ODBA_HUMAN
ID ODBA_HUMAN Reviewed; 445 AA.
AC P12694; B4DP47; E7EW46; Q16034; Q16472;
DT 01-OCT-1989, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-1994, sequence version 2.
DT 03-AUG-2022, entry version 238.
DE RecName: Full=2-oxoisovalerate dehydrogenase subunit alpha, mitochondrial {ECO:0000305};
DE EC=1.2.4.4 {ECO:0000269|PubMed:7883996};
DE AltName: Full=Branched-chain alpha-keto acid dehydrogenase E1 component alpha chain;
DE Short=BCKDE1A;
DE Short=BCKDH E1-alpha;
DE Flags: Precursor;
GN Name=BCKDHA {ECO:0000312|HGNC:HGNC:986};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=1420356; DOI=10.1016/0167-4781(92)90149-t;
RA McKean M.C., Winkeler K.A., Danner D.J.;
RT "Nucleotide sequence of the 5' end including the initiation codon of cDNA
RT for the E1 alpha subunit of the human branched chain alpha-ketoacid
RT dehydrogenase complex.";
RL Biochim. Biophys. Acta 1171:109-112(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057824; DOI=10.1038/nature02399;
RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E.,
RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A.,
RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S.,
RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A.,
RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J.,
RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M.,
RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W.,
RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V.,
RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D.,
RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I.,
RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L.,
RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A.,
RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M.,
RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J.,
RA Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA Rubin E.M., Lucas S.M.;
RT "The DNA sequence and biology of human chromosome 19.";
RL Nature 428:529-535(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Bone marrow, and Lung;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 3-445 (ISOFORM 1).
RX PubMed=2914958; DOI=10.1016/s0021-9258(18)94087-1;
RA Fisher C.W., Chuang J.L., Griffin T.A., Lau K.S., Cox R.P., Chuang D.T.;
RT "Molecular phenotypes in cultured maple syrup urine disease cells. Complete
RT E1 alpha cDNA sequence and mRNA and subunit contents of the human branched
RT chain alpha-keto acid dehydrogenase complex.";
RL J. Biol. Chem. 264:3448-3453(1989).
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 3-445, AND VARIANT MSUD1A ASN-438.
RX PubMed=2060625; DOI=10.1016/0014-5793(91)80755-r;
RA Dariush N., Fisher C.W., Cox R.P., Chuang D.T.;
RT "Structure of the gene encoding the entire mature E1 alpha subunit of human
RT branched-chain alpha-keto acid dehydrogenase complex.";
RL FEBS Lett. 284:34-38(1991).
RN [7]
RP ERRATUM OF PUBMED:2060625.
RX PubMed=1682165; DOI=10.1016/0014-5793(91)81324-2;
RA Dariush N., Fisher C.W., Cox R.P., Chuang D.T.;
RL FEBS Lett. 291:376-377(1991).
RN [8]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 68-445 (ISOFORM 1).
RC TISSUE=Liver;
RX PubMed=3224821; DOI=10.1016/0378-1119(88)90390-3;
RA Zhang B., Crabb D.W., Harris R.A.;
RT "Nucleotide and deduced amino acid sequence of the E1 alpha subunit of
RT human liver branched-chain alpha-ketoacid dehydrogenase.";
RL Gene 69:159-164(1988).
RN [9]
RP PROTEIN SEQUENCE OF 46-57.
RX PubMed=7918575; DOI=10.1016/0304-4165(94)90161-9;
RA Wynn R.M., Kochi H., Cox R.P., Chuang D.T.;
RT "Differential processing of human and rat E1 alpha precursors of the
RT branched-chain alpha-keto acid dehydrogenase complex caused by an N-
RT terminal proline in the rat sequence.";
RL Biochim. Biophys. Acta 1201:125-128(1994).
RN [10]
RP X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 46-445 IN COMPLEX WITH THIAMINE
RP PYROPHOSPHATE AND POTASSIUM IONS, COFACTOR, AND SUBUNIT STRUCTURE.
RX PubMed=10745006; DOI=10.1016/s0969-2126(00)00105-2;
RA Aevarsson A., Chuang J.L., Wynn R.M., Turley S., Chuang D.T., Hol W.G.J.;
RT "Crystal structure of human branched-chain alpha-ketoacid dehydrogenase and
RT the molecular basis of multienzyme complex deficiency in maple syrup urine
RT disease.";
RL Structure 8:277-291(2000).
