GroEL

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0006457 protein folding	IBA GO_REF:0000033	ACCEPT	Summary: IBA annotation for protein folding, supported by phylogenetic inference across chaperonin family members including human HSPD1 (P10809) and M. tuberculosis GroEL1/2. GroEL is the prototypical chaperonin that assists protein folding in vivo and in vitro (PMID:2573517, PMID:10532860, PMID:14517228). This is a core biological process annotation for GroEL. Reason: Protein folding is the central biological process for GroEL. The IBA annotation is well supported by extensive experimental evidence. UniProt states GroEL "plays an essential role in assisting protein folding" (PMID:10532860, PMID:2573517). PMID:2573517 demonstrates that groEL mutations cause a beta-lactamase export defect and supports a client-specific cytoplasmic chaperone role in vivo. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000143677 · PANTHER:PTN000143677 SUPPORTS TRANSFER Current PTHR45633 PAINT retains protein folding at this node. SGD:S000004249 · SGD:S000004249 SUPPORTS TRANSFER Listed descendant evidence for the current folding assertion. UniProtKB:P0A6F5 · GroEL SUPPORTS TRANSFER GroEL's own experimental folding evidence validly seeds the ancestral assertion. UniProtKB:P10809 · UniProtKB:P10809 SUPPORTS TRANSFER Listed descendant evidence for the conserved chaperonin process. UniProtKB:P9WPE7 · UniProtKB:P9WPE7 SUPPORTS TRANSFER Listed bacterial descendant evidence. UniProtKB:P9WPE9 · UniProtKB:P9WPE9 SUPPORTS TRANSFER Listed bacterial descendant evidence. Supporting Evidence: PMID:2573517 Escherichia coli heat-shock proteins GroES and GroEL are essential cytoplasmic proteins, which have been termed 'chaperonins' because of their ability to assist protein assembly of bacteriophage capsids and multimeric enzymes of foreign origin. PMID:14517228 Role of the gamma-phosphate of ATP in triggering protein folding by GroEL-GroES: function, structure and energetics. file:ECOLI/GroEL/GroEL-deep-research-falcon.md GroEL is the archetypal bacterial chaperonin
GO:0005524 ATP binding	IBA GO_REF:0000033	ACCEPT	Summary: IBA annotation for ATP binding supported by phylogenetic inference. GroEL binds ATP in the equatorial domain, and this binding is essential for triggering conformational changes that drive the chaperonin cycle (PMID:8564544, PMID:9285585). Reason: ATP binding is a well-characterized molecular function of GroEL. The crystal structure of GroEL complexed with ATPgammaS (PMID:8564544) directly demonstrates ATP binding. The asymmetric GroEL-GroES-(ADP)7 structure (PMID:9285585) also confirms nucleotide binding in the equatorial domain. This is integral to the chaperonin cycle. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000143644 · PANTHER:PTN000143644 SUPPORTS TRANSFER Current PTHR45633 PAINT retains ATP binding at this bacterial node. UniProtKB:P0A6F5 · GroEL SUPPORTS TRANSFER Direct GroEL nucleotide-bound structures are valid descendant evidence. Supporting Evidence: PMID:8564544 The 2.4 A crystal structure of the bacterial chaperonin GroEL complexed with ATP gamma S. PMID:9285585 The crystal structure of the asymmetric GroEL-GroES-(ADP)7 chaperonin complex.
GO:0009408 response to heat	IBA GO_REF:0000033	ACCEPT	Summary: IBA annotation for response to heat based on phylogenetic inference across Hsp60 family members. GroEL is a classical heat shock protein whose expression is strongly upregulated during heat stress (PMID:8349564). Reason: GroEL (also called Hsp60/Cpn60) is a canonical heat shock protein in E. coli. Its expression is induced by heat stress and it functions to prevent protein aggregation under thermal stress conditions. The IBA annotation is consistent with the well-known heat shock response role of GroEL across species. PMID:8349564 characterizes groEL as a heat shock gene. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000143644 · PANTHER:PTN000143644 SUPPORTS TRANSFER Current PTHR45633 PAINT retains response to heat at this bacterial node. UniProtKB:P0A6F5 · GroEL SUPPORTS TRANSFER GroEL's heat-shock induction validly seeds this conserved process. UniProtKB:P9WPE7 · UniProtKB:P9WPE7 SUPPORTS TRANSFER Listed bacterial descendant evidence. UniProtKB:P9WPE9 · UniProtKB:P9WPE9 SUPPORTS TRANSFER Listed bacterial descendant evidence. Supporting Evidence: PMID:8349564 Characterization of twenty-six new heat shock genes of Escherichia coli.
