Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0005829 cytosol	IBA GO_REF:0000033	ACCEPT	Summary: SecB is a soluble, cytosolic protein. This is well-established by purification as a cytosolic factor (PMID:2649892) and proteomics profiling (PMID:18304323). The IBA annotation is consistent with multiple IDA annotations for the same term. Reason: SecB is definitively a cytosolic protein. Watanabe and Blobel purified it as a "cytosolic factor" (PMID:2649892), and it was identified in cytosolic proteomics (PMID:18304323). UniProt annotation confirms "Cytoplasm" subcellular location. The IBA annotation is fully supported. Supporting Evidence: PMID:2649892 We have purified to homogeneity a cytosolic factor from Escherichia coli that is required for the translocation of a preprotein into inverted vesicles of the E. coli plasma membrane. PMID:18304323 we identified 1103 proteins from the cytosolic fraction of the Escherichia coli strain MC4100
GO:0036506 maintenance of unfolded protein	IBA GO_REF:0000033	ACCEPT	Summary: SecB maintains precursor proteins in an unfolded, translocation-competent state. This antifolding/holdase activity is the core biological process of SecB, demonstrated by both in vivo and in vitro experiments (PMID:2834066, PMID:2848249, PMID:18048690). Reason: This is a core function of SecB. Collier et al. showed that SecB prevents premature folding of MBP precursor (PMID:2834066). Weiss et al. demonstrated that purified SecB "quantitatively retarded folding of precursor MBP into a stable, protease-resistant conformation" (PMID:2848249). Bechtluft et al. showed by single-molecule optical tweezers that SecB "completely prevent stable tertiary contacts" and "retains MBP in this [molten-globule] state" (PMID:18048690). The IBA annotation is well-supported by experimental evidence. Supporting Evidence: PMID:2834066 Evidence is presented that the E. coli secB gene encodes a soluble protein that interacts with the mature region of the precursor maltose-binding protein (MBP), and promotes MBP export by preventing premature folding of the newly synthesized polypeptide into an export-incompetent form. PMID:2848249 The purified protein also quantitatively retarded folding of precursor MBP into a stable, protease-resistant conformation in the absence of membranes. PMID:18048690 Interactions with SecB completely prevent stable tertiary contacts in the core structure but have no detectable effect on the folding of the external alpha helices. It appears that SecB only binds to the extended or molten globulelike structure and retains MBP in this latter state.
GO:0043952 protein transport by the Sec complex	IBA GO_REF:0000033	ACCEPT	Summary: SecB is a dedicated component of the Sec-dependent protein export pathway. It delivers unfolded preproteins to SecA, which is the peripheral ATPase of the SecYEG translocon (PMID:2170023, PMID:9321390). SecB mutations cause pleiotropic defects in protein secretion (PMID:6403503). Reason: SecB is specifically dedicated to the Sec translocation pathway. The GO term comment notes this is for "proteins that compose the transport complex but not the proteins being transported." SecB is not a structural component of the translocon itself, but rather functions as the dedicated chaperone that delivers substrates to the Sec machinery. The original secB mutant was identified by defective protein secretion (PMID:6403503), and the SecB-SecA-SecYEG binding cascade is well-established (PMID:2170023). The IBA annotation is appropriate. Supporting Evidence: PMID:2170023 The binding cascade of SecB to SecA to SecY/E mediates preprotein targeting to the E. coli plasma membrane. PMID:6403503 These secB mutants were defective in the localization of maltose-binding protein and, in at least one case, OmpF protein.
GO:0051082 unfolded protein binding	IBA GO_REF:0000033	MODIFY	Summary: SecB does bind unfolded proteins, but GO:0051082 (unfolded protein binding) under-represents the actual molecular function. SecB is not merely a passive binder of unfolded proteins; it actively carries unfolded precursors from the ribosome/cytosol to SecA at the membrane (PMID:2170023, PMID:16962134). GO:0140309 (unfolded protein carrier activity) better captures this carrier/escort function. Reason: SecB is a canonical example of a protein carrier chaperone. It binds unfolded preproteins and escorts them to SecA at translocation sites. Crane et al. mapped the path of unfolded precursor on SecB surface and described a "model for transfer of the ligand" from SecB to SecA (PMID:16962134). Hartl et al. described SecB as having "a dual function in stabilizing the precursor and in passing it on to membrane-bound SecA" (PMID:2170023). The GO term GO:0140309 "unfolded protein carrier activity" (defined as "A protein carrier activity that binds to a protein in an unfolded state and escorts it between two different cellular components") precisely describes SecB function. GO:0051082 is slated for obsoletion, and the carrier term is the correct replacement. Proposed replacements: unfolded protein carrier activity Supporting Evidence: PMID:16962134 Capture of the precursor polypeptides before they fold is achieved by the promiscuous binding to the chaperone SecB. SecB delivers its ligand to export sites through its specific binding to SecA, a peripheral component of the membrane translocon. At the translocon the ligand is passed from SecB to SecA and subsequently through the SecYEG channel. PMID:2170023 SecB has a dual function in stabilizing the precursor and in passing it on to membrane-bound SecA, the next step in the pathway. SecA itself is bound to the membrane by its affinity (Kd approximately 4 x 10(-8) M) for SecY/E and for acidic lipids.
GO:0070678 preprotein binding	IBA GO_REF:0000033	ACCEPT	Summary: SecB binds specifically to precursor (preprotein) forms of exported proteins in vivo and in vitro (PMID:2664780). Kumamoto showed that SecB associates with precursor forms of MBP, LamB, and OmpA but not cytoplasmic beta-galactosidase (PMID:2664780). This is a core molecular function. Reason: Preprotein binding is a core and well-characterized function of SecB. The IBA annotation is strongly supported by experimental data showing SecB-preprotein complexes in vivo (PMID:2664780) and the extensive characterization of SecB substrates (UniProt lists DegP, FhuA, FkpA, GBP, LamB, MalE, OmpA, OmpF, OmpT, OmpX, OppA, PhoE, TolB, TolC and others). Supporting Evidence: PMID:2664780 in wild-type growing cells, SecB protein associates with precursor forms of exported proteins, such as the periplasmic maltose-binding protein (MBP) and the outer-membrane proteins LamB and OmpA. In contrast, the cytoplasmic protein beta-galactosidase was not found in association with SecB.
GO:0005737 cytoplasm	IEA GO_REF:0000120	ACCEPT	Summary: SecB is a cytoplasmic/cytosolic protein. This IEA annotation to cytoplasm is broader than the IBA/IDA annotations to cytosol (GO:0005829) but is not incorrect. Reason: This is a broader localization annotation. Since cytosol is part of cytoplasm, the IEA annotation is technically correct though less specific than the IDA cytosol annotations. Acceptable as a supplementary annotation.
GO:0006457 protein folding	IEA GO_REF:0000104	REMOVE	Summary: SecB is annotated to protein folding via automated transfer from UniRule. However, SecB is an anti-folding chaperone: its function is to PREVENT folding, not to assist in it. SecB maintains proteins in an unfolded state for translocation (PMID:2834066, PMID:2848249, PMID:18048690). Reason: SecB is functionally opposite to a protein folding chaperone. While GroEL/DnaK assist in proper folding, SecB specifically prevents folding. Collier et al. described SecB's function as "antifolding activity" (PMID:2834066). Bechtluft et al. showed SecB "completely prevent stable tertiary contacts" (PMID:18048690). Weiss et al. demonstrated SecB "retards folding" (PMID:2848249). The correct biological process annotation is GO:0036506 "maintenance of unfolded protein" (already present). The protein folding annotation is misleading. Supporting Evidence: PMID:2834066 The antifolding activity of SecB promotes the export of the E. coli maltose-binding protein. PMID:18048690 Interactions with SecB completely prevent stable tertiary contacts in the core structure
GO:0015031 protein transport	IEA GO_REF:0000120	ACCEPT	Summary: SecB is involved in the transport of preproteins to the membrane for translocation. This IEA annotation to the broad term protein transport is acceptable as a general description, though the more specific GO:0043952 (protein transport by the Sec complex) is present and more informative. Reason: SecB plays an essential role in protein transport, specifically in the Sec-dependent export pathway. The IEA annotation is correct and consistent with the more specific IBA annotation to GO:0043952. Since this is a broader IEA, it is acceptable alongside the more specific annotation.
GO:0051082 unfolded protein binding	IEA GO_REF:0000002	MODIFY	Summary: This IEA annotation to unfolded protein binding from InterPro is the same term as the IBA annotation above. The same reasoning applies: SecB is more accurately described as having unfolded protein carrier activity (GO:0140309) rather than mere binding. Reason: Same rationale as the IBA annotation for GO:0051082. SecB does not merely bind unfolded proteins; it actively carries them to SecA. GO:0140309 (unfolded protein carrier activity) is the appropriate replacement. Proposed replacements: unfolded protein carrier activity Supporting Evidence: PMID:16962134 SecB delivers its ligand to export sites through its specific binding to SecA, a peripheral component of the membrane translocon.
GO:0051262 protein tetramerization	IEA GO_REF:0000002	ACCEPT	Summary: SecB forms a homotetramer (dimer of dimers) as confirmed by crystal structure (PMID:14643199) and biochemical characterization (PMID:2649892). This IEA annotation is consistent with experimental evidence. Reason: SecB is a well-characterized homotetramer. Watanabe and Blobel determined SecB is "a 64-kDa tetramer consisting of four identical 16-kDa subunits" (PMID:2649892). The crystal structure confirms the dimer-of-dimers architecture (UniProt cites PubMed:14643199, PubMed:27501151). While tetramerization is structural rather than a core evolved function, the annotation is factually accurate. Supporting Evidence: PMID:2649892 The purified factor amounts to 0.08% of the cytosolic proteins and is a 64-kDa tetramer consisting of four identical 16-kDa subunits.
GO:0005515 protein binding	IPI PMID:15690043 Interaction network containing conserved and essential prote...	MARK AS OVER ANNOTATED	Summary: High-throughput affinity purification/mass spectrometry study identified SecB interactions with CpxR and SecA (PMID:15690043). The annotation to generic "protein binding" is uninformative; more specific terms exist. Reason: "Protein binding" (GO:0005515) is uninformative per curation guidelines. The interaction with SecA is well-captured by the preprotein binding and carrier function annotations. The interaction with CpxR from this high-throughput study has uncertain functional significance and does not warrant a specific annotation. The interaction with SecA is already covered by more specific annotations. Supporting Evidence: PMID:15690043 648 could be purified to homogeneity and their interacting protein partners identified by mass spectrometry
GO:0005515 protein binding	IPI PMID:19402753 Global functional atlas of Escherichia coli encompassing pre...	MARK AS OVER ANNOTATED	Summary: Large-scale E. coli functional atlas study (PMID:19402753) showing SecB-CpxR interaction. Same uninformative generic binding annotation. Reason: Same rationale as the PMID:15690043 annotation. Generic "protein binding" is uninformative. The functionally meaningful interactions are captured by more specific terms (preprotein binding, carrier activity). Supporting Evidence: PMID:19402753 we performed an extensive proteomic survey using affinity-tagged E. coli strains and generated comprehensive genomic context inferences to derive a high-confidence compendium for virtually the entire proteome consisting of 5,993 putative physical interactions
GO:0005515 protein binding	IPI PMID:21037004 Orientation of SecA and SecB in complex, derived from disulf...	MARK AS OVER ANNOTATED	Summary: Suo et al. used disulfide cross-linking to determine the orientation of SecA and SecB in complex (PMID:21037004). This demonstrates the specific SecA-SecB interaction that is central to SecB carrier function. The annotation to generic "protein binding" is uninformative. Reason: This study characterizes the SecB-SecA interaction in detail, which is better captured by the carrier activity and preprotein binding annotations. Generic "protein binding" does not convey the functional significance. Supporting Evidence: PMID:21037004 The tetrameric cytoplasmic chaperone SecB binds to precursors of exported proteins before they can become stably folded and delivers them to SecA.
