Gene Ontology annotation through association of InterPro records with GO terms
Annotation inferences using phylogenetic trees
Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping
Gene Ontology annotation based on curation of immunofluorescence data
Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara
Combined Automated Annotation using Multiple IEA Methods
Identification and functional characterization of a novel, tissue-specific NAD(+)-dependent isocitrate dehydrogenase beta subunit isoform.
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IDH3B exists as two isoforms (beta1 and beta2) due to alternative splicing
"the smaller beta(2) transcript (1.3 kilobases) is primarily expressed in heart and skeletal muscle, whereas the larger beta(1) mRNA (1.6 kilobases) is prevalent in nonmuscle tissues"
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Beta subunit alone has no detectable IDH activity
"subunits produced alone and betagamma showed no detectable activity"
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Alpha is the catalytic subunit
"These data suggest that the alpha is the catalytic subunit and that at least one of the other two subunits plays an essential supporting role for activity"
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Alphabeta and alphagamma dimers have IDH activity
"alphabetagamma, alphabeta, and alphagamma combinations exhibited significant amounts of IDH activity"
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Beta isoforms affect pH optimum of enzyme activity
"Substitution of beta(1) with beta(2) in the co-expression system lowered the pH optimum for IDH activity from 8.0 to 7.6"
Evaluation by mutagenesis of the importance of 3 arginines in alpha, beta, and gamma subunits of human NAD-dependent isocitrate dehydrogenase.
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IDH3 complex has 2alpha:1beta:1gamma stoichiometry with 315 kDa molecular mass
"Wild type (WT) and mutant enzymes ... were purified to homogeneity yielding enzymes with 2alpha:1beta:1gamma subunit composition and a native molecular mass of 315 kDa"
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Beta-R99Q mutant retains 64% of wild-type activity (14 vs 22 micromol NADH/min/mg)
"Specific activities of 22, 14, and 2 micromol of NADH/min/mg were measured, respectively, for WT, beta-R99Q, and gamma-R97Q enzymes"
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Beta-Arg99 is required for normal ADP activation but not essential for catalysis
"for beta-R99Q and gamma-R97Q enzymes, the Km for isocitrate is the same in the absence or presence of ADP, although all the enzymes bind ADP"
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Alpha-Arg88 is essential for catalysis (alpha-R88Q has no activity)
"mutant enzymes with normal beta and gamma subunits and alpha-R88Q mutant subunit has no detectable activity, demonstrating that ... alpha-Arg88 is essential for catalysis"
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Beta and gamma subunits have roles in nucleotide functions of the allosteric enzyme
"the beta and gamma subunits have roles in the nucleotide functions of this allosteric enzyme"
Molecular basis for the function of the αβ heterodimer of human NAD-dependent isocitrate dehydrogenase.
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Crystal structures of the human NAD-IDH αβ heterodimer determined in apo, Ca2+-bound, NAD-bound, and NADH-bound forms
"We report here the crystal structures of the αβ heterodimer of human NAD-IDH with the α subunit in apo form and in Ca2+-bound, NAD-bound, and NADH-bound forms"
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The active site is formed jointly by the α subunit large/small domains and the β subunit small domain
"The active site is located in the cleft formed by the large and small domains of the α subunit and the small domain of the β subunit"
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In the αβ heterodimer the active site has a distorted geometry unable to bind the metal ion productively
"the active site has a distorted geometry that is unable to bind the metal ion effectively or in a catalysis-relevant manner"
Structures of a constitutively active mutant of human IDH3 reveal new insights into the mechanisms of allosteric activation and the catalytic reaction.
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Human IDH3 functions as the (αβαγ)2 heterooctamer composed of α, β, and γ subunits
"It consists of three types of subunits (α, β, and γ) and exists and functions as the (αβαγ)2 heterooctamer"
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Structures provide the first pseudo-Michaelis complex of HsIDH3 identifying cofactor, substrate, and metal-ion binding residues
"the αQ139AICT+Ca+NADβNAD structure presents the first pseudo-Michaelis complex of HsIDH3, which allows us to identify the key residues involved in the binding of cofactor, substrate, and metal ion"
Proteomic characterization of the human sperm nucleus.
Quantitative high-confidence human mitochondrial proteome and its dynamics in cellular context.
IDH3 complex decarboxylates isocitrate
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IDH3 complex catalyzes isocitrate + NAD+ to alpha-ketoglutarate + CO2 + NADH in mitochondrial matrix
"Mitochondrial isocitrate dehydrogenase IDH3 catalyzes the irreversible reaction of isocitrate and NAD+ to form alpha-ketoglutarate, CO2, and NADH"
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Complex is heterooctamer with 2alpha:1beta:1gamma heterotetramer repeated twice plus Mn++
"The enzyme is a heterooctamer containing two copies of a heterotetramer of two IDH3A, one IDH3B, one IDH3G, and two Mn++"
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Activated by ADP, inhibited by NADH and high ATP
"It is activated by ADP (Soundar et al., 2003, 2006; Bzymek and Colman, 2007) and inhibited by NADH and high concentrations of ATP"
Deep research summary for IDH3B
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IDH3 complex has alpha2-beta-gamma stoichiometry where beta plays structural/regulatory role
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AlphaBeta dimer has ~16% of heterotetramer activity while AlphaGamma dimer has ~36%
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Allosteric regulation by citrate and ADP occurs through gamma subunit, not beta
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IDH3B required for spermiogenesis in mouse knockout studies
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Biallelic IDH3B variants cause retinitis pigmentosa 46