grpE

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0000774 adenyl-nucleotide exchange factor activity	IBA GO_REF:0000033	ACCEPT	Summary: PAINT transfers adenyl-nucleotide exchange factor activity through the GrpE family. E. coli GrpE directly catalyzes release of DnaK-bound ATP or ADP and is itself one of the experimentally supported descendants in this node. Reason: GrpE's core activity is ADP/ATP exchange on the DnaK Hsp70 ATPase cycle. The placement at PTHR21237/PTN000478264 is appropriate because bacterial, mitochondrial, and fungal GrpE-family proteins are Hsp70 nucleotide-exchange factors. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000478264 · PANTHER:PTN000478264 SUPPORTS TRANSFER Current PTHR21237 PAINT retains adenyl-nucleotide exchange factor activity at this GrpE-family node. UniProtKB:P09372 · GrpE SUPPORTS TRANSFER GrpE's own experimental nucleotide-exchange evidence validly seeds the ancestral assertion. MGI:MGI:1334416 · MGI:MGI:1334416 SUPPORTS TRANSFER Listed descendant evidence for the conserved GrpE-family nucleotide-exchange assertion. SGD:S000005758 · SGD:S000005758 SUPPORTS TRANSFER Listed descendant evidence for the conserved GrpE-family nucleotide-exchange assertion. UniProtKB:Q8TAA5 · UniProtKB:Q8TAA5 SUPPORTS TRANSFER Listed descendant evidence for the conserved GrpE-family nucleotide-exchange assertion. UniProtKB:Q9HAV7 · UniProtKB:Q9HAV7 SUPPORTS TRANSFER Listed descendant evidence for the conserved GrpE-family nucleotide-exchange assertion. Supporting Evidence: PMID:1826368 The presence of GrpE alone increases the rate of release of bound ATP or ADP without affecting the rate of hydrolysis.
GO:0000774 adenyl-nucleotide exchange factor activity	IDA PMID:1826368 Escherichia coli DnaJ and GrpE heat shock proteins jointly s...	ACCEPT	Summary: Liberek et al. showed that GrpE accelerates release of DnaK-bound ATP or ADP and, together with DnaJ, can strongly stimulate DnaK ATPase cycling. Reason: The IDA directly establishes GrpE as the DnaK nucleotide-exchange factor; nucleotide release is the biochemical step that GrpE contributes to the Hsp70 chaperone cycle. Supporting Evidence: PMID:1826368 The presence of GrpE alone increases the rate of release of bound ATP or ADP without affecting the rate of hydrolysis.
GO:0000774 adenyl-nucleotide exchange factor activity	IDA PMID:8599944 A cycle of binding and release of the DnaK, DnaJ and GrpE ch...	ACCEPT	Summary: Gamer et al. showed that GrpE promotes nucleotide release from DnaK-DnaJ-sigma32 complexes, driving ATP-dependent dissociation in the heat-shock feedback cycle. Reason: The sigma32 work applies the same core GrpE nucleotide-exchange mechanism to a regulatory DnaK substrate; GrpE stimulates nucleotide release from the DnaK complex and thereby reverses stable DnaK-ADP binding. Supporting Evidence: PMID:8599944 GrpE binding to these complexes stimulates nucleotide release and subsequent complex dissociation by ATP.
GO:0000774 adenyl-nucleotide exchange factor activity	IEA GO_REF:0000002	ACCEPT	Summary: InterPro2GO maps the GrpE family domain IPR000740 to adenyl-nucleotide exchange factor activity. Reason: The family-level mapping is correct for E. coli GrpE, whose defining activity is DnaK ADP/ATP exchange. Supporting Evidence: PMID:17976642 GrpE acts as a nucleotide exchange factor for DnaK, the main Hsp70 protein in bacteria
GO:0005515 protein binding	IPI PMID:15690043 Interaction network containing conserved and essential prote...	REMOVE	Summary: Large-scale affinity-purification/mass-spectrometry row with GroEL as the interacting partner. Reason: The generic GO:0005515 row is uninformative, and this broad physical interaction with GroEL does not by itself establish a specific GrpE molecular function. GrpE's core chaperone-system binding is its interaction with DnaK, which is captured by separate GO:0051087 replacement rows.
GO:0005515 protein binding	IPI PMID:15690043 Interaction network containing conserved and essential prote...	MODIFY	Summary: Large-scale affinity-purification/mass-spectrometry row with DnaK as the interacting partner. Reason: The observed DnaK-GrpE interaction is a bona fide co-chaperone interaction and is better represented by GO:0051087 protein-folding chaperone binding than by generic protein binding. Proposed replacements: protein-folding chaperone binding Supporting Evidence: PMID:2522091 Coimmunoprecipitation of DnaK+ and GrpE+ proteins from cell lysates with anti-DnaK antibodies demonstrated their interaction in vitro.
