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P12694 (ODBA_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified March 19, 2014. Version 172. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:BCKDHA
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length445 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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).

Catalytic activity

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

Cofactor

Thiamine pyrophosphate.

Subunit structure

Heterotetramer of alpha and beta chains. Ref.16

Subcellular location

Mitochondrion matrix.

Involvement in disease

Maple syrup urine disease 1A (MSUD1A) [MIM:248600]: A 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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.4 Ref.17 Ref.18 Ref.19 Ref.20 Ref.21 Ref.22 Ref.23 Ref.24

Miscellaneous

Bound potassium ions stabilize the protein structure.

Sequence similarities

Belongs to the BCKDHA family.

Sequence caution

The sequence AAB59549.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

Binary interactions

With

Entry

#Exp.

IntAct

Notes

BCKDHBP2195314EBI-1029053,EBI-1029067

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Transit peptide1 – 4545Mitochondrion Ref.7
Chain46 – 4454002-oxoisovalerate dehydrogenase subunit alpha, mitochondrial
PRO_0000020465

Regions

Region157 – 1593Thiamine pyrophosphate binding

Sites

Metal binding2061Potassium
Metal binding2111Potassium
Metal binding2121Potassium

Amino acid modifications

Modified residue3371Phosphoserine Ref.13 Ref.15
Modified residue3471Phosphoserine Ref.8 Ref.12 Ref.13 Ref.15
Modified residue3561N6-acetyllysine; alternate By similarity
Modified residue3561N6-succinyllysine; alternate By similarity
Modified residue3801N6-succinyllysine By similarity

Natural variations

Natural variant391P → H.
Corresponds to variant rs34589432 [ dbSNP | Ensembl ].
VAR_034360
Natural variant1511T → M.
Corresponds to variant rs34442879 [ dbSNP | Ensembl ].
VAR_034361
Natural variant1591R → W in MSUD1A. Ref.22
VAR_004968
Natural variant1901Q → K in MSUD1A. Ref.22
VAR_004969
Natural variant2111T → M in MSUD1A. Ref.24
VAR_069748
Natural variant2201A → V in MSUD1A. Ref.24
VAR_069749
Natural variant2531A → T in MSUD1A. Ref.22
VAR_004970
Natural variant2901G → R in MSUD1A. Ref.23
VAR_015101
Natural variant3261I → T in MSUD1A. Ref.22
VAR_004971
Natural variant3461R → C in MSUD1A. Ref.24
VAR_069750
Natural variant4031P → PKP in MSUD1A.
VAR_069751
Natural variant4091F → C in MSUD1A. Ref.23
VAR_015102
Natural variant4131Y → C in MSUD1A. Ref.17
VAR_004972
Natural variant427 – 4282LA → P in MSUD1A.
VAR_069752
Natural variant4381Y → N in MSUD1A; impedes assembly of the E1 component. Ref.4 Ref.18 Ref.19 Ref.20 Ref.21
VAR_004973

Experimental info

Sequence conflict31V → G in AAB20222. Ref.4
Sequence conflict31V → G in AAB19268. Ref.4
Sequence conflict361S → A in AAB59549. Ref.3
Sequence conflict2481A → D in AAA35590. Ref.6

Secondary structure

.................................................................... 445
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P12694 [UniParc].

Last modified June 1, 1994. Version 2.
Checksum: 2B4DD658924DB0C3

FASTA44550,471
        10         20         30         40         50         60 
MAVAIAAARV WRLNRGLSQA ALLLLRQPGA RGLARSHPPR QQQQFSSLDD KPQFPGASAE 

        70         80         90        100        110        120 
FIDKLEFIQP NVISGIPIYR VMDRQGQIIN PSEDPHLPKE KVLKLYKSMT LLNTMDRILY 

       130        140        150        160        170        180 
ESQRQGRISF YMTNYGEEGT HVGSAAALDN TDLVFGQYRE AGVLMYRDYP LELFMAQCYG 

       190        200        210        220        230        240 
NISDLGKGRQ MPVHYGCKER HFVTISSPLA TQIPQAVGAA YAAKRANANR VVICYFGEGA 

       250        260        270        280        290        300 
ASEGDAHAGF NFAATLECPI IFFCRNNGYA ISTPTSEQYR GDGIAARGPG YGIMSIRVDG 

       310        320        330        340        350        360 
NDVFAVYNAT KEARRRAVAE NQPFLIEAMT YRIGHHSTSD DSSAYRSVDE VNYWDKQDHP 

