ID   ODP2_RAT                Reviewed;         632 AA.
AC   P08461; Q3B7V7;
DT   01-AUG-1988, integrated into UniProtKB/Swiss-Prot.
DT   12-DEC-2006, sequence version 3.
DT   27-MAR-2024, entry version 197.
DE   RecName: Full=Dihydrolipoyllysine-residue acetyltransferase component of pyruvate dehydrogenase complex, mitochondrial {ECO:0000305};
DE            EC=2.3.1.12 {ECO:0000250|UniProtKB:P11180};
DE   AltName: Full=70 kDa mitochondrial autoantigen of primary biliary cirrhosis {ECO:0000305|PubMed:3571977};
DE            Short=PBC;
DE   AltName: Full=Dihydrolipoamide acetyltransferase component of pyruvate dehydrogenase complex {ECO:0000305|PubMed:1581353};
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:0000312|RGD:619859};
OS   Rattus norvegicus (Rat).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Rattus.
OX   NCBI_TaxID=10116;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Testis;
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA project:
RT   the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 92-632, AND PROTEIN SEQUENCE OF 78-91.
RC   TISSUE=Heart;
RX   PubMed=1581353; DOI=10.1016/0167-4781(92)90109-d;
RA   Matuda S., Nakano K., Ohta S., Shimura M., Yamanaka T., Nakagawa S.,
RA   Titani K., Miyata T.;
RT   "Molecular cloning of dihydrolipoamide acetyltransferase of the rat
RT   pyruvate dehydrogenase complex: sequence comparison and evolutionary
RT   relationship to other dihydrolipoamide acyltransferases.";
RL   Biochim. Biophys. Acta 1131:114-118(1992).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 163-632, AND SUBCELLULAR LOCATION.
RC   TISSUE=Liver;
RX   PubMed=3571977;
RA   Gershwin M.E., McKay I.R., Sturgess A., Coppel R.L.;
RT   "Identification and specificity of a cDNA encoding the 70 kd mitochondrial
RT   antigen recognized in primary biliary cirrhosis.";
RL   J. Immunol. 138:3525-3531(1987).
RN   [4]
RP   PROTEIN SEQUENCE OF 397-414, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC   STRAIN=Sprague-Dawley; TISSUE=Hippocampus;
RA   Lubec G., Chen W.-Q.;
RL   Submitted (APR-2007) to UniProtKB.
RN   [5]
RP   IDENTIFICATION BY MASS SPECTROMETRY, AND TISSUE SPECIFICITY.
RX   PubMed=19423663; DOI=10.1530/rep-09-0052;
RA   Khan S.A., Suryawanshi A.R., Ranpura S.A., Jadhav S.V., Khole V.V.;
RT   "Identification of novel immunodominant epididymal sperm proteins using
RT   combinatorial approach.";
RL   Reproduction 138:81-93(2009).
CC   -!- FUNCTION: As part of the pyruvate dehydrogenase complex, catalyzes the
CC       transfers of an acetyl group to a lipoic acid moiety. The pyruvate
CC       dehydrogenase complex, catalyzes the overall conversion of pyruvate to
CC       acetyl-CoA and CO(2), and thereby links cytoplasmic glycolysis and the
CC       mitochondrial tricarboxylic acid (TCA) cycle.
CC       {ECO:0000250|UniProtKB:P11180}.
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:0000250|UniProtKB:P11180};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:17018;
CC         Evidence={ECO:0000250|UniProtKB:P11180};
CC   -!- COFACTOR:
CC       Name=(R)-lipoate; Xref=ChEBI:CHEBI:83088;
CC         Evidence={ECO:0000250|UniProtKB:P10515};
CC       Note=Binds 2 lipoyl cofactors covalently.
CC       {ECO:0000250|UniProtKB:P10515};
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) (By similarity).
CC       In terms of structural architecture, the E2 and E3BP components
CC       assemble into a 60meric central core with icosahedral symmetry (By
CC       similarity). The central core is decorated with E1 and E3 proteins (By
CC       similarity). 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:0000250|UniProtKB:P11180}.
CC   -!- SUBCELLULAR LOCATION: Mitochondrion matrix
CC       {ECO:0000305|PubMed:3571977}.
