ID   ODP2_BOVIN              Reviewed;         647 AA.
AC   P11180; F1N690; V6F7T1;
DT   01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
DT   24-JAN-2024, sequence version 2.
DT   27-MAR-2024, entry version 90.
DE   RecName: Full=Dihydrolipoyllysine-residue acetyltransferase component of pyruvate dehydrogenase complex {ECO:0000250|UniProtKB:P10515};
DE            EC=2.3.1.12 {ECO:0000269|PubMed:3117054};
DE   AltName: Full=Dihydrolipoamide acetyltransferase component of pyruvate dehydrogenase complex {ECO:0000250|UniProtKB:P08461};
DE   AltName: Full=Pyruvate dehydrogenase complex component E2;
DE            Short=PDC-E2 {ECO:0000250|UniProtKB:P10515};
DE            Short=PDCE2;
DE   Flags: Precursor;
GN   Name=DLAT {ECO:0000250|UniProtKB:P10515};
OS   Bos taurus (Bovine).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC   Bovinae; Bos.
OX   NCBI_TaxID=9913;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=Hereford;
RX   PubMed=19393038; DOI=10.1186/gb-2009-10-4-r42;
RA   Zimin A.V., Delcher A.L., Florea L., Kelley D.R., Schatz M.C., Puiu D.,
RA   Hanrahan F., Pertea G., Van Tassell C.P., Sonstegard T.S., Marcais G.,
RA   Roberts M., Subramanian P., Yorke J.A., Salzberg S.L.;
RT   "A whole-genome assembly of the domestic cow, Bos taurus.";
RL   Genome Biol. 10:R42.01-R42.10(2009).
RN   [2]
RP   PROTEIN SEQUENCE OF 128-137, LIPOYLATION AT LYS-132, FUNCTION, CATALYTIC
RP   ACTIVITY, AND COFACTOR.
RX   PubMed=3117054; DOI=10.1042/bj2450919;
RA   Bradford A.P., Howell S., Aitken A., James L.A., Yeaman S.J.;
RT   "Primary structure around the lipoate-attachment site on the E2 component
RT   of bovine heart pyruvate dehydrogenase complex.";
RL   Biochem. J. 245:919-922(1987).
RN   [3]
RP   SUBUNIT.
RX   PubMed=20361979; DOI=10.1016/j.jmb.2010.03.043;
RA   Vijayakrishnan S., Kelly S.M., Gilbert R.J., Callow P., Bhella D.,
RA   Forsyth T., Lindsay J.G., Byron O.;
RT   "Solution structure and characterisation of the human pyruvate
RT   dehydrogenase complex core assembly.";
RL   J. Mol. Biol. 399:71-93(2010).
RN   [4] {ECO:0007744|PDB:7UOM}
RP   STRUCTURE BY ELECTRON MICROSCOPY (3.80 ANGSTROMS), AND SUBUNIT.
RX   PubMed=36414632; DOI=10.1038/s41421-022-00487-y;
RA   Liu S., Xia X., Zhen J., Li Z., Zhou Z.H.;
RT   "Structures and comparison of endogenous 2-oxoglutarate and pyruvate
RT   dehydrogenase complexes from bovine kidney.";
RL   Cell Discov. 8:126-126(2022).
CC   -!- FUNCTION: As part of the pyruvate dehydrogenase complex, catalyzes the
CC       transfers of an acetyl group to a lipoic acid moiety (PubMed:3117054).
