LOCUS NP_000700 445 aa linear PRI 22-OCT-2008
DEFINITION branched chain keto acid dehydrogenase E1, alpha polypeptide [Homo
sapiens].
ACCESSION NP_000700
VERSION NP_000700.1 GI:11386135
DBSOURCE REFSEQ: accession NM_000709.2
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 445)
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 445)
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 3 (residues 1 to 445)
AUTHORS Ewing,R.M., Chu,P., Elisma,F., Li,H., Taylor,P., Climie,S.,
McBroom-Cerajewski,L., Robinson,M.D., O'Connor,L., Li,M.,
Taylor,R., Dharsee,M., Ho,Y., Heilbut,A., Moore,L., Zhang,S.,
Ornatsky,O., Bukhman,Y.V., Ethier,M., Sheng,Y., Vasilescu,J.,
Abu-Farha,M., Lambert,J.P., Duewel,H.S., Stewart,I.I., Kuehl,B.,
Hogue,K., Colwill,K., Gladwish,K., Muskat,B., Kinach,R.,
Adams,S.L., Moran,M.F., Morin,G.B., Topaloglou,T. and Figeys,D.
TITLE Large-scale mapping of human protein-protein interactions by mass
spectrometry
JOURNAL Mol. Syst. Biol. 3, 89 (2007)
PUBMED 17353931
REFERENCE 4 (residues 1 to 445)
AUTHORS Olsen,J.V., Blagoev,B., Gnad,F., Macek,B., Kumar,C., Mortensen,P.
and Mann,M.
TITLE Global, in vivo, and site-specific phosphorylation dynamics in
signaling networks
JOURNAL Cell 127 (3), 635-648 (2006)
PUBMED 17081983
REFERENCE 5 (residues 1 to 445)
AUTHORS Naik,M.T. and Huang,T.H.
TITLE Conformational stability and thermodynamic characterization of the
lipoic acid bearing domain of human mitochondrial branched chain
alpha-ketoacid dehydrogenase
JOURNAL Protein Sci. 13 (9), 2483-2492 (2004)
PUBMED 15322287
REMARK GeneRIF: the conformational stability underlying the folding of
this lipoic acid bearing domain of human mitochondrial branched
chain alpha-ketoacid dehydrogenase
REFERENCE 6 (sites)
AUTHORS Lynch,C.J., Halle,B., Fujii,H., Vary,T.C., Wallin,R., Damuni,Z. and
Hutson,S.M.
TITLE Potential role of leucine metabolism in the leucine-signaling
pathway involving mTOR
JOURNAL Am. J. Physiol. Endocrinol. Metab. 285 (4), E854-E863 (2003)
PUBMED 12812918
REFERENCE 7 (residues 1 to 445)
AUTHORS McKean,M.C., Winkeler,K.A. and Danner,D.J.
TITLE 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
JOURNAL Biochim. Biophys. Acta 1171 (1), 109-112 (1992)
PUBMED 1420356
REFERENCE 8 (residues 1 to 445)
AUTHORS Mitsubuchi,H., Matsuda,I., Nobukuni,Y., Heidenreich,R., Indo,Y.,
Endo,F., Mallee,J. and Segal,S.
TITLE Gene analysis of Mennonite maple syrup urine disease kindred using
primer-specified restriction map modification
JOURNAL J. Inherit. Metab. Dis. 15 (2), 181-187 (1992)
PUBMED 1356170
REFERENCE 9 (residues 1 to 445)
AUTHORS Dariush,N., Fisher,C.W., Cox,R.P. and Chuang,D.T.
TITLE Structure of the gene encoding the entire mature E1 alpha subunit
of human branched-chain alpha-keto acid dehydrogenase complex
(1991) FEBS Letters 284, 34-38
JOURNAL FEBS Lett. 291 (2), 376-377 (1991)
PUBMED 1682165
REMARK Correction to:[FEBS Lett. 1991 Jun 17;284(1):34-8. PMID: 2060625]
REFERENCE 10 (residues 1 to 445)
AUTHORS Fisher,C.R., Fisher,C.W., Chuang,D.T. and Cox,R.P.