RN [11]
RP VARIANT MSUD1A CYS-413.
RX PubMed=8037208;
RA Chuang J.L., Fisher C.R., Cox R.P., Chuang D.T.;
RT "Molecular basis of maple syrup urine disease: novel mutations at the E1
RT alpha locus that impair E1(alpha 2 beta 2) assembly or decrease steady-
RT state E1 alpha mRNA levels of branched-chain alpha-keto acid dehydrogenase
RT complex.";
RL Am. J. Hum. Genet. 55:297-304(1994).
RN [12]
RP VARIANT MSUD1A ASN-438.
RX PubMed=2703538; DOI=10.1172/jci114033;
RA Zhang B., Edenberg H.J., Crabb D.W., Harris R.A.;
RT "Evidence for both a regulatory mutation and a structural mutation in a
RT family with maple syrup urine disease.";
RL J. Clin. Invest. 83:1425-1429(1989).
RN [13]
RP VARIANT MSUD1A ASN-438.
RX PubMed=2241958; DOI=10.1016/0006-291x(90)90723-z;
RA Matsuda I., Nobukuni Y., Mitsubuchi H., Indo Y., Endo F., Asaka J.,
RA Harada A.;
RT "A T-to-A substitution in the E1 alpha subunit gene of the branched-chain
RT alpha-ketoacid dehydrogenase complex in two cell lines derived from
RT Menonite maple syrup urine disease patients.";
RL Biochem. Biophys. Res. Commun. 172:646-651(1990).
RN [14]
RP VARIANT MSUD1A ASN-438.
RX PubMed=1867199;
RA Fisher C.R., Fisher C.W., Chuang D.T., Cox R.P.;
RT "Occurrence of a Tyr393-->Asn (Y393N) mutation in the E1 alpha gene of the
RT branched-chain alpha-keto acid dehydrogenase complex in maple syrup urine
RT disease patients from a Mennonite population.";
RL Am. J. Hum. Genet. 49:429-434(1991).
RN [15]
RP VARIANT MSUD1A ASN-438.
RX PubMed=1885764; DOI=10.1172/jci115363;
RA Fisher C.R., Chuang J.L., Cox R.P., Fisher C.W., Star R.A., Chuang D.T.;
RT "Maple syrup urine disease in Mennonites. Evidence that the Y393N mutation
RT in E1 alpha impedes assembly of the E1 component of branched-chain alpha-
RT keto acid dehydrogenase complex.";
RL J. Clin. Invest. 88:1034-1037(1991).
RN [16]
RP VARIANTS MSUD1A TRP-159; LYS-190; THR-253 AND THR-326.
RX PubMed=8161368; DOI=10.1016/0925-4439(93)90123-i;
RA Nobukuni Y., Mitsubuchi H., Hayashida Y., Ohta K., Indo Y., Ichiba Y.,
RA Endo F., Matsuda I.;
RT "Heterogeneity of mutations in maple syrup urine disease (MSUD): screening
RT and identification of affected E1 alpha and E1 beta subunits of the
RT branched-chain alpha-keto-acid dehydrogenase multienzyme complex.";
RL Biochim. Biophys. Acta 1225:64-70(1993).
RN [17]
RP VARIANTS MSUD1A ARG-290 AND CYS-409, CATALYTIC ACTIVITY, AND FUNCTION.
RX PubMed=7883996; DOI=10.1172/jci117804;
RA Chuang J.L., Davie J.R., Chinsky J.M., Wynn R.M., Cox R.P., Chuang D.T.;
RT "Molecular and biochemical basis of intermediate maple syrup urine disease:
RT occurrence of homozygous G245R and F364C mutations at the E1-alpha locus of
RT Hispanic-Mexican patients.";
RL J. Clin. Invest. 95:954-963(1995).
RN [18]
RP VARIANTS MSUD1A MET-211; VAL-220; CYS-346; LYS-PRO-403 INS AND
RP 427-LEU-ALA-428 DELINS PRO.
RX PubMed=21844576;
RA Park H.D., Lee D.H., Hong Y.H., Kang D.H., Lee Y.K., Song J., Lee S.Y.,
RA Kim J.W., Ki C.S., Lee Y.W.;
RT "Three Korean patients with maple syrup urine disease: four novel mutations
RT in the BCKDHA gene.";
RL Ann. Clin. Lab. Sci. 41:167-173(2011).
