Names & Taxonomy
- Uniprot ID:
- P14618
- Entry Name:
- KPYM_HUMAN
- Status:
- reviewed
- Protein Names:
- Pyruvate kinase PKM (EC 2.7.1.40) (Cytosolic thyroid hormone-binding protein) (CTHBP) (Opa-interacting protein 3) (OIP-3) (Pyruvate kinase 2/3) (Pyruvate kinase muscle isozyme) (Thyroid hormone-binding protein 1) (THBP1) (Tumor M2-PK) (p58)
- Gene Names:
- PKM OIP3 PK2 PK3 PKM2
- Gene Names Primary:
- PKM
- Organism:
- Homo sapiens (Human)
Structure
- Length:
- 531
- Sequence:
- MSKPHSEAGTAFIQTQQLHAAMADTFLEHMCRLDIDSPPITARNTGIICTIGPASRSVETLKEMIKSGMNVARLNFSHGTHEYHAETIKNVRTATESFASDPILYRPVAVALDTKGPEIRTGLIKGSGTAEVELKKGATLKITLDNAYMEKCDENILWLDYKNICKVVEVGSKIYVDDGLISLQVKQKGADFLVTEVENGGSLGSKKGVNLPGAAVDLPAVSEKDIQDLKFGVEQDVDMVFASFIRKASDVHEVRKVLGEKGKNIKIISKIENHEGVRRFDEILEASDGIMVARGDLGIEIPAEKVFLAQKMMIGRCNRAGKPVICATQMLESMIKKPRPTRAEGSDVANAVLDGADCIMLSGETAKGDYPLEAVRMQHLIAREAEAAIYHLQLFEELRRLAPITSDPTEATAVGAVEASFKCCSGAIIVLTKSGRSAHQVARYRPRAPIIAVTRNPQTARQAHLYRGIFPVLCKDPVQEAWAEDVDLRVNFAMNVGKARGFFKKGDVVIVLTGWRPGSGFTNTMRVVPVP
- Proteomes:
- UP000005640
Subcellular location
- Subcellular Location:
- Cytoplasm. Nucleus. Note=Translocates to the nucleus in response to different apoptotic stimuli. Nuclear translocation is sufficient to induce cell death that is caspase independent, isoform-specific and independent of its enzymatic activity.
Function
- Function:
- Glycolytic enzyme that catalyzes the transfer of a phosphoryl group from phosphoenolpyruvate (PEP) to ADP, generating ATP. Stimulates POU5F1-mediated transcriptional activation. Plays a general role in caspase independent cell death of tumor cells. The ratio betwween the highly active tetrameric form and nearly inactive dimeric form determines whether glucose carbons are channeled to biosynthetic processes or used for glycolytic ATP production. The transition between the 2 forms contributes to the control of glycolysis and is important for tumor cell proliferation and survival.
- Pathway:
- Carbohydrate degradation; glycolysis; pyruvate from D-glyceraldehyde 3-phosphate: step 5/5.
- Catalytic Activity:
- ATP + pyruvate = ADP + phosphoenolpyruvate.
- Cofactor:
- COFACTOR: Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
- Kinetics:
- BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=2.7 mM for phosphoenolpyruvate (at 32 degrees Celsius, pH 8.0)
- Enzyme Regulation:
- ENZYME REGULATION: Isoform M2 is allosterically activated by D-fructose 1,6-bisphosphate (FBP). Inhibited by oxalate and 3,3',5-triiodo-L-thyronine (T3). The activity of the tetrameric form is inhibited by PML. Selective binding to tyrosine-phosphorylated peptides releases the allosteric activator FBP, leading to inhibition of PKM enzymatic activity, this diverts glucose metabolites from energy production to anabolic processes when cells are stimulated by certain growth factors. Glycolytic flux are highly dependent on de novo biosynthesis of serine and glycine, and serine is a natural ligand and allosteric activator of isoform M2.
- Cross Reference Drug Bank:
- DB00119
- Gene Ontology Go:
- cilium
cytoplasm
cytosol
extracellular exosome
extracellular matrix
extracellular vesicle
mitochondrion
myelin sheath
nucleus
plasma membrane
vesicle
ADP binding
ATP binding
kinase activity
magnesium ion binding
MHC class II protein complex binding
poly(A) RNA binding
potassium ion binding
pyruvate kinase activity
ATP biosynthetic process
canonical glycolysis
carbohydrate metabolic process
glucose metabolic process
liver development
organ regeneration
programmed cell death
pyruvate biosynthetic process
response to gravity
response to hypoxia
response to insulin
response to muscle inactivity
response to nutrient
skeletal muscle tissue regeneration
small molecule metabolic process - Gene Ontology Biological Process:
- ATP biosynthetic process
canonical glycolysis
carbohydrate metabolic process
glucose metabolic process
liver development
organ regeneration
programmed cell death
pyruvate biosynthetic process
response to gravity
response to hypoxia
response to insulin
response to muscle inactivity
response to nutrient
skeletal muscle tissue regeneration
small molecule metabolic process - Gene Ontology Molecular Function:
- ADP binding
ATP binding
kinase activity
magnesium ion binding
MHC class II protein complex binding
poly(A) RNA binding
potassium ion binding
pyruvate kinase activity - Gene Ontology Cellular Component:
- cilium
cytoplasm
cytosol
extracellular exosome
extracellular matrix
extracellular vesicle
mitochondrion
myelin sheath
nucleus
plasma membrane
vesicle - Keywords:
- 3D-structure
ATP-binding
Acetylation
Allosteric enzyme
Alternative splicing
Complete proteome
Cytoplasm
Direct protein sequencing
Glycolysis
Hydroxylation
Kinase
Magnesium
Metal-binding
Nucleotide-binding
Nucleus
Phosphoprotein
Polymorphism
Potassium
Pyruvate
Reference proteome
Transferase
Ubl conjugation - Interacts With:
- Q9WMX2; P10398; P49407; P32121; P53355; Q9H6Z9; Q16665; P68431; P42858; P27361; P04049; Q9BSI4
Publication
- PubMed ID:
- 2854097 2813362 2040271 14702039 16572171 15489334 1854723 12665801 9466265 12650930 16139798 15592455 17081983 16964243 17308100 18298799 18191611 18088087 18691976 18669648 19413330 19690332 19608861 20068231 21269460 21620138 21483450 21700219 21406692 24275569 25944712 15996096 18337815 23064226 23530218