LOCUS NP_000047 392 aa linear PRI 04-NOV-2008
DEFINITION branched chain keto acid dehydrogenase E1 beta polypeptide
precursor [Homo sapiens].
ACCESSION NP_000047
VERSION NP_000047.1 GI:4557353
DBSOURCE REFSEQ: accession NM_000056.3
KEYWORDS .
SOURCE Homo sapiens (human)
ORGANISM Homo sapiens
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
Catarrhini; Hominidae; Homo.
REFERENCE 1 (residues 1 to 392)
AUTHORS Quental,S., Macedo-Ribeiro,S., Matos,R., Vilarinho,L., Martins,E.,
Teles,E.L., Rodrigues,E., Diogo,L., Garcia,P., Eusebio,F.,
Gaspar,A., Sequeira,S., Furtado,F., Lanca,I., Amorim,A. and
Prata,M.J.
TITLE Molecular and structural analyses of maple syrup urine disease and
identification of a founder mutation in a Portuguese Gypsy
community
JOURNAL Mol. Genet. Metab. 94 (2), 148-156 (2008)
PUBMED 18378174
REMARK GeneRIF: 30 Maple syrup urine disease Portuguese patients studied;
17 putative mutations have been identified (6 in BCKDHA, 5 in
BCKDHB and 6 in DBT); 7 of are described for the first time.
REFERENCE 2 (residues 1 to 392)
AUTHORS Kang,H., Lee,S.K., Cho,S.W., Lee,S.H. and Kwack,K.
TITLE Branched chain alpha-keto acid dehydrogenase, E1-beta subunit gene
is associated with premature ovarian failure
JOURNAL Fertil. Steril. 89 (3), 728-731 (2008)
PUBMED 17524396
REMARK GeneRIF: Reconstructed haplotype from BCKDHB variants was
associated with premature ovarian failure.
REFERENCE 3 (residues 1 to 392)
AUTHORS Flaschker,N., Feyen,O., Fend,S., Simon,E., Schadewaldt,P. and
Wendel,U.
TITLE Description of the mutations in 15 subjects with variant forms of
maple syrup urine disease
JOURNAL J. Inherit. Metab. Dis. 30 (6), 903-909 (2007)
PUBMED 17922217
REMARK GeneRIF: in our cohort more severe enzyme & clinical phenotypes of
variant maple syrup urine disease were mainly associated with
specific genotypes in BCKDHA gene; milder enzyme & clinical
phenotypes were associated with specific genotypes in BCKDHB & DBT
genes
REFERENCE 4 (residues 1 to 392)
AUTHORS Li,J., Machius,M., Chuang,J.L., Wynn,R.M. and Chuang,D.T.
TITLE The two active sites in human branched-chain alpha-keto acid
dehydrogenase operate independently without an obligatory
alternating-site mechanism
JOURNAL J. Biol. Chem. 282 (16), 11904-11913 (2007)
PUBMED 17329260
REMARK GeneRIF: the two active sites in the E1b heterotetramer operate
independently during the ThDP-dependent decarboxylation reaction
REFERENCE 5 (residues 1 to 392)
AUTHORS Machius,M., Wynn,R.M., Chuang,J.L., Li,J., Kluger,R., Yu,D.,
Tomchick,D.R., Brautigam,C.A. and Chuang,D.T.
TITLE A versatile conformational switch regulates reactivity in human
branched-chain alpha-ketoacid dehydrogenase
JOURNAL Structure 14 (2), 287-298 (2006)
PUBMED 16472748
REMARK GeneRIF: A key tyrosine residue in the E1b active site functions as
a conformational switch to reduce the reactivity of the thiamine
diphosphate cofactor through interactions with its thiazolium ring.
Erratum:[Structure. 2006 Mar;14(3):625]
REFERENCE 6 (residues 1 to 392)
AUTHORS Mitsubuchi,H., Nobukuni,Y., Endo,F. and Matsuda,I.
TITLE Structural organization and chromosomal localization of the gene
for the E1 beta subunit of human branched chain alpha-keto acid
dehydrogenase
JOURNAL J. Biol. Chem. 266 (22), 14686-14691 (1991)
PUBMED 1860867
REFERENCE 7 (residues 1 to 392)
AUTHORS Zneimer,S.M., Lau,K.S., Eddy,R.L., Shows,T.B., Chuang,J.L.,
Chuang,D.T. and Cox,R.P.
TITLE Regional assignment of two genes of the human branched-chain
alpha-keto acid dehydrogenase complex: the E1 beta gene (BCKDHB) to
chromosome 6p21-22 and the E2 gene (DBT) to chromosome 1p31
JOURNAL Genomics 10 (3), 740-747 (1991)
PUBMED 1889817
REFERENCE 8 (residues 1 to 392)
AUTHORS Nobukuni,Y., Mitsubuchi,H., Akaboshi,I., Indo,Y., Endo,F.,
Yoshioka,A. and Matsuda,I.
