ID ODBB_HUMAN Reviewed; 392 AA. AC P21953; Q5T2J3; Q9BQL0; DT 01-AUG-1991, integrated into UniProtKB/Swiss-Prot. DT 01-AUG-1992, sequence version 2. DT 02-SEP-2026, entry version 237. DE RecName: Full=2-oxoisovalerate dehydrogenase subunit beta, mitochondrial {ECO:0000305|PubMed:9582350}; DE EC=1.2.4.4 {ECO:0000269|PubMed:10745006, ECO:0000269|PubMed:9582350}; DE AltName: Full=Branched-chain alpha-keto acid dehydrogenase E1 component beta chain; DE Short=BCKDE1B; DE Short=BCKDH E1-beta; DE Flags: Precursor; GN Name=BCKDHB {ECO:0000312|HGNC:HGNC:987}; 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=2365818; DOI=10.1172/jci114690; RA Matsuda I., Asaka J., Akaboshi I., Endo F., Mitsubuchi H., Nobukuni Y.; RT "Maple syrup urine disease. Complete primary structure of the E1 beta RT subunit of human branched chain alpha-ketoacid dehydrogenase complex RT deduced from the nucleotide sequence and a gene analysis of patients with RT this disease."; RL J. Clin. Invest. 86:242-247(1990). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC TISSUE=Placenta; RX PubMed=8651316; RA Chuang J.L., Cox R.P., Chuang D.T.; RT "Maple syrup urine disease: the E1beta gene of human branched-chain alpha- RT ketoacid dehydrogenase complex has 11 rather than 10 exons, and the 3' UTR RT in one of the two E1beta mRNAs arises from intronic sequences."; RL Am. J. Hum. Genet. 58:1373-1377(1996). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Hippocampus; 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 [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., RA Phelan M., Farmer A.; RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector."; RL Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=14574404; DOI=10.1038/nature02055; RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., RA Rogers J., Beck S.; RT "The DNA sequence and analysis of human chromosome 6."; RL Nature 425:805-811(2003). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). RC TISSUE=Eye, and Testis; 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 [8] RP NUCLEOTIDE SEQUENCE [MRNA] OF 20-392 (ISOFORM 1). RX PubMed=2335211; DOI=10.1016/0014-5793(90)80215-5; RA Chuang J.L., Cox R.P., Chuang D.T.; RT "Molecular cloning of the mature E1b-beta subunit of human branched-chain RT alpha-keto acid dehydrogenase complex."; RL FEBS Lett. 262:305-309(1990). RN [9] RP PROTEIN SEQUENCE OF 36-62. 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 FUNCTION, CATALYTIC ACTIVITY, AND SUBUNIT. RX PubMed=9582350; DOI=10.1074/jbc.273.21.13110; RA Wynn R.M., Davie J.R., Chuang J.L., Cote C.D., Chuang D.T.; RT "Impaired assembly of E1 decarboxylase of the branched-chain alpha-ketoacid RT dehydrogenase complex in type IA maple syrup urine disease."; RL J. Biol. Chem. 273:13110-13118(1998). RN [11] RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-241, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19608861; DOI=10.1126/science.1175371; RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., RA Olsen J.V., Mann M.; RT "Lysine acetylation targets protein complexes and co-regulates major RT cellular functions."; RL Science 