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 protein folding defects in vivo. 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.
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. 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. 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 being obsoleted. 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 being obsoleted as part of the unfolded protein binding obsoletion project. 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.
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. Supporting Evidence: PMID:9285585 The crystal structure of the asymmetric GroEL-GroES-(ADP)7 chaperonin complex.
GO:0000166 nucleotide binding	IEA GO_REF:0000043	ACCEPT	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 (it binds ATP and ADP). This is correctly inferred from the UniProt keyword. While more general than the specific ATP binding annotation, it is not wrong. The IBA/IDA annotations for ATP binding provide the more specific annotation.
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	ACCEPT	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: Correct electronic inference. GroEL is a cytoplasmic protein. UniProt states "Cytoplasm" as subcellular location. The broader "cytoplasm" term is not wrong even though a more specific "cytosol" annotation exists with IDA evidence.
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	ACCEPT	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, placing it in the isomerase class (EC 5). The IEA mapping from the Isomerase keyword to GO:0016853 is technically correct. However, the more specific GO:0140662 "ATP-dependent protein folding chaperone" annotation better captures the specific activity.
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 being obsoleted. 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 ...	MODIFY	Summary: IPI annotation for protein binding with UP12/YjgF (P39177). This study identifies YjgF as a putative in vivo substrate of GroEL. This reflects a chaperone-substrate interaction. Reason: "Protein binding" is uninformative. This is a chaperone-substrate interaction and is better captured by GO:0044183 or GO:0140662 (protein folding chaperone / ATP-dependent protein folding chaperone). However, since the IPI evidence shows a physical interaction with a substrate, modifying to the chaperone activity term is most appropriate. Proposed replacements: ATP-dependent protein folding chaperone
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...	MODIFY	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), KasA (P0A717), RpsA (P0A7H0), DegP (P0A9W0), MalE (P0AEY3), AceE (P0AFG8), etc. Many of these likely represent chaperone-substrate relationships in a large-scale interactome study. Reason: "Protein binding" is uninformative. These large-scale interactome hits likely include both genuine chaperone-substrate interactions and co-complex partners. For a chaperonin that interacts with 10-15% of the proteome, generic "protein binding" is essentially meaningless. The core molecular function is better captured by GO:0140662. Proposed replacements: ATP-dependent protein folding chaperone
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...	MODIFY	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: "Protein binding" is uninformative. Large-scale interactome study detecting many chaperone-substrate interactions. The core function is better captured by GO:0140662. Proposed replacements: ATP-dependent protein folding chaperone
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 ...	MODIFY	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: "Protein binding" is uninformative. The GroEL-sigma32 interaction reflects GroEL's role as a chaperone that sequesters sigma-32 under non-stress conditions, contributing to heat shock response regulation. This is a chaperone-substrate interaction. Proposed replacements: ATP-dependent protein folding chaperone
GO:0005515 protein binding	IPI PMID:18394994 Monitoring protein conformation along the pathway of chapero...	MODIFY	Summary: IPI annotation for protein binding with GroES (P0A6F9) and MalZ (P0AEX9). Study monitoring protein conformation along the pathway of chaperonin-assisted folding. Reason: "Protein binding" is uninformative. Interactions reflect GroEL-GroES co-chaperonin and GroEL-substrate (MalZ) chaperone interactions. Proposed replacements: ATP-dependent protein folding chaperone
GO:0005515 protein binding	IPI PMID:18418386 Essential role of the chaperonin folding compartment in vivo...	MODIFY	Summary: IPI annotation for protein binding with OrnC (P00586) and DegP (P0A817). Study on essential role of the chaperonin folding compartment in vivo (Tang et al. 2008). These are chaperone-substrate interactions. Reason: "Protein binding" is uninformative. These interactions reflect GroEL's chaperone-substrate relationships in the essential folding compartment. GO:0140662 better captures this. Proposed replacements: ATP-dependent protein folding chaperone
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...	MODIFY	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: "Protein binding" is uninformative. Large-scale interactome study. For a chaperonin, these interactions represent chaperone-substrate relationships. Proposed replacements: ATP-dependent protein folding chaperone
GO:0005515 protein binding	IPI PMID:26545493 GroEL to DnaK chaperone network behind the stability modulat...	MODIFY	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: "Protein binding" is uninformative. GroEL-sigma32 regulatory chaperone interaction. Proposed replacements: ATP-dependent protein folding chaperone
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...	MODIFY	Summary: IPI annotation for protein binding with GroES homolog/Gim complex component (P60010). Study on compartmentation of protein folding in vivo -- sequestration of non-native polypeptide by the chaperonin-GimC system. Chaperone-substrate interaction. Reason: "Protein binding" is uninformative. Reflects chaperonin-substrate interaction in the context of protein folding quality control. Proposed replacements: ATP-dependent protein folding chaperone
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: GroEL self-interaction is valid regardless of the experimental context.
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 (Byrne et al. 2014). 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: "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. Better annotated as GO:0140662. 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 being obsoleted. 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.
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 being obsoleted. 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.
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.
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 and important evidence for GroEL's in vivo protein folding role. groEL mutations cause protein misfolding/export defects, demonstrating the chaperonin is required for proper protein folding in the cell. 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 the forward progression of the folding cycle, although it is not required for the folding reaction itself (PMID:9285593). This is a core molecular function.
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.
GO:0140662 ATP-dependent protein folding chaperone	IDA PMID:9285585 The crystal structure of the asymmetric GroEL-GroES-(ADP)7 c...	NEW	Summary: NEW annotation. GroEL is the prototypical ATP-dependent protein folding chaperone. The crystal structure of the GroEL-GroES-(ADP)7 complex (PMID:9285585) together with the catalytic activity annotation (EC 5.6.1.7: ATP + H2O + unfolded polypeptide = ADP + phosphate + folded polypeptide) provides direct evidence for this molecular function. This term is already annotated via IEA but lacks direct experimental support in the current annotation set. Reason: GO:0140662 "ATP-dependent protein folding chaperone" is the single most accurate molecular function term for GroEL. It captures both the ATP dependence and the protein folding chaperone activity. UniProt assigns EC 5.6.1.7 with evidence from PMID:9285585 and PMID:9285593. While an IEA annotation exists, there is no experimental annotation for this term in the current GOA set. Given that multiple GO:0051082 annotations are being recommended for modification to this term, having an explicit experimental annotation is important. Supporting Evidence: PMID:9285585 The crystal structure of the asymmetric GroEL-GroES-(ADP)7 chaperonin complex. PMID:7935796 Chaperonins are ring-shaped protein complexes that are essential in the cell, mediating ATP-dependent polypeptide folding in a variety of compartments.

Core Functions

GroEL is the prototypical ATP-dependent protein folding chaperone (EC 5.6.1.7). It catalyzes the reaction: ATP + H2O + unfolded polypeptide = ADP + phosphate + folded polypeptide within the GroEL-GroES complex in the cytosol. Multiple crystal structures (PMID:8564544, PMID:9285585), mutational analyses (PMID:7935796), and functional studies establish this as the core molecular function. GroEL also has intrinsic ATPase activity (PMID:379350) that drives the chaperonin conformational cycle. Approximately 10-15% of E. coli cytoplasmic proteins are obligate GroEL substrates. groEL mutations cause protein misfolding in vivo (PMID:2573517).

Molecular Function:

ATP-dependent protein folding chaperone

Directly Involved In:

protein folding

Cellular Locations:

cytosol

In Complex:

GroEL-GroES complex

Supporting Evidence:

PMID:9285585
The crystal structure of the asymmetric GroEL-GroES-(ADP)7 chaperonin complex.
PMID:7935796
Chaperonins are ring-shaped protein complexes that are essential in the cell, mediating ATP-dependent polypeptide folding in a variety of compartments.
PMID:2573517
temperature-sensitive mutations in groES and groEL genes cause defective export of the plasmid-encoded beta-lactamase (Bla) in vivo.