GO:0036506 maintenance of unfolded protein	IMP PMID:2834066 The antifolding activity of SecB promotes the export of the ...	ACCEPT	Summary: Collier et al. demonstrated the antifolding activity of SecB in vivo using genetic approaches. SecB- cells showed defective MBP export that was suppressed by mutations affecting MBP folding, and the rate of MBP folding was retarded in the presence of excess SecB (PMID:2834066). Reason: This is strong experimental evidence (IMP) for SecB's core antifolding function. The genetic suppression experiments directly demonstrate that SecB's role is to prevent premature folding of export substrates. This is a core function. Supporting Evidence: PMID:2834066 The antifolding activity of SecB was demonstrated by the following: the defect in MBP export in SecB- cells was suppressed by mutational alterations affecting MBP folding; export of a mutant MBP that is accomplished in a strictly posttranslational mode was totally blocked in SecB- cells; and the rate of folding of wild-type MBP synthesized in vitro was found to be accelerated when SecB was absent and greatly retarded when excess SecB was present.
GO:0036506 maintenance of unfolded protein	IDA PMID:2848249 Purified secB protein of Escherichia coli retards folding an...	ACCEPT	Summary: Weiss et al. purified SecB and demonstrated directly that it retards folding of precursor MBP in vitro and promotes membrane translocation. Purified SecB both retarded folding and prolonged translocation competence (PMID:2848249). Reason: Direct biochemical demonstration of SecB antifolding activity using purified protein. This IDA evidence is strong support for maintenance of unfolded protein as a core function. Supporting Evidence: PMID:2848249 The purified protein also quantitatively retarded folding of precursor MBP into a stable, protease-resistant conformation in the absence of membranes. Finally, the inclusion of excess purified SecB in a SecB+ in vitro system significantly prolonged the time in which precursor MBP remained competent for posttranslational import into membrane vesicles.
GO:0005515 protein binding	IPI PMID:15811382 Asymmetric binding between SecA and SecB two symmetric prote...	MARK AS OVER ANNOTATED	Summary: Randall et al. characterized the asymmetric binding between SecA and SecB, showing that SecB C-terminal alpha-helices bind in the SecA dimer interface (PMID:15811382). This documents the specific SecA-SecB interaction central to the carrier/delivery function. Reason: The specific SecB-SecA interaction studied here is functionally meaningful and central to the carrier function, but generic "protein binding" does not convey this. The carrier activity and preprotein binding annotations better capture the functional significance. Per curation guidelines, protein binding is uninformative. Supporting Evidence: PMID:15811382 SecB also demonstrates specific recognition of, and binding to, SecA. SecB with the precursor tightly bound enters an export-active complex with SecA and must pass the ligand to SecA at the translocon in the membrane.
GO:0005515 protein binding	IPI PMID:2170023 The binding cascade of SecB to SecA to SecY/E mediates prepr...	MARK AS OVER ANNOTATED	Summary: Hartl et al. characterized the SecB-SecA-SecYEG binding cascade and determined binding affinities (PMID:2170023). This is a foundational paper for understanding SecB's carrier function. The annotation to generic "protein binding" is uninformative. Reason: This landmark study defines the binding cascade that constitutes SecB's carrier activity. Generic "protein binding" fails to capture this. The carrier activity and preprotein binding annotations are more informative. Supporting Evidence: PMID:2170023 SecB has a dual function in stabilizing the precursor and in passing it on to membrane-bound SecA, the next step in the pathway.
GO:0070678 preprotein binding	IDA PMID:2664780 Escherichia coli SecB protein associates with exported prote...	ACCEPT	Summary: Kumamoto showed that SecB associates with precursor forms of exported proteins (MBP, LamB, OmpA) in vivo, and that these complexes are transient intermediates in the export pathway (PMID:2664780). This is direct experimental evidence for preprotein binding. Reason: Strong IDA evidence for a core function. SecB specifically recognizes and binds preprotein forms of exported proteins. This is the binding component of its carrier function. Supporting Evidence: PMID:2664780 in wild-type growing cells, SecB protein associates with precursor forms of exported proteins, such as the periplasmic maltose-binding protein (MBP) and the outer-membrane proteins LamB and OmpA. In contrast, the cytoplasmic protein beta-galactosidase was not found in association with SecB. Pulse-chase analysis showed that the SecB-precursor MBP complex was short lived, as expected for a complex that represents an intermediate in the protein-export pathway.
GO:0005515 protein binding	IPI PMID:9321390 The molecular chaperone SecB is released from the carboxy-te...	MARK AS OVER ANNOTATED	Summary: Fekkes et al. identified the SecB binding site on SecA (the extreme C-terminal 22 residues) and showed SecB is released upon ATP binding by SecA (PMID:9321390). This characterizes the mechanistic detail of the SecB-SecA handoff. Reason: This important mechanistic study defines the SecB-SecA interaction site and the release mechanism. However, annotation to generic "protein binding" is uninformative. The carrier activity annotation better captures this delivery/handoff function. Supporting Evidence: PMID:9321390 The chaperone SecB keeps precursor proteins in a translocation-competent state and targets them to SecA at the translocation sites in the cytoplasmic membrane of Escherichia coli. ... SecB is released from this site at the onset of translocation.
GO:0008104 intracellular protein localization	IMP PMID:6403503 Mutations in a new gene, secB, cause defective protein local...	ACCEPT	Summary: Kumamoto and Beckwith identified secB mutants with defective protein localization, showing SecB is required for proper localization of MBP and OmpF (PMID:6403503). This is the founding paper for SecB function. Reason: This is the original identification of the secB gene and its role in protein localization. While the more specific annotations (protein transport by the Sec complex, protein targeting) also capture this, the broader intracellular protein localization term is appropriate for what the mutant phenotype directly demonstrates. Supporting Evidence: PMID:6403503 These secB mutants were defective in the localization of maltose-binding protein and, in at least one case, OmpF protein. Double mutants with lesions in both secA and secB had strong defects in the secretion of maltose-binding protein and OmpF protein.
GO:0051082 unfolded protein binding	IDA PMID:16962134 Sites of interaction of a precursor polypeptide on the expor...	MODIFY	Summary: Crane et al. used site-directed spin labeling and EPR to map the binding pathway of unfolded precursor galactose-binding protein on SecB (PMID:16962134). They showed the precursor makes contact with a large portion of the SecB surface and established a model for transfer of the ligand from SecB to SecA. Reason: While this paper confirms SecB binds unfolded proteins, the study explicitly describes the delivery/transfer function: "SecB delivers its ligand to export sites through its specific binding to SecA" and discusses "a model for transfer of the ligand." This is carrier activity, not mere binding. GO:0140309 (unfolded protein carrier activity) captures the complete function. Proposed replacements: unfolded protein carrier activity Supporting Evidence: PMID:16962134 Export of protein into the periplasm of Escherichia coli via the general secretory system requires that the transported polypeptides be devoid of stably folded tertiary structure. Capture of the precursor polypeptides before they fold is achieved by the promiscuous binding to the chaperone SecB. SecB delivers its ligand to export sites through its specific binding to SecA, a peripheral component of the membrane translocon. At the translocon the ligand is passed from SecB to SecA and subsequently through the SecYEG channel.
GO:0051082 unfolded protein binding	IMP PMID:18048690 Direct observation of chaperone-induced changes in a protein...	MODIFY	Summary: Bechtluft et al. used optical tweezers and molecular dynamics to show SecB prevents stable tertiary contacts in MBP and retains it in a molten-globule-like state (PMID:18048690). This demonstrates the holdase activity that is part of the carrier function. Reason: Same reasoning as other GO:0051082 annotations. While this paper focuses on the antifolding/holdase mechanism, the broader context of SecB function is carrier activity: binding unfolded proteins and delivering them. GO:0140309 (unfolded protein carrier activity) is the appropriate replacement that encompasses both binding and delivery. Proposed replacements: unfolded protein carrier activity Supporting Evidence: PMID:18048690 It appears that SecB only binds to the extended or molten globulelike structure and retains MBP in this latter state. Thus during MBP translocation, no energy is required to disrupt stable tertiary interactions.
GO:0005829 cytosol	IDA PMID:18304323 Protein abundance profiling of the Escherichia coli cytosol.	ACCEPT	Summary: Ishihama et al. identified SecB in the cytosolic proteome of E. coli by mass spectrometry (PMID:18304323). Direct experimental evidence for cytosolic localization. Reason: Proteomic identification of SecB in the cytosolic fraction is direct evidence for cytosol localization. Supporting Evidence: PMID:18304323 we identified 1103 proteins from the cytosolic fraction of the Escherichia coli strain MC4100
GO:0005829 cytosol	IDA PMID:2649892 Cytosolic factor purified from Escherichia coli is necessary...	ACCEPT	Summary: Watanabe and Blobel purified SecB as a cytosolic factor required for preprotein translocation (PMID:2649892). This is foundational evidence for SecB cytosolic localization. Reason: SecB was originally purified as a cytosolic factor, providing direct evidence for cytosol localization. Supporting Evidence: PMID:2649892 We have purified to homogeneity a cytosolic factor from Escherichia coli that is required for the translocation of a preprotein into inverted vesicles of the E. coli plasma membrane.
GO:0006605 protein targeting	IMP PMID:6403503 Mutations in a new gene, secB, cause defective protein local...	ACCEPT	Summary: SecB mutations cause defective protein targeting/localization. The original secB mutants showed pleiotropic defects in secretion of envelope proteins (PMID:6403503). Reason: SecB is essential for targeting a subset of preproteins to the Sec translocon. The GO:0006605 definition ("targeting specific proteins to particular regions of the cell") accurately describes SecB's role in directing preproteins to the inner membrane for translocation. This is consistent with but slightly different from the protein transport annotations. Supporting Evidence: PMID:6403503 We isolated a new class of Escherichia coli mutants with pleiotropic defects in protein secretion. ... the selection also yielded mutants with mutations in a new locus, which was designated secB.
GO:0015031 protein transport	IMP PMID:6403503 Mutations in a new gene, secB, cause defective protein local...	ACCEPT	Summary: SecB mutations cause defective protein transport across the inner membrane (PMID:6403503). This is a broader term that encompasses the Sec-complex-specific annotation. Reason: Accurate but broad. SecB is clearly involved in protein transport as shown by the secB mutant phenotype. The more specific GO:0043952 (protein transport by the Sec complex) is also present. Supporting Evidence: PMID:6403503 These secB mutants were defective in the localization of maltose-binding protein and, in at least one case, OmpF protein.
GO:0043952 protein transport by the Sec complex	IMP PMID:6403503 Mutations in a new gene, secB, cause defective protein local...	ACCEPT	Summary: The original secB mutant identification showed defective protein secretion, placing SecB in the Sec-dependent export pathway (PMID:6403503). Later work confirmed SecB functions specifically in the Sec pathway. Reason: The original paper identifies secB as a gene required for protein secretion alongside secA. While the original paper did not explicitly name the "Sec complex," subsequent work established SecB as a dedicated component of the Sec pathway. The IMP annotation from EcoliWiki is appropriate. Supporting Evidence: PMID:6403503 The properties of secB mutants suggest that the secB product could be a component of the E. coli secretory apparatus.

