UniProtKB - P09623 (DLDH_PIG)
Dihydrolipoyl dehydrogenase, mitochondrial
DLD
Functioni
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) (By similarity).
The 2-oxoglutarate dehydrogenase complex is mainly active in the mitochondrion (By similarity).
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 (By similarity).
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).
By similarity1 PublicationMiscellaneous
Catalytic activityi
- (R)-N6-dihydrolipoyl-L-lysyl-[protein] + NAD+ = (R)-N6-lipoyl-L-lysyl-[protein] + H+ + NADHBy similarityEC:1.8.1.4By similarity
Cofactori
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 89 | FADBy similarity | 1 | |
Binding sitei | 154 | FAD; via amide nitrogen and carbonyl oxygenBy similarity | 1 | |
Binding sitei | 243 | NADBy similarity | 1 | |
Binding sitei | 278 | NAD; via amide nitrogen and carbonyl oxygenBy similarity | 1 | |
Binding sitei | 314 | NAD; via amide nitrogenBy similarity | 1 | |
Binding sitei | 355 | FADBy similarity | 1 | |
Sitei | 448 | Important for interaction with PDHX and activity of pyruvate dehydrogenase complexBy similarity | 1 | |
Sitei | 473 | Important for interaction with PDHX and activity of pyruvate dehydrogenase complexBy similarity | 1 | |
Active sitei | 487 | Proton acceptorBy similarity | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Nucleotide bindingi | 71 – 80 | FADBy similarity | 10 | |
Nucleotide bindingi | 183 – 185 | FADBy similarity | 3 | |
Nucleotide bindingi | 220 – 227 | NADBy similarity | 8 | |
Nucleotide bindingi | 361 – 364 | FADBy similarity | 4 |
GO - Molecular functioni
- dihydrolipoyl dehydrogenase activity Source: UniProtKB
- flavin adenine dinucleotide binding Source: GO_Central
GO - Biological processi
- cell redox homeostasis Source: InterPro
- histone succinylation Source: UniProtKB
Keywordsi
Molecular function | Oxidoreductase |
Ligand | FAD, Flavoprotein, NAD |
Enzyme and pathway databases
BRENDAi | 1.8.1.4, 6170 |
SABIO-RKi | P09623 |
Names & Taxonomyi
Protein namesi | Recommended name: Dihydrolipoyl dehydrogenase, mitochondrial (EC:1.8.1.4By similarity)Alternative name(s): Dihydrolipoamide dehydrogenase |
Gene namesi | Name:DLD Synonyms:LAD |
Organismi | Sus scrofa (Pig) |
Taxonomic identifieri | 9823 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Laurasiatheria › Artiodactyla › Suina › Suidae › Sus |
Proteomesi |
|
Subcellular locationi
Nucleus
- Nucleus By similarity
Mitochondrion
- Mitochondrion matrix 1 Publication
Other locations
Note: Mainly localizes in the mitochondrion. A small fraction localizes to the nucleus, where the 2-oxoglutarate dehydrogenase complex is required for histone succinylation.By similarity
Mitochondrion
- mitochondrial matrix Source: UniProtKB-SubCell
- mitochondrion Source: UniProtKB
Nucleus
- nucleus Source: UniProtKB
Other locations
- acrosomal vesicle Source: UniProtKB-SubCell
- motile cilium Source: UniProtKB-SubCell
- oxoglutarate dehydrogenase complex Source: UniProtKB
Keywords - Cellular componenti
Cell projection, Cilium, Cytoplasmic vesicle, Flagellum, Mitochondrion, NucleusPTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Transit peptidei | 1 – 35 | Mitochondrion1 PublicationAdd BLAST | 35 | |
ChainiPRO_0000030298 | 36 – 509 | Dihydrolipoyl dehydrogenase, mitochondrialAdd BLAST | 474 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 66 | N6-acetyllysine; alternateBy similarity | 1 | |
