Gene Ontology annotation through association of InterPro records with GO terms
Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity
Annotation inferences using phylogenetic trees
Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara
Combined Automated Annotation using Multiple IEA Methods
Discovery and characterization of a second mammalian thiol dioxygenase, cysteamine dioxygenase.
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Identified ADO (mouse Gm237 / human C10orf22) as the mammalian cysteamine dioxygenase; recombinant ADO oxidizes cysteamine to hypotaurine and RNAi of human ADO in HepG2/C3A cells reduces hypotaurine production.
"When expressed as a recombinant protein, ADO exhibited significant cysteamine dioxygenase activity in vitro."
Architecture of the human interactome defines protein communities and disease networks.
Cofactor Biogenesis in Cysteamine Dioxygenase: C-F Bond Cleavage with Genetically Incorporated Unnatural Tyrosine.
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Human ADO contains an autocatalytically formed Cys220-Tyr222 thioether cross-linked cofactor; mutagenesis of Tyr222 (but not Tyr223) strongly reduces cysteamine dioxygenase activity.
"the discovery and elucidation of a Cys-Tyr cofactor in human ADO, crosslinked between Cys220 and Tyr222 through a thioether (C-S) bond."
Conserved N-terminal cysteine dioxygenases transduce responses to hypoxia in animals and plants.
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ADO is the animal N-terminal cysteine dioxygenase of the Cys/N-degron pathway: it dioxygenates the N-terminal cysteine of RGS4, RGS5 and IL-32 to cysteine sulfinic acid and is required for their oxygen-dependent degradation, acting as an enzymatic oxygen sensor with high apparent KmO2.
"Thus ADO is required for oxygen-dependent degradation of RGS proteins."
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Loss of ADO stabilizes RGS4/5 constitutively, independent of oxygen.
"Inactivation of ADO but not CDO1 led to constitutive upregulation of endogenous and transfected RGS4 and RGS5 proteins irrespective of oxygen levels"
A reference map of the human binary protein interactome.
Characterization of the nonheme iron center of cysteamine dioxygenase and its interaction with substrates.
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Spectroscopic characterization of the ferrous non-heme iron center of human and mouse ADO; both cysteamine and the N-terminal RGS5 peptide bind the iron through their free thiol in a monodentate mode.
"both the small molecule and the peptide substrates coordinate the iron center with their free thiols in a monodentate binding mode"
Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.
Crystal structure of human cysteamine dioxygenase provides a structural rationale for its function as an oxygen sensor.
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First crystal structure of human ADO (1.78 A, PDB 7REI); the metal center is octahedrally coordinated by three histidine residues (His112, His114, His193), and the loop-rich, open cavity rationalizes ADO handling both small-molecule and protein substrates as an oxygen sensor.
"metal ion octahedrally coordinated by three histidine residues"
Quantitative high-confidence human mitochondrial proteome and its dynamics in cellular context.
Ado-Mediated Depletion of Taurine Impairs Mitochondrial Respiratory Capacity and Alters the Chromatin Landscape of Inguinal Adipose Tissue.
ADO oxidises 2AET to HTAU
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Reactome models the cytosolic reaction in which ADO adds molecular oxygen to the sulfhydryl group of cysteamine to form hypotaurine, an essential step in hypotaurine/taurine biosynthesis.
"ADO adds molecular oxygen to the sulfhydryl group of 2-aminoethanethiol (2AET, cysteamine) to form the sulfinic acid hypotaurine (HTAU)"