Core Functions

SecB functions as a dedicated export chaperone/carrier in the Sec-dependent protein translocation pathway. It binds unfolded preprotein substrates in the cytosol, prevents their premature folding (holdase/antifolding activity), and delivers them to SecA at the inner membrane translocon (carrier activity). This is an ATP-independent process.

Molecular Function:

unfolded protein carrier activity

Directly Involved In:

protein transport by the Sec complex maintenance of unfolded protein

Cellular Locations:

cytosol

Supporting Evidence:

PMID:2170023
SecB has a dual function in stabilizing the precursor and in passing it on to membrane-bound SecA, the next step in the pathway.
PMID:16962134
SecB delivers its ligand to export sites through its specific binding to SecA, a peripheral component of the membrane translocon.
PMID:2848249
The purified protein also quantitatively retarded folding of precursor MBP into a stable, protease-resistant conformation in the absence of membranes.

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: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:14643199

Crystal structure of SecB from Escherichia coli.

SecB forms a homotetramer (dimer of dimers) as shown by X-ray crystallography at 2.35 angstrom resolution.

"The chaperone SecB from Escherichia coli is primarily involved in passing precursor proteins into the Sec system via specific interactions with SecA. The crystal structure of SecB from E. coli has been solved to 2.35 A resolution."

PMID:15690043

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

Large-scale affinity purification/mass spectrometry identified SecB interactions with CpxR and SecA.

"A total of 857 proteins, including 198 of the most highly conserved, soluble non-ribosomal proteins essential in at least one bacterial species, were tagged successfully, whereas 648 could be purified to homogeneity and their interacting protein partners identified by mass spectrometry."

PMID:15811382

Asymmetric binding between SecA and SecB two symmetric proteins: implications for function in export.

SecB C-terminal alpha-helices bind in the interfacial region of the SecA dimer, and this asymmetric binding facilitates conformational changes for precursor transfer.

"unexpectedly, the binding between the two symmetric molecules is asymmetric and that the C-terminal alpha-helices of SecB bind in the interfacial region of the SecA dimer."

PMID:16352602

Defining the role of the Escherichia coli chaperone SecB using comparative proteomics.

Comparative proteomics identified the full set of SecB substrates including DegP, FhuA, FkpA, GBP, LamB, MalE, OmpA, OmpF, OmpT, OmpX, OppA, PhoE, TolB, TolC, YbgF, YcgK, YgiW and YncE.

"The SecB/A dependence of 12 secretory proteins affected by the secB null mutation (DegP, FhuA, FkpA, OmpT, OmpX, OppA, TolB, TolC, YbgF, YcgK, YgiW, and YncE) was confirmed by "classical" pulse-labeling experiments. Our study more than triples the number of known SecB-dependent secretory proteins and shows that the primary role of SecB is to facilitate the targeting of secretory proteins to the Sec-translocase."

PMID:16962134

Sites of interaction of a precursor polypeptide on the export chaperone SecB mapped by site-directed spin labeling.

Site-directed spin labeling and EPR mapped the binding sites of unfolded precursor galactose-binding protein on SecB surface, showing contact with a large portion of the small chaperone surface. A model for transfer of the ligand from SecB to SecA was proposed.

"Capture of the precursor polypeptides before they fold is achieved by the promiscuous binding to the chaperone SecB. SecB delivers its ligand to export sites through its specific binding to SecA"

PMID:18048690

Direct observation of chaperone-induced changes in a protein folding pathway.

Single-molecule optical tweezers and MD simulations showed SecB completely prevents stable tertiary contacts in MBP, retaining it in a molten-globule-like state.

"Interactions with SecB completely prevent stable tertiary contacts in the core structure but have no detectable effect on the folding of the external alpha helices."

PMID:18304323

Protein abundance profiling of the Escherichia coli cytosol.

SecB identified in the cytosolic proteome of E. coli MC4100.

"we identified 1103 proteins from the cytosolic fraction of the Escherichia coli strain MC4100"

PMID:19402753

Global functional atlas of Escherichia coli encompassing previously uncharacterized proteins.

Large-scale functional atlas showing SecB-CpxR interaction.

"we performed an extensive proteomic survey using affinity-tagged E. coli strains and generated comprehensive genomic context inferences to derive a high-confidence compendium for virtually the entire proteome consisting of 5,993 putative physical interactions"

PMID:21037004

Orientation of SecA and SecB in complex, derived from disulfide cross-linking.

Disulfide cross-linking defined the relative orientation of SecA and SecB within the complex. Two SecA protomers bind one SecB tetramer.

"The tetrameric cytoplasmic chaperone SecB binds to precursors of exported proteins before they can become stably folded and delivers them to SecA."

PMID:2170023

The binding cascade of SecB to SecA to SecY/E mediates preprotein targeting to the E. coli plasma membrane.

SecB has a dual function in stabilizing precursors and delivering them to membrane-bound SecA. The SecB-SecA-SecYEG binding cascade was characterized with binding affinities.

"SecB has a dual function in stabilizing the precursor and in passing it on to membrane-bound SecA, the next step in the pathway."

PMID:2649892

Cytosolic factor purified from Escherichia coli is necessary and sufficient for the export of a preprotein and is a homotetramer of SecB.

SecB purified as a 64-kDa homotetramer of identical 16-kDa subunits from the cytosol. It is necessary and sufficient for translocation of preproteins into inverted membrane vesicles.

"The purified factor amounts to 0.08% of the cytosolic proteins and is a 64-kDa tetramer consisting of four identical 16-kDa subunits."

PMID:2664780

Escherichia coli SecB protein associates with exported protein precursors in vivo.

SecB associates with precursor forms of exported proteins (MBP, LamB, OmpA) in vivo. The SecB-precursor complex is short-lived, consistent with an export intermediate.

"in wild-type growing cells, SecB protein associates with precursor forms of exported proteins, such as the periplasmic maltose-binding protein (MBP) and the outer-membrane proteins LamB and OmpA."

PMID:27501151

Structural basis for the antifolding activity of a molecular chaperone.

NMR structures of SecB in complex with substrates showed that precursor proteins wrap around the SecB homotetramer, providing the structural basis for antifolding activity.

"The most remarkable feature is that PhoA wraps around SecB in an overall arrangement that maximizes the interacting surface between the client protein, which is held in an unfolded conformation, and the chaperone."

PMID:2834066

The antifolding activity of SecB promotes the export of the E. coli maltose-binding protein.

SecB prevents premature folding of newly synthesized MBP precursor, promoting export. The antifolding activity was demonstrated by genetic suppression and in vitro folding assays.

"The antifolding activity of SecB was demonstrated by the following: the defect in MBP export in SecB- cells was suppressed by mutational alterations affecting MBP folding"

PMID:2848249

Purified secB protein of Escherichia coli retards folding and promotes membrane translocation of the maltose-binding protein in vitro.

Purified SecB retards folding of precursor MBP and promotes its translocation into inverted membrane vesicles in vitro. SecB is a soluble, cytoplasmic, multimeric protein of identical 17-kDa subunits.

"The purified protein also quantitatively retarded folding of precursor MBP into a stable, protease-resistant conformation in the absence of membranes."

PMID:6403503

Mutations in a new gene, secB, cause defective protein localization in Escherichia coli.

SecB was identified as a new gene required for protein secretion. secB mutants showed defective localization of MBP and OmpF. The secB product was proposed as a component of the E. coli secretory apparatus.

"These secB mutants were defective in the localization of maltose-binding protein and, in at least one case, OmpF protein."

PMID:9321390

The molecular chaperone SecB is released from the carboxy-terminus of SecA during initiation of precursor protein translocation.

The SecB-binding site on SecA is confined to the extreme C-terminal 22 amino acids. SecB is released from SecA upon ATP binding, at the onset of translocation.

"The chaperone SecB keeps precursor proteins in a translocation-competent state and targets them to SecA at the translocation sites in the cytoplasmic membrane of Escherichia coli."

📚 Additional Documentation

Deep Research Bioreason

(SecB-deep-research-bioreason.md)

BioReason Chat Export

Exported on March 22, 2026 at 02:14 AM

Organism: Escherichia coli

Sequence:

MSEQNNTEMTFQIQRIYTKDISFEAPNAPHVFQKDWQPEVKLDLDTASSQLADDVYEVVLRVTVTASLGEETAFLCEVQQGGIFSIAGIEGTQMAHCLGAYCPNILFPYARECITSMVSRGTFPQLNLAPVNFDALFMNYLQQQAGEGTEEHQDA

Thinking Trace

The sequence architecture is dominated by two closely aligned InterPro signatures that span essentially the entire polypeptide: IPR003708 (Bacterial protein export chaperone SecB family, residues 1–154) and IPR035958 (SecB-like superfamily, residues 1–155). This full-length coverage by SecB family and superfamily signatures defines a compact, acidic, oligomer-forming chaperone fold. The SecB architecture forms stable trimers whose inter-subunit grooves and central cavity bind exposed hydrophobic segments of non-native secretory substrates. The absence of catalytic motifs and the presence of a chaperone family signature together indicate a non-enzymatic, ATP-independent holdase mechanism rather than an enzyme.

From this architecture, the molecular function emerges as selective, ATP-independent chaperoning of presecretory proteins. The SecB fold stabilizes non-native polypeptides through multivalent hydrophobic contacts and ordered oligomerization; this causally supports the functional class of ATP-independent chaperone activity that prevents premature folding and aggregation. Such chaperones exert their role primarily through transient substrate binding and avidity-driven sequestration rather than ATP hydrolysis, aligning with a non-enzymatic, substrate-stabilizing mechanism.

These molecular activities feed directly into the broader biological process of Sec-dependent protein secretion and proteostasis. By stabilizing presecretory proteins and maintaining them in an export-competent state, SecB drives the early steps of the Sec pathway—cargo capture, prevention of cytosolic misfolding, and delivery to the membrane translocon. Consequently, the chaperone’s action is a prerequisite for efficient protein secretion and for broader proteome quality control during biogenesis.

Cellular localization follows from function and architecture. The SecB fold lacks transmembrane segments and secretion signals and operates on soluble substrates prior to membrane translocation, which situates it in the cytoplasm. This cytosolic residency allows SecB to encounter newly synthesized presecretory proteins, prevent their aggregation, and hand them off to the membrane-embedded export machinery.

Mechanistically, I hypothesize that SecB assembles into trimers that avidly bind unfolded presecretory substrates, shielding hydrophobic cores and presenting them to the secretion apparatus. Likely interaction partners include the central Sec pathway components and co-chaperones: SecA as the ATPase motor driving translocation, the SecYEG translocon that accepts secretory cargo, and DnaK/DnaJ systems that coordinate broader folding cycles. Through these transient assemblies, SecB orchestrates substrate readiness and ensures directional flow into the Sec-dependent export route.

Functional Summary

A cytosolic, ATP-independent chaperone that stabilizes newly synthesized presecretory proteins and keeps them soluble and export-competent en route to the membrane translocation machinery. By forming oligomeric assemblies that avidly bind exposed hydrophobic segments, it prevents premature folding and aggregation and channels substrates toward the secretion apparatus, thereby supporting efficient protein export and proteostasis in the bacterial cytoplasm.

UniProt Summary

Acts as a chaperone, required for protein export.

InterPro Domains

Bacterial protein export chaperone SecB (IPR003708, family) — residues 1-154
SecB-like superfamily (IPR035958, homologous_superfamily) — residues 1-155

GO Terms

Molecular Function: molecular_function (GO:0003674), binding (GO:0005488), protein binding (GO:0005515), unfolded protein binding (GO:0051082)

Biological Process: biological_process (GO:0008150), cellular process (GO:0009987), biological regulation (GO:0065007), localization (GO:0051179), establishment of localization (GO:0051234), cellular localization (GO:0051641), regulation of biological quality (GO:0065008), transmembrane transport (GO:0055085), macromolecule localization (GO:0033036), cellular macromolecule localization (GO:0070727), establishment of localization in cell (GO:0051649), regulation of protein stability (GO:0031647), intracellular transport (GO:0046907), establishment of protein localization (GO:0045184), protein transmembrane transport (GO:0071806), transport (GO:0006810), organic substance transport (GO:0071702), intracellular protein transport (GO:0006886), nitrogen compound transport (GO:0071705), protein localization (GO:0008104), protein transport (GO:0015031)

Cellular Component: cellular_component (GO:0005575), protein-containing complex (GO:0032991)

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Deep Research Bioreason Rl

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BioReason Chat Export

Exported on March 22, 2026 at 02:14 AM

Organism: Escherichia coli

Sequence:

MSEQNNTEMTFQIQRIYTKDISFEAPNAPHVFQKDWQPEVKLDLDTASSQLADDVYEVVLRVTVTASLGEETAFLCEVQQGGIFSIAGIEGTQMAHCLGAYCPNILFPYARECITSMVSRGTFPQLNLAPVNFDALFMNYLQQQAGEGTEEHQDA

Thinking Trace

Functional Summary

UniProt Summary

Acts as a chaperone, required for protein export.

