaction_DB	ceramidepathway. Ceramide signaling pathway.
Gene expression databases
ArrayExpress	Q9NY59.
Bgee	Q9NY59.
CleanEx	HS_SMPD3.
Genevestigator	Q9NY59.
GermOnline	ENSG00000103056. Homo sapiens.
Family and domain databases
InterPro	IPR005135. Endo/exonuclease/phosphatase. [Graphical view]
Pfam	PF03372. Exo_endo_phos. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
DrugBank	DB00144. Phosphatidylserine.
NextBio	59926.
SOURCE	Search...

Entry information

Entry name

NSMA2_HUMAN

Accession

Primary (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 19, 2010
This is version 56 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

Disclaimer

Any 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.