Reactome | UniProt:P12694 BCKDHA

chain	transit peptide:1-45 chain:46-445
checksum	2B4DD658924DB0C3
comment	FUNCTION Together with BCKDHB forms the heterotetrameric E1 subunit of the mitochondrial branched-chain alpha-ketoacid dehydrogenase (BCKD) complex. The BCKD complex catalyzes the multi-step oxidative decarboxylation of alpha-ketoacids derived from the branched-chain amino-acids valine, leucine and isoleucine producing CO2 and acyl-CoA which is subsequently utilized to produce energy. The E1 subunit catalyzes the first step with the decarboxylation of the alpha-ketoacid forming an enzyme-product intermediate. A reductive acylation mediated by the lipoylamide cofactor of E2 extracts the acyl group from the E1 active site for the next step of the reaction.CATALYTIC ACTIVITY N(6)-[(R)-lipoyl]-L-lysyl-[protein] + 3-methyl-2-oxobutanoate + H(+) = N(6)-[(R)-S(8)-2-methylpropanoyldihydrolipoyl]-L-lysyl-[protein] + CO2CATALYTIC ACTIVITY N(6)-[(R)-lipoyl]-L-lysyl-[protein] + 4-methyl-2-oxopentanoate + H(+) = N(6)-[(R)-S(8)-3-methylbutanoyldihydrolipoyl]-L-lysyl-[protein] + CO2CATALYTIC ACTIVITY N(6)-[(R)-lipoyl]-L-lysyl-[protein] + (S)-3-methyl-2-oxopentanoate + H(+) = N(6)-{(R)-S(8)-[(2S)-2-methylbutanoyl]dihydrolipoyl}-L-lysyl-[protein] + CO2COFACTOR Heterotetramer of 2 alpha/BCKDHA and 2 beta chains/BCKDHB that forms the branched-chain alpha-keto acid decarboxylase (E1) component of the BCKD complex (PubMed:10745006, PubMed:9582350). The branched-chain alpha-ketoacid dehydrogenase is a large complex composed of three major building blocks E1, E2 and E3. It is organized around E2, a 24-meric cubic core composed of DBT, to which are associated 6 to 12 copies of E1, and approximately 6 copies of the dehydrogenase E3, a DLD dimer (PubMed:10745006). Interacts with PPM1K.INTERACTION Phosphorylated at Ser-337 by BCKDK and dephosphorylated by protein phosphatase PPM1K.DISEASE The disease is caused by variants affecting the gene represented in this entry.SIMILARITY Belongs to the BCKDHA family.SEQUENCE CAUTION Truncated N-terminus.
crossReference	[DatabaseIdentifier:12183239] PDB:2BFB [DatabaseIdentifier:12415338] RefSeq:NP_000700.1 [DatabaseIdentifier:12415339] RefSeq:NP_001158255.1 [DatabaseIdentifier:12286153] Pharos - Targets:P12694 [DatabaseIdentifier:12245950] PRO:P12694 [DatabaseIdentifier:12183230] PDB:2J9F [DatabaseIdentifier:12183227] PDB:1V1R [DatabaseIdentifier:12183240] PDB:1OLX [DatabaseIdentifier:12183225] PDB:1OLU [DatabaseIdentifier:12183242] PDB:1X7Z [DatabaseIdentifier:12183229] PDB:1V11 [DatabaseIdentifier:12183224] PDB:1X80 [DatabaseIdentifier:12183223] PDB:2BFF [DatabaseIdentifier:12183244] PDB:1X7X [DatabaseIdentifier:12183236] PDB:2BFD [DatabaseIdentifier:12183233] PDB:2BEV [DatabaseIdentifier:11493486] ENSEMBL:ENSG00000248098 [DatabaseIdentifier:11600959] ENSEMBL:ENSP00000416000 [DatabaseIdentifier:11600958] ENSEMBL:ENSP00000269980 [DatabaseIdentifier:11723657] ENSEMBL:ENST00000269980 [DatabaseIdentifier:11723658] ENSEMBL:ENST00000457836 [DatabaseIdentifier:11788261] GeneCards:BCKDHA [DatabaseIdentifier:11832875] HMDB Protein:HMDBP00300 [DatabaseIdentifier:11841317] HPA:ENSG00000248098-BCKDHA [DatabaseIdentifier:12125879] OpenTargets:ENSG00000248098 [DatabaseIdentifier:12137199] Orphanet:BCKDHA [DatabaseIdentifier:12183241] PDB:1V16 [DatabaseIdentifier:12183243] PDB:1X7Y [DatabaseIdentifier:12183232] PDB:1V1M [DatabaseIdentifier:12183228] PDB:1OLS [DatabaseIdentifier:12183237] PDB:2BFC [DatabaseIdentifier:12183222] PDB:1U5B [DatabaseIdentifier:12183234] PDB:2BEU [DatabaseIdentifier:12183221] PDB:1DTW [DatabaseIdentifier:12183231] PDB:2BEW [DatabaseIdentifier:12183226] PDB:1X7W [DatabaseIdentifier:12183235] PDB:2BFE [DatabaseIdentifier:12183238] PDB:1WCI
databaseName	UniProt
dbId	60858
description	recommendedName: fullName evidence="21"2-oxoisovalerate dehydrogenase subunit alpha, mitochondrial ecNumber evidence="4 13 17"1.2.4.4 alternativeName: Branched-chain alpha-keto acid dehydrogenase E1 component alpha chain shortName: BCKDE1A shortName: BCKDH E1-alpha
displayName	UniProt:P12694 BCKDHA
geneName	BCKDHA
identifier	P12694
isSequenceChanged	false
keyword	3D-structure Acetylation Alternative splicing Direct protein sequencing Disease variant Maple syrup urine disease Metal-binding Mitochondrion Oxidoreductase Phosphoprotein Potassium Proteomics identification Reference proteome Thiamine pyrophosphate Transit peptide
modified	[InstanceEdit:9983091] Weiser, Joel, 2026-02-20
moleculeType	Protein
name	BCKDHA
otherIdentifier	11733731_s_at 16862504 202331_PM_at 202331_at 37704_at 3834206 3834209 3834210 3834211 3834212 3834213 3834215 3834217 3834218 3834219 3834220 3834221 3834222 3834223 3834224 3834225 3834226 593 8029065 A_23_P67188 A_33_P3302305 GE60352 GO:0003863 GO:0005515 GO:0005739 GO:0005759 GO:0006520 GO:0009083 GO:0016491 GO:0016624 GO:0016829 GO:0016831 GO:0046872 GO:0120552 GO:0160157 HMNXSV003002234 ILMN_1735979 PH_hs_0020110 PH_hs_0040098 TC19002636.hg Z14093_at g11386134_3p_at
physicalEntity	[EntityWithAccessionedSequence:R-HSA-70014] BCKDHA [mitochondrial matrix] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-9865058] Y438N BCKDHA [mitochondrial matrix] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-9865056] A285P BCKDHA [mitochondrial matrix] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-9865040] G290R BCKDHA [mitochondrial matrix] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-9865052] T310R BCKDHA [mitochondrial matrix] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-9865067] G249S BCKDHA [mitochondrial matrix] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-9865065] Y413C BCKDHA [mitochondrial matrix] - Homo sapiens
referenceDatabase	[ReferenceDatabase:2] UniProt
referenceGene	[ReferenceDNASequence:ensembl:ENSG00000248098] ENSEMBL:ENSG00000248098 BCKDHA [ReferenceDNASequence:12698896] UCSC:P12694 BCKDHA [ReferenceDNASequence:11359109] BioGPS Gene:593 BCKDHA [ReferenceDNASequence:11394160] COSMIC - genes:BCKDHA BCKDHA [ReferenceDNASequence:11414427] CTD Gene:593 BCKDHA [ReferenceDNASequence:11430209] dbSNP Gene:593 BCKDHA [ReferenceDNASequence:11819912] HGNC:986 BCKDHA [ReferenceDNASequence:11898273] KEGG:hsa:593 BCKDHA [ReferenceDNASequence:11988898] Monarch:593 BCKDHA [ReferenceDNASequence:12072991] NCBI Gene:593 BCKDHA [ReferenceDNASequence:12111056] OMIM:608348 BCKDHA
referenceTranscript	[ReferenceRNASequence:12597030] RefSeq:NM_001164783.1 BCKDHA [ReferenceRNASequence:12597029] RefSeq:NM_000709.4 BCKDHA
schemaClass	ReferenceGeneProduct
secondaryIdentifier	ODBA_HUMAN B4DP47 E7EW46 Q16034 Q16472
sequenceLength	445
species	[Species:48887] Homo sapiens
stId	uniprot:P12694
url	http://purl.uniprot.org/uniprot/P12694

