| IED ID | IndEnz0002004769 |
| Enzyme Type ID | protease004769 |
| Protein Name |
Dihydrolipoyl dehydrogenase, mitochondrial EC 1.8.1.4 Dihydrolipoamide dehydrogenase Glycine cleavage system L protein |
| Gene Name | DLD GCSL LAD PHE3 |
| Organism | Homo sapiens (Human) |
| Taxonomic Lineage | cellular organisms Eukaryota Opisthokonta Metazoa Eumetazoa Bilateria Deuterostomia Chordata Craniata Vertebrata Gnathostomata (jawed vertebrates) Teleostomi Euteleostomi Sarcopterygii Dipnotetrapodomorpha Tetrapoda Amniota Mammalia Theria Eutheria Boreoeutheria Euarchontoglires Primates Haplorrhini Simiiformes Catarrhini Hominoidea (apes) Hominidae (great apes) Homininae Homo Homo sapiens (Human) |
| Enzyme Sequence | MQSWSRVYCSLAKRGHFNRISHGLQGLSAVPLRTYADQPIDADVTVIGSGPGGYVAAIKAAQLGFKTVCIEKNETLGGTCLNVGCIPSKALLNNSHYYHMAHGKDFASRGIEMSEVRLNLDKMMEQKSTAVKALTGGIAHLFKQNKVVHVNGYGKITGKNQVTATKADGGTQVIDTKNILIATGSEVTPFPGITIDEDTIVSSTGALSLKKVPEKMVVIGAGVIGVELGSVWQRLGADVTAVEFLGHVGGVGIDMEISKNFQRILQKQGFKFKLNTKVTGATKKSDGKIDVSIEAASGGKAEVITCDVLLVCIGRRPFTKNLGLEELGIELDPRGRIPVNTRFQTKIPNIYAIGDVVAGPMLAHKAEDEGIICVEGMAGGAVHIDYNCVPSVIYTHPEVAWVGKSEEQLKEEGIEYKVGKFPFAANSRAKTNADTDGMVKILGQKSTDRVLGAHILGPGAGEMVNEAALALEYGASCEDIARVCHAHPTLSEAFREANLAASFGKSINF |
| Enzyme Length | 509 |
| Uniprot Accession Number | P09622 |
| Absorption | |
| Active Site | ACT_SITE 487; /note=Proton acceptor; /evidence=ECO:0000250|UniProtKB:P09624 |
| Activity Regulation | ACTIVITY REGULATION: Disruption of native heterodimer state inhibits primary dihydrolipoamide dehydrogenase activity and induces serine protease activity. {ECO:0000269|PubMed:17404228}. |
| Binding Site | BINDING 89; /note=FAD; /evidence=ECO:0000269|PubMed:15946682; BINDING 154; /note=FAD; via amide nitrogen and carbonyl oxygen; /evidence=ECO:0000269|PubMed:15946682; BINDING 243; /note=NAD; /evidence=ECO:0000269|PubMed:15946682; BINDING 278; /note=NAD; via amide nitrogen and carbonyl oxygen; /evidence=ECO:0000269|PubMed:15946682; BINDING 314; /note=NAD; via amide nitrogen; /evidence=ECO:0000269|PubMed:15946682; BINDING 355; /note=FAD; /evidence=ECO:0000269|PubMed:15946682 |
| Calcium Binding | |
| catalytic Activity | CATALYTIC ACTIVITY: Reaction=(R)-N(6)-dihydrolipoyl-L-lysyl-[protein] + NAD(+) = (R)-N(6)-lipoyl-L-lysyl-[protein] + H(+) + NADH; Xref=Rhea:RHEA:15045, Rhea:RHEA-COMP:10474, Rhea:RHEA-COMP:10475, ChEBI:CHEBI:15378, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:83099, ChEBI:CHEBI:83100; EC=1.8.1.4; Evidence={ECO:0000269|PubMed:15712224, ECO:0000269|PubMed:16442803, ECO:0000269|PubMed:16770810, ECO:0000269|PubMed:17404228, ECO:0000269|PubMed:20160912, ECO:0000269|PubMed:20385101}; |
| DNA Binding | |
| EC Number | 1.8.1.4 |
| Enzyme 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). {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}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | NP_BIND 71..80; /note=FAD; /evidence=ECO:0000269|PubMed:15946682; NP_BIND 183..185; /note=FAD; /evidence=ECO:0000269|PubMed:15946682; NP_BIND 220..227; /note=NAD; /evidence=ECO:0000269|PubMed:15946682; NP_BIND 361..364; /note=FAD; /evidence=ECO:0000269|PubMed:15946682 |
| Features | Active site (1); Alternative sequence (2); Beta strand (25); Binding site (6); Chain (1); Disulfide bond (1); Erroneous initiation (1); Helix (18); Modified residue (25); Mutagenesis (15); Natural variant (13); Nucleotide binding (4); Sequence conflict (3); Site (2); Transit peptide (1); Turn (1) |
