ID   ODBA_BOVIN              Reviewed;         455 AA.
AC   P11178;
DT   01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
DT   01-JUL-1989, sequence version 1.
DT   04-NOV-2026, entry version 147.
DE   RecName: Full=2-oxoisovalerate dehydrogenase subunit alpha, mitochondrial {ECO:0000305|PubMed:5656388};
DE            EC=1.2.4.4 {ECO:0000269|PubMed:5656388};
DE   AltName: Full=Branched-chain alpha-keto acid dehydrogenase E1 component alpha chain;
DE            Short=BCKDE1A;
DE            Short=BCKDH E1-alpha;
DE   Flags: Precursor;
GN   Name=BCKDHA;
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 [MRNA].
RX   PubMed=3379058; DOI=10.1016/s0021-9258(18)68408-x;
RA   Hu C.-W.C., Lau K.S., Griffin T.A., Chuang J.L., Fisher C.W., Cox R.P.,
RA   Chuang D.T.;
RT   "Isolation and sequencing of a cDNA encoding the decarboxylase (E1)alpha
RT   precursor of bovine branched-chain alpha-keto acid dehydrogenase complex.
RT   Expression of E1 alpha mRNA and subunit in maple-syrup-urine-disease and
RT   3T3-L1 cells.";
RL   J. Biol. Chem. 263:9007-9014(1988).
RN   [2]
RP   FUNCTION, AND CATALYTIC ACTIVITY.
RX   PubMed=5656388; DOI=10.1016/s0021-9258(18)93339-9;
RA   Bowden J.A., Connelly J.L.;
RT   "Branched chain alpha-keto acid metabolism. II. Evidence for the common
RT   identity of alpha-ketoisocaproic acid and alpha-keto-beta-methyl-valeric
RT   acid dehydrogenases.";
RL   J. Biol. Chem. 243:3526-3531(1968).
RN   [3]
RP   FUNCTION, CATALYTIC ACTIVITY, SUBUNIT, SUBCELLULAR LOCATION, AND TISSUE
RP   SPECIFICITY.
RX   PubMed=283398; DOI=10.1073/pnas.75.10.4881;
RA   Pettit F.H., Yeaman S.J., Reed L.J.;
RT   "Purification and characterization of branched chain alpha-keto acid
RT   dehydrogenase complex of bovine kidney.";
RL   Proc. Natl. Acad. Sci. U.S.A. 75:4881-4885(1978).
RN   [4]
RP   CATALYTIC ACTIVITY, AND SUBUNIT.
RX   PubMed=447664; DOI=10.1016/s0021-9258(18)50626-8;
RA   Danner D.J., Lemmon S.K., Besharse J.C., Elsas L.J. II;
RT   "Purification and characterization of branched chain alpha-ketoacid
RT   dehydrogenase from bovine liver mitochondria.";
RL   J. Biol. Chem. 254:5522-5526(1979).
CC   -!- FUNCTION: Together with BCKDHB forms the heterotetrameric E1 subunit of
CC       the mitochondrial branched-chain alpha-ketoacid dehydrogenase (BCKD)
CC       complex. The BCKD complex catalyzes the multi-step oxidative
CC       decarboxylation of alpha-ketoacids derived from the branched-chain
CC       amino-acids valine, leucine and isoleucine producing CO2 and acyl-CoA
CC       which is subsequently utilized to produce energy. The E1 subunit
CC       catalyzes the first step with the decarboxylation of the alpha-ketoacid
CC       forming an enzyme-product intermediate. A reductive acylation mediated
CC       by the lipoylamide cofactor of E2 extracts the acyl group from the E1
CC       active site for the next step of the reaction.
