Q9JJY3 (NSMA2_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:

Smpd3

Organism

Mus musculus (Mouse)

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

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. 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. Ref.5 Ref.6 Ref.7 Ref.8
Catalytic activity	Sphingomyelin + H2O = N-acylsphingosine + choline phosphate. Ref.4
Cofactor	Magnesium. Ref.4
Enzyme regulation	Inhibited by nSMase inhibitor GW4869. Ref.4
Subcellular location	Golgi apparatus membrane; Lipid-anchor. Cell membrane; Lipid-anchor By similarity. Note: May localize to detergent-resistant subdomains of Golgi membranes of hypothalamic neurosecretory neurons. Ref.8 Ref.9
Tissue specificity	Predominantly expressed in brain (at protein level). Ref.1
Post-translational modification	Palmitoylated, palmitoylation-deficient proteins are targeted for lysosomal degradation. Ref.9
Disruption phenotype	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. Ref.8
Sequence similarities	Belongs to the neutral sphingomyelinase family.

Ontologies

Keywords
Biological process	Cell cycle
Cellular component	Cell membrane Golgi apparatus Membrane
Ligand	Magnesium Metal-binding
Molecular function	Developmental protein Hydrolase
PTM	Lipoprotein Palmitate
Technical term	Complete proteome Reference 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 peptide hormone secretion Inferred from mutant phenotype Ref.8. Source: MGI response to stress Traceable author statement Ref.1. Source: MGI signal transduction Traceable author statement Ref.1. Source: MGI sphingomyelin metabolic process Inferred from direct assay Ref.1. Source: MGI
Cellular component	Golgi cis cisterna Inferred from direct assay Ref.8. Source: MGI Golgi membrane Inferred from electronic annotation. Source: UniProtKB-SubCell integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW sphingomyelin phosphodiesterase activity Inferred from direct assay Ref.1. Source: MGI
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_0000075693
Regions
	Topological domain	1 – 10	10	Cytoplasmic Potential
	Intramembrane	11 – 31	21	Helical; Potential
	Topological domain	32 – 64	33	Cytoplasmic Potential
	Intramembrane	65 – 85	21	Helical; Potential
	Topological domain	86 – 655	570	Cytoplasmic Potential
Sites
	Active site	639	1	Proton acceptor By similarity
	Metal binding	362	1	Magnesium By similarity
	Site	510	1	Important for substrate recognition By similarity
Amino acid modifications
	Lipidation	53	1	S-palmitoyl cysteine Ref.9
	Lipidation	54	1	S-palmitoyl cysteine Ref.9
	Lipidation	59	1	S-palmitoyl cysteine Ref.9
	Lipidation	395	1	S-palmitoyl cysteine Ref.9
	Lipidation	396	1	S-palmitoyl cysteine Ref.9