GO:0005515 protein binding	IPI PMID:15690043 Interaction network containing conserved and essential prote...	REMOVE	Summary: Large-scale affinity-purification/mass-spectrometry row with MntH as the interacting partner. Reason: MntH is an unrelated divalent metal/proton antiporter, and this large-scale physical interaction does not support a more specific GrpE molecular function. The generic GO:0005515 annotation is removed rather than retained as a gene-function assertion.
GO:0005515 protein binding	IPI PMID:16606699 Large-scale identification of protein-protein interaction of...	MODIFY	Summary: Large-scale pull-down row with DnaK as the interacting partner. Reason: DnaK is the functional target of the GrpE nucleotide-exchange factor, so this DnaK interaction is more informatively captured by GO:0051087 protein-folding chaperone binding. Proposed replacements: protein-folding chaperone binding Supporting Evidence: PMID:2522091 Coimmunoprecipitation of DnaK+ and GrpE+ proteins from cell lysates with anti-DnaK antibodies demonstrated their interaction in vitro.
GO:0005515 protein binding	IPI PMID:16858726 A complexomic study of Escherichia coli using two-dimensiona...	MODIFY	Summary: Blue-native/SDS-PAGE complexomics row with DnaK as the interacting partner. Reason: DnaK-GrpE complex formation is a core co-chaperone interaction in the Hsp70 cycle; GO:0051087 is the specific binding term for this row. Proposed replacements: protein-folding chaperone binding Supporting Evidence: PMID:2522091 Coimmunoprecipitation of DnaK+ and GrpE+ proteins from cell lysates with anti-DnaK antibodies demonstrated their interaction in vitro.
GO:0005515 protein binding	IPI PMID:17976642 GrpE N-terminal domain contributes to the interaction with D...	MODIFY	Summary: Isothermal-titration and proteolysis analysis of wild-type and N-terminally truncated GrpE binding to the DnaK nucleotide-binding domain. Reason: The paper directly dissects GrpE binding to DnaK, its cognate protein-folding chaperone. GO:0051087 captures this specific co-chaperone interaction. Proposed replacements: protein-folding chaperone binding Supporting Evidence: PMID:17976642 GrpE association to DnaK nucleotide-binding domain involves side-chain and backbone interactions located within the "headpiece" of the cochaperone
GO:0005515 protein binding	IPI PMID:19402753 Global functional atlas of Escherichia coli encompassing pre...	REMOVE	Summary: High-throughput functional-atlas row with MntH as the interacting partner. Reason: This generic binding row comes from a systems-scale interaction map and links GrpE to the unrelated MntH transporter. It does not define GrpE's DnaK nucleotide-exchange function and no specific GO replacement is supported.
GO:0005515 protein binding	IPI PMID:24561554 The binary protein-protein interaction landscape of Escheric...	REMOVE	Summary: Yeast-two-hybrid interaction row with GroEL as the interacting partner. Reason: Binary interaction evidence with GroEL is not sufficient to infer a specific GrpE activity, and GrpE's established protein-folding chaperone partner is DnaK. The generic GO:0005515 assertion is therefore removed.
GO:0005515 protein binding	IPI PMID:2522091 Escherichia coli DnaK and GrpE heat shock proteins interact ...	MODIFY	Summary: Johnson et al. showed that DnaK and GrpE interact by genetic suppression and by coimmunoprecipitation of the two heat-shock proteins. Reason: The evidence supports the DnaK-GrpE co-chaperone interaction, and GO:0051087 is more informative than generic protein binding for a GrpE-DnaK row. Proposed replacements: protein-folding chaperone binding Supporting Evidence: PMID:2522091 Coimmunoprecipitation of DnaK+ and GrpE+ proteins from cell lysates with anti-DnaK antibodies demonstrated their interaction in vitro.
GO:0005515 protein binding	IPI PMID:9103205 Crystal structure of the nucleotide exchange factor GrpE bou...	MODIFY	Summary: Harrison et al. solved the crystal structure of an asymmetric DnaK ATPase-domain complex with a GrpE dimer. Reason: The crystal structure directly demonstrates GrpE binding to DnaK. Because DnaK is the protein-folding chaperone whose nucleotide state GrpE controls, GO:0051087 is the appropriate replacement for generic GO:0005515. Proposed replacements: protein-folding chaperone binding Supporting Evidence: PMID:9103205 A dimer of GrpE binds asymmetrically to a single molecule of DnaK