TITLE Maple syrup urine disease. Complete defect of the E1 beta subunit
of the branched chain alpha-ketoacid dehydrogenase complex due to a
deletion of an 11-bp repeat sequence which encodes a mitochondrial
targeting leader peptide in a family with the disease
JOURNAL J. Clin. Invest. 87 (5), 1862-1866 (1991)
PUBMED 2022752
REFERENCE 9 (residues 1 to 392)
AUTHORS Nobukuni,Y., Mitsubuchi,H., Endo,F., Akaboshi,I., Asaka,J. and
Matsuda,I.
TITLE Maple syrup urine disease. Complete primary structure of the E1
beta subunit of human branched chain alpha-ketoacid dehydrogenase
complex deduced from the nucleotide sequence and a gene analysis of
patients with this disease
JOURNAL J. Clin. Invest. 86 (1), 242-247 (1990)
PUBMED 2365818
REFERENCE 10 (residues 1 to 392)
AUTHORS Chuang,J.L., Cox,R.P. and Chuang,D.T.
TITLE Molecular cloning of the mature E1b-beta subunit of human
branched-chain alpha-keto acid dehydrogenase complex
JOURNAL FEBS Lett. 262 (2), 305-309 (1990)
PUBMED 2335211
COMMENT REVIEWED REFSEQ: This record has been curated by NCBI staff. The
reference sequence was derived from DC372349.1, U50708.1,
BC034481.1 and DB548202.1.
Summary: Branched-chain keto acid dehydrogenase is a multienzyme
complex associated with the inner membrane of mitochondria, and
functions in the catabolism of branched-chain amino acids. The
complex consists of multiple copies of 3 components: branched-chain
alpha-keto acid decarboxylase (E1), lipoamide acyltransferase (E2)
and lipoamide dehydrogenase (E3). This gene encodes the E1 beta
subunit, and mutations therein have been associated with maple
syrup urine disease (MSUD), type 1B, a disease characterized by a
maple syrup odor to the urine in addition to mental and physical
retardation, and feeding problems. Alternative splicing at this
locus results in transcript variants with different 3' non-coding
regions, but encoding the same isoform. [provided by RefSeq].
Transcript Variant: This variant (2) is missing a segment in the 3'
UTR compared to transcript variant 1, and thus has a shorter 3'
UTR. Both variants 1 and 2 encode the same protein.
Publication Note: This RefSeq record includes a subset of the
publications that are available for this gene. Please see the
Entrez Gene record to access additional publications.
FEATURES Location/Qualifiers
source 1..392
/organism="Homo sapiens"
/db_xref="taxon:9606"
/chromosome="6"
/map="6q13-q15"
Protein 1..392
/product="branched chain keto acid dehydrogenase E1 beta
polypeptide precursor"
/EC_number="1.2.4.4"
/note="2-oxoisovalerate dehydrogenase beta subunit;
E1b-beta subunit of the branched-chain complex; branched
chain alpha-ketoacid dehydrogenase E1-beta subunit;
branched-chain alpha-keto acid dehydrogenase E1 component
beta chain"
transit_peptide 1..50
/calculated_mol_wt=5275
mat_peptide 51..392
/product="branched chain keto acid dehydrogenase E1, beta
polypeptide"
/calculated_mol_wt=37866
CDS 1..392
/gene="BCKDHB"
/gene_synonym="E1B"
/gene_synonym="FLJ17880"
/gene_synonym="dJ279A18.1"
/coded_by="NM_000056.3:68..1246"
/db_xref="CCDS:CCDS4994.1"
/db_xref="GeneID:594"
/db_xref="HGNC:987"
/db_xref="HPRD:02011"
/db_xref="MIM:248611"
ORIGIN
1 mavvaaaagw llrlraagae ghwrrlpgag largflhpaa tvedaaqrrq vahftfqpdp
61 epreygqtqk mnlfqsvtsa ldnslakdpt avifgedvaf ggvfrctvgl rdkygkdrvf
121 ntplceqgiv gfgigiavtg ataiaeiqfa dyifpafdqi vneaakyryr sgdlfncgsl
181 tirspwgcvg hgalyhsqsp eaffahcpgi kvviprspfq akglllscie dknpciffep
241 kilyraaaee vpiepynipl sqaeviqegs dvtlvawgtq vhvirevasm akeklgvsce
301 vidlrtiipw dvdticksvi ktgrllishe apltggfase isstvqeecf lnleapisrv
361 cgydtpfphi fepfyipdkw kcydalrkmi ny
//