(referenceEntity)	[EntityWithAccessionedSequence:R-HSA-70014] BCKDHA [mitochondrial matrix] [EntityWithAccessionedSequence:R-HSA-9865058] Y438N BCKDHA [mitochondrial matrix] [EntityWithAccessionedSequence:R-HSA-9865056] A285P BCKDHA [mitochondrial matrix] [EntityWithAccessionedSequence:R-HSA-9865040] G290R BCKDHA [mitochondrial matrix] [EntityWithAccessionedSequence:R-HSA-9865052] T310R BCKDHA [mitochondrial matrix] [EntityWithAccessionedSequence:R-HSA-9865067] G249S BCKDHA [mitochondrial matrix] [EntityWithAccessionedSequence:R-HSA-9865065] Y413C BCKDHA [mitochondrial matrix]
(referenceSequence)	[ReplacedResidue:9865025] L-tyrosine 438 replaced with L-asparagine [ReplacedResidue:9865016] L-alanine 285 replaced with L-proline [ReplacedResidue:9865015] glycine 290 replaced with L-asparagine [ReplacedResidue:9865014] L-threonine 310 replaced with L-arginine [ReplacedResidue:9865019] glycine 249 replaced with L-serine [ReplacedResidue:9865011] L-tyrosine 413 replaced with L-cysteine
(interactor)	[UndirectedInteraction:11169125] UniProt:Q9Y5J3 <-> UniProt:P12694 (IntAct) [UndirectedInteraction:11260859] UniProt:P06746 <-> UniProt:P12694 (IntAct)

UniProt:P12694 BCKDHA Show undefined attributes

Referrals