       370        380        390        400        410        420 
ISRLRHYLLS QGWWDEEQEK AWRKQSRRKV MEAFEQAERK PKPNPNLLFS DVYQEMPAQL 

       430        440 
RKQQESLARH LQTYGEHYPL DHFDK 

« Hide

References

« Hide 'large scale' references
[1]"Nucleotide sequence of the 5' end including the initiation codon of cDNA for the E1 alpha subunit of the human branched chain alpha-ketoacid dehydrogenase complex."
McKean M.C., Winkeler K.A., Danner D.J.
Biochim. Biophys. Acta 1171:109-112(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Bone marrow and Lung.
[3]"Molecular phenotypes in cultured maple syrup urine disease cells. Complete E1 alpha cDNA sequence and mRNA and subunit contents of the human branched chain alpha-keto acid dehydrogenase complex."
Fisher C.W., Chuang J.L., Griffin T.A., Lau K.S., Cox R.P., Chuang D.T.
J. Biol. Chem. 264:3448-3453(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 3-445.
[4]"Structure of the gene encoding the entire mature E1 alpha subunit of human branched-chain alpha-keto acid dehydrogenase complex."
Dariush N., Fisher C.W., Cox R.P., Chuang D.T.
FEBS Lett. 284:34-38(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 3-445, VARIANT MSUD1A ASN-438.
[5]Erratum
Dariush N., Fisher C.W., Cox R.P., Chuang D.T.
FEBS Lett. 291:376-377(1991) [PubMed] [Europe PMC] [Abstract]
[6]"Nucleotide and deduced amino acid sequence of the E1 alpha subunit of human liver branched-chain alpha-ketoacid dehydrogenase."
Zhang B., Crabb D.W., Harris R.A.
Gene 69:159-164(1988) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 68-445.
Tissue: Liver.
[7]"Differential processing of human and rat E1 alpha precursors of the branched-chain alpha-keto acid dehydrogenase complex caused by an N-terminal proline in the rat sequence."
Wynn R.M., Kochi H., Cox R.P., Chuang D.T.
Biochim. Biophys. Acta 1201:125-128(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 46-57.
[8]"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks."
Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.
Cell 127:635-648(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-347, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[9]"Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis."
Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III
J. Proteome Res. 7:1346-1351(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[10]"Phosphoproteome of resting human platelets."
Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J., Schuetz C., Walter U., Gambaryan S., Sickmann A.
J. Proteome Res. 7:526-534(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Platelet.
[11]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[12]"Large-scale phosphoproteome analysis of human liver tissue by enrichment and fractionation of phosphopeptides with strong anion exchange chromatography."
Han G., Ye M., Zhou H., Jiang X., Feng S., Jiang X., Tian R., Wan D., Zou H., Gu J.
Proteomics 8:1346-1361(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-347, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Liver.
[13]"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-337 AND SER-347, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[14]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[15]"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation."
Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.
Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-337 AND SER-347, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[16]"Crystal structure of human branched-chain alpha-ketoacid dehydrogenase and the molecular basis of multienzyme complex deficiency in maple syrup urine disease."
Aevarsson A., Chuang J.L., Wynn R.M., Turley S., Chuang D.T., Hol W.G.J.
Structure 8:277-291(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 46-445 IN COMPLEX WITH THIAMINE PYROPHOSPHATE AND POTASSIUM IONS, SUBUNIT STRUCTURE.
[17]"Molecular basis of maple syrup urine disease: novel mutations at the E1 alpha locus that impair E1(alpha 2 beta 2) assembly or decrease steady-state E1 alpha mRNA levels of branched-chain alpha-keto acid dehydrogenase complex."
Chuang J.L., Fisher C.R., Cox R.P., Chuang D.T.
Am. J. Hum. Genet. 55:297-304(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT MSUD1A CYS-413.
[18]"Evidence for both a regulatory mutation and a structural mutation in a family with maple syrup urine disease."
Zhang B., Edenberg H.J., Crabb D.W., Harris R.A.
J. Clin. Invest. 83:1425-1429(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT MSUD1A ASN-438.
[19]"A T-to-A substitution in the E1 alpha subunit gene of the branched-chain alpha-ketoacid dehydrogenase complex in two cell lines derived from Menonite maple syrup urine disease patients."
Matsuda I., Nobukuni Y., Mitsubuchi H., Indo Y., Endo F., Asaka J., Harada A.
Biochem. Biophys. Res. Commun. 172:646-651(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT MSUD1A ASN-438.
[20]"Occurrence of a Tyr393-->Asn (Y393N) mutation in the E1 alpha gene of the branched-chain alpha-keto acid dehydrogenase complex in maple syrup urine disease patients from a Mennonite population."
Fisher C.R., Fisher C.W., Chuang D.T., Cox R.P.
Am. J. Hum. Genet. 49:429-434(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT MSUD1A ASN-438.
[21]"Maple syrup urine disease in Mennonites. Evidence that the Y393N mutation in E1 alpha impedes assembly of the E1 component of branched-chain alpha-keto acid dehydrogenase complex."
Fisher C.R., Chuang J.L., Cox R.P., Fisher C.W., Star R.A., Chuang D.T.
J. Clin. Invest. 88:1034-1037(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT MSUD1A ASN-438.
[22]"Heterogeneity of mutations in maple syrup urine disease (MSUD): screening and identification of affected E1 alpha and E1 beta subunits of the branched-chain alpha-keto-acid dehydrogenase multienzyme complex."
Nobukuni Y., Mitsubuchi H., Hayashida Y., Ohta K., Indo Y., Ichiba Y., Endo F., Matsuda I.
Biochim. Biophys. Acta 1225:64-70(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS MSUD1A TRP-159; LYS-190; THR-253 AND THR-326.
[23]"Molecular and biochemical basis of intermediate maple syrup urine disease: occurrence of homozygous G245R and F364C mutations at the E1-alpha locus of Hispanic-Mexican patients."
Chuang J.L., Davie J.R., Chinsky J.M., Wynn R.M., Cox R.P., Chuang D.T.
J. Clin. Invest. 95:954-963(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS MSUD1A ARG-290 AND CYS-409.
[24]"Three Korean patients with maple syrup urine disease: four novel mutations in the BCKDHA gene."
Park H.D., Lee D.H., Hong Y.H., Kang D.H., Lee Y.K., Song J., Lee S.Y., Kim J.W., Ki C.S., Lee Y.W.
Ann. Clin. Lab. Sci. 41:167-173(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS MSUD1A MET-211; VAL-220; CYS-346; LYS-PRO-403 INS AND 427-LEU-ALA-428 DELINS PRO.
+Additional computationally mapped references.

