DLDH_CANLF
ID DLDH_CANLF Reviewed; 509 AA.
AC P49819;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 1.
DT 03-AUG-2022, entry version 153.
DE RecName: Full=Dihydrolipoyl dehydrogenase, mitochondrial;
DE EC=1.8.1.4 {ECO:0000250|UniProtKB:P09622};
DE AltName: Full=Dihydrolipoamide dehydrogenase;
DE Flags: Precursor;
GN Name=DLD;
OS Canis lupus familiaris (Dog) (Canis familiaris).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Carnivora; Caniformia; Canidae; Canis.
OX NCBI_TaxID=9615;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Mongrel; TISSUE=Skeletal muscle;
RX PubMed=7665089; DOI=10.1016/0378-1119(95)00268-b;
RA Martins A.S., Greene L.J., Yoho L.L., Milsted A.;
RT "The cDNA encoding canine dihydrolipoamide dehydrogenase contains multiple
RT termination signals.";
RL Gene 161:253-257(1995).
RN [2]
RP PROTEIN SEQUENCE OF 36-49.
RC TISSUE=Heart;
RX PubMed=9504812; DOI=10.1002/elps.1150181514;
RA Dunn M.J., Corbett J.M., Wheeler C.H.;
RT "HSC-2DPAGE and the two-dimensional gel electrophoresis database of dog
RT heart proteins.";
RL Electrophoresis 18:2795-2802(1997).
CC -!- FUNCTION: Lipoamide dehydrogenase is a component of the glycine
CC cleavage system as well as an E3 component of three alpha-ketoacid
CC dehydrogenase complexes (pyruvate-, alpha-ketoglutarate-, and branched-
CC chain amino acid-dehydrogenase complex). The 2-oxoglutarate
CC dehydrogenase complex is mainly active in the mitochondrion. A fraction
CC of the 2-oxoglutarate dehydrogenase complex also localizes in the
CC nucleus and is required for lysine succinylation of histones:
CC associates with KAT2A on chromatin and provides succinyl-CoA to histone
CC succinyltransferase KAT2A. In monomeric form may have additional
CC moonlighting function as serine protease (By similarity). Involved in
CC the hyperactivation of spermatazoa during capacitation and in the
CC spermatazoal acrosome reaction (By similarity).
CC {ECO:0000250|UniProtKB:P09622, ECO:0000250|UniProtKB:Q811C4}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(R)-N(6)-dihydrolipoyl-L-lysyl-[protein] + NAD(+) = (R)-N(6)-
CC lipoyl-L-lysyl-[protein] + H(+) + NADH; Xref=Rhea:RHEA:15045,
CC Rhea:RHEA-COMP:10474, Rhea:RHEA-COMP:10475, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:83099,
CC ChEBI:CHEBI:83100; EC=1.8.1.4;
CC Evidence={ECO:0000250|UniProtKB:P09622};
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692;
CC Evidence={ECO:0000250|UniProtKB:P09622};
CC Note=Binds 1 FAD per subunit. {ECO:0000250|UniProtKB:P09622};
CC -!- SUBUNIT: Homodimer. Part of the multimeric pyruvate dehydrogenase
CC complex that contains multiple copies of pyruvate dehydrogenase
CC (subunits PDHA (PDHA1 or PDHA2) and PDHB, E1), dihydrolipoamide
CC acetyltransferase (DLAT, E2) and lipoamide dehydrogenase (DLD, E3).
CC These subunits are bound to an inner core composed of about 48 DLAT and
CC 12 PDHX molecules (by non covalent bonds). The 2-oxoglutarate
CC dehydrogenase complex is composed of OGDH (2-oxoglutarate
CC dehydrogenase; E1), DLST (dihydrolipoamide succinyltransferase; E2) and
CC DLD (dihydrolipoamide dehydrogenase; E3). It contains multiple copies
CC of the three enzymatic components (E1, E2 and E3). In the nucleus, the
CC 2-oxoglutarate dehydrogenase complex associates with KAT2A. Interacts
CC with PDHX. {ECO:0000250|UniProtKB:P09622}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion matrix
CC {ECO:0000250|UniProtKB:P09622}. Nucleus {ECO:0000250|UniProtKB:P09622}.
