LOCUS       NM_000709               1742 bp    mRNA    linear   PRI 09-FEB-2025
DEFINITION  Homo sapiens branched chain keto acid dehydrogenase E1 subunit
            alpha (BCKDHA), transcript variant 1, mRNA; nuclear gene for
            mitochondrial product.
ACCESSION   NM_000709
VERSION     NM_000709.4
KEYWORDS    RefSeq; MANE Select.
SOURCE      Homo sapiens (human)
  ORGANISM  Homo sapiens
            Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
            Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
            Catarrhini; Hominidae; Homo.
REFERENCE   1  (bases 1 to 1742)
  AUTHORS   Yang,J., Xiu,J., Sun,Y., Liu,F., Shang,X. and Li,G.
  TITLE     Three novel mutations of the BCKDHA, BCKDHB and DBT genes in
            Chinese children with maple syrup urine disease
  JOURNAL   J Pediatr Endocrinol Metab 35 (3), 303-312 (2021)
   PUBMED   34883003
  REMARK    GeneRIF: Three novel mutations of the BCKDHA, BCKDHB and DBT genes
            in Chinese children with maple syrup urine disease.
            Publication Status: Online-Only
REFERENCE   2  (bases 1 to 1742)
  AUTHORS   Morgenstern,M., Peikert,C.D., Lubbert,P., Suppanz,I., Klemm,C.,
            Alka,O., Steiert,C., Naumenko,N., Schendzielorz,A., Melchionda,L.,
            Muhlhauser,W.W.D., Knapp,B., Busch,J.D., Stiller,S.B.,
            Dannenmaier,S., Lindau,C., Licheva,M., Eickhorst,C., Galbusera,R.,
            Zerbes,R.M., Ryan,M.T., Kraft,C., Kozjak-Pavlovic,V., Drepper,F.,
            Dennerlein,S., Oeljeklaus,S., Pfanner,N., Wiedemann,N. and
            Warscheid,B.
  TITLE     Quantitative high-confidence human mitochondrial proteome and its
            dynamics in cellular context
  JOURNAL   Cell Metab 33 (12), 2464-2483 (2021)
   PUBMED   34800366
REFERENCE   3  (bases 1 to 1742)
  AUTHORS   Vargas-Morales,J.M., Guizar-Heredia,R., Mendez-Garcia,A.L.,
            Palacios-Gonzalez,B., Schcolnik-Cabrera,A., Granados,O.,
            Lopez-Barradas,A.M., Vazquez-Manjarrez,N., Medina-Vera,I.,
            Aguilar-Lopez,M., Tovar-Palacio,C., Ordaz-Nava,G.,
            Rocha-Viggiano,A.K., Medina-Cerda,E., Torres,N., Ordovas,J.M.,
            Tovar,A.R., Guevara-Cruz,M. and Noriega,L.G.
  TITLE     Association of BCAT2 and BCKDH polymorphisms with clinical,
            anthropometric and biochemical parameters in young adults
  JOURNAL   Nutr Metab Cardiovasc Dis 31 (11), 3210-3218 (2021)
   PUBMED   34511290
  REMARK    GeneRIF: Association of BCAT2 and BCKDH polymorphisms with
            clinical, anthropometric and biochemical parameters in young
            adults.
REFERENCE   4  (bases 1 to 1742)
  AUTHORS   Huttlin,E.L., Bruckner,R.J., Navarrete-Perea,J., Cannon,J.R.,
            Baltier,K., Gebreab,F., Gygi,M.P., Thornock,A., Zarraga,G., Tam,S.,
            Szpyt,J., Gassaway,B.M., Panov,A., Parzen,H., Fu,S., Golbazi,A.,
            Maenpaa,E., Stricker,K., Guha Thakurta,S., Zhang,T., Rad,R.,
            Pan,J., Nusinow,D.P., Paulo,J.A., Schweppe,D.K., Vaites,L.P.,
            Harper,J.W. and Gygi,S.P.
