PPM1K
entrez
152926
canonical
uniprot
Q8N3J5
canonical
ensembl
ENSG00000163644
resolver
ensp
ENSP00000477341
resolver
ensp
ENSP00000553024
resolver
ensp
ENSP00000677868
resolver
ensp
ENSP00000725273
resolver
ensp
ENSP00000725282
resolver
genesymbol
PPM1K
resolver
genesymbol_syn
PP2CM
resolver
hgnc
HGNC:25415
resolver
uniprot
B2RAZ1
resolver
uniprot
Q05CT5
resolver
uniprot
Q49AB5
resolver
uniprot
Q4W5E6
resolver
uniprot
Q56AN8
resolver
uniprot
Q8IUZ7
resolver
uniprot
Q8IXG7
resolver
uniprot
Q8ND70
resolver
uniprot
Q96NT4
resolver
uniprot_entry
PPM1K_HUMAN
resolver
uniprot_sec
B2RAZ1
resolver
uniprot_sec
Q05CT5
resolver
uniprot_sec
Q49AB5
resolver
uniprot_sec
Q4W5E6
resolver
uniprot_sec
Q56AN8
resolver
uniprot_sec
Q8IUZ7
resolver
uniprot_sec
Q8IXG7
resolver
uniprot_sec
Q8ND70
resolver
uniprot_sec
Q96NT4
resolver
activity_regulation
ACTIVITY REGULATION: Up-regulated upon interaction with the 24-meric DBT/E2 core of the BCKDH complex. Inhibited by Mg(2+) and Ca(2+) ions likely by competing with Mn(2+) ions for binding to the same metal-binding sites. {ECO:0000269|PubMed:22291014}.
uniprot
proteins
amino_acid_sequence
MSTAALITLVRSGGNQVRRRVLLSSRLLQDDRRVTPTCHSSTSEPRCSRFDPDGSGSPATWDNFGIWDNRIDEPILLPPSIKYGKPIPKISLENVGCASQIGKRKENEDRFDFAQLTDEVLYFAVYDGHGGPAAADFCHTHMEKCIMDLLPKEKNLETLLTLAFLEIDKAFSSHARLSADATLLTSGTTATVALLRDGIELVVASVGDSRAILCRKGKPMKLTIDHTPERKDEKERIKKCGGFVAWNSLGQPHVNGRLAMTRSIGDLDLKTSGVIAEPETKRIKLHHADDSFLVLTTDGINFMVNSQEICDFVNQCHDPNEAAHAVTEQAIQYGTEDNSTAVVVPFGAWGKYKNSEINFSFSRSFASSGRWA
uniprot
proteins
disease_involvement
DISEASE: Maple syrup urine disease, mild variant (MSUDMV) [MIM:615135]: A mild form of maple syrup urine disease, a metabolic disorder due to an enzyme defect in the catabolic pathway of the branched-chain amino acids leucine, isoleucine, and valine. Accumulation of these 3 amino acids and their corresponding keto acids leads to encephalopathy and progressive neurodegeneration. Clinical features include mental and physical retardation, feeding problems, and a maple syrup odor to the urine. The keto acids of the branched-chain amino acids are present in the urine. If untreated, maple syrup urine disease can lead to seizures, coma, and death. The disease is often classified by its pattern of signs and symptoms. The most common and severe form of the disease is the classic type, which becomes apparent soon after birth. Variant forms of the disorder become apparent later in infancy or childhood and are typically milder, but they still involve developmental delay and other medical problems if not treated. MSUDMV is characterized by increased plasma levels of branched-chain amino acids (BCAA) apparent at birth. Treatment with a low-protein diet free of BCAA can result in normal psychomotor development and lack of metabolic episodes. {ECO:0000269|PubMed:23086801}. Note=The gene represented in this entry is involved in disease pathogenesis.