References

GO_REF:0000002

Gene Ontology annotation through association of InterPro records with GO terms

GO_REF:0000033

Annotation inferences using phylogenetic trees

GO_REF:0000043

Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword mapping

GO_REF:0000104

Electronic Gene Ontology annotations created by transferring manual GO annotations between related proteins based on shared sequence features

GO_REF:0000120

Combined Automated Annotation using Multiple IEA Methods

PMID:10077571

GroES in the asymmetric GroEL14-GroES7 complex exchanges via an associative mechanism.

Demonstrates dynamic GroES exchange on the GroEL complex via an associative mechanism.

PMID:11779463

ATP-bound states of GroEL captured by cryo-electron microscopy.

Cryo-EM reveals ATP-bound conformational states of GroEL.

PMID:12071968

Identification and characterization of the Escherichia coli stress protein UP12, a putative in vivo substrate of GroEL.

Identifies YjgF/UP12 as an in vivo substrate of GroEL.

PMID:14517228

Role of the gamma-phosphate of ATP in triggering protein folding by GroEL-GroES: function, structure and energetics.

Demonstrates that gamma-phosphate of ATP is required to trigger productive folding by GroEL-GroES.

PMID:15313620

Exploring the structural dynamics of the E.coli chaperonin GroEL using translation-libration-screw crystallographic refinement of intermediate states.

Reveals structural dynamics of GroEL intermediate conformational states.

PMID:15690043

Interaction network containing conserved and essential protein complexes in Escherichia coli.

Large-scale identification of E. coli protein complexes, including GroEL interactions with multiple substrates.

PMID:16239229

Leu309 plays a critical role in the encapsulation of substrate protein into the internal cavity of GroEL.

Identifies Leu309 as critical for substrate encapsulation in the GroEL cavity.

PMID:16429154

Allosteric signaling of ATP hydrolysis in GroEL-GroES complexes.

Demonstrates allosteric communication of ATP hydrolysis between GroEL rings.

PMID:16606699

Large-scale identification of protein-protein interaction of Escherichia coli K-12.

Large-scale E. coli interactome study identifying GroEL interactions with many proteins.

PMID:16858726

A complexomic study of Escherichia coli using two-dimensional blue native/SDS polyacrylamide gel electrophoresis.

Identifies GroEL in both cytosolic and membrane-associated protein complexes.

PMID:16977315

Fast-scanning atomic force microscopy reveals the ATP/ADP-dependent conformational changes of GroEL.

AFM imaging shows ATP/ADP-dependent conformational changes in GroEL.

PMID:17032756

Proton-proton Overhauser NMR spectroscopy with polypeptide chains in large structures.

NMR study of polypeptide behavior in GroEL complexes.

PMID:17098196

An expanded conformation of single-ring GroEL-GroES complex encapsulates an 86 kDa substrate.

Shows that single-ring GroEL-GroES can encapsulate large substrates up to 86 kDa.

PMID:17968012

Analysis of sigma32 mutants defective in chaperone-mediated feedback control reveals unexpected complexity of the heat shock response.

Demonstrates GroEL-sigma32 interaction in heat shock response regulation.

PMID:18304323

Protein abundance profiling of the Escherichia coli cytosol.

Identifies GroEL as one of the most abundant cytosolic proteins in E. coli.

PMID:18334219

De novo backbone trace of GroEL from single particle electron cryomicroscopy.

High-resolution cryo-EM backbone trace of GroEL structure.

PMID:18394994

Monitoring protein conformation along the pathway of chaperonin-assisted folding.

Tracks substrate protein conformational changes during GroEL-assisted folding.

PMID:18418386

Essential role of the chaperonin folding compartment in vivo.

Demonstrates that the enclosed GroEL cavity is essential for in vivo protein folding activity.

PMID:18568038

GroEL as a molecular scaffold for structural analysis of the anthrax toxin pore.

GroEL used as structural scaffold in cryo-EM, not a physiological interaction.

PMID:20308583

Out-of-equilibrium conformational cycling of GroEL under saturating ATP concentrations.

Reveals non-equilibrium conformational cycling of GroEL-GroES.

PMID:20959808

Polypeptide in the chaperonin cage partly protrudes out and then folds inside or escapes outside.

Shows substrate polypeptide behavior during encapsulation in the GroEL cage.

PMID:22575645

Fibrillogenic propensity of the GroEL apical domain: a Janus-faced minichaperone.

Characterizes GroEL apical domain self-association and fibrillogenic properties.

PMID:23746846

Visualizing GroEL/ES in the act of encapsulating a folding protein.

Cryo-EM visualization of GroEL/ES actively encapsulating a substrate protein.

PMID:24561554

The binary protein-protein interaction landscape of Escherichia coli.

Large-scale binary interactome study identifying GroEL interaction partners.

PMID:2573517

Effects of mutations in heat-shock genes groES and groEL on protein export in Escherichia coli.

groEL mutations cause defective protein export, demonstrating in vivo chaperone function.

PMID:26545493

GroEL to DnaK chaperone network behind the stability modulation of σ(32) at physiological temperature in Escherichia coli.

Demonstrates GroEL-DnaK chaperone network in sigma-32 stability regulation.

PMID:27718375

Screen for genes involved in radiation survival of Escherichia coli and construction of a reference database.

groEL identified in screen for radiation survival genes.

PMID:379350

Purification and properties of groE, a host protein involved in bacteriophage assembly.

Original purification of GroE showing ATPase activity and role in phage assembly.

PMID:7015340

Identification of a second Escherichia coli groE gene whose product is necessary for bacteriophage morphogenesis.

Identifies groEL and groES as two genes in the groE locus, both essential for phage morphogenesis and bacterial growth.

PMID:7935790

The crystal structure of the bacterial chaperonin GroEL at 2.8 A.

Landmark crystal structure reveals the homo-tetradecameric double-ring architecture of GroEL with three domains per subunit.

PMID:7935796

Residues in chaperonin GroEL required for polypeptide binding and release.

Identifies hydrophobic polypeptide binding site on the inner surface of the apical domain. Same residues required for GroES binding. Asp87 essential for ATP hydrolysis.

PMID:8097882

A polypeptide bound by the chaperonin groEL is localized within a central cavity.

STEM microscopy shows gold-labeled DHFR folding intermediates bound inside the central cavity of GroEL rings, establishing the Anfinsen cage concept.

PMID:8349564

Characterization of twenty-six new heat shock genes of Escherichia coli.

Characterizes groEL as a heat shock gene with expression induced by thermal stress.

PMID:8564544

The 2.4 A crystal structure of the bacterial chaperonin GroEL complexed with ATP gamma S.

Crystal structure shows ATPgammaS and Mg2+ binding in the equatorial domain of GroEL.

PMID:8618836

The protein-folding activity of chaperonins correlates with the symmetric GroEL14(GroES7)2 heterooligomer.

Shows that protein folding activity correlates with the symmetric GroEL-GroES2 complex.

PMID:9285585

The crystal structure of the asymmetric GroEL-GroES-(ADP)7 chaperonin complex.

Landmark 3.0 A crystal structure of the functional asymmetric GroEL-GroES-(ADP)7 complex. Reveals the structural basis for substrate encapsulation and folding within the central cavity.

PMID:9285593

Distinct actions of cis and trans ATP within the double ring of the chaperonin GroEL.

Demonstrates that cis ATP hydrolysis weakens GroEL-GroES interaction and trans ATP binding triggers complex disassembly and product release. Establishes the catalytic cycle.

PMID:9878052

Compartmentation of protein folding in vivo: sequestration of non-native polypeptide by the chaperonin-GimC system.

Demonstrates in vivo sequestration of non-native polypeptides by chaperonin system.