InterPro Domains

Bacterial protein export chaperone SecB (IPR003708, family) — residues 1-154
SecB-like superfamily (IPR035958, homologous_superfamily) — residues 1-155

GO Terms

Molecular Function: molecular_function (GO:0003674), binding (GO:0005488), protein binding (GO:0005515), unfolded protein binding (GO:0051082)

Cellular Component: cellular_component (GO:0005575), protein-containing complex (GO:0032991)

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Deep Research Falcon

(SecB-deep-research-falcon.md)

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protein_description: 'RecName: Full=Protein-export protein SecB; AltName: Full=Chaperone
SecB;'
gene_info: Name=secB; OrderedLocusNames=b3609, JW3584;
organism_full: Escherichia coli (strain K12).
protein_family: Belongs to the SecB family. .
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Question

Gene Research for Functional Annotation

⚠️ CRITICAL: Gene/Protein Identification Context

BEFORE YOU BEGIN RESEARCH: You MUST verify you are researching the CORRECT gene/protein. Gene symbols can be ambiguous, especially for less well-characterized genes from non-model organisms.

Target Gene/Protein Identity (from UniProt):

UniProt Accession: P0AG86
Protein Description: RecName: Full=Protein-export protein SecB; AltName: Full=Chaperone SecB;
Gene Information: Name=secB; OrderedLocusNames=b3609, JW3584;
Organism (full): Escherichia coli (strain K12).
Protein Family: Belongs to the SecB family. .
Key Domains: SecB. (IPR003708); SecB-like_sf. (IPR035958); SecB (PF02556)

MANDATORY VERIFICATION STEPS:

Check if the gene symbol "secB" matches the protein description above
Verify the organism is correct: Escherichia coli (strain K12).
Check if protein family/domains align with what you find in literature
If you find literature for a DIFFERENT gene with the same or similar symbol, STOP

If Gene Symbol is Ambiguous or You Cannot Find Relevant Literature:

DO NOT PROCEED WITH RESEARCH ON A DIFFERENT GENE. Instead:
- State clearly: "The gene symbol 'secB' is ambiguous or literature is limited for this specific protein"
- Explain what you found (e.g., "Found extensive literature on a different gene with the same symbol in a different organism")
- Describe the protein based ONLY on the UniProt information provided above
- Suggest that the protein function can be inferred from domain/family information

Research Target:

Please provide a comprehensive research report on the gene secB (gene ID: SecB, UniProt: P0AG86) in ECOLI.

The research report should be a detailed narrative explaining the function, biological processes, and localization of the gene product. Citations should be given for all claims.

You should prioritize authoritative reviews and primary scientific literature when conducting research. You can supplement
this with annotations you find in gene/protein databases, but these can be outdated or inaccurate.

We are specifically interested in the primary function of the gene - for enzymes, what reaction is catalyzed, and what is the substrate specificity? For transporters, what is the substrate? For structural proteins or adapters, what is the broader structural role? For signaling molecules, what is the role in the pathway.

We are interested in where in or outside the cell the gene product carries out its function.

We are also interested in the signaling or biochemical pathways in which the gene functions. We are less interested in broad pleiotropic effects, except where these elucidate the precise role.

Include evidence where possible. We are interested in both experimental evidence as well as inference from structure, evolution, or bioinformatic analysis. Precise studies should be prioritized over high-throughput, where available.

Output

Question: You are an expert researcher providing comprehensive, well-cited information.

Provide detailed information focusing on:
1. Key concepts and definitions with current understanding
2. Recent developments and latest research (prioritize 2023-2024 sources)
3. Current applications and real-world implementations
4. Expert opinions and analysis from authoritative sources
5. Relevant statistics and data from recent studies

Format as a comprehensive research report with proper citations. Include URLs and publication dates where available.
Always prioritize recent, authoritative sources and provide specific citations for all major claims.

Gene Research for Functional Annotation

⚠️ CRITICAL: Gene/Protein Identification Context

BEFORE YOU BEGIN RESEARCH: You MUST verify you are researching the CORRECT gene/protein. Gene symbols can be ambiguous, especially for less well-characterized genes from non-model organisms.

Target Gene/Protein Identity (from UniProt):

UniProt Accession: P0AG86
Protein Description: RecName: Full=Protein-export protein SecB; AltName: Full=Chaperone SecB;
Gene Information: Name=secB; OrderedLocusNames=b3609, JW3584;
Organism (full): Escherichia coli (strain K12).
Protein Family: Belongs to the SecB family. .
Key Domains: SecB. (IPR003708); SecB-like_sf. (IPR035958); SecB (PF02556)

MANDATORY VERIFICATION STEPS:

Check if the gene symbol "secB" matches the protein description above
Verify the organism is correct: Escherichia coli (strain K12).
Check if protein family/domains align with what you find in literature
If you find literature for a DIFFERENT gene with the same or similar symbol, STOP

If Gene Symbol is Ambiguous or You Cannot Find Relevant Literature:

Research Target:

Please provide a comprehensive research report on the gene secB (gene ID: SecB, UniProt: P0AG86) in ECOLI.

The research report should be a detailed narrative explaining the function, biological processes, and localization of the gene product. Citations should be given for all claims.

We are interested in where in or outside the cell the gene product carries out its function.

We are also interested in the signaling or biochemical pathways in which the gene functions. We are less interested in broad pleiotropic effects, except where these elucidate the precise role.

Research report: secB (UniProt P0AG86) functional annotation in Escherichia coli K-12

1) Identity verification (mandatory)

The gene symbol secB in Escherichia coli (strain K-12) corresponds to the protein-export protein SecB (also called chaperone SecB), a cytosolic secretion chaperone in the bacterial Sec pathway. In authoritative E. coli Sec-system reviews, SecB is explicitly described as a cytoplasmic factor whose binding partners are precursor proteins and SecA, matching the UniProt-provided identity for accession P0AG86 and the SecB-family annotation (SecB/PF02556). (crane2017thesecsystem pages 2-4, crane2017thesecsystem pages 4-6)

2) Key concepts and definitions (current understanding)

2.1. What SecB is (molecular function)

SecB is classically defined as an export chaperone / holdase: it binds secretory preproteins (precursor proteins carrying an N-terminal signal peptide) in nonnative/unfolded conformations, preventing premature folding and aggregation, thereby maintaining translocation competence (the ability of a preprotein to be transported through the Sec channel). (crane2017thesecsystem pages 7-9, crane2017thesecsystem pages 4-6)

SecB is a small acidic protein (155 aa) whose functional unit is a homotetramer (a dimer of dimers; ~68.6 kDa total). (crane2017thesecsystem pages 4-6, findik2017determinationofthe pages 1-2, crane2017thesecsystem pages 7-9)

2.2. “Post-translational Sec pathway” and “translocation-competent state”

In the SecA/SecB post-translational route, preproteins are typically synthesized in the cytosol and must remain devoid of their final stable tertiary structure long enough to be targeted to the Sec translocase (SecA + SecYEG). SecB contributes by capturing nascent or newly synthesized precursors and holding them in an unfolded, soluble, secretion-competent state until handoff to SecA. (crane2017thesecsystem pages 7-9, crane2017thesecsystem pages 4-6)

Mechanistically, SecB uses multiple low-specificity binding subsites and binds unfolded chains promiscuously; peptide binding studies indicate preference for 8–9 aa segments enriched in aromatic and basic residues. For many experimentally tested substrates (36–61 kDa), the binding stoichiometry is typically one polypeptide per SecB tetramer. (crane2017thesecsystem pages 7-9)

2.3. Pathway role and interaction partners

A central concept is that SecB targets and hands off preproteins to SecA, which in turn drives translocation through SecYEG using ATP hydrolysis (with additional contributions from the proton motive force in vivo). (crane2017thesecsystem pages 4-6)

SecB has specific interaction sites for SecA (a “side site” on the SecB tetramer and mobile C-terminal “tail” contacts). Full SecA:SecB complexes can bind two SecA protomers per SecB tetramer and are described as more efficient in coupling SecA ATPase cycles to translocation than partial-contact complexes. (crane2017thesecsystem pages 12-13)

SecB also sits within a broader cytosolic chaperone network; SecB’s requirement for export is often substrate- and condition-dependent, with other chaperones (e.g., DnaK/DnaJ, GroEL/GroES, and trigger factor) sometimes overlapping or modulating export efficiency. (crane2017thesecsystem pages 11-12, crane2017thesecsystem pages 12-13)

3) Cellular localization and biological processes

SecB is a cytosolic chaperone. Its biological role is in Sec-dependent protein export, primarily supporting the post-translational targeting/translocation of a subset of periplasmic and outer-membrane proteins by maintaining precursor proteins in an export-competent state and delivering them to SecA/SecYEG. (crane2017thesecsystem pages 2-4, crane2017thesecsystem pages 4-6)

SecB deletion is not universally lethal in E. coli but can cause cytosolic accumulation of secretory substrates and stress responses; a 2023 Sec-machinery thesis summarizes that secB perturbation leads to accumulation of Sec substrates in the cytoplasm and induction of the σ32 heat-shock response, consistent with loss of cytosolic holdase capacity. (wynne2023investigationofthe pages 33-39)

4) Quantitative statistics and data (mechanism-relevant)

4.1. Intracellular concentration / abundance

A key quantitative measurement is SecB’s intracellular level. Using quantitative immunoblotting of chromosomally expressed SecB, SecB tetramer concentration was measured at 1.6 ± 0.2 µM (rich medium) and 2.5 ± 0.6 µM (minimal medium). (findik2017determinationofthe pages 1-2)

A commonly cited earlier range of copy numbers per cell varies substantially depending on conditions and methods; Table 4 in the EcoSal review compiles values spanning roughly ~1,000 to ~6,100 copies/cell across conditions/studies (visual evidence). (crane2017thesecsystem media a4673c7a)

4.2. Binding affinities and pathway coupling

Multiple quantitative binding parameters have been compiled in the EcoSal Sec-system review:

SecA–SecB affinity in solution: Kd ≈ 2 µM (wild-type SecA:SecB). (crane2017thesecsystem pages 12-13)
SecB binding to SecA increases when SecA is membrane/SecYEG-associated: Kd reported 30–200 nM; if SecB carries a precursor, affinity tightens further by ~2–3× to ~10–60 nM. (crane2017thesecsystem pages 4-6)
SecB can increase apparent substrate affinity in the pathway: for example, PhoA binding to SecA:SecYEG is reported as Kd = 230 nM, while SecB-mediated delivery yields an approximately 4-fold tighter apparent affinity (Kd ≈ 60 nM). (crane2017thesecsystem pages 11-12)

4.3. Quantitative context from recent (2023) Sec-system synthesis

A 2023 review providing a modern synthesis of the core Sec mechanism reports quantitative context useful for interpreting SecB’s role: approximately ~500 SecYEG sites per E. coli cell, and roughly ~20% of total protein biomass is destined for the cell envelope. SecB is described as a specific secretion chaperone needed for a subset of preproteins that interacts directly with SecA. (allen2023aunifyingmechanism pages 2-3)

5) Recent developments and latest research (prioritizing 2023–2024)

Direct SecB-focused primary research in 2023–2024 was limited in the retrieved corpus; however, several 2023 sources provide authoritative “latest understanding” at the systems/mechanistic level:

Unifying mechanistic model of Sec transport (2023): Allen & Collinson synthesize recent structural biology and biophysics into a largely complete model of core SecYEG–SecA transport and explicitly position SecB as an accessory chaperone that maintains substrates secretion-competent and interacts with SecA for a subset of preproteins. (allen2023aunifyingmechanism pages 2-3)
Expanded chaperone-network framing (2023): A 2023 Sec-machinery thesis (SecH) reiterates and updates SecB’s recognition logic (a 9-aa motif enriched in basic/aromatic residues) and highlights phenotypes consistent with cytosolic trafficking failure (σ32 heat shock induction upon secB perturbation), as well as conceptual linkage of SecB interaction modules to SecA-like metal-binding domains. (wynne2023investigationofthe pages 33-39, wynne2023investigationofthe pages 29-33)

These sources are summarized in the “recent literature” table below.

