[3-methyl-2-oxobutanoate dehydrogenase [lipoamide]] kinase, mitochondrial (EC 2.7.11.4) (Branched-chain alpha-ketoacid dehydrogenase kinase) (BCKD-kinase) (BCKDHKIN)
1_MILAS 6_ VLRSG 11_ PGGGL 16_ PLRPL 21_ LGPAL 26_ ALRAR 31_ STSAT 36_ DTHHV 41_ EMARE 46_ RSKTV 51_ TSFYN 56_ QSAID 61_ AAAEK 66_ PSVRL 71_ TPTMM 76_ LYAGR 81_ SQDGS 86_ HLLKS 91_ ARYLQ 96_ QELPV 101_ RIAHR 106_ IKGFR 111_ CLPFI 116_ IGCNP 121_ TILHV 126_ HELYI 131_ RAFQK 136_ LTDFP 141_ PIKDQ 146_ ADEAQ 151_ YCQLV 156_ RQLLD 161_ DHKDV 166_ VTLLA 171_ EGLRE 176_ SRKHI 181_ EDEKL 186_ VRYFL 191_ DKTLT 196_ SRLGI 201_ RMLAT 206_ HHLAL 211_ HEDKP 216_ DFVGI 221_ ICTRL 226_ SPKKI 231_ IEKWV 236_ DFARR 241_ LCEHK 246_ YGNAP 251_ RVRIN 256_ GHVAA 261_ RFPFI 266_ PMPLD 271_ YILPE 276_ LLKNA 281_ MRATM 286_ ESHLD 291_ TPYNV 296_ PDVVI 301_ TIANN 306_ DVDLI 311_ IRISD 316_ RGGGI 321_ AHKDL 326_ DRVMD 331_ YHFTT 336_ AEAST 341_ QDPRI 346_ SPLFG 351_ HLDMH 356_ SGAQS 361_ GPMHG 366_ FGFGL 371_ PTSRA 376_ YAEYL 381_ GGSLQ 386_ LQSLQ 391_ GIGTD 396_ VYLRL 401_ RHIDG 406_REESF
1: Serine/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 (PubMed:24449431, PubMed:29779826, PubMed:37558654). 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-337, leading to conformational changes that interrupt substrate channeling between E1 and E2 and inactivates the BCKDH complex (PubMed:29779826, PubMed:37558654). 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 (PubMed:29779826). Recognizes phosphosites having SxxE/D canonical motif (PubMed:29779826)