📚 Additional Documentation

Deep Research Bioreason

(GroEL-deep-research-bioreason.md)

BioReason Chat Export

Exported on March 22, 2026 at 02:53 AM

Organism: Escherichia coli

Sequence:

MAAKDVKFGNDARVKMLRGVNVLADAVKVTLGPKGRNVVLDKSFGAPTITKDGVSVAREIELEDKFENMGAQMVKEVASKANDAAGDGTTTATVLAQAIITEGLKAVAAGMNPMDLKRGIDKAVTAAVEELKALSVPCSDSKAIAQVGTISANSDETVGKLIAEAMDKVGKEGVITVEDGTGLQDELDVVEGMQFDRGYLSPYFINKPETGAVELESPFILLADKKISNIREMLPVLEAVAKAGKPLLIIAEDVEGEALATLVVNTMRGIVKVAAVKAPGFGDRRKAMLQDIATLTGGTVISEEIGMELEKATLEDLGQAKRVVINKDTTTIIDGVGEEAAIQGRVAQIRQQIEEATSDYDREKLQERVAKLAGGVAVIKVGAATEVEMKEKKARVEDALHATRAAVEEGVVAGGGVALIRVASKLADLRGQNEDQNVGIKVALRAMEAPLRQIVLNCGEEPSVVANTVKGGDGNYGYNAATEEYGNMIDMGILDPTKVTRSALQYAASVAGLMITTECMVTDLPKNDAADLGAAGGMGGMGGMGGMM

Thinking Trace

I begin by dissecting the InterPro architecture. The polypeptide is covered almost end-to-end by IPR001844 (Chaperonin Cpn60/GroEL family, residues 2–547) and IPR002423 (Chaperonin Cpn60/GroEL/TCP-1 family, residues 23–522), which define a canonical group I chaperonin scaffold. Within this framework, three structural superfamilies partition the fold: IPR027413 (GroEL-like equatorial domain superfamily, residues 6–522) forms the large ATPase-bearing equatorial base; IPR027410 (TCP-1-like chaperonin intermediate domain superfamily, residues 137–410) provides the hinge that transmits nucleotide-state changes; and IPR027409 (GroEL-like apical domain superfamily, residues 185–376) creates the substrate/GroES recognition surface. A conserved functional patch, IPR018370 (Chaperonin Cpn60 conserved site, residues 405–416), sits near the equatorial–intermediate interface where catalytic residues and allosteric networks control ATP hydrolysis and ring cooperativity. The ordered arrangement—equatorial ATPase core, mobile intermediate hinge, and apical substrate-binding crown—is diagnostic of an ATP-driven chaperonin that cycles between open and closed conformations.

This domain architecture dictates the molecular function. The equatorial domain supplies the nucleotide pocket and catalytic machinery that binds and hydrolyzes ATP, while the apical domain binds non-native polypeptides and the co-chaperonin cap. The intermediate domain transduces the chemical energy of ATP into large-scale conformational shifts that encapsulate client proteins inside a folding chamber. This causal chain—ATP binding and hydrolysis in the equatorial core driving apical substrate capture and GroES-capping—establishes an ATP-dependent protein-folding mechanism. At the GO molecular-function level, the most direct inference is ATP binding and hydrolysis coupled to client engagement; operationally this manifests as high-affinity, reversible protein binding during the chaperone cycle.

From molecular function flows biological process. By trapping and encapsulating non-native chains, the machine accelerates productive folding and suppresses misassembly, which is the essence of chaperone-mediated protein folding and refolding. The system becomes especially important during thermal or physiological stress, when unfolded proteins accumulate. Thus the process aligns with ATP-dependent chaperone-driven folding and refolding pathways that maintain proteostasis.

Cellular localization follows from the soluble, ring-forming chaperonin fold and the absence of transmembrane features. The GroEL/Cpn60 architecture assembles into cytoplasmic double-ring particles that operate freely in the cytosol. Therefore, the cellular component is cytoplasm, consistent with a soluble folding machine that patrols the intracellular protein pool.

Mechanistically, I hypothesize that the protein forms heptameric rings that assemble into a double-ring particle. ATP binding at the equatorial domain triggers cooperative transitions that close the apical crown and recruit the co-chaperonin cap, forming a nano-cage that enforces an optimized folding environment. Likely interaction partners include the co-chaperonin cap protein and diverse nascent or stress-denatured cytosolic proteins; transient contacts with translation and RNA-processing assemblies would be expected as the chaperonin intercepts newly synthesized or misfolded clients in the cytoplasm.

Functional Summary

An ATP-dependent cytosolic chaperonin that assembles into ring complexes to capture, encapsulate, and release non-native polypeptides during protein folding. Its equatorial nucleotide-binding core powers conformational cycles that drive a hinge-mediated rearrangement of the apical crown, enabling recruitment of a co-chaperonin cap and formation of a folding chamber. Operating in the cytoplasm, it safeguards proteostasis by accelerating productive folding and preventing aggregation of stress-denatured client proteins.

UniProt Summary

Together with its co-chaperonin GroES, GroEL serves as a molecular chaperone, assisting the folding of proteins in an ATP-dependent manner.

InterPro Domains

Chaperonin Cpn60/GroEL (IPR001844, family) — residues 2-547
GroEL-like equatorial domain superfamily (IPR027413, homologous_superfamily) — residues 6-522
Chaperonin Cpn60/GroEL/TCP-1 family (IPR002423, family) — residues 23-522
TCP-1-like chaperonin intermediate domain superfamily (IPR027410, homologous_superfamily) — residues 137-410
GroEL-like apical domain superfamily (IPR027409, homologous_superfamily) — residues 185-376
Chaperonin Cpn60, conserved site (IPR018370, conserved_site) — residues 405-416

GO Terms

Molecular Function: molecular_function (GO:0003674), binding (GO:0005488), protein binding (GO:0005515)

Biological Process: biological_process (GO:0008150), cellular process (GO:0009987), protein folding (GO:0006457)

Cellular Component: cellular_component (GO:0005575), cellular anatomical entity (GO:0110165), protein-containing complex (GO:0032991), cytosol (GO:0005829), intracellular anatomical structure (GO:0005622), cytoplasm (GO:0005737), intracellular protein-containing complex (GO:0140535), chaperone complex (GO:0101031)

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Deep Research Bioreason Rl

(GroEL-deep-research-bioreason-rl.md)

BioReason Chat Export

Exported on March 22, 2026 at 02:53 AM

Organism: Escherichia coli

Sequence:

MAAKDVKFGNDARVKMLRGVNVLADAVKVTLGPKGRNVVLDKSFGAPTITKDGVSVAREIELEDKFENMGAQMVKEVASKANDAAGDGTTTATVLAQAIITEGLKAVAAGMNPMDLKRGIDKAVTAAVEELKALSVPCSDSKAIAQVGTISANSDETVGKLIAEAMDKVGKEGVITVEDGTGLQDELDVVEGMQFDRGYLSPYFINKPETGAVELESPFILLADKKISNIREMLPVLEAVAKAGKPLLIIAEDVEGEALATLVVNTMRGIVKVAAVKAPGFGDRRKAMLQDIATLTGGTVISEEIGMELEKATLEDLGQAKRVVINKDTTTIIDGVGEEAAIQGRVAQIRQQIEEATSDYDREKLQERVAKLAGGVAVIKVGAATEVEMKEKKARVEDALHATRAAVEEGVVAGGGVALIRVASKLADLRGQNEDQNVGIKVALRAMEAPLRQIVLNCGEEPSVVANTVKGGDGNYGYNAATEEYGNMIDMGILDPTKVTRSALQYAASVAGLMITTECMVTDLPKNDAADLGAAGGMGGMGGMGGMM

Thinking Trace

Functional Summary

UniProt Summary

Together with its co-chaperonin GroES, GroEL serves as a molecular chaperone, assisting the folding of proteins in an ATP-dependent manner.