CC   -!- TISSUE SPECIFICITY: Expressed in flagella of epididymal sperm.
CC       {ECO:0000269|PubMed:19423663}.
CC   -!- PTM: Delipoylated at Lys-123 and Lys-249 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; BC107440; AAI07441.1; -; mRNA.
DR   EMBL; D10655; BAA01504.1; -; mRNA.
DR   EMBL; D00092; BAA20956.1; -; mRNA.
DR   EMBL; M16075; AAA41813.1; -; mRNA.
DR   PIR; S21766; S21766.
DR   RefSeq; NP_112287.1; NM_031025.1.
DR   AlphaFoldDB; P08461; -.
DR   EMDB; EMD-16672; -.
DR   SMR; P08461; -.
DR   BioGRID; 249554; 4.
DR   IntAct; P08461; 5.
DR   MINT; P08461; -.
DR   STRING; 10116.ENSRNOP00000032890; -.
DR   GlyGen; P08461; 2 sites, 1 O-linked glycan (2 sites).
DR   iPTMnet; P08461; -.
DR   PhosphoSitePlus; P08461; -.
DR   SwissPalm; P08461; -.
DR   jPOST; P08461; -.
DR   PaxDb; 10116-ENSRNOP00000032890; -.
DR   Ensembl; ENSRNOT00000032152.5; ENSRNOP00000032890.4; ENSRNOG00000009994.6.
DR   Ensembl; ENSRNOT00055048858; ENSRNOP00055040168; ENSRNOG00055028232.
DR   Ensembl; ENSRNOT00060027521; ENSRNOP00060022110; ENSRNOG00060016068.
DR   Ensembl; ENSRNOT00065028610; ENSRNOP00065022660; ENSRNOG00065017146.
DR   GeneID; 81654; -.
DR   KEGG; rno:81654; -.
DR   UCSC; RGD:619859; rat.
DR   AGR; RGD:619859; -.
DR   CTD; 1737; -.
DR   RGD; 619859; Dlat.
DR   eggNOG; KOG0557; Eukaryota.
DR   GeneTree; ENSGT00940000154943; -.
DR   HOGENOM; CLU_016733_10_2_1; -.
DR   InParanoid; P08461; -.
DR   OMA; TMEFESF; -.
DR   OrthoDB; 5483022at2759; -.
DR   PhylomeDB; P08461; -.
DR   TreeFam; TF106145; -.
DR   Reactome; R-RNO-204174; Regulation of pyruvate dehydrogenase (PDH) complex.
DR   Reactome; R-RNO-389661; Glyoxylate metabolism and glycine degradation.
DR   Reactome; R-RNO-5362517; Signaling by Retinoic Acid.
DR   Reactome; R-RNO-70268; Pyruvate metabolism.
DR   PRO; PR:P08461; -.
DR   Proteomes; UP000002494; Chromosome 8.
DR   Bgee; ENSRNOG00000009994; Expressed in heart and 18 other cell types or tissues.
DR   GO; GO:0005759; C:mitochondrial matrix; ISO:RGD.
DR   GO; GO:0005967; C:mitochondrial pyruvate dehydrogenase complex; ISO:RGD.
DR   GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
DR   GO; GO:0045254; C:pyruvate dehydrogenase complex; IDA:RGD.
DR   GO; GO:0016407; F:acetyltransferase activity; ISO:RGD.
DR   GO; GO:0004742; F:dihydrolipoyllysine-residue acetyltransferase activity; IDA:RGD.
DR   GO; GO:0042802; F:identical protein binding; ISO:RGD.
DR   GO; GO:0000166; F:nucleotide binding; TAS:RGD.
DR   GO; GO:0006086; P:acetyl-CoA biosynthetic process from pyruvate; IDA:RGD.
DR   GO; GO:0006006; P:glucose metabolic process; IEA:UniProtKB-KW.
DR   GO; GO:0006099; P:tricarboxylic acid cycle; ISS: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.
DR   World-2DPAGE; 0004:P08461; -.
