true2000-05-302024-03-27185BCKD_MOUSEMurine branched chain alpha ketoacid dehydrogenase kinase; cDNA cloning, tissue distribution, and temporal expression during embryonic development.Doering C.B.Coursey C.Spangler W.Danner D.J.doi:10.1016/s0378-1119(98)00182-61998Gene212213-219NUCLEOTIDE SEQUENCE [MRNA]C57BL/6JThe status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).The MGC Project Teamdoi:10.1101/gr.25965042004Genome Res.142121-2127NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]Olfactory epitheliumImpaired growth and neurological abnormalities in branched-chain alpha-keto acid dehydrogenase kinase-deficient mice.Joshi M.A.Jeoung N.H.Obayashi M.Hattab E.M.Brocken E.G.Liechty E.A.Kubek M.J.Vattem K.M.Wek R.C.Harris R.A.doi:10.1042/bj200608692006Biochem. J.400153-162DISRUPTION PHENOTYPEComprehensive identification of phosphorylation sites in postsynaptic density preparations.Trinidad J.C.Specht C.G.Thalhammer A.Schoepfer R.Burlingame A.L.doi:10.1074/mcp.t500041-mcp2002006Mol. Cell. Proteomics5914-922IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]BrainMitochondrial phosphoproteome revealed by an improved IMAC method and MS/MS/MS.Lee J.Xu Y.Chen Y.Sprung R.Kim S.C.Xie S.Zhao Y.doi:10.1074/mcp.m600218-mcp2002007Mol. Cell. Proteomics6669-676IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]LiverThe phagosomal proteome in interferon-gamma-activated macrophages.Trost M.English L.Lemieux S.Courcelles M.Desjardins M.Thibault P.doi:10.1016/j.immuni.2008.11.0062009Immunity30143-154IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]A tissue-specific atlas of mouse protein phosphorylation and expression.Huttlin E.L.Jedrychowski M.P.Elias J.E.Goswami T.Rad R.Beausoleil S.A.Villen J.Haas W.Sowa M.E.Gygi S.P.doi:10.1016/j.cell.2010.12.0012010Cell1431174-1189PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-356IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]Brown adipose tissueHeartKidneyLungPancreasSpleenMutations in BCKD-kinase lead to a potentially treatable form of autism with epilepsy.Novarino G.El-Fishawy P.Kayserili H.Meguid N.A.Scott E.M.Schroth J.Silhavy J.L.Kara M.Khalil R.O.Ben-Omran T.Ercan-Sencicek A.G.Hashish A.F.Sanders S.J.Gupta A.R.Hashem H.S.Matern D.Gabriel S.Sweetman L.Rahimi Y.Harris R.A.State M.W.Gleeson J.G.doi:10.1126/science.12246312012Science338394-397DISRUPTION PHENOTYPELabel-free quantitative proteomics of the lysine acetylome in mitochondria identifies substrates of SIRT3 in metabolic pathways.Rardin M.J.Newman J.C.Held J.M.Cusack M.P.Sorensen D.J.Li B.Schilling B.Mooney S.D.Kahn C.R.Verdin E.Gibson B.W.doi:10.1073/pnas.13029611102013Proc. Natl. Acad. Sci. U.S.A.1106601-6606ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-192IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]312 sites, 1 O-linked glycan (2 sites)389 antibodies from 30 providersmouseBckdkEukaryota3474Branched-chain amino acid catabolism2 hits in 80 CRISPR screensmouseProteinExpressed in lacrimal gland and 266 other cell types or tissuesbaseline and differentialHATPase_PDK-likeAlpha-ketoacid/pyruvate dehydrogenase kinase, N-terminal domainHistidine kinase-like ATPase, C-terminal domainAK/P_DHK_N_sfBCDHK/PDK_NBCKD/PDKHATPase_CHATPase_C_sfHis_kinase_domSig_transdc_His_kin-like_C[3-METHYL-2-OXOBUTANOATE DEHYDROGENASE [LIPOAMIDE]] KINASE, MITOCHONDRIALPYRUVATE DEHYDROGENASE KINASEBCDHK_Adom3HATPase_cBCTRLSENSORHATPase_calpha-ketoacid dehydrogenase kinase, N-terminal domainATPase domain of HSP90 chaperone/DNA topoisomerase II/histidine kinaseHIS_KINMMBranched-chain alpha-ketoacid dehydrogenase kinaseBCKDH