InterPro Domains

Chaperonin Cpn60/GroEL (IPR001844, family) — residues 2-547
GroEL-like equatorial domain superfamily (IPR027413, homologous_superfamily) — residues 6-522
Chaperonin Cpn60/GroEL/TCP-1 family (IPR002423, family) — residues 23-522
TCP-1-like chaperonin intermediate domain superfamily (IPR027410, homologous_superfamily) — residues 137-410
GroEL-like apical domain superfamily (IPR027409, homologous_superfamily) — residues 185-376
Chaperonin Cpn60, conserved site (IPR018370, conserved_site) — residues 405-416

GO Terms

Molecular Function: molecular_function (GO:0003674), binding (GO:0005488), protein binding (GO:0005515)

Biological Process: biological_process (GO:0008150), cellular process (GO:0009987), protein folding (GO:0006457)

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Bioreason Rl Review

(GroEL-bioreason-rl-review.md)

BioReason-Pro RL Review: GroEL (E. coli)

Source: GroEL-deep-research-bioreason-rl.md

Correctness: 5/5
Completeness: 4/5

Functional Summary Review

The BioReason functional summary describes GroEL as:

An ATP-dependent cytosolic chaperonin that assembles into ring complexes to capture, encapsulate, and release non-native polypeptides during protein folding. Its equatorial nucleotide-binding core powers conformational cycles that drive a hinge-mediated rearrangement of the apical crown, enabling recruitment of a co-chaperonin cap and formation of a folding chamber. Operating in the cytoplasm, it safeguards proteostasis by accelerating productive folding and preventing aggregation of stress-denatured client proteins.

This is an excellent summary that accurately captures the core function of GroEL. All major elements are correct:
- ATP-dependent chaperonin mechanism
- Ring complex assembly (heptameric double-ring)
- Substrate encapsulation in the central cavity
- Conformational cycling driven by ATP hydrolysis
- Co-chaperonin (GroES) recruitment
- Folding chamber formation
- Cytoplasmic localization
- Prevention of aggregation

The thinking trace demonstrates good structural understanding of the three-domain architecture (equatorial ATPase, intermediate hinge, apical substrate-binding crown) and correctly describes the allosteric mechanism.

Minor omissions reducing completeness:
- Does not mention the specific stoichiometry (homo-tetradecameric double-ring)
- Does not mention that approximately 10-15% of E. coli cytoplasmic proteins are obligate GroEL substrates
- Does not mention the original identification as a host factor for bacteriophage assembly
- Does not mention the catalytic activity classification (EC 5.6.1.7)
- Does not mention GroES by name (refers to "co-chaperonin cap")

Comparison with interpro2go:

The curated review's interpro2go annotations include protein folding (GO:0006457) and ATP-dependent protein folding chaperone (GO:0140662), both accepted as correct. BioReason closely recapitulates these interpro2go annotations in its functional summary. The narrative adds structural mechanistic detail (equatorial/intermediate/apical domain architecture) that goes modestly beyond what interpro2go provides, making this a case where BioReason adds genuine value by synthesizing domain architecture into a coherent mechanistic picture.

Notes on thinking trace

The trace is well-structured and demonstrates understanding of chaperonin biology. The cooperative allosteric mechanism is correctly described. The mention of "translation and RNA-processing assemblies" as transient contacts is appropriate for GroEL, which does interact with ribosome-associated clients.