  TITLE     Dual proteome-scale networks reveal cell-specific remodeling of the
            human interactome
  JOURNAL   Cell 184 (11), 3022-3040 (2021)
   PUBMED   33961781
REFERENCE   5  (bases 1 to 1742)
  AUTHORS   Fernandez-Lainez,C., Alaez-Verson,C., Ibarra-Gonzalez,I.,
            Enriquez-Flores,S., Carrillo-Sanchez,K., Flores-Lagunes,L.,
            Guillen-Lopez,S., Belmont-Martinez,L. and Vela-Amieva,M.
  TITLE     In silico prediction of the pathogenic effect of a novel variant of
            BCKDHA leading to classical maple syrup urine disease identified
            using clinical exome sequencing
  JOURNAL   Clin Chim Acta 483, 33-38 (2018)
   PUBMED   29673582
  REMARK    GeneRIF: pathogenic effect of a novel variant of BCKDHA leading to
            classical maple syrup urine disease
REFERENCE   6  (bases 1 to 1742)
  AUTHORS   Strauss,K.A., Puffenberger,E.G. and Carson,V.J.
  TITLE     Maple Syrup Urine Disease
  JOURNAL   (in) Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE and
            Amemiya A (Eds.);
            GENEREVIEWS(R);
            (1993)
   PUBMED   20301495
REFERENCE   7  (bases 1 to 1742)
  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  (bases 1 to 1742)
  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  (bases 1 to 1742)
  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. doi:
            10.1016/0014-5793(91)80755-r.. PMID: 2060625]
REFERENCE   10 (bases 1 to 1742)
  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     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from BC023983.1, AK298188.1 and
            BQ018849.1.
            This sequence is a reference standard in the RefSeqGene project.
            
            On Nov 23, 2018 this sequence version replaced NM_000709.3.
            
            Summary: The branched-chain alpha-keto acid (BCAA) dehydrogenase
            (BCKD) complex is an innter mitochondrial enzyme complex that
            catalyzes the second major step in the catabolism of the
            branched-chain amino acids leucine, isoleucine, and valine. The
            BCKD complex consists of three catalytic components: a
            heterotetrameric (alpha2-beta2) branched-chain alpha-keto acid
            decarboxylase (E1), a dihydrolipoyl transacylase (E2), and a
            dihydrolipoamide dehydrogenase (E3). This gene encodes the alpha
            subunit of the decarboxylase (E1) component. Mutations in this gene
            result in maple syrup urine disease, type IA. Multiple transcript
            variants encoding different isoforms have been found for this
            gene.[provided by RefSeq, Sep 2009].
            
            Transcript Variant: This variant (1) represents the longest
            transcript and encodes the longest isoform (1).
            
            Publication Note:  This RefSeq record includes a subset of the
            publications that are available for this gene. Please see the Gene
            record to access additional publications.
