PKM (Pyruvate Kinase M) encodes pyruvate kinase isoforms that catalyze the final step of glycolysis: conversion of phosphoenolpyruvate and ADP to pyruvate and ATP. CRITICAL ISOFORM BIOLOGY: Alternative splicing of mutually exclusive exons 9/10 produces isoforms with FUNDAMENTALLY DIFFERENT metabolic properties: (1) PKM1 (P14618-2, M1-PK) is expressed in ADULT differentiated tissues (muscle, brain, heart). It is a constitutively active homotetramer with HIGH pyruvate kinase activity, supporting efficient ATP generation via complete glycolysis and oxidative metabolism. (2) PKM2 (P14618-1, M2-PK) is expressed in EMBRYONIC tissues, PROLIFERATING cells, and nearly all CANCERS. It has LOW basal activity and is allosterically regulated by fructose-1,6-bisphosphate (FBP). PKM2 can exist as inactive monomer/dimer or active tetramer. LOW activity allows glycolytic intermediates to accumulate for biosynthetic pathways (nucleotides, amino acids, lipids) - the metabolic basis of the WARBURG EFFECT in cancer. PKM2-SPECIFIC FUNCTIONS (not shared by PKM1): - Protein kinase activity (phosphorylates histone H3 at Tyr11) - Nuclear translocation and transcription coactivator activity (with HIF-1alpha) - These non-glycolytic functions contribute to cancer cell proliferation. The PKM1-to-PKM2 switch is controlled by hnRNP splicing factors (hnRNPA1, hnRNPA2, PTBP1) and is a metabolic hallmark distinguishing differentiated vs proliferating cells.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0004743 pyruvate kinase activity | IBA GO_REF:0000033 | ACCEPT | Summary: Both PKM1 and PKM2 isoforms possess pyruvate kinase activity, catalyzing the final step of glycolysis (PEP + ADP -> pyruvate + ATP). However, these isoforms have FUNDAMENTALLY DIFFERENT enzymatic properties. PKM1 (P14618-2) is constitutively active with HIGH activity [PMID:20847263]. PKM2 (P14618-1) has LOW basal activity and requires allosteric activation by fructose-1,6-bisphosphate (FBP) to form active tetramers [PMID:15996096, PMID:18337815]. The IBA annotation is correct but does not capture this critical isoform-specific difference in activity levels. Reason: Core function for both isoforms. Pyruvate kinase activity is the canonical function of PKM. Both isoforms catalyze this reaction, though with vastly different kinetic properties and regulation. Supporting Evidence: PMID:20847263 Paradoxically, decreased pyruvate kinase enzyme activity accompanies the expression of PKM2 in rapidly dividing cancer cells and tissues. file:human/PKM/PKM-deep-research-falcon.md PKM catalyzes the terminal glycolytic step: PEP + ADP -> pyruvate + ATP, coupling high-energy phosphate transfer to ATP production. |
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | ACCEPT | Summary: Both PKM1 and PKM2 localize to the cytoplasm where they perform their glycolytic function. PKM1 is exclusively cytoplasmic [UniProt P14618]. PKM2 is predominantly cytoplasmic but can translocate to the nucleus upon specific stimuli such as EGFR activation [PMID:22056988, PMID:17308100]. Reason: Cytoplasmic localization is correct for both isoforms and represents the primary site of glycolytic function. Supporting Evidence: PMID:22056988 EGF treatment resulted in the nuclear accumulation of PKM2 in U87/EGFR human glioblastoma (GBM) cells... In addition, PKM1 failed to translocate into the nucleus upon EGF stimulation |
| GO:0006096 glycolytic process | IBA GO_REF:0000033 | ACCEPT | Summary: Both isoforms participate in glycolysis. PKM1 supports efficient glycolysis for ATP production. PKM2's low activity in cancer cells diverts glycolytic intermediates to biosynthetic pathways (the Warburg effect) [PMID:20847263]. Reason: Core function for both isoforms. Both participate in glycolysis though PKM2's low activity fundamentally alters glycolytic flux in proliferating cells. Supporting Evidence: PMID:20847263 The M2 isoform of pyruvate kinase (PKM2) promotes the metabolism of glucose by aerobic glycolysis and contributes to anabolic metabolism. |
| GO:0032869 cellular response to insulin stimulus | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: PKM expression and activity can be regulated by insulin signaling. This is a phylogenetically conserved function supported by IBA evidence. Reason: This represents a regulatory response rather than a core biochemical function. PKM participates in insulin-mediated metabolic regulation but this is secondary to its primary glycolytic function. |