325:834-840(2009). RN [12] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [13] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [14] RP CLEAVAGE OF TRANSIT PEPTIDE [LARGE SCALE ANALYSIS] AFTER GLN-50, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25944712; DOI=10.1002/pmic.201400617; RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D., RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.; RT "N-terminome analysis of the human mitochondrial proteome."; RL Proteomics 15:2519-2524(2015). RN [15] {ECO:0007744|PDB:1DTW} RP X-RAY CRYSTALLOGRAPHY (2.70 ANGSTROMS) OF 51-392 IN COMPLEX WITH BCKDHA; RP THIAMINE PYROPHOSPHATE AND POTASSIUM IONS, FUNCTION, CATALYTIC ACTIVITY, RP COFACTOR, SUBUNIT, SUBCELLULAR LOCATION, VARIANT MSUD1B TYR-176, AND RP CHARACTERIZATION OF VARIANT MSUD1B TYR-176 AND ARG-206. 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 [16] RP VARIANT MSUD1B ARG-206. 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 MSUD1B PRO-183 AND SER-278. RX PubMed=11509994; DOI=10.1086/323677; RA Edelmann L., Wasserstein M.P., Kornreich R., Sansaricq C., Snyderman S.E., RA Diaz G.A.; RT "Maple syrup urine disease: identification and carrier-frequency RT determination of a novel founder mutation in the Ashkenazi Jewish RT population."; RL Am. J. Hum. Genet. 69:863-868(2001). RN [18] RP VARIANTS MSUD1B HIS-170 AND ARG-346. RX PubMed=22326532; DOI=10.1016/j.gene.2012.01.082; RA Wang Y.P., Qi M.L., Li T.T., Zhao Y.J.; RT "Two novel mutations in the BCKDHB gene (R170H, Q346R) cause the classic RT form of maple syrup urine disease (MSUD)."; RL Gene 498:112-115(2012). CC -!- FUNCTION: Together with BCKDHA forms the heterotetrameric E1 subunit of CC the mitochondrial branched-chain alpha-ketoacid dehydrogenase (BCKD) CC complex. The BCKD complex catalyzes the multi-step oxidative CC decarboxylation of alpha-ketoacids derived from the branched-chain CC amino-acids valine, leucine and isoleucine producing CO2 and acyl-CoA CC which is subsequently utilized to produce energy. The E1 subunit CC catalyzes the first step with the decarboxylation of the alpha-ketoacid CC forming an enzyme-product intermediate. A reductive acylation mediated CC by the lipoylamide cofactor of E2 extracts the acyl group from the E1 CC active site for the next step of the reaction. CC {ECO:0000269|PubMed:10745006, ECO:0000269|PubMed:9582350}. CC -!- CATALYTIC ACTIVITY: CC Reaction=N(6)-[(R)-lipoyl]-L-lysyl-[protein] + 3-methyl-2-oxobutanoate CC + H(+) = N(6)-[(R)-S(8)-2-methylpropanoyldihydrolipoyl]-L-lysyl- CC [protein] + CO2; Xref=Rhea:RHEA:13457, Rhea:RHEA-COMP:10474, CC Rhea:RHEA-COMP:10497, ChEBI:CHEBI:11851, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:16526, ChEBI:CHEBI:83099, ChEBI:CHEBI:83142; EC=1.2.4.4; CC Evidence={ECO:0000269|PubMed:10745006, ECO:0000269|PubMed:9582350}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:13458; CC Evidence={ECO:0000305|PubMed:9582350}; CC -!