GO:0051082 unfolded protein binding	IBA GO_REF:0000033	MODIFY	Summary: IBA annotation for unfolded protein binding. While GroEL does bind unfolded/non-native proteins, GO:0051082 is now formally obsolete. The function of GroEL is better described as an ATP-dependent protein folding chaperone (GO:0140662) because GroEL does not merely bind unfolded proteins -- it actively facilitates their folding through ATP-driven encapsulation cycles. Reason: GO:0051082 "unfolded protein binding" is a passive binding term that fails to capture GroEL's active foldase function. GroEL is the canonical ATP-dependent chaperonin that encapsulates substrates in a central cavity and promotes folding through an iterative ATP hydrolysis cycle (PMID:7935796, PMID:8097882, PMID:9285585). The appropriate replacement is GO:0140662 "ATP-dependent protein folding chaperone" which is a child of GO:0044183 "protein folding chaperone" and accurately captures the ATP-dependent foldase mechanism. GO:0051082 is now formally obsolete as part of the unfolded protein binding obsoletion project (go-ontology#30962). Propagation Review Root cause: SOURCE STALE OR MISSING Failure modes: SOURCE EVIDENCE WEAK Sources checked: PANTHER:PTN000143644 · PANTHER:PTN000143644 SOURCE STALE OR MISSING The refreshed PTHR45633 PAINT cache does not retain GO:0051082 at this node; the legacy GOA row persists after the obsolete term was removed. UniProtKB:P0A6F5 · GroEL SOURCE STALE OR MISSING The historical direct seed is biologically related, but current PAINT no longer asserts this obsolete binding term. Proposed replacements: ATP-dependent protein folding chaperone Supporting Evidence: PMID:8097882 We conclude that folding intermediates are bound inside central cavities within individual chaperonin rings. PMID:7935796 Chaperonins are ring-shaped protein complexes that are essential in the cell, mediating ATP-dependent polypeptide folding in a variety of compartments. file:projects/UNFOLDED_PROTEIN_BINDING.md GO:0051082 is now formally obsolete
GO:1990220 GroEL-GroES complex	IBA GO_REF:0000033	ACCEPT	Summary: IBA annotation for GroEL-GroES complex. GroEL forms the double-ring barrel that together with the GroES heptameric lid constitutes the functional chaperonin complex (PMID:9285585). Reason: GroEL is the defining subunit of the GroEL-GroES complex. The crystal structure of the asymmetric GroEL-GroES-(ADP)7 complex (PMID:9285585) directly demonstrates this. This is a core cellular component annotation. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000143644 · PANTHER:PTN000143644 SUPPORTS TRANSFER Current PTHR45633 PAINT retains GroEL-GroES complex membership at this node. UniProtKB:P0A6F5 · GroEL SUPPORTS TRANSFER The target's direct complex evidence is a valid descendant seed. Supporting Evidence: PMID:9285585 The crystal structure of the asymmetric GroEL-GroES-(ADP)7 chaperonin complex.
GO:0000166 nucleotide binding	IEA GO_REF:0000043	MODIFY	Summary: IEA annotation from UniProt keyword mapping (KW-0547 Nucleotide-binding). This is a parent term of GO:0005524 ATP binding, which is already annotated with IBA and IDA evidence. The IEA is broader but not incorrect. Reason: GroEL is unambiguously a nucleotide-binding protein, but this parent is uninformative when ATP binding is directly established and already annotated. Proposed replacements: ATP binding
GO:0005524 ATP binding	IEA GO_REF:0000120	ACCEPT	Summary: IEA annotation for ATP binding via InterPro domain mapping (IPR002423, IPR018370). Duplicates the IBA and IDA annotations for the same term but with electronic evidence. Reason: Correct electronic inference. GroEL contains the GroEL/Hsp60 family InterPro domains that include the ATP-binding equatorial domain. Consistent with crystal structures showing ATP/ADP binding (PMID:8564544, PMID:9285585).
GO:0005737 cytoplasm	IEA GO_REF:0000120	MODIFY	Summary: IEA annotation for cytoplasm from UniProt subcellular location and UniRule mapping. GroEL is a cytoplasmic protein. A more specific IDA annotation for cytosol (GO:0005829) exists from PMID:18304323. Reason: Cytoplasm is not wrong, but direct proteomics and a second HDA row support the more informative cytosol term for GroEL's functional localization. Proposed replacements: cytosol
GO:0006457 protein folding	IEA GO_REF:0000002	ACCEPT	Summary: IEA annotation for protein folding from InterPro domain mapping (IPR018370). Consistent with IBA and IDA annotations for the same term. Reason: Correct electronic inference. The GroEL/Hsp60 InterPro domain is directly associated with protein folding function. Consistent with all other evidence.
GO:0016853 isomerase activity	IEA GO_REF:0000043	MODIFY	Summary: IEA annotation for isomerase activity from UniProt keyword KW-0413. GroEL is classified as EC 5.6.1.7 (protein-folding chaperone) in the isomerase class, which catalyzes the conversion of unfolded polypeptides to folded polypeptides. This is a technically correct but very broad classification. Reason: UniProt assigns EC 5.6.1.7 to GroEL, so the broad isomerase mapping is related but loses the defining substrate and ATP-dependent chaperone mechanism. Proposed replacements: ATP-dependent protein folding chaperone Supporting Evidence: file:projects/UNFOLDED_PROTEIN_BINDING.md GO:0051082 is now formally obsolete
GO:0042026 protein refolding	IEA GO_REF:0000120	ACCEPT	Summary: IEA annotation for protein refolding from InterPro (IPR001844) and UniRule. GroEL/ES can refold denatured proteins back to their native state in vitro and in vivo. Reason: GroEL/ES is well-established to catalyze protein refolding. UniProt describes how the system can "rescue kinetically trapped intermediates" (PMID:20603018) and multiple studies show refolding of denatured substrates (PMID:10532860). The IEA annotation is correct.