kinaseBCKDHKINBDK2.7.11.1[3-methyl-2-oxobutanoate dehydrogenase [lipoamide]] kinase, mitochondrial2.7.11.4BckdkSerine/threonine-protein kinase component of macronutrients metabolism. Forms a functional kinase and phosphatase pair with PPM1K, serving as a metabolic regulatory node that coordinates branched-chain amino acids (BCAAs) with glucose and lipid metabolism via two distinct phosphoprotein targets: mitochondrial BCKDHA subunit of the branched-chain alpha-ketoacid dehydrogenase (BCKDH) complex and cytosolic ACLY, a lipogenic enzyme of Krebs cycle (By similarity). Phosphorylates and inactivates mitochondrial BCKDH complex a multisubunit complex consisting of three multimeric components each involved in different steps of BCAA catabolism: E1 composed of BCKDHA and BCKDHB, E2 core composed of DBT monomers, and E3 composed of DLD monomers. Associates with the E2 component of BCKDH complex and phosphorylates BCKDHA on Ser-334, leading to conformational changes that interrupt substrate channeling between E1 and E2 and inactivates the BCKDH complex (By similarity). Phosphorylates ACLY on Ser-455 in response to changes in cellular carbohydrate abundance such as occurs during fasting to feeding metabolic transition. Refeeding stimulates MLXIPL/ChREBP transcription factor, leading to increased BCKDK to PPM1K expression ratio, phosphorylation and activation of ACLY that ultimately results in the generation of malonyl-CoA and oxaloacetate immediate substrates of de novo lipogenesis and glucogenesis, respectively (By similarity). Recognizes phosphosites having SxxE/D canonical motif (By similarity).Homodimer. Homotetramer (By similarity). Dimerizes through interaction of two opposing nucleotide-binding domains. Interacts with E2 component of the branched-chain alpha-ketoacid dehydrogenase (BCKDH) complex. Competes with BCKDK for binding to the E2 component; this interaction is modulated by branched-chain alpha-keto acids. At steady state, BCKDH holoenzyme contains BCKDK and BCKDHA is phosphorylated. In response to high levels of branched-chain alpha-keto acids, the inhibitory BCKDK is replaced by activating PPM1K leading to BCKDHA dephosphorylation and BCAA degradation (By similarity).Ubiquitous.Expression in female liver is influenced by circadian rhythm.Autophosphorylated.Mutant animals are born at the expected Mendelian ratio, but they exhibit a decreased fertility. They are healthy at birth. At 3 weeks of age, they start showing growth retardation. At 12 weeks, they are 15% smaller than their wild-type littermates. Adults develop neurological abnormalities, such as tremors, epileptic seizures and hindlimb clasping. These neurological deficits can be completely abolished when mice are fed with a diet enriched in branched amino acids.Belongs to the PDK/BCKDK protein kinase family.Mitochondrion130Branched-chain alpha-ketoacid dehydrogenase kinase4337731412Histidine kinase159404279315328330333334335364367370PhosphoserinePhosphoserine; by autocatalysis52N6-acetyllysine192N6-acetyllysine233Phosphoserine356Phosphoserine360structuralstructural1998-06-011true46588d7dcd8cf455706756414b72df453da3fMILTSVLGSGPRSWSSLWPLLGSSLSLRARSTSATDTHHVELARERSKTVTSFYNQSAIDVAAEKPSVRLTPTMMLYSGRSQDGSHLLKSGRYLQQELPVRIAHRIKGFRSLPFIIGCNPTILHVHELYIRAFQKLTDFPPIKDQADEAQYCQLVRQLLDDHKDVVTLLAEGLRESRKHIQDEKLVRYFLDKTLTSRLGIRMLATHHLALHEDKPDFVGIICTRLSPKKIIEKWVDFARRLCEHKYGNAPRVRINGHVAARFPFIPMPLDYILPELLKNAMRATMESHLDTPYNVPDVVITIANNDIDLIIRISDRGGGIAHKDLDRVMDYHFTTAEASTQDPRINPLFGHLDMHSGGQSGPMHGFGFGLPTSRAYAEYLGGSLQLQSLQGIGTDVYLRLRHIDGREESFRItruetruetruetruetruetruetruetruetruetruetruetruetruetrue