| GO:0000166 nucleotide binding | IEA GO_REF:0000043 | ACCEPT | Summary: PKM binds ADP as a substrate for the pyruvate kinase reaction. This is a correct but overly general annotation - the more specific pyruvate kinase activity annotation is more informative. Reason: Correct parent term of ATP binding, which is required for pyruvate kinase activity. Both isoforms bind nucleotides. |
| GO:0000287 magnesium ion binding | IEA GO_REF:0000002 | ACCEPT | Summary: Pyruvate kinase requires Mg2+ as a cofactor [UniProt P14618]. This applies to both isoforms. Reason: Mg2+ is an essential cofactor for pyruvate kinase activity. Both isoforms require this ion. |
| GO:0003824 catalytic activity | IEA GO_REF:0000120 | ACCEPT | Summary: PKM has catalytic activity. This is an overly broad parent term - the specific pyruvate kinase activity annotation is more informative. Reason: True but uninformative parent term. Both isoforms have catalytic activity. |
| GO:0004674 protein serine/threonine kinase activity | IEA GO_REF:0000003 | MODIFY | Summary: PKM2 (NOT PKM1) has protein threonine kinase activity. PKM2 phosphorylates histone H3 at Thr-11 (H3T11ph) [PMID:22901803, UniProt]. This is a PKM2-SPECIFIC function that occurs when PKM2 is in the nuclear dimeric form. PKM1 does NOT have this activity. Reason: CRITICAL ISOFORM CONFLATION: This annotation applies ONLY to PKM2 (P14618-1), not PKM1. The IEA annotation fails to capture this isoform specificity; the requested modification is to retain GO:0004674 but add the isoform qualifier isoform: P14618-1. Proposed replacements: protein serine/threonine kinase activity |
| GO:0004713 protein tyrosine kinase activity | IEA GO_REF:0000116 | MODIFY | Summary: PKM2 (NOT PKM1) has protein tyrosine kinase activity. PKM2 phosphorylates STAT3 at Tyr-705 [PMID:22306293, UniProt]. This is a PKM2-SPECIFIC function that occurs in the nuclear dimeric form. PKM1 does NOT have this activity. Reason: CRITICAL ISOFORM CONFLATION: This annotation applies ONLY to PKM2 (P14618-1), not PKM1. The IEA annotation fails to capture this isoform specificity; the requested modification is to retain GO:0004713 but add the isoform qualifier isoform: P14618-1. Proposed replacements: protein tyrosine kinase activity |
| GO:0004715 non-membrane spanning protein tyrosine kinase activity | IEA GO_REF:0000003 | MODIFY | Summary: PKM2 (NOT PKM1) has non-membrane spanning protein tyrosine kinase activity. This is consistent with its cytosolic/nuclear localization. PKM1 does NOT have this activity. Reason: CRITICAL ISOFORM CONFLATION: This annotation applies ONLY to PKM2 (P14618-1), not PKM1. The requested modification is to retain GO:0004715 but add the isoform qualifier isoform: P14618-1. Proposed replacements: non-membrane spanning protein tyrosine kinase activity |
| GO:0004743 pyruvate kinase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Duplicate of IBA annotation. Both isoforms have pyruvate kinase activity, though with vastly different kinetic properties. Reason: Core function for both isoforms. This IEA annotation is redundant with the IBA annotation but not incorrect. |
| GO:0005524 ATP binding | IEA GO_REF:0000043 | ACCEPT | Summary: PKM binds ATP/ADP as substrates for pyruvate kinase reaction. Both isoforms bind ATP. Reason: Correct annotation for both isoforms as ATP/ADP binding is essential for pyruvate kinase activity. |
| GO:0005634 nucleus | IEA GO_REF:0000044 | MODIFY | Summary: PKM2 (NOT PKM1) translocates to the nucleus upon EGFR activation and other stimuli [PMID:22056988, PMID:17308100]. PKM1 does NOT translocate to the nucleus. This is a PKM2-SPECIFIC localization. Reason: CRITICAL ISOFORM CONFLATION: Nuclear localization applies ONLY to PKM2 (P14618-1); the requested modification is to retain GO:0005634 but add the isoform qualifier isoform: P14618-1. PMID:22056988 explicitly states "PKM1 failed to translocate into the nucleus upon EGF stimulation". Proposed replacements: nucleus Supporting Evidence: PMID:22056988 In addition, PKM1 failed to translocate into the nucleus upon EGF stimulation |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | ACCEPT | Summary: Both PKM1 and PKM2 localize to the cytoplasm. This is the primary site of glycolytic function. Reason: Correct for both isoforms. Cytoplasmic localization is the primary location for glycolytic function. |