Citation (authors, year, title)	Publication date & URL/DOI	Type	SecB-relevant contribution (mechanism, quant context, target/antibiotic, chaperone network)	Key quantitative/statements
Allen & Collinson, 2023, A unifying mechanism for protein transport through the core bacterial Sec machinery	Aug 2023; https://doi.org/10.1098/rsob.230166	Peer-reviewed review	Places SecB in the current mechanistic model of the E. coli Sec pathway as a specific secretion chaperone for a subset of preproteins that interacts directly with SecA and helps keep substrates secretion-competent; useful as the main recent authoritative overview for pathway context. (allen2023aunifyingmechanism pages 2-3)	Reports ~500 SecYEG sites per E. coli cell and that roughly 20% of cellular protein biomass is destined for the cell envelope; emphasizes that SecB is needed only for a subset of preproteins, not all Sec substrates. (allen2023aunifyingmechanism pages 2-3)
Salter, 2023, The bacterial Sec-machinery as an antibiotic target	2023; DOI/URL not fully available in retrieved snippet	Review/thesis-style antibiotic-target analysis	Frames the Sec machinery as an antibacterial target, but in retrieved sections the focus is overwhelmingly on SecA, signal peptidase I, SecYEG/HTL, and screening strategies; SecB appears only as an accessory chaperone and is not developed as a primary drug target in the available excerpts. (salter2023thebacterialsecmachinery pages 51-53, salter2023thebacterialsecmachinery pages 25-28, salter2023thebacterialsecmachinery pages 56-58, salter2023thebacterialsecmachinery pages 92-94, salter2023thebacterialsecmachinery pages 20-22)	States Sec translocates the vast majority of extracytoplasmic proteins in E. coli (reported as 96% in one excerpt) and is therefore a strong target space; validated screens included a primary screen with median Z' = 0.71 across >60 plates and ~5000 compounds; optimized arylomycin analogs reached MICs <0.5 µg/mL against multidrug-resistant Gram-negatives, but these advances are not SecB-specific. (salter2023thebacterialsecmachinery pages 121-123, salter2023thebacterialsecmachinery pages 56-58, salter2023thebacterialsecmachinery pages 20-22)
Wynne, 2023, Investigation of the structure and function of SecH, a novel component of the Sec machinery in Escherichia coli	2023; journal/URL not fully available in retrieved snippet	Thesis/dissertation	Provides SecB-relevant mechanistic updates from a broader Sec-machinery perspective: SecB is described as a cytoplasmic holdase/export chaperone that binds certain preproteins, recognizes a 9-aa motif enriched in basic and aromatic residues, keeps clients translocation-competent, and interfaces with the wider chaperone network; also links SecB biology to SecA-like metal-binding domains via SecH. (wynne2023investigationofthe pages 33-39, wynne2023investigationofthe pages 29-33)	Notes that secB perturbation causes cytoplasmic accumulation of Sec substrates and induction of the σ32 heat-shock response; reports overlap with DnaJ/chaperone networks and describes a 9-aa recognition motif for SecB-enriched substrate recognition. (wynne2023investigationofthe pages 33-39, wynne2023investigationofthe pages 29-33)
Snoeck, Guidi & De Mey, 2024, “Metabolic burden” explained: stress symptoms and its related responses induced by (over)expression of (heterologous) proteins in Escherichia coli	Mar 2024; https://doi.org/10.1186/s12934-024-02370-9	Peer-reviewed review	Included here for completeness as a recent E. coli production/stress review, but no SecB-specific content was recovered in the retrieved snippets; therefore it should not be overinterpreted as a SecB-focused source.	In the retrieved evidence, no specific SecB statements or quantitative SecB findings were available; use only as peripheral context on recombinant-expression stress rather than as evidence for SecB biology. (paper search metadata only; no SecB-specific context extracted)

Table: This table summarizes the main 2023–2024 sources retrieved that are relevant to E. coli SecB, emphasizing what each contributes to mechanism, pathway context, antibiotic-target relevance, and quantitative interpretation. It is useful for distinguishing genuinely SecB-informative sources from broader Sec-system literature with only minimal SecB coverage.

6) Current applications and real-world implementations

6.1. Biotechnology: secretion/periplasmic export engineering (conceptual lever)

SecB’s mechanism makes it a plausible engineering lever for improving post-translational Sec export of aggregation-prone recombinant proteins, because it can maintain precursors in soluble unfolded states and promote targeting to SecA/SecYEG. This is supported mechanistically by the reviewed binding/affinity changes and by the measured micromolar cellular concentration range that makes SecB abundant enough to form cytosolic SecB:preprotein complexes while waiting for available translocons. (crane2017thesecsystem pages 4-6, findik2017determinationofthe pages 1-2)

Limitation of retrieved evidence: within the accessible full-text set for this run, I did not recover peer-reviewed 2023–2024 case studies reporting explicit quantitative fold-improvements in secretion yields upon SecB co-expression/overexpression. Therefore, this report restricts itself to mechanism-supported application rationale rather than asserting specific process performance gains.

6.2. Antimicrobial relevance: Sec pathway as target space (SecB as accessory)

The Sec machinery is frequently analyzed as an antibiotic target space because it is responsible for exporting most extracytoplasmic proteins in E. coli. In the 2023 antibiotic-target analysis retrieved here, the emphasis is on SecA and signal peptidase I as practical enzymatic targets for small-molecule discovery, whereas SecB is not emphasized as a primary target (consistent with its accessory role and nonessentiality in E. coli). (salter2023thebacterialsecmachinery pages 56-58, salter2023thebacterialsecmachinery pages 51-53, salter2023thebacterialsecmachinery pages 25-28)

7) Expert opinions / authoritative analysis

Two authoritative review-level perspectives converge on the following expert interpretation:

SecB is best understood as a substrate-selective secretion holdase that improves the efficiency and fidelity of post-translational Sec export by buffering a subset of preproteins against folding/aggregation and enhancing productive engagement with SecA/SecYEG. (crane2017thesecsystem pages 11-12, allen2023aunifyingmechanism pages 2-3)
In modern Sec-mechanism models, SecB remains important but is one of several cytosolic factors shaping the kinetics of targeting and translocation (e.g., interplay with trigger factor and other chaperones), which helps explain why SecB dependence is conditional and substrate-dependent. (crane2017thesecsystem pages 11-12, crane2017thesecsystem pages 12-13, wynne2023investigationofthe pages 33-39)

8) Consolidated functional annotation summary

Aspect	Evidence summary	Key sources (with year)
Identity / domains	Verified target matches secB of Escherichia coli K-12, UniProt P0AG86. SecB is a cytoplasmic export chaperone in the Sec pathway, described as binding precursors and SecA; the user-supplied domain assignment (SecB family; IPR003708 / IPR035958 / PF02556) is consistent with the literature describing the canonical SecB secretion chaperone rather than a different ambiguous gene product. SecB is a 155-residue acidic protein with monomer mass ~17.3 kDa. (crane2017thesecsystem pages 2-4, crane2017thesecsystem pages 4-6)	Crane & Randall 2017; user-supplied UniProt/domain context (crane2017thesecsystem pages 2-4, crane2017thesecsystem pages 4-6)
Localization	SecB is localized in the cytoplasm/cytosol, where it binds nonnative precursor proteins before delivery to membrane-associated SecA/SecYEG. It is not a membrane protein or periplasmic factor. (crane2017thesecsystem pages 2-4, crane2017thesecsystem pages 7-9, jiang2025useofhighdensity pages 34-38)	Crane & Randall 2017; Jiang 2025 citing E. coli Sec pathway context (crane2017thesecsystem pages 2-4, crane2017thesecsystem pages 7-9, jiang2025useofhighdensity pages 34-38)
Oligomeric state	Functional SecB is a homotetramer organized as a dimer of dimers; tetramer mass is ~68.6 kDa. Dimer exchange is reported as very tight (equilibrium constant well below 20 nM), supporting a stable tetrameric chaperone assembly in vivo. (crane2017thesecsystem pages 7-9, findik2017determinationofthe pages 1-2, crane2017thesecsystem pages 4-6)	Crane & Randall 2017; Findik & Randall 2017 (crane2017thesecsystem pages 7-9, findik2017determinationofthe pages 1-2, crane2017thesecsystem pages 4-6)
Substrates / recognition	SecB binds unfolded or nonnative Sec-dependent precursor proteins and keeps them translocation-competent. It binds pMBP but not mature MBP, indicating preference for precursor/non-native conformers. Recognition is broad/promiscuous, but peptide work indicates preference for 8-9 aa motifs enriched in aromatic and basic residues; a 2023 SecH thesis likewise describes a 9-aa motif and notes SecB’s role in maintaining preproteins for uncoupled translocation. For tested 36-61 kDa substrates, stoichiometry is typically one polypeptide per SecB tetramer. (crane2017thesecsystem pages 7-9, wynne2023investigationofthe pages 33-39)	Crane & Randall 2017; Wynne 2023 (crane2017thesecsystem pages 7-9, wynne2023investigationofthe pages 33-39)
Interaction partners	Principal partners are preproteins and SecA. SecB engages SecA through the SecB side site (including residues D20, E24, L75, E77) and tail sites on the mobile C-terminus; full contacts allow a tetramer to bind two SecA protomers, whereas partial-contact complexes bind one and are less efficient. SecB also functionally and physically interfaces with trigger factor (TF) in the secretory chaperone network; 2020 work showed SecB can bind TF:proOmpA and, at the membrane, enhance TF/TF:substrate affinity for the translocase, helping secretion resume. (crane2017thesecsystem pages 12-13, findik2017determinationofthe pages 10-11)	Crane & Randall 2017; Findik & Randall 2017 references; De Geyter et al. 2020 (crane2017thesecsystem pages 12-13, findik2017determinationofthe pages 10-11)
Role in pathway	SecB is a specialized post-translational export chaperone for a subset of Sec substrates. Its primary function is to capture slowly folding/aggregation-prone precursors in the cytoplasm, maintain them in an export-competent state, and deliver them to SecA, which then feeds substrate into SecYEG for translocation across the inner membrane. SecB is not essential for viability but improves efficiency and fidelity of export for selected proteins; dependence varies with substrate, signal/mature-region mutations, temperature, and physiological conditions. (crane2017thesecsystem pages 11-12, crane2017thesecsystem pages 4-6, allen2023aunifyingmechanism pages 2-3)	Crane & Randall 2017; Allen & Collinson 2023 (crane2017thesecsystem pages 11-12, crane2017thesecsystem pages 4-6, allen2023aunifyingmechanism pages 2-3)
Key quantitative values	Intracellular SecB tetramer concentration: 1.6 ± 0.2 µM in rich medium, 2.5 ± 0.6 µM in minimal medium. SecA:SecB Kd in solution: ~2 µM. Membrane/SecYEG-bound SecA to SecB Kd: 30-200 nM. If SecB carries precursor, affinity tightens to ~10-60 nM. PhoA binding to SecA:SecYEG: 230 nM, versus ~60 nM when delivered via SecB (~4-fold tighter apparent affinity). SecYEG sites per E. coli cell: ~500. Protein biomass destined for cell envelope: ~20%. Historical abundance estimates also span roughly ~1,000 to 6,100 copies/cell depending on growth conditions and measurement approach. (findik2017determinationofthe pages 1-2, crane2017thesecsystem pages 12-13, crane2017thesecsystem pages 11-12, crane2017thesecsystem pages 4-6, allen2023aunifyingmechanism pages 2-3, crane2017thesecsystem pages 7-9)	Findik & Randall 2017; Crane & Randall 2017; Allen & Collinson 2023 (findik2017determinationofthe pages 1-2, crane2017thesecsystem pages 12-13, crane2017thesecsystem pages 11-12, crane2017thesecsystem pages 4-6, allen2023aunifyingmechanism pages 2-3, crane2017thesecsystem pages 7-9)
Recent 2023-2024 perspective / applications relevance	Allen & Collinson 2023 position SecB as a specific secretion chaperone for a subset of preproteins that directly interacts with SecA within the broader modern mechanistic view of the Sec machine. Wynne 2023 highlights SecB recognition motifs, overlap with other chaperones, and that secB perturbation causes cytoplasmic accumulation of Sec substrates and induction of the σ32 heat-shock response. Salter 2023 frames the Sec machinery as an antibiotic target, which is relevant to SecB mainly as a nonessential accessory factor and pathway context rather than as the dominant direct target. In biotechnology, secretion engineering reviews cite SecB overexpression/manipulation as one lever to improve periplasmic export of recombinant proteins, though recent 2023-2024 SecB-specific industrial implementations appear limited in the retrieved evidence. (wynne2023investigationofthe pages 33-39, allen2023aunifyingmechanism pages 2-3)	Allen & Collinson 2023; Wynne 2023; broader Sec/biotech reviews in prior search results (wynne2023investigationofthe pages 33-39, allen2023aunifyingmechanism pages 2-3)

