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 Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt
Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara
Combined Automated Annotation using Multiple IEA Methods
Lysine degradation through the saccharopine pathway in mammals: involvement of both bifunctional and monofunctional lysine-degrading enzymes in mouse.
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Characterizes a mammalian (mouse) bifunctional lysine-oxoglutarate reductase/saccharopine dehydrogenase and infers mitochondrial localization; also reports starvation induction.
"the bifunctional enzyme is likely to be a mitochondrial protein."
Identification of the alpha-aminoadipic semialdehyde synthase gene, which is defective in familial hyperlysinemia.
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Identifies human AASS as a bifunctional enzyme (N-terminal LKR ~ yeast LYS1, C-terminal SDH ~ yeast LYS9) catalyzing the first two steps of lysine degradation; inactivating mutations cause hyperlysinemia.
"we propose that AASS catalyzes the first two steps of the major lysine-degradation pathway in human cells and that inactivating mutations in the AASS gene are a cause of hyperlysinemia."
Quantitative high-confidence human mitochondrial proteome and its dynamics in cellular context.
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Human AASS is included in MitoCoP: Supplementary Table S1, sheet (B) MitoCoP (1,134 genes), row 5 lists Q9UDR5, AASS, protein group 11286 and MitoCoP=1.
"mitochondrial high-confidence proteome of >1,100 proteins (MitoCoP)"
Familial hyperlysinemia: enzyme studies, diagnostic methods, comments on terminology.
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Human patient fibroblasts show combined deficiency of lysine-ketoglutarate reductase and saccharopine dehydrogenase; liver purification did not separate the reported activities. The abstract does not independently demonstrate subcellular localization or a single polypeptide.
"In all instances there was a deficiency in lysine-ketoglutarate reductase, saccharopine dehydrogenase, and saccharopine oxidoreductase activities."
lysine + alpha-ketoglutarate +NADPH + H+ => saccharopine + NADP+ + H2O
saccharopine + NAD+ + H2O => alpha-aminoadipic semialdehyde + glutamate + NADH + H+
Characterization and structure of the human lysine-2-oxoglutarate reductase domain, a novel therapeutic target for treatment of glutaric aciduria type 1.
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Human LOR uses NADPH, and both full-length AASS and isolated LOR show a slower reverse reaction in vitro.
"Another important difference between LYS1 and LOR is that the human protein evolved to use NADPH while yeast uses NADH."
dLKR/SDH regulates hormone-mediated histone arginine methylation and transcription of cell death genes.
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Fly dLKR/SDH binds histones and represses ecdysone-responsive transcription independently of its metabolic catalytic activity.
"dLKR/SDH binds histones H3 and H4 and suppresses ecdysone-mediated transcription of cell death genes by inhibiting histone H3R17me2 mediated by the Drosophila arginine methyl transferase CARMER."
The lysine catabolite saccharopine impairs development by disrupting mitochondrial homeostasis.
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Selective SDH defects cause saccharopine accumulation, mitochondrial damage and developmental toxicity in worm and mouse models; an LKR defect has a different phenotype.
"Aass(R65Q) homozygous mice were viable and developmentally indistinguishable from WT; in contrast, Aass(G489E) homozygous mice displayed progressive postnatal growth retardation and succumbed to death at ∼6 wk of age (Fig. 6, A–C)."
Genetic basis of hyperlysinemia.
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Human AASS variants establish hyperlysinemia; severe neurological findings in two patients with a contiguous AASS/PTPRZ1 deletion may reflect the additional gene loss.
"As hyperlysinemia is generally considered a benign metabolic variant, the more severe neurological disease course in two patients with a contiguous deletion syndrome may be explained by the additional loss of PTPRZ1."
Familial hyperlysinemias. Purification and characterization of the bifunctional aminoadipic semialdehyde synthase with lysine-ketoglutarate reductase and saccharopine dehydrogenase activities.
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Co-purified mammalian reductase and dehydrogenase activities support a bifunctional, likely tetrameric enzyme; the purified material was baboon and bovine liver.
"The native enzyme from baboon and bovine livers has an apparent Mr of 468,000 (Stokes radius = 69.5 A) as determined by gel filtration, which suggests a tetrameric structure of identical subunits."
Alpha-aminoadipate delta-semialdehyde synthase mRNA knockdown reduces the lysine requirement of a mouse hepatic cell line.
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Aass knockdown in a mouse hepatic cell line reduces LKR activity and lysine catabolism.
"These results indicate AASS knockdown decreases the lysine requirement of the cell via a reduction of lysine catabolism through the saccharopine pathway"
The Metabolite Saccharopine Impairs Neuronal Development by Inhibiting the Neurotrophic Function of Glucose-6-Phosphate Isomerase.
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Mouse selective SDH impairment causes cerebral saccharopine accumulation and altered neuronal development, unlike the tested LKR mutant.
"the accumulated saccharopine, but not lysine, leads to impaired neuronal development by inhibiting the neurotrophic effect of glucose-6-phosphate isomerase (GPI)."
A case of hyperlysinemia identified by urine newborn screening.
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A screened child with biallelic AASS variants was doing well at 11 months; this limited observation supports a mild biochemical phenotype without establishing long-term penetrance.
"The 11-month-old boy is currently doing well without any therapeutic interventions."
Structural and biochemical insight into allosteric regulation of the human 2-aminoadipic semialdehyde synthase, a bifunctional enzyme involved in lysine catabolism.
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A 2026 preprint reports full-length human AASS structural organization and in vitro allosteric regulation; the physiological regulatory significance remains provisional.
"connected by a long alpha-helix group and flexible loops to a core LOR tetramer."
UniProt record for human AASS (Q9UDR5)
Falcon deep research on human AASS