| Tbio | Dihydrolipoyl dehydrogenase, mitochondrial |
Lipoamide dehydrogenase is a component of the glycine cleavage system as well as of the alpha-ketoacid dehydrogenase complexes. Involved in the hyperactivation of spermatazoa during capacitation and in the spermatazoal acrosome reaction.
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]
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]
Comments
| Disease | Target Count |
|---|---|
| Leigh disease | 81 |
| NADH cytochrome B5 reductase deficiency | 2 |
| Disease | Target Count | P-value |
|---|---|---|
| cystic fibrosis | 1670 | 1.73127810358962E-4 |
| ovarian cancer | 8492 | 2.33357337609348E-4 |
| Multiple myeloma | 1328 | 0.00117877233940563 |
| pancreatic ductal adenocarcinoma liver metastasis | 1795 | 0.0254696056073907 |
| Disease | Target Count | Z-score | Confidence |
|---|---|---|---|
| Crohn's disease | 304 | 0.0 | 2.0 |
| ulcerative colitis | 2087 | 0.0 | 1.0 |
| Disease | Target Count | Z-score | Confidence |
|---|---|---|---|
| Lactic acidosis | 43 | 3.123 | 1.6 |
| Disease | Target Count |
|---|---|
| Maple syrup urine disease | 25 |
| Dihydrolipoamide dehydrogenase deficiency | 1 |
| Disease | log2 FC | p |
|---|---|---|
| Multiple myeloma | 1.482 | 0.001 |
| cystic fibrosis | -1.186 | 0.000 |
| pancreatic ductal adenocarcinoma liver m... | -1.947 | 0.025 |
| ovarian cancer | 2.500 | 0.000 |
| Species | Source |
|---|---|
| Chimp | OMA EggNOG |
| Macaque | OMA EggNOG Inparanoid |
| Mouse | OMA EggNOG Inparanoid |
| Rat | OMA EggNOG Inparanoid |
| Dog | OMA EggNOG Inparanoid |
| Cow | OMA EggNOG Inparanoid |
| Pig | OMA EggNOG Inparanoid |
| Opossum | OMA EggNOG Inparanoid |
| Platypus | OMA EggNOG |
| Chicken | OMA EggNOG Inparanoid |
| Anole lizard | OMA EggNOG Inparanoid |
| Xenopus | OMA EggNOG Inparanoid |
| C. elegans | OMA Inparanoid |
| S.cerevisiae | OMA EggNOG Inparanoid |
| PMID | Text |
|---|---|
| 26078703 | Mitochondrial dihydrolipoamide dehydrogenase is upregulated in response to the brain intermittent hypoxic preconditioning. |
| 25202086 | IgA autoantibody against DLD could be a novel diagnostic marker for endometrial cancer. |
| 24012808 | This molecular dynamics study proposes the structural changes that may lead to the modulation in reactive oxygen species generation by pathogenic mutants of human dihydrolipoamide dehydrogenase. |
| 23475850 | ATP consumption is demonstrated in respiration-impaired isolated and in situ neuronal somal mitochondria from transgenic mice that exhibit a 20-48% decrease in alpha-ketoglutarate dehydrogenase activity. |
| 22944692 | Positional proteomics analysis identifies the cleavage of human dihydrolipoamide dehydrogenase (DLD) at amino acid residues 470-471 by the HIV-1 protease |
| 21930696 | the cryptic activities of DLD promote oxidative damage to neighboring molecules and thus contribute to the clinical severity of DLD mutations |
| 21543315 | Structural and thermodynamic basis for weak interactions between dihydrolipoamide dehydrogenase and subunit-binding domain of the branched-chain alpha-ketoacid dehydrogenase complex. |
| 20877624 | Observational study of gene-disease association. (HuGE Navigator) |
| 20652410 | Case Report: novel mutation in the DLD interface giving rise to DLD deficiency. |
| 19405953 | This protein has been found differentially expressed in the Wernicke's Area from patients with schizophrenia. |
| More... |
MQSWSRVYCSLAKRGHFNRISHGLQGLSAVPLRTYADQPIDADVTVIGSGPGGYVAAIKAAQLGFKTVCI 1 - 70 EKNETLGGTCLNVGCIPSKALLNNSHYYHMAHGKDFASRGIEMSEVRLNLDKMMEQKSTAVKALTGGIAH 71 - 140 LFKQNKVVHVNGYGKITGKNQVTATKADGGTQVIDTKNILIATGSEVTPFPGITIDEDTIVSSTGALSLK 141 - 210 KVPEKMVVIGAGVIGVELGSVWQRLGADVTAVEFLGHVGGVGIDMEISKNFQRILQKQGFKFKLNTKVTG 211 - 280 ATKKSDGKIDVSIEAASGGKAEVITCDVLLVCIGRRPFTKNLGLEELGIELDPRGRIPVNTRFQTKIPNI 281 - 350 YAIGDVVAGPMLAHKAEDEGIICVEGMAGGAVHIDYNCVPSVIYTHPEVAWVGKSEEQLKEEGIEYKVGK 351 - 420 FPFAANSRAKTNADTDGMVKILGQKSTDRVLGAHILGPGAGEMVNEAALALEYGASCEDIARVCHAHPTL 421 - 490 SEAFREANLAASFGKSINF 491 - 509 //
| PMID | Year | Title |
|---|---|---|
| 26078703 | 2015 | Mitochondrial Dihydrolipoamide Dehydrogenase is Upregulated in Response to Intermittent Hypoxic Preconditioning. |
| 25944712 | 2015 | N-terminome analysis of the human mitochondrial proteome. |
| 25202086 | 2014 | Proteomic identification of dihydrolipoamide dehydrogenase as a target of autoantibodies in patients with endometrial cancer. |
| 24275569 | 2014 | An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. |
| 24012808 | 2013 | Molecular dynamics study of the structural basis of dysfunction and the modulation of reactive oxygen species generation by pathogenic mutants of human dihydrolipoamide dehydrogenase. |
| 23475850 | 2013 | The negative impact of ?-ketoglutarate dehydrogenase complex deficiency on matrix substrate-level phosphorylation. |
| 23186163 | 2013 | Toward a comprehensive characterization of a human cancer cell phosphoproteome. |
| 23128233 | 2012 | Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease. |
| 22905912 | 2012 | Resveratrol-induced changes of the human adipocyte secretion profile. |
| 21930696 | 2011 | Mutations in the dimer interface of dihydrolipoamide dehydrogenase promote site-specific oxidative damages in yeast and human cells. |
| More... |