GO:0005737 cytoplasm	HDA PMID:16858726 A complexomic study of Escherichia coli using two-dimensiona...	ACCEPT	Summary: Blue-native/SDS-PAGE proteomics detected GrpE in the cytosolic complexome. Reason: Cytoplasmic localization is consistent with GrpE's role in the DnaK/DnaJ chaperone cycle. Supporting Evidence: PMID:16858726 the cytosolic and membrane protein complexes of Escherichia coli were separated
GO:0005737 cytoplasm	IEA GO_REF:0000120	ACCEPT	Summary: Automated UniProt subcellular localization inference places GrpE in the cytoplasm. Reason: GrpE acts on cytosolic DnaK and is repeatedly recovered from soluble/cytosolic proteome fractions. Supporting Evidence: PMID:18304323 we identified 1103 proteins from the cytosolic fraction of the Escherichia coli strain MC4100
GO:0005829 cytosol	IBA GO_REF:0000033	ACCEPT	Summary: PAINT transfers cytosolic localization for bacterial GrpE, using E. coli GrpE as descendant evidence. Reason: Cytosol is the correct activity location for E. coli GrpE and its DnaK substrate. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN008575294 · PANTHER:PTN008575294 SUPPORTS TRANSFER Current PTHR21237 PAINT places bacterial GrpE cytosol at this node. UniProtKB:P09372 · GrpE SUPPORTS TRANSFER E. coli GrpE cytosolic evidence supports the node and target. Supporting Evidence: PMID:18304323 we identified 1103 proteins from the cytosolic fraction of the Escherichia coli strain MC4100
GO:0005829 cytosol	IDA PMID:15911532 Localization, annotation, and comparison of the Escherichia ...	ACCEPT	Summary: Fractionation proteomics assigned GrpE to the E. coli cytosol. Reason: This localization directly matches the known soluble DnaK/DnaJ/GrpE system. Supporting Evidence: PMID:15911532 2,160 were annotated and assigned to the cytosol, periplasm, inner membrane, and outer membrane by biochemical fractionation
GO:0005829 cytosol	IDA PMID:18304323 Protein abundance profiling of the Escherichia coli cytosol.	ACCEPT	Summary: Ishihama et al. detected GrpE in their quantitative E. coli cytosol proteome. Reason: The row independently supports the cytosol as GrpE's normal compartment. Supporting Evidence: PMID:18304323 we identified 1103 proteins from the cytosolic fraction of the Escherichia coli strain MC4100
GO:0006457 protein folding	IEA GO_REF:0000002	ACCEPT	Summary: InterPro2GO infers protein folding from the GrpE family and head domains. Reason: GrpE performs nucleotide exchange for DnaK, allowing repeated substrate-binding and release cycles that are required for efficient Hsp70-mediated protein folding. Supporting Evidence: PMID:1826368 The stimulation of the ATPase activity of DnaK may contribute to its more efficient recycling
GO:0009408 response to heat	IDA PMID:11084044 Reversible thermal transition in GrpE, the nucleotide exchan...	ACCEPT	Summary: Grimshaw et al. showed that GrpE undergoes a reversible thermal transition over the physiologically relevant heat-shock range that modulates DnaK cycling. Reason: GrpE is a heat-shock chaperone-system component whose own thermally reversible conformation can tune DnaK substrate affinity at elevated temperatures. Supporting Evidence: PMID:11084044 GrpE undergoes extensive but fully reversible conformational changes in the physiologically relevant temperature range
GO:0009408 response to heat	IEP PMID:8349564 Characterization of twenty-six new heat shock genes of Esche...	ACCEPT	Summary: Neidhardt et al. characterized grpE among heat-shock genes. Reason: GrpE is part of the sigma32-regulated heat-shock chaperone network and functions with DnaK/DnaJ under thermal protein-folding stress. Supporting Evidence: PMID:8349564 Characterization of twenty-six new heat shock genes of Escherichia coli.
GO:0019904 protein domain specific binding	IPI PMID:9103205 Crystal structure of the nucleotide exchange factor GrpE bou...	MODIFY	Summary: The crystal structure resolved GrpE bound to the DnaK ATPase domain. Reason: The row is mechanistically a DnaK nucleotide-binding-domain interaction, but the more informative GO molecular-function term is GO:0051087, since the bound DnaK domain is part of a protein-folding chaperone controlled by GrpE. Proposed replacements: protein-folding chaperone binding Supporting Evidence: PMID:9103205 A dimer of GrpE binds asymmetrically to a single molecule of DnaK
