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Literature summary extracted from

  • Dotson Ii, P.P.; Karakashian, A.A.; Nikolova-Karakashian, M.N.
    Neutral sphingomyelinase-2 is a redox sensitive enzyme: role of catalytic cysteine residues in regulation of enzymatic activity through changes in oligomeric state (2015), Biochem. J., 465, 371-382.
    View publication on PubMedView publication on EuropePMC

Activating Compound

EC Number Activating Compound Comment Organism Structure
3.1.4.12 2-mercaptoethanol activates in vivo by severalfold Mus musculus
3.1.4.12 DTT activates in vivo by severalfold Mus musculus
3.1.4.12 glutathione activates in vivo by severalfold Mus musculus
3.1.4.12 additional information the enzyme requires a hydrophobic environment for activity Mus musculus

Cloned(Commentary)

EC Number Cloned (Comment) Organism
3.1.4.12 gene SMPD3, expression of GFP-tagged and of N-terminally RFP-tagged enzyme in HEK-293-IL1R cells, recombinant expression of C-terminally FLAG-tagged enzyme and of enzyme-2-FLAG-6xHis construct in wildtype Escherichia coli strain Rosetta-gami2, and the mutated strain lacking endogenous thioredoxin, results in increased oligomer formation and lower enzyme activity, the phenotype can be rescued by with recombinant human thioredoxin Mus musculus

Protein Variants

EC Number Protein Variants Comment Organism
3.1.4.12 C617S site-directed mutagenesis, gain-of-function mutation associated with a decreased propensity for oligomerization Mus musculus

Inhibitors

EC Number Inhibitors Comment Organism Structure
3.1.4.12 deoxycholate inhibits almost 90% of the activity at 3 mM Mus musculus
3.1.4.12 Diamide
-
 Mus musculus
3.1.4.12 hydrogen peroxide
-
 Mus musculus
3.1.4.12 additional information oxidizing agents inhibit enzyme activity in a dose-dependent manner that correlates with hyperaggregation of the enzyme protein, which can be restored by immediate addition of DTT Mus musculus
3.1.4.12 oxidized glutathione
-
 Mus musculus
3.1.4.12 Triton X-100 inhibits almost 90% of the activity at 0.1% Mus musculus

Localization

EC Number Localization Comment Organism GeneOntology No. Textmining
3.1.4.12 membrane bound Mus musculus 16020
-

Metals/Ions

EC Number Metals/Ions Comment Organism Structure
3.1.4.12 Mg2+ required Mus musculus

Molecular Weight [Da]

EC Number Molecular Weight [Da] Molecular Weight Maximum [Da] Comment Organism
3.1.4.12 74000
-
 2 * 74000, SDS-PAGE Mus musculus
3.1.4.12 74000
-
 1 * 74000, SDS-PAGE Mus musculus
3.1.4.12 74000
-
 3 * 74000, SDS-PAGE Mus musculus

Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
3.1.4.12 a sphingomyelin + H2O Mus musculus
-
 a ceramide + phosphocholine a ceramide is an N-acylsphingosine ?

Organism

EC Number Organism UniProt Comment Textmining
3.1.4.12 Mus musculus Q9JJY3 gene SMPD3
-

Purification (Commentary)

EC Number Purification (Comment) Organism
3.1.4.12 recombinant enzyme-2-FLAG-6xHis construct from Escherichia coli by affinity chromatography Mus musculus

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
3.1.4.12 a sphingomyelin + H2O
-
 Mus musculus a ceramide + phosphocholine a ceramide is an N-acylsphingosine ?
3.1.4.12 a sphingomyelin + H2O 6-N-(7-N´nitro-benz-2-oxa-1,3-diazol-4-yl)aminosphingomyelin is used as substrate Mus musculus a ceramide + phosphocholine a ceramide is an N-acylsphingosine ?

Subunits

EC Number Subunits Comment Organism
3.1.4.12 dimer 2 * 74000, SDS-PAGE Mus musculus
3.1.4.12 monomer 1 * 74000, SDS-PAGE Mus musculus
3.1.4.12 More the enzyme exists as both monomers and multimers that are associated with high and low enzymatic activity, respectively. Several oxidant-sensitive cysteine residues of the C-terminal catalytic domain are involved in enzyme oligomerization, but cysteines in the non-catalytic region of the enzyme (i.e. amino acids 1 to 337), as well as Cys359, Cys392, Cys420, Cys425, and Cys457 in the beginning of the catalytic domain, do not participate in oligomerization. Thioredoxin-mediated reduction of enzyme multimers to monomers Mus musculus
3.1.4.12 trimer 3 * 74000, SDS-PAGE Mus musculus

Synonyms

EC Number Synonyms Comment Organism
3.1.4.12 neutral sphingomyelinase-2
-
 Mus musculus
3.1.4.12 nSMase
-
 Mus musculus
3.1.4.12 NSMase-2
-
 Mus musculus

Temperature Optimum [°C]

EC Number Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
3.1.4.12 37
-
 assay at Mus musculus

pH Optimum

EC Number pH Optimum Minimum pH Optimum Maximum Comment Organism
3.1.4.12 7.4
-
 assay at Mus musculus

General Information

EC Number General Information Comment Organism
3.1.4.12 additional information a redox sensitive enzyme Mus musculus
3.1.4.12 physiological function neutral sphingomyelinase-2 is the major sphingomyelinase activated in response to proinflammatory cytokines and during oxidative stress. The enzyme may be a novel substrate for thioredoxin Mus musculus