CC -!- FUNCTION: E1 subunit of the branched-chain alpha-keto dehydrogenase
CC complex that catalyzes both the decarboxylation of the alpha-ketoacid
CC and the subsequent reductive acylation of the lipoyl moiety (another
CC catalytic cofactor) that is covalently bound to E2 (PubMed:7883996).
CC The branched-chain alpha-keto dehydrogenase complex catalyzes the
CC overall conversion of alpha-keto acids to acyl-CoA and CO(2). It
CC contains multiple copies of three enzymatic components: branched-chain
CC alpha-keto acid decarboxylase (E1), lipoamide acyltransferase (E2) and
CC lipoamide dehydrogenase (E3). {ECO:0000269|PubMed:7883996}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(R)-N(6)-lipoyl-L-lysyl-[dihydrolipoyllysine-residue (2-
CC methylpropanoyl)transferase] + 3-methyl-2-oxobutanoate + H(+) = (R)-
CC N(6)-(S(8)-2-methylpropanoyldihydrolipoyl)-L-lysyl-
CC [dihydrolipoyllysine-residue (2-methylpropanoyl)transferase] + CO2;
CC Xref=Rhea:RHEA:13457, Rhea:RHEA-COMP:10488, Rhea:RHEA-COMP:10489,
CC ChEBI:CHEBI:11851, ChEBI:CHEBI:15378, ChEBI:CHEBI:16526,
CC ChEBI:CHEBI:83099, ChEBI:CHEBI:83142; EC=1.2.4.4;
CC Evidence={ECO:0000269|PubMed:7883996};
CC -!- COFACTOR:
CC Name=thiamine diphosphate; Xref=ChEBI:CHEBI:58937;
CC Evidence={ECO:0000269|PubMed:10745006};
CC -!- SUBUNIT: Heterotetramer of alpha and beta chains.
CC {ECO:0000269|PubMed:10745006}.
CC -!- INTERACTION:
CC P12694; P21953: BCKDHB; NbExp=14; IntAct=EBI-1029053, EBI-1029067;
CC P12694-1; P21953-1: BCKDHB; NbExp=3; IntAct=EBI-15489562, EBI-15489569;
CC -!- SUBCELLULAR LOCATION: Mitochondrion matrix.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P12694-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P12694-2; Sequence=VSP_056156, VSP_056157;
CC -!- DISEASE: Maple syrup urine disease 1A (MSUD1A) [MIM:248600]: A
CC metabolic disorder due to an enzyme defect in the catabolic pathway of
CC the branched-chain amino acids leucine, isoleucine, and valine.
CC Accumulation of these 3 amino acids and their corresponding keto acids
CC leads to encephalopathy and progressive neurodegeneration. Clinical
CC features include mental and physical retardation, feeding problems, and
CC a maple syrup odor to the urine. The keto acids of the branched-chain
CC amino acids are present in the urine. If untreated, maple syrup urine
CC disease can lead to seizures, coma, and death. The disease is often
CC classified by its pattern of signs and symptoms. The most common and
CC severe form of the disease is the classic type, which becomes apparent
CC soon after birth. Variant forms of the disorder become apparent later
CC in infancy or childhood and are typically milder, but they still
CC involve developmental delay and other medical problems if not treated.
CC {ECO:0000269|PubMed:1867199, ECO:0000269|PubMed:1885764,
CC ECO:0000269|PubMed:2060625, ECO:0000269|PubMed:21844576,
CC ECO:0000269|PubMed:2241958, ECO:0000269|PubMed:2703538,
CC ECO:0000269|PubMed:7883996, ECO:0000269|PubMed:8037208,
CC ECO:0000269|PubMed:8161368}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- MISCELLANEOUS: Bound potassium ions stabilize the protein structure.
CC -!- SIMILARITY: Belongs to the BCKDHA family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAB59549.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; Z14093; CAA78475.1; -; mRNA.
DR EMBL; AK298188; BAG60459.1; -; mRNA.
DR EMBL; AC011462; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC007878; AAH07878.1; -; mRNA.
DR EMBL; BC008933; AAH08933.1; -; mRNA.
DR EMBL; BC023983; AAH23983.1; -; mRNA.
DR EMBL; J04474; AAB59549.1; ALT_INIT; mRNA.
DR EMBL; AH003771; AAB20222.2; -; Genomic_DNA.
DR EMBL; AH003707; AAB19268.2; -; Genomic_DNA.