CC       {ECO:0000269|PubMed:283398, ECO:0000269|PubMed:5656388}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=N(6)-[(R)-lipoyl]-L-lysyl-[protein] + 3-methyl-2-oxobutanoate
CC         + H(+) = N(6)-[(R)-S(8)-2-methylpropanoyldihydrolipoyl]-L-lysyl-
CC         [protein] + CO2; Xref=Rhea:RHEA:13457, Rhea:RHEA-COMP:10474,
CC         Rhea:RHEA-COMP:10497, ChEBI:CHEBI:11851, ChEBI:CHEBI:15378,
CC         ChEBI:CHEBI:16526, ChEBI:CHEBI:83099, ChEBI:CHEBI:83142; EC=1.2.4.4;
CC         Evidence={ECO:0000269|PubMed:283398, ECO:0000269|PubMed:447664,
CC         ECO:0000269|PubMed:5656388};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:13458;
CC         Evidence={ECO:0000305|PubMed:5656388};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=N(6)-[(R)-lipoyl]-L-lysyl-[protein] + 4-methyl-2-oxopentanoate
CC         + H(+) = N(6)-[(R)-S(8)-3-methylbutanoyldihydrolipoyl]-L-lysyl-
CC         [protein] + CO2; Xref=Rhea:RHEA:84639, Rhea:RHEA-COMP:10474,
CC         Rhea:RHEA-COMP:20408, ChEBI:CHEBI:15378, ChEBI:CHEBI:16526,
CC         ChEBI:CHEBI:17865, ChEBI:CHEBI:83099, ChEBI:CHEBI:233973;
CC         Evidence={ECO:0000269|PubMed:447664, ECO:0000269|PubMed:5656388};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:84640;
CC         Evidence={ECO:0000305|PubMed:5656388};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=N(6)-[(R)-lipoyl]-L-lysyl-[protein] + (S)-3-methyl-2-
CC         oxopentanoate + H(+) = N(6)-{(R)-S(8)-[(2S)-2-
CC         methylbutanoyl]dihydrolipoyl}-L-lysyl-[protein] + CO2;
CC         Xref=Rhea:RHEA:84643, Rhea:RHEA-COMP:10474, Rhea:RHEA-COMP:20409,
CC         ChEBI:CHEBI:15378, ChEBI:CHEBI:16526, ChEBI:CHEBI:35146,
CC         ChEBI:CHEBI:83099, ChEBI:CHEBI:233974;
CC         Evidence={ECO:0000269|PubMed:447664, ECO:0000269|PubMed:5656388};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:84644;
CC         Evidence={ECO:0000305|PubMed:5656388};
CC   -!- COFACTOR:
CC       Name=thiamine diphosphate; Xref=ChEBI:CHEBI:58937;
CC         Evidence={ECO:0000250|UniProtKB:P12694};
CC       Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC         Evidence={ECO:0000250|UniProtKB:P12694};
CC   -!- SUBUNIT: Heterotetramer of 2 alpha/BCKDHA and 2 beta chains/BCKDHB that
CC       forms the branched-chain alpha-keto acid decarboxylase (E1) component
CC       of the BCKD complex (PubMed:283398). The branched-chain alpha-ketoacid
CC       dehydrogenase is a large complex composed of three major building
CC       blocks E1, E2 and E3. It is organized around E2, a 24-meric cubic core
CC       composed of DBT, to which are associated 6 to 12 copies of E1, and
CC       approximately 6 copies of the dehydrogenase E3, a DLD dimer
CC       (PubMed:283398, PubMed:447664). Interacts with PPM1K.
CC       {ECO:0000250|UniProtKB:P12694, ECO:0000269|PubMed:283398,
CC       ECO:0000269|PubMed:447664}.
CC   -!- SUBCELLULAR LOCATION: Mitochondrion matrix {ECO:0000269|PubMed:283398}.
CC   -!- TISSUE SPECIFICITY: Expressed in kidney (at protein level).
CC       {ECO:0000269|PubMed:283398}.
CC   -!- PTM: Phosphorylated at Ser-347 by BCKDK and dephosphorylated by protein
CC       phosphatase PPM1K. {ECO:0000250|UniProtKB:P12694}.
CC   -!- SIMILARITY: Belongs to the BCKDHA family. {ECO:0000305}.
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DR   EMBL; J03759; AAA30595.1; -; mRNA.
