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Protein

Sphingomyelin phosphodiesterase 3

Gene

Smpd3

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi362 – 3621MagnesiumBy similarity
Sitei510 – 5101Important for substrate recognitionBy similarity
Active sitei639 – 6391Proton acceptorBy similarity

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
  • multicellular organism development Source: UniProtKB-KW
  • negative regulation of cytosolic calcium ion concentration 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
  • sphingolipid metabolic process Source: UniProtKB-UniPathway
Complete GO annotation...

Keywords - Molecular functioni

Developmental protein, Hydrolase

Keywords - Biological processi

Cell cycle, Lipid metabolism, Sphingolipid metabolism

Keywords - Ligandi

Magnesium, Metal-binding

Enzyme and pathway databases

SABIO-RKO35049.
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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi619754. Smpd3.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 1010CytoplasmicSequence analysis
Intramembranei11 – 3121HelicalSequence analysisAdd
BLAST
Topological domaini32 – 6433CytoplasmicSequence analysisAdd
BLAST
Intramembranei65 – 8521HelicalSequence analysisAdd
BLAST
Topological domaini86 – 655570CytoplasmicSequence analysisAdd
BLAST

GO - Cellular componenti

  • cytoplasm Source: RGD
  • Golgi membrane Source: UniProtKB-SubCell
  • membrane Source: RGD
  • plasma membrane Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Golgi apparatus, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 655655Sphingomyelin phosphodiesterase 3PRO_0000075694Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Lipidationi53 – 531S-palmitoyl cysteineBy similarity
Lipidationi59 – 591S-palmitoyl cysteineBy similarity
Modified residuei178 – 1781PhosphoserineBy similarity
Modified residuei289 – 2891PhosphoserineCombined sources
Lipidationi395 – 3951S-palmitoyl cysteineBy similarity
Lipidationi396 – 3961S-palmitoyl cysteineBy similarity

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.
PhosphoSiteiO35049.

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 interaction.
STRINGi10116.ENSRNOP00000000274.

Structurei

3D structure databases

ProteinModelPortaliO35049.
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

Gene3Di3.60.10.10. 1 hit.
InterProiIPR005135. Endo/exonuclease/phosphatase.
[Graphical view]
PfamiPF03372. Exo_endo_phos. 1 hit.
[Graphical view]
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.

Cross-referencesi

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.

3D structure databases

ProteinModelPortaliO35049.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi250193. 1 interaction.
STRINGi10116.ENSRNOP00000000274.

PTM databases

iPTMnetiO35049.
PhosphoSiteiO35049.

Proteomic databases

PaxDbiO35049.
PRIDEiO35049.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi94338.
KEGGirno:94338.
UCSCiRGD:619754. rat.

Organism-specific databases

CTDi55512.
RGDi619754. Smpd3.

Phylogenomic databases

eggNOGiENOG410IEKS. Eukaryota.
ENOG41104QW. LUCA.
HOGENOMiHOG000049296.
HOVERGENiHBG079416.
InParanoidiO35049.
KOiK12352.
PhylomeDBiO35049.

Enzyme and pathway databases

UniPathwayiUPA00222.
SABIO-RKO35049.

Miscellaneous databases

PROiO35049.

Family and domain databases

Gene3Di3.60.10.10. 1 hit.
InterProiIPR005135. Endo/exonuclease/phosphatase.
[Graphical view]
PfamiPF03372. Exo_endo_phos. 1 hit.
[Graphical view]
SUPFAMiSSF56219. SSF56219. 2 hits.
ProtoNetiSearch...

Entry informationi

Entry nameiNSMA2_RAT
AccessioniPrimary (citable) accession number: O35049
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 30, 2005
Last sequence update: August 30, 2005
Last modified: September 7, 2016
This is version 102 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.