- CATALYTIC ACTIVITY: CC Reaction=N(6)-[(R)-lipoyl]-L-lysyl-[protein] + 4-methyl-2-oxopentanoate CC + H(+) = N(6)-[(R)-S(8)-3-methylbutanoyldihydrolipoyl]-L-lysyl- CC [protein] + CO2; Xref=Rhea:RHEA:84639, Rhea:RHEA-COMP:10474, CC Rhea:RHEA-COMP:20408, ChEBI:CHEBI:15378, ChEBI:CHEBI:16526, CC ChEBI:CHEBI:17865, ChEBI:CHEBI:83099, ChEBI:CHEBI:233973; CC Evidence={ECO:0000250|UniProtKB:P21839}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:84640; CC Evidence={ECO:0000250|UniProtKB:P21839}; CC -!- CATALYTIC ACTIVITY: CC Reaction=N(6)-[(R)-lipoyl]-L-lysyl-[protein] + (S)-3-methyl-2- CC oxopentanoate + H(+) = N(6)-{(R)-S(8)-[(2S)-2- CC methylbutanoyl]dihydrolipoyl}-L-lysyl-[protein] + CO2; CC Xref=Rhea:RHEA:84643, Rhea:RHEA-COMP:10474, Rhea:RHEA-COMP:20409, CC ChEBI:CHEBI:15378, ChEBI:CHEBI:16526, ChEBI:CHEBI:35146, CC ChEBI:CHEBI:83099, ChEBI:CHEBI:233974; CC Evidence={ECO:0000250|UniProtKB:P21839}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:84644; CC Evidence={ECO:0000250|UniProtKB:P21839}; CC -!- COFACTOR: CC Name=thiamine diphosphate; Xref=ChEBI:CHEBI:58937; CC Evidence={ECO:0000269|PubMed:10745006}; CC -!- SUBUNIT: Heterotetramer of 2 alpha/BCKDHA and 2 beta chains/BCKDHB that CC forms the branched-chain alpha-keto acid decarboxylase (E1) component CC of the BCKD complex (PubMed:10745006, PubMed:9582350). The branched- CC chain alpha-ketoacid dehydrogenase is a large complex composed of three CC major building blocks E1, E2 and E3. It is organized around E2, a 24- CC meric cubic core composed of DBT, to which are associated 6 to 12 CC copies of E1, and approximately 6 copies of the dehydrogenase E3, a DLD CC dimer (PubMed:10745006). {ECO:0000269|PubMed:10745006, CC ECO:0000269|PubMed:9582350, ECO:0000303|PubMed:10745006}. CC -!- INTERACTION: CC P21953; P12694: BCKDHA; NbExp=15; IntAct=EBI-1029067, EBI-1029053; CC P21953-1; P12694-1: BCKDHA; NbExp=3; IntAct=EBI-15489569, EBI-15489562; CC -!- SUBCELLULAR LOCATION: Mitochondrion matrix CC {ECO:0000303|PubMed:10745006}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=P21953-1; Sequence=Displayed; CC Name=2; CC IsoId=P21953-2; Sequence=VSP_056370, VSP_056371; CC -!- DISEASE: Maple syrup urine disease 1B (MSUD1B) [MIM:620698]: A form of CC maple syrup urine disease, an autosomal recessive metabolic disorder CC due to an enzyme defect in the catabolic pathway of the branched-chain CC amino acids leucine, isoleucine, and valine. Accumulation of these 3 CC amino acids and their corresponding keto acids leads to encephalopathy CC and progressive neurodegeneration. Clinical features include mental and CC physical retardation, feeding problems, and a maple syrup odor to the CC urine. The keto acids of the branched-chain amino acids are present in CC the urine. If untreated, maple syrup urine disease can lead to CC seizures, coma, and death. The disease is often classified by its CC pattern of signs and symptoms. The most common and severe form of the CC disease is the classic type, which becomes apparent soon after birth. CC Variant forms of the disorder become apparent later in infancy or CC childhood and are typically milder, but they still involve CC developmental delay and other medical problems if not treated. CC {ECO:0000269|PubMed:10745006, ECO:0000269|PubMed:11509994, CC