Literature summary for 3.1.4.12 extracted from

Lee, C.Y.; Tamura, T.; Rabah, N.; Lee, D.Y.; Ruel, I.; Hafiane, A.; Iatan, I.; Nyholt, D.; Laporte, F.; Lazure, C.; Wada, I.; Krimbou, L.; Genest, J.
Carboxyl-terminal disulfide bond of acid sphingomyelinase is critical for its secretion and enzymatic function (2007), Biochemistry, 46, 14969-14978.

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Cloned(Commentary)

Cloned (Comment)	Organism
transient transfection of the His/V5-tagged wild-type and mutant recombinant ASM in CHO cells	Homo sapiens

Protein Variants

Protein Variants	Comment	Organism
G577A	naturally occuring mutation, the mutant has severely defective enzymatic function	Homo sapiens
additional information	DELTAR608 is a naturally occuring deletion mutation, construction of five serial carboxyl-terminal deletion mutants N620, N590, N570, N510, and N490, none of which, except the smallest deletion mutant N620 that preserves all post-translational modifications, are found capable of secretion to the medium, only the N620 deletion mutant conserves functional integrity with 100% wild type activity, all other mutants completely loose the ability to catalyze sphingomyelin hydrolysis, mutant DELTAR608 transfected CHO cells and fibroblasts from a compound heterozygous Niemann-Pick disease type B patient, DELTAR608 and R441X, have defective translocation to the plasma membrane, deletion mutants DELTAR608 and N590 are trapped in the endoplasmic reticulum quality control checkpoint in contrast to the wild-type lysosomal localization, steady-state levels of ubiquitination are minimal for the wild-type ASM, a significant amount of Lys63-linked polyubiquitinated DELTAR608 and N590 can be purified by S5a-affinity chromatography, indicating an important misfolding in the carboxyl-terminal mutants	Homo sapiens
R496L	naturally occuring mutation, the mutant has severely defective enzymatic function	Homo sapiens
Y537H	naturally occuring mutation, the mutant has severely defective enzymatic function	Homo sapiens

Localization

Localization	Comment	Organism	GeneOntology No.	Textmining
extracellular	ASM is a secretory protein	Homo sapiens	-	-
lysosome	ASM is a secretory protein	Homo sapiens	5764	-

Molecular Weight [Da]

Molecular Weight [Da]	Molecular Weight Maximum [Da]	Comment	Organism
70000	-	x * 70000	Homo sapiens

Natural Substrates/ Products (Substrates)

Natural Substrates	Organism	Comment (Nat. Sub.)	Natural Products	Comment (Nat. Pro.)	Rev.	Reac.
sphingomyelin + H2O	Homo sapiens	degradation of sphingomyelin	N-acylsphingosine + choline phosphate	-	?

Organism

Organism	UniProt	Comment	Textmining
Homo sapiens	-	acid sphingomyelinase, gene SMPD-1	-

Posttranslational Modification

Posttranslational Modification	Comment	Organism
additional information	steady-state levels of ubiquitination are minimal for the wild-type ASM	Homo sapiens

Specific Activity [micromol/min/mg]

Specific Activity Minimum [µmol/min/mg]	Specific Activity Maximum [µmol/min/mg]	Comment	Organism
additional information	-	activity of wild-type and mutant enzymes, overview	Homo sapiens

Substrates and Products (Substrate)

Substrates	Comment Substrates	Organism	Products	Comment (Products)	Rev.	Reac.
additional information	structural-functional properties of its carboxyl-terminus, amino acids 462-629, the carboxyl-terminus of the ASM is crucial for its protein structure, which in turns dictates the enzymatic function and secretion, overview	Homo sapiens	?	-	?
sphingomyelin + H2O	-	Homo sapiens	N-acylsphingosine + choline phosphate	-	?
sphingomyelin + H2O	degradation of sphingomyelin	Homo sapiens	N-acylsphingosine + choline phosphate	-	?

Subunits

Subunits	Comment	Organism
?	x * 70000	Homo sapiens
More	structural-functional properties of its carboxyl-terminus, amino acids 462-629, overview, ASM consists of a signal peptide, amino acids 1-46, in the N-terminal region, a small transmembrane domain, amino acids 25-47, a saposin B region, amino acids 87-165, that serves as an activator of various lysosomal lipid-degrading enzymes, a proline-rich region, amino acids 179-197, followed by the metallophosphoesterase catalytic domain, amino acids 199-461	Homo sapiens

Synonyms

Synonyms	Comment	Organism
acid sphingomyelinase	-	Homo sapiens
ASM	-	Homo sapiens
SMPD-1	-	Homo sapiens
sphingomyelin phosphodiesterase 1	-	Homo sapiens

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Release 2023.1 (January 2023)