BCKD_HUMAN
ID BCKD_HUMAN Reviewed; 412 AA.
AC O14874; A8MY43; Q6FGL4; Q96G95; Q96IN5;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT 06-JUN-2002, sequence version 2.
DT 03-AUG-2022, entry version 199.
DE RecName: Full=[3-methyl-2-oxobutanoate dehydrogenase [lipoamide]] kinase, mitochondrial;
DE EC=2.7.11.4;
DE AltName: Full=Branched-chain alpha-ketoacid dehydrogenase kinase;
DE Short=BCKD-kinase;
DE Short=BCKDHKIN;
DE Flags: Precursor;
GN Name=BCKDK;
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).
RA Chuang J.C., Cox R.P., Chuang D.T.;
RL Submitted (SEP-1997) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
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 MRNA] (ISOFORM 1).
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15616553; DOI=10.1038/nature03187;
RA Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G.,
RA Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E.,
RA Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J., Buckingham J.M.,
RA Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C.,
RA Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M.,
RA Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M.,
RA Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D.,
RA Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L.,
RA Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E.,
RA Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H.,
RA Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y.,
RA Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J.,
RA Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D.,
RA Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S.,
RA Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A.,
RA Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M.,
RA Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H.,
RA Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A.,
RA Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J.,
RA DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J.,
RA Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M.,
RA Myers R.M., Rubin E.M., Pennacchio L.A.;
RT "The sequence and analysis of duplication-rich human chromosome 16.";
RL Nature 432:988-994(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Lung, and Placenta;
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 [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling
RT networks.";
RL Cell 127:635-648(2006).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18220336; DOI=10.1021/pr0705441;
RA Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III;
RT "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient
RT phosphoproteomic analysis.";
RL J. Proteome Res. 7:1346-1351(2008).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the
RT kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [10]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-192 AND LYS-233, AND
RP IDENTIFICATION BY MASS 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 [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [12]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [14]
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 [15]
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 [16]
RP VARIANT BCKDKD PRO-224.
RX PubMed=22956686; DOI=10.1126/science.1224631;
RA Novarino G., El-Fishawy P., Kayserili H., Meguid N.A., Scott E.M.,
RA Schroth J., Silhavy J.L., Kara M., Khalil R.O., Ben-Omran T.,
RA Ercan-Sencicek A.G., Hashish A.F., Sanders S.J., Gupta A.R., Hashem H.S.,
RA Matern D., Gabriel S., Sweetman L., Rahimi Y., Harris R.A., State M.W.,
RA Gleeson J.G.;
RT "Mutations in BCKD-kinase lead to a potentially treatable form of autism
RT with epilepsy.";
RL Science 338:394-397(2012).
RN [17]
RP VARIANTS BCKDKD GLY-174 AND PRO-389, CHARACTERIZATION OF VARIANTS BCKDKD
RP GLY-174 AND PRO-389, FUNCTION, SUBCELLULAR LOCATION, AND
RP AUTOPHOSPHORYLATION.
RX PubMed=24449431; DOI=10.1002/humu.22513;
RA Garcia-Cazorla A., Oyarzabal A., Fort J., Robles C., Castejon E.,
RA Ruiz-Sala P., Bodoy S., Merinero B., Lopez-Sala A., Dopazo J., Nunes V.,
RA Ugarte M., Artuch R., Palacin M., Rodriguez-Pombo P., Alcaide P.,
RA Navarrete R., Sanz P., Font-Llitjos M., Vilaseca M.A., Ormaizabal A.,
RA Pristoupilova A., Agullo S.B.;
RT "Two novel mutations in the BCKDK (branched-chain keto-acid dehydrogenase
RT kinase) gene are responsible for a neurobehavioral deficit in two pediatric
RT unrelated patients.";
RL Hum. Mutat. 35:470-477(2014).
CC -!- FUNCTION: Catalyzes the phosphorylation and inactivation of the
CC branched-chain alpha-ketoacid dehydrogenase complex, the key regulatory
CC enzyme of the valine, leucine and isoleucine catabolic pathways. Key
CC enzyme that regulate the activity state of the BCKD complex.