| GO:0006096 glycolytic process | IEA GO_REF:0000120 | ACCEPT | Summary: Duplicate of IBA annotation. Both isoforms participate in glycolysis. Reason: Core function for both isoforms. Redundant with IBA annotation but not incorrect. |
| GO:0006417 regulation of translation | IEA GO_REF:0000043 | KEEP AS NON CORE | Summary: PKM2 may act as a translation regulator for a subset of mRNAs, associating with ER-bound ribosomes and promoting translation of ER-destined mRNAs [UniProt, by similarity]. This function is attributed to PKM2 specifically. Reason: This is a non-canonical moonlighting function of PKM2 based on similarity evidence. Not a core function. |
| GO:0016301 kinase activity | IEA GO_REF:0000043 | ACCEPT | Summary: PKM has kinase activity - pyruvate kinase activity for both isoforms, and protein kinase activity for PKM2 only. This is a broad parent term. Reason: True but uninformative parent term encompassing both pyruvate kinase and protein kinase activities. |
| GO:0016740 transferase activity | IEA GO_REF:0000043 | ACCEPT | Summary: PKM has transferase activity (phosphotransferase). This is a very broad parent term. Reason: True but uninformative high-level parent term. Both isoforms have transferase activity. |
| GO:0030955 potassium ion binding | IEA GO_REF:0000002 | ACCEPT | Summary: Pyruvate kinase requires K+ as a cofactor [UniProt P14618]. This applies to both isoforms. Reason: K+ is an essential cofactor for pyruvate kinase activity. Both isoforms require this ion. |
| GO:0046872 metal ion binding | IEA GO_REF:0000043 | ACCEPT | Summary: PKM binds metal ions (Mg2+, K+) as cofactors. Parent term of magnesium and potassium binding. Reason: True parent term. Both isoforms bind metal ion cofactors. |
| GO:0005515 protein binding | IPI PMID:12620389 Novel raf kinase protein-protein interactions found by an ex... | MARK AS OVER ANNOTATED | Summary: Yeast two-hybrid study identifying RAF kinase protein-protein interactions. PKM was identified as an interactor. This is a generic protein binding annotation from high-throughput screening. Reason: Generic protein binding from Y2H screen. Does not provide functional insight into PKM's core activities. More specific interaction terms would be more informative. Supporting Evidence: PMID:12620389 Novel raf kinase protein-protein interactions found by an exhaustive yeast two-hybrid analysis. |
| GO:0005515 protein binding | IPI PMID:17500595 Huntingtin interacting proteins are genetic modifiers of neu... | MARK AS OVER ANNOTATED | Summary: PKM identified as a Huntingtin interacting protein and potential modifier of neurodegeneration. High-throughput interactome study. Reason: Generic protein binding from interactome study. Does not distinguish between isoforms or provide functional context. Supporting Evidence: PMID:17500595 Huntingtin interacting proteins are genetic modifiers of neurodegeneration. |
| GO:0005515 protein binding | IPI PMID:17620599 Functional specialization of beta-arrestin interactions reve... | MARK AS OVER ANNOTATED | Summary: PKM identified in beta-arrestin interactome study. High-throughput proteomics. Reason: Generic protein binding from proteomics study. Uninformative without functional context. Supporting Evidence: PMID:17620599 Functional specialization of beta-arrestin interactions revealed by proteomic analysis. |
| GO:0005515 protein binding | IPI PMID:18519040 Isoform-specific interaction of pyruvate kinase with hepatit... | KEEP AS NON CORE | Summary: Isoform-specific interaction of pyruvate kinase with HCV NS5B. The study specifically examines PKM2 interaction with viral protein. Reason: Interaction with viral protein is interesting for host-pathogen biology but not a core function. Appears to be PKM2-specific based on the study context. Supporting Evidence: PMID:18519040 Epub 2008 Jun 2. Isoform-specific interaction of pyruvate kinase with hepatitis C virus NS5B. |
| GO:0005515 protein binding | IPI PMID:21044950 Genome-wide YFP fluorescence complementation screen identifi... | MARK AS OVER ANNOTATED | Summary: PKM identified in telomere signaling regulator screen. High-throughput study. Reason: Generic protein binding from screening study. Lacks functional specificity. Supporting Evidence: PMID:21044950 Epub 2010 Nov 2. Genome-wide YFP fluorescence complementation screen identifies new regulators for telomere signaling in human cells. |
