Reviewed, UniProtKB/Swiss-Prot O35049 (NSMA2_RAT)

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
    Confluent 3Y1 cell-associated protein 1

Gene names

Name:	Smpd3
Synonyms:	Cca1

Organism

Rattus norvegicus (Rat)

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

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

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. May be involved in IL-1-beta-induced JNK activation in hepatocytes. May act as a mediator in transcriptional regulation of NOS2/iNOS via the NF-kappa-B activation under inflammatory conditions. Ref.3 Ref.4
Catalytic activity	Sphingomyelin + H2O = N-acylsphingosine + choline phosphate. Ref.3
Cofactor	Magnesium. Ref.3
Subcellular location	Golgi apparatus membrane; Multi-pass membrane protein By similarity. Cell membrane; Multi-pass membrane protein. Note: May localize to detergent-resistant subdomains of Golgi membranes of hypothalamic neurosecretory neurons By similarity. May also localize to the plasma membrane. Ref.3 Ref.2
Tissue specificity	In brain sections, it is restricted to neurons and especially prominent in large cells, including Purkinje cells, pyramidal cells, neurons of the dentate gyrus granular layer, and neurons in the pontine nuclei. Also present in the hypothalamic nuclei, neurons in the piriform cortex, and nuclei of the brainstem (at protein level). Mainly expressed in brain and jejunum. Weakly or not expressed in heart, spleen, lung, liver, kidney and testis. Ref.2
Sequence similarities	Belongs to the neutral sphingomyelinase family.
Sequence caution	The sequence BAA22932.1 differs from that shown. Reason: Frameshift at position 616.

Ontologies

Keywords
Biological process	Cell cycle
Cellular component	Cell membrane Golgi apparatus Membrane
Domain	Transmembrane
Ligand	Magnesium Metal-binding
Molecular function	Developmental protein Hydrolase
Gene Ontology (GO)
Biological process	cell cycle Inferred from electronic annotation. Source: UniProtKB-KW multicellular organismal development Inferred from electronic annotation. Source: UniProtKB-KW
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_0000075694
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	362	1	Magnesium By similarity
	Site	510	1	Important for substrate recognition By similarity

Sequences

	Sequence		Length	Mass (Da)
	O35049-1 [UniParc]. Last modified August 30, 2005. Version 2. Checksum: 2338F6EBACDA8AD4	FASTA	655	71,272
	10 20 30 40 50 60 MVLYTTPFPN SCLSALHAVS WALIFPCYWL VDRLVASFIP TTYEKRQRAD DPCYLQLFCT 70 80 90 100 110 120 VLFTPVYLAL LVAALPFAFL GFIFWSPLQS ARRPYSYSRL EDKSPAGGAA LLSEWKGTGA 130 140 150 160 170 180 GKSFCFATAN VCLLPDSLAR LNNVFNTQAR AKEIGQRIRN GAARPQIKIY IDSPTNTSIS 190 200 210 220 230 240 AASFSSLVSP QGSDGARAVP GSIKRTASVE YKGDGGRHPS DEAANGPASG EQADGSLEDS 250 260 270 280 290 300 CIVRIGGEEG GRAQEADDPA PGSQARNGAG GTPKGQTPNH NQRDGDSGSL GSPSASRESL 310 320 330 340 350 360 VKARAGQDSG GSGEPGSNSK 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 HAPPEDSAIR CEQLDLLQDW 490 500 510 520 530 540 LADFRKSTSS TSTANPEELV VFDVICGDLN FDNCSSDDKL EQQHSLFTRY KDPCRLGPGE 550 560 570 580 590 600 EKPWAIGTLL DINGLYDEDV CTPDNLQKVL ESEEGRREYL AFPTSKSPGA GQKGRKDLLK 610 620 630 640 650 GNGRRIDYML HAEEGLCPDW KAEVEEFSFI TQLSGLTDHL PVAMRLMVSA GEEEA

References

[1]	"cca1 is required for formation of growth-arrested confluent monolayer of rat 3Y1 cells." Hayashi Y., Kiyono T., Fujita M., Ishibashi M. J. Biol. Chem. 272:18082-18086(1997) [PubMed: 9218439] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"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: SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[3]	"Expression of neutral sphingomyelinase-2 (NSMase-2) in primary rat hepatocytes modulates IL-beta-induced JNK activation." Karakashian A.A., Giltiay N.V., Smith G.M., Nikolova-Karakashian M.N. FASEB J. 18:968-970(2004) [PubMed: 15059969] [Abstract] Cited for: FUNCTION, ENZYME ACTIVITY, COFACTOR, SUBCELLULAR LOCATION.
[4]	"The role of neutral sphingomyelinase produced ceramide in lipopolysaccharide-mediated expression of inducible nitric oxide synthase." Won J.-S., Im Y.-B., Khan M., Singh A.K., Singh I. J. Neurochem. 88:583-593(2004) [PubMed: 14720208] [Abstract] Cited for: FUNCTION.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AB000215 mRNA. Translation: BAA22932.1. Frameshift.
IPI	IPI00475992.
PIR	T00011.
RefSeq	NP_446057.1.
UniGene	Rn.54555
3D structure databases
SMR	O35049. Positions 349-517, 353-647.
ModBase	Search...
Protein-protein interaction databases
STRING	O35049.
Genome annotation databases
Ensembl	ENSRNOT00000000274; ENSRNOP00000000274; ENSRNOG00000000257; Rattus norvegicus. [Genome view]
GeneID	94338.
KEGG	rno:94338.
UCSC	AB000215. rat.
Organism-specific databases
CTD	94338.
RGD	619754. Smpd3.
Phylogenomic databases
eggNOG	roNOG05117.
HOVERGEN	O35049.
InParanoid	O35049.
Enzyme and pathway databases
BRENDA	3.1.4.12. 248.
Gene expression databases
ArrayExpress	O35049.
Genevestigator	O35049.
GermOnline	ENSRNOG00000000257. Rattus norvegicus.
Family and domain databases
InterPro	IPR005135. Endo/exonuclease/phosphatase. [Graphical view]
Pfam	PF03372. Exo_endo_phos. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	617921.

Entry information

Entry name

NSMA2_RAT

Accession

Primary (citable) accession number: O35049

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 30, 2005
Last sequence update:	August 30, 2005
Last modified:	January 19, 2010
This is version 55 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)