DR EMBL; M22221; AAA35590.1; -; mRNA.
DR CCDS; CCDS12581.1; -. [P12694-1]
DR PIR; S27156; DEHUXA.
DR RefSeq; NP_000700.1; NM_000709.3. [P12694-1]
DR RefSeq; NP_001158255.1; NM_001164783.1.
DR PDB; 1DTW; X-ray; 2.70 A; A=46-445.
DR PDB; 1OLS; X-ray; 1.85 A; A=46-445.
DR PDB; 1OLU; X-ray; 1.90 A; A=46-445.
DR PDB; 1OLX; X-ray; 2.25 A; A=46-445.
DR PDB; 1U5B; X-ray; 1.83 A; A=46-445.
DR PDB; 1V11; X-ray; 1.95 A; A=46-445.
DR PDB; 1V16; X-ray; 1.90 A; A=46-445.
DR PDB; 1V1M; X-ray; 2.00 A; A=46-445.
DR PDB; 1V1R; X-ray; 1.80 A; A=46-445.
DR PDB; 1WCI; X-ray; 1.84 A; A=46-445.
DR PDB; 1X7W; X-ray; 1.73 A; A=46-445.
DR PDB; 1X7X; X-ray; 2.10 A; A=46-445.
DR PDB; 1X7Y; X-ray; 1.57 A; A=46-445.
DR PDB; 1X7Z; X-ray; 1.72 A; A=46-445.
DR PDB; 1X80; X-ray; 2.00 A; A=46-445.
DR PDB; 2BEU; X-ray; 1.89 A; A=46-445.
DR PDB; 2BEV; X-ray; 1.80 A; A=46-445.
DR PDB; 2BEW; X-ray; 1.79 A; A=46-445.
DR PDB; 2BFB; X-ray; 1.77 A; A=46-445.
DR PDB; 2BFC; X-ray; 1.64 A; A=46-445.
DR PDB; 2BFD; X-ray; 1.39 A; A=46-445.
DR PDB; 2BFE; X-ray; 1.69 A; A=46-445.
DR PDB; 2BFF; X-ray; 1.46 A; A=46-445.
DR PDB; 2J9F; X-ray; 1.88 A; A/C=46-445.
DR PDBsum; 1DTW; -.
DR PDBsum; 1OLS; -.
DR PDBsum; 1OLU; -.
DR PDBsum; 1OLX; -.
DR PDBsum; 1U5B; -.
DR PDBsum; 1V11; -.
DR PDBsum; 1V16; -.
DR PDBsum; 1V1M; -.
DR PDBsum; 1V1R; -.
DR PDBsum; 1WCI; -.
DR PDBsum; 1X7W; -.
DR PDBsum; 1X7X; -.
DR PDBsum; 1X7Y; -.
DR PDBsum; 1X7Z; -.
DR PDBsum; 1X80; -.
DR PDBsum; 2BEU; -.
DR PDBsum; 2BEV; -.
DR PDBsum; 2BEW; -.
DR PDBsum; 2BFB; -.
DR PDBsum; 2BFC; -.
DR PDBsum; 2BFD; -.
DR PDBsum; 2BFE; -.
DR PDBsum; 2BFF; -.
DR PDBsum; 2J9F; -.
DR AlphaFoldDB; P12694; -.
DR SMR; P12694; -.
DR BioGRID; 107065; 194.
DR ComplexPortal; CPX-2216; Mitochondrial 2-oxoisovalerate dehydrogenase complex.
DR DIP; DIP-6146N; -.
DR IntAct; P12694; 48.
DR MINT; P12694; -.
DR STRING; 9606.ENSP00000269980; -.
DR iPTMnet; P12694; -.
DR PhosphoSitePlus; P12694; -.
DR BioMuta; BCKDHA; -.
DR EPD; P12694; -.
DR jPOST; P12694; -.
DR MassIVE; P12694; -.
DR MaxQB; P12694; -.
DR PaxDb; P12694; -.
DR PeptideAtlas; P12694; -.
DR PRIDE; P12694; -.
DR ProteomicsDB; 4756; -.
DR ProteomicsDB; 52863; -. [P12694-1]
DR Antibodypedia; 35354; 146 antibodies from 25 providers.
DR DNASU; 593; -.
DR Ensembl; ENST00000269980.7; ENSP00000269980.2; ENSG00000248098.12. [P12694-1]
DR Ensembl; ENST00000457836.6; ENSP00000416000.2; ENSG00000248098.12. [P12694-2]
DR GeneID; 593; -.