| Keywords | 3D-structure;Acetylation;Alternative splicing;Cell projection;Cilium;Cytoplasmic vesicle;Disease variant;Disulfide bond;FAD;Flagellum;Flavoprotein;Mitochondrion;NAD;Nucleus;Oxidoreductase;Phosphoprotein;Redox-active center;Reference proteome;Transit peptide |
| Interact With | P42858; O14713; O00330; P30041; P62258 |
| Induction | |
| 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}. |
| Modified Residue | MOD_RES 66; /note=N6-acetyllysine; alternate; /evidence=ECO:0000250|UniProtKB:O08749; MOD_RES 66; /note=N6-succinyllysine; alternate; /evidence=ECO:0000250|UniProtKB:O08749; MOD_RES 104; /note=N6-acetyllysine; alternate; /evidence=ECO:0000250|UniProtKB:O08749; MOD_RES 104; /note=N6-succinyllysine; alternate; /evidence=ECO:0000250|UniProtKB:O08749; MOD_RES 122; /note=N6-acetyllysine; alternate; /evidence=ECO:0000250|UniProtKB:O08749; MOD_RES 122; /note=N6-succinyllysine; alternate; /evidence=ECO:0000250|UniProtKB:O08749; MOD_RES 132; /note=N6-acetyllysine; alternate; /evidence=ECO:0000250|UniProtKB:O08749; MOD_RES 132; /note=N6-succinyllysine; alternate; /evidence=ECO:0000250|UniProtKB:O08749; MOD_RES 143; /note=N6-acetyllysine; alternate; /evidence=ECO:0007744|PubMed:19608861; MOD_RES 143; /note=N6-succinyllysine; alternate; /evidence=ECO:0000250|UniProtKB:O08749; MOD_RES 159; /note=N6-succinyllysine; /evidence=ECO:0000250|UniProtKB:O08749; MOD_RES 166; /note=N6-succinyllysine; /evidence=ECO:0000250|UniProtKB:O08749; MOD_RES 273; /note=N6-succinyllysine; /evidence=ECO:0000250|UniProtKB:O08749; MOD_RES 277; /note=N6-succinyllysine; /evidence=ECO:0000250|UniProtKB:O08749; MOD_RES 285; /note=Phosphoserine; /evidence=ECO:0000250|UniProtKB:O08749; MOD_RES 297; /note=Phosphoserine; /evidence=ECO:0000250|UniProtKB:Q6P6R2; MOD_RES 346; /note=N6-acetyllysine; /evidence=ECO:0000250|UniProtKB:O08749; MOD_RES 410; /note=N6-acetyllysine; alternate; /evidence=ECO:0007744|PubMed:19608861; MOD_RES 410; /note=N6-succinyllysine; alternate; /evidence=ECO:0000250|UniProtKB:O08749; MOD_RES 417; /note=N6-acetyllysine; /evidence=ECO:0007744|PubMed:19608861; MOD_RES 420; /note=N6-acetyllysine; /evidence=ECO:0000250|UniProtKB:O08749; MOD_RES 430; /note=N6-succinyllysine; /evidence=ECO:0000250|UniProtKB:O08749; MOD_RES 502; /note=Phosphoserine; /evidence=ECO:0007744|PubMed:23186163; MOD_RES 505; /note=N6-acetyllysine; alternate; /evidence=ECO:0000250|UniProtKB:O08749; MOD_RES 505; /note=N6-succinyllysine; alternate; /evidence=ECO:0000250|UniProtKB:O08749 |
| Post Translational Modification | PTM: Tyrosine phosphorylated. {ECO:0000250|UniProtKB:Q811C4}. |
| Signal Peptide | |
| Structure 3D | X-ray crystallography (15) |
| Cross Reference PDB | 1ZMC; 1ZMD; 1ZY8; 2F5Z; 3RNM; 5J5Z; 5NHG; 6HG8; 6I4P; 6I4Q; 6I4R; 6I4S; 6I4T; 6I4U; 6I4Z; |
| Mapped Pubmed ID | 10103005; 10679936; 10745006; 11485553; 11486000; 11752427; 11839747; 11935326; 12297006; 12577067; 15138885; 15166214; 15389771; 15576032; 15826505; 15855260; 16049940; 16584639; 17171578; 17532339; 17960497; 19122664; 19405953; 19738201; 20186120; 20228799; 20562859; 20652410; 20877624; 21543315; 2188967; 21930696; 22291014; 22304920; 22956686; 23475850; 23902751; 24012808; 24256811; 24341803; 24449431; 25202086; 25525879; 25604459; 25609649; 26078703; 26496610; 26752685; 27303803; 28247484; 29908278; 31334547; 7499431; 7918575; 8798399; 9242632; 9395502; 9405293; 9651365; 9727038; |
| Motif | |
| Gene Encoded By | |
| Mass | 54,177 |
| Kinetics | |
| Metal Binding | |
| Rhea ID | RHEA:15045 |
| Cross Reference Brenda | 1.8.1.4; |