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Protein

Dihydrolipoyl dehydrogenase, mitochondrial

Gene

Dld

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

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). The 2-oxoglutarate dehydrogenase complex is mainly active in the mitochondrion. 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. In monomeric form may have additional moonlighting function as serine protease (By similarity). Involved in the hyperactivation of spermatazoa during capacitation and in the spermatazoal acrosome reaction (By similarity).By similarity

Miscellaneous

The active site is a redox-active disulfide bond.By similarity

Catalytic activityi

Protein N6-(dihydrolipoyl)lysine + NAD+ = protein N6-(lipoyl)lysine + NADH.By similarity

Cofactori

FADBy similarityNote: Binds 1 FAD per subunit.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei89FADBy similarity1
Binding sitei154FAD; via amide nitrogen and carbonyl oxygenBy similarity1
Binding sitei243NADBy similarity1
Binding sitei278NAD; via amide nitrogen and carbonyl oxygenBy similarity1
Binding sitei314NAD; via amide nitrogenBy similarity1
Binding sitei355FADBy similarity1
Sitei448Important for interaction with PDHX and activity of pyruvate dehydrogenase complexBy similarity1
Sitei473Important for interaction with PDHX and activity of pyruvate dehydrogenase complexBy similarity1
Active sitei487Proton acceptorBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi71 – 80FADBy similarity10
Nucleotide bindingi183 – 185FADBy similarity3
Nucleotide bindingi220 – 227NADBy similarity8
Nucleotide bindingi361 – 364FADBy similarity4

GO - Molecular functioni

  • dihydrolipoyl dehydrogenase activity Source: RGD
  • electron transfer activity Source: InterPro
  • flavin adenine dinucleotide binding Source: RGD
  • lipoamide binding Source: RGD
  • NAD binding Source: RGD
  • pyruvate dehydrogenase (NAD+) activity Source: Ensembl

GO - Biological processi

  • 2-oxoglutarate metabolic process Source: RGD
  • acetyl-CoA biosynthetic process from pyruvate Source: RGD
  • aging Source: RGD
  • cell redox homeostasis Source: InterPro
  • dihydrolipoamide metabolic process Source: RGD
  • gastrulation Source: RGD
  • histone succinylation Source: UniProtKB
  • lipoate metabolic process Source: RGD
  • mitochondrial electron transport, NADH to ubiquinone Source: RGD
  • proteolysis Source: RGD
  • regulation of membrane potential Source: RGD
  • sperm capacitation Source: RGD

Keywordsi

Molecular functionOxidoreductase
LigandFAD, Flavoprotein, NAD

Enzyme and pathway databases

ReactomeiR-RNO-204174 Regulation of pyruvate dehydrogenase (PDH) complex
R-RNO-389661 Glyoxylate metabolism and glycine degradation
R-RNO-5362517 Signaling by Retinoic Acid
R-RNO-6783984 Glycine degradation
R-RNO-70268 Pyruvate metabolism
R-RNO-70895 Branched-chain amino acid catabolism
R-RNO-71064 Lysine catabolism
R-RNO-71403 Citric acid cycle (TCA cycle)
SABIO-RKiQ6P6R2

Names & Taxonomyi

Protein namesi
Recommended name:
Dihydrolipoyl dehydrogenase, mitochondrial (EC:1.8.1.4By similarity)
Alternative name(s):
Dihydrolipoamide dehydrogenase
Gene namesi
Name:Dld
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 6

Organism-specific databases

RGDi735073 Dld

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell projection, Cilium, Cytoplasmic vesicle, Flagellum, Mitochondrion, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Transit peptidei1 – 35MitochondrionBy similarityAdd BLAST35
ChainiPRO_000026022836 – 509Dihydrolipoyl dehydrogenase, mitochondrialAdd BLAST474

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei66N6-acetyllysine; alternateBy similarity1
Modified residuei66N6-succinyllysine; alternateBy similarity1
Disulfide bondi80 ↔ 85Redox-activeBy similarity
Modified residuei104N6-acetyllysine; alternateBy similarity1
Modified residuei104N6-succinyllysine; alternateBy similarity1
Modified residuei122N6-acetyllysine; alternateBy similarity1
Modified residuei122N6-succinyllysine; alternateBy similarity1
Modified residuei132N6-acetyllysine; alternateBy similarity1
Modified residuei132N6-succinyllysine; alternateBy similarity1
Modified residuei143N6-acetyllysine; alternateBy similarity1
Modified residuei143N6-succinyllysine; alternateBy similarity1
Modified residuei159N6-succinyllysineBy similarity1
Modified residuei273N6-succinyllysineBy similarity1
Modified residuei277N6-succinyllysineBy similarity1
Modified residuei285PhosphoserineBy similarity1
Modified residuei297PhosphoserineCombined sources1
Modified residuei346N6-acetyllysineBy similarity1
Modified residuei410N6-acetyllysine; alternateBy similarity1
Modified residuei410N6-succinyllysine; alternateBy similarity1
Modified residuei417N6-acetyllysineBy similarity1
Modified residuei420N6-acetyllysineBy similarity1
Modified residuei430N6-succinyllysineBy similarity1
Modified residuei502PhosphoserineBy similarity1
Modified residuei505N6-acetyllysine; alternateBy similarity1
Modified residuei505N6-succinyllysine; alternateBy similarity1

