DLD
entrez
1738
canonical
uniprot
P09622
canonical
ensembl
ENSG00000091140
resolver
ensp
ENSP00000205402
resolver
ensp
ENSP00000387542
resolver
ensp
ENSP00000417016
resolver
ensp
ENSP00000627382
resolver
enst
ENST00000440410
resolver
genesymbol
DLD
resolver
genesymbol_syn
GCSL
resolver
genesymbol_syn
LAD
resolver
genesymbol_syn
PHE3
resolver
hgnc
HGNC:2898
resolver
uniprot
A0A024R713
resolver
uniprot
B2R5X0
resolver
uniprot
B4DHG0
resolver
uniprot
B4DT69
resolver
uniprot
E9PEX6
resolver
uniprot
Q14131
resolver
uniprot
Q14167
resolver
uniprot
Q59EV8
resolver
uniprot
Q8WTS4
resolver
uniprot_entry
A0A024R713_HUMAN
resolver
uniprot_entry
DLDH_HUMAN
resolver
uniprot_entry
E9PEX6_HUMAN
resolver
uniprot_sec
B2R5X0
resolver
uniprot_sec
B4DHG0
resolver
uniprot_sec
B4DT69
resolver
uniprot_sec
Q14131
resolver
uniprot_sec
Q14167
resolver
uniprot_sec
Q59EV8
resolver
uniprot_sec
Q8WTS4
resolver
activity_regulation
ACTIVITY REGULATION: Disruption of native heterodimer state inhibits primary dihydrolipoamide dehydrogenase activity and induces serine protease activity. {ECO:0000269|PubMed:17404228}.
uniprot
proteins
amino_acid_sequence
MQSWSRVYCSLAKRGHFNRISHGLQGLSAVPLRTYADQPIDADVTVIGSGPGGYVAAIKAAQLGFKTVCIEKNETLGGTCLNVGCIPSKALLNNSHYYHMAHGKDFASRGIEMSEVRLNLDKMMEQKSTAVKALTGGIAHLFKQNKVVHVNGYGKITGKNQVTATKADGGTQVIDTKNILIATGSEVTPFPGITIDEDTIVSSTGALSLKKVPEKMVVIGAGVIGVELGSVWQRLGADVTAVEFLGHVGGVGIDMEISKNFQRILQKQGFKFKLNTKVTGATKKSDGKIDVSIEAASGGKAEVITCDVLLVCIGRRPFTKNLGLEELGIELDPRGRIPVNTRFQTKIPNIYAIGDVVAGPMLAHKAEDEGIICVEGMAGGAVHIDYNCVPSVIYTHPEVAWVGKSEEQLKEEGIEYKVGKFPFAANSRAKTNADTDGMVKILGQKSTDRVLGAHILGPGAGEMVNEAALALEYGASCEDIARVCHAHPTLSEAFREANLAASFGKSINF
uniprot
proteins
disease_involvement
DISEASE: Dihydrolipoamide dehydrogenase deficiency (DLDD) [MIM:246900]: An autosomal recessive metabolic disorder characterized biochemically by a combined deficiency of the branched-chain alpha-keto acid dehydrogenase complex (BCKDC), pyruvate dehydrogenase complex (PDC), and alpha-ketoglutarate dehydrogenase complex (KGDC). Clinically, affected individuals have lactic acidosis and neurologic deterioration due to sensitivity of the central nervous system to defects in oxidative metabolism. {ECO:0000269|PubMed:10448086, ECO:0000269|PubMed:11687750, ECO:0000269|PubMed:12925875, ECO:0000269|PubMed:15712224, ECO:0000269|PubMed:16442803, ECO:0000269|PubMed:16770810, ECO:0000269|PubMed:17404228, ECO:0000269|PubMed:20160912, ECO:0000269|PubMed:8506365, ECO:0000269|PubMed:8968745, ECO:0000269|PubMed:9540846, ECO:0000269|PubMed:9934985}. Note=The disease is caused by variants affecting the gene represented in this entry.
uniprot
proteins
ec_number
1.8.1.4
uniprot
proteins
function
FUNCTION: 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). The pyruvate dehydrogenase (PDH) complex catalyzes the overall conversion of pyruvate to acetyl-CoA and CO(2), and thereby links cytoplasmic glycolysis and the mitochondrial tricarboxylic acid (TCA) cycle (Probable). It contains multiple copies of three enzymatic components: pyruvate dehydrogenase (E1), dihydrolipoamide acetyltransferase (E2) and dihydrolipoamide dehydrogenase (E3) (Probable). The E3 subunit catalyzes reoxidation of the dihydrolipoyl moiety on lipoyl-bearing domains (LBDs) of E2 with NAD+ as the ultimate electron acceptor (PubMed:16442803, PubMed:16770810, PubMed:20160912, PubMed:20385101). {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, ECO:0000305|PubMed:14638692}.