CC {ECO:0000269|PubMed:24449431}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[3-methyl-2-oxobutanoate dehydrogenase] = ADP +
CC H(+) + O-phospho-L-seryl-[3-methyl-2-oxobutanoate dehydrogenase];
CC Xref=Rhea:RHEA:17301, Rhea:RHEA-COMP:13695, Rhea:RHEA-COMP:13696,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.4;
CC -!- SUBUNIT: Monomer. {ECO:0000250}.
CC -!- INTERACTION:
CC O14874; P02549: SPTA1; NbExp=3; IntAct=EBI-1046765, EBI-375617;
CC O14874; P40763: STAT3; NbExp=2; IntAct=EBI-1046765, EBI-518675;
CC O14874; PRO_0000037548 [Q9WMX2]; Xeno; NbExp=2; IntAct=EBI-1046765, EBI-6863741;
CC O14874-2; Q8WUW1: BRK1; NbExp=3; IntAct=EBI-25895587, EBI-2837444;
CC -!- SUBCELLULAR LOCATION: Mitochondrion matrix. Mitochondrion
CC {ECO:0000269|PubMed:24449431}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=O14874-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O14874-2; Sequence=VSP_054604, VSP_054605;
CC Name=3;
CC IsoId=O14874-3; Sequence=VSP_054605;
CC -!- TISSUE SPECIFICITY: Ubiquitous.
CC -!- PTM: Autophosphorylated. {ECO:0000269|PubMed:24449431}.
CC -!- DISEASE: Branched-chain ketoacid dehydrogenase kinase deficiency
CC (BCKDKD) [MIM:614923]: A metabolic disorder characterized by autism,
CC epilepsy, intellectual disability, and reduced branched-chain amino
CC acids. {ECO:0000269|PubMed:22956686, ECO:0000269|PubMed:24449431}.
CC Note=The disease is caused by variants affecting the gene represented
CC in this entry. A diet enriched in branched amino acids (BCAAs) allows
CC to normalize plasma BCAA levels. This suggests that it may be possible
CC to treat patients with mutations in BCKDK with BCAA supplementation.
CC -!- SIMILARITY: Belongs to the PDK/BCKDK protein kinase family.
CC {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Protein Spotlight; Note=The silence within - Issue
CC 147 of March 2013;
CC URL="https://web.expasy.org/spotlight/back_issues/147";
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DR EMBL; AF026548; AAB82714.1; -; mRNA.
DR EMBL; AK130145; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; CR542093; CAG46890.1; -; mRNA.
DR EMBL; AC135050; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471192; EAW52160.1; -; Genomic_DNA.
DR EMBL; CH471192; EAW52161.1; -; Genomic_DNA.
DR EMBL; CH471192; EAW52163.1; -; Genomic_DNA.
DR EMBL; BC007363; AAH07363.1; -; mRNA.
DR EMBL; BC009872; AAH09872.1; -; mRNA.
DR CCDS; CCDS10705.1; -. [O14874-1]
DR CCDS; CCDS45467.1; -. [O14874-3]
DR CCDS; CCDS61917.1; -. [O14874-2]
DR RefSeq; NP_001116429.1; NM_001122957.2. [O14874-3]
DR RefSeq; NP_001258855.1; NM_001271926.1. [O14874-2]
DR RefSeq; NP_005872.2; NM_005881.3. [O14874-1]
DR AlphaFoldDB; O14874; -.
DR SMR; O14874; -.
DR BioGRID; 115583; 134.
DR IntAct; O14874; 64.
DR MINT; O14874; -.
DR STRING; 9606.ENSP00000378405; -.
DR DrugBank; DB02930; Adenosine 5'-[gamma-thio]triphosphate.
DR GlyGen; O14874; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; O14874; -.
DR PhosphoSitePlus; O14874; -.
DR SwissPalm; O14874; -.
DR BioMuta; BCKDK; -.
DR EPD; O14874; -.
DR jPOST; O14874; -.
DR MassIVE; O14874; -.
DR MaxQB; O14874; -.
DR PaxDb; O14874; -.
DR PeptideAtlas; O14874; -.
DR PRIDE; O14874; -.
DR ProteomicsDB; 2373; -.
DR ProteomicsDB; 48278; -. [O14874-1]
DR ProteomicsDB; 76605; -.