DR KEGG; hsa:593; -.
DR MANE-Select; ENST00000269980.7; ENSP00000269980.2; NM_000709.4; NP_000700.1.
DR UCSC; uc002oqq.4; human. [P12694-1]
DR CTD; 593; -.
DR DisGeNET; 593; -.
DR GeneCards; BCKDHA; -.
DR GeneReviews; BCKDHA; -.
DR HGNC; HGNC:986; BCKDHA.
DR HPA; ENSG00000248098; Low tissue specificity.
DR MalaCards; BCKDHA; -.
DR MIM; 248600; phenotype.
DR MIM; 608348; gene.
DR neXtProt; NX_P12694; -.
DR OpenTargets; ENSG00000248098; -.
DR Orphanet; 268145; Classic maple syrup urine disease.
DR Orphanet; 268162; Intermediate maple syrup urine disease.
DR Orphanet; 268173; Intermittent maple syrup urine disease.
DR Orphanet; 268184; Thiamine-responsive maple syrup urine disease.
DR PharmGKB; PA25297; -.
DR VEuPathDB; HostDB:ENSG00000248098; -.
DR eggNOG; KOG1182; Eukaryota.
DR GeneTree; ENSGT00530000063174; -.
DR HOGENOM; CLU_029393_1_0_1; -.
DR InParanoid; P12694; -.
DR OMA; LQYWGGD; -.
DR PhylomeDB; P12694; -.
DR TreeFam; TF300863; -.
DR BioCyc; MetaCyc:MON-12005; -.
DR PathwayCommons; P12694; -.
DR Reactome; R-HSA-389661; Glyoxylate metabolism and glycine degradation.
DR Reactome; R-HSA-70895; Branched-chain amino acid catabolism.
DR SABIO-RK; P12694; -.
DR SignaLink; P12694; -.
DR SIGNOR; P12694; -.
DR BioGRID-ORCS; 593; 16 hits in 1079 CRISPR screens.
DR ChiTaRS; BCKDHA; human.
DR EvolutionaryTrace; P12694; -.
DR GeneWiki; BCKDHA; -.
DR GenomeRNAi; 593; -.
DR Pharos; P12694; Tbio.
DR PRO; PR:P12694; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; P12694; protein.
DR Bgee; ENSG00000248098; Expressed in lower esophagus mucosa and 97 other tissues.
DR ExpressionAtlas; P12694; baseline and differential.
DR Genevisible; P12694; HS.
DR GO; GO:0005947; C:mitochondrial alpha-ketoglutarate dehydrogenase complex; IDA:HGNC-UCL.
DR GO; GO:0005759; C:mitochondrial matrix; TAS:Reactome.
DR GO; GO:0005739; C:mitochondrion; HDA:UniProtKB.
DR GO; GO:0003863; F:3-methyl-2-oxobutanoate dehydrogenase (2-methylpropanoyl-transferring) activity; IDA:HGNC-UCL.
DR GO; GO:0016831; F:carboxy-lyase activity; TAS:HGNC-UCL.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0009083; P:branched-chain amino acid catabolic process; IDA:HGNC-UCL.
DR InterPro; IPR034616; BCKDH_E1-a.
DR InterPro; IPR001017; DH_E1.
DR InterPro; IPR029061; THDP-binding.
DR PANTHER; PTHR43380:SF1; PTHR43380:SF1; 1.
DR Pfam; PF00676; E1_dh; 1.
DR SUPFAM; SSF52518; SSF52518; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Direct protein sequencing;
KW Disease variant; Maple syrup urine disease; Metal-binding; Mitochondrion;
KW Oxidoreductase; Phosphoprotein; Potassium; Reference proteome;
KW Thiamine pyrophosphate; Transit peptide.
