DLDH_MESAU
ID DLDH_MESAU Reviewed; 479 AA.
AC Q811C4;
DT 15-JUN-2010, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2003, sequence version 1.
DT 03-AUG-2022, entry version 93.
DE RecName: Full=Dihydrolipoyl dehydrogenase, mitochondrial {ECO:0000250|UniProtKB:P09622};
DE EC=1.8.1.4 {ECO:0000269|PubMed:15888450};
DE AltName: Full=Dihydrolipoamide dehydrogenase {ECO:0000250|UniProtKB:P09622};
DE Flags: Precursor; Fragment;
GN Name=DLD;
OS Mesocricetus auratus (Golden hamster).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea;
OC Cricetidae; Cricetinae; Mesocricetus.
OX NCBI_TaxID=10036;
RN [1] {ECO:0000305, ECO:0000312|EMBL:CAD61860.1}
RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 20-51, FUNCTION, AND
RP PHOSPHORYLATION.
RC TISSUE=Sperm {ECO:0000269|PubMed:14645106}, and
RC Testis {ECO:0000312|EMBL:CAD61860.1};
RX PubMed=14645106; DOI=10.1095/biolreprod.103.022780;
RA Mitra K., Shivaji S.;
RT "Novel tyrosine-phosphorylated post-pyruvate metabolic enzyme,
RT dihydrolipoamide dehydrogenase, involved in capacitation of hamster
RT spermatozoa.";
RL Biol. Reprod. 70:887-899(2004).
RN [2]
RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND
RP PHOSPHORYLATION.
RX PubMed=15888450; DOI=10.1074/jbc.m500310200;
RA Mitra K., Rangaraj N., Shivaji S.;
RT "Novelty of the pyruvate metabolic enzyme dihydrolipoamide dehydrogenase in
RT spermatozoa: correlation of its localization, tyrosine phosphorylation, and
RT activity during sperm capacitation.";
RL J. Biol. Chem. 280:25743-25753(2005).
RN [3]
RP IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=20400973; DOI=10.1038/aja.2010.19;
RA Kameshwari D.B., Bhande S., Sundaram C.S., Kota V., Siva A.B., Shivaji S.;
RT "Glucose-regulated protein precursor (GRP78) and tumor rejection antigen
RT (GP96) are unique to hamster caput epididymal spermatozoa.";
RL Asian J. Androl. 12:344-355(2010).
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) (PubMed:15888450). The 2-
CC oxoglutarate dehydrogenase complex is mainly active in the
CC mitochondrion (By similarity). A fraction of the 2-oxoglutarate
CC dehydrogenase complex also localizes in the nucleus and is required for
CC lysine succinylation of histones: associates with KAT2A on chromatin
CC and provides succinyl-CoA to histone succinyltransferase KAT2A (By
CC similarity). In monomeric form may have additional moonlighting
CC function as serine protease (By similarity). Involved in the
CC hyperactivation of spermatazoa during capacitation and in the
CC spermatazoal acrosome reaction (PubMed:14645106, PubMed:15888450).
CC {ECO:0000250|UniProtKB:P09622, ECO:0000269|PubMed:14645106,
CC ECO:0000269|PubMed:15888450}.
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:0000269|PubMed:15888450};
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:0000269|PubMed:15888450}.
CC Cytoplasmic vesicle, secretory vesicle, acrosome
CC {ECO:0000269|PubMed:15888450}. 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 -!- TISSUE SPECIFICITY: Expressed in testis (at protein level).
CC {ECO:0000269|PubMed:15888450}.
CC -!- PTM: Tyrosine phosphorylated. {ECO:0000269|PubMed:14645106,
CC ECO:0000269|PubMed:15888450}.
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}.
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DR EMBL; AJ538298; CAD61860.1; -; mRNA.
DR STRING; 10036.XP_005076287.1; -.
DR eggNOG; KOG1335; Eukaryota.
DR BRENDA; 1.8.1.4; 3239.
DR Proteomes; UP000189706; 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..19
FT /note="Mitochondrion"
FT /evidence="ECO:0000269|PubMed:14645106"
FT CHAIN 20..>479
FT /note="Dihydrolipoyl dehydrogenase, mitochondrial"
FT /evidence="ECO:0000269|PubMed:14645106"
FT /id="PRO_5000070424"
FT ACT_SITE 471
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:P09624"
FT BINDING 55..64
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:P09622"
FT BINDING 73
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:P09622"
FT BINDING 138
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:P09622"
FT BINDING 167..169
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:P09622"
FT BINDING 204..211
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P09622"
FT BINDING 227
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P09622"
FT BINDING 262
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P09622"
FT BINDING 298
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P09622"
FT BINDING 339
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:P09622"
FT BINDING 345..348
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:P09622"
FT SITE 432
FT /note="Important for interaction with PDHX and activity of
FT pyruvate dehydrogenase complex"
FT /evidence="ECO:0000250|UniProtKB:P09622"
FT SITE 457
FT /note="Important for interaction with PDHX and activity of
FT pyruvate dehydrogenase complex"
FT /evidence="ECO:0000250|UniProtKB:P09622"
FT MOD_RES 50
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:O08749"
FT MOD_RES 50
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:O08749"
FT MOD_RES 88
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:O08749"
FT MOD_RES 88
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:O08749"
FT MOD_RES 106
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:O08749"
FT MOD_RES 106
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:O08749"
FT MOD_RES 116
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:O08749"
FT MOD_RES 116
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:O08749"
FT MOD_RES 127
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P09622"
FT MOD_RES 127
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:O08749"
FT MOD_RES 143
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:O08749"
FT MOD_RES 150
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:O08749"
FT MOD_RES 257
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:O08749"
FT MOD_RES 261
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:O08749"
FT MOD_RES 269
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O08749"
FT MOD_RES 330
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:O08749"
FT MOD_RES 394
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P09622"
FT MOD_RES 394
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:O08749"
FT MOD_RES 401
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P09622"
FT MOD_RES 404
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:O08749"
FT MOD_RES 414
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:O08749"
FT DISULFID 64..69
FT /note="Redox-active"
FT /evidence="ECO:0000250|UniProtKB:P09624"
FT NON_TER 1
FT /evidence="ECO:0000312|EMBL:CAD61860.1"
FT NON_TER 479
FT /evidence="ECO:0000312|EMBL:CAD61860.1"
SQ SEQUENCE 479 AA; 50723 MW; 1F2EA60777B3DCE4 CRC64;
FNRXSPGLQG VSSVPLRTYA DQPIDADVTV IGSGPGGYVA AIKAAQLGFK TVCIEKNETL
GGTCLNVGCI PSKALLNNSH YYHLAHGKDF ASRGIELSEV RLNLEKMMEQ KSSAVKALTG
GIAHLFKQNK VVHVNGFGNI TGKNQVTATK ADGSSQVIGT KNILIATGSE VTPFPGITID
EDTIVSSTGA LSLKKVPEKL VVIGAGVIGV ELGSVWQRLG AEVTAVEFLG HVGGIGIDME
ISKKFQRILQ KQGFKFKLNP KVPGATKRSD GKIDVSVEAA PGGKAEVIPC DVLLVCIGRR
PFTQNLGLEE LGIELDPRGR IPVNTRFQTK IPNIYAIGDV VAGPMLAHKA EDEGIICVEG
MAGGAVHIDY NCVPSVIYTH PEVAWVGKSE EQLKEEGIEY KVGKFPFAAN SRAKTNADTD
GMVKILGQKS TDRVLGAHIL GPGAGEMVNE AALALEYGAS CEDIARVCHA HPTLSEAFR