Modified residuei | 66 | N6-succinyllysine; alternateBy similarity | 1 | |
Disulfide bondi | 80 ↔ 85 | Redox-activeBy similarity | ||
Modified residuei | 104 | N6-acetyllysine; alternateBy similarity | 1 | |
Modified residuei | 104 | N6-succinyllysine; alternateBy similarity | 1 | |
Modified residuei | 122 | N6-acetyllysine; alternateBy similarity | 1 | |
Modified residuei | 122 | N6-succinyllysine; alternateBy similarity | 1 | |
Modified residuei | 132 | N6-acetyllysine; alternateBy similarity | 1 | |
Modified residuei | 132 | N6-succinyllysine; alternateBy similarity | 1 | |
Modified residuei | 143 | N6-acetyllysine; alternateBy similarity | 1 | |
Modified residuei | 143 | N6-succinyllysine; alternateBy similarity | 1 | |
Modified residuei | 159 | N6-succinyllysineBy similarity | 1 | |
Modified residuei | 166 | N6-succinyllysineBy similarity | 1 | |
Modified residuei | 273 | N6-succinyllysineBy similarity | 1 | |
Modified residuei | 277 | N6-succinyllysineBy similarity | 1 | |
Modified residuei | 285 | PhosphoserineBy similarity | 1 | |
Modified residuei | 297 | PhosphoserineBy similarity | 1 | |
Modified residuei | 346 | N6-acetyllysineBy similarity | 1 | |
Modified residuei | 410 | N6-acetyllysine; alternateBy similarity | 1 | |
Modified residuei | 410 | N6-succinyllysine; alternateBy similarity | 1 | |
Modified residuei | 417 | N6-acetyllysineBy similarity | 1 | |
Modified residuei | 420 | N6-acetyllysineBy similarity | 1 | |
Modified residuei | 430 | N6-succinyllysineBy similarity | 1 | |
Modified residuei | 502 | PhosphoserineBy similarity | 1 | |
Modified residuei | 505 | N6-acetyllysine; alternateBy similarity | 1 | |
Modified residuei | 505 | N6-succinyllysine; alternateBy similarity | 1 |
Post-translational modificationi
Keywords - PTMi
Acetylation, Disulfide bond, PhosphoproteinProteomic databases
PaxDbi | P09623 |
PeptideAtlasi | P09623 |
PRIDEi | P09623 |
Expressioni
Tissue specificityi
Interactioni
Subunit structurei
Homodimer. Part of the multimeric pyruvate dehydrogenase complex that contains multiple copies of pyruvate dehydrogenase (subunits PDHA (PDHA1 or PDHA2) and PDHB, E1), dihydrolipoamide acetyltransferase (DLAT, E2) and lipoamide dehydrogenase (DLD, E3). These subunits are bound to an inner core composed of about 48 DLAT and 12 PDHX molecules (by non covalent bonds). The 2-oxoglutarate dehydrogenase complex is composed of OGDH (2-oxoglutarate dehydrogenase; E1), DLST (dihydrolipoamide succinyltransferase; E2) and DLD (dihydrolipoamide dehydrogenase; E3). It contains multiple copies of the three enzymatic components (E1, E2 and E3). In the nucleus, the 2-oxoglutarate dehydrogenase complex associates with KAT2A.
Interacts with PDHX.
By similarityProtein-protein interaction databases
STRINGi | 9823.ENSSSCP00000016374 |
Chemistry databases
BindingDBi | P09623 |
Family & Domainsi
Sequence similaritiesi
Keywords - Domaini
Redox-active center, Transit peptidePhylogenomic databases
eggNOGi | KOG1335, Eukaryota |
InParanoidi | P09623 |
OrthoDBi | 581771at2759 |
Family and domain databases
Gene3Di | 3.30.390.30, 1 hit 3.50.50.60, 2 hits |
InterProi | View protein in InterPro IPR036188, FAD/NAD-bd_sf IPR023753, FAD/NAD-binding_dom IPR016156, FAD/NAD-linked_Rdtase_dimer_sf IPR006258, Lipoamide_DH IPR001100, Pyr_nuc-diS_OxRdtase IPR004099, Pyr_nucl-diS_OxRdtase_dimer IPR012999, Pyr_OxRdtase_I_AS |
Pfami | View protein in Pfam PF07992, Pyr_redox_2, 1 hit PF02852, Pyr_redox_dim, 1 hit |