CC       The pyruvate dehydrogenase complex, catalyzes the overall conversion of
CC       pyruvate to acetyl-CoA and CO(2), and thereby links cytoplasmic
CC       glycolysis and the mitochondrial tricarboxylic acid (TCA) cycle
CC       (Probable). {ECO:0000269|PubMed:3117054, ECO:0000305|PubMed:3117054}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=acetyl-CoA + N(6)-[(R)-dihydrolipoyl]-L-lysyl-[protein] = CoA
CC         + N(6)-[(R)-S(8)-acetyldihydrolipoyl]-L-lysyl-[protein];
CC         Xref=Rhea:RHEA:17017, Rhea:RHEA-COMP:10475, Rhea:RHEA-COMP:10478,
CC         ChEBI:CHEBI:57287, ChEBI:CHEBI:57288, ChEBI:CHEBI:83100,
CC         ChEBI:CHEBI:83111; EC=2.3.1.12;
CC         Evidence={ECO:0000269|PubMed:3117054};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:17018;
CC         Evidence={ECO:0000269|PubMed:3117054};
CC   -!- COFACTOR:
CC       Name=(R)-lipoate; Xref=ChEBI:CHEBI:83088;
CC         Evidence={ECO:0000269|PubMed:3117054};
CC       Note=Binds 2 lipoyl cofactors covalently. {ECO:0000305|PubMed:3117054};
CC   -!- SUBUNIT: Part of the pyruvate dehydrogenase complex (PDHc) that is a
CC       multi-enzyme complex composed of multiple copies of three enzymes,
CC       pyruvate dehydrogenase (subunits PDH1A and PDHB, E1 component),
CC       dihydrolipoamide acetyltransferase (DLAT, E2 component), and
CC       dihydrolipoamide dehydrogenase (DLD, E3 component) to which is added an
CC       additional protein the E3-binding protein (PDHX, E3BP) (Probable). In
CC       terms of structural architecture, the E2 and E3BP components assemble
CC       into a 60meric central core with icosahedral symmetry (PubMed:20361979,
CC       PubMed:36414632). The central core is decorated with E1 and E3 proteins
CC       (Probable). Currently, two alternative models for the E2:E3BP
CC       stoichiometry are considered as being either 48:12 (E2(48)-E3BP(12)) or
CC       40:20 (E2(40)-E3BP(20)). Interacts with PDK2 and PDK3. Interacts with
CC       SIRT4. Interacts with PDHB (By similarity).
CC       {ECO:0000250|UniProtKB:P10515, ECO:0000269|PubMed:20361979,
CC       ECO:0000269|PubMed:36414632, ECO:0000305|PubMed:36414632}.
CC   -!- SUBCELLULAR LOCATION: Mitochondrion matrix
CC       {ECO:0000250|UniProtKB:P08461}.
CC   -!- PTM: Delipoylated at Lys-132 and Lys-259 by SIRT4, delipoylation
CC       decreases the PHD complex activity. {ECO:0000250|UniProtKB:P10515}.
CC   -!- SIMILARITY: Belongs to the 2-oxoacid dehydrogenase family.
CC       {ECO:0000305}.
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DR   EMBL; GJ062397; DAA22403.1; -; Genomic_DNA.
DR   RefSeq; NP_001192659.2; NM_001205730.2.
DR   PDB; 7UOM; EM; 3.80 A; 01/02/03/04/05/0z/1a/1b/1c/1d/1e/1f/1g/1h/1i/1j/1k/1l/1m/1n/1o/1p/1q/1r/1s/1t/1u/1v/1w/1x=1-647.
DR   PDBsum; 7UOM; -.
DR   AlphaFoldDB; F1N690; -.
DR   EMDB; EMD-26650; -.
DR   CORUM; P11180; -.
DR   SwissPalm; P11180; -.
DR   PaxDb; 9913-ENSBTAP00000014176; -.
DR   Ensembl; ENSBTAT00000014176.6; ENSBTAP00000014176.5; ENSBTAG00000010709.6.
DR   GeneID; 512723; -.
DR   KEGG; bta:512723; -.
DR   CTD; 1737; -.
DR   VEuPathDB; HostDB:ENSBTAG00000010709; -.
DR   VGNC; VGNC:109392; DLAT.
DR   eggNOG; KOG0557; Eukaryota.
DR   GeneTree; ENSGT00940000154943; -.