GO:0051082 unfolded protein binding	IEA GO_REF:0000104	MODIFY	Summary: IEA annotation for unfolded protein binding from UniRule (UR000098153). Like the IBA annotation for this term, this should be modified to the more appropriate protein folding chaperone term. Reason: Same rationale as for the IBA annotation of GO:0051082. GroEL is not merely an unfolded protein binder -- it is an ATP-dependent foldase. GO:0051082 is now formally obsolete (go-ontology#30962). The correct replacement is GO:0140662 "ATP-dependent protein folding chaperone". Proposed replacements: ATP-dependent protein folding chaperone
GO:0140662 ATP-dependent protein folding chaperone	IEA GO_REF:0000002	ACCEPT	Summary: IEA annotation for ATP-dependent protein folding chaperone from InterPro (IPR001844). This is the most accurate MF term for GroEL's core enzymatic activity. GroEL uses ATP hydrolysis to drive iterative cycles of substrate binding, encapsulation, folding, and release. Reason: This is the correct and most specific molecular function term for GroEL. It captures both the ATP dependence and the protein folding chaperone activity. UniProt catalytic activity: "ATP + H2O + an unfolded polypeptide = ADP + phosphate + a folded polypeptide" (EC 5.6.1.7, PMID:9285585, PMID:9285593). This IEA annotation should ideally be supported by experimental evidence as well.
GO:0005515 protein binding	IPI PMID:10077571 GroES in the asymmetric GroEL14-GroES7 complex exchanges via...	MODIFY	Summary: IPI annotation for protein binding with GroES (P0A6F9). This study examines GroES exchange in the asymmetric GroEL14-GroES7 complex via an associative mechanism. The interaction with GroES is the defining co-chaperonin interaction of the GroEL/ES system. Reason: "Protein binding" is uninformative per curation guidelines. The GroEL-GroES interaction is the core co-chaperonin interaction. This should be annotated as GO:0051087 "protein-folding chaperone binding" since GroES is the co-chaperonin partner. Proposed replacements: protein-folding chaperone binding
GO:0005515 protein binding	IPI PMID:11779463 ATP-bound states of GroEL captured by cryo-electron microsco...	MODIFY	Summary: IPI annotation for protein binding with GroES (P0A6F9). Study of ATP-bound states of GroEL captured by cryo-electron microscopy. Interaction with GroES. Reason: "Protein binding" is uninformative. This is a GroEL-GroES co-chaperonin interaction. Proposed replacements: protein-folding chaperone binding
GO:0005515 protein binding	IPI PMID:12071968 Identification and characterization of the Escherichia coli ...	KEEP AS NON CORE	Summary: IPI annotation for protein binding with the universal stress protein UspG/UP12 (P39177). This study identifies UP12 as a putative in vivo substrate of GroEL. This reflects a chaperone-substrate interaction. Reason: The IPI supports a true GroEL-UP12 client interaction, but this single client-binding row is uninformative as a molecular function and cannot be replaced by an activity term without changing what the experiment asserts.
GO:0005515 protein binding	IPI PMID:14517228 Role of the gamma-phosphate of ATP in triggering protein fol...	MODIFY	Summary: IPI annotation for protein binding with GroES (P0A6F9). Study on role of gamma-phosphate of ATP in triggering protein folding by GroEL-GroES. Co-chaperonin interaction. Reason: "Protein binding" is uninformative. This is the GroEL-GroES co-chaperonin interaction. Proposed replacements: protein-folding chaperone binding
GO:0005515 protein binding	IPI PMID:15313620 Exploring the structural dynamics of the E.coli chaperonin G...	MODIFY	Summary: IPI annotation for protein binding with GroES (P0A6F9). Structural dynamics study of GroEL using crystallographic refinement. Co-chaperonin interaction. Reason: "Protein binding" is uninformative. GroEL-GroES co-chaperonin interaction. Proposed replacements: protein-folding chaperone binding
GO:0005515 protein binding	IPI PMID:15690043 Interaction network containing conserved and essential prote...	KEEP AS NON CORE	Summary: IPI annotation for protein binding from a large-scale protein complex study in E. coli (Butland et al. 2005). Shows interactions with multiple proteins including GrpE (P09372), ribose-phosphate pyrophosphokinase Prs (P0A717), RecF (P0A7H0), UlaR (P0A9W0), MazG (P0AEY3), AceE (P0AFG8), etc. Many of these likely represent chaperone-substrate relationships in a large-scale interactome study. Reason: The heterogeneous affinity-purification partners are valid IPI observations without contradictory evidence, but they do not share one evidence-matched specific activity replacement. Retain the grouped signature as non-core.
