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Literature summary for 3.5.1.23 extracted from

  • Sun, W.; Jin, J.; Xu, R.; Hu, W.; Szulc, Z.M.; Bielawski, J.; Obeid, L.M.; Mao, C.
    Substrate specificity, membrane topology, and activity regulation of human alkaline ceramidase 2 (ACER2) (2010), J. Biol. Chem., 285, 8995-9007.
    View publication on PubMedView publication on EuropePMC

Cloned(Commentary)

Cloned (Comment) Organism
expression of FLAG-tagged wild-type ACER2 and FLAG-tagged ACER2 mutants in Saccharomyces cerevisiae mutant cell microsomes, DELTAypc1 and DELTAydc1, that lack endogenous ceramidase activity Homo sapiens

Protein Variants

Protein Variants Comment Organism
additional information ACER2 mutant, ACER2DELTAN36, lacking the N-terminal tail, the first 36 amino acid residues, exhibits undetectable activity and is mislocalized to the endoplasmic reticulum. Overexpression of ACER2, ACER2DELTAN13, but not ACER2DELTAN36 increased the release of sphingosine 1-phosphate from cells, suggesting that its mislocalization does not affect the ability of ACER2 to regulate sphingosine 1-phosphate secretion. However, overexpression of ACER2 but not ACER2DELTAN13 or ACER2DELTAN36 inhibits the glycosylation of integrin beta1 subunit and Lamp1, suggesting that its mistargeting abolishes the ability of ACER2 to regulation protein glycosylation Homo sapiens

Inhibitors

Inhibitors Comment Organism Structure
Cu2+
-
Homo sapiens
additional information cellular ACER2 activity is inhibited by depletion of Ca2+ from Golgi lumen Homo sapiens
Zn2+
-
Homo sapiens

KM Value [mM]

KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
additional information
-
additional information ACER2 follows Michaelis-Menten kinetics Homo sapiens
0.0721
-
C20:1-ceramide pH 9.0, 37°C Homo sapiens
0.0773
-
C18:1-ceramide pH 9.0, 37°C Homo sapiens
0.0814
-
D-erythro-C24:1-ceramide pH 9.0, 37°C Homo sapiens
0.0915
-
C20:0-ceramide pH 9.0, 37°C Homo sapiens
0.0948
-
C18:0-ceramide pH 9.0, 37°C Homo sapiens
0.0985
-
C16:0-ceramide pH 9.0, 37°C Homo sapiens
0.1146
-
C14:0-ceramide pH 9.0, 37°C Homo sapiens
0.1338
-
C12:0-ceramide pH 9.0, 37°C Homo sapiens
0.1432
-
C24:0-ceramide pH 9.0, 37°C Homo sapiens
0.2242
-
C6:0-ceramide pH 9.0, 37°C Homo sapiens

Localization

Localization Comment Organism GeneOntology No. Textmining
Golgi membrane ACER2 has 7 putative transmembrane domains, ACER2 membrane topology, overview. The N-terminal tail is necessary for both ACER2 activity and Golgi localization Homo sapiens 139
-
microsome
-
Homo sapiens
-
-
additional information ACER2 C- and N-termini are oriented in the lumen of the Golgi complex and cytosol, respectively Homo sapiens
-
-

Metals/Ions

Metals/Ions Comment Organism Structure
Ca2+ activates, required by ACER2 for both its in vitro and cellular activities. Cellular ACER2 activity is inhibited by depletion of Ca2+ from Golgi lumen Homo sapiens
additional information Mg2+ and Mn2+ have no effect on ceramidase activity in ACER2 microsomes Homo sapiens

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
C12:0-ceramide + H2O Homo sapiens
-
laurate + sphingosine
-
?
C14:0-ceramide + H2O Homo sapiens
-
myristate + sphingosine
-
?
C16:0-ceramide + H2O Homo sapiens
-
palmitate + sphingosine
-
?
C18:0-ceramide + H2O Homo sapiens
-
stearate + sphingosine
-
?
C18:1-ceramide + H2O Homo sapiens
-
oleate + sphingosine
-
?
C20:0-ceramide + H2O Homo sapiens
-
eicosanoic acid + sphingosine
-
?
C20:1-ceramide + H2O Homo sapiens
-
C20:1 fatty acid + sphingosine
-
?
C24:0-ceramide + H2O Homo sapiens
-
C24:0 fatty acid + sphingosine
-
?
C6:0-ceramide + H2O Homo sapiens
-
hexanoate + sphingosine
-
?
D-erythro-C24:1-ceramide + H2O Homo sapiens
-
C24:1 fatty acid + D-erythro-sphingosine
-
?

Organism

Organism UniProt Comment Textmining
Homo sapiens
-
-
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
C12:0-ceramide + H2O
-
Homo sapiens laurate + sphingosine
-
?
C14:0-ceramide + H2O
-
Homo sapiens myristate + sphingosine
-
?
C16:0-ceramide + H2O
-
Homo sapiens palmitate + sphingosine
-
?
C18:0-ceramide + H2O
-
Homo sapiens stearate + sphingosine
-
?
C18:1-ceramide + H2O
-
Homo sapiens oleate + sphingosine
-
?
C20:0-ceramide + H2O
-
Homo sapiens eicosanoic acid + sphingosine
-
?
C20:1-ceramide + H2O
-
Homo sapiens C20:1 fatty acid + sphingosine
-
?
C24:0-ceramide + H2O
-
Homo sapiens C24:0 fatty acid + sphingosine
-
?
C24:1-ceramide + H2O
-
Homo sapiens C24:1 fatty acid + sphingosine
-
?
C6:0-ceramide + H2O
-
Homo sapiens hexanoate + sphingosine
-
?
D-erythro-C24:1-ceramide + H2O
-
Homo sapiens C24:1 fatty acid + D-erythro-sphingosine
-
?
additional information ACER2 shows a broader substrate specificity catalyzing the hydrolysis of various ceramides. The luminal ACER2 N-terminal tail, comprising 36 amino acid residues, is important for ACER2 activity, but the terminal 13 amino acid residues are not required for its activity Homo sapiens ?
-
?

Subunits

Subunits Comment Organism
More the luminal ACER2 N-terminal tail, comprising 36 amino acid residues, is important for ACER2 activity, but the terminal 13 amino acid residues are not required for its activity Homo sapiens

Synonyms

Synonyms Comment Organism
ACER2
-
Homo sapiens
alkaline ceramidase 2
-
Homo sapiens

Temperature Optimum [°C]

Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
37
-
assay at Homo sapiens

pH Optimum

pH Optimum Minimum pH Optimum Maximum Comment Organism
7.5 9
-
Homo sapiens

General Information

General Information Comment Organism
physiological function ACER2 plays an important role in cellular responses by regulating the hydrolysis of ceramides in cells, activity regulation, overview Homo sapiens