Sequences

	Sequence		Length	Mass (Da)
	Q9JJY3 [UniParc]. Last modified October 1, 2000. Version 1. Checksum: 6764769EEAB5A168	FASTA	655	71,197
	10 20 30 40 50 60 MVLYTTPFPN SCLSALHAVS WALIFPCYWL VDRLLASFIP TTYEKRQRAD DPCCLQLFCT 70 80 90 100 110 120 VLFTPVYLAL LVAALPFAFL GFIFWSPLQS ARRPYSYSRL EDKNPAGGAA LLSEWKGTGA 130 140 150 160 170 180 GKSFCFATAN VCLLPDSLAR LNNVFNTQAR AKEIGQRIRN GAARPQIKIY IDSPTNTSIS 190 200 210 220 230 240 AASFSSLVSP QGGDGSRAVP GSIKRTASVE YKGDGGRHPS DEAANGPASG EQADGSLEDS 250 260 270 280 290 300 CIVRIGGEEG GRPQEADDPA AGSQARNGAG GTPKGQTPNH NQRDGDSGSL GSPSASRESL 310 320 330 340 350 360 VKARAGQDSG GSGEPGANSK LLYKTSVVKK AAARRRRHPD EAFDHEVSAF FPANLDFLCL 370 380 390 400 410 420 QEVFDKRAAA KLKEQLHGYF EYILYDVGVY GCHGCCNFKC LNSGLFFASR YPVMDVAYHC 430 440 450 460 470 480 YPNGCSFDAL ASKGALFLKV QVGSTPQDQR IVGYIACTHL HAPPEDSAVR CEQLDLLQDW 490 500 510 520 530 540 LADFRKSTSS TSTANPEELV VFDVICGDLN FDNCSSDDKL EQQHSLFTRY KDPCRLGPGE 550 560 570 580 590 600 EKPWAIGTLL DTNGLYDEDV CTPDNLQKVL ESEEGRREYL AFPTSKSPGA GQKGRKDLLK 610 620 630 640 650 GNGRRIDYML HAEEGLCPDW KAEVEEFSFI TQLSGLTDHL PVAMRLMVSA 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], TISSUE SPECIFICITY.
[2]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed: 16141072] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: C57BL/6J. Tissue: Cerebellum and Skin.
[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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: C57BL/6 and FVB/N. Tissue: Brain and Colon.
[4]	"Biochemical properties of mammalian neutral sphingomyelinase 2 and its role in sphingolipid metabolism." Marchesini N., Luberto C., Hannun Y.A. J. Biol. Chem. 278:13775-13783(2003) [PubMed: 12566438] [Abstract] Cited for: CATALYTIC ACTIVITY, COFACTOR, ENZYME REGULATION.
[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: 15051724] [Abstract] Cited for: FUNCTION.
[6]	"Differential regulation of ceramide in lipid-rich microdomains (rafts): antagonistic role of palmitoyl:protein thioesterase and neutral sphingomyelinase 2." Goswami R., Ahmed M., Kilkus J., Han T., Dawson S.A., Dawson G. J. Neurosci. Res. 81:208-217(2005) [PubMed: 15929065] [Abstract] Cited for: FUNCTION.
[7]	"A deletion in the gene encoding sphingomyelin phosphodiesterase 3 (Smpd3) results in osteogenesis and dentinogenesis imperfecta in the mouse." Aubin I., Adams C.P., Opsahl S., Septier D., Bishop C.E., Auge N., Salvayre R., Negre-Salvayre A., Goldberg M., Guenet J.-L., Poirier C. Nat. Genet. 37:803-805(2005) [PubMed: 16025116] [Abstract] Cited for: FUNCTION.
[8]	"Neutral sphingomyelinase 2 (smpd3) in the control of postnatal growth and development." Stoffel W., Jenke B., Bloeck B., Zumbansen M., Koebke J. Proc. Natl. Acad. Sci. U.S.A. 102:4554-4559(2005) [PubMed: 15764706] [Abstract] Cited for: FUNCTION, DISRUPTION PHENOTYPE, SUBCELLULAR LOCATION.
[9]	"Neutral sphingomyelinase 2 is palmitoylated on multiple cysteine residues. Role of palmitoylation in subcellular localization." Tani M., Hannun Y.A. J. Biol. Chem. 282:10047-10056(2007) [PubMed: 17272284] [Abstract] Cited for: SUBCELLULAR LOCATION, PALMITOYLATION AT CYS-53; CYS-54; CYS-59; CYS-395 AND CYS-396.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	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.
IPI	IPI00122396.
RefSeq	NP_067466.1. NM_021491.3.
UniGene	Mm.23298.
3D structure databases
ProteinModelPortal	Q9JJY3.
SMR	Q9JJY3. Positions 353-519.
ModBase	Search...
Protein-protein interaction databases
STRING	Q9JJY3.
PTM databases
PhosphoSite	Q9JJY3.
Proteomic databases
PRIDE	Q9JJY3.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000067512; ENSMUSP00000069255; ENSMUSG00000031906.
GeneID	58994.
KEGG	mmu:58994.
UCSC	uc009nfx.1. mouse.
Organism-specific databases
CTD	55512.
MGI	MGI:1927578. Smpd3.
Phylogenomic databases
GeneTree	ENSGT00400000022168.
HOGENOM	HBG444551.
HOVERGEN	HBG079416.
InParanoid	Q9JJY3.
OMA	RTASVEY.
OrthoDB	EOG4PVNZ9.
PhylomeDB	Q9JJY3.
Gene expression databases
ArrayExpress	Q9JJY3.
Bgee	Q9JJY3.
CleanEx	MM_SMPD3.
Genevestigator	Q9JJY3.
GermOnline	ENSMUSG00000031906. Mus musculus.
Family and domain databases
InterPro	IPR005135. Endo/exonuclease/phosphatase. [Graphical view]
KO	K12352.
Pfam	PF03372. Exo_endo_phos. 1 hit. [Graphical view]
SUPFAM	SSF56219. Exo_endo_phos. 1 hit.
ProtoNet	Search...
Other
NextBio	314498.
SOURCE	Search...

Entry information

Entry name

NSMA2_MOUSE

Accession

Primary (citable) accession number: Q9JJY3
Secondary accession number(s): Q3UTQ5

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 30, 2005
Last sequence update:	October 1, 2000
Last modified:	January 25, 2012
This is version 80 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program