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Protein

2-oxoisovalerate dehydrogenase subunit alpha, mitochondrial

Gene

BCKDHA

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

The branched-chain alpha-keto dehydrogenase complex catalyzes the overall conversion of alpha-keto acids to acyl-CoA and CO2. It contains multiple copies of three enzymatic components: branched-chain alpha-keto acid decarboxylase (E1), lipoamide acyltransferase (E2) and lipoamide dehydrogenase (E3).

Miscellaneous

Bound potassium ions stabilize the protein structure.

Catalytic activityi

3-methyl-2-oxobutanoate + [dihydrolipoyllysine-residue (2-methylpropanoyl)transferase] lipoyllysine = [dihydrolipoyllysine-residue (2-methylpropanoyl)transferase] S-(2-methylpropanoyl)dihydrolipoyllysine + CO2.

Cofactori

thiamine diphosphate1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi206Potassium1 Publication1
Metal bindingi211Potassium1 Publication1
Metal bindingi212Potassium1 Publication1

GO - Molecular functioni

  • 3-methyl-2-oxobutanoate dehydrogenase (2-methylpropanoyl-transferring) activity Source: ProtInc
  • alpha-ketoacid dehydrogenase activity Source: HGNC
  • carboxy-lyase activity Source: HGNC
  • metal ion binding Source: UniProtKB-KW

GO - Biological processi

Keywordsi

Molecular functionOxidoreductase
LigandMetal-binding, Potassium, Thiamine pyrophosphate

Enzyme and pathway databases

BioCyciMetaCyc:MONOMER-12005
ReactomeiR-HSA-389661 Glyoxylate metabolism and glycine degradation
R-HSA-70895 Branched-chain amino acid catabolism
SABIO-RKiP12694
SIGNORiP12694

Names & Taxonomyi

Protein namesi
Recommended name:
2-oxoisovalerate dehydrogenase subunit alpha, mitochondrial (EC:1.2.4.4)
Alternative name(s):
Branched-chain alpha-keto acid dehydrogenase E1 component alpha chain
Short name:
BCKDE1A
Short name:
BCKDH E1-alpha
Gene namesi
Name:BCKDHA
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 19

Organism-specific databases

EuPathDBiHostDB:ENSG00000248098.10
HGNCiHGNC:986 BCKDHA
MIMi608348 gene
neXtProtiNX_P12694

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Mitochondrion

Pathology & Biotechi

Involvement in diseasei

Maple syrup urine disease 1A (MSUD1A)9 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA metabolic disorder due to an enzyme defect in the catabolic pathway of the branched-chain amino acids leucine, isoleucine, and valine. Accumulation of these 3 amino acids and their corresponding keto acids leads to encephalopathy and progressive neurodegeneration. Clinical features include mental and physical retardation, feeding problems, and a maple syrup odor to the urine. The keto acids of the branched-chain amino acids are present in the urine. If untreated, maple syrup urine disease can lead to seizures, coma, and death. The disease is often classified by its pattern of signs and symptoms. The most common and severe form of the disease is the classic type, which becomes apparent soon after birth. Variant forms of the disorder become apparent later in infancy or childhood and are typically milder, but they still involve developmental delay and other medical problems if not treated.
See also OMIM:248600
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_004968159R → W in MSUD1A. 1 PublicationCorresponds to variant dbSNP:rs769688327EnsemblClinVar.1
Natural variantiVAR_004969190Q → K in MSUD1A. 1 Publication1
Natural variantiVAR_069748211T → M in MSUD1A. 1 PublicationCorresponds to variant dbSNP:rs398123503EnsemblClinVar.1
Natural variantiVAR_069749220A → V in MSUD1A. 1 PublicationCorresponds to variant dbSNP:rs375785084EnsemblClinVar.1
Natural variantiVAR_004970253A → T in MSUD1A. 1 PublicationCorresponds to variant dbSNP:rs199599175EnsemblClinVar.1
Natural variantiVAR_015101290G → R in MSUD1A. 1 PublicationCorresponds to variant dbSNP:rs137852871EnsemblClinVar.1
Natural variantiVAR_004971326I → T in MSUD1A. 1 Publication1
Natural variantiVAR_069750346R → C in MSUD1A. 1 PublicationCorresponds to variant dbSNP:rs182923857EnsemblClinVar.1
Natural variantiVAR_069751403P → PKP in MSUD1A. 1
Natural variantiVAR_015102409F → C in MSUD1A. 1 PublicationCorresponds to variant dbSNP:rs137852872EnsemblClinVar.1
Natural variantiVAR_004972413Y → C in MSUD1A. 1 Publication1
Natural variantiVAR_069752427 – 428LA → P in MSUD1A. 1 Publication2
Natural variantiVAR_004973438Y → N in MSUD1A; impedes assembly of the E1 component. 5 PublicationsCorresponds to variant dbSNP:rs137852870EnsemblClinVar.1