| GO:0005515 protein binding | IPI PMID:21725354 Death-associated protein kinase increases glycolytic rate th... | KEEP AS NON CORE | Summary: Death-associated protein kinase (DAPK) binds and activates pyruvate kinase. This is functionally relevant for PKM regulation. Reason: Functionally relevant interaction but the generic protein binding term is uninformative. Would be better captured by a more specific term or in the regulation context. Supporting Evidence: PMID:21725354 Death-associated protein kinase increases glycolytic rate through binding and activation of pyruvate kinase. |
| GO:0005515 protein binding | IPI PMID:22056988 Nuclear PKM2 regulates Ξ²-catenin transactivation upon EGFR a... | MODIFY | Summary: PKM2 (specifically) interacts with beta-catenin (CTNNB1) in the nucleus to regulate transcription of CCND1 [PMID:22056988]. This is a PKM2-SPECIFIC interaction that requires c-Src phosphorylation of beta-catenin at Y333. Reason: This is a functionally significant PKM2-specific interaction. The generic protein binding term fails to capture the isoform specificity and functional significance. Should be annotated as beta-catenin binding for PKM2 specifically. Proposed replacements: beta-catenin binding Supporting Evidence: PMID:22056988 EGF stimulation resulted in an interaction between endogenous PKM2 and beta-catenin in the nuclear, but not cytosolic, fraction |
| GO:0005515 protein binding | IPI PMID:22898364 Comparative analysis of virus-host interactomes with a mamma... | MARK AS OVER ANNOTATED | Summary: PKM identified in virus-host interactome study using protein complementation assay. High-throughput screening. Reason: Generic protein binding from high-throughput viral interactome study. Supporting Evidence: PMID:22898364 Aug 8. Comparative analysis of virus-host interactomes with a mammalian high-throughput protein complementation assay based on Gaussia princeps luciferase. |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | MARK AS OVER ANNOTATED | Summary: PKM identified in neurodegenerative disease protein interactome mapping study. Reason: Generic protein binding from disease-focused interactome study. Supporting Evidence: PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins and Uncovers Widespread Protein Aggregation in Affected Brains. |
| GO:0005515 protein binding | IPI PMID:9990017 Modulation of type M2 pyruvate kinase activity by the human ... | KEEP AS NON CORE | Summary: HPV-16 E7 oncoprotein modulates M2-type pyruvate kinase activity. E7 binding promotes PKM2 homodimerization [UniProt]. Reason: Interaction with viral oncoprotein is relevant for understanding PKM2 in cancer but represents host-pathogen interaction rather than core function. Supporting Evidence: PMID:9990017 Modulation of type M2 pyruvate kinase activity by the human papillomavirus type 16 E7 oncoprotein. |
| GO:0003729 mRNA binding | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: PKM2 may bind mRNAs as part of its moonlighting function in translation regulation [UniProt, by similarity]. Associates with ER-bound ribosomes. Reason: Non-canonical moonlighting function of PKM2 based on similarity evidence. Not a core function. |
| GO:0005791 rough endoplasmic reticulum | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: PKM2 may associate with rough ER as part of its translation regulation function [UniProt, by similarity]. Reason: Associated with moonlighting function in translation regulation. Not a primary localization. |
| GO:0005829 cytosol | IEA GO_REF:0000107 | ACCEPT | Summary: Both PKM1 and PKM2 are cytosolic enzymes where they perform glycolysis. Reason: Correct localization for both isoforms. Primary site of glycolytic activity. |
| GO:0005929 cilium | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: PKM localization to cilium based on ortholog evidence. Limited direct evidence. Reason: Ortholog-based evidence for specialized localization. Not a primary site of function. |
| GO:0061621 canonical glycolysis | IEA GO_REF:0000107 | ACCEPT | Summary: Both isoforms participate in canonical glycolysis. PKM catalyzes the final step converting PEP to pyruvate. Reason: Core function for both isoforms. More specific than generic glycolytic process term. |
