2-oxoglutarate dehydrogenase, mitochondrial (OGDH)

The protein contains 1023 amino acids for an estimated molecular weight of 115935 Da.

 

2-oxoglutarate dehydrogenase (E1) component of the 2-oxoglutarate dehydrogenase complex (OGDHC), which mediates the decarboxylation of alpha-ketoglutarate (PubMed:24495017). The 2-oxoglutarate dehydrogenase complex catalyzes the overall conversion of 2-oxoglutarate to succinyl-CoA and CO(2) (PubMed:24495017). The 2-oxoglutarate dehydrogenase complex is 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). (updated: April 7, 2021)

Protein identification was indicated in the following studies:

  1. Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
  2. Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
  3. Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.

Methods

The following articles were analysed to gather the proteome content of erythrocytes.

The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.

PublicationIdentification 1Uniprot mapping 2Not mapped /
Obsolete
TrEMBLSwiss-Prot
Goodman (2013)2289 (gene list)227853205992269
Lange (2014)123412347281224
Hegedus (2015)2638262202352387
Wilson (2016)165815281702911068
d'Alessandro (2017)18261817201815
Bryk (2017)20902060101081942
Chu (2018)18531804553621387

1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry

The compilation of older studies can be retrieved from the Red Blood Cell Collection database.

The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.

No sequence conservation computed yet.

Interpro domains
Total structural coverage: 96%
Model score: 41

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VariantDescription
dbSNP:rs2070607

The reference OMIM entry for this protein is 613022

Oxoglutarate dehydrogenase; ogdh
Alpha-ketoglutarate dehydrogenase; akgdh
E1k

DESCRIPTION

The alpha-ketoglutarate dehydrogenase complex is a multienzyme complex consisting of 3 protein subunits, oxoglutarate dehydrogenase, also known as alpha-ketoglutarate dehydrogenase or E1k (EC 1.2.4.2.), dihydrolipoyl succinyltransferase (DLST, or E2k; 126063), and dihydrolipoyl dehydrogenase (DLD, or E3; 238331). The complex catalyzes a key reaction in the Krebs tricarboxylic acid cycle (summary by Szabo et al., 1994).

CLONING

Koike et al. (1992) cloned a human OGDH cDNA from a fetal liver cDNA library. The ORF encodes a presequence of 40 amino acids and a mature protein of 963 amino acids with a molecular mass of 108,642 daltons. It is located in mitochondria within the inner membrane/matrix compartment.

GENE STRUCTURE

Koike (1995) found that the human OGDH gene contains 22 exons spanning approximately 85 kb. All exon/intron splice junctions follow the GT/AG rule. Primary extension analysis showed that the OGDH transcription start point is a thymine residue 55 bp upstream from the ATG start codon. The 5-prime-flanking region lacked canonical TATA or CAAT boxes.

MAPPING

Using 2 human/rodent somatic cell hybrid panels, Szabo et al. (1994) mapped the OGDH gene to 7p13-p11.2. A second related sequence, possibly a pseudogene, was identified and mapped to chromosome 10. Using DNAs from human/rodent somatic cell hybrids in conjunction with fluorescence in situ hybridization, Koike (1995) assigned the OGDH gene to the boundary between bands 7p13 and 7p14.

GENE FUNCTION

Oxoglutarate dehydrogenase is a component of the enzyme complex that catalyzes the conversion of 2-oxoglutarate to succinyl coenzyme A (Koike et al., 1992). Szabo et al. (1994) pointed to a possible significance to the finding of a reduction in the activity of this complex in Alzheimer disease brain and cultured skin fibroblasts from Alzheimer disease patients. See 203740 for a discussion of alpha-ketoglutarate dehydrogenase deficiency. ... More on the omim web site

Subscribe to this protein entry history

April 10, 2021: Protein entry updated
Automatic update: Entry updated from uniprot information.

April 12, 2018: Protein entry updated
Automatic update: Entry updated from uniprot information.

Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated

Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated

Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated

June 20, 2017: Protein entry updated
Automatic update: comparative model was added.

March 15, 2016: Protein entry updated
Automatic update: OMIM entry 613022 was added.

Jan. 24, 2016: Protein entry updated
Automatic update: model status changed