uniprot
proteins
mass_dalton
54177
uniprot
proteins
mutagenesis
MUTAGEN 89; /note="K->E: Abolishes dihydrolipoyl dehydrogenase activity. Does not affect interaction with PDHX."; /evidence="ECO:0000269|PubMed:20160912"; MUTAGEN 383; /note="H->A: Reduces dihydrolipoyl dehydrogenase activity."; /evidence="ECO:0000269|PubMed:20385101"; MUTAGEN 383; /note="H->L: Reduces dihydrolipoyl dehydrogenase activity."; /evidence="ECO:0000269|PubMed:20385101"; MUTAGEN 448; /note="D->A: Reduces interaction with PDHX. Inhibits multienzyme pyruvate dehydrogenase complex activity. Does not affect dihydrolipoyl dehydrogenase activity."; /evidence="ECO:0000269|PubMed:20385101"; MUTAGEN 448; /note="D->N: Does not affect dihydrolipoyl dehydrogenase activity."; /evidence="ECO:0000269|PubMed:20385101"; MUTAGEN 466; /note="E->A: Decreases dehydrogenase activity. Loss of proteolytic activity."; /evidence="ECO:0000269|PubMed:17404228"; MUTAGEN 473; /note="Y->A: Reduces interaction with PDHX. Inhibits multienzyme pyruvate dehydrogenase complex activity. Does not affect dihydrolipoyl dehydrogenase activity."; /evidence="ECO:0000269|PubMed:20385101"; MUTAGEN 473; /note="Y->F: Does not affect dihydrolipoyl dehydrogenase activity."; /evidence="ECO:0000269|PubMed:20385101"; MUTAGEN 473; /note="Y->H: Reduces interaction with PDHX. Inhibits multienzyme pyruvate dehydrogenase complex activity. Does not affect dihydrolipoyl dehydrogenase activity."; /evidence="ECO:0000269|PubMed:20385101"; MUTAGEN 482; /note="R->A: Does not affect dihydrolipoyl dehydrogenase activity."; /evidence="ECO:0000269|PubMed:20385101"; MUTAGEN 482; /note="R->M: Does not affect interaction with PDHX."; /evidence="ECO:0000269|PubMed:20160912"; MUTAGEN 485; /note="H->A: Loss of dehydrogenase activity. Increases proteolytic activity."; /evidence="ECO:0000269|PubMed:17404228"; MUTAGEN 491; /note="S->A: Loss of proteolytic activity. Does not affect dehydrogenase activity."; /evidence="ECO:0000269|PubMed:17404228"; MUTAGEN 492; /note="E->Q: Reduces dihydrolipoyl dehydrogenase activity. Does not affect interaction with PDHX."; /evidence="ECO:0000269|PubMed:20160912"; MUTAGEN 505; /note="K->M: Reduces dihydrolipoyl dehydrogenase activity. Does not affect interaction with PDHX."; /evidence="ECO:0000269|PubMed:20160912
uniprot
proteins
post_translational_modification
PTM: Tyrosine phosphorylated. {ECO:0000250|UniProtKB:Q811C4}.
uniprot
proteins
protein_family
Class-I pyridine nucleotide-disulfide oxidoreductase family
uniprot
proteins
pubmed
10448086
uniprot
proteins
pubmed
11687750
uniprot
proteins
pubmed
12690205
uniprot
proteins
pubmed
12853948
uniprot
proteins
pubmed
12925875
uniprot
proteins
pubmed
1332063
uniprot
proteins
pubmed
14638692
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15712224
uniprot
proteins
pubmed
15888450
uniprot
proteins
pubmed
15946682
uniprot
proteins
pubmed
16263718
uniprot
proteins
pubmed
16442803
uniprot
proteins
pubmed
16770810
uniprot
proteins
pubmed
17404228
uniprot
proteins
pubmed
19608861
uniprot
proteins
pubmed
20160912
uniprot
proteins
pubmed
20361979
uniprot
proteins
pubmed
20385101
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
22905912
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
24275569
uniprot
proteins
pubmed
25944712
uniprot
proteins
pubmed
29211711
uniprot
proteins
pubmed
3278312
uniprot
proteins
pubmed
3693355
uniprot
proteins
pubmed
8406489
uniprot
proteins
pubmed
8506365
uniprot
proteins
pubmed
8968745
uniprot
proteins
pubmed
9540846
uniprot
proteins
pubmed
9934985
uniprot
proteins
sequence_length
509
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Mitochondrion matrix {ECO:0000305|PubMed:29211711, ECO:0000305|PubMed:3693355}. Nucleus {ECO:0000269|PubMed:29211711}. Cell projection, cilium, flagellum {ECO:0000250|UniProtKB:Q811C4}. Cytoplasmic vesicle, secretory vesicle, acrosome {ECO:0000269|PubMed:15888450}. Note=Mainly localizes in the mitochondrion. A small fraction localizes to the nucleus, where the 2-oxoglutarate dehydrogenase complex is required for histone succinylation. {ECO:0000269|PubMed:29211711}.
uniprot
proteins