| GO:2000767 positive regulation of cytoplasmic translation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: PKM2 may positively regulate translation of ER-destined mRNAs [UniProt, by similarity]. Moonlighting function. Reason: Non-canonical moonlighting function based on similarity evidence. Not a core function. |
| GO:0005829 cytosol | IDA GO_REF:0000052 | ACCEPT | Summary: Direct assay evidence for cytosolic localization based on immunofluorescence. Both isoforms are cytosolic. Reason: Validated cytosolic localization. Primary site of glycolytic function for both isoforms. |
| GO:0004743 pyruvate kinase activity | IDA PMID:20847263 Evidence for an alternative glycolytic pathway in rapidly pr... | ACCEPT | Summary: Direct demonstration of pyruvate kinase activity. This study examined both PKM1 and PKM2 and showed that PKM2 has lower activity and contributes to the Warburg effect by allowing glycolytic intermediates to accumulate for biosynthesis. Reason: Core function with direct experimental evidence. Both isoforms have activity but with different kinetic properties. Supporting Evidence: PMID:20847263 Paradoxically, decreased pyruvate kinase enzyme activity accompanies the expression of PKM2 in rapidly dividing cancer cells and tissues. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9766062 | MODIFY | Summary: Reactome pathway annotation for PKM and TGIF2 binding CDH1 gene promoter. This nuclear function is PKM2-specific based on literature evidence. Reason: ISOFORM CONFLATION: Nucleoplasm localization is PKM2-specific. PKM1 does not translocate to nucleus. The requested modification is to retain GO:0005654 but add the isoform qualifier isoform: P14618-1. Proposed replacements: nucleoplasm |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9861640 | ACCEPT | Summary: Reactome annotation for CTLH E3 ligase ubiquitinating PKM-1. Cytosolic localization is correct for both isoforms. Reason: Correct localization for both isoforms. |
| GO:0005515 protein binding | IPI PMID:27573352 TSC22D2 interacts with PKM2 and inhibits cell growth in colo... | KEEP AS NON CORE | Summary: TSC22D2 interacts with PKM2 and inhibits cell growth in colorectal cancer. The interaction reduces nuclear PKM2 levels and represses cyclin D1 transcription. Reason: Functionally relevant interaction specific to PKM2. Generic protein binding term lacks specificity. Supporting Evidence: PMID:27573352 TSC22D2 interacts with PKM2 and inhibits cell growth in colorectal cancer. |
| GO:0005634 nucleus | IDA PMID:27573352 TSC22D2 interacts with PKM2 and inhibits cell growth in colo... | ACCEPT | Summary: Direct evidence for PKM nuclear localization. The study specifically examines PKM2 (isoform M2) nuclear localization and its regulation by TSC22D2. Reason: Direct experimental evidence for nuclear localization. This is PKM2-specific function but IDA evidence is strong. Supporting Evidence: PMID:27573352 TSC22D2 interacts with PKM2 and inhibits cell growth in colorectal cancer. |
| GO:0005737 cytoplasm | IDA PMID:27573352 TSC22D2 interacts with PKM2 and inhibits cell growth in colo... | ACCEPT | Summary: Direct evidence for PKM cytoplasmic localization. Both isoforms are cytoplasmic. Reason: Correct for both isoforms. Primary site of glycolytic function. Supporting Evidence: PMID:27573352 TSC22D2 interacts with PKM2 and inhibits cell growth in colorectal cancer. |
| GO:0003729 mRNA binding | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Sequence similarity-based annotation for mRNA binding. Moonlighting function of PKM2. Reason: Non-canonical function based on similarity. Not a core function. |
| GO:0005791 rough endoplasmic reticulum | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Sequence similarity-based annotation. Associated with translation regulation moonlighting function. Reason: Non-canonical localization associated with moonlighting function. |
| GO:2000767 positive regulation of cytoplasmic translation | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Sequence similarity-based annotation for translation regulation. Moonlighting function. Reason: Non-canonical moonlighting function based on sequence similarity. |
| GO:0005515 protein binding | IPI PMID:27199445 JMJD8 Regulates Angiogenic Sprouting and Cellular Metabolism... | KEEP AS NON CORE | Summary: JMJD8 interacts with PKM2 and regulates angiogenic sprouting and cellular metabolism. Reason: Functionally relevant interaction but generic protein binding term is uninformative. Supporting Evidence: PMID:27199445 JMJD8 Regulates Angiogenic Sprouting and Cellular Metabolism by Interacting With Pyruvate Kinase M2 in Endothelial Cells. |
