Dihydrolipoyllysine-residue succinyltransferase component of 2-oxoglutarate dehydrogenase complex, (DLST)
The protein contains 453 amino acids for an estimated molecular weight of 48755 Da.
Dihydrolipoamide succinyltransferase (E2) component of the 2-oxoglutarate dehydrogenase complex. The 2-oxoglutarate dehydrogenase complex catalyzes the overall conversion of 2-oxoglutarate to succinyl-CoA and CO(2). The 2-oxoglutarate dehydrogenase complex is mainly active in the mitochondrion (PubMed:29211711, PubMed:30929736). 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: Feb. 26, 2020)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- 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.
- Wilson and co-workers. (2016) Comparison of the Proteome of Adult and Cord Erythroid Cells, and Changes in the Proteome Following Reticulocyte Maturation. Mol Cell Proteomics. 15(6), 1938-1946.
- Chu and co-workers. (2018) Quantitative mass spectrometry of human reticulocytes reveal proteome-wide modifications during maturation. Br J Haematol. 180(1), 118-133.
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.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
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.
Biological Process
2-oxoglutarate metabolic process
Cellular metabolic process
Cellular nitrogen compound metabolic process
Generation of precursor metabolites and energy
Histone succinylation
L-lysine catabolic process to acetyl-CoA via saccharopine
Lysine catabolic process
Small molecule metabolic process
Succinyl-CoA metabolic process
Tricarboxylic acid cycle
Cellular Component
Centriolar satellite
Cytosol
Extracellular exosome
Membrane
Mitochondrial matrix
Mitochondrion
Myelin sheath
Nucleoplasm
Nucleus
Oxoglutarate dehydrogenase complex
Molecular Function
Acyltransferase activity
Dihydrolipoyllysine-residue succinyltransferase activity
The reference OMIM entry for this protein is 126063
Dihydrolipoamide s-succinyltransferase; dlst
Alpha-ketoglutarate dehydrogenase complex, e2 component of
CLONING
The alpha-keto acid dehydrogenase complexes (pyruvate dehydrogenase complex, alpha-ketoglutarate dehydrogenase complex, and branched chain alpha-keto acid dehydrogenase complex) are a family of multienzyme complexes. They are localized in mitochondria and catalyze the oxidative decarboxylation of alpha-keto acids. These 3 alpha-keto acid dehydrogenase complexes are composed of 3 different enzymes: alpha-keto acid dehydrogenase (E1; 300502), dihydrolipoamide acyltransferase (E2), and dihydrolipoamide dehydrogenase (E3; 238331). Dihydrolipoamide succinyltransferase, which is a component of the structural core of the alpha-keto glutarate dehydrogenase complex, was studied by Nakano et al. (1993), who isolated a cDNA from a human fibroblast cDNA library. Amino acid sequence analysis supported their previous observation (Nakano et al., 1993) that human dihydrolipoamide succinyltransferase lacks a sequence motif for an E1 and/or E3 binding site. By Northern blot analysis, Ali et al. (1994) detected ubiquitous expression of DLST in peripheral tissues and brain.GENE STRUCTURE
Nakano et al. (1993) found that the DLST gene contains 3 exons and 4 introns and that the nucleotide sequence at the 5-prime donor and 3-prime acceptor sites of all introns conformed to the gt-ag rule.GENE FUNCTION
DLST is the E2 component of the alpha-ketoglutarate dehydrogenase complex. In contrast to the E2 components of the other 2 alpha-keto acid dehydrogenase complexes, the pyruvate dehydrogenase complex (see 300502) and the branched-chain alpha-keto acid dehydrogenase complex (see 608348), the alpha-KGDC E2 has a unique structure consisting of 2 domains and lacking a sequence motif of an E3 and/or E1 binding site (Patel and Harris, 1995).MAPPING
By fluorescence in situ hybridization, Nakano et al. (1993) found that the DLST gene is located on 14q24.2-q24.3 and that a related sequence is located on 1p31. The gene for the dihydrolipoamide acyltransferase of the branched chain alpha-keto acid dehydrogenase complex (DBT; 248610), the site of the mutation in type 2 maple syrup urine disease (see 248600), is located on 1p31. Nakano et al. (1993) mentioned the possibility that mutation of the DLST gene may be a cause of familial Alzheimer disease that maps to 14q24.3 (AD3; 607822). Ali et al. (1994) mapped the DLST gene (symbolized by them KGDHC) to 14q24.3 by isotopic in situ hybridization. The cDNA they used also cross-hybridized to an apparent E2k pseudogene on 1p31. ... More on the omim web site
March 3, 2020: 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
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 126063 was added.