GO:0005515 protein binding	IPI PMID:16239229 Leu309 plays a critical role in the encapsulation of substra...	MODIFY	Summary: IPI annotation for protein binding with GroES (P0A6F9). Study on Leu309 role in substrate encapsulation into the GroEL internal cavity. Co-chaperonin interaction. Reason: "Protein binding" is uninformative. GroEL-GroES co-chaperonin interaction. Proposed replacements: protein-folding chaperone binding
GO:0005515 protein binding	IPI PMID:16429154 Allosteric signaling of ATP hydrolysis in GroEL-GroES comple...	MODIFY	Summary: IPI annotation for protein binding with GroES (P0A6F9). Study on allosteric signaling of ATP hydrolysis in GroEL-GroES complexes. Co-chaperonin interaction. Reason: "Protein binding" is uninformative. GroEL-GroES co-chaperonin interaction. Proposed replacements: protein-folding chaperone binding
GO:0005515 protein binding	IPI PMID:16606699 Large-scale identification of protein-protein interaction of...	KEEP AS NON CORE	Summary: IPI annotation for protein binding from a large-scale interactome study (Arifuzzaman et al. 2006). Shows interactions with numerous proteins. As a chaperonin that assists folding of ~10-15% of the proteome, many of these represent chaperone-substrate relationships. Reason: This high-throughput grouped signature contains heterogeneous physical partners. The IPI observations are retained, but no single more-specific GO term describes all partners without converting binding evidence into an activity claim.
GO:0005515 protein binding	IPI PMID:16977315 Fast-scanning atomic force microscopy reveals the ATP/ADP-de...	MODIFY	Summary: IPI annotation for protein binding with GroES (P0A6F9). Fast-scanning AFM study of ATP/ADP-dependent conformational changes of GroEL. Reason: "Protein binding" is uninformative. GroEL-GroES co-chaperonin interaction. Proposed replacements: protein-folding chaperone binding
GO:0005515 protein binding	IPI PMID:17032756 Proton-proton Overhauser NMR spectroscopy with polypeptide c...	MODIFY	Summary: IPI annotation for protein binding with GroES (P0A6F9). NMR spectroscopy study of polypeptide chains in large GroEL structures. Reason: "Protein binding" is uninformative. GroEL-GroES co-chaperonin interaction. Proposed replacements: protein-folding chaperone binding
GO:0005515 protein binding	IPI PMID:17098196 An expanded conformation of single-ring GroEL-GroES complex ...	MODIFY	Summary: IPI annotation for protein binding with GroES (P0A6F9). Study showing expanded conformation of single-ring GroEL-GroES complex encapsulating an 86 kDa substrate. Reason: "Protein binding" is uninformative. GroEL-GroES co-chaperonin interaction. Proposed replacements: protein-folding chaperone binding
GO:0005515 protein binding	IPI PMID:17968012 Analysis of sigma32 mutants defective in chaperone-mediated ...	KEEP AS NON CORE	Summary: IPI annotation for protein binding with sigma-32/RpoH (P0AGB3). Study on sigma-32 mutants defective in chaperone-mediated feedback control. GroEL binds sigma-32 to regulate the heat shock response -- this is a regulatory chaperone-substrate interaction. Reason: The abstract supports GroEL association with sigma32 in feedback control, but the IPI alone does not establish a distinct binding-activity term. Retain this biologically meaningful regulatory interaction as non-core.
GO:0005515 protein binding	IPI PMID:18394994 Monitoring protein conformation along the pathway of chapero...	KEEP AS NON CORE	Summary: IPI annotation for protein binding with GroES (P0A6F9) and the maltose-binding protein MalE/MBP (P0AEX9). Study monitoring protein conformation along the pathway of chaperonin-assisted folding. Reason: This grouped signature combines the GroES co-chaperonin and a client protein. Because the partners represent different roles, forcing one replacement across both would overstate the row; retain the true interactions as non-core.
GO:0005515 protein binding	IPI PMID:18418386 Essential role of the chaperonin folding compartment in vivo...	KEEP AS NON CORE	Summary: IPI annotation for protein binding with bovine thiosulfate sulfurtransferase TST/rhodanese (P00586; xenogeneic) and E. coli S-adenosylmethionine synthase MetK (P0A817). Study on essential role of the chaperonin folding compartment in vivo (Tang et al. 2008). These are chaperone-substrate interactions. Reason: These are experimentally observed client interactions, but an IPI row cannot by itself be rewritten as ATP-dependent chaperone activity. Retain the grouped client-binding evidence as non-core.
GO:0005515 protein binding	IPI PMID:18568038 GroEL as a molecular scaffold for structural analysis of the...	MARK AS OVER ANNOTATED	Summary: IPI annotation for protein binding with anthrax PA63 pore (P13423). Study using GroEL as a molecular scaffold for structural analysis. This is an in vitro structural biology application, not a physiological chaperone-substrate interaction. Reason: This interaction reflects an in vitro structural biology experiment where GroEL was used as a scaffold for cryo-EM analysis of the anthrax toxin pore. It does not represent a physiological protein-protein interaction or chaperone-substrate relationship. The annotation is over-annotated from an experimental artifact.