ECO:0000269|PubMed:22326532, ECO:0000269|PubMed:8161368}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; M55575; AAA51812.1; -; mRNA. DR EMBL; D90391; BAA14389.1; -; Genomic_DNA. DR EMBL; AK289977; BAF82666.1; -; mRNA. DR EMBL; BT020063; AAV38866.1; -; mRNA. DR EMBL; AL049696; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL391595; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471051; EAW48696.1; -; Genomic_DNA. DR EMBL; CH471051; EAW48697.1; -; Genomic_DNA. DR EMBL; CH471051; EAW48698.1; -; Genomic_DNA. DR EMBL; BC034481; AAH34481.1; -; mRNA. DR EMBL; BC040139; AAH40139.1; -; mRNA. DR EMBL; U50708; AAB16763.1; -; mRNA. DR EMBL; X52446; CAA36685.1; -; mRNA. DR CCDS; CCDS4994.1; -. [P21953-1] DR PIR; A37157; A37157. DR RefSeq; NP_000047.1; NM_000056.5. [P21953-1] DR RefSeq; NP_001305904.1; NM_001318975.1. DR RefSeq; NP_001410965.1; NM_001424036.1. [P21953-1] DR RefSeq; NP_898871.1; NM_183050.4. [P21953-1] DR RefSeq; XP_047275163.1; XM_047419207.1. [P21953-1] DR RefSeq; XP_054212115.1; XM_054356140.1. [P21953-1] DR PDB; 1DTW; X-ray; 2.70 A; B=51-392. DR PDB; 1OLS; X-ray; 1.85 A; B=51-392. DR PDB; 1OLU; X-ray; 1.90 A; B=51-392. DR PDB; 1OLX; X-ray; 2.25 A; B=51-392. DR PDB; 1U5B; X-ray; 1.83 A; B=51-392. DR PDB; 1V11; X-ray; 1.95 A; B=51-392. DR PDB; 1V16; X-ray; 1.90 A; B=51-392. DR PDB; 1V1M; X-ray; 2.00 A; B=51-392. DR PDB; 1V1R; X-ray; 1.80 A; B=51-392. DR PDB; 1WCI; X-ray; 1.84 A; B=51-392. DR PDB; 1X7W; X-ray; 1.73 A; B=51-392. DR PDB; 1X7X; X-ray; 2.10 A; B=51-392. DR PDB; 1X7Y; X-ray; 1.57 A; B=51-392. DR PDB; 1X7Z; X-ray; 1.72 A; B=51-392. DR PDB; 1X80; X-ray; 2.00 A; B=51-392. DR PDB; 2BEU; X-ray; 1.89 A; B=51-392. DR PDB; 2BEV; X-ray; 1.80 A; B=51-392. DR PDB; 2BEW; X-ray; 1.79 A; B=51-392. DR PDB; 2BFB; X-ray; 1.77 A; B=51-392. DR PDB; 2BFC; X-ray; 1.64 A; B=51-392. DR PDB; 2BFD; X-ray; 1.39 A; B=51-392. DR PDB; 2BFE; X-ray; 1.69 A; B=51-392. DR PDB; 2BFF; X-ray; 1.46 A; B=51-392. DR PDB; 2J9F; X-ray; 1.88 A; B/D=51-392. DR AlphaFoldDB; P21953; -. DR MDRepo; P21953; -. DR SMR; P21953; -. DR BioGRID; 107066; 81. DR ComplexPortal; CPX-2216; Mitochondrial 2-oxoisovalerate dehydrogenase complex. DR DIP; DIP-6147N; -. DR FunCoup; P21953; 1093. DR IntAct; P21953; 38. DR MINT; P21953; -. DR NDEx; IQUERY-CP-BCKDHB; 1 NDEx IQuery Curated Pathway. DR STRING; 9606.ENSP00000318351; -. DR ChEMBL; CHEMBL5465287; -. DR GlyGen; P21953; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; P21953; -. DR PhosphoSitePlus; P21953; -. DR SwissPalm; P21953; -. DR BioMuta; BCKDHB; -. DR DMDM; 129034; -. DR REPRODUCTION-2DPAGE; IPI00011276; -. DR jPOST; P21953; -. DR MassIVE; P21953; -. DR PaxDb; 9606-ENSP00000318351; -. DR PeptideAtlas; P21953; -. DR ProteomicsDB; 53944; -. [P21953-1] DR ProteomicsDB; 64342; -. DR Pumba; P21953; -. DR TopDownProteomics; P21953-1; -. [P21953-1] DR Antibodypedia; 49986; 106 antibodies from 23 providers. DR DNASU; 594; -. DR Ensembl; ENST00000320393.9; ENSP00000318351.5; ENSG00000083123.16. [P21953-1] DR Ensembl; ENST00000356489.9; ENSP00000348880.5; ENSG00000083123.16. [P21953-1] DR Ensembl; ENST00000369760.8; ENSP00000358775.4; ENSG00000083123.16. [P21953-2] DR Ensembl; ENST00000879176.1; ENSP00000549235.1; ENSG00000083123.16. [P21953-1] DR