DR   HOGENOM; CLU_016733_10_2_1; -.
DR   InParanoid; P11180; -.
DR   OMA; TMEFESF; -.
DR   OrthoDB; 5483022at2759; -.
DR   TreeFam; TF106145; -.
DR   Reactome; R-BTA-204174; Regulation of pyruvate dehydrogenase (PDH) complex.
DR   Reactome; R-BTA-389661; Glyoxylate metabolism and glycine degradation.
DR   Reactome; R-BTA-5362517; Signaling by Retinoic Acid.
DR   Reactome; R-BTA-70268; Pyruvate metabolism.
DR   Proteomes; UP000009136; Chromosome 15.
DR   Bgee; ENSBTAG00000010709; Expressed in cardiac ventricle and 104 other tissues.
DR   GO; GO:0005759; C:mitochondrial matrix; IEA:UniProtKB-SubCell.
DR   GO; GO:0004742; F:dihydrolipoyllysine-residue acetyltransferase activity; IDA:UniProtKB.
DR   GO; GO:0006006; P:glucose metabolic process; IEA:UniProtKB-KW.
DR   GO; GO:0006099; P:tricarboxylic acid cycle; IDA:UniProtKB.
DR   CDD; cd06849; lipoyl_domain; 2.
DR   Gene3D; 2.40.50.100; -; 2.
DR   Gene3D; 3.30.559.10; Chloramphenicol acetyltransferase-like domain; 1.
DR   Gene3D; 4.10.320.10; E3-binding domain; 1.
DR   InterPro; IPR003016; 2-oxoA_DH_lipoyl-BS.
DR   InterPro; IPR001078; 2-oxoacid_DH_actylTfrase.
DR   InterPro; IPR000089; Biotin_lipoyl.
DR   InterPro; IPR023213; CAT-like_dom_sf.
DR   InterPro; IPR045257; E2/Pdx1.
DR   InterPro; IPR036625; E3-bd_dom_sf.
DR   InterPro; IPR006257; LAT1.
DR   InterPro; IPR004167; PSBD.
DR   InterPro; IPR011053; Single_hybrid_motif.
DR   NCBIfam; TIGR01349; PDHac_trf_mito; 1.
DR   PANTHER; PTHR23151; DIHYDROLIPOAMIDE ACETYL/SUCCINYL-TRANSFERASE-RELATED; 1.
DR   PANTHER; PTHR23151:SF90; DIHYDROLIPOYLLYSINE-RESIDUE ACETYLTRANSFERASE COMPONENT OF PYRUVATE DEHYDROGENASE COMPLEX, MITOCHONDRIAL; 1.
DR   Pfam; PF00198; 2-oxoacid_dh; 1.
DR   Pfam; PF00364; Biotin_lipoyl; 2.
DR   Pfam; PF02817; E3_binding; 1.
DR   SUPFAM; SSF52777; CoA-dependent acyltransferases; 1.
DR   SUPFAM; SSF47005; Peripheral subunit-binding domain of 2-oxo acid dehydrogenase complex; 1.
DR   SUPFAM; SSF51230; Single hybrid motif; 2.
DR   PROSITE; PS50968; BIOTINYL_LIPOYL; 2.
DR   PROSITE; PS00189; LIPOYL; 2.
DR   PROSITE; PS51826; PSBD; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Acetylation; Acyltransferase; Carbohydrate metabolism;
KW   Direct protein sequencing; Glucose metabolism; Lipoyl; Mitochondrion;
KW   Phosphoprotein; Reference proteome; Repeat; Transferase; Transit peptide;
KW   Tricarboxylic acid cycle.