CC Cell projection, cilium, flagellum {ECO:0000250|UniProtKB:Q811C4}.
CC Cytoplasmic vesicle, secretory vesicle, acrosome
CC {ECO:0000250|UniProtKB:P09622}. Note=Mainly localizes in the
CC mitochondrion. A small fraction localizes to the nucleus, where the 2-
CC oxoglutarate dehydrogenase complex is required for histone
CC succinylation. {ECO:0000250|UniProtKB:P09622}.
CC -!- PTM: Tyrosine phosphorylated. {ECO:0000250|UniProtKB:Q811C4}.
CC -!- MISCELLANEOUS: The active site is a redox-active disulfide bond.
CC {ECO:0000250|UniProtKB:P09624}.
CC -!- SIMILARITY: Belongs to the class-I pyridine nucleotide-disulfide
CC oxidoreductase family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; U19872; AAA87174.1; -; mRNA.
DR PIR; JC4241; JC4241.
DR RefSeq; NP_001003294.1; NM_001003294.1.
DR AlphaFoldDB; P49819; -.
DR SMR; P49819; -.
DR STRING; 9612.ENSCAFP00000005721; -.
DR UCD-2DPAGE; P49819; -.
DR PaxDb; P49819; -.
DR PRIDE; P49819; -.
DR GeneID; 403978; -.
DR KEGG; cfa:403978; -.
DR CTD; 1738; -.
DR eggNOG; KOG1335; Eukaryota.
DR InParanoid; P49819; -.
DR OrthoDB; 581771at2759; -.
DR SABIO-RK; P49819; -.
DR Proteomes; UP000002254; Unplaced.
DR GO; GO:0001669; C:acrosomal vesicle; IEA:UniProtKB-SubCell.
DR GO; GO:0005759; C:mitochondrial matrix; IEA:UniProtKB-SubCell.
DR GO; GO:0005739; C:mitochondrion; ISS:UniProtKB.
DR GO; GO:0031514; C:motile cilium; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0045252; C:oxoglutarate dehydrogenase complex; ISS:UniProtKB.
DR GO; GO:0004148; F:dihydrolipoyl dehydrogenase activity; ISS:UniProtKB.
DR GO; GO:0050660; F:flavin adenine dinucleotide binding; IEA:InterPro.
DR GO; GO:0045454; P:cell redox homeostasis; IEA:InterPro.
DR GO; GO:0106077; P:histone succinylation; ISS:UniProtKB.
DR Gene3D; 3.30.390.30; -; 1.
DR Gene3D; 3.50.50.60; -; 2.
DR InterPro; IPR036188; FAD/NAD-bd_sf.
DR InterPro; IPR023753; FAD/NAD-binding_dom.
DR InterPro; IPR016156; FAD/NAD-linked_Rdtase_dimer_sf.
DR InterPro; IPR006258; Lipoamide_DH.
DR InterPro; IPR001100; Pyr_nuc-diS_OxRdtase.
DR InterPro; IPR004099; Pyr_nucl-diS_OxRdtase_dimer.
DR InterPro; IPR012999; Pyr_OxRdtase_I_AS.
DR Pfam; PF07992; Pyr_redox_2; 1.
DR Pfam; PF02852; Pyr_redox_dim; 1.
DR PIRSF; PIRSF000350; Mercury_reductase_MerA; 1.
DR SUPFAM; SSF51905; SSF51905; 1.
DR SUPFAM; SSF55424; SSF55424; 1.
DR TIGRFAMs; TIGR01350; lipoamide_DH; 1.
DR PROSITE; PS00076; PYRIDINE_REDOX_1; 1.