GeneID; 594; -. DR KEGG; hsa:594; -. DR MANE-Select; ENST00000320393.9; ENSP00000318351.5; NM_183050.4; NP_898871.1. DR UCSC; uc003pjd.3; human. [P21953-1] DR AGR; HGNC:987; -. DR ClinPGx; PA25298; -. DR CTD; 594; -. DR DisGeNET; 594; -. DR GeneCards; BCKDHB; -. DR GeneReviews; BCKDHB; -. DR HGNC; HGNC:987; BCKDHB. DR HPA; ENSG00000083123; Tissue enhanced (liver). DR MalaCards; BCKDHB; -. DR MIM; 248600; phenotype. DR MIM; 248611; gene. DR MIM; 620698; phenotype. DR OpenTargets; ENSG00000083123; -. 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 VEuPathDB; HostDB:ENSG00000083123; -. DR eggNOG; KOG0525; Eukaryota. DR GeneTree; ENSGT00940000156533; -. DR HOGENOM; CLU_012907_1_5_1; -. DR InParanoid; P21953; -. DR OMA; SEAYYMA; -. DR OrthoDB; 878at2759; -. DR PAN-GO; P21953; 3 GO annotations based on evolutionary models. DR PhylomeDB; P21953; -. DR BioCyc; MetaCyc:MONOMER-12006; -. DR BRENDA; 1.2.1.25; 2681. DR PathwayCommons; P21953; -. DR Reactome; R-HSA-70895; Branched-chain amino acid catabolism. DR Reactome; R-HSA-9859138; BCKDH synthesizes BCAA-CoA from KIC, KMVA, KIV. DR Reactome; R-HSA-9865113; Loss-of-function mutations in DBT cause MSUD2. DR Reactome; R-HSA-9865125; Loss-of-function mutations in BCKDHA or BCKDHB cause MSUD. DR Reactome; R-HSA-9907570; Loss-of-function mutations in DLD cause MSUD3/DLDD. DR Reactome; R-HSA-9912481; Branched-chain ketoacid dehydrogenase kinase deficiency. DR Reactome; R-HSA-9912529; H139Hfs13* PPM1K causes a mild variant of MSUD. DR SABIO-RK; P21953; -. DR SignaLink; P21953; -. DR Agora; ENSG00000083123; -. DR BioGRID-ORCS; 594; 14 hits in 1158 CRISPR screens. DR ChiTaRS; BCKDHB; human. DR EvolutionaryTrace; P21953; -. DR GeneWiki; BCKDHB; -. DR GenomeRNAi; 594; -. DR Pharos; P21953; Tbio. DR PRO; PR:P21953; -. DR Proteomes; UP000005640; Chromosome 6. DR RNAct; P21953; protein. DR Bgee; ENSG00000083123; Expressed in right lobe of liver and 166 other cell types or tissues. DR ExpressionAtlas; P21953; baseline and differential. DR GO; GO:0160157; C:branched-chain alpha-ketoacid dehydrogenase complex; IDA:UniProtKB. DR GO; GO:0005759; C:mitochondrial matrix; ISS:UniProtKB. DR GO; GO:0005739; C:mitochondrion; IDA:HPA. DR GO; GO:0003863; F:branched-chain 2-oxo acid dehydrogenase activity; IEA:UniProtKB-EC. DR GO; GO:0120552; P:branched-chain alpha-keto acid decarboxylation to branched-chain acyl-CoA; IDA:FlyBase. DR GO; GO:0009083; P:branched-chain amino acid catabolic process; IDA:ComplexPortal. DR GO; GO:0006550; P:L-isoleucine catabolic process; IEA:Ensembl. DR GO; GO:0006552; P:L-leucine catabolic process; IEA:Ensembl. DR GO; GO:0006574; P:L-valine catabolic process; IEA:Ensembl. DR GO; GO:0007584; P:response to nutrient; IBA:GO_Central. DR CDD; cd07036; TPP_PYR_E1-PDHc-beta_like; 1. DR FunFam; 3.40.50.920:FF:000004; 2-oxoisovalerate dehydrogenase subunit beta 1, mitochondrial; 1. DR FunFam; 3.40.50.970:FF:000001; Pyruvate dehydrogenase E1 beta subunit; 1. DR Gene3D; 3.40.50.920; -; 1. DR Gene3D; 3.40.50.970; -; 1. DR InterPro; IPR029061; THDP-binding. DR InterPro; IPR009014; Transketo_C/PFOR_II. DR