TITLE 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
JOURNAL Am. J. Hum. Genet. 49 (2), 429-434 (1991)
PUBMED 1867199
REFERENCE 11 (residues 1 to 445)
AUTHORS Eisenstein,R.S., Hoganson,G., Miller,R.H. and Harper,A.E.
TITLE Altered phosphorylation state of branched-chain 2-oxo acid
dehydrogenase in a branched-chain acyltransferase deficient human
fibroblast cell line
JOURNAL J. Inherit. Metab. Dis. 14 (1), 37-44 (1991)
PUBMED 1861457
COMMENT VALIDATED REFSEQ: This record has undergone validation or
preliminary review. The reference sequence was derived from
BI910860.1, BG742673.1, BM702667.1, BE223026.1 and BQ018849.1.
Summary: The BCKDHA gene encodes the E1-alpha subunit of the
branched-chain alpha-keto acid (BCAA) dehydrogenase complex (BCKD;
EC 1.2.4.4), an inner-mitochondrial enzyme complex that catalyzes
the oxidative decarboxylation of the branched-chain alpha-ketoacids
derived from isoleucine, leucine, and valine. This reaction is the
second major step in the catabolism of the branched-chain amino
acids (Wynn et al., 1998 [PubMed 9582350]). The BCKD complex
consists of 3 catalytic components: a heterotetrameric
(alpha2-beta2) branched-chain alpha-keto acid decarboxylase (E1), a
homo-24-meric dihydrolipoyl transacylase (E2; MIM 248610), and a
homodimeric dihydrolipoamide dehydrogenase (E3; MIM 238331). E1 is
a thiamine pyrophosphate (TPP)-dependent enzyme. The reaction is
irreversible and constitutes the first committed step in BCAA
oxidation. The BCKDHB gene (MIM 248611) encodes the beta subunit of
E1. The complex also contains 2 regulatory enzymes, a kinase and a
phosphorylase.[supplied by OMIM].
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..445
/organism="Homo sapiens"
/db_xref="taxon:9606"
/chromosome="19"
/map="19q13.1-q13.2"
Protein 1..445
/product="branched chain keto acid dehydrogenase E1, alpha
polypeptide"
/EC_number="1.2.4.4"
/note="maple syrup urine disease; 2-oxoisovalerate
dehydrogenase (lipoamide); branched-chain alpha-keto acid
dehydrogenase complex E1 alpha subunit"
/calculated_mol_wt=50340
Site 337
/site_type="phosphorylation"
/experiment="experimental evidence, no additional details
recorded"
/citation=[6]
Site 347
/site_type="phosphorylation"
/experiment="experimental evidence, no additional details
recorded"
/citation=[6]
CDS 1..445
/gene="BCKDHA"
/gene_synonym="MSU"
/gene_synonym="MSUD1"
/gene_synonym="OVD1A"
/gene_synonym="BCKDE1A"
/gene_synonym="FLJ45695"
/coded_by="NM_000709.2:30..1367"
/db_xref="CCDS:CCDS12581.1"
/db_xref="GeneID:593"
/db_xref="HGNC:986"
/db_xref="HPRD:02009"
/db_xref="MIM:608348"
ORIGIN
1 mavaiaaarv wrlnrglsqa allllrqpga rglarshppr qqqqfssldd kpqfpgasae
61 fidklefiqp nvisgipiyr vmdrqgqiin psedphlpke kvlklyksmt llntmdrily
121 esqrqgrisf ymtnygeegt hvgsaaaldn tdlvfgqyre agvlmyrdyp lelfmaqcyg
181 nisdlgkgrq mpvhygcker hfvtisspla tqipqavgaa yaakrananr vvicyfgega
241 asegdahagf nfaatlecpi iffcrnngya istptseqyr gdgiaargpg ygimsirvdg
301 ndvfavynat kearrravae nqpflieamt yrighhstsd dssayrsvde vnywdkqdhp
361 isrlrhylls qgwwdeeqek awrkqsrrkv meafeqaerk pkpnpnllfs dvyqempaql
421 rkqqeslarh lqtygehypl dhfdk
//