GO:0005515 protein binding	IPI PMID:20308583 Out-of-equilibrium conformational cycling of GroEL under sat...	MODIFY	Summary: IPI annotation for protein binding with GroES (P0A6F9). Study of out-of-equilibrium conformational cycling of GroEL under saturating ATP. Co-chaperonin interaction. Reason: "Protein binding" is uninformative. GroEL-GroES co-chaperonin interaction. Proposed replacements: protein-folding chaperone binding
GO:0005515 protein binding	IPI PMID:20959808 Polypeptide in the chaperonin cage partly protrudes out and ...	MODIFY	Summary: IPI annotation for protein binding with GroES (P0A6F9). Study of polypeptide behavior in the chaperonin cage. Co-chaperonin interaction. Reason: "Protein binding" is uninformative. GroEL-GroES co-chaperonin interaction. Proposed replacements: protein-folding chaperone binding
GO:0005515 protein binding	IPI PMID:23746846 Visualizing GroEL/ES in the act of encapsulating a folding p...	MODIFY	Summary: IPI annotation for protein binding with GroES (P0A6F9). Cryo-EM study visualizing GroEL/ES in the act of encapsulating a folding protein. Co-chaperonin interaction. Reason: "Protein binding" is uninformative. GroEL-GroES co-chaperonin interaction. Proposed replacements: protein-folding chaperone binding
GO:0005515 protein binding	IPI PMID:24561554 The binary protein-protein interaction landscape of Escheric...	KEEP AS NON CORE	Summary: IPI annotation for protein binding from a binary protein-protein interaction landscape study of E. coli (Rajagopala et al. 2014). Shows interactions with multiple proteins. Large-scale interactome data, likely chaperone-substrate interactions. Reason: The yeast two-hybrid partners are affirmative physical-interaction observations, but this heterogeneous set does not justify one mechanistic replacement. Retain as non-core rather than infer chaperone activity from IPI alone.
GO:0005515 protein binding	IPI PMID:26545493 GroEL to DnaK chaperone network behind the stability modulat...	KEEP AS NON CORE	Summary: IPI annotation for protein binding with sigma-32/RpoH (P0AGB3). Study on GroEL to DnaK chaperone network behind sigma-32 stability modulation. Regulatory chaperone-substrate interaction. Reason: The abstract directly reports in vivo GroEL-sigma32 association and places GroEL upstream of DnaK, but no more-specific binding MF is established. Retain the true regulatory interaction as non-core.
GO:0005515 protein binding	IPI PMID:8618836 The protein-folding activity of chaperonins correlates with ...	MODIFY	Summary: IPI annotation for protein binding with GroES (P0A6F9). Study showing protein-folding activity of chaperonins correlates with the symmetric GroEL14(GroES7)2 heterooligomer (Azem et al. 1995). Reason: "Protein binding" is uninformative. GroEL-GroES co-chaperonin interaction. Proposed replacements: protein-folding chaperone binding
GO:0005515 protein binding	IPI PMID:9285585 The crystal structure of the asymmetric GroEL-GroES-(ADP)7 c...	MODIFY	Summary: IPI annotation for protein binding with GroES (P0A6F9). Crystal structure of the asymmetric GroEL-GroES-(ADP)7 chaperonin complex (Xu et al. 1997). Landmark structural study of the co-chaperonin interaction. Reason: "Protein binding" is uninformative. This is the landmark GroEL-GroES crystal structure. Proposed replacements: protein-folding chaperone binding Supporting Evidence: PMID:9285585 The crystal structure of the asymmetric GroEL-GroES-(ADP)7 chaperonin complex.
GO:0005515 protein binding	IPI PMID:9878052 Compartmentation of protein folding in vivo: sequestration o...	KEEP AS NON CORE	Summary: IPI annotation with Saccharomyces cerevisiae ACT1/actin (P60010). The study examines actin folding by the yeast TRiC-GimC system and uses a heterologous chaperonin trap, yielding a cross-system GroEL-actin interaction. Reason: The cached abstract is a yeast TRiC/GimC study that uses a heterologous chaperonin trap; the experimental IPI is retained with curator deference, but this cross-system client interaction is not a core GroEL function annotation.
GO:0042802 identical protein binding	IPI PMID:16858726 A complexomic study of Escherichia coli using two-dimensiona...	ACCEPT	Summary: IPI for identical protein binding (GroEL-GroEL self-interaction). GroEL forms a homo-tetradecameric double-ring structure. Blue native/SDS-PAGE complexomic study. Reason: GroEL's homo-oligomeric self-assembly is a core structural feature. The 14-subunit double-ring architecture requires extensive GroEL-GroEL interactions both within and between rings (PMID:7935790). This annotation is valid.
GO:0042802 identical protein binding	IPI PMID:17098196 An expanded conformation of single-ring GroEL-GroES complex ...	ACCEPT	Summary: IPI for identical protein binding. Single-ring GroEL-GroES complex study showing GroEL self-interaction. Reason: Valid annotation reflecting GroEL homo-oligomerization.
GO:0042802 identical protein binding	IPI PMID:18334219 De novo backbone trace of GroEL from single particle electro...	ACCEPT	Summary: IPI for identical protein binding. Backbone trace of GroEL from cryo-EM showing GroEL self-interaction in the oligomeric complex. Reason: Valid annotation reflecting GroEL homo-oligomerization.