Table: This table summarizes the core functional annotation of E. coli K-12 SecB (UniProt P0AG86), including identity, localization, interactions, pathway role, and quantitative parameters. It also highlights what recent 2023 sources add to the current mechanistic understanding of SecB within the bacterial Sec export system.

9) Key source URLs and publication dates (as retrieved)

Crane JM, Randall LL. The Sec System: Protein Export in Escherichia coli. EcoSal Plus. Dec 2017. https://doi.org/10.1128/ecosalplus.esp-0002-2017 (crane2017thesecsystem pages 7-9)
Findik BT, Randall LL. Determination of the intracellular concentration of the export chaperone SecB in Escherichia coli. PLoS ONE. Aug 2017. https://doi.org/10.1371/journal.pone.0183231 (findik2017determinationofthe pages 1-2)
Allen WJ, Collinson I. A unifying mechanism for protein transport through the core bacterial Sec machinery. Open Biology. Aug 2023. https://doi.org/10.1098/rsob.230166 (allen2023aunifyingmechanism pages 2-3)

10) Evidence gaps and recommended next steps (for completeness)

Because the 2023–2024 SecB-focused primary literature was sparse in the retrieved corpus, additional targeted retrieval would likely be required to (i) enumerate newly discovered SecB client sets under specific conditions, (ii) capture any 2024 cryo-EM/structural refinements specifically involving SecB complexes, and (iii) provide quantitative secretion-yield improvements from industrial strain-engineering papers explicitly manipulating SecB.

References

(crane2017thesecsystem pages 2-4): Jennine M. Crane and Linda L. Randall. The sec system: protein export in escherichia coli. Dec 2017. URL: https://doi.org/10.1128/ecosalplus.esp-0002-2017, doi:10.1128/ecosalplus.esp-0002-2017. This article has 144 citations.
(crane2017thesecsystem pages 4-6): Jennine M. Crane and Linda L. Randall. The sec system: protein export in escherichia coli. Dec 2017. URL: https://doi.org/10.1128/ecosalplus.esp-0002-2017, doi:10.1128/ecosalplus.esp-0002-2017. This article has 144 citations.
(crane2017thesecsystem pages 7-9): Jennine M. Crane and Linda L. Randall. The sec system: protein export in escherichia coli. Dec 2017. URL: https://doi.org/10.1128/ecosalplus.esp-0002-2017, doi:10.1128/ecosalplus.esp-0002-2017. This article has 144 citations.
(findik2017determinationofthe pages 1-2): Bahar T. Findik and Linda L. Randall. Determination of the intracellular concentration of the export chaperone secb in escherichia coli. PLoS ONE, 12:e0183231, Aug 2017. URL: https://doi.org/10.1371/journal.pone.0183231, doi:10.1371/journal.pone.0183231. This article has 10 citations and is from a peer-reviewed journal.
(crane2017thesecsystem pages 12-13): Jennine M. Crane and Linda L. Randall. The sec system: protein export in escherichia coli. Dec 2017. URL: https://doi.org/10.1128/ecosalplus.esp-0002-2017, doi:10.1128/ecosalplus.esp-0002-2017. This article has 144 citations.
(crane2017thesecsystem pages 11-12): Jennine M. Crane and Linda L. Randall. The sec system: protein export in escherichia coli. Dec 2017. URL: https://doi.org/10.1128/ecosalplus.esp-0002-2017, doi:10.1128/ecosalplus.esp-0002-2017. This article has 144 citations.
(wynne2023investigationofthe pages 33-39): MA Wynne. Investigation of the structure and function of sech, a novel component of the sec machinery in escherichia coli. Unknown journal, 2023.
(crane2017thesecsystem media a4673c7a): Jennine M. Crane and Linda L. Randall. The sec system: protein export in escherichia coli. Dec 2017. URL: https://doi.org/10.1128/ecosalplus.esp-0002-2017, doi:10.1128/ecosalplus.esp-0002-2017. This article has 144 citations.
(allen2023aunifyingmechanism pages 2-3): William J. Allen and Ian Collinson. A unifying mechanism for protein transport through the core bacterial sec machinery. Open Biology, Aug 2023. URL: https://doi.org/10.1098/rsob.230166, doi:10.1098/rsob.230166. This article has 12 citations and is from a peer-reviewed journal.
(wynne2023investigationofthe pages 29-33): MA Wynne. Investigation of the structure and function of sech, a novel component of the sec machinery in escherichia coli. Unknown journal, 2023.
(salter2023thebacterialsecmachinery pages 51-53): T Salter. The bacterial sec-machinery as an antibiotic target. Unknown journal, 2023.
(salter2023thebacterialsecmachinery pages 25-28): T Salter. The bacterial sec-machinery as an antibiotic target. Unknown journal, 2023.
(salter2023thebacterialsecmachinery pages 56-58): T Salter. The bacterial sec-machinery as an antibiotic target. Unknown journal, 2023.
(salter2023thebacterialsecmachinery pages 92-94): T Salter. The bacterial sec-machinery as an antibiotic target. Unknown journal, 2023.
(salter2023thebacterialsecmachinery pages 20-22): T Salter. The bacterial sec-machinery as an antibiotic target. Unknown journal, 2023.
(salter2023thebacterialsecmachinery pages 121-123): T Salter. The bacterial sec-machinery as an antibiotic target. Unknown journal, 2023.
(jiang2025useofhighdensity pages 34-38): C Jiang. Use of high-density transposon libraries to analyze oxidative protein folding and protein translocation in escherichia coli. Unknown journal, 2025.
(findik2017determinationofthe pages 10-11): Bahar T. Findik and Linda L. Randall. Determination of the intracellular concentration of the export chaperone secb in escherichia coli. PLoS ONE, 12:e0183231, Aug 2017. URL: https://doi.org/10.1371/journal.pone.0183231, doi:10.1371/journal.pone.0183231. This article has 10 citations and is from a peer-reviewed journal.

Citations

crane2017thesecsystem pages 7-9
crane2017thesecsystem pages 4-6
crane2017thesecsystem pages 12-13
wynne2023investigationofthe pages 33-39
findik2017determinationofthe pages 1-2
crane2017thesecsystem pages 11-12
allen2023aunifyingmechanism pages 2-3
crane2017thesecsystem pages 2-4
wynne2023investigationofthe pages 29-33
salter2023thebacterialsecmachinery pages 51-53
salter2023thebacterialsecmachinery pages 25-28
salter2023thebacterialsecmachinery pages 56-58
salter2023thebacterialsecmachinery pages 92-94
salter2023thebacterialsecmachinery pages 20-22
salter2023thebacterialsecmachinery pages 121-123
jiang2025useofhighdensity pages 34-38
findik2017determinationofthe pages 10-11
https://doi.org/10.1098/rsob.230166
https://doi.org/10.1186/s12934-024-02370-9
https://doi.org/10.1128/ecosalplus.esp-0002-2017
https://doi.org/10.1371/journal.pone.0183231
https://doi.org/10.1128/ecosalplus.esp-0002-2017,
https://doi.org/10.1371/journal.pone.0183231,
https://doi.org/10.1098/rsob.230166,

Bioreason Rl Review

(SecB-bioreason-rl-review.md)

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

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

Correctness: 4/5
Completeness: 4/5

Functional Summary Review

The BioReason functional summary describes SecB as:

A cytosolic, ATP-independent chaperone that stabilizes newly synthesized presecretory proteins and keeps them soluble and export-competent en route to the membrane translocation machinery. By forming oligomeric assemblies that avidly bind exposed hydrophobic segments, it prevents premature folding and aggregation and channels substrates toward the secretion apparatus, thereby supporting efficient protein export and proteostasis in the bacterial cytoplasm.

This is a well-written and largely accurate summary. The key elements are correctly captured:
- ATP-independent chaperone mechanism
- Binding of presecretory proteins in unfolded state
- Prevention of premature folding and aggregation
- Delivery to the membrane translocation machinery
- Cytoplasmic localization
- Oligomeric assembly (though described as generic "oligomeric" rather than the specific homotetramer/dimer-of-dimers architecture)

Minor gaps:
- Does not specify SecB forms a homotetramer (dimer of dimers)
- Does not name SecA as the specific delivery target at the membrane
- Does not name the SecYEG translocon
- Does not mention that substrates wrap around the tetrameric surface (PMID:16962134)
- The thinking trace says "trimers" which is incorrect -- SecB is a tetramer

The thinking trace's mention of "trimers" is an error, though the functional summary avoids specifying the oligomeric state. The curated review identifies SecB's function as GO:0140309 (unfolded protein carrier activity), which is more specific than the generic "chaperone" description but aligned with the narrative.

Comparison with interpro2go:

The curated review's interpro2go annotations include unfolded protein binding (GO:0051082, noted as better described as carrier activity) and protein tetramerization (GO:0051262, accepted). BioReason's functional summary essentially recapitulates the interpro2go-level "unfolded protein binding" narrative, adding the secretory pathway context which is informative. The model correctly infers the Sec pathway connection from the InterPro family signature, which adds value beyond raw interpro2go annotations. However, the GO term predictions include generic transport-related terms without specifying the Sec complex.

Notes on thinking trace

The trace correctly identifies both InterPro signatures (IPR003708, IPR035958) and infers the ATP-independent holdase mechanism. The mention of "DnaK/DnaJ systems that coordinate broader folding cycles" as interaction partners is appropriate since SecB and DnaK have overlapping substrate pools. The incorrect "trimer" assembly prediction is a notable factual error in the trace.