            
            ##Evidence-Data-START##
            Transcript exon combination :: BC023983.1, SRR3476690.198658.1
                                           [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA1965299, SAMEA1966682
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            gene product(s) localized to mito. :: reported by MitoCarta
            MANE Ensembl match                 :: ENST00000269980.7/
                                                  ENSP00000269980.2
            RefSeq Select criteria             :: based on conservation,
                                                  expression, longest protein
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-981               BC023983.1         5-985
            982-982             AK298188.1         913-913
            983-1230            BC023983.1         987-1234
            1231-1741           AK298188.1         1237-1747
            1742-1742           BQ018849.1         21-21               c
FEATURES             Location/Qualifiers
     source          1..1742
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="19"
                     /map="19q13.2"
     gene            1..1742
                     /gene="BCKDHA"
                     /gene_synonym="BCKDE1A; MSU; MSUD1; MSUD1A; OVD1A"
                     /note="branched chain keto acid dehydrogenase E1 subunit
                     alpha"
                     /db_xref="GeneID:593"
                     /db_xref="HGNC:HGNC:986"
                     /db_xref="MIM:608348"
     exon            1..118
                     /gene="BCKDHA"
                     /gene_synonym="BCKDE1A; MSU; MSUD1; MSUD1A; OVD1A"
                     /inference="alignment:Splign:2.1.0"
     CDS             11..1348
                     /gene="BCKDHA"
                     /gene_synonym="BCKDE1A; MSU; MSUD1; MSUD1A; OVD1A"
                     /EC_number="1.2.4.4"
                     /note="isoform 1 precursor is encoded by transcript
                     variant 1; 2-oxoisovalerate dehydrogenase (lipoamide);
                     2-oxoisovalerate dehydrogenase subunit alpha,
                     mitochondrial; branched-chain alpha-keto acid
                     dehydrogenase E1 component alpha chain; BCKDH E1-alpha;
                     branched chain keto acid dehydrogenase E1 alpha protein;
                     branched chain keto acid dehydrogenase E1, alpha
                     polypeptide"
                     /codon_start=1
                     /product="2-oxoisovalerate dehydrogenase subunit alpha,
                     mitochondrial isoform 1 precursor"
                     /protein_id="NP_000700.1"
                     /db_xref="CCDS:CCDS12581.1"
                     /db_xref="GeneID:593"
                     /db_xref="HGNC:HGNC:986"
                     /db_xref="MIM:608348"
                     /translation="MAVAIAAARVWRLNRGLSQAALLLLRQPGARGLARSHPPRQQQQ
                     FSSLDDKPQFPGASAEFIDKLEFIQPNVISGIPIYRVMDRQGQIINPSEDPHLPKEKV
                     LKLYKSMTLLNTMDRILYESQRQGRISFYMTNYGEEGTHVGSAAALDNTDLVFGQYRE
                     AGVLMYRDYPLELFMAQCYGNISDLGKGRQMPVHYGCKERHFVTISSPLATQIPQAVG
                     AAYAAKRANANRVVICYFGEGAASEGDAHAGFNFAATLECPIIFFCRNNGYAISTPTS
                     EQYRGDGIAARGPGYGIMSIRVDGNDVFAVYNATKEARRRAVAENQPFLIEAMTYRIG
                     HHSTSDDSSAYRSVDEVNYWDKQDHPISRLRHYLLSQGWWDEEQEKAWRKQSRRKVME
                     AFEQAERKPKPNPNLLFSDVYQEMPAQLRKQQESLARHLQTYGEHYPLDHFDK"
     exon            119..298
                     /gene="BCKDHA"
                     /gene_synonym="BCKDE1A; MSU; MSUD1; MSUD1A; OVD1A"
                     /inference="alignment:Splign:2.1.0"
     exon            299..385
                     /gene="BCKDHA"
                     /gene_synonym="BCKDE1A; MSU; MSUD1; MSUD1A; OVD1A"
                     /inference="alignment:Splign:2.1.0"