PE   1: Evidence at protein level;
KW   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..77
FT                   /note="Mitochondrion"
FT                   /evidence="ECO:0000269|PubMed:1581353"
FT   CHAIN           78..632
FT                   /note="Dihydrolipoyllysine-residue acetyltransferase
FT                   component of pyruvate dehydrogenase complex, mitochondrial"
FT                   /id="PRO_0000162298"
FT   DOMAIN          82..158
FT                   /note="Lipoyl-binding 1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01066"
FT   DOMAIN          208..284
FT                   /note="Lipoyl-binding 2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01066"
FT   DOMAIN          342..379
FT                   /note="Peripheral subunit-binding (PSBD)"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01170"
FT   ACT_SITE        605
FT                   /evidence="ECO:0000250|UniProtKB:Q9N0F1"
FT   ACT_SITE        609
FT                   /evidence="ECO:0000250|UniProtKB:Q9N0F1"
FT   BINDING         446
FT                   /ligand="CoA"
FT                   /ligand_id="ChEBI:CHEBI:57287"
FT                   /evidence="ECO:0000250|UniProtKB:P11181"
FT   BINDING         460
FT                   /ligand="CoA"
FT                   /ligand_id="ChEBI:CHEBI:57287"
FT                   /evidence="ECO:0000250|UniProtKB:P11181"
FT   BINDING         551
FT                   /ligand="CoA"
FT                   /ligand_id="ChEBI:CHEBI:57287"
FT                   /evidence="ECO:0000250|UniProtKB:P11181"
FT   BINDING         552
FT                   /ligand="CoA"
FT                   /ligand_id="ChEBI:CHEBI:57287"
FT                   /evidence="ECO:0000250|UniProtKB:P11181"
FT   BINDING         576
FT                   /ligand="CoA"
FT                   /ligand_id="ChEBI:CHEBI:57287"
FT                   /evidence="ECO:0000250|UniProtKB:P11181"
FT   MOD_RES         91
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P10515"
FT   MOD_RES         123
FT                   /note="N6-lipoyllysine"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01066"
FT   MOD_RES         249
FT                   /note="N6-lipoyllysine"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01066"
FT   MOD_RES         451
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:P10515"
FT   MOD_RES         458
FT                   /note="N6-succinyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:Q8BMF4"
FT   MOD_RES         532
FT                   /note="N6-succinyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:Q8BMF4"
FT   CONFLICT        150..152
FT                   /note="VGS -> IGC (in Ref. 2; BAA01504)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        163..164
FT                   /note="DI -> GP (in Ref. 3; BAA20956/AAA41813)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        601..632
FT                   /note="LSCDHRVVDGAVGAQWLAEFKKYLEKPVTMLL -> HSAVIIELWMEQLEPS
FT                   GLL (in Ref. 3; BAA20956)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   632 AA;  67166 MW;  3F0EDBD44D93EB68 CRC64;
     MWRVCARRVQ SAVPRAGFRA RWATLKGPRT GPAAVRCGSG IPSYGVRSLC GWSYGSATVP
     RNRILQQLLG SPSRRSYSLP PHQKVPLPSL SPTMQAGTIA RWEKKEGEKI SEGDLIAEVE
     TDKATVGFES LEECYMAKIL VPEGTRDVPV GSIICITVEK PQDIEAFKNY TLDSATAATQ
     AAPAPAAAPA AAPAAPSASA PGSSYPVHMQ IVLPALSPTM TMGTVQRWEK KVGEKLSEGD
     LLAEIETDKA TIGFEVQEEG YLAKILVPEG TRDVPLGTPL CIIVEKQEDI AAFADYRPTE
     VTSLKPQAPP PVPPPVAAVP PIPQPLAPTP SAAPAGPKGR VFVSPLAKKL AAEKGIDLTQ
     VKGTGPEGRI IKKDIDSFVP TKAAPAAAAA APPGPRVAPT PAGVFIDIPI SNIRRVIAQR
     LMQSKQTIPH YYLSVDVNMG EVLLVRKELN KMLEGKGKIS VNDFIIKASA LACLKVPEAN
     SSWMDTVIRQ NHVVDVSVAV STPAGLITPI VFNAHIKGLE TIASDVVSLA SKAREGKLQP
     HEFQGGTFTI SNLGMFGIKN FSAIINPPQA CILAIGASED KLIPADNEKG FDVASVMSVT
     LSCDHRVVDG AVGAQWLAEF KKYLEKPVTM LL
//