📄 View Raw YAML

id: P0AG86
gene_symbol: SecB
product_type: PROTEIN
status: IN_PROGRESS
taxon:
  id: NCBITaxon:83333
  label: Escherichia coli (strain K12)
description: 'SecB is a dedicated export chaperone in E. coli that functions as a
  cytosolic homotetramer (dimer of dimers) in the general secretory (Sec) pathway.
  It binds newly synthesized precursor proteins in an unfolded or molten-globule state,
  preventing their premature folding and aggregation, and delivers them to the membrane-associated
  ATPase SecA for translocation across the inner membrane via the SecYEG translocon
  (PMID:2170023). SecB functions as an ATP-independent holdase/carrier: it captures
  unfolded preproteins, wraps them around its tetrameric surface (PMID:16962134),
  maintains them in a translocation-competent state (PMID:2848249), and then transfers
  them to SecA through specific binding at the SecA C-terminus (PMID:9321390). Its
  substrates include a defined subset of exported proteins such as MalE (MBP), OmpA,
  OmpF, LamB, PhoA, and others (PMID:16352602). SecB was first identified through
  mutations causing defective protein localization (PMID:6403503). The crystal structure
  shows a beta-sheet-rich tetramer with helical elements (PDB:1QYN), and NMR studies
  reveal that substrates wrap around the tetramer, making contact with a large portion
  of the chaperone surface (PMID:16962134, PMID:27501151).'
existing_annotations:
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: SecB is a soluble, cytosolic protein. This is well-established by purification
      as a cytosolic factor (PMID:2649892) and proteomics profiling (PMID:18304323).
      The IBA annotation is consistent with multiple IDA annotations for the same
      term.
    action: ACCEPT
    reason: SecB is definitively a cytosolic protein. Watanabe and Blobel purified
      it as a "cytosolic factor" (PMID:2649892), and it was identified in cytosolic
      proteomics (PMID:18304323). UniProt annotation confirms "Cytoplasm" subcellular
      location. The IBA annotation is fully supported.
    supported_by:
    - reference_id: PMID:2649892
      supporting_text: We have purified to homogeneity a cytosolic factor from Escherichia
        coli that is required for the translocation of a preprotein into inverted
        vesicles of the E. coli plasma membrane.
    - reference_id: PMID:18304323
      supporting_text: we identified 1103 proteins from the cytosolic fraction of
        the Escherichia coli strain MC4100
- term:
    id: GO:0036506
    label: maintenance of unfolded protein
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: SecB maintains precursor proteins in an unfolded, translocation-competent
      state. This antifolding/holdase activity is the core biological process of SecB,
      demonstrated by both in vivo and in vitro experiments (PMID:2834066, PMID:2848249,
      PMID:18048690).
    action: ACCEPT
    reason: This is a core function of SecB. Collier et al. showed that SecB prevents
      premature folding of MBP precursor (PMID:2834066). Weiss et al. demonstrated
      that purified SecB "quantitatively retarded folding of precursor MBP into a
      stable, protease-resistant conformation" (PMID:2848249). Bechtluft et al. showed
      by single-molecule optical tweezers that SecB "completely prevent stable tertiary
      contacts" and "retains MBP in this [molten-globule] state" (PMID:18048690).
      The IBA annotation is well-supported by experimental evidence.
    supported_by:
    - reference_id: PMID:2834066
      supporting_text: Evidence is presented that the E. coli secB gene encodes a
        soluble protein that interacts with the mature region of the precursor maltose-binding
        protein (MBP), and promotes MBP export by preventing premature folding of
        the newly synthesized polypeptide into an export-incompetent form.
    - reference_id: PMID:2848249
      supporting_text: The purified protein also quantitatively retarded folding of
        precursor MBP into a stable, protease-resistant conformation in the absence
        of membranes.
    - reference_id: PMID:18048690
      supporting_text: Interactions with SecB completely prevent stable tertiary contacts
        in the core structure but have no detectable effect on the folding of the
        external alpha helices. It appears that SecB only binds to the extended or
        molten globulelike structure and retains MBP in this latter state.
- term:
    id: GO:0043952
    label: protein transport by the Sec complex
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: SecB is a dedicated component of the Sec-dependent protein export pathway.
      It delivers unfolded preproteins to SecA, which is the peripheral ATPase of
      the SecYEG translocon (PMID:2170023, PMID:9321390). SecB mutations cause pleiotropic
      defects in protein secretion (PMID:6403503).
    action: ACCEPT
    reason: SecB is specifically dedicated to the Sec translocation pathway. The GO
      term comment notes this is for "proteins that compose the transport complex
      but not the proteins being transported." SecB is not a structural component
      of the translocon itself, but rather functions as the dedicated chaperone that
      delivers substrates to the Sec machinery. The original secB mutant was identified
      by defective protein secretion (PMID:6403503), and the SecB-SecA-SecYEG binding
      cascade is well-established (PMID:2170023). The IBA annotation is appropriate.
    supported_by:
    - reference_id: PMID:2170023
      supporting_text: The binding cascade of SecB to SecA to SecY/E mediates preprotein
        targeting to the E. coli plasma membrane.
    - reference_id: PMID:6403503
      supporting_text: These secB mutants were defective in the localization of maltose-binding
        protein and, in at least one case, OmpF protein.
- term:
    id: GO:0051082
    label: unfolded protein binding
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: SecB does bind unfolded proteins, but GO:0051082 (unfolded protein binding)
      under-represents the actual molecular function. SecB is not merely a passive
      binder of unfolded proteins; it actively carries unfolded precursors from the
      ribosome/cytosol to SecA at the membrane (PMID:2170023, PMID:16962134). GO:0140309
      (unfolded protein carrier activity) better captures this carrier/escort function.
    action: MODIFY
    reason: SecB is a canonical example of a protein carrier chaperone. It binds unfolded
      preproteins and escorts them to SecA at translocation sites. Crane et al. mapped
      the path of unfolded precursor on SecB surface and described a "model for transfer
      of the ligand" from SecB to SecA (PMID:16962134). Hartl et al. described SecB
      as having "a dual function in stabilizing the precursor and in passing it on
      to membrane-bound SecA" (PMID:2170023). The GO term GO:0140309 "unfolded protein
      carrier activity" (defined as "A protein carrier activity that binds to a protein
      in an unfolded state and escorts it between two different cellular components")
      precisely describes SecB function. GO:0051082 is slated for obsoletion, and
      the carrier term is the correct replacement.
    proposed_replacement_terms:
    - id: GO:0140309
      label: unfolded protein carrier activity
    supported_by:
    - reference_id: PMID:16962134
      supporting_text: Capture of the precursor polypeptides before they fold is achieved
        by the promiscuous binding to the chaperone SecB. SecB delivers its ligand
        to export sites through its specific binding to SecA, a peripheral component
        of the membrane translocon. At the translocon the ligand is passed from SecB
        to SecA and subsequently through the SecYEG channel.
    - reference_id: PMID:2170023
      supporting_text: SecB has a dual function in stabilizing the precursor and in
        passing it on to membrane-bound SecA, the next step in the pathway. SecA itself
        is bound to the membrane by its affinity (Kd approximately 4 x 10(-8) M) for
        SecY/E and for acidic lipids.
- term:
    id: GO:0070678
    label: preprotein binding
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: SecB binds specifically to precursor (preprotein) forms of exported proteins
      in vivo and in vitro (PMID:2664780). Kumamoto showed that SecB associates with
      precursor forms of MBP, LamB, and OmpA but not cytoplasmic beta-galactosidase
      (PMID:2664780). This is a core molecular function.
    action: ACCEPT
    reason: Preprotein binding is a core and well-characterized function of SecB.
      The IBA annotation is strongly supported by experimental data showing SecB-preprotein
      complexes in vivo (PMID:2664780) and the extensive characterization of SecB
      substrates (UniProt lists DegP, FhuA, FkpA, GBP, LamB, MalE, OmpA, OmpF, OmpT,
      OmpX, OppA, PhoE, TolB, TolC and others).
    supported_by:
    - reference_id: PMID:2664780
      supporting_text: in wild-type growing cells, SecB protein associates with precursor
        forms of exported proteins, such as the periplasmic maltose-binding protein
        (MBP) and the outer-membrane proteins LamB and OmpA. In contrast, the cytoplasmic
        protein beta-galactosidase was not found in association with SecB.
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: SecB is a cytoplasmic/cytosolic protein. This IEA annotation to cytoplasm
      is broader than the IBA/IDA annotations to cytosol (GO:0005829) but is not incorrect.
    action: ACCEPT
    reason: This is a broader localization annotation. Since cytosol is part of cytoplasm,
      the IEA annotation is technically correct though less specific than the IDA
      cytosol annotations. Acceptable as a supplementary annotation.
- term:
    id: GO:0006457
    label: protein folding
  evidence_type: IEA
  original_reference_id: GO_REF:0000104
  review:
    summary: 'SecB is annotated to protein folding via automated transfer from UniRule.
      However, SecB is an anti-folding chaperone: its function is to PREVENT folding,
      not to assist in it. SecB maintains proteins in an unfolded state for translocation
      (PMID:2834066, PMID:2848249, PMID:18048690).'
    action: REMOVE
    reason: SecB is functionally opposite to a protein folding chaperone. While GroEL/DnaK
      assist in proper folding, SecB specifically prevents folding. Collier et al.
      described SecB's function as "antifolding activity" (PMID:2834066). Bechtluft
      et al. showed SecB "completely prevent stable tertiary contacts" (PMID:18048690).
      Weiss et al. demonstrated SecB "retards folding" (PMID:2848249). The correct
      biological process annotation is GO:0036506 "maintenance of unfolded protein"
      (already present). The protein folding annotation is misleading.
    supported_by:
    - reference_id: PMID:2834066
      supporting_text: The antifolding activity of SecB promotes the export of the
        E. coli maltose-binding protein.
    - reference_id: PMID:18048690
      supporting_text: Interactions with SecB completely prevent stable tertiary contacts
        in the core structure
- term:
    id: GO:0015031
    label: protein transport
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: SecB is involved in the transport of preproteins to the membrane for
      translocation. This IEA annotation to the broad term protein transport is acceptable
      as a general description, though the more specific GO:0043952 (protein transport
      by the Sec complex) is present and more informative.
    action: ACCEPT
    reason: SecB plays an essential role in protein transport, specifically in the
      Sec-dependent export pathway. The IEA annotation is correct and consistent with
      the more specific IBA annotation to GO:0043952. Since this is a broader IEA,
      it is acceptable alongside the more specific annotation.
- term:
    id: GO:0051082
    label: unfolded protein binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  review:
    summary: 'This IEA annotation to unfolded protein binding from InterPro is the
      same term as the IBA annotation above. The same reasoning applies: SecB is more
      accurately described as having unfolded protein carrier activity (GO:0140309)
      rather than mere binding.'
    action: MODIFY
    reason: Same rationale as the IBA annotation for GO:0051082. SecB does not merely
      bind unfolded proteins; it actively carries them to SecA. GO:0140309 (unfolded
      protein carrier activity) is the appropriate replacement.
    proposed_replacement_terms:
    - id: GO:0140309
      label: unfolded protein carrier activity
    supported_by:
    - reference_id: PMID:16962134
      supporting_text: SecB delivers its ligand to export sites through its specific
        binding to SecA, a peripheral component of the membrane translocon.
- term:
    id: GO:0051262
    label: protein tetramerization
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  review:
    summary: SecB forms a homotetramer (dimer of dimers) as confirmed by crystal structure
      (PMID:14643199) and biochemical characterization (PMID:2649892). This IEA annotation
      is consistent with experimental evidence.
    action: ACCEPT
    reason: SecB is a well-characterized homotetramer. Watanabe and Blobel determined
      SecB is "a 64-kDa tetramer consisting of four identical 16-kDa subunits" (PMID:2649892).
      The crystal structure confirms the dimer-of-dimers architecture (UniProt cites
      PubMed:14643199, PubMed:27501151). While tetramerization is structural rather
      than a core evolved function, the annotation is factually accurate.
    supported_by:
    - reference_id: PMID:2649892
      supporting_text: The purified factor amounts to 0.08% of the cytosolic proteins
        and is a 64-kDa tetramer consisting of four identical 16-kDa subunits.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:15690043