DR Antibodypedia; 13936; 348 antibodies from 30 providers.
DR DNASU; 10295; -.
DR Ensembl; ENST00000219794.11; ENSP00000219794.6; ENSG00000103507.14. [O14874-1]
DR Ensembl; ENST00000287507.7; ENSP00000287507.3; ENSG00000103507.14. [O14874-2]
DR Ensembl; ENST00000394950.7; ENSP00000378404.3; ENSG00000103507.14. [O14874-3]
DR Ensembl; ENST00000394951.5; ENSP00000378405.1; ENSG00000103507.14. [O14874-1]
DR GeneID; 10295; -.
DR KEGG; hsa:10295; -.
DR MANE-Select; ENST00000219794.11; ENSP00000219794.6; NM_005881.4; NP_005872.2.
DR UCSC; uc002eav.6; human. [O14874-1]
DR CTD; 10295; -.
DR DisGeNET; 10295; -.
DR GeneCards; BCKDK; -.
DR HGNC; HGNC:16902; BCKDK.
DR HPA; ENSG00000103507; Low tissue specificity.
DR MalaCards; BCKDK; -.
DR MIM; 614901; gene.
DR MIM; 614923; phenotype.
DR neXtProt; NX_O14874; -.
DR OpenTargets; ENSG00000103507; -.
DR Orphanet; 308410; Autism-epilepsy syndrome due to branched chain ketoacid dehydrogenase kinase deficiency.
DR PharmGKB; PA134899581; -.
DR VEuPathDB; HostDB:ENSG00000103507; -.
DR eggNOG; KOG0787; Eukaryota.
DR GeneTree; ENSGT01030000234646; -.
DR HOGENOM; CLU_023861_4_0_1; -.
DR InParanoid; O14874; -.
DR OMA; IHHLALH; -.
DR PhylomeDB; O14874; -.
DR TreeFam; TF331303; -.
DR PathwayCommons; O14874; -.
DR Reactome; R-HSA-70895; Branched-chain amino acid catabolism.
DR SignaLink; O14874; -.
DR SIGNOR; O14874; -.
DR BioGRID-ORCS; 10295; 12 hits in 1092 CRISPR screens.
DR ChiTaRS; BCKDK; human.
DR GeneWiki; BCKDK; -.
DR GenomeRNAi; 10295; -.
DR Pharos; O14874; Tbio.
DR PRO; PR:O14874; -.
DR Proteomes; UP000005640; Chromosome 16.
DR RNAct; O14874; protein.
DR Bgee; ENSG00000103507; Expressed in apex of heart and 170 other tissues.
DR ExpressionAtlas; O14874; baseline and differential.
DR Genevisible; O14874; HS.
DR GO; GO:0005947; C:mitochondrial alpha-ketoglutarate dehydrogenase complex; ISS:HGNC-UCL.
DR GO; GO:0005759; C:mitochondrial matrix; TAS:Reactome.
DR GO; GO:0005739; C:mitochondrion; IDA:HPA.
DR GO; GO:0047323; F:[3-methyl-2-oxobutanoate dehydrogenase (acetyl-transferring)] kinase activity; TAS:Reactome.
DR GO; GO:0005524; F:ATP binding; ISS:HGNC-UCL.
DR GO; GO:0016301; F:kinase activity; TAS:HGNC-UCL.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; ISS:HGNC-UCL.
DR GO; GO:0004740; F:pyruvate dehydrogenase (acetyl-transferring) kinase activity; IBA:GO_Central.
DR GO; GO:0009083; P:branched-chain amino acid catabolic process; ISS:HGNC-UCL.
DR GO; GO:0009063; P:cellular amino acid catabolic process; NAS:UniProtKB.
DR GO; GO:0045763; P:negative regulation of cellular amino acid metabolic process; TAS:Reactome.
DR GO; GO:0016310; P:phosphorylation; ISS:HGNC-UCL.
DR GO; GO:0006468; P:protein phosphorylation; IBA:GO_Central.
DR GO; GO:0010906; P:regulation of glucose metabolic process; IBA:GO_Central.
DR Gene3D; 1.20.140.20; -; 1.
