Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity
Annotation inferences using phylogenetic trees
Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword mapping
Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt
Electronic Gene Ontology annotations created by ARBA machine learning models
Combined Automated Annotation using Multiple IEA Methods
Molecular cloning and characterization of a human mitochondrial ceramidase.
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Cloning and initial characterization of human ASAH2
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Demonstrated ceramidase activity at neutral-alkaline pH
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Reported mitochondrial localization (later disputed)
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Showed ubiquitous expression with higher levels in kidney, skeletal muscle, heart
Biochemical characterization of the reverse activity of rat brain ceramidase. A CoA-independent and fumonisin B1-insensitive ceramide synthase.
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ASAH2 catalyzes reverse reaction synthesizing ceramide from sphingosine and fatty acids
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CoA-independent ceramide synthase activity
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Not inhibited by fumonisin B1
Roles for C16-ceramide and sphingosine 1-phosphate in regulating hepatocyte apoptosis in response to tumor necrosis factor-alpha.
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ASAH2 overexpression protects hepatocytes from TNF-alpha-induced apoptosis
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Protection via ceramide reduction and S1P/AKT activation
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Demonstrates ceramide/S1P rheostat in apoptosis regulation
Identification of a novel amidase motif in neutral ceramidase.
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Identified novel amidase motif with critical Ser354 residue
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Characterized kinetic parameters at pH 7.5
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Identified conserved catalytic residues through mutagenesis
Purification and characterization of human intestinal neutral ceramidase.
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Purified ASAH2 from human ileostomy content
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Confirmed both hydrolytic and synthetic activities
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Demonstrated major role in ceramide metabolism in human gut
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Inhibited by Cu2+, Zn2+, and cholesterol
Downregulation of neutral ceramidase by gemcitabine: Implications for cell cycle regulation.
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ASAH2 knockdown causes cell cycle arrest at G0/G1
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ASAH2 loss leads to ceramide accumulation
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Demonstrates link between ceramide levels and cell cycle
Low-dose cytokine-induced neutral ceramidase secretion from INS-1 cells via exosomes and its anti-apoptotic effect.
Structural Basis for Ceramide Recognition and Hydrolysis by Human Neutral Ceramidase.
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2.6 Angstrom crystal structure of human ASAH2
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Revealed 20 Angstrom deep hydrophobic active site pocket
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Zn2+-dependent amidase mechanism
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Explained ceramide specificity via headgroup recognition
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Identified Ca2+ binding sites
Functions of neutral ceramidase in the Golgi apparatus.
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ASAH2 localized to both plasma membrane and Golgi
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Golgi ASAH2 metabolizes ceramide and protects from C6-ceramide-induced cell death
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Compartmentalized sphingolipid metabolism
Deep research report on ASAH2