======= DLD ======= == Gene Information == * **Official Symbol**: DLD * **Official Name**: dihydrolipoamide dehydrogenase * **Aliases and Previous Symbols**: N/A * **Entrez ID**: [[https://www.ncbi.nlm.nih.gov/gene/?term=1738|1738]] * **UniProt**: [[https://www.uniprot.org/uniprot/P09622|P09622]] * **Interactions**: [[https://thebiogrid.org/search.php?search=DLD&organism=9606|BioGRID]] * **PubMed articles**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20DLD|Open PubMed]] * **OMIM**: [[https://omim.org/entry/238331|Open OMIM]] == Function Summary == * **Entrez Summary**: This gene encodes a member of the class-I pyridine nucleotide-disulfide oxidoreductase family. The encoded protein has been identified as a moonlighting protein based on its ability to perform mechanistically distinct functions. In homodimeric form, the encoded protein functions as a dehydrogenase and is found in several multi-enzyme complexes that regulate energy metabolism. However, as a monomer, this protein can function as a protease. Mutations in this gene have been identified in patients with E3-deficient maple syrup urine disease and lipoamide dehydrogenase deficiency. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2014]. * **UniProt Summary**: Lipoamide dehydrogenase is a component of the glycine cleavage system as well as an E3 component of three alpha-ketoacid dehydrogenase complexes (pyruvate-, alpha-ketoglutarate-, and branched-chain amino acid-dehydrogenase complex) (PubMed:15712224, PubMed:16442803, PubMed:16770810, PubMed:17404228, PubMed:20160912, PubMed:20385101). 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). In monomeric form may have additional moonlighting function as serine protease (PubMed:17404228). Involved in the hyperactivation of spermatazoa during capacitation and in the spermatazoal acrosome reaction (By similarity). {ECO:0000250|UniProtKB:Q811C4, ECO:0000269|PubMed:15712224, ECO:0000269|PubMed:16442803, ECO:0000269|PubMed:16770810, ECO:0000269|PubMed:17404228, ECO:0000269|PubMed:20160912, ECO:0000269|PubMed:20385101, ECO:0000269|PubMed:29211711}. |GIDA| |FAD binding 2| |Pyr redox dim| |FAD oxidored| |Pyr redox 2| |Pyr redox| |dihydrolipoyl dehydrogenase activity| |dihydrolipoamide metabolic process| |lipoamide binding| |lipoate metabolic process| |protein succinylation| |acrosomal matrix| |histone succinylation| |pyruvate dehydrogenase complex| |mitochondrial acetyl-CoA biosynthetic process from pyruvate| |oxoglutarate dehydrogenase complex| |pyruvate dehydrogenase (NAD+) activity| |acetyl-CoA biosynthetic process from pyruvate| |lysine catabolic process| |lysine metabolic process| |acetyl-CoA biosynthetic process| |2-oxoglutarate metabolic process| |branched-chain amino acid catabolic process| |branched-chain amino acid metabolic process| |aspartate family amino acid catabolic process| |sperm capacitation| |acetyl-CoA metabolic process| |tricarboxylic acid cycle| |NAD binding| |thioester biosynthetic process| |acyl-CoA biosynthetic process| |mitochondrial electron transport, NADH to ubiquinone| |aspartate family amino acid metabolic process| |flavin adenine dinucleotide binding| |nucleoside bisphosphate biosynthetic process| |ribonucleoside bisphosphate biosynthetic process| |purine nucleoside bisphosphate biosynthetic process| |pyruvate metabolic process| |cell redox homeostasis| |electron transfer activity| |aerobic respiration| |mitochondrial ATP synthesis coupled electron transport| |ATP synthesis coupled electron transport| |dicarboxylic acid metabolic process| |thioester metabolic process| |acyl-CoA metabolic process| |motile cilium| |alpha-amino acid catabolic process| |respiratory electron transport chain| |oxidative phosphorylation| |cellular amino acid catabolic process| |ribonucleoside bisphosphate metabolic process| |purine nucleoside bisphosphate metabolic process| |nucleoside bisphosphate metabolic process| |coenzyme biosynthetic process| |purine ribonucleotide biosynthetic process| |spermatid development| |purine nucleotide biosynthetic process| |spermatid differentiation| |cell maturation| |gastrulation| |ribonucleotide biosynthetic process| |cellular respiration| |ribose phosphate biosynthetic process| |purine-containing compound biosynthetic process| |electron transport chain| |sulfur