  review:
    summary: High-throughput affinity purification/mass spectrometry study identified
      SecB interactions with CpxR and SecA (PMID:15690043). The annotation to generic
      "protein binding" is uninformative; more specific terms exist.
    action: MARK_AS_OVER_ANNOTATED
    reason: '"Protein binding" (GO:0005515) is uninformative per curation guidelines.
      The interaction with SecA is well-captured by the preprotein binding and carrier
      function annotations. The interaction with CpxR from this high-throughput study
      has uncertain functional significance and does not warrant a specific annotation.
      The interaction with SecA is already covered by more specific annotations.'
    supported_by:
    - reference_id: PMID:15690043
      supporting_text: 648 could be purified to homogeneity and their interacting
        protein partners identified by mass spectrometry
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:19402753
  review:
    summary: Large-scale E. coli functional atlas study (PMID:19402753) showing SecB-CpxR
      interaction. Same uninformative generic binding annotation.
    action: MARK_AS_OVER_ANNOTATED
    reason: Same rationale as the PMID:15690043 annotation. Generic "protein binding"
      is uninformative. The functionally meaningful interactions are captured by more
      specific terms (preprotein binding, carrier activity).
    supported_by:
    - reference_id: PMID:19402753
      supporting_text: we performed an extensive proteomic survey using affinity-tagged
        E. coli strains and generated comprehensive genomic context inferences to
        derive a high-confidence compendium for virtually the entire proteome consisting
        of 5,993 putative physical interactions
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:21037004
  review:
    summary: Suo et al. used disulfide cross-linking to determine the orientation
      of SecA and SecB in complex (PMID:21037004). This demonstrates the specific
      SecA-SecB interaction that is central to SecB carrier function. The annotation
      to generic "protein binding" is uninformative.
    action: MARK_AS_OVER_ANNOTATED
    reason: This study characterizes the SecB-SecA interaction in detail, which is
      better captured by the carrier activity and preprotein binding annotations.
      Generic "protein binding" does not convey the functional significance.
    supported_by:
    - reference_id: PMID:21037004
      supporting_text: The tetrameric cytoplasmic chaperone SecB binds to precursors
        of exported proteins before they can become stably folded and delivers them
        to SecA.
- term:
    id: GO:0036506
    label: maintenance of unfolded protein
  evidence_type: IMP
  original_reference_id: PMID:2834066
  review:
    summary: Collier et al. demonstrated the antifolding activity of SecB in vivo
      using genetic approaches. SecB- cells showed defective MBP export that was suppressed
      by mutations affecting MBP folding, and the rate of MBP folding was retarded
      in the presence of excess SecB (PMID:2834066).
    action: ACCEPT
    reason: This is strong experimental evidence (IMP) for SecB's core antifolding
      function. The genetic suppression experiments directly demonstrate that SecB's
      role is to prevent premature folding of export substrates. This is a core function.
    supported_by:
    - reference_id: PMID:2834066
      supporting_text: 'The antifolding activity of SecB was demonstrated by the following:
        the defect in MBP export in SecB- cells was suppressed by mutational alterations
        affecting MBP folding; export of a mutant MBP that is accomplished in a strictly
        posttranslational mode was totally blocked in SecB- cells; and the rate of
        folding of wild-type MBP synthesized in vitro was found to be accelerated
        when SecB was absent and greatly retarded when excess SecB was present.'
- term:
    id: GO:0036506
    label: maintenance of unfolded protein
  evidence_type: IDA
  original_reference_id: PMID:2848249
  review:
    summary: Weiss et al. purified SecB and demonstrated directly that it retards
      folding of precursor MBP in vitro and promotes membrane translocation. Purified
      SecB both retarded folding and prolonged translocation competence (PMID:2848249).
    action: ACCEPT
    reason: Direct biochemical demonstration of SecB antifolding activity using purified
      protein. This IDA evidence is strong support for maintenance of unfolded protein
      as a core function.
    supported_by:
    - reference_id: PMID:2848249
      supporting_text: The purified protein also quantitatively retarded folding of
        precursor MBP into a stable, protease-resistant conformation in the absence
        of membranes. Finally, the inclusion of excess purified SecB in a SecB+ in
        vitro system significantly prolonged the time in which precursor MBP remained
        competent for posttranslational import into membrane vesicles.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:15811382
  review:
    summary: Randall et al. characterized the asymmetric binding between SecA and
      SecB, showing that SecB C-terminal alpha-helices bind in the SecA dimer interface
      (PMID:15811382). This documents the specific SecA-SecB interaction central to
      the carrier/delivery function.
    action: MARK_AS_OVER_ANNOTATED
    reason: The specific SecB-SecA interaction studied here is functionally meaningful
      and central to the carrier function, but generic "protein binding" does not
      convey this. The carrier activity and preprotein binding annotations better
      capture the functional significance. Per curation guidelines, protein binding
      is uninformative.
    supported_by:
    - reference_id: PMID:15811382
      supporting_text: SecB also demonstrates specific recognition of, and binding
        to, SecA. SecB with the precursor tightly bound enters an export-active complex
        with SecA and must pass the ligand to SecA at the translocon in the membrane.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:2170023
  review:
    summary: Hartl et al. characterized the SecB-SecA-SecYEG binding cascade and determined
      binding affinities (PMID:2170023). This is a foundational paper for understanding
      SecB's carrier function. The annotation to generic "protein binding" is uninformative.
    action: MARK_AS_OVER_ANNOTATED
    reason: This landmark study defines the binding cascade that constitutes SecB's
      carrier activity. Generic "protein binding" fails to capture this. The carrier
      activity and preprotein binding annotations are more informative.
    supported_by:
    - reference_id: PMID:2170023
      supporting_text: SecB has a dual function in stabilizing the precursor and in
        passing it on to membrane-bound SecA, the next step in the pathway.
- term:
    id: GO:0070678
    label: preprotein binding
  evidence_type: IDA
  original_reference_id: PMID:2664780
  review:
    summary: Kumamoto showed that SecB associates with precursor forms of exported
      proteins (MBP, LamB, OmpA) in vivo, and that these complexes are transient intermediates
      in the export pathway (PMID:2664780). This is direct experimental evidence for
      preprotein binding.
    action: ACCEPT
    reason: Strong IDA evidence for a core function. SecB specifically recognizes
      and binds preprotein forms of exported proteins. This is the binding component
      of its carrier function.
    supported_by:
    - reference_id: PMID:2664780
      supporting_text: in wild-type growing cells, SecB protein associates with precursor
        forms of exported proteins, such as the periplasmic maltose-binding protein
        (MBP) and the outer-membrane proteins LamB and OmpA. In contrast, the cytoplasmic
        protein beta-galactosidase was not found in association with SecB. Pulse-chase
        analysis showed that the SecB-precursor MBP complex was short lived, as expected
        for a complex that represents an intermediate in the protein-export pathway.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:9321390
  review:
    summary: Fekkes et al. identified the SecB binding site on SecA (the extreme C-terminal
      22 residues) and showed SecB is released upon ATP binding by SecA (PMID:9321390).
      This characterizes the mechanistic detail of the SecB-SecA handoff.
    action: MARK_AS_OVER_ANNOTATED
    reason: This important mechanistic study defines the SecB-SecA interaction site
      and the release mechanism. However, annotation to generic "protein binding"
      is uninformative. The carrier activity annotation better captures this delivery/handoff
      function.
    supported_by:
    - reference_id: PMID:9321390
      supporting_text: The chaperone SecB keeps precursor proteins in a translocation-competent
        state and targets them to SecA at the translocation sites in the cytoplasmic
        membrane of Escherichia coli. ... SecB is released from this site at the onset
        of translocation.
- term:
    id: GO:0008104
    label: intracellular protein localization
  evidence_type: IMP
  original_reference_id: PMID:6403503
  review:
    summary: Kumamoto and Beckwith identified secB mutants with defective protein
      localization, showing SecB is required for proper localization of MBP and OmpF
      (PMID:6403503). This is the founding paper for SecB function.
    action: ACCEPT
    reason: This is the original identification of the secB gene and its role in protein
      localization. While the more specific annotations (protein transport by the
      Sec complex, protein targeting) also capture this, the broader intracellular
      protein localization term is appropriate for what the mutant phenotype directly
      demonstrates.
    supported_by:
    - reference_id: PMID:6403503
      supporting_text: These secB mutants were defective in the localization of maltose-binding
        protein and, in at least one case, OmpF protein. Double mutants with lesions
        in both secA and secB had strong defects in the secretion of maltose-binding
        protein and OmpF protein.
- term:
    id: GO:0051082
    label: unfolded protein binding
  evidence_type: IDA
  original_reference_id: PMID:16962134
  review:
    summary: Crane et al. used site-directed spin labeling and EPR to map the binding
      pathway of unfolded precursor galactose-binding protein on SecB (PMID:16962134).
      They showed the precursor makes contact with a large portion of the SecB surface
      and established a model for transfer of the ligand from SecB to SecA.
    action: MODIFY
    reason: 'While this paper confirms SecB binds unfolded proteins, the study explicitly
      describes the delivery/transfer function: "SecB delivers its ligand to export
      sites through its specific binding to SecA" and discusses "a model for transfer
      of the ligand." This is carrier activity, not mere binding. GO:0140309 (unfolded
      protein carrier activity) captures the complete function.'
    proposed_replacement_terms:
    - id: GO:0140309
      label: unfolded protein carrier activity
    supported_by:
    - reference_id: PMID:16962134
      supporting_text: Export of protein into the periplasm of Escherichia coli via
        the general secretory system requires that the transported polypeptides be
        devoid of stably folded tertiary structure. Capture of the precursor polypeptides
        before they fold is achieved by the promiscuous binding to the chaperone SecB.
        SecB delivers its ligand to export sites through its specific binding to SecA,
        a peripheral component of the membrane translocon. At the translocon the ligand
        is passed from SecB to SecA and subsequently through the SecYEG channel.
- term:
    id: GO:0051082
    label: unfolded protein binding
  evidence_type: IMP
  original_reference_id: PMID:18048690
  review:
    summary: Bechtluft et al. used optical tweezers and molecular dynamics to show
      SecB prevents stable tertiary contacts in MBP and retains it in a molten-globule-like
      state (PMID:18048690). This demonstrates the holdase activity that is part of
      the carrier function.
    action: MODIFY
    reason: 'Same reasoning as other GO:0051082 annotations. While this paper focuses
      on the antifolding/holdase mechanism, the broader context of SecB function is
      carrier activity: binding unfolded proteins and delivering them. GO:0140309
      (unfolded protein carrier activity) is the appropriate replacement that encompasses
      both binding and delivery.'
    proposed_replacement_terms:
    - id: GO:0140309
      label: unfolded protein carrier activity
    supported_by:
    - reference_id: PMID:18048690
      supporting_text: It appears that SecB only binds to the extended or molten globulelike
        structure and retains MBP in this latter state. Thus during MBP translocation,
        no energy is required to disrupt stable tertiary interactions.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IDA
  original_reference_id: PMID:18304323
  review:
    summary: Ishihama et al. identified SecB in the cytosolic proteome of E. coli
      by mass spectrometry (PMID:18304323). Direct experimental evidence for cytosolic
      localization.
    action: ACCEPT
    reason: Proteomic identification of SecB in the cytosolic fraction is direct evidence
      for cytosol localization.
    supported_by:
    - reference_id: PMID:18304323
      supporting_text: we identified 1103 proteins from the cytosolic fraction of
        the Escherichia coli strain MC4100
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IDA
  original_reference_id: PMID:2649892
  review:
    summary: Watanabe and Blobel purified SecB as a cytosolic factor required for
      preprotein translocation (PMID:2649892). This is foundational evidence for