GO:0042802 identical protein binding	IPI PMID:18568038 GroEL as a molecular scaffold for structural analysis of the...	ACCEPT	Summary: IPI for identical protein binding using GroEL as a molecular scaffold for anthrax toxin pore structural analysis. GroEL self-interaction detected. Reason: The paper uses intact double-ring GroEL as an experimental scaffold and explicitly reasons about negative cooperativity between its rings. Together with definitive GroEL structures, this supports the core oligomeric interaction. Supporting Evidence: PMID:18568038 Fewer than 1% of the GroEL–pore complexes had PA pore bound at both ends of GroEL, suggesting negative cooperativity between two rings of GroEL
GO:0042802 identical protein binding	IPI PMID:22575645 Fibrillogenic propensity of the GroEL apical domain: a Janus...	ACCEPT	Summary: IPI for identical protein binding. Study on fibrillogenic propensity of the GroEL apical domain -- the apical domain minichaperone can self-associate. Reason: GroEL self-interaction is a well-established structural property.
GO:0042802 identical protein binding	IPI PMID:7935790 The crystal structure of the bacterial chaperonin GroEL at 2...	ACCEPT	Summary: IPI for identical protein binding from the landmark crystal structure of GroEL at 2.8 A (Braig et al. 1994) showing the homo-tetradecameric structure. Reason: The crystal structure (PMID:7935790) is the definitive demonstration of GroEL's homo-oligomeric architecture. Core structural annotation. Supporting Evidence: PMID:7935790 The crystal structure of the bacterial chaperonin GroEL at 2.8 A.
GO:0042802 identical protein binding	IPI PMID:8618836 The protein-folding activity of chaperonins correlates with ...	ACCEPT	Summary: IPI for identical protein binding. Study on symmetric GroEL14(GroES7)2 heterooligomer demonstrating GroEL self-interaction. Reason: Valid annotation reflecting GroEL homo-oligomerization.
GO:0042802 identical protein binding	IPI PMID:9878052 Compartmentation of protein folding in vivo: sequestration o...	ACCEPT	Summary: IPI for identical protein binding. Study on protein folding compartmentation in vivo. GroEL self-interaction detected. Reason: Valid annotation reflecting GroEL homo-oligomerization.
GO:0006457 protein folding	IDA PMID:14517228 Role of the gamma-phosphate of ATP in triggering protein fol...	ACCEPT	Summary: IDA annotation for protein folding from ComplexPortal (PMID:14517228). This study demonstrates the role of the gamma-phosphate of ATP in triggering protein folding by GroEL-GroES, providing direct assay evidence for the protein folding activity. Reason: Direct assay evidence for GroEL's protein folding activity. PMID:14517228 demonstrates that gamma-phosphate binding triggers conformational changes enabling productive substrate protein folding. This is a core annotation.
GO:0009314 response to radiation	IMP PMID:27718375 Screen for genes involved in radiation survival of Escherich...	KEEP AS NON CORE	Summary: IMP annotation for response to radiation from a systematic screen for genes involved in radiation survival of E. coli (Sargentini et al. 2016). groEL mutations affect radiation survival, likely through indirect effects on protein homeostasis under radiation stress. Reason: GroEL's role in radiation resistance is likely an indirect consequence of its general protein folding chaperone function rather than a specific radiation response pathway. Radiation causes protein damage and aggregation, and GroEL helps refold or prevent aggregation of damaged proteins. This is a pleiotropic effect, not a core function.
GO:1990220 GroEL-GroES complex	IDA PMID:9285585 The crystal structure of the asymmetric GroEL-GroES-(ADP)7 c...	ACCEPT	Summary: IDA annotation for GroEL-GroES complex from the crystal structure of the asymmetric GroEL-GroES-(ADP)7 complex (Xu et al. 1997). This is definitive structural evidence. Reason: The 3.0 A crystal structure (PMID:9285585) directly demonstrates GroEL as a component of the GroEL-GroES complex. This is the strongest possible evidence for this CC annotation. Supporting Evidence: PMID:9285585 The crystal structure of the asymmetric GroEL-GroES-(ADP)7 chaperonin complex.
GO:0000287 magnesium ion binding	IDA PMID:8564544 The 2.4 A crystal structure of the bacterial chaperonin GroE...	ACCEPT	Summary: IDA annotation for magnesium ion binding from the crystal structure of GroEL complexed with ATPgammaS (Boisvert et al. 1996). Mg2+ is coordinated in the nucleotide binding site and is required for ATP hydrolysis. Reason: The crystal structure at 2.4 A (PMID:8564544) directly shows Mg2+ coordination in the nucleotide binding pocket. Mg-ATP is required for GroEL/ES chaperonin function (UniProt: "Activity of the GroEL-GroES chaperonin complex requires Mg-ATP"). Supporting Evidence: PMID:8564544 The 2.4 A crystal structure of the bacterial chaperonin GroEL complexed with ATP gamma S.