Post-translational modificationi

Tyrosine phosphorylated.By similarity

Keywords - PTMi

Acetylation, Disulfide bond, Phosphoprotein

Proteomic databases

PaxDbiQ6P6R2
PRIDEiQ6P6R2

PTM databases

iPTMnetiQ6P6R2
PhosphoSitePlusiQ6P6R2

Expressioni

Gene expression databases

BgeeiENSRNOG00000006364
GenevisibleiQ6P6R2 RN

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 similarity

Protein-protein interaction databases

BioGridi256067, 1 interactor
IntActiQ6P6R2, 1 interactor
STRINGi10116.ENSRNOP00000008980

Structurei

3D structure databases

ProteinModelPortaliQ6P6R2
SMRiQ6P6R2
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Keywords - Domaini

Redox-active center, Transit peptide

Phylogenomic databases

eggNOGiKOG1335 Eukaryota
COG1249 LUCA
GeneTreeiENSGT00550000074844
HOGENOMiHOG000276708
HOVERGENiHBG002290
InParanoidiQ6P6R2
KOiK00382
OMAiTMSEAVM
OrthoDBiEOG091G05AA
PhylomeDBiQ6P6R2
TreeFamiTF300414

Family and domain databases

Gene3Di3.30.390.30, 1 hit
3.50.50.60, 3 hits
InterProiView 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
PfamiView protein in Pfam
PF07992 Pyr_redox_2, 1 hit
PF02852 Pyr_redox_dim, 1 hit
PIRSFiPIRSF000350 Mercury_reductase_MerA, 1 hit
SUPFAMiSSF51905 SSF51905, 1 hit
SSF55424 SSF55424, 1 hit
TIGRFAMsiTIGR01350 lipoamide_DH, 1 hit
PROSITEiView protein in PROSITE
PS00076 PYRIDINE_REDOX_1, 1 hit

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q6P6R2-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MQSWSRVYCS LAKKGHFNRL SHGLQGASSV PLRTYSDQPI DADVTVIGSG
60 70 80 90 100
PGGYVAAIKA AQLGFKTVCI EKNETLGGTC LNVGCIPSKA LLNNSHYYHL
110 120 130 140 150
AHGKDFASRG IEIPEVRLNL EKMMEQKRSA VKALTGGIAH LFKQNKVVHV
160 170 180 190 200
NGFGKITGKN QVTATTADGS TQVIGTKNIL IATGSEVTPF PGITIDEDTI
210 220 230 240 250
VSSTGALSLK KVPEKLVVIG AGVIGVELGS VWQRLGADVT AVEFLGHVGG
260 270 280 290 300
IGIDMEISKN FQRILQKQGF KFKLNTKVTG ATKKSDGKID VSVEAASGGK
310 320 330 340 350
AEVITCDVLL VCIGRRPFTQ NLGLEELGIE LDPKGRIPVN TRFQTKIPNI
360 370 380 390 400
FAIGDVVAGP MLAHKAEDEG IICVEGMAGG AVHIDYNCVP SVIYTHPEVA
410 420 430 440 450
WVGKSEEQLK EEGVEFKVGK FPFAANSRAK TNADTDGMVK ILGHKSTDRI
460 470 480 490 500
LGAHILGPGA GEMVNEAALA LEYGASCEDV ARVCHAHPTL SEAFREANLA

ASFGKPINF
Length:509
Mass (Da):54,038
Last modified:July 5, 2004 - v1
Checksum:i854802DBFE36573A
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
BC062069 mRNA Translation: AAH62069.1
RefSeqiNP_955417.1, NM_199385.2
UniGeneiRn.86962

Genome annotation databases

EnsembliENSRNOT00000008980; ENSRNOP00000008980; ENSRNOG00000006364
GeneIDi298942
KEGGirno:298942
UCSCiRGD:735073 rat

Similar proteinsi

Entry informationi

Entry nameiDLDH_RAT
AccessioniPrimary (citable) accession number: Q6P6R2
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 28, 2006
Last sequence update: July 5, 2004
Last modified: March 28, 2018
This is version 122 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health