| GO:1903672 positive regulation of sprouting angiogenesis | IMP PMID:27199445 JMJD8 Regulates Angiogenic Sprouting and Cellular Metabolism... | KEEP AS NON CORE | Summary: PKM regulates angiogenic sprouting through interaction with JMJD8 in endothelial cells. Likely PKM2-mediated based on cancer/proliferation context. Reason: Pleiotropic downstream effect in specialized cell type context. Not a core function of PKM. Supporting Evidence: PMID:27199445 JMJD8 Regulates Angiogenic Sprouting and Cellular Metabolism by Interacting With Pyruvate Kinase M2 in Endothelial Cells. |
| GO:0045296 cadherin binding | HDA PMID:25468996 E-cadherin interactome complexity and robustness resolved by... | KEEP AS NON CORE | Summary: High-throughput proteomics study of E-cadherin interactome. PKM identified as an interactor. Reason: High-throughput proteomics finding. More informative than generic protein binding but not a core function. Supporting Evidence: PMID:25468996 E-cadherin interactome complexity and robustness resolved by quantitative proteomics. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-6798748 | KEEP AS NON CORE | Summary: Reactome annotation for exocytosis of secretory granule lumen proteins. PKM found in extracellular region via secretion. Reason: PKM can be secreted but extracellular localization is not a primary site of function. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-6800434 | KEEP AS NON CORE | Summary: Reactome annotation for ficolin-rich granule exocytosis. PKM present in extracellular region. Reason: Secondary localization from secretory process. |
| GO:0034774 secretory granule lumen | TAS Reactome:R-HSA-6798748 | KEEP AS NON CORE | Summary: PKM present in secretory granule lumen per Reactome annotation. Reason: Specialized localization related to secretory function. |
| GO:1904813 ficolin-1-rich granule lumen | TAS Reactome:R-HSA-6800434 | KEEP AS NON CORE | Summary: PKM present in ficolin-1-rich granule lumen per Reactome annotation. Reason: Specialized localization in immune cell granules. |
| GO:0070062 extracellular exosome | HDA PMID:12519789 Proteomic and biochemical analyses of human B cell-derived e... | KEEP AS NON CORE | Summary: PKM detected in B cell-derived exosomes by proteomics. Reason: Exosomal localization from proteomics study. Not primary functional location. Supporting Evidence: PMID:12519789 2003 Jan 7. Proteomic and biochemical analyses of human B cell-derived exosomes. |
| GO:0070062 extracellular exosome | HDA PMID:11487543 Intestinal epithelial cells secrete exosome-like vesicles. | KEEP AS NON CORE | Summary: PKM detected in intestinal epithelial cell exosomes. Reason: Exosomal cargo. Not primary functional location. Supporting Evidence: PMID:11487543 Intestinal epithelial cells secrete exosome-like vesicles. |
| GO:1903561 extracellular vesicle | HDA PMID:24769233 Proteomic analysis of cerebrospinal fluid extracellular vesi... | KEEP AS NON CORE | Summary: PKM detected in CSF extracellular vesicles by proteomics. Reason: Extracellular vesicle cargo from proteomics. Supporting Evidence: PMID:24769233 2014 Apr 24. Proteomic analysis of cerebrospinal fluid extracellular vesicles: a comprehensive dataset. |
| GO:0070062 extracellular exosome | HDA PMID:23533145 In-depth proteomic analyses of exosomes isolated from expres... | KEEP AS NON CORE | Summary: PKM detected in prostatic secretion exosomes. Reason: Exosomal cargo from proteomics. Supporting Evidence: PMID:23533145 2013 Apr 23. In-depth proteomic analyses of exosomes isolated from expressed prostatic secretions in urine. |
| GO:0031982 vesicle | HDA PMID:19190083 Characterization of exosome-like vesicles released from huma... | KEEP AS NON CORE | Summary: PKM detected in tracheobronchial epithelial exosome-like vesicles. Reason: Vesicular localization from proteomics. Supporting Evidence: PMID:19190083 Characterization of exosome-like vesicles released from human tracheobronchial ciliated epithelium: a possible role in innate defense. |