Keywords - Diseasei

Disease mutation, Maple syrup urine disease

Organism-specific databases

DisGeNETi593
GeneReviewsiBCKDHA
MalaCardsiBCKDHA
MIMi248600 phenotype
OpenTargetsiENSG00000248098
Orphaneti268145 Classic maple syrup urine disease
268162 Intermediate maple syrup urine disease
268173 Intermittent maple syrup urine disease
268184 Thiamine-responsive maple syrup urine disease
PharmGKBiPA25297

Polymorphism and mutation databases

BioMutaiBCKDHA

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Transit peptidei1 – 45Mitochondrion1 PublicationAdd BLAST45
ChainiPRO_000002046546 – 4452-oxoisovalerate dehydrogenase subunit alpha, mitochondrialAdd BLAST400

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei337PhosphoserineBy similarity1
Modified residuei338PhosphothreonineBy similarity1
Modified residuei339PhosphoserineBy similarity1
Modified residuei347PhosphoserineBy similarity1
Modified residuei356N6-acetyllysine; alternateBy similarity1
Modified residuei356N6-succinyllysine; alternateBy similarity1
Modified residuei380N6-succinyllysineBy similarity1

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiP12694
MaxQBiP12694
PaxDbiP12694
PeptideAtlasiP12694
PRIDEiP12694
ProteomicsDBi52863

PTM databases

iPTMnetiP12694
PhosphoSitePlusiP12694

Expressioni

Gene expression databases

BgeeiENSG00000248098 Expressed in 91 organ(s), highest expression level in heart
CleanExiHS_BCKDHA
ExpressionAtlasiP12694 baseline and differential
GenevisibleiP12694 HS

Organism-specific databases

HPAiHPA036640

Interactioni

Subunit structurei

Heterotetramer of alpha and beta chains.1 Publication

Binary interactionsi

Protein-protein interaction databases

BioGridi107065, 30 interactors
DIPiDIP-6146N
IntActiP12694, 26 interactors
STRINGi9606.ENSP00000269980

Structurei

Secondary structure

1445
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliP12694
SMRiP12694
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP12694

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni157 – 159Thiamine pyrophosphate binding1 Publication3

Sequence similaritiesi

Belongs to the BCKDHA family.Curated

Keywords - Domaini

Transit peptide

Phylogenomic databases

eggNOGiKOG1182 Eukaryota
COG1071 LUCA
GeneTreeiENSGT00530000063174
HOGENOMiHOG000281337
HOVERGENiHBG002459
InParanoidiP12694
KOiK00166
OrthoDBiEOG091G073F
PhylomeDBiP12694
TreeFamiTF300863

Family and domain databases

InterProiView protein in InterPro
IPR034616 BCKDH_E1-a
IPR001017 DH_E1
IPR029061 THDP-binding
PANTHERiPTHR43380:SF1 PTHR43380:SF1, 1 hit
PfamiView protein in Pfam
PF00676 E1_dh, 1 hit
SUPFAMiSSF52518 SSF52518, 1 hit

Sequences (2+)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 2 described isoforms and 3 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: P12694-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide
        10         20         30         40         50
MAVAIAAARV WRLNRGLSQA ALLLLRQPGA RGLARSHPPR QQQQFSSLDD
60 70 80 90 100
KPQFPGASAE FIDKLEFIQP NVISGIPIYR VMDRQGQIIN PSEDPHLPKE
110 120 130 140 150
KVLKLYKSMT LLNTMDRILY ESQRQGRISF YMTNYGEEGT HVGSAAALDN
160 170 180 190 200
TDLVFGQYRE AGVLMYRDYP LELFMAQCYG NISDLGKGRQ MPVHYGCKER
210 220 230 240 250
HFVTISSPLA TQIPQAVGAA YAAKRANANR VVICYFGEGA ASEGDAHAGF
260 270 280 290 300
NFAATLECPI IFFCRNNGYA ISTPTSEQYR GDGIAARGPG YGIMSIRVDG
310 320 330 340 350
NDVFAVYNAT KEARRRAVAE NQPFLIEAMT YRIGHHSTSD DSSAYRSVDE
360 370 380 390 400
VNYWDKQDHP ISRLRHYLLS QGWWDEEQEK AWRKQSRRKV MEAFEQAERK
410 420 430 440
PKPNPNLLFS DVYQEMPAQL RKQQESLARH LQTYGEHYPL DHFDK
Length:445
Mass (Da):50,471
Last modified:June 1, 1994 - v2
Checksum:i2B4DD658924DB0C3
GO
Isoform 2 (identifier: P12694-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     19-40: Missing.
     331-331: Y → YSSSPILPPDPHSREPTLTWGPLPLC