📄 View Raw YAML

id: P0A6F5
gene_symbol: GroEL
product_type: PROTEIN
status: IN_PROGRESS
taxon:
  id: NCBITaxon:83333
  label: Escherichia coli (strain K12)
description: 'GroEL (Cpn60/Hsp60) is the large subunit of the essential E. coli chaperonin
  complex. It forms a barrel-shaped homo-tetradecameric double-ring structure (two
  stacked heptameric rings) that, together with its co-chaperonin GroES (Hsp10), functions
  as an ATP-dependent protein folding machine (EC 5.6.1.7). The GroEL/ES system encapsulates
  non-native substrate proteins within a central cavity (the "Anfinsen cage"), providing
  a sequestered environment that prevents aggregation and actively accelerates folding
  through iterative cycles of ATP binding, GroES capping, substrate encapsulation,
  ATP hydrolysis, and product release. Approximately 10-15% of E. coli cytoplasmic
  proteins are obligate GroEL substrates. GroEL is essential for viability and is
  heat-shock inducible. It was originally identified as a host factor required for
  bacteriophage lambda and T4 head assembly. UniProt catalytic activity annotation:
  ATP + H2O + an unfolded polypeptide = ADP + phosphate + a folded polypeptide (PMID:9285585,
  PMID:9285593).'
existing_annotations:
- term:
    id: GO:0006457
    label: protein folding
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    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.
    action: ACCEPT
    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 protein folding defects
      in vivo.
    supported_by:
    - reference_id: PMID:2573517
      supporting_text: 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.
    - reference_id: PMID:14517228
      supporting_text: 'Role of the gamma-phosphate of ATP in triggering protein folding
        by GroEL-GroES: function, structure and energetics.'
- term:
    id: GO:0005524
    label: ATP binding
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    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).
    action: ACCEPT
    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.
    supported_by:
    - reference_id: PMID:8564544
      supporting_text: The 2.4 A crystal structure of the bacterial chaperonin GroEL
        complexed with ATP gamma S.
    - reference_id: PMID:9285585
      supporting_text: The crystal structure of the asymmetric GroEL-GroES-(ADP)7
        chaperonin complex.
- term:
    id: GO:0009408
    label: response to heat
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    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).
    action: ACCEPT
    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.
    supported_by:
    - reference_id: PMID:8349564
      supporting_text: Characterization of twenty-six new heat shock genes of Escherichia
        coli.
- term:
    id: GO:0051082
    label: unfolded protein binding
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: IBA annotation for unfolded protein binding. While GroEL does bind unfolded/non-native
      proteins, GO:0051082 is being obsoleted. 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.
    action: MODIFY
    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 being obsoleted as part of
      the unfolded protein binding obsoletion project.
    proposed_replacement_terms:
    - id: GO:0140662
      label: ATP-dependent protein folding chaperone
    supported_by:
    - reference_id: PMID:8097882
      supporting_text: We conclude that folding intermediates are bound inside central
        cavities within individual chaperonin rings.
    - reference_id: PMID:7935796
      supporting_text: Chaperonins are ring-shaped protein complexes that are essential
        in the cell, mediating ATP-dependent polypeptide folding in a variety of compartments.
- term:
    id: GO:1990220
    label: GroEL-GroES complex
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    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).
    action: ACCEPT
    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.
    supported_by:
    - reference_id: PMID:9285585
      supporting_text: The crystal structure of the asymmetric GroEL-GroES-(ADP)7
        chaperonin complex.
- term:
    id: GO:0000166
    label: nucleotide binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000043
  review:
    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.
    action: ACCEPT
    reason: GroEL is unambiguously a nucleotide-binding protein (it binds ATP and
      ADP). This is correctly inferred from the UniProt keyword. While more general
      than the specific ATP binding annotation, it is not wrong. The IBA/IDA annotations
      for ATP binding provide the more specific annotation.
- term:
    id: GO:0005524
    label: ATP binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    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.
    action: ACCEPT
    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).
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    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.
    action: ACCEPT
    reason: Correct electronic inference. GroEL is a cytoplasmic protein. UniProt
      states "Cytoplasm" as subcellular location. The broader "cytoplasm" term is
      not wrong even though a more specific "cytosol" annotation exists with IDA evidence.
- term:
    id: GO:0006457
    label: protein folding
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  review:
    summary: IEA annotation for protein folding from InterPro domain mapping (IPR018370).
      Consistent with IBA and IDA annotations for the same term.
    action: ACCEPT
    reason: Correct electronic inference. The GroEL/Hsp60 InterPro domain is directly
      associated with protein folding function. Consistent with all other evidence.
- term:
    id: GO:0016853
    label: isomerase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000043
  review:
    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.
    action: ACCEPT
    reason: UniProt assigns EC 5.6.1.7 to GroEL, placing it in the isomerase class
      (EC 5). The IEA mapping from the Isomerase keyword to GO:0016853 is technically
      correct. However, the more specific GO:0140662 "ATP-dependent protein folding
      chaperone" annotation better captures the specific activity.
- term:
    id: GO:0042026
    label: protein refolding
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    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.
    action: ACCEPT
    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.
- term:
    id: GO:0051082
    label: unfolded protein binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000104
  review:
    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.
    action: MODIFY
    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
      being obsoleted. The correct replacement is GO:0140662 "ATP-dependent protein
      folding chaperone".
    proposed_replacement_terms:
    - id: GO:0140662
      label: ATP-dependent protein folding chaperone
- term:
    id: GO:0140662
    label: ATP-dependent protein folding chaperone
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  review:
    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.
    action: ACCEPT
    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.'
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:10077571
  review:
    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.
    action: MODIFY
    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_replacement_terms:
    - id: GO:0051087
      label: protein-folding chaperone binding
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:11779463
  review:
    summary: IPI annotation for protein binding with GroES (P0A6F9). Study of ATP-bound
      states of GroEL captured by cryo-electron microscopy. Interaction with GroES.
    action: MODIFY
    reason: '"Protein binding" is uninformative. This is a GroEL-GroES co-chaperonin
      interaction.'
    proposed_replacement_terms:
    - id: GO:0051087
      label: protein-folding chaperone binding
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:12071968
  review:
    summary: IPI annotation for protein binding with UP12/YjgF (P39177). This study
      identifies YjgF as a putative in vivo substrate of GroEL. This reflects a chaperone-substrate
      interaction.
    action: MODIFY
    reason: '"Protein binding" is uninformative. This is a chaperone-substrate interaction
      and is better captured by GO:0044183 or GO:0140662 (protein folding chaperone
      / ATP-dependent protein folding chaperone). However, since the IPI evidence
      shows a physical interaction with a substrate, modifying to the chaperone activity
      term is most appropriate.'
    proposed_replacement_terms:
    - id: GO:0140662
      label: ATP-dependent protein folding chaperone
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:14517228
  review:
    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.
    action: MODIFY
    reason: '"Protein binding" is uninformative. This is the GroEL-GroES co-chaperonin
      interaction.'
    proposed_replacement_terms:
    - id: GO:0051087
      label: protein-folding chaperone binding
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:15313620
  review:
    summary: IPI annotation for protein binding with GroES (P0A6F9). Structural dynamics
      study of GroEL using crystallographic refinement. Co-chaperonin interaction.
    action: MODIFY
    reason: '"Protein binding" is uninformative. GroEL-GroES co-chaperonin interaction.'
    proposed_replacement_terms:
    - id: GO:0051087
      label: protein-folding chaperone binding
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:15690043
  review:
    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), KasA (P0A717), RpsA (P0A7H0), DegP (P0A9W0), MalE (P0AEY3),
      AceE (P0AFG8), etc. Many of these likely represent chaperone-substrate relationships
      in a large-scale interactome study.
    action: MODIFY
    reason: '"Protein binding" is uninformative. These large-scale interactome hits
      likely include both genuine chaperone-substrate interactions and co-complex
      partners. For a chaperonin that interacts with 10-15% of the proteome, generic
      "protein binding" is essentially meaningless. The core molecular function is
      better captured by GO:0140662.'
    proposed_replacement_terms:
    - id: GO:0140662
      label: ATP-dependent protein folding chaperone
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:16239229
  review:
