PPM1K
Description
The PPM1K (protein phosphatase, Mg2+/Mn2+ dependent 1K) is a protein-coding gene located on chromosome 4.
Protein phosphatase 1K, mitochondrial is an enzyme that in humans is encoded by the PPM1K gene.
PPM1K is a serine/threonine-protein phosphatase that plays a key role in macronutrient metabolism. It forms a functional kinase and phosphatase pair with BCKDK, acting as a regulatory node that coordinates branched-chain amino acids (BCAAs) with glucose and lipid metabolism. PPM1K targets two specific phosphoproteins: BCKDHA, a subunit of the branched-chain alpha-ketoacid dehydrogenase (BCKDH) complex in mitochondria, and ACLY, a lipogenic enzyme in the cytoplasm involved in the Krebs cycle. At high levels of branched-chain ketoacids, PPM1K dephosphorylates and activates the BCKDH complex, a multi-subunit complex essential for BCAA catabolism. PPM1K directly interacts with the E2 component of the BCKDH complex and dephosphorylates BCKDHA at Ser-337. PPM1K also regulates the reversible phosphorylation of ACLY in response to changes in cellular carbohydrate levels, such as during fasting and feeding transitions. During fasting, PPM1K dephosphorylates ACLY at Ser-455, inactivating it. Upon refeeding, increased expression of BCKDK relative to PPM1K leads to ACLY phosphorylation and activation, ultimately resulting in the production of malonyl-CoA and oxaloacetate, key substrates for de novo lipogenesis and gluconeogenesis, respectively. PPM1K recognizes phosphosites containing SxS or RxxS motifs and requires Mn(2+) ions for its phosphatase activity. PPM1K also regulates Ca(2+)-induced opening of the mitochondrial transition pore and apoptotic cell death.
PPM1K is also known as BCKDH, BDP, MSUDMV, PP2Ckappa, PP2Cm, PTMP, UG0882E07.