Note: No experimental confirmation available.
Show »
Length:448
Mass (Da):50,790
Checksum:i25C9E70619832776
GO

Computationally mapped potential isoform sequencesi

There are 3 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
F5GXU9F5GXU9_HUMAN
2-oxoisovalerate dehydrogenase subu...
BCKDHA
328Annotation score:
H0YH31H0YH31_HUMAN
2-oxoisovalerate dehydrogenase subu...
BCKDHA
211Annotation score:
H0YH20H0YH20_HUMAN
2-oxoisovalerate dehydrogenase subu...
BCKDHA
94Annotation score:

Sequence cautioni

The sequence AAB59549 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti3V → G in AAB20222 (PubMed:2060625).Curated1
Sequence conflicti3V → G in AAB19268 (PubMed:2060625).Curated1
Sequence conflicti36S → A in AAB59549 (PubMed:2914958).Curated1
Sequence conflicti248A → D in AAA35590 (PubMed:3224821).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_03436039P → H. Corresponds to variant dbSNP:rs11549936EnsemblClinVar.1
Natural variantiVAR_034361151T → M. Corresponds to variant dbSNP:rs34442879EnsemblClinVar.1
Natural variantiVAR_004968159R → W in MSUD1A. 1 PublicationCorresponds to variant dbSNP:rs769688327EnsemblClinVar.1
Natural variantiVAR_004969190Q → K in MSUD1A. 1 Publication1
Natural variantiVAR_069748211T → M in MSUD1A. 1 PublicationCorresponds to variant dbSNP:rs398123503EnsemblClinVar.1
Natural variantiVAR_069749220A → V in MSUD1A. 1 PublicationCorresponds to variant dbSNP:rs375785084EnsemblClinVar.1
Natural variantiVAR_004970253A → T in MSUD1A. 1 PublicationCorresponds to variant dbSNP:rs199599175EnsemblClinVar.1
Natural variantiVAR_015101290G → R in MSUD1A. 1 PublicationCorresponds to variant dbSNP:rs137852871EnsemblClinVar.1
Natural variantiVAR_004971326I → T in MSUD1A. 1 Publication1
Natural variantiVAR_069750346R → C in MSUD1A. 1 PublicationCorresponds to variant dbSNP:rs182923857EnsemblClinVar.1
Natural variantiVAR_069751403P → PKP in MSUD1A. 1
Natural variantiVAR_015102409F → C in MSUD1A. 1 PublicationCorresponds to variant dbSNP:rs137852872EnsemblClinVar.1
Natural variantiVAR_004972413Y → C in MSUD1A. 1 Publication1
Natural variantiVAR_069752427 – 428LA → P in MSUD1A. 1 Publication2
Natural variantiVAR_004973438Y → N in MSUD1A; impedes assembly of the E1 component. 5 PublicationsCorresponds to variant dbSNP:rs137852870EnsemblClinVar.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_05615619 – 40Missing in isoform 2. 1 PublicationAdd BLAST22
Alternative sequenceiVSP_056157331Y → YSSSPILPPDPHSREPTLTW GPLPLC in isoform 2. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Z14093 mRNA Translation: CAA78475.1
AK298188 mRNA Translation: BAG60459.1
AC011462 Genomic DNA No translation available.
BC007878 mRNA Translation: AAH07878.1
BC008933 mRNA Translation: AAH08933.1
BC023983 mRNA Translation: AAH23983.1
J04474 mRNA Translation: AAB59549.1 Different initiation.
AH003771 Genomic DNA Translation: AAB20222.2
AH003707 Genomic DNA Translation: AAB19268.2
M22221 mRNA Translation: AAA35590.1
CCDSiCCDS12581.1 [P12694-1]
PIRiS27156 DEHUXA
RefSeqiNP_000700.1, NM_000709.3 [P12694-1]
NP_001158255.1, NM_001164783.1
UniGeneiHs.433307

Genome annotation databases

EnsembliENST00000269980; ENSP00000269980; ENSG00000248098 [P12694-1]
ENST00000457836; ENSP00000416000; ENSG00000248098 [P12694-2]
GeneIDi593
KEGGihsa:593
UCSCiuc002oqq.4 human [P12694-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Z14093 mRNA Translation: CAA78475.1
AK298188 mRNA Translation: BAG60459.1
AC011462 Genomic DNA No translation available.
BC007878 mRNA Translation: AAH07878.1
BC008933 mRNA Translation: AAH08933.1
BC023983 mRNA Translation: AAH23983.1
J04474 mRNA Translation: AAB59549.1 Different initiation.
AH003771 Genomic DNA Translation: AAB20222.2
AH003707 Genomic DNA Translation: AAB19268.2
M22221 mRNA Translation: AAA35590.1
CCDSiCCDS12581.1 [P12694-1]
PIRiS27156 DEHUXA
RefSeqiNP_000700.1, NM_000709.3 [P12694-1]
NP_001158255.1, NM_001164783.1
UniGeneiHs.433307