    summary: IPI annotation for protein binding with GroES (P0A6F9). Study on Leu309
      role in substrate encapsulation into the GroEL internal cavity. Co-chaperonin
      interaction.
    action: MODIFY
    reason: '"Protein binding" is uninformative. GroEL-GroES co-chaperonin interaction.'
    proposed_replacement_terms:
    - id: GO:0051087
      label: protein-folding chaperone binding
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:16429154
  review:
    summary: IPI annotation for protein binding with GroES (P0A6F9). Study on allosteric
      signaling of ATP hydrolysis in GroEL-GroES complexes. Co-chaperonin interaction.
    action: MODIFY
    reason: '"Protein binding" is uninformative. GroEL-GroES co-chaperonin interaction.'
    proposed_replacement_terms:
    - id: GO:0051087
      label: protein-folding chaperone binding
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:16606699
  review:
    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.
    action: MODIFY
    reason: '"Protein binding" is uninformative. Large-scale interactome study detecting
      many chaperone-substrate interactions. The core function is better captured
      by GO:0140662.'
    proposed_replacement_terms:
    - id: GO:0140662
      label: ATP-dependent protein folding chaperone
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:16977315
  review:
    summary: IPI annotation for protein binding with GroES (P0A6F9). Fast-scanning
      AFM study of ATP/ADP-dependent conformational changes of GroEL.
    action: MODIFY
    reason: '"Protein binding" is uninformative. GroEL-GroES co-chaperonin interaction.'
    proposed_replacement_terms:
    - id: GO:0051087
      label: protein-folding chaperone binding
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:17032756
  review:
    summary: IPI annotation for protein binding with GroES (P0A6F9). NMR spectroscopy
      study of polypeptide chains in large GroEL structures.
    action: MODIFY
    reason: '"Protein binding" is uninformative. GroEL-GroES co-chaperonin interaction.'
    proposed_replacement_terms:
    - id: GO:0051087
      label: protein-folding chaperone binding
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:17098196
  review:
    summary: IPI annotation for protein binding with GroES (P0A6F9). Study showing
      expanded conformation of single-ring GroEL-GroES complex encapsulating an 86
      kDa substrate.
    action: MODIFY
    reason: '"Protein binding" is uninformative. GroEL-GroES co-chaperonin interaction.'
    proposed_replacement_terms:
    - id: GO:0051087
      label: protein-folding chaperone binding
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:17968012
  review:
    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.
    action: MODIFY
    reason: '"Protein binding" is uninformative. The GroEL-sigma32 interaction reflects
      GroEL''s role as a chaperone that sequesters sigma-32 under non-stress conditions,
      contributing to heat shock response regulation. This is a chaperone-substrate
      interaction.'
    proposed_replacement_terms:
    - id: GO:0140662
      label: ATP-dependent protein folding chaperone
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:18394994
  review:
    summary: IPI annotation for protein binding with GroES (P0A6F9) and MalZ (P0AEX9).
      Study monitoring protein conformation along the pathway of chaperonin-assisted
      folding.
    action: MODIFY
    reason: '"Protein binding" is uninformative. Interactions reflect GroEL-GroES
      co-chaperonin and GroEL-substrate (MalZ) chaperone interactions.'
    proposed_replacement_terms:
    - id: GO:0140662
      label: ATP-dependent protein folding chaperone
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:18418386
  review:
    summary: IPI annotation for protein binding with OrnC (P00586) and DegP (P0A817).
      Study on essential role of the chaperonin folding compartment in vivo (Tang
      et al. 2008). These are chaperone-substrate interactions.
    action: MODIFY
    reason: '"Protein binding" is uninformative. These interactions reflect GroEL''s
      chaperone-substrate relationships in the essential folding compartment. GO:0140662
      better captures this.'
    proposed_replacement_terms:
    - id: GO:0140662
      label: ATP-dependent protein folding chaperone
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:18568038
  review:
    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.
    action: MARK_AS_OVER_ANNOTATED
    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.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:20308583
  review:
    summary: IPI annotation for protein binding with GroES (P0A6F9). Study of out-of-equilibrium
      conformational cycling of GroEL under saturating ATP. Co-chaperonin interaction.
    action: MODIFY
    reason: '"Protein binding" is uninformative. GroEL-GroES co-chaperonin interaction.'
    proposed_replacement_terms:
    - id: GO:0051087
      label: protein-folding chaperone binding
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:20959808
  review:
    summary: IPI annotation for protein binding with GroES (P0A6F9). Study of polypeptide
      behavior in the chaperonin cage. Co-chaperonin interaction.
    action: MODIFY
    reason: '"Protein binding" is uninformative. GroEL-GroES co-chaperonin interaction.'
    proposed_replacement_terms:
    - id: GO:0051087
      label: protein-folding chaperone binding
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:23746846
  review:
    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.
    action: MODIFY
    reason: '"Protein binding" is uninformative. GroEL-GroES co-chaperonin interaction.'
    proposed_replacement_terms:
    - id: GO:0051087
      label: protein-folding chaperone binding
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:24561554
  review:
    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.
    action: MODIFY
    reason: '"Protein binding" is uninformative. Large-scale interactome study. For
      a chaperonin, these interactions represent chaperone-substrate relationships.'
    proposed_replacement_terms:
    - id: GO:0140662
      label: ATP-dependent protein folding chaperone
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:26545493
  review:
    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.
    action: MODIFY
    reason: '"Protein binding" is uninformative. GroEL-sigma32 regulatory chaperone
      interaction.'
    proposed_replacement_terms:
    - id: GO:0140662
      label: ATP-dependent protein folding chaperone
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:8618836
  review:
    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).
    action: MODIFY
    reason: '"Protein binding" is uninformative. GroEL-GroES co-chaperonin interaction.'
    proposed_replacement_terms:
    - id: GO:0051087
      label: protein-folding chaperone binding
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:9285585
  review:
    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.
    action: MODIFY
    reason: '"Protein binding" is uninformative. This is the landmark GroEL-GroES
      crystal structure.'
    proposed_replacement_terms:
    - id: GO:0051087
      label: protein-folding chaperone binding
    supported_by:
    - reference_id: PMID:9285585
      supporting_text: The crystal structure of the asymmetric GroEL-GroES-(ADP)7
        chaperonin complex.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:9878052
  review:
    summary: IPI annotation for protein binding with GroES homolog/Gim complex component
      (P60010). Study on compartmentation of protein folding in vivo -- sequestration
      of non-native polypeptide by the chaperonin-GimC system. Chaperone-substrate
      interaction.
    action: MODIFY
    reason: '"Protein binding" is uninformative. Reflects chaperonin-substrate interaction
      in the context of protein folding quality control.'
    proposed_replacement_terms:
    - id: GO:0140662
      label: ATP-dependent protein folding chaperone
- term:
    id: GO:0042802
    label: identical protein binding
  evidence_type: IPI
  original_reference_id: PMID:16858726
  review:
    summary: IPI for identical protein binding (GroEL-GroEL self-interaction). GroEL
      forms a homo-tetradecameric double-ring structure. Blue native/SDS-PAGE complexomic
      study.
    action: ACCEPT
    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.
- term:
    id: GO:0042802
    label: identical protein binding
  evidence_type: IPI
  original_reference_id: PMID:17098196
  review:
    summary: IPI for identical protein binding. Single-ring GroEL-GroES complex study
      showing GroEL self-interaction.
    action: ACCEPT
    reason: Valid annotation reflecting GroEL homo-oligomerization.
- term:
    id: GO:0042802
    label: identical protein binding
  evidence_type: IPI
  original_reference_id: PMID:18334219
  review:
    summary: IPI for identical protein binding. Backbone trace of GroEL from cryo-EM
      showing GroEL self-interaction in the oligomeric complex.
    action: ACCEPT
    reason: Valid annotation reflecting GroEL homo-oligomerization.
- term:
    id: GO:0042802
    label: identical protein binding
  evidence_type: IPI
  original_reference_id: PMID:18568038
  review:
    summary: IPI for identical protein binding using GroEL as a molecular scaffold
      for anthrax toxin pore structural analysis. GroEL self-interaction detected.
    action: ACCEPT
    reason: GroEL self-interaction is valid regardless of the experimental context.
- term:
    id: GO:0042802
    label: identical protein binding
  evidence_type: IPI
  original_reference_id: PMID:22575645
  review:
    summary: IPI for identical protein binding. Study on fibrillogenic propensity
      of the GroEL apical domain -- the apical domain minichaperone can self-associate.
    action: ACCEPT
    reason: GroEL self-interaction is a well-established structural property.
- term:
    id: GO:0042802
    label: identical protein binding
  evidence_type: IPI
  original_reference_id: PMID:7935790
  review:
    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.
    action: ACCEPT
    reason: The crystal structure (PMID:7935790) is the definitive demonstration of
      GroEL's homo-oligomeric architecture. Core structural annotation.
    supported_by:
    - reference_id: PMID:7935790
      supporting_text: The crystal structure of the bacterial chaperonin GroEL at
        2.8 A.
- term:
    id: GO:0042802
    label: identical protein binding
  evidence_type: IPI