uniprot
proteins
ec_number
3.1.3.16
uniprot
proteins
ec_number
3.1.3.52
uniprot
proteins
function
FUNCTION: Serine/threonine-protein phosphatase component of macronutrients metabolism. Forms a functional kinase and phosphatase pair with BCKDK, 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:17336929, PubMed:17374715, PubMed:19411760, PubMed:22291014, PubMed:22589535, PubMed:23086801, PubMed:29779826). At high levels of branched-chain ketoacids, dephosphorylates and activates 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. Tightly associates with the E2 component of BCKDH complex and dephosphorylates BCKDHA on Ser-337 (PubMed:17336929, PubMed:17374715, PubMed:19411760, PubMed:22291014, PubMed:22589535, PubMed:23086801, PubMed:29779826). Regulates the reversible phosphorylation of ACLY in response to changes in cellular carbohydrate abundance such as occurs during fasting to feeding metabolic transition. At fasting state, appears to dephosphorylate ACLY on Ser-455 and inactivate it. 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 gluconeogenesis, respectively (PubMed:29779826). Recognizes phosphosites having SxS or RxxS motifs and strictly depends on Mn(2+) ions for the phosphatase activity (PubMed:29779826). Regulates Ca(2+)-induced opening of mitochondrial transition pore and apoptotic cell death (PubMed:17374715). {ECO:0000269|PubMed:17336929, ECO:0000269|PubMed:17374715, ECO:0000269|PubMed:19411760, ECO:0000269|PubMed:22291014, ECO:0000269|PubMed:22589535, ECO:0000269|PubMed:23086801, ECO:0000269|PubMed:29779826}.
uniprot
proteins
mass_dalton
40997
uniprot
proteins
mutagenesis
MUTAGEN 104; /note="R->A: Decreases the affinity toward BCKDHA by 61-fold. Decreases the catalytic efficiency toward BCKDHA down to 2%."; /evidence="ECO:0000269|PubMed:22291014"; MUTAGEN 109; /note="D->A: Loss of serine/threonine phosphatase activity toward BCKDHA."; /evidence="ECO:0000269|PubMed:22291014"; MUTAGEN 127; /note="D->A: Loss of serine/threonine phosphatase activity toward BCKDHA."; /evidence="ECO:0000269|PubMed:22291014"; MUTAGEN 129; /note="H->A: Slightly decreases the catalytic efficiency toward BCKDHA. Does not affect the interaction with DBT."; /evidence="ECO:0000269|PubMed:19411760, ECO:0000269|PubMed:22291014"; MUTAGEN 236; /note="R->G: Complete loss of serine/threonine phosphatase activity toward BCKDHA. Does not affect the interaction with DBT."; /evidence="ECO:0000269|PubMed:19411760"; MUTAGEN 298; /note="D->A: Loss of serine/threonine phosphatase activity toward BCKDHA. Does not affect the interaction with DBT."; /evidence="ECO:0000269|PubMed:17374715, ECO:0000269|PubMed:19411760, ECO:0000269|PubMed:22291014"; MUTAGEN 337; /note="D->A: Loss of serine/threonine phosphatase activity toward BCKDHA."; /evidence="ECO:0000269|PubMed:22291014
uniprot
proteins
pathway_participation
PATHWAY: Protein modification. {ECO:0000269|PubMed:17336929, ECO:0000269|PubMed:17374715, ECO:0000269|PubMed:22291014, ECO:0000269|PubMed:29779826}.
uniprot
proteins
protein_family
PP2C family
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15815621
uniprot
proteins
pubmed
17336929
uniprot
proteins
pubmed
17374715
uniprot
proteins
pubmed
17974005
uniprot
proteins
pubmed
18058037
uniprot
proteins
pubmed
19411760
uniprot
proteins
pubmed
22291014
uniprot
proteins
pubmed
22589535
uniprot
proteins
pubmed
23086801
uniprot
proteins
pubmed
23200863
uniprot
proteins
pubmed
29779826
uniprot
proteins
sequence_length
372
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Mitochondrion matrix {ECO:0000269|PubMed:17336929, ECO:0000269|PubMed:17374715, ECO:0000269|PubMed:23086801}. Note=Detected in the cytosolic compartment of liver cells. {ECO:0000250|UniProtKB:A6K136}.
uniprot
proteins