     exon            386..494
                     /gene="BCKDHA"
                     /gene_synonym="BCKDE1A; MSU; MSUD1; MSUD1A; OVD1A"
                     /inference="alignment:Splign:2.1.0"
     exon            495..656
                     /gene="BCKDHA"
                     /gene_synonym="BCKDE1A; MSU; MSUD1; MSUD1A; OVD1A"
                     /inference="alignment:Splign:2.1.0"
     exon            657..863
                     /gene="BCKDHA"
                     /gene_synonym="BCKDE1A; MSU; MSUD1; MSUD1A; OVD1A"
                     /inference="alignment:Splign:2.1.0"
     exon            864..1005
                     /gene="BCKDHA"
                     /gene_synonym="BCKDE1A; MSU; MSUD1; MSUD1A; OVD1A"
                     /inference="alignment:Splign:2.1.0"
     exon            1006..1177
                     /gene="BCKDHA"
                     /gene_synonym="BCKDE1A; MSU; MSUD1; MSUD1A; OVD1A"
                     /inference="alignment:Splign:2.1.0"
     exon            1178..1742
                     /gene="BCKDHA"
                     /gene_synonym="BCKDE1A; MSU; MSUD1; MSUD1A; OVD1A"
                     /inference="alignment:Splign:2.1.0"
     regulatory      1712..1717
                     /regulatory_class="polyA_signal_sequence"
                     /gene="BCKDHA"
                     /gene_synonym="BCKDE1A; MSU; MSUD1; MSUD1A; OVD1A"
                     /note="hexamer: AATAAA"
     polyA_site      1742
                     /gene="BCKDHA"
                     /gene_synonym="BCKDE1A; MSU; MSUD1; MSUD1A; OVD1A"
                     /note="major polyA site"
ORIGIN      
        1 gttagccaag atggcggtag cgatcgctgc agcgagggtc tggcggctaa accgtggttt
       61 gagccaggct gccctcctgc tgctgcggca gcctggggct cggggactgg ctagatctca
      121 cccccccagg cagcagcagc agttttcatc tctggatgac aagccccagt tcccaggggc
      181 ctcggcggag tttatagata agttggaatt catccagccc aacgtcatct ctggaatccc
      241 catctaccgc gtcatggacc ggcaaggcca gatcatcaac cccagcgagg acccccacct
      301 gccgaaggag aaggtgctga agctctacaa gagcatgaca ctgcttaaca ccatggaccg
      361 catcctctat gagtctcagc ggcagggccg gatctccttc tacatgacca actatggtga
      421 ggagggcacg cacgtgggga gtgccgccgc cctggacaac acggacctgg tgtttggcca
      481 gtaccgggag gcaggtgtgc tgatgtatcg ggactacccc ctggaactat tcatggccca
      541 gtgctatggc aacatcagtg acttgggcaa ggggcgccag atgcctgtcc actacggctg
      601 caaggaacgc cacttcgtca ctatctcctc tccactggcc acgcagatcc ctcaggcggt
      661 gggggcggcg tacgcagcca agcgggccaa tgccaacagg gtcgtcatct gttacttcgg
      721 cgagggggca gccagtgagg gggacgccca tgccggcttc aacttcgctg ccacacttga
      781 gtgccccatc atcttcttct gccggaacaa tggctacgcc atctccacgc ccacctctga
      841 gcagtatcgc ggcgatggca ttgcagcacg aggccccggg tatggcatca tgtcaatccg
      901 cgtggatggt aatgatgtgt ttgccgtata caacgccaca aaggaggccc gacggcgggc
      961 tgtggcagag aaccagccct tcctcatcga ggccatgacc tacaggatcg ggcaccacag
     1021 caccagtgac gacagttcag cgtaccgctc ggtggatgag gtcaattact gggataaaca
     1081 ggaccacccc atctcccggc tgcggcacta tctgctgagc caaggctggt gggatgagga
     1141 gcaggagaag gcctggagga agcagtcccg caggaaggtg atggaggcct ttgagcaggc
     1201 cgagcggaag cccaaaccca accccaacct actcttctca gacgtgtatc aggagatgcc
     1261 cgcccagctc cgcaagcagc aggagtctct ggcccgccac ctgcagacct acggggagca
     1321 ctacccactg gatcacttcg ataagtgaga cctgctcagc ccacccccac ccatcctcag
     1381 ctaccccgag aggtagcccc actctaaggg gagcaggggg acctgacagc acaccactgt
     1441 cttccccagt cagctccctc taaaatactc agcggccagg gcggctgcca ctcttcaccc
     1501 ctgctcctcc cggctgttac attgtcaggg gacagcatct gcagcagttg ctgaggctcc
     1561 gtcagccccc tcttcacctg ttgttacagt gccttctccc aggggctggg tgagggcaca
     1621 ttcaggacta gaagcccctc tgggcatggg gtggacatgg caggtcagcc tgtggaactt
     1681 gcgcaggtgc gagtggccag cagaggtcac gaataaactg catctctgcg cctggctctc
     1741 ta
//