| GO:0005634 nucleus | HDA PMID:21630459 Proteomic characterization of the human sperm nucleus. | KEEP AS NON CORE | Summary: PKM detected in sperm nucleus by proteomics. Supports nuclear localization capability. Reason: Nuclear detection in specialized cell type. PKM2-specific function. Supporting Evidence: PMID:21630459 Jun 1. Proteomic characterization of the human sperm nucleus. |
| GO:0003723 RNA binding | HDA PMID:22658674 Insights into RNA biology from an atlas of mammalian mRNA-bi... | KEEP AS NON CORE | Summary: PKM identified in mRNA-binding protein atlas. Supports moonlighting function in translation regulation. Reason: Non-canonical moonlighting function from proteomics study. Supporting Evidence: PMID:22658674 May 31. Insights into RNA biology from an atlas of mammalian mRNA-binding proteins. |
| GO:0005739 mitochondrion | HDA PMID:20833797 Phosphoproteome analysis of functional mitochondria isolated... | KEEP AS NON CORE | Summary: PKM detected in mitochondrial phosphoproteome. May represent association with mitochondria or contamination. Reason: Unexpected localization from phosphoproteomics. PKM is canonically cytosolic. Supporting Evidence: PMID:20833797 Epub 2010 Sep 10. Phosphoproteome analysis of functional mitochondria isolated from resting human muscle reveals extensive phosphorylation of inner membrane protein complexes and enzymes. |
| GO:0070062 extracellular exosome | HDA PMID:19199708 Proteomic analysis of human parotid gland exosomes by multid... | KEEP AS NON CORE | Summary: PKM detected in parotid gland exosomes. Reason: Exosomal cargo from proteomics. Supporting Evidence: PMID:19199708 Proteomic analysis of human parotid gland exosomes by multidimensional protein identification technology (MudPIT). |
| GO:0070062 extracellular exosome | HDA PMID:19056867 Large-scale proteomics and phosphoproteomics of urinary exos... | KEEP AS NON CORE | Summary: PKM detected in urinary exosomes by proteomics. Reason: Exosomal cargo from proteomics. Supporting Evidence: PMID:19056867 2008 Dec 3. Large-scale proteomics and phosphoproteomics of urinary exosomes. |
| GO:0023026 MHC class II protein complex binding | HDA PMID:20458337 MHC class II-associated proteins in B-cell exosomes and pote... | KEEP AS NON CORE | Summary: PKM identified as MHC class II-associated protein in B-cell exosomes. Reason: High-throughput proteomics finding. Specialized immune function context. Supporting Evidence: PMID:20458337 2010 May 11. MHC class II-associated proteins in B-cell exosomes and potential functional implications for exosome biogenesis. |
| GO:0070062 extracellular exosome | HDA PMID:20458337 MHC class II-associated proteins in B-cell exosomes and pote... | KEEP AS NON CORE | Summary: PKM detected in B-cell exosomes. Reason: Exosomal cargo from proteomics. Supporting Evidence: PMID:20458337 2010 May 11. MHC class II-associated proteins in B-cell exosomes and potential functional implications for exosome biogenesis. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-71670 | ACCEPT | Summary: Reactome annotation for pyruvate kinase reaction. Cytosolic localization correct for glycolytic function. Reason: Core localization for glycolytic function. |
| GO:0004743 pyruvate kinase activity | IDA PMID:20005212 Identification of small molecule inhibitors of pyruvate kina... | ACCEPT | Summary: Study identifying small molecule inhibitors of PKM2. Directly demonstrates pyruvate kinase activity. Reason: Core function with direct experimental evidence. Supporting Evidence: PMID:20005212 Epub 2009 Dec 11. Identification of small molecule inhibitors of pyruvate kinase M2. |
| GO:0070062 extracellular exosome | HDA PMID:21362503 Protein profile of exosomes from trabecular meshwork cells. | KEEP AS NON CORE | Summary: PKM detected in trabecular meshwork cell exosomes. Reason: Exosomal cargo from proteomics. Supporting Evidence: PMID:21362503 Epub 2011 Mar 8. Protein profile of exosomes from trabecular meshwork cells. |
| GO:0005737 cytoplasm | IDA GO_REF:0000054 | ACCEPT | Summary: Direct assay evidence for cytoplasmic localization from fusion protein studies. Reason: Core localization for both isoforms. |
| GO:0005634 nucleus | IDA PMID:18191611 Pyruvate kinase isozyme type M2 (PKM2) interacts and coopera... | ACCEPT | Summary: PKM2 interacts with Oct-4 in the nucleus and cooperates in regulating transcription. This is PKM2-SPECIFIC nuclear function. Reason: Direct experimental evidence for PKM2 nuclear localization and function. Supporting Evidence: PMID:18191611 PKM2 is an isozyme of pyruvate kinase that is specifically expressed in proliferating cells, such as embryonic stem cells, embryonic carcinoma cells, as well as cancer cells. |