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1DTWX-ray2.70A46-445[»]
1OLSX-ray1.85A46-445[»]
1OLUX-ray1.90A46-445[»]
1OLXX-ray2.25A46-445[»]
1U5BX-ray1.83A46-445[»]
1V11X-ray1.95A46-445[»]
1V16X-ray1.90A46-445[»]
1V1MX-ray2.00A46-445[»]
1V1RX-ray1.80A46-445[»]
1WCIX-ray1.84A46-445[»]
1X7WX-ray1.73A46-445[»]
1X7XX-ray2.10A46-445[»]
1X7YX-ray1.57A46-445[»]
1X7ZX-ray1.72A46-445[»]
1X80X-ray2.00A46-445[»]
2BEUX-ray1.89A46-445[»]
2BEVX-ray1.80A46-445[»]
2BEWX-ray1.79A46-445[»]
2BFBX-ray1.77A46-445[»]
2BFCX-ray1.64A46-445[»]
2BFDX-ray1.39A46-445[»]
2BFEX-ray1.69A46-445[»]
2BFFX-ray1.46A46-445[»]
2J9FX-ray1.88A/C46-445[»]
ProteinModelPortaliP12694
SMRiP12694
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi107065, 30 interactors
DIPiDIP-6146N
IntActiP12694, 26 interactors
STRINGi9606.ENSP00000269980

PTM databases

iPTMnetiP12694
PhosphoSitePlusiP12694

Polymorphism and mutation databases

BioMutaiBCKDHA

Proteomic databases

EPDiP12694
MaxQBiP12694
PaxDbiP12694
PeptideAtlasiP12694
PRIDEiP12694
ProteomicsDBi52863

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000269980; ENSP00000269980; ENSG00000248098 [P12694-1]
ENST00000457836; ENSP00000416000; ENSG00000248098 [P12694-2]
GeneIDi593
KEGGihsa:593
UCSCiuc002oqq.4 human [P12694-1]

Organism-specific databases

CTDi593
DisGeNETi593
EuPathDBiHostDB:ENSG00000248098.10
GeneCardsiBCKDHA
GeneReviewsiBCKDHA
HGNCiHGNC:986 BCKDHA
HPAiHPA036640
MalaCardsiBCKDHA
MIMi248600 phenotype
608348 gene
neXtProtiNX_P12694
OpenTargetsiENSG00000248098
Orphaneti268145 Classic maple syrup urine disease
268162 Intermediate maple syrup urine disease
268173 Intermittent maple syrup urine disease
268184 Thiamine-responsive maple syrup urine disease
PharmGKBiPA25297
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1182 Eukaryota
COG1071 LUCA
GeneTreeiENSGT00530000063174
HOGENOMiHOG000281337
HOVERGENiHBG002459
InParanoidiP12694
KOiK00166
OrthoDBiEOG091G073F
PhylomeDBiP12694
TreeFamiTF300863

Enzyme and pathway databases

BioCyciMetaCyc:MONOMER-12005
ReactomeiR-HSA-389661 Glyoxylate metabolism and glycine degradation
R-HSA-70895 Branched-chain amino acid catabolism
SABIO-RKiP12694
SIGNORiP12694

Miscellaneous databases

ChiTaRSiBCKDHA human
EvolutionaryTraceiP12694
GeneWikiiBCKDHA
GenomeRNAii593
PROiPR:P12694
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000248098 Expressed in 91 organ(s), highest expression level in heart
CleanExiHS_BCKDHA
ExpressionAtlasiP12694 baseline and differential
GenevisibleiP12694 HS

Family and domain databases

InterProiView protein in InterPro
IPR034616 BCKDH_E1-a
IPR001017 DH_E1
IPR029061 THDP-binding
PANTHERiPTHR43380:SF1 PTHR43380:SF1, 1 hit
PfamiView protein in Pfam
PF00676 E1_dh, 1 hit
SUPFAMiSSF52518 SSF52518, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiODBA_HUMAN
AccessioniPrimary (citable) accession number: P12694
Secondary accession number(s): B4DP47
, E7EW46, Q16034, Q16472
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 1, 1989
Last sequence update: June 1, 1994
Last modified: November 7, 2018
This is version 217 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. Human chromosome 19
    Human chromosome 19: entries, gene names and cross-references to MIM
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
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