P12694 (ODBA_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:

BCKDHA

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	445 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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.8
Subcellular location	Mitochondrion matrix.
Involvement in disease	Maple syrup urine disease type IA (MSUD1A) [MIM:248600]: Autosomal recessive disorder characterized by mental and physical retardation, feeding problems, and a maple syrup odor to the urine. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.4 Ref.9 Ref.10 Ref.11 Ref.12 Ref.13 Ref.14 Ref.15
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.

Ontologies

Keywords
Cellular component	Mitochondrion
Coding sequence diversity	Polymorphism
Disease	Disease mutation Maple syrup urine disease
Domain	Transit peptide
Ligand	Metal-binding Potassium Thiamine pyrophosphate
Molecular function	Oxidoreductase
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	branched-chain amino acid catabolic process Inferred from direct assay Ref.15. Source: HGNC cellular nitrogen compound metabolic process Traceable author statement. Source: Reactome
Cellular_component	mitochondrial alpha-ketoglutarate dehydrogenase complex Inferred from direct assay Ref.15. Source: HGNC
Molecular_function	3-methyl-2-oxobutanoate dehydrogenase (2-methylpropanoyl-transferring) activity Traceable author statement Ref.6. Source: ProtInc alpha-ketoacid dehydrogenase activity Inferred from direct assay Ref.15. Source: HGNC carboxy-lyase activity Traceable author statement PubMed 11839747. Source: HGNC metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
BCKDHB	P21953	14	EBI-1029053,EBI-1029067

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Transit peptide

1 – 45

45

Mitochondrion Ref.7

Chain

46 – 445

400

2-oxoisovalerate dehydrogenase subunit alpha, mitochondrial

PRO_0000020465

Regions

Region

157 – 159

3

Thiamine pyrophosphate binding

Sites

Metal binding

206

1

Potassium

Metal binding

211

1

Potassium

Metal binding

212

1

Potassium

Amino acid modifications

Modified residue

337

1

Phosphoserine By similarity

Modified residue

347

1

Phosphoserine By similarity

Natural variations

Natural variant

39

1

P → H.
Corresponds to variant rs34589432 [ dbSNP | Ensembl ].

VAR_034360

Natural variant

151

1

T → M.
Corresponds to variant rs34442879 [ dbSNP | Ensembl ].

VAR_034361

Natural variant

159

1

R → W in MSUD1A. Ref.14

VAR_004968

Natural variant

190

1

Q → K in MSUD1A. Ref.14

VAR_004969

Natural variant

253

1

A → T in MSUD1A. Ref.14

VAR_004970

Natural variant

290

1

G → R in MSUD1A. Ref.15

VAR_015101

Natural variant

326

1

I → T in MSUD1A. Ref.14

VAR_004971

Natural variant

409

1

F → C in MSUD1A. Ref.15

VAR_015102

Natural variant

413

1

Y → C in MSUD1A. Ref.9

VAR_004972

Natural variant

438

1

Y → N in MSUD1A; impedes assembly of the E1 component. Ref.4 Ref.10 Ref.11 Ref.12 Ref.13

VAR_004973

Experimental info

Sequence conflict

3

1

V → G in AAB20222. Ref.4

Sequence conflict

3

1

V → G in AAB19268. Ref.4

Sequence conflict

36

1

S → A in AAB59549. Ref.3

Sequence conflict

248

1

A → D in AAA35590. Ref.6

Secondary structure

1

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445

Helix Strand Turn

Details...