| GO:0005737 cytoplasm | IDA PMID:18298799 Modulation of M2-type pyruvate kinase activity by the cytopl... | ACCEPT | Summary: Study showing cytoplasmic PML modulates PKM2 activity. Confirms cytoplasmic localization. Reason: Core localization confirmed by direct evidence. Supporting Evidence: PMID:18298799 cytoplasmic PML (cPML) directly interacts with M2-type pyruvate kinase (PKM2) |
| GO:0005515 protein binding | IPI PMID:18191611 Pyruvate kinase isozyme type M2 (PKM2) interacts and coopera... | MODIFY | Summary: PKM2 interacts with Oct-4 transcription factor. The interaction enhances Oct-4 transcriptional activity. PKM2-SPECIFIC interaction. Reason: Functionally significant interaction with transcription factor. Generic protein binding term is uninformative. Should be more specific (e.g., transcription factor binding). Proposed replacements: DNA-binding transcription factor binding Supporting Evidence: PMID:18191611 ectopic expression of the PKM2 enhanced Oct-4-mediated transcription |
| GO:0005515 protein binding | IPI PMID:18298799 Modulation of M2-type pyruvate kinase activity by the cytopl... | KEEP AS NON CORE | Summary: PKM2 interacts with PML tumor suppressor. PML modulates PKM2 tetrameric activity. Reason: Functionally relevant interaction for PKM2 regulation but generic protein binding term is uninformative. Supporting Evidence: PMID:18298799 cytoplasmic PML (cPML) directly interacts with M2-type pyruvate kinase (PKM2) |
| GO:0005634 nucleus | IDA PMID:17308100 Nuclear translocation of the tumor marker pyruvate kinase M2... | ACCEPT | Summary: PKM2 translocates to nucleus in response to apoptotic stimuli and TT-232. Nuclear translocation induces cell death. PKM2-SPECIFIC function. Reason: Direct experimental evidence for PKM2-specific nuclear translocation. Supporting Evidence: PMID:17308100 Nuclear translocation of PKM2 is sufficient to induce cell death that is caspase independent, isoform specific, and independent of its enzymatic activity. |
| GO:0012501 programmed cell death | IDA PMID:17308100 Nuclear translocation of the tumor marker pyruvate kinase M2... | KEEP AS NON CORE | Summary: Nuclear PKM2 translocation induces programmed cell death. This is a PKM2-SPECIFIC function that is caspase-independent and independent of pyruvate kinase activity. Reason: PKM2-specific non-metabolic function. Not a core function but well-documented. Supporting Evidence: PMID:17308100 Nuclear translocation of PKM2 is sufficient to induce cell death that is caspase independent, isoform specific, and independent of its enzymatic activity. |
| GO:0004743 pyruvate kinase activity | TAS PMID:2854097 Human M2-type pyruvate kinase: cDNA cloning, chromosomal ass... | ACCEPT | Summary: Original cloning of human M2-type pyruvate kinase cDNA. Establishes pyruvate kinase activity as core function. Reason: Core function from original characterization of PKM2. Supporting Evidence: PMID:2854097 Human M2-type pyruvate kinase: cDNA cloning, chromosomal assignment and expression in hepatoma. |
| GO:0004743 pyruvate kinase activity | TAS PMID:2040271 Isolation and characterization of the human pyruvate kinase ... | ACCEPT | Summary: Isolation and characterization of human pyruvate kinase M gene. Reason: Core function from gene characterization. Supporting Evidence: PMID:2040271 Isolation and characterization of the human pyruvate kinase M gene. |
| GO:0004743 pyruvate kinase activity | TAS PMID:2813362 Cytosolic thyroid hormone-binding protein is a monomer of py... | ACCEPT | Summary: Demonstrates PKM is a cytosolic thyroid hormone-binding protein that is a monomer of pyruvate kinase with enzymatic activity. Reason: Core function established in characterization study. Supporting Evidence: PMID:2813362 Cytosolic thyroid hormone-binding protein is a monomer of pyruvate kinase. |
| GO:0005829 cytosol | NAS PMID:2813362 Cytosolic thyroid hormone-binding protein is a monomer of py... | ACCEPT | Summary: PKM identified as cytosolic thyroid hormone-binding protein. Reason: Core localization established in early characterization. Supporting Evidence: PMID:2813362 Cytosolic thyroid hormone-binding protein is a monomer of pyruvate kinase. |
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