  original_reference_id: PMID:8618836
  review:
    summary: IPI for identical protein binding. Study on symmetric GroEL14(GroES7)2
      heterooligomer demonstrating GroEL self-interaction.
    action: ACCEPT
    reason: Valid annotation reflecting GroEL homo-oligomerization.
- term:
    id: GO:0042802
    label: identical protein binding
  evidence_type: IPI
  original_reference_id: PMID:9878052
  review:
    summary: IPI for identical protein binding. Study on protein folding compartmentation
      in vivo. GroEL self-interaction detected.
    action: ACCEPT
    reason: Valid annotation reflecting GroEL homo-oligomerization.
- term:
    id: GO:0006457
    label: protein folding
  evidence_type: IDA
  original_reference_id: PMID:14517228
  review:
    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.
    action: ACCEPT
    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.
- term:
    id: GO:0009314
    label: response to radiation
  evidence_type: IMP
  original_reference_id: PMID:27718375
  review:
    summary: IMP annotation for response to radiation from a systematic screen for
      genes involved in radiation survival of E. coli (Byrne et al. 2014). groEL mutations
      affect radiation survival, likely through indirect effects on protein homeostasis
      under radiation stress.
    action: KEEP_AS_NON_CORE
    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.
- term:
    id: GO:1990220
    label: GroEL-GroES complex
  evidence_type: IDA
  original_reference_id: PMID:9285585
  review:
    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.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: PMID:9285585
      supporting_text: The crystal structure of the asymmetric GroEL-GroES-(ADP)7
        chaperonin complex.
- term:
    id: GO:0000287
    label: magnesium ion binding
  evidence_type: IDA
  original_reference_id: PMID:8564544
  review:
    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.
    action: ACCEPT
    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").'
    supported_by:
    - reference_id: PMID:8564544
      supporting_text: The 2.4 A crystal structure of the bacterial chaperonin GroEL
        complexed with ATP gamma S.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IMP
  original_reference_id: PMID:7935796
  review:
    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.
    action: MODIFY
    reason: '"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. Better annotated as GO:0140662.'
    proposed_replacement_terms:
    - id: GO:0140662
      label: ATP-dependent protein folding chaperone
    supported_by:
    - reference_id: PMID:7935796
      supporting_text: 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.
- term:
    id: GO:0005524
    label: ATP binding
  evidence_type: IDA
  original_reference_id: PMID:8564544
  review:
    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.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: PMID:8564544
      supporting_text: The 2.4 A crystal structure of the bacterial chaperonin GroEL
        complexed with ATP gamma S.
- term:
    id: GO:0042802
    label: identical protein binding
  evidence_type: IDA
  original_reference_id: PMID:7935790
  review:
    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.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: PMID:7935790
      supporting_text: The crystal structure of the bacterial chaperonin GroEL at
        2.8 A.
- term:
    id: GO:0051082
    label: unfolded protein binding
  evidence_type: IMP
  original_reference_id: PMID:7935796
  review:
    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.
    action: MODIFY
    reason: GO:0051082 is being obsoleted. 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_replacement_terms:
    - id: GO:0140662
      label: ATP-dependent protein folding chaperone
    supported_by:
    - reference_id: PMID:7935796
      supporting_text: Chaperonins are ring-shaped protein complexes that are essential
        in the cell, mediating ATP-dependent polypeptide folding in a variety of compartments.
- term:
    id: GO:0051082
    label: unfolded protein binding
  evidence_type: IDA
  original_reference_id: PMID:8097882
  review:
    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.
    action: MODIFY
    reason: GO:0051082 is being obsoleted. 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_replacement_terms:
    - id: GO:0140662
      label: ATP-dependent protein folding chaperone
    supported_by:
    - reference_id: PMID:8097882
      supporting_text: 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.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IDA
  original_reference_id: PMID:18304323
  review:
    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.
    action: ACCEPT
    reason: Direct proteomics evidence for cytosolic localization. GroEL is one of
      the most abundant proteins in the E. coli cytosol. UniProt confirms cytoplasmic
      localization.
- term:
    id: GO:0019068
    label: virion assembly
  evidence_type: IMP
  original_reference_id: PMID:7015340
  review:
    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.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: PMID:7015340
      supporting_text: 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.
- term:
    id: GO:0009408
    label: response to heat
  evidence_type: IEP
  original_reference_id: PMID:8349564
  review:
    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.
    action: ACCEPT
    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.
- term:
    id: GO:0005524
    label: ATP binding
  evidence_type: IDA
  original_reference_id: PMID:9285585
  review:
    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.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: PMID:9285585
      supporting_text: The crystal structure of the asymmetric GroEL-GroES-(ADP)7
        chaperonin complex.
- term:
    id: GO:0006457
    label: protein folding
  evidence_type: IMP
  original_reference_id: PMID:2573517
  review:
    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.
    action: ACCEPT
    reason: Early and important evidence for GroEL's in vivo protein folding role.
      groEL mutations cause protein misfolding/export defects, demonstrating the chaperonin
      is required for proper protein folding in the cell.
    supported_by:
    - reference_id: PMID:2573517
      supporting_text: 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.
- term:
    id: GO:0016887
    label: ATP hydrolysis activity
  evidence_type: IDA
  original_reference_id: PMID:379350
  review:
    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.
    action: ACCEPT
    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 the forward progression of the folding cycle, although it is not
      required for the folding reaction itself (PMID:9285593). This is a core molecular
      function.
- term:
    id: GO:0016020
    label: membrane
  evidence_type: HDA
  original_reference_id: PMID:16858726
  review:
    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.
    action: KEEP_AS_NON_CORE
    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.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: HDA
  original_reference_id: PMID:16858726
  review:
    summary: HDA annotation for cytosol from the same complexomic study (Maddalo et
      al. 2006). GroEL is one of the most abundant cytosolic proteins.
    action: ACCEPT
    reason: GroEL is unambiguously a cytosolic protein. This HDA annotation is consistent
      with the IDA annotation from PMID:18304323 and UniProt subcellular location
      data.
- term:
    id: GO:0140662
    label: ATP-dependent protein folding chaperone
  evidence_type: IDA
  original_reference_id: PMID:9285585
  review:
    summary: 'NEW annotation. GroEL is the prototypical ATP-dependent protein folding
      chaperone. The crystal structure of the GroEL-GroES-(ADP)7 complex (PMID:9285585)
      together with the catalytic activity annotation (EC 5.6.1.7: ATP + H2O + unfolded
      polypeptide = ADP + phosphate + folded polypeptide) provides direct evidence
      for this molecular function. This term is already annotated via IEA but lacks
      direct experimental support in the current annotation set.'
    action: NEW
    reason: GO:0140662 "ATP-dependent protein folding chaperone" is the single most
      accurate molecular function term for GroEL. It captures both the ATP dependence
      and the protein folding chaperone activity. UniProt assigns EC 5.6.1.7 with
      evidence from PMID:9285585 and PMID:9285593. While an IEA annotation exists,
      there is no experimental annotation for this term in the current GOA set. Given
      that multiple GO:0051082 annotations are being recommended for modification
      to this term, having an explicit experimental annotation is important.
    supported_by:
    - reference_id: PMID:9285585
      supporting_text: The crystal structure of the asymmetric GroEL-GroES-(ADP)7
        chaperonin complex.
    - reference_id: PMID:7935796
      supporting_text: Chaperonins are ring-shaped protein complexes that are essential
        in the cell, mediating ATP-dependent polypeptide folding in a variety of compartments.
references:
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with GO
    terms
  findings: []
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
- id: GO_REF:0000043
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword mapping
  findings: []
- id: GO_REF:0000104
  title: Electronic Gene Ontology annotations created by transferring manual GO annotations
    between related proteins based on shared sequence features
  findings: []
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods
  findings: []
- id: PMID:10077571
  title: GroES in the asymmetric GroEL14-GroES7 complex exchanges via an associative
    mechanism.
  findings:
  - statement: Demonstrates dynamic GroES exchange on the GroEL complex via an associative
      mechanism.
- id: PMID:11779463
  title: ATP-bound states of GroEL captured by cryo-electron microscopy.
  findings:
  - statement: Cryo-EM reveals ATP-bound conformational states of GroEL.
- id: PMID:12071968
  title: Identification and characterization of the Escherichia coli stress protein
    UP12, a putative in vivo substrate of GroEL.
  findings:
  - statement: Identifies YjgF/UP12 as an in vivo substrate of GroEL.
- id: PMID:14517228
  title: 'Role of the gamma-phosphate of ATP in triggering protein folding by GroEL-GroES:
    function, structure and energetics.'
  findings:
  - statement: Demonstrates that gamma-phosphate of ATP is required to trigger productive
      folding by GroEL-GroES.
- id: PMID:15313620
  title: Exploring the structural dynamics of the E.coli chaperonin GroEL using translation-libration-screw
    crystallographic refinement of intermediate states.
  findings:
  - statement: Reveals structural dynamics of GroEL intermediate conformational states.
- id: PMID:15690043
  title: Interaction network containing conserved and essential protein complexes
    in Escherichia coli.
  findings:
  - statement: Large-scale identification of E. coli protein complexes, including
      GroEL interactions with multiple substrates.
- id: PMID:16239229
  title: Leu309 plays a critical role in the encapsulation of substrate protein into
    the internal cavity of GroEL.
  findings:
  - statement: Identifies Leu309 as critical for substrate encapsulation in the GroEL
      cavity.
- id: PMID:16429154
  title: Allosteric signaling of ATP hydrolysis in GroEL-GroES complexes.
  findings:
  - statement: Demonstrates allosteric communication of ATP hydrolysis between GroEL
      rings.
- id: PMID:16606699
  title: Large-scale identification of protein-protein interaction of Escherichia
    coli K-12.
  findings:
  - statement: Large-scale E. coli interactome study identifying GroEL interactions
      with many proteins.
- id: PMID:16858726
  title: A complexomic study of Escherichia coli using two-dimensional blue native/SDS
    polyacrylamide gel electrophoresis.
  findings:
  - statement: Identifies GroEL in both cytosolic and membrane-associated protein
      complexes.
- id: PMID:16977315
  title: Fast-scanning atomic force microscopy reveals the ATP/ADP-dependent conformational
    changes of GroEL.
  findings:
  - statement: AFM imaging shows ATP/ADP-dependent conformational changes in GroEL.
- id: PMID:17032756
  title: Proton-proton Overhauser NMR spectroscopy with polypeptide chains in large
    structures.
  findings:
  - statement: NMR study of polypeptide behavior in GroEL complexes.
- id: PMID:17098196
  title: An expanded conformation of single-ring GroEL-GroES complex encapsulates
    an 86 kDa substrate.
  findings:
  - statement: Shows that single-ring GroEL-GroES can encapsulate large substrates
      up to 86 kDa.
- id: PMID:17968012
  title: Analysis of sigma32 mutants defective in chaperone-mediated feedback control
    reveals unexpected complexity of the heat shock response.
  findings:
  - statement: Demonstrates GroEL-sigma32 interaction in heat shock response regulation.
- id: PMID:18304323
  title: Protein abundance profiling of the Escherichia coli cytosol.
  findings:
  - statement: Identifies GroEL as one of the most abundant cytosolic proteins in
      E. coli.
- id: PMID:18334219
  title: De novo backbone trace of GroEL from single particle electron cryomicroscopy.
  findings:
  - statement: High-resolution cryo-EM backbone trace of GroEL structure.
- id: PMID:18394994
  title: Monitoring protein conformation along the pathway of chaperonin-assisted
    folding.
  findings:
  - statement: Tracks substrate protein conformational changes during GroEL-assisted
      folding.
- id: PMID:18418386
  title: Essential role of the chaperonin folding compartment in vivo.
  findings:
  - statement: Demonstrates that the enclosed GroEL cavity is essential for in vivo
      protein folding activity.
- id: PMID:18568038
  title: GroEL as a molecular scaffold for structural analysis of the anthrax toxin
    pore.
  findings:
  - statement: GroEL used as structural scaffold in cryo-EM, not a physiological interaction.
- id: PMID:20308583
  title: Out-of-equilibrium conformational cycling of GroEL under saturating ATP concentrations.
  findings:
  - statement: Reveals non-equilibrium conformational cycling of GroEL-GroES.
- id: PMID:20959808
  title: Polypeptide in the chaperonin cage partly protrudes out and then folds inside
    or escapes outside.
  findings:
  - statement: Shows substrate polypeptide behavior during encapsulation in the GroEL
      cage.
- id: PMID:22575645
  title: 'Fibrillogenic propensity of the GroEL apical domain: a Janus-faced minichaperone.'
  findings:
  - statement: Characterizes GroEL apical domain self-association and fibrillogenic
      properties.
- id: PMID:23746846
  title: Visualizing GroEL/ES in the act of encapsulating a folding protein.
  findings:
  - statement: Cryo-EM visualization of GroEL/ES actively encapsulating a substrate
      protein.
- id: PMID:24561554
  title: The binary protein-protein interaction landscape of Escherichia coli.
  findings:
  - statement: Large-scale binary interactome study identifying GroEL interaction
      partners.
- id: PMID:2573517
  title: Effects of mutations in heat-shock genes groES and groEL on protein export
    in Escherichia coli.
  findings:
  - statement: groEL mutations cause defective protein export, demonstrating in vivo
      chaperone function.
- id: PMID:26545493
  title: GroEL to DnaK chaperone network behind the stability modulation of σ(32)
    at physiological temperature in Escherichia coli.
  findings:
  - statement: Demonstrates GroEL-DnaK chaperone network in sigma-32 stability regulation.
- id: PMID:27718375
  title: Screen for genes involved in radiation survival of Escherichia coli and construction
    of a reference database.
  findings:
  - statement: groEL identified in screen for radiation survival genes.
- id: PMID:379350
  title: Purification and properties of groE, a host protein involved in bacteriophage
    assembly.
  findings:
  - statement: Original purification of GroE showing ATPase activity and role in phage
      assembly.
- id: PMID:7015340
  title: Identification of a second Escherichia coli groE gene whose product is necessary
    for bacteriophage morphogenesis.
  findings:
  - statement: Identifies groEL and groES as two genes in the groE locus, both essential
      for phage morphogenesis and bacterial growth.
- id: PMID:7935790
  title: The crystal structure of the bacterial chaperonin GroEL at 2.8 A.
  findings:
  - statement: Landmark crystal structure reveals the homo-tetradecameric double-ring
      architecture of GroEL with three domains per subunit.
- id: PMID:7935796
  title: Residues in chaperonin GroEL required for polypeptide binding and release.
  findings:
  - statement: Identifies hydrophobic polypeptide binding site on the inner surface
      of the apical domain. Same residues required for GroES binding. Asp87 essential
      for ATP hydrolysis.
- id: PMID:8097882
  title: A polypeptide bound by the chaperonin groEL is localized within a central
    cavity.
  findings:
  - statement: STEM microscopy shows gold-labeled DHFR folding intermediates bound
      inside the central cavity of GroEL rings, establishing the Anfinsen cage concept.
- id: PMID:8349564
  title: Characterization of twenty-six new heat shock genes of Escherichia coli.
  findings:
  - statement: Characterizes groEL as a heat shock gene with expression induced by
      thermal stress.
- id: PMID:8564544
  title: The 2.4 A crystal structure of the bacterial chaperonin GroEL complexed with
    ATP gamma S.
  findings:
  - statement: Crystal structure shows ATPgammaS and Mg2+ binding in the equatorial
      domain of GroEL.
- id: PMID:8618836
  title: The protein-folding activity of chaperonins correlates with the symmetric
    GroEL14(GroES7)2 heterooligomer.
  findings:
  - statement: Shows that protein folding activity correlates with the symmetric GroEL-GroES2
      complex.
- id: PMID:9285585
  title: The crystal structure of the asymmetric GroEL-GroES-(ADP)7 chaperonin complex.
  findings:
  - statement: Landmark 3.0 A crystal structure of the functional asymmetric GroEL-GroES-(ADP)7
      complex. Reveals the structural basis for substrate encapsulation and folding
      within the central cavity.
- id: PMID:9285593
  title: Distinct actions of cis and trans ATP within the double ring of the chaperonin
    GroEL.
  findings:
  - statement: Demonstrates that cis ATP hydrolysis weakens GroEL-GroES interaction
      and trans ATP binding triggers complex disassembly and product release. Establishes
      the catalytic cycle.
- id: PMID:9878052
  title: 'Compartmentation of protein folding in vivo: sequestration of non-native
    polypeptide by the chaperonin-GimC system.'
  findings:
  - statement: Demonstrates in vivo sequestration of non-native polypeptides by chaperonin
      system.
core_functions:
- description: 'GroEL is the prototypical ATP-dependent protein folding chaperone
    (EC 5.6.1.7). It catalyzes the reaction: ATP + H2O + unfolded polypeptide = ADP
    + phosphate + folded polypeptide within the GroEL-GroES complex in the cytosol.
    Multiple crystal structures (PMID:8564544, PMID:9285585), mutational analyses
    (PMID:7935796), and functional studies establish this as the core molecular function.
    GroEL also has intrinsic ATPase activity (PMID:379350) that drives the chaperonin
    conformational cycle. Approximately 10-15% of E. coli cytoplasmic proteins are
    obligate GroEL substrates. groEL mutations cause protein misfolding in vivo (PMID:2573517).'
  molecular_function:
    id: GO:0140662
    label: ATP-dependent protein folding chaperone
  directly_involved_in:
  - id: GO:0006457
    label: protein folding
  locations:
  - id: GO:0005829
    label: cytosol
  in_complex:
    id: GO:1990220
    label: GroEL-GroES complex
  supported_by:
  - reference_id: PMID:9285585
    supporting_text: The crystal structure of the asymmetric GroEL-GroES-(ADP)7 chaperonin
      complex.
  - reference_id: PMID:7935796
    supporting_text: Chaperonins are ring-shaped protein complexes that are essential
      in the cell, mediating ATP-dependent polypeptide folding in a variety of compartments.
  - reference_id: PMID:2573517
    supporting_text: temperature-sensitive mutations in groES and groEL genes cause
      defective export of the plasmid-encoded beta-lactamase (Bla) in vivo.

GroEL

Gene Description

Existing Annotations Review

Core Functions

References

📚 Additional Documentation

Deep Research Bioreason

BioReason Chat Export

Thinking Trace

Functional Summary

UniProt Summary

InterPro Domains

GO Terms

Deep Research Bioreason Rl

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Thinking Trace

Functional Summary

UniProt Summary

InterPro Domains

GO Terms

Bioreason Rl Review

BioReason-Pro RL Review: GroEL (E. coli)

Functional Summary Review

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