Beta strand

61 – 64

4

Beta strand

88 – 90

3

Helix

91 – 93

3

Helix

99 – 124

26

Beta strand

127 – 129

3

Turn

135 – 137

3

Helix

138 – 146

9

Beta strand

152 – 155

4

Helix

161 – 166

6

Helix

171 – 179

9

Turn

185 – 188

4

Turn

198 – 201

4

Turn

209 – 211

3

Helix

212 – 226

15

Beta strand

232 – 237

6

Helix

240 – 242

3

Helix

244 – 255

12

Beta strand

260 – 266

7

Beta strand

268 – 270

3

Helix

275 – 277

3

Beta strand

280 – 282

3

Helix

285 – 287

3

Helix

289 – 291

3

Beta strand

294 – 299

6

Helix

303 – 320

18

Beta strand

324 – 329

6

Helix

342 – 344

3

Helix

351 – 357

7

Helix

360 – 368

9

Turn

369 – 372

4

Helix

376 – 399

24

Helix

405 – 408

4

Turn

409 – 411

3

Beta strand

412 – 415

4

Helix

418 – 434

17

Helix

435 – 437

3

Helix

440 – 442

3

Sequences

	Sequence		Length	Mass (Da)
	P12694 [UniParc]. Last modified June 1, 1994. Version 2. Checksum: 2B4DD658924DB0C3	FASTA	445	50,471
	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

References

	« Hide 'large scale' referencesShow '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]	"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.
[9]	"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.
[10]	"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.
[11]	"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.
[12]	"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.
[13]	"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.
[14]	"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.
[15]	"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.
+	Additional computationally mapped references.

Web resources

GeneReviews

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.

IPI

IPI00025100.

PIR

DEHUXA. S27156.

RefSeq

NP_000700.1. NM_000709.3.

UniGene

Hs.433307.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1DTW	X-ray	2.70	A	46-445	[»]
1OLS	X-ray	1.85	A	46-445	[»]
1OLU	X-ray	1.90	A	46-445	[»]
1OLX	X-ray	2.25	A	46-445	[»]
1U5B	X-ray	1.83	A	46-445	[»]
1V11	X-ray	1.95	A	46-445	[»]
1V16	X-ray	1.90	A	46-445	[»]
1V1M	X-ray	2.00	A	46-445	[»]
1V1R	X-ray	1.80	A	46-445	[»]
1WCI	X-ray	1.84	A	46-445	[»]
1X7W	X-ray	1.73	A	46-445	[»]
1X7X	X-ray	2.10	A	46-445	[»]
1X7Y	X-ray	1.57	A	46-445	[»]
1X7Z	X-ray	1.72	A	46-445	[»]
1X80	X-ray	2.00	A	46-445	[»]
2BEU	X-ray	1.89	A	46-445	[»]
2BEV	X-ray	1.80	A	46-445	[»]
2BEW	X-ray	1.79	A	46-445	[»]
2BFB	X-ray	1.77	A	46-445	[»]
2BFC	X-ray	1.64	A	46-445	[»]
2BFD	X-ray	1.39	A	46-445	[»]
2BFE	X-ray	1.69	A	46-445	[»]
2BFF	X-ray	1.46	A	46-445	[»]
2J9F	X-ray	1.88	A/C	46-445	[»]

ProteinModelPortal

P12694.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-6146N.

IntAct

P12694. 3 interactions.

MINT

MINT-271818.

STRING

9606.ENSP00000269980.

PTM databases

PhosphoSite

P12694.

Polymorphism databases

DMDM

548403.

Proteomic databases

PaxDb

P12694.

PRIDE

P12694.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000269980; ENSP00000269980; ENSG00000248098.

GeneID

593.

KEGG

hsa:593.

UCSC

uc002oqp.2. human.

Organism-specific databases

CTD

593.

GeneCards

GC19P041903.

HGNC

HGNC:986. BCKDHA.

HPA

HPA036640.

MIM

248600. phenotype.
608348. gene.

neXtProt

NX_P12694.

Orphanet

511. Maple syrup urine disease.

PharmGKB

PA25297.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG1071.

HOVERGEN

HBG002459.

InParanoid

P12694.

KO

K00166.

PhylomeDB

P12694.

Enzyme and pathway databases

BioCyc

MetaCyc:MONOMER-12005.

Reactome

REACT_111217. Metabolism.

SABIO-RK

P12694.

Gene expression databases

ArrayExpress

P12694.

Bgee

P12694.

CleanEx

HS_BCKDHA.

Genevestigator

P12694.

GermOnline

ENSG00000142046. Homo sapiens.

Family and domain databases

InterPro

IPR001017. DH_E1.
[Graphical view]

Pfam

PF00676. E1_dh. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

P12694.

GenomeRNAi

593.

NextBio

2409.

SOURCE

Search...

Entry information

Entry name

ODBA_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 163 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.