PIRSFi | PIRSF000350, Mercury_reductase_MerA, 1 hit |
SUPFAMi | SSF51905, SSF51905, 1 hit SSF55424, SSF55424, 1 hit |
TIGRFAMsi | TIGR01350, lipoamide_DH, 1 hit |
PROSITEi | View protein in PROSITE PS00076, PYRIDINE_REDOX_1, 1 hit |
i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
10 20 30 40 50
MQSWSRVYCT LAKRGHFNRI AHGLQGVSAV PLRTYADQPI DADVTVIGSG
60 70 80 90 100
PGGYVAAIKA AQLGFKTVCI EKNETLGGTC LNVGCIPSKA LLNNSHYYHM
110 120 130 140 150
AHGKDFASRG IEMSEVRLNL EKMMEQKSNA VKALTGGIAH LFKQNKVVRV
160 170 180 190 200
NGYGKITGKN QVTATKADGS TEVINTKNIL IATGSEVTPF PGITIDEDTV
210 220 230 240 250
VSSTGALSLK KVPEKMVVIG AGVIGVELGS VWQRLGADVT AVELLGHVGG
260 270 280 290 300
IGIDMEVSKN FQRILQKQGF KFKLNTKVIG ATKKSDGNID VSIEAASGGK
310 320 330 340 350
AEVITCDVLL VCIGRRPFTQ NLGLEELGIE LDPRGRIPVN TRFQTKIPNI
360 370 380 390 400
YAIGDVVAGP MLAHKAEDEG IICVEGMAGG AVHIDYNCVP SVIYTHPEVA
410 420 430 440 450
WVGKSEEQLK EEGIEYKVGK FPFAANSRAK TNADTDGMVK ILGQKSTDRV
460 470 480 490 500
LGAHIIGPGA GEMINEAALA LEYGASCEDI ARVCHAHPTL SEAFREANLA
ASFGKAINF
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 95 – 97 | SHY → GHA AA sequence (PubMed:6954534).Curated | 3 | |
Sequence conflicti | 346 | K → R AA sequence (PubMed:6954534).Curated | 1 | |
Sequence conflicti | 351 | Y → A AA sequence (PubMed:6954534).Curated | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | J03489 mRNA Translation: AAA31069.1 |
PIRi | A28448, DEPGLP |
RefSeqi | NP_999227.1, NM_214062.1 |
Genome annotation databases
GeneIDi | 397129 |
KEGGi | ssc:397129 |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | J03489 mRNA Translation: AAA31069.1 |
PIRi | A28448, DEPGLP |
RefSeqi | NP_999227.1, NM_214062.1 |
3D structure databases
SMRi | P09623 |
ModBasei | Search... |
Protein-protein interaction databases
STRINGi | 9823.ENSSSCP00000016374 |
Chemistry databases
BindingDBi | P09623 |
ChEMBLi | CHEMBL4061 |
Proteomic databases
PaxDbi | P09623 |
PeptideAtlasi | P09623 |
PRIDEi | P09623 |
Genome annotation databases
GeneIDi | 397129 |
KEGGi | ssc:397129 |
Organism-specific databases
CTDi | 1738 |
Phylogenomic databases
eggNOGi | KOG1335, Eukaryota |
InParanoidi | P09623 |
OrthoDBi | 581771at2759 |
Enzyme and pathway databases
BRENDAi | 1.8.1.4, 6170 |
SABIO-RKi | P09623 |
Miscellaneous databases
PROi | PR:P09623 |
Family and domain databases
Gene3Di | 3.30.390.30, 1 hit 3.50.50.60, 2 hits |
InterProi | View protein in InterPro IPR036188, FAD/NAD-bd_sf IPR023753, FAD/NAD-binding_dom IPR016156, FAD/NAD-linked_Rdtase_dimer_sf IPR006258, Lipoamide_DH IPR001100, Pyr_nuc-diS_OxRdtase IPR004099, Pyr_nucl-diS_OxRdtase_dimer IPR012999, Pyr_OxRdtase_I_AS |
Pfami | View protein in Pfam PF07992, Pyr_redox_2, 1 hit PF02852, Pyr_redox_dim, 1 hit |
PIRSFi | PIRSF000350, Mercury_reductase_MerA, 1 hit |
SUPFAMi | SSF51905, SSF51905, 1 hit SSF55424, SSF55424, 1 hit |
TIGRFAMsi | TIGR01350, lipoamide_DH, 1 hit |
PROSITEi | View protein in PROSITE PS00076, PYRIDINE_REDOX_1, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | DLDH_PIG | |
Accessioni | P09623Primary (citable) accession number: P09623 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | July 1, 1989 |
Last sequence update: | July 1, 1989 | |
Last modified: | April 7, 2021 | |
This is version 162 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
Direct protein sequencing, Reference proteomeDocuments
- SIMILARITY comments
Index of protein domains and families