PE 1: Evidence at protein level;
KW Acetylation; Cell projection; Cilium; Cytoplasmic vesicle;
KW Direct protein sequencing; Disulfide bond; FAD; Flagellum; Flavoprotein;
KW Mitochondrion; NAD; Nucleus; Oxidoreductase; Phosphoprotein;
KW Redox-active center; Reference proteome; Transit peptide.
FT TRANSIT 1..35
FT /note="Mitochondrion"
FT /evidence="ECO:0000269|PubMed:9504812"
FT CHAIN 36..509
FT /note="Dihydrolipoyl dehydrogenase, mitochondrial"
FT /id="PRO_0000030294"
FT ACT_SITE 487
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:P09624"
FT BINDING 71..80
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:P09622"
FT BINDING 89
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:P09622"
FT BINDING 154
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:P09622"
FT BINDING 183..185
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:P09622"
FT BINDING 220..227
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P09622"
FT BINDING 243
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P09622"
FT BINDING 278
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P09622"
FT BINDING 314
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P09622"
FT BINDING 355
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:P09622"
FT BINDING 361..364
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:P09622"
FT SITE 448
FT /note="Important for interaction with PDHX and activity of
FT pyruvate dehydrogenase complex"
FT /evidence="ECO:0000250|UniProtKB:P09622"
FT SITE 473
FT /note="Important for interaction with PDHX and activity of
FT pyruvate dehydrogenase complex"
FT /evidence="ECO:0000250|UniProtKB:P09622"
FT MOD_RES 66
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:O08749"
FT MOD_RES 66
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:O08749"
FT MOD_RES 104
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:O08749"
FT MOD_RES 104
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:O08749"
FT MOD_RES 122
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:O08749"
FT MOD_RES 122
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:O08749"
FT MOD_RES 132
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:O08749"
FT MOD_RES 132
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:O08749"
FT MOD_RES 143
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P09622"
FT MOD_RES 143
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:O08749"
FT MOD_RES 159
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:O08749"
FT MOD_RES 166
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:O08749"
FT MOD_RES 273
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:O08749"
FT MOD_RES 277
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:O08749"
FT MOD_RES 285
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O08749"
FT MOD_RES 297
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q6P6R2"
FT MOD_RES 346
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:O08749"
FT MOD_RES 410
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P09622"
FT MOD_RES 410
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:O08749"
FT MOD_RES 417
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P09622"
FT MOD_RES 420
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:O08749"
FT MOD_RES 430
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:O08749"
FT MOD_RES 502
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P09622"
FT MOD_RES 505
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:O08749"
FT MOD_RES 505
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:O08749"
FT DISULFID 80..85
FT /note="Redox-active"
FT /evidence="ECO:0000250|UniProtKB:P09624"
SQ SEQUENCE 509 AA; 54153 MW; BC2553C52AB30E20 CRC64;
MQSWSRVYCS LAKRGHFSRI SHGLQAVSAV PLRTYADQPI DADVTVIGSG PGGYVAAIKA
AQLGFKTVCV EKNETLGGTC LNVGCIPSKA LLNNSHYYHM AHGKDFASRG IEMSEVRLNL
EKMMEQKSTA VKALTGGIAH LFKQNKVVHV NGYGKITGKN QVTAKKADGS TQVIDTKNIL
IATGSEVTPF PGITIDEDTI VSSTGALSLK KVPEKMVVIG AGVIGVELGS VWQRLGADVT
AVEFLGHVGG VGIDMEISKN FQRILQKQGF KFKLNTKVTG ATKKSDGKID VSIEGASGGK
AEVITCDVLL VCIGRRPFTQ NLGLEELGIE LDPRGRIPVN TRFQTKIPNI YAIGDVVAGP
MLAHKAEDEG IICVEGMAGG AVPIDYNCVP SVIYTHPEVA WVGKSEEQLK EEGIEYKVGK
FPFAANSRAK TNADTDGMVK ILGQKSTDRV LGAHILGPGA GEMVNEAALA LEYGASCEDI
ARVCHAHPTL SEAFREANLA ASFGKSINF