compound biosynthetic process| |protein acylation| |ATP metabolic process| |alpha-amino acid metabolic process| |cofactor biosynthetic process| |energy derivation by oxidation of organic compounds| |developmental maturation| |nucleotide biosynthetic process| |nucleoside phosphate biosynthetic process| |coenzyme metabolic process| |germ cell development| |organic acid catabolic process| |carboxylic acid catabolic process| |aging| |cellular amino acid metabolic process| |purine ribonucleotide metabolic process| |fatty acid metabolic process| |ribonucleotide metabolic process| |purine nucleotide metabolic process| |ribose phosphate metabolic process| |cellular process involved in reproduction in multicellular organism| |sulfur compound metabolic process| |purine-containing compound metabolic process| |mitochondrial matrix| |generation of precursor metabolites and energy| |regulation of membrane potential| |small molecule catabolic process| |cofactor metabolic process| |nucleotide metabolic process| |nucleoside phosphate metabolic process| |amide biosynthetic process| |monocarboxylic acid metabolic process| |organophosphate biosynthetic process| |nucleobase-containing small molecule metabolic process| |spermatogenesis| |male gamete generation| |embryonic morphogenesis| |carbohydrate derivative biosynthetic process| |developmental process involved in reproduction| |gamete generation| |cellular amide metabolic process| |multicellular organismal reproductive process| |sexual reproduction| |multicellular organism reproduction| |organophosphate metabolic process| |cellular homeostasis| |carboxylic acid metabolic process| |cellular lipid metabolic process| |oxidation-reduction process| |embryo development| |multi-organism reproductive process| |oxoacid metabolic process| |organic acid metabolic process| |carbohydrate derivative metabolic process| |organonitrogen compound catabolic process| |nucleobase-containing compound biosynthetic process| |heterocycle biosynthetic process| |aromatic compound biosynthetic process| |lipid metabolic process| |mitochondrion| |proteolysis| |phosphorylation| |organic cyclic compound biosynthetic process| |organonitrogen compound biosynthetic process| |reproductive process| |reproduction| |cellular nitrogen compound biosynthetic process| |homeostatic process| |cell development| |small molecule metabolic process| |organic substance catabolic process| |cellular catabolic process| \\ === CRISPR Data === ^Screen^Score^ |[[:results:exp454|Bafilomycin-A1 0.009μM R08 exp454]]|-2.16| |[[:results:exp480|ETC-159 50μM R08 exp480]]|-2.12| |[[:results:exp431|Rotenone 0.07μM R08 exp431]]|-1.9| |[[:results:exp458|Bisphenol S 100μM R08 exp458]]|-1.75| |[[:results:exp512|Olaparib 4μM R08 exp512]]|-1.73| |[[:results:exp344|Chlorpromazine 10μM R07 exp344]]|1.72| |[[:results:exp342|Calcium Ionophore 0.4μM R07 exp342]]|1.73| |[[:results:exp85|UM0129480 7μM R02 exp85]]|1.73| |[[:results:exp7|Bortezomib 0.05μM R00 exp7]]|1.98| |[[:results:exp466|Cannabidiol 20μM R08 exp466]]|2| |[[:results:exp450|Artemisinin 50μM R08 exp450]]|2.69| |[[:results:exp116|AICAR 240μM R03 exp116]]|2.97| |[[:results:exp465|Cannabidiol 13μM R08 exp465]]|3.66| |[[:results:exp211|AICAR 240μM R05 exp211]]|4.99| ^Gene^Correlation^ |[[:human genes:s:slc25a19|SLC25A19]]|0.675| |[[:human genes:f:fdx1|FDX1]]|0.628| |[[:human genes:l:lipt1|LIPT1]]|0.579| |[[:human genes:l:lias|LIAS]]|0.576| |[[:human genes:i:isca2|ISCA2]]|0.48| |[[:human genes:a:adsl|ADSL]]|0.437| |[[:human genes:l:lipt2|LIPT2]]|0.431| |[[:human genes:t:tpk1|TPK1]]|0.428| |[[:human genes:r:rfk|RFK]]|0.427| Global Fraction of Cell Lines Where Essential: 6/726 ^Tissue^Fraction Of Cell Lines Where Essential^ |1290807.0|0/1| |909776.0|0/1| |bile duct|0/28| |blood|0/28| |bone|0/25| |breast|2/33| |central nervous system|1/56| |cervix|0/4| |colorectal|0/17| |esophagus|0/13| |fibroblast|0/1| |gastric|1/15| |kidney|1/21| |liver|0/20| |lung|0/75| |lymphocyte|0/14| |ovary|0/26| |pancreas|0/24| |peripheral nervous system|0/16| |plasma cell|0/15| |prostate|0/1| |skin|0/24| |soft tissue|0/7| |thyroid|0/2| |upper aerodigestive|0/22| |urinary tract|0/29| |uterus|0/5| == Essentiality in NALM6 == * **Essentiality Rank**: 240 * **Expression level (log2 read counts)**: 6.76 {{:chemogenomics:nalm6 dist.png?nolink |}}