DLD [The Human Chemical-Genetic Interaction Map Project]

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======= DLD =======


== Gene Information ==
  * **<color #00a2e8>Official Symbol</color>**: DLD
  * **<color #00a2e8>Official Name</color>**: dihydrolipoamide dehydrogenase
  * **<color #00a2e8>Aliases and Previous Symbols</color>**: N/A
  * **<color #00a2e8>Entrez ID</color>**: [[https://www.ncbi.nlm.nih.gov/gene/?term=1738|1738]]
  * **<color #00a2e8>UniProt</color>**: [[https://www.uniprot.org/uniprot/P09622|P09622]]
  * **<color #00a2e8>Interactions</color>**: [[https://thebiogrid.org/search.php?search=DLD&organism=9606|BioGRID]]
  * **<color #00a2e8>PubMed articles</color>**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20DLD|Open PubMed]]
  * **<color #00a2e8>OMIM</color>**: [[https://omim.org/entry/238331|Open OMIM]]

== Function Summary ==
  * **<color #00a2e8>Entrez Summary</color>**:  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]. 
  * **<color #00a2e8>UniProt Summary</color>**:  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}.

<button type='primary' size='sm' modal='Pfam_Domains'>Pfam Domains</button>
<button type='primary' size='sm' modal='GO_terms'>GO Terms</button>


<modal id='Pfam_Domains' size='lg' title='Pfam Domains'>
|GIDA|
|FAD binding 2|
|Pyr redox dim|
|FAD oxidored|
|Pyr redox 2|
|Pyr redox|
</modal>

<modal id='GO_terms' size='lg' title='GO Terms'>
|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|
</modal>
\\

 === CRISPR Data ===
<button type='primary' size='small' modal='Compound_Hit'>Compound Hit</button>
<button type='primary' size='small' modal='Most_Correlated_Genes'>Most Correlated Genes in Chemogenomics</button>
<button type='primary' size='small' modal='Essential_Avana'>Tissues where Essential in the Avana Dataset (DepMap 20Q1)</button>

<modal id='Compound_Hit' size='lg' title='Compound Hit'>
^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|
</modal>

<modal id='Most_Correlated_Genes' size='lg' title='Most Correlated Genes in Chemogenomics'>
^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|
</modal>

<modal id='Essential_Avana' size='lg' title='Tissues where Essential in the Avana Dataset (DepMap 20Q1)'>
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|
</modal>

== Essentiality in NALM6  ==
    * **<color #00a2e8>Essentiality Rank</color>**: 240
    * **<color #00a2e8>Expression level (log2 read counts)</color>**: 6.76 
<button type='primary' size='small' modal='Dist_expr'>Expression Distribution</button>
<modal id='Dist_expr' size='lg' title='DLD Expression in NALM6 Cells: 6.76'>
{{:chemogenomics:nalm6 dist.png?nolink |}}
</modal>