GO:0005515 protein binding	IMP PMID:7935796 Residues in chaperonin GroEL required for polypeptide bindin...	MODIFY	Summary: IMP annotation for protein binding from Fenton et al. 1994, which identifies residues in GroEL required for polypeptide binding and release through mutational analysis. Hydrophobic residues on the inside surface of the apical domain form the polypeptide binding site. Reason: Generic protein binding is uninformative. This landmark study identifies the substrate polypeptide binding site on the apical domain interior. The molecular function being demonstrated is chaperone activity -- binding to unfolded/non-native polypeptides as part of the folding cycle. Unlike a simple IPI, the IMP is based on mutations that alter polypeptide binding, ATP hydrolysis, and productive release, so replacement by the coupled ATP-dependent activity is evidence-matched. Proposed replacements: ATP-dependent protein folding chaperone Supporting Evidence: PMID:7935796 Our functional tests identify a putative polypeptide-binding site on the inside surface of the apical domain, facing the central channel, consisting of hydrophobic residues. These same residues are essential for binding of the co-chaperonin GroES, which is required for productive polypeptide release.
GO:0005524 ATP binding	IDA PMID:8564544 The 2.4 A crystal structure of the bacterial chaperonin GroE...	ACCEPT	Summary: IDA annotation for ATP binding from the crystal structure of GroEL complexed with ATPgammaS at 2.4 A (Boisvert et al. 1996). Directly shows nucleotide binding in the equatorial domain. Reason: Direct structural evidence for ATP binding from the ATPgammaS co-crystal structure. This is definitive IDA evidence for a core molecular function of GroEL. Supporting Evidence: PMID:8564544 The 2.4 A crystal structure of the bacterial chaperonin GroEL complexed with ATP gamma S.
GO:0042802 identical protein binding	IDA PMID:7935790 The crystal structure of the bacterial chaperonin GroEL at 2...	ACCEPT	Summary: IDA annotation for identical protein binding from the 2.8 A crystal structure of GroEL (Braig et al. 1994) showing the homo-tetradecameric double-ring structure. Reason: The crystal structure directly demonstrates GroEL-GroEL subunit interactions forming the heptameric rings and the double-ring barrel. This is definitive evidence for homo-oligomeric self-interaction. Supporting Evidence: PMID:7935790 The crystal structure of the bacterial chaperonin GroEL at 2.8 A.
GO:0051082 unfolded protein binding	IMP PMID:7935796 Residues in chaperonin GroEL required for polypeptide bindin...	MODIFY	Summary: IMP annotation for unfolded protein binding from Fenton et al. 1994. Mutations in hydrophobic residues of the apical domain interior abolish polypeptide binding, demonstrating that GroEL binds non-native polypeptides. However, this binding is part of the active folding chaperone mechanism, not merely passive binding. Reason: GO:0051082 is now formally obsolete (go-ontology#30962). While this study demonstrates that GroEL binds unfolded/non-native polypeptides, the binding is part of the active ATP-dependent folding cycle. The appropriate term is GO:0140662 "ATP-dependent protein folding chaperone". PMID:7935796 states that the same residues are "essential for binding of the co-chaperonin GroES, which is required for productive polypeptide release" -- demonstrating that binding is coupled to the folding/release cycle. Proposed replacements: ATP-dependent protein folding chaperone Supporting Evidence: PMID:7935796 Chaperonins are ring-shaped protein complexes that are essential in the cell, mediating ATP-dependent polypeptide folding in a variety of compartments. file:projects/UNFOLDED_PROTEIN_BINDING.md GO:0051082 is now formally obsolete
GO:0051082 unfolded protein binding	IDA PMID:8097882 A polypeptide bound by the chaperonin groEL is localized wit...	MODIFY	Summary: IDA annotation for unfolded protein binding from Braig et al. 1993. STEM microscopy shows gold-labeled DHFR folding intermediates bound inside the central cavity of GroEL. This directly demonstrates that unfolded polypeptides are bound within the chaperonin cage. However, this binding is part of the active folding mechanism. Reason: GO:0051082 is now formally obsolete (go-ontology#30962). This landmark study (PMID:8097882) shows substrate localization within the central cavity, which is the defining feature of the chaperonin folding mechanism. The appropriate replacement is GO:0140662 "ATP-dependent protein folding chaperone" because the binding demonstrated is part of the Anfinsen cage foldase mechanism, not merely passive unfolded protein binding. Proposed replacements: ATP-dependent protein folding chaperone Supporting Evidence: PMID:8097882 We conclude that folding intermediates are bound inside central cavities within individual chaperonin rings. In this potentially sequestered location, folding intermediates with a compact conformation can be bound at multiple sites by surrounding monomeric members of the ring; localization of folding within the cavity could also facilitate rebinding of structures that initially fail to incorporate properly into the folding protein. file:projects/UNFOLDED_PROTEIN_BINDING.md GO:0051082 is now formally obsolete
GO:0005829 cytosol	IDA PMID:18304323 Protein abundance profiling of the Escherichia coli cytosol.	ACCEPT	Summary: IDA annotation for cytosol from protein abundance profiling of the E. coli cytosol (Ishihama et al. 2008). GroEL was identified as one of the most abundant cytosolic proteins. Reason: Direct proteomics evidence for cytosolic localization. GroEL is one of the most abundant proteins in the E. coli cytosol. UniProt confirms cytoplasmic localization. Supporting Evidence: PMID:18304323 we identified 1103 proteins from the cytosolic fraction of the Escherichia coli strain MC4100
GO:0019068 virion assembly	IMP PMID:7015340 Identification of a second Escherichia coli groE gene whose ...	KEEP AS NON CORE	Summary: IMP annotation for virion assembly from Tilly et al. 1981. groEL mutations prevent normal bacteriophage lambda head assembly and T4 morphogenesis. GroEL was originally named "groE" because it was required for bacteriophage growth. Reason: GroEL's role in virion assembly is historical and well-documented (this is where the gene name comes from). However, it is not a "core" function of GroEL in the sense that GroEL is not a dedicated viral assembly factor -- rather, phage capsid proteins are obligate GroEL substrates that require chaperonin-assisted folding. The virion assembly phenotype is a downstream consequence of the protein folding chaperone activity. Supporting Evidence: PMID:7015340 Previous work has uncovered the existence of an Escherichia coli locus, groE, that is essential for bacterial growth, lambda phage and T4 phage head morphogenesis, and T5 phage tail assembly.