DR   PIR; A28073; DEBOXA.
DR   RefSeq; NP_776931.1; NM_174506.1.
DR   AlphaFoldDB; P11178; -.
DR   SMR; P11178; -.
DR   FunCoup; P11178; 1057.
DR   IntAct; P11178; 1.
DR   STRING; 9913.ENSBTAP00000021342; -.
DR   PaxDb; 9913-ENSBTAP00000021342; -.
DR   GeneID; 282149; -.
DR   KEGG; bta:282149; -.
DR   CTD; 593; -.
DR   eggNOG; KOG1182; Eukaryota.
DR   InParanoid; P11178; -.
DR   OrthoDB; 3845at2759; -.
DR   SABIO-RK; P11178; -.
DR   Proteomes; UP000009136; Unplaced.
DR   GO; GO:0160157; C:branched-chain alpha-ketoacid dehydrogenase complex; IDA:UniProtKB.
DR   GO; GO:0005759; C:mitochondrial matrix; IDA:UniProtKB.
DR   GO; GO:0003863; F:branched-chain 2-oxo acid dehydrogenase activity; EXP:UniProtKB.
DR   GO; GO:0120552; P:branched-chain alpha-keto acid decarboxylation to branched-chain acyl-CoA; IDA:UniProtKB.
DR   GO; GO:0009083; P:branched-chain amino acid catabolic process; IBA:GO_Central.
DR   CDD; cd02000; TPP_E1_PDC_ADC_BCADC; 1.
DR   FunFam; 3.40.50.970:FF:000015; 2-oxoisovalerate dehydrogenase subunit alpha; 1.
DR   Gene3D; 3.40.50.970; -; 1.
DR   InterPro; IPR050771; Alpha-ketoacid_DH_E1_comp.
DR   InterPro; IPR001017; DH_E1.
DR   InterPro; IPR029061; THDP-binding.
DR   PANTHER; PTHR43380; 2-OXOISOVALERATE DEHYDROGENASE SUBUNIT ALPHA, MITOCHONDRIAL; 1.
DR   PANTHER; PTHR43380:SF1; 2-OXOISOVALERATE DEHYDROGENASE SUBUNIT ALPHA, MITOCHONDRIAL; 1.
DR   Pfam; PF00676; E1_dh; 1.
DR   SUPFAM; SSF52518; Thiamin diphosphate-binding fold (THDP-binding); 1.
PE   1: Evidence at protein level;
KW   Acetylation; Magnesium; Metal-binding; Mitochondrion; Oxidoreductase;
KW   Phosphoprotein; Potassium; Reference proteome; Thiamine pyrophosphate;
KW   Transit peptide.
FT   TRANSIT         1..55
FT                   /note="Mitochondrion"
FT   CHAIN           56..455
FT                   /note="2-oxoisovalerate dehydrogenase subunit alpha,
FT                   mitochondrial"
FT                   /id="PRO_0000020464"
FT   BINDING         168
FT                   /ligand="thiamine diphosphate"
FT                   /ligand_id="ChEBI:CHEBI:58937"
FT                   /ligand_note="ligand shared with beta subunit"
FT                   /evidence="ECO:0000250|UniProtKB:P12694"
FT   BINDING         169
FT                   /ligand="thiamine diphosphate"
FT                   /ligand_id="ChEBI:CHEBI:58937"
FT                   /ligand_note="ligand shared with beta subunit"
FT                   /evidence="ECO:0000250|UniProtKB:P12694"
FT   BINDING         216
FT                   /ligand="K(+)"
FT                   /ligand_id="ChEBI:CHEBI:29103"
FT                   /ligand_note="structural"
FT                   /evidence="ECO:0000250|UniProtKB:P12694"
FT   BINDING         217
FT                   /ligand="thiamine diphosphate"
FT                   /ligand_id="ChEBI:CHEBI:58937"
FT                   /ligand_note="ligand shared with beta subunit"
FT                   /evidence="ECO:0000250|UniProtKB:P12694"
FT   BINDING         218
FT                   /ligand="K(+)"
FT                   /ligand_id="ChEBI:CHEBI:29103"
FT                   /ligand_note="structural"
FT                   /evidence="ECO:0000250|UniProtKB:P12694"
FT   BINDING         221
FT                   /ligand="K(+)"