GO:0032991 protein-containing complex	IDA PMID:9103205 Crystal structure of the nucleotide exchange factor GrpE bou...	KEEP AS NON CORE	Summary: The DnaK ATPase-domain/GrpE crystal structure demonstrates a stable GrpE-containing protein complex. Reason: The statement is true, but GO:0032991 is a root-level cellular-component term that says only that GrpE is part of some protein complex. The specific functional interaction is better represented by GrpE's DnaK nucleotide-exchange activity and protein-folding chaperone binding. Supporting Evidence: PMID:9103205 A dimer of GrpE binds asymmetrically to a single molecule of DnaK
GO:0042803 protein homodimerization activity	IDA PMID:8444859 Initiation of lambda DNA replication. The Escherichia coli s...	KEEP AS NON CORE	Summary: IDA homodimerization row assigned by CAFA. GrpE homodimerization is well established, although the cached Osipiuk abstract is focused on lambda P/DnaK/GrpE complexes rather than isolated GrpE dimerization. Reason: GrpE is a homodimer, but homodimerization is structural architecture supporting its DnaK nucleotide-exchange activity rather than the terminal molecular function. Supporting Evidence: PMID:9103205 A dimer of GrpE binds asymmetrically to a single molecule of DnaK
GO:0042803 protein homodimerization activity	IDA PMID:9103205 Crystal structure of the nucleotide exchange factor GrpE bou...	KEEP AS NON CORE	Summary: Harrison et al. directly observed a GrpE dimer in complex with one DnaK ATPase-domain molecule. Reason: The homodimeric state is real and functionally important, but the core activity of the dimer is DnaK nucleotide exchange. Supporting Evidence: PMID:9103205 A dimer of GrpE binds asymmetrically to a single molecule of DnaK
GO:0042803 protein homodimerization activity	IEA GO_REF:0000002	KEEP AS NON CORE	Summary: InterPro2GO infers homodimerization from the GrpE family domain. Reason: This family-level assertion is correct for E. coli GrpE, but homodimerization is a non-core architectural feature of the nucleotide-exchange factor. Supporting Evidence: PMID:9103205 A dimer of GrpE binds asymmetrically to a single molecule of DnaK
GO:0043335 protein unfolding	IDA PMID:20953191 The kinetic parameters and energy cost of the Hsp70 chaperon...	ACCEPT	Summary: Sharma et al. characterized a bacterial Hsp70-Hsp40-NEF system that uses ATP to unfold stably misfolded polypeptides into intermediates that can refold after chaperone release. Reason: In E. coli, GrpE is the nucleotide-exchange factor that recycles DnaK in this Hsp70/Hsp40/NEF unfoldase reaction. GrpE directly performs the nucleotide-exchange step that resets DnaK for substrate release and rebinding, even though DnaK and DnaJ rather than GrpE contact the client polypeptide. Supporting Evidence: PMID:20953191 Hsp70-Hsp40-NEF and possibly Hsp100 are the only known molecular chaperones that can use the energy of ATP to convert stably pre-aggregated polypeptides into natively refolded proteins.
GO:0051087 protein-folding chaperone binding	IEA GO_REF:0000002	ACCEPT	Summary: InterPro2GO maps the GrpE family to protein-folding chaperone binding. Reason: GrpE binds the protein-folding chaperone DnaK to catalyze nucleotide exchange; the family mapping correctly captures this chaperone-partner interaction. Supporting Evidence: PMID:9103205 A dimer of GrpE binds asymmetrically to a single molecule of DnaK
GO:0065003 protein-containing complex assembly	IMP PMID:9103205 Crystal structure of the nucleotide exchange factor GrpE bou...	KEEP AS NON CORE	Summary: CAFA-assigned row citing the GrpE-DnaK crystal-structure paper. GrpE forms DnaK-bound co-chaperone complexes, but no named GO complex exists for the transient GrpE2:DnaK nucleotide-exchange assembly. Reason: DnaK-GrpE complex formation is a mechanistic intermediate in the nucleotide-exchange cycle rather than a core biological process in its own right. The annotation is kept as a true but generic non-core statement. Supporting Evidence: PMID:9103205 A dimer of GrpE binds asymmetrically to a single molecule of DnaK

Gene Description

Existing Annotations Review

Core Functions

GrpE binds DnaK as its cognate protein-folding-chaperone partner. This direct binding targets the DnaK nucleotide-binding domain and is required for GrpE's control of the Hsp70 ATPase cycle, including both client folding and sigma32 feedback regulation.

References

Suggested Questions for Experts

Suggested Experiments

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Notes

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