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Protein

Sphingomyelin phosphodiesterase 3

Gene

Smpd3

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: -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. 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.2 Publications

Catalytic activityi

Sphingomyelin + H2O = N-acylsphingosine + phosphocholine.1 Publication

Cofactori

Mg2+1 Publication

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)DescriptionActionsGraphical viewLength
Metal bindingi362MagnesiumBy similarity1
Sitei510Important for substrate recognitionBy similarity1
Active sitei639Proton acceptorBy similarity1

GO - Molecular functioni

GO - Biological processi

  • aging Source: RGD
  • artery smooth muscle contraction Source: RGD
  • cell cycle Source: UniProtKB-KW
  • cellular response to interleukin-1 Source: RGD
  • dopamine uptake Source: RGD
  • hematopoietic progenitor cell differentiation Source: RGD
  • negative regulation of cytosolic calcium ion concentration Source: RGD
  • peptide hormone secretion Source: RGD
  • positive regulation of ceramide biosynthetic process Source: RGD
  • positive regulation of exosomal secretion Source: BHF-UCL
  • positive regulation of NIK/NF-kappaB signaling Source: RGD
  • positive regulation of nitric oxide biosynthetic process Source: RGD
  • sphingomyelin metabolic process Source: RGD

Keywordsi

Molecular functionDevelopmental protein, Hydrolase
Biological processCell cycle, Lipid metabolism, Sphingolipid metabolism
LigandMagnesium, Metal-binding

Enzyme and pathway databases

SABIO-RKiO35049
UniPathwayiUPA00222

Names & Taxonomyi

Protein namesi
Recommended name:
Sphingomyelin phosphodiesterase 3 (EC:3.1.4.12)
Alternative name(s):
Confluent 3Y1 cell-associated protein 1
Neutral sphingomyelinase 2
Short name:
nSMase-2
Short name:
nSMase2
Neutral sphingomyelinase II
Gene namesi
Name:Smpd3
Synonyms:Cca1
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi619754 Smpd3

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 10CytoplasmicSequence analysis10
Intramembranei11 – 31HelicalSequence analysisAdd BLAST21
Topological domaini32 – 64CytoplasmicSequence analysisAdd BLAST33
Intramembranei65 – 85HelicalSequence analysisAdd BLAST21
Topological domaini86 – 655CytoplasmicSequence analysisAdd BLAST570

Keywords - Cellular componenti

Cell membrane, Golgi apparatus, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000756941 – 655Sphingomyelin phosphodiesterase 3Add BLAST655

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Lipidationi53S-palmitoyl cysteineBy similarity1
Lipidationi59S-palmitoyl cysteineBy similarity1
Modified residuei178PhosphoserineBy similarity1
Modified residuei289PhosphoserineCombined sources1
Lipidationi395S-palmitoyl cysteineBy similarity1
Lipidationi396S-palmitoyl cysteineBy similarity1

Post-translational modificationi

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

Keywords - PTMi

Lipoprotein, Palmitate, Phosphoprotein

Proteomic databases

PaxDbiO35049
PRIDEiO35049

PTM databases

iPTMnetiO35049
PhosphoSitePlusiO35049

Expressioni

Tissue specificityi

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.1 Publication

Interactioni

Protein-protein interaction databases

BioGridi250193, 1 interactor
STRINGi10116.ENSRNOP00000000274

Structurei

3D structure databases

ProteinModelPortaliO35049
SMRiO35049
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the neutral sphingomyelinase family.Curated

Phylogenomic databases

eggNOGiENOG410IEKS Eukaryota
ENOG41104QW LUCA
HOGENOMiHOG000049296
HOVERGENiHBG079416
InParanoidiO35049
KOiK12352
PhylomeDBiO35049

Family and domain databases

InterProiView protein in InterPro
IPR036691 Endo/exonu/phosph_ase_sf
SUPFAMiSSF56219 SSF56219, 2 hits

Sequencei

Sequence statusi: Complete.

O35049-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MVLYTTPFPN SCLSALHAVS WALIFPCYWL VDRLVASFIP TTYEKRQRAD
60 70 80 90 100
DPCYLQLFCT VLFTPVYLAL LVAALPFAFL GFIFWSPLQS ARRPYSYSRL
110 120 130 140 150
EDKSPAGGAA LLSEWKGTGA GKSFCFATAN VCLLPDSLAR LNNVFNTQAR
160 170 180 190 200
AKEIGQRIRN GAARPQIKIY IDSPTNTSIS AASFSSLVSP QGSDGARAVP
210 220 230 240 250
GSIKRTASVE YKGDGGRHPS DEAANGPASG EQADGSLEDS CIVRIGGEEG
260 270 280 290 300
GRAQEADDPA PGSQARNGAG GTPKGQTPNH NQRDGDSGSL GSPSASRESL
310 320 330 340 350
VKARAGQDSG GSGEPGSNSK LLYKTSVVKK AAARRRRHPD EAFDHEVSAF
360 370 380 390 400
FPANLDFLCL QEVFDKRAAA KLKEQLHGYF EYILYDVGVY GCHGCCNFKC
410 420 430 440 450
LNSGLFFASR YPVMDVAYHC YPNGCSFDAL ASKGALFLKV QVGSTPQDQR
460 470 480 490 500
IVGYIACTHL HAPPEDSAIR CEQLDLLQDW LADFRKSTSS TSTANPEELV
510 520 530 540 550
VFDVICGDLN FDNCSSDDKL EQQHSLFTRY KDPCRLGPGE EKPWAIGTLL
560 570 580 590 600
DINGLYDEDV CTPDNLQKVL ESEEGRREYL AFPTSKSPGA GQKGRKDLLK
610 620 630 640 650
GNGRRIDYML HAEEGLCPDW KAEVEEFSFI TQLSGLTDHL PVAMRLMVSA

GEEEA
Length:655
Mass (Da):71,272
Last modified:August 30, 2005 - v2
Checksum:i2338F6EBACDA8AD4
GO

Sequence cautioni

The sequence BAA22932 differs from that shown. Reason: Frameshift at position 616.Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB000215 mRNA Translation: BAA22932.1 Frameshift.
PIRiT00011
RefSeqiNP_446057.1, NM_053605.1
UniGeneiRn.54555

Genome annotation databases

GeneIDi94338
KEGGirno:94338
UCSCiRGD:619754 rat

Similar proteinsi

Entry informationi

Entry nameiNSMA2_RAT
AccessioniPrimary (citable) accession number: O35049
Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 30, 2005
Last sequence update: August 30, 2005
Last modified: April 25, 2018
This is version 110 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health