DR Gene3D; 3.30.565.10; -; 1.
DR InterPro; IPR036784; AK/P_DHK_N_sf.
DR InterPro; IPR018955; BCDHK/PDK_N.
DR InterPro; IPR039028; BCKD/PDK.
DR InterPro; IPR003594; HATPase_C.
DR InterPro; IPR036890; HATPase_C_sf.
DR InterPro; IPR005467; His_kinase_dom.
DR InterPro; IPR004358; Sig_transdc_His_kin-like_C.
DR PANTHER; PTHR11947; PTHR11947; 1.
DR Pfam; PF10436; BCDHK_Adom3; 1.
DR Pfam; PF02518; HATPase_c; 1.
DR PRINTS; PR00344; BCTRLSENSOR.
DR SMART; SM00387; HATPase_c; 1.
DR SUPFAM; SSF55874; SSF55874; 1.
DR SUPFAM; SSF69012; SSF69012; 1.
DR PROSITE; PS50109; HIS_KIN; 1.
PE 1: Evidence at protein level;
KW Acetylation; Alternative splicing; ATP-binding; Autism;
KW Autism spectrum disorder; Disease variant; Epilepsy;
KW Intellectual disability; Kinase; Mitochondrion; Nucleotide-binding;
KW Phosphoprotein; Reference proteome; Transferase; Transit peptide.
FT TRANSIT 1..30
FT /note="Mitochondrion"
FT /evidence="ECO:0000250"
FT CHAIN 31..412
FT /note="[3-methyl-2-oxobutanoate dehydrogenase [lipoamide]]
FT kinase, mitochondrial"
FT /id="PRO_0000023452"
FT DOMAIN 159..404
FT /note="Histidine kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00107"
FT MOD_RES 31
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q00972"
FT MOD_RES 52
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 192
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 233
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 356
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O55028"
FT MOD_RES 360
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q00972"
FT VAR_SEQ 282..311
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_054604"
FT VAR_SEQ 366..412
FT /note="Missing (in isoform 2 and isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_054605"
FT VARIANT 174
FT /note="R -> G (in BCKDKD; partial loss of kinase activity)"
FT /evidence="ECO:0000269|PubMed:24449431"
FT /id="VAR_072184"
FT VARIANT 224
FT /note="R -> P (in BCKDKD; dbSNP:rs147210405)"
FT /evidence="ECO:0000269|PubMed:22956686"
FT /id="VAR_069037"
FT VARIANT 389
FT /note="L -> P (in BCKDKD; complete loss of kinase
FT activity)"
FT /evidence="ECO:0000269|PubMed:24449431"
FT /id="VAR_072185"
FT CONFLICT 3
FT /note="L -> P (in Ref. 2; AK130145)"
FT /evidence="ECO:0000305"
FT CONFLICT 114
FT /note="F -> S (in Ref. 2; AK130145)"
FT /evidence="ECO:0000305"
FT CONFLICT 218
FT /note="V -> F (in Ref. 1; AAB82714)"
FT /evidence="ECO:0000305"
FT CONFLICT 227
FT /note="P -> S (in Ref. 2; AK130145)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 412 AA; 46360 MW; AC97CF5D151FEFB4 CRC64;
MILASVLRSG PGGGLPLRPL LGPALALRAR STSATDTHHV EMARERSKTV TSFYNQSAID
AAAEKPSVRL TPTMMLYAGR SQDGSHLLKS ARYLQQELPV RIAHRIKGFR CLPFIIGCNP
TILHVHELYI RAFQKLTDFP PIKDQADEAQ YCQLVRQLLD DHKDVVTLLA EGLRESRKHI
EDEKLVRYFL DKTLTSRLGI RMLATHHLAL HEDKPDFVGI ICTRLSPKKI IEKWVDFARR
LCEHKYGNAP RVRINGHVAA RFPFIPMPLD YILPELLKNA MRATMESHLD TPYNVPDVVI
TIANNDVDLI IRISDRGGGI AHKDLDRVMD YHFTTAEAST QDPRISPLFG HLDMHSGAQS
GPMHGFGFGL PTSRAYAEYL GGSLQLQSLQ GIGTDVYLRL RHIDGREESF RI