InterPro; IPR005475; Transketolase-like_Pyr-bd. DR InterPro; IPR033248; Transketolase_C. DR PANTHER; PTHR42980:SF1; 2-OXOISOVALERATE DEHYDROGENASE SUBUNIT BETA, MITOCHONDRIAL; 1. DR PANTHER; PTHR42980; 2-OXOISOVALERATE DEHYDROGENASE SUBUNIT BETA-RELATED; 1. DR Pfam; PF02779; Transket_pyr; 1. DR Pfam; PF02780; Transketolase_C; 1. DR SMART; SM00861; Transket_pyr; 1. DR SUPFAM; SSF52518; Thiamin diphosphate-binding fold (THDP-binding); 1. DR SUPFAM; SSF52922; TK C-terminal domain-like; 1. 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; -. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Alternative splicing; Direct protein sequencing; KW Disease variant; Lipid metabolism; Maple syrup urine disease; KW Mitochondrion; Oxidoreductase; Proteomics identification; KW Reference proteome; Transit peptide. FT TRANSIT 1..50 FT /note="Mitochondrion" FT /evidence="ECO:0007744|PubMed:25944712" FT CHAIN 51..392 FT /note="2-oxoisovalerate dehydrogenase subunit beta, FT mitochondrial" FT /id="PRO_0000020470" FT BINDING 152 FT /ligand="thiamine diphosphate" FT /ligand_id="ChEBI:CHEBI:58937" FT /ligand_note="ligand shared with alpha subunit" FT /evidence="ECO:0000269|PubMed:10745006, FT ECO:0007744|PDB:1DTW" FT BINDING 178 FT /ligand="K(+)" FT /ligand_id="ChEBI:CHEBI:29103" FT /ligand_note="structural" FT /evidence="ECO:0000269|PubMed:10745006, FT ECO:0007744|PDB:1DTW" FT BINDING 180 FT /ligand="K(+)" FT /ligand_id="ChEBI:CHEBI:29103" FT /ligand_note="structural" FT /evidence="ECO:0000269|PubMed:10745006, FT ECO:0007744|PDB:1DTW" FT BINDING 181 FT /ligand="K(+)" FT /ligand_id="ChEBI:CHEBI:29103" FT /ligand_note="structural" FT /evidence="ECO:0000269|PubMed:10745006, FT ECO:0007744|PDB:1DTW" FT BINDING 228 FT /ligand="K(+)" FT /ligand_id="ChEBI:CHEBI:29103" FT /ligand_note="structural" FT /evidence="ECO:0000269|PubMed:10745006, FT ECO:0007744|PDB:1DTW" FT BINDING 231 FT /ligand="K(+)" FT /ligand_id="ChEBI:CHEBI:29103" FT /ligand_note="structural" FT /evidence="ECO:0000269|PubMed:10745006, FT ECO:0007744|PDB:1DTW" FT BINDING 233 FT /ligand="K(+)" FT /ligand_id="ChEBI:CHEBI:29103" FT /ligand_note="structural" FT /evidence="ECO:0000269|PubMed:10745006, FT ECO:0007744|PDB:1DTW" FT MOD_RES 232 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:Q6P3A8" FT MOD_RES 241 FT /note="N6-acetyllysine" FT /evidence="ECO:0007744|PubMed:19608861" FT VAR_SEQ 212..218 FT /note="VVIPRSP -> IKVISLS (in isoform 2)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_056370" FT VAR_SEQ 219..392 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_056371" FT VARIANT 41 FT /note="T -> I (in dbSNP:rs35470366)" FT /id="VAR_050437" FT VARIANT 170 FT /note="R -> H (in MSUD1B; dbSNP:rs371518124)" FT /evidence="ECO:0000269|PubMed:22326532" FT /id="VAR_068348" FT VARIANT 176 FT /note="N -> Y (in MSUD1B; uncertain significance; loss of FT 3-methyl-2-oxobutanoate dehydrogenase activity)" FT /evidence="ECO:0000269|PubMed:10745006" FT /id="VAR_088297" FT VARIANT 183 FT /note="R -> P (in MSUD1B; dbSNP:rs79761867)" FT /evidence="ECO:0000269|PubMed:11509994" FT /id="VAR_024851" FT VARIANT 206 FT /note="H -> R (in MSUD1B; loss of 