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Details on Person UniProt:Q02218 OGDH

Class:IdReferenceGeneProduct:60868
_chainChangeLogtransit peptide:1-40 added on Fri February 6 2015;chain:41-1023 added on Fri February 6 2015
_displayNameUniProt:Q02218 OGDH
_timestamp2026-02-20 23:08:47
chaintransit peptide:1-40
chain:41-1023
checksumF428DD342F232E7C
commentFUNCTION 2-oxoglutarate dehydrogenase (E1o) component of the 2-oxoglutarate dehydrogenase complex (OGDHC) (PubMed:24495017, PubMed:25210035, PubMed:28435050). Participates in the first step, rate limiting for the overall conversion of 2-oxoglutarate to succinyl-CoA and CO(2) catalyzed by the whole OGDHC (PubMed:24495017, PubMed:25210035, PubMed:28435050). Catalyzes the irreversible decarboxylation of 2-oxoglutarate (alpha-ketoglutarate) via the thiamine diphosphate (ThDP) cofactor and subsequent transfer of the decarboxylated acyl intermediate on an oxidized dihydrolipoyl group that is covalently amidated to the E2 enzyme (dihydrolipoyllysine-residue succinyltransferase or DLST) (PubMed:24495017, PubMed:25210035, PubMed:28435050, PubMed:35272141). Plays a key role in the Krebs (citric acid) cycle, which is a common pathway for oxidation of fuel molecules, including carbohydrates, fatty acids, and amino acids (PubMed:25210035). Can catalyze the decarboxylation of 2-oxoadipate in vitro, but at a much lower rate than 2-oxoglutarate (PubMed:28435050). Can also convert 2-keto-4-hydroxyglutarate (KHG) and CoA into malyl-CoA (By similarity). Mainly active in the mitochondrion (PubMed:29211711). A fraction of the 2-oxoglutarate dehydrogenase complex also localizes in the nucleus and is required for lysine succinylation of histones: associates with KAT2A on chromatin and provides succinyl-CoA to histone succinyltransferase KAT2A (PubMed:29211711).CATALYTIC ACTIVITY N(6)-[(R)-lipoyl]-L-lysyl-[protein] + 2-oxoglutarate + H(+) = N(6)-[(R)-S(8)-succinyldihydrolipoyl]-L-lysyl-[protein] + CO2COFACTOR Calcium ions and ADP stimulate, whereas ATP and NADH reduce catalytic activity.BIOPHYSICOCHEMICAL PROPERTIES Optimum temperature is 37 degrees Celsius. Activity decreases with increasing temperature.SUBUNIT Homodimer (PubMed:35272141). The 2-oxoglutarate dehydrogenase complex is composed of OGDH (2-oxoglutarate dehydrogenase; E1), DLST (dihydrolipoamide succinyltransferase; E2), DLD (dihydrolipoamide dehydrogenase; E3), and the assembly factor KGD4 (By similarity). It contains multiple copies of the three enzymatic components (E1, E2 and E3). In the nucleus, the 2-oxoglutarate dehydrogenase complex associates with KAT2A (PubMed:29211711). Interacts with ABHD11; this interaction maintains the functional lipoylation of the 2-oxoglutarate dehydrogenase complex (PubMed:32792488).INTERACTION Mainly localizes in the mitochondrion. A small fraction localizes to the nucleus, where the 2-oxoglutarate dehydrogenase complex is required for histone succinylation.ALTERNATIVE PRODUCTS Probably insensitive to calcium.MISCELLANEOUS The mitochondrial 2-oxoglutarate and 2-oxoadipate dehydrogenase complexes (OGDHC and OADHC, respectively) share their E2 (DLST) and E3 (dihydrolipoyl dehydrogenase or DLD) components, but the E1 component is specific to each complex (E1o and E1a (DHTK1), respectively).SIMILARITY Belongs to the alpha-ketoglutarate dehydrogenase family.SEQUENCE CAUTION Alpha-ketoglutarate dehydrogenase entry
descriptionrecommendedName: fullName evidence="17"2-oxoglutarate dehydrogenase complex component E1 shortName: E1o shortName evidence="16"HsOGDH shortName: OGDC-E1 shortName: OGDH-E1 ecNumber evidence="7 8 9 10 12"1.2.4.2 alternativeName: 2-oxoglutarate dehydrogenase, mitochondrial alternativeName: Alpha-ketoglutarate dehydrogenase shortName: Alpha-KGDH-E1 alternativeName: Thiamine diphosphate (ThDP)-dependent 2-oxoglutarate dehydrogenase
geneNameOGDH
identifierQ02218
isSequenceChangedFALSE
keyword3D-structure
Acetylation
Alternative splicing
Calcium
Glycolysis
Isopeptide bond
Magnesium
Metal-binding
Mitochondrion
Nucleus
Oxidoreductase
Phosphoprotein
Proteomics identification
Reference proteome
Thiamine pyrophosphate
Transit peptide
Ubl conjugation
modified[InstanceEdit:9836292] Weiser, Joel, 2023-05-25
[InstanceEdit:9852000] Weiser, Joel, 2023-11-03
[InstanceEdit:9862192] Weiser, Joel, 2024-02-26
[InstanceEdit:9926675] Weiser, Joel, 2024-11-03
[InstanceEdit:9939033] Weiser, Joel, 2025-02-21
[InstanceEdit:9948485] Weiser, Joel, 2025-05-21
[InstanceEdit:9983091] Weiser, Joel, 2026-02-20
nameOGDH
referenceDatabase[ReferenceDatabase:2] UniProt
referenceGene[ReferenceDNASequence:8993194] ENSEMBL:ENSG00000105953 OGDH [Homo sapiens]
secondaryIdentifierODO1_HUMAN
B4E2U9
D3DVL0
E9PBM1
Q96DD3
Q9UDX0
sequenceLength1023
species[Species:48887] Homo sapiens
(isoformParent)[ReferenceIsoform:8977125] UniProt:Q02218-1 OGDH [Homo sapiens]
[ReferenceIsoform:8977126] UniProt:Q02218-2 OGDH [Homo sapiens]
[ReferenceIsoform:8977127] UniProt:Q02218-3 OGDH [Homo sapiens]
(referenceEntity)[EntityWithAccessionedSequence:69981] OGDH [mitochondrial matrix] [Homo sapiens]
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