GO:0009408 response to heat	IEP PMID:8349564 Characterization of twenty-six new heat shock genes of Esche...	ACCEPT	Summary: IEP annotation for response to heat based on expression pattern evidence. groEL expression is induced during heat shock (PMID:8349564). Consistent with the IBA annotation for the same term. Reason: GroEL is a heat shock protein (Hsp60) whose expression is strongly upregulated during thermal stress. The IEP evidence from expression profiling is appropriate and consistent with GroEL's established role as a heat shock protein.
GO:0005524 ATP binding	IDA PMID:9285585 The crystal structure of the asymmetric GroEL-GroES-(ADP)7 c...	ACCEPT	Summary: IDA annotation for ATP binding from the crystal structure of the asymmetric GroEL-GroES-(ADP)7 complex (Xu et al. 1997). Shows ADP (product of ATP hydrolysis) bound in the equatorial domain of the cis ring. Reason: The crystal structure at 3.0 A (PMID:9285585) directly demonstrates nucleotide binding. This is definitive structural evidence, consistent with the other IDA annotation from PMID:8564544. Supporting Evidence: PMID:9285585 The crystal structure of the asymmetric GroEL-GroES-(ADP)7 chaperonin complex.
GO:0006457 protein folding	IMP PMID:2573517 Effects of mutations in heat-shock genes groES and groEL on ...	ACCEPT	Summary: IMP annotation for protein folding from Kusukawa et al. 1989. Temperature-sensitive groEL mutations cause defective protein export, demonstrating GroEL's in vivo role in protein folding/maturation. This was one of the early demonstrations that GroEL functions as a chaperone in vivo. Reason: Early evidence for an in vivo GroEL chaperone role. The abstract directly reports defective export of plasmid-encoded beta-lactamase and interprets this as client-specific chaperone assistance; it does not directly assay global misfolding. Supporting Evidence: PMID:2573517 temperature-sensitive mutations in groES and groEL genes cause defective export of the plasmid-encoded beta-lactamase (Bla) in vivo... these results suggest that both GroES and GroEL proteins possess a chaperone function by which they facilitate export of Bla.
GO:0016887 ATP hydrolysis activity	IDA PMID:379350 Purification and properties of groE, a host protein involved...	ACCEPT	Summary: IDA annotation for ATP hydrolysis activity from Hendrix 1979, the original purification and characterization of the groE protein. This study demonstrated ATPase activity of the purified protein. GroEL's ATPase activity drives the chaperonin conformational cycle. Reason: GroEL has intrinsic ATPase activity that drives the chaperonin cycle. UniProt notes "GroEL shows ATPase activity (PubMed:1676490, PubMed:379350, PubMed:9285593)." The ATP hydrolysis is essential for the conformational changes that allow substrate release and forward progression of the folding cycle (PMID:9285593). This is a mechanistic subactivity of the core ATP-dependent folding-chaperone function, rather than a separate biological endpoint.
GO:0016020 membrane	HDA PMID:16858726 A complexomic study of Escherichia coli using two-dimensiona...	KEEP AS NON CORE	Summary: HDA annotation for membrane localization from a complexomic study using 2D blue native/SDS-PAGE (Maddalo et al. 2006). GroEL was detected in membrane fractions. Reason: GroEL is primarily a cytosolic protein, but has been detected associated with membranes in some studies. This likely reflects GroEL's role in assisting folding of membrane-associated or membrane-translocating substrates, or its reported polar localization. UniProt states GroEL is in the cytoplasm, with foci near cell poles. The membrane association is not a core localization but may reflect physiological substrate interactions.
GO:0005829 cytosol	HDA PMID:16858726 A complexomic study of Escherichia coli using two-dimensiona...	ACCEPT	Summary: HDA annotation for cytosol from the same complexomic study (Maddalo et al. 2006). GroEL is one of the most abundant cytosolic proteins. Reason: GroEL is unambiguously a cytosolic protein. This HDA annotation is consistent with the IDA annotation from PMID:18304323 and UniProt subcellular location data.

Gene Description

Existing Annotations Review

Core Functions

References

Deep Research

Falcon

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Notes

Bioreason Rl Predictions

Bioreason Rl Review

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