3-methyl-2-oxobutanoate FT dehydrogenase activity)" FT /evidence="ECO:0000269|PubMed:10745006, FT ECO:0000269|PubMed:8161368" FT /id="VAR_004974" FT VARIANT 278 FT /note="G -> S (in MSUD1B; dbSNP:rs386834233)" FT /evidence="ECO:0000269|PubMed:11509994" FT /id="VAR_024852" FT VARIANT 346 FT /note="Q -> R (in MSUD1B)" FT /evidence="ECO:0000269|PubMed:22326532" FT /id="VAR_068349" FT CONFLICT 20..23 FT /note="EGHW -> RLPP (in Ref. 8)" FT /evidence="ECO:0000305" FT CONFLICT 322 FT /note="T -> S (in Ref. 8; CAA36685)" FT /evidence="ECO:0000305" FT STRAND 68..71 FT /evidence="ECO:0007829|PDB:2BFD" FT HELIX 73..87 FT /evidence="ECO:0007829|PDB:2BFD" FT STRAND 92..95 FT /evidence="ECO:0007829|PDB:2BFD" FT TURN 96..101 FT /evidence="ECO:0007829|PDB:2BFD" FT TURN 106..109 FT /evidence="ECO:0007829|PDB:2BFD" FT HELIX 110..114 FT /evidence="ECO:0007829|PDB:2BFD" FT TURN 116..118 FT /evidence="ECO:0007829|PDB:2BFD" FT STRAND 119..121 FT /evidence="ECO:0007829|PDB:2BFD" FT HELIX 126..138 FT /evidence="ECO:0007829|PDB:2BFD" FT STRAND 143..146 FT /evidence="ECO:0007829|PDB:2BFD" FT HELIX 150..152 FT /evidence="ECO:0007829|PDB:2BFD" FT HELIX 154..156 FT /evidence="ECO:0007829|PDB:2BFD" FT HELIX 159..163 FT /evidence="ECO:0007829|PDB:2BFD" FT HELIX 164..166 FT /evidence="ECO:0007829|PDB:2BFD" FT HELIX 167..170 FT /evidence="ECO:0007829|PDB:2BFD" FT TURN 171..173 FT /evidence="ECO:0007829|PDB:2BFD" FT STRAND 180..187 FT /evidence="ECO:0007829|PDB:2BFD" FT HELIX 193..195 FT /evidence="ECO:0007829|PDB:2BFD" FT HELIX 201..205 FT /evidence="ECO:0007829|PDB:2BFD" FT STRAND 211..213 FT /evidence="ECO:0007829|PDB:2BFD" FT HELIX 218..230 FT /evidence="ECO:0007829|PDB:2BFD" FT STRAND 231..233 FT /evidence="ECO:0007829|PDB:2BFD" FT STRAND 235..240 FT /evidence="ECO:0007829|PDB:2BFD" FT HELIX 241..243 FT /evidence="ECO:0007829|PDB:2BFD" FT TURN 244..246 FT /evidence="ECO:0007829|PDB:1V1R" FT STRAND 249..254 FT /evidence="ECO:0007829|PDB:2BFD" FT STRAND 264..267 FT /evidence="ECO:0007829|PDB:2BFD" FT STRAND 270..276 FT /evidence="ECO:0007829|PDB:2BFD" FT HELIX 280..295 FT /evidence="ECO:0007829|PDB:2BFD" FT STRAND 299..303 FT /evidence="ECO:0007829|PDB:2BFD" FT STRAND 306..309 FT /evidence="ECO:0007829|PDB:2BFD" FT HELIX 312..322 FT /evidence="ECO:0007829|PDB:2BFD" FT STRAND 325..333 FT /evidence="ECO:0007829|PDB:2BFD" FT HELIX 337..348 FT /evidence="ECO:0007829|PDB:2BFD" FT HELIX 350..352 FT /evidence="ECO:0007829|PDB:2BFD" FT STRAND 358..362 FT /evidence="ECO:0007829|PDB:2BFD" FT HELIX 366..368 FT /evidence="ECO:0007829|PDB:2BFC" FT HELIX 372..375 FT /evidence="ECO:0007829|PDB:2BFD" FT HELIX 379..390 FT /evidence="ECO:0007829|PDB:2BFD" SQ SEQUENCE 392 AA; 43122 MW; D78097834D063BB7 CRC64; MAVVAAAAGW LLRLRAAGAE GHWRRLPGAG LARGFLHPAA TVEDAAQRRQ VAHFTFQPDP EPREYGQTQK MNLFQSVTSA LDNSLAKDPT AVIFGEDVAF GGVFRCTVGL RDKYGKDRVF NTPLCEQGIV GFGIGIAVTG ATAIAEIQFA DYIFPAFDQI VNEAAKYRYR SGDLFNCGSL TIRSPWGCVG HGALYHSQSP EAFFAHCPGI KVVIPRSPFQ AKGLLLSCIE DKNPCIFFEP KILYRAAAEE VPIEPYNIPL SQAEVIQEGS DVTLVAWGTQ VHVIREVASM AKEKLGVSCE VIDLRTIIPW DVDTICKSVI KTGRLLISHE APLTGGFASE ISSTVQEECF LNLEAPISRV CGYDTPFPHI FEPFYIPDKW KCYDALRKMI NY //