FT TRANSIT 1..45
FT /note="Mitochondrion"
FT /evidence="ECO:0000269|PubMed:7918575"
FT CHAIN 46..445
FT /note="2-oxoisovalerate dehydrogenase subunit alpha,
FT mitochondrial"
FT /id="PRO_0000020465"
FT REGION 33..52
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 37..51
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 157..159
FT /ligand="thiamine diphosphate"
FT /ligand_id="ChEBI:CHEBI:58937"
FT /evidence="ECO:0000269|PubMed:10745006"
FT BINDING 206
FT /ligand="K(+)"
FT /ligand_id="ChEBI:CHEBI:29103"
FT /evidence="ECO:0000269|PubMed:10745006"
FT BINDING 211
FT /ligand="K(+)"
FT /ligand_id="ChEBI:CHEBI:29103"
FT /evidence="ECO:0000269|PubMed:10745006"
FT BINDING 212
FT /ligand="K(+)"
FT /ligand_id="ChEBI:CHEBI:29103"
FT /evidence="ECO:0000269|PubMed:10745006"
FT MOD_RES 337
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P50136"
FT MOD_RES 338
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P50136"
FT MOD_RES 339
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P50136"
FT MOD_RES 347
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P50136"
FT MOD_RES 356
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P50136"
FT MOD_RES 356
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P50136"
FT MOD_RES 380
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:P50136"
FT VAR_SEQ 19..40
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_056156"
FT VAR_SEQ 331
FT /note="Y -> YSSSPILPPDPHSREPTLTWGPLPLC (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_056157"
FT VARIANT 39
FT /note="P -> H (in dbSNP:rs11549936)"
FT /id="VAR_034360"
FT VARIANT 151
FT /note="T -> M (in dbSNP:rs34442879)"
FT /id="VAR_034361"
FT VARIANT 159
FT /note="R -> W (in MSUD1A; dbSNP:rs769688327)"
FT /evidence="ECO:0000269|PubMed:8161368"
FT /id="VAR_004968"
FT VARIANT 190
FT /note="Q -> K (in MSUD1A)"
FT /evidence="ECO:0000269|PubMed:8161368"
FT /id="VAR_004969"
FT VARIANT 211
FT /note="T -> M (in MSUD1A; dbSNP:rs398123503)"
FT /evidence="ECO:0000269|PubMed:21844576"
FT /id="VAR_069748"
FT VARIANT 220
FT /note="A -> V (in MSUD1A; dbSNP:rs375785084)"
FT /evidence="ECO:0000269|PubMed:21844576"
FT /id="VAR_069749"
FT VARIANT 253
FT /note="A -> T (in MSUD1A; dbSNP:rs199599175)"
FT /evidence="ECO:0000269|PubMed:8161368"
FT /id="VAR_004970"
FT VARIANT 290
FT /note="G -> R (in MSUD1A; dbSNP:rs137852871)"
FT /evidence="ECO:0000269|PubMed:7883996"
FT /id="VAR_015101"
FT VARIANT 326
FT /note="I -> T (in MSUD1A)"
FT /evidence="ECO:0000269|PubMed:8161368"
FT /id="VAR_004971"
FT VARIANT 346
FT /note="R -> C (in MSUD1A; dbSNP:rs182923857)"
FT /evidence="ECO:0000269|PubMed:21844576"
FT /id="VAR_069750"
FT VARIANT 403
FT /note="P -> PKP (in MSUD1A)"
FT /id="VAR_069751"
FT VARIANT 409
FT /note="F -> C (in MSUD1A; dbSNP:rs137852872)"
FT /evidence="ECO:0000269|PubMed:7883996"
FT /id="VAR_015102"
FT VARIANT 413
FT /note="Y -> C (in MSUD1A)"
FT /evidence="ECO:0000269|PubMed:8037208"
FT /id="VAR_004972"
FT VARIANT 427..428
FT /note="LA -> P (in MSUD1A)"
FT /evidence="ECO:0000269|PubMed:21844576"
FT /id="VAR_069752"
FT VARIANT 438
