ID Q59EI3_HUMAN Unreviewed; 444 AA. AC Q59EI3; DT 26-APR-2005, integrated into UniProtKB/TrEMBL. DT 26-APR-2005, sequence version 1. DT 29-MAY-2024, entry version 101. DE RecName: Full=2-oxoisovalerate dehydrogenase subunit alpha {ECO:0000256|RuleBase:RU365014}; DE EC=1.2.4.4 {ECO:0000256|RuleBase:RU365014}; DE AltName: Full=Branched-chain alpha-keto acid dehydrogenase E1 component alpha chain {ECO:0000256|RuleBase:RU365014}; DE Flags: Fragment; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606 {ECO:0000313|EMBL:BAD93065.1}; RN [1] {ECO:0000313|EMBL:BAD93065.1} RP NUCLEOTIDE SEQUENCE. RC TISSUE=Brain {ECO:0000313|EMBL:BAD93065.1}; RA Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S., RA Ohara O., Nagase T., Kikuno R.F.; RT "Homo sapiens protein coding cDNA."; RL Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases. 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:0000256|ARBA:ARBA00037052, ECO:0000256|RuleBase:RU365014}. CC -!- CATALYTIC ACTIVITY: CC Reaction=3-methyl-2-oxobutanoate + H(+) + N(6)-[(R)-lipoyl]-L-lysyl- CC [dihydrolipoyllysine-residue (2-methylpropanoyl)transferase] = CO2 + CC N(6)-[(R)-S(8)-2-methylpropanoyldihydrolipoyl]-L-lysyl- CC [dihydrolipoyllysine-residue (2-methylpropanoyl)transferase]; CC Xref=Rhea:RHEA:13457, Rhea:RHEA-COMP:10488, Rhea:RHEA-COMP:10489, CC ChEBI:CHEBI:11851, ChEBI:CHEBI:15378, ChEBI:CHEBI:16526, CC ChEBI:CHEBI:83099, ChEBI:CHEBI:83142; EC=1.2.4.4; CC Evidence={ECO:0000256|ARBA:ARBA00043720}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:13458; CC Evidence={ECO:0000256|ARBA:ARBA00043720}; CC -!- COFACTOR: CC Name=thiamine diphosphate; Xref=ChEBI:CHEBI:58937; CC Evidence={ECO:0000256|RuleBase:RU365014}; CC -!- SIMILARITY: Belongs to the BCKDHA family. CC {ECO:0000256|ARBA:ARBA00008646, ECO:0000256|RuleBase:RU365014}. 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; AB209828; BAD93065.1; -; mRNA. DR RefSeq; NP_001158255.1; NM_001164783.1. DR AlphaFoldDB; Q59EI3; -. DR MaxQB; Q59EI3; -. DR PeptideAtlas; Q59EI3; -. DR DNASU; 593; -. DR GeneID; 593; -. DR CTD; 593; -. DR DisGeNET; 593; -. DR PharmGKB; PA25297; -. DR OrthoDB; 952at2759; -. DR BioGRID-ORCS; 593; 18 hits in 1160 CRISPR screens. DR GenomeRNAi; 593; -. DR GO; GO:0005759; C:mitochondrial matrix; IEA:UniProt. DR GO; GO:0003863; F:3-methyl-2-oxobutanoate dehydrogenase (2-methylpropanoyl-transferring) activity; IEA:UniProtKB-EC. DR GO; GO:0009083; P:branched-chain amino acid catabolic process; IEA:TreeGrafter. DR CDD; cd02000; TPP_E1_PDC_ADC_BCADC; 1. DR Gene3D; 3.40.50.970; -; 1. 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 2: Evidence at transcript level; KW Oxidoreductase {ECO:0000256|ARBA:ARBA00023002, KW ECO:0000256|RuleBase:RU365014}; Potassium {ECO:0000256|ARBA:ARBA00022958}; KW Thiamine pyrophosphate {ECO:0000256|RuleBase:RU365014}; KW Transit peptide {ECO:0000256|ARBA:ARBA00022946}. FT DOMAIN 106..404 FT /note="Dehydrogenase E1 component" FT /evidence="ECO:0000259|Pfam:PF00676" FT REGION 33..52 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 37..51 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT NON_TER 1 FT /evidence="ECO:0000313|EMBL:BAD93065.1" SQ SEQUENCE 444 AA; 50400 MW; C5A54AFF6AB9BF87 CRC64; MAVAIAAARV WRLNRGLSQA ALLLLRQPGA RGLARSHPPR QQQQFSSLDD KPQFPGASAE FIDKLEFIQP NVISGIPIYR VMDRQGQIIN PSEDPHLPKE KVLKLYKSMT LLNTMDRILY ESQRQGRISF YMTNYGEEGT HVGSAAALDN TDLVFGQYRE AGVLMYRDYP LELFMAQCYG NISDLGKGRQ MPVHYGCKER HFVTISSPLA TQIPQAVGAA YAAKRANANR VVICYFGEGA ASEGDAHAGF NFAATLECPI IFFCRNNGYA ISTPTSEQYR GDGIARGPGY GIMSIRVDGN DVFAVYNATK EARRRAVAEN QPFLIEAMTY RIGHHSTSDD SSAYRSVDEV NYWDKQDHPI SRLRHYLLSQ GWWDEEQEKA WRKQSRRKVM EAFEQAERKP KPNPNLLFSD VYQEMPAQLR KQQESLARHL QTYGEHYPLD HFDK //