UniProtKB record for human PKM (P14618)
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UniProt annotates nuclear homodimeric PKM2 (Isoform M2) as a protein threonine and tyrosine kinase phosphorylating STAT3 (Tyr-705) and histone H3 (Thr-11).
"Translocates into the nucleus in response to various signals, such as EGF receptor activation, and homodimerizes, leading to its conversion into a protein threonine- and tyrosine-protein kinase"
Lack of Evidence for PKM2 Protein Kinase Activity.
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Biochemical assays using [32P]-PEP, [gamma-32P]-ATP, recombinant wild-type or R399E PKM2, and PKM2-null cell extracts detected no direct PKM2-dependent protein kinase activity, showing instead that PKM2-dependent phosphotransfer reflects canonical ATP regeneration from PEP and ADP.
"We investigated the protein kinase activity of PKM2; however, we were unable to demonstrate PKM2-dependent phosphorylation of any proteins in vitro using either PEP or ATP as a phosphate donor. Instead, all PKM2-dependent phosphotransfer events observed involved regeneration of ATP from ADP and PEP, the known function of PKM2 in glycolysis."
Affinage mechanistic annotation for PKM (human)
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Tetrameric PKM drives canonical glycolytic pyruvate kinase flux, whereas dimeric/monomeric PKM2 translocates to the nucleus to coordinate transcription, cell-cycle progression, and inflammatory signaling.
"PKM (PKM2 isoform) is a multifunctional glycolytic pyruvate kinase whose tetrameric form drives metabolic flux but whose dimeric/monomeric forms acquire non-canonical activities upon translocation to the nucleus, coordinating metabolism with gene expression, cell-cycle control, and inflammation [PMID:22056988, PMID:24316223]."
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Biochemical reconstitution with [32P]-PEP challenged direct PKM2-dependent protein kinase activity, highlighting controversy over non-canonical protein phosphorylation claims.
"Using [32P]-phosphoenolpyruvate (PEP) with recombinant enzyme and PKM2-deleted in vitro systems, no PKM2-dependent protein kinase activity was detected; labeled protein species required ADP and were not PKM2-dependent, and direct phosphate transfer from ATP to protein by PKM2 was not observed."
Gene Ontology annotation through association of InterPro records with GO terms
Gene Ontology annotation based on Enzyme Commission mapping
Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity
Annotation inferences using phylogenetic trees
Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword mapping
Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt
Gene Ontology annotation based on curation of immunofluorescence data
Gene Ontology annotation based on curation of intracellular localizations of expressed fusion proteins in living cells
Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara
Automatic Gene Ontology annotation based on Rhea mapping
Combined Automated Annotation using Multiple IEA Methods
Falcon deep research report for human PKM
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PKM encodes pyruvate kinase M1/M2, with canonical activity catalyzing PEP + ADP to pyruvate + ATP in the terminal ATP-generating step of glycolysis.
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The report distinguishes the core glycolytic enzyme function from PKM2-specific noncanonical kinase and transcription-associated activities.
Intestinal epithelial cells secrete exosome-like vesicles.
Proteomic and biochemical analyses of human B cell-derived exosomes. Potential implications for their function and multivesicular body formation.
Novel raf kinase protein-protein interactions found by an exhaustive yeast two-hybrid analysis.
Nuclear translocation of the tumor marker pyruvate kinase M2 induces programmed cell death.
Huntingtin interacting proteins are genetic modifiers of neurodegeneration.
Functional specialization of beta-arrestin interactions revealed by proteomic analysis.
Pyruvate kinase isozyme type M2 (PKM2) interacts and cooperates with Oct-4 in regulating transcription.
Modulation of M2-type pyruvate kinase activity by the cytoplasmic PML tumor suppressor protein.
Isoform-specific interaction of pyruvate kinase with hepatitis C virus NS5B.
Large-scale proteomics and phosphoproteomics of urinary exosomes.
Characterization of exosome-like vesicles released from human tracheobronchial ciliated epithelium: a possible role in innate defense.
Proteomic analysis of human parotid gland exosomes by multidimensional protein identification technology (MudPIT).
Identification of small molecule inhibitors of pyruvate kinase M2.
Isolation and characterization of the human pyruvate kinase M gene.
MHC class II-associated proteins in B-cell exosomes and potential functional implications for exosome biogenesis.
Phosphoproteome analysis of functional mitochondria isolated from resting human muscle reveals extensive phosphorylation of inner membrane protein complexes and enzymes.
Evidence for an alternative glycolytic pathway in rapidly proliferating cells.
Genome-wide YFP fluorescence complementation screen identifies new regulators for telomere signaling in human cells.
Protein profile of exosomes from trabecular meshwork cells.
Proteomic characterization of the human sperm nucleus.
Death-associated protein kinase increases glycolytic rate through binding and activation of pyruvate kinase.
Nuclear PKM2 regulates β-catenin transactivation upon EGFR activation.
Insights into RNA biology from an atlas of mammalian mRNA-binding proteins.
Comparative analysis of virus-host interactomes with a mammalian high-throughput protein complementation assay based on Gaussia princeps luciferase.
In-depth proteomic analyses of exosomes isolated from expressed prostatic secretions in urine.
Proteomic analysis of cerebrospinal fluid extracellular vesicles: a comprehensive dataset.
E-cadherin interactome complexity and robustness resolved by quantitative proteomics.
JMJD8 Regulates Angiogenic Sprouting and Cellular Metabolism by Interacting With Pyruvate Kinase M2 in Endothelial Cells.
TSC22D2 interacts with PKM2 and inhibits cell growth in colorectal cancer.
Cytosolic thyroid hormone-binding protein is a monomer of pyruvate kinase.
Human M2-type pyruvate kinase: cDNA cloning, chromosomal assignment and expression in hepatoma.
Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins and Uncovers Widespread Protein Aggregation in Affected Brains.
Modulation of type M2 pyruvate kinase activity by the human papillomavirus type 16 E7 oncoprotein.
Exocytosis of secretory granule lumen proteins
Exocytosis of ficolin-rich granule lumen proteins
Pyruvate kinase dephosphorylates PEP to PYR
PKM and TGIF2 bind CDH1 gene promoter
CTLH E3 ligase ubiquitinates PKM-1