FT   TRANSIT         1..86
FT                   /note="Mitochondrion"
FT                   /evidence="ECO:0000255"
FT   CHAIN           87..647
FT                   /note="Dihydrolipoyllysine-residue acetyltransferase
FT                   component of pyruvate dehydrogenase complex"
FT                   /evidence="ECO:0000255"
FT                   /id="PRO_0000162297"
FT   DOMAIN          91..167
FT                   /note="Lipoyl-binding 1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01066"
FT   DOMAIN          218..294
FT                   /note="Lipoyl-binding 2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01066"
FT   DOMAIN          356..393
FT                   /note="Peripheral subunit-binding (PSBD)"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01170"
FT   REGION          184..216
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          311..352
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        188..209
FT                   /note="Pro residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        313..347
FT                   /note="Pro residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   ACT_SITE        620
FT                   /evidence="ECO:0000250|UniProtKB:Q9N0F1"
FT   ACT_SITE        624
FT                   /evidence="ECO:0000250|UniProtKB:Q9N0F1"
FT   BINDING         461
FT                   /ligand="CoA"
FT                   /ligand_id="ChEBI:CHEBI:57287"
FT                   /evidence="ECO:0000250|UniProtKB:P11181"
FT   BINDING         475
FT                   /ligand="CoA"
FT                   /ligand_id="ChEBI:CHEBI:57287"
FT                   /evidence="ECO:0000250|UniProtKB:P11181"
FT   BINDING         566
FT                   /ligand="CoA"
FT                   /ligand_id="ChEBI:CHEBI:57287"
FT                   /evidence="ECO:0000250|UniProtKB:P11181"
FT   BINDING         567
FT                   /ligand="CoA"
FT                   /ligand_id="ChEBI:CHEBI:57287"
FT                   /evidence="ECO:0000250|UniProtKB:P11181"
FT   BINDING         591
FT                   /ligand="CoA"
FT                   /ligand_id="ChEBI:CHEBI:57287"
FT                   /evidence="ECO:0000250|UniProtKB:P11181"
FT   MOD_RES         100
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P10515"
FT   MOD_RES         132
FT                   /note="N6-lipoyllysine"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01066,
FT                   ECO:0000269|PubMed:3117054"
FT   MOD_RES         259
FT                   /note="N6-lipoyllysine"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01066"
FT   MOD_RES         466
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:P10515"
FT   MOD_RES         473
FT                   /note="N6-succinyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:Q8BMF4"
FT   MOD_RES         547
FT                   /note="N6-succinyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:Q8BMF4"
SQ   SEQUENCE   647 AA;  69067 MW;  2BB4F441AC02791A CRC64;
     MWRVCARRAQ NAAPRAGFGA RWTAFREEPG APCVTPQAGS ALARCSSKTP GYGRVRALCG
     WSPVSRATPR NRVLLQLWGS PSRRWYSLPP HQKVPLPSLS PTMQAGTIAR WEKKEGEKIN
     EGELIAEVET DKATVGFESV EECYMAKILV AEGTRDVPVG AIICITVDKP EDVEAFKNYT
     LDSSAAPAPP AAPAPTPAAP APSPTPSAQA PGSSYPTHMQ VLLPALSPTM TMGTVQRWEK
     KVGEKLNEGD LLAEIETDKA TIGFEVQEEG YLAKILIPEG TRDVPLGTPL CIIVEKEADI
     PAFADYRPAE VTDLKPPAPP PIPSPAAPVP PAPQPVAPPP SAPRPAAPAG PKGRVFVSPL
     AKKLAAEKGI DLTQVKGTGP DGRIIKKDID SFVPTKAAPT PAAAVPPPSP GVAPVPTGVF
     TDIPISNIRR VIAQRLMQSK QTIPHYYLSI DVNMGEVLLV RKELNKMLEG KSKISVNDFI
     IKASALACLK VPEANSSWMD TVIRQNHVVD ISVAVSTPAG LITPIVFNAH IKGLETIAND
     VVSLATKARE GKLQPHEFQG GTFTISNLGM FGIKNFSAII NPPQACILAI GASEDRLVPA
     DNEKGFDVAS MMSVTLSCDH RVVDGAVGAQ WLAEFRKYLE KPITMLL
//