Web resources

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
Z14093 mRNA. Translation: CAA78475.1.
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.
PIRDEHUXA. S27156.
RefSeqNP_000700.1. NM_000709.3.
UniGeneHs.433307.

3D structure databases

PDBe
RCSB PDB
PDBj
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[»]
ProteinModelPortalP12694.
SMRP12694. Positions 20-445.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid107065. 3 interactions.
DIPDIP-6146N.
IntActP12694. 3 interactions.
MINTMINT-271818.
STRING9606.ENSP00000269980.

PTM databases

PhosphoSiteP12694.

Polymorphism databases

DMDM548403.

Proteomic databases

PaxDbP12694.
PRIDEP12694.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000269980; ENSP00000269980; ENSG00000248098.
GeneID593.
KEGGhsa:593.
UCSCuc002oqp.2. human.

Organism-specific databases

CTD593.
GeneCardsGC19P041857.
HGNCHGNC:986. BCKDHA.
HPAHPA036640.
MIM248600. phenotype.
608348. gene.
neXtProtNX_P12694.
Orphanet268145. Classic maple syrup urine disease.
268162. Intermediate maple syrup urine disease.
268173. Intermittent maple syrup urine disease.
268184. Thiamine-responsive maple syrup urine disease.
PharmGKBPA25297.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG1071.
HOVERGENHBG002459.
InParanoidP12694.
KOK00166.
OrthoDBEOG7WT41H.
PhylomeDBP12694.
TreeFamTF300863.

Enzyme and pathway databases

BioCycMetaCyc:MONOMER-12005.
ReactomeREACT_111217. Metabolism.
SABIO-RKP12694.

Gene expression databases

ArrayExpressP12694.
BgeeP12694.
CleanExHS_BCKDHA.
GenevestigatorP12694.

Family and domain databases

InterProIPR001017. DH_E1.
[Graphical view]
PfamPF00676. E1_dh. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP12694.
GeneWikiBCKDHA.
GenomeRNAi593.
NextBio2409.
PROP12694.
SOURCESearch...

Entry information

Entry nameODBA_HUMAN
AccessionPrimary (citable) accession number: P12694
Secondary accession number(s): Q16034, Q16472
Entry history
Integrated into UniProtKB/Swiss-Prot: October 1, 1989
Last sequence update: June 1, 1994
Last modified: March 19, 2014
This is version 172 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 19

Human chromosome 19: entries, gene names and cross-references to MIM