FT                   /ligand_id="ChEBI:CHEBI:29103"
FT                   /ligand_note="structural"
FT                   /evidence="ECO:0000250|UniProtKB:P12694"
FT   BINDING         222
FT                   /ligand="K(+)"
FT                   /ligand_id="ChEBI:CHEBI:29103"
FT                   /ligand_note="structural"
FT                   /evidence="ECO:0000250|UniProtKB:P12694"
FT   BINDING         248
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /evidence="ECO:0000250|UniProtKB:P12694"
FT   BINDING         249
FT                   /ligand="thiamine diphosphate"
FT                   /ligand_id="ChEBI:CHEBI:58937"
FT                   /ligand_note="ligand shared with beta subunit"
FT                   /evidence="ECO:0000250|UniProtKB:P12694"
FT   BINDING         250
FT                   /ligand="thiamine diphosphate"
FT                   /ligand_id="ChEBI:CHEBI:58937"
FT                   /ligand_note="ligand shared with beta subunit"
FT                   /evidence="ECO:0000250|UniProtKB:P12694"
FT   BINDING         275
FT                   /ligand="thiamine diphosphate"
FT                   /ligand_id="ChEBI:CHEBI:58937"
FT                   /ligand_note="ligand shared with beta subunit"
FT                   /evidence="ECO:0000250|UniProtKB:P12694"
FT   BINDING         277
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /evidence="ECO:0000250|UniProtKB:P12694"
FT   BINDING         279
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /evidence="ECO:0000250|UniProtKB:P12694"
FT   BINDING         346
FT                   /ligand="thiamine diphosphate"
FT                   /ligand_id="ChEBI:CHEBI:58937"
FT                   /ligand_note="ligand shared with beta subunit"
FT                   /evidence="ECO:0000250|UniProtKB:P12694"
FT   MOD_RES         347
FT                   /note="Phosphoserine; by BCKDK"
FT                   /evidence="ECO:0000250|UniProtKB:P12694"
FT   MOD_RES         348
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0000250|UniProtKB:P50136"
FT   MOD_RES         349
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P50136"
FT   MOD_RES         357
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P50136"
FT   MOD_RES         366
FT                   /note="N6-acetyllysine; alternate"
FT                   /evidence="ECO:0000250|UniProtKB:P50136"
FT   MOD_RES         366
FT                   /note="N6-succinyllysine; alternate"
FT                   /evidence="ECO:0000250|UniProtKB:P50136"
FT   MOD_RES         390
FT                   /note="N6-succinyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:P50136"
SQ   SEQUENCE   455 AA;  51678 MW;  66A7CA6003E0B846 CRC64;
     MQGSAKMAMA VAVAVARVWR PSRGLGRTGL PLLRLLGARG LARFHPHRWQ QQQHFSSLDD
     KPQFPGASAE FIDKLEFIQP NVISGIPIYR VMDRQGQIIN PSEDPHLPQE KVLKFYKSMT
     LLNTMDRILY ESQRQGRISF YMTNYGEEGT HVGSAAALDD TDLVFGQYRE AGVLMYRDYP
     LELFMAQCYG NVSDLGKGRQ MPVHYGCRER HFVTISSPLA TQIPQAVGAA YAAKRANANR
     VVICYFGEGA ASEGDAHAGF NFAATLECPI IFFCRNNGYA ISTPTSEQYR GDGIAARGPG
     YGILSIRVDG NDVFAVYNAT KEARRRAVAE NQPFLIEAMT YRIGHHSTSD DSSAYRSVDE
     VNYWDKQDHP ISRLRHHLQS RGWWDDEQEK AWRKQSRKKV MEAFEQAERK LKPNPSLIFS
     DVYQEMPAQL RKQQESLARH LQTYGEHYPL DHFEK
//