FT /note="Y -> N (in MSUD1A; impedes assembly of the E1
FT component; dbSNP:rs137852870)"
FT /evidence="ECO:0000269|PubMed:1867199,
FT ECO:0000269|PubMed:1885764, ECO:0000269|PubMed:2060625,
FT ECO:0000269|PubMed:2241958, ECO:0000269|PubMed:2703538"
FT /id="VAR_004973"
FT CONFLICT 3
FT /note="V -> G (in Ref. 6; AAB20222/AAB19268)"
FT /evidence="ECO:0000305"
FT CONFLICT 36
FT /note="S -> A (in Ref. 5; AAB59549)"
FT /evidence="ECO:0000305"
FT CONFLICT 248
FT /note="A -> D (in Ref. 8; AAA35590)"
FT /evidence="ECO:0000305"
FT STRAND 61..64
FT /evidence="ECO:0007829|PDB:2J9F"
FT STRAND 88..90
FT /evidence="ECO:0007829|PDB:1DTW"
FT HELIX 91..93
FT /evidence="ECO:0007829|PDB:2BFD"
FT HELIX 99..124
FT /evidence="ECO:0007829|PDB:2BFD"
FT STRAND 127..129
FT /evidence="ECO:0007829|PDB:2BFD"
FT TURN 135..137
FT /evidence="ECO:0007829|PDB:2BFB"
FT HELIX 138..146
FT /evidence="ECO:0007829|PDB:2BFD"
FT STRAND 152..155
FT /evidence="ECO:0007829|PDB:2BFD"
FT HELIX 161..166
FT /evidence="ECO:0007829|PDB:2BFD"
FT HELIX 171..179
FT /evidence="ECO:0007829|PDB:2BFD"
FT TURN 185..188
FT /evidence="ECO:0007829|PDB:2BFD"
FT TURN 198..201
FT /evidence="ECO:0007829|PDB:2BFD"
FT TURN 209..211
FT /evidence="ECO:0007829|PDB:2BFD"
FT HELIX 212..226
FT /evidence="ECO:0007829|PDB:2BFD"
FT STRAND 232..237
FT /evidence="ECO:0007829|PDB:2BFD"
FT HELIX 240..242
FT /evidence="ECO:0007829|PDB:2BFD"
FT HELIX 244..255
FT /evidence="ECO:0007829|PDB:2BFD"
FT STRAND 260..266
FT /evidence="ECO:0007829|PDB:2BFD"
FT STRAND 268..270
FT /evidence="ECO:0007829|PDB:2BFD"
FT HELIX 275..277
FT /evidence="ECO:0007829|PDB:2BFD"
FT STRAND 280..282
FT /evidence="ECO:0007829|PDB:2BFD"
FT HELIX 285..287
FT /evidence="ECO:0007829|PDB:2BFD"
FT HELIX 289..291
FT /evidence="ECO:0007829|PDB:2BFD"
FT STRAND 294..299
FT /evidence="ECO:0007829|PDB:2BFD"
FT HELIX 303..320
FT /evidence="ECO:0007829|PDB:2BFD"
FT STRAND 324..329
FT /evidence="ECO:0007829|PDB:2BFD"
FT HELIX 342..344
FT /evidence="ECO:0007829|PDB:2BFF"
FT HELIX 351..357
FT /evidence="ECO:0007829|PDB:2BFF"
FT HELIX 360..368
FT /evidence="ECO:0007829|PDB:2BFD"
FT TURN 369..372
FT /evidence="ECO:0007829|PDB:2BFD"
FT HELIX 376..399
FT /evidence="ECO:0007829|PDB:2BFD"
FT HELIX 405..408
FT /evidence="ECO:0007829|PDB:2BFD"
FT TURN 409..411
FT /evidence="ECO:0007829|PDB:2BEW"
FT STRAND 412..415
FT /evidence="ECO:0007829|PDB:2BFD"
FT HELIX 418..434
FT /evidence="ECO:0007829|PDB:2BFD"
FT HELIX 435..437
FT /evidence="ECO:0007829|PDB:2BFD"
FT HELIX 440..442
FT /evidence="ECO:0007829|PDB:2BFD"
SQ SEQUENCE 445 AA; 50471 MW; 2B4DD658924DB0C3 CRC64;
MAVAIAAARV WRLNRGLSQA ALLLLRQPGA RGLARSHPPR QQQQFSSLDD KPQFPGASAE
FIDKLEFIQP NVISGIPIYR VMDRQGQIIN PSEDPHLPKE KVLKLYKSMT LLNTMDRILY
ESQRQGRISF YMTNYGEEGT HVGSAAALDN TDLVFGQYRE AGVLMYRDYP LELFMAQCYG
NISDLGKGRQ MPVHYGCKER HFVTISSPLA TQIPQAVGAA YAAKRANANR VVICYFGEGA
ASEGDAHAGF NFAATLECPI IFFCRNNGYA ISTPTSEQYR GDGIAARGPG YGIMSIRVDG
NDVFAVYNAT KEARRRAVAE NQPFLIEAMT YRIGHHSTSD DSSAYRSVDE VNYWDKQDHP
ISRLRHYLLS QGWWDEEQEK AWRKQSRRKV MEAFEQAERK PKPNPNLLFS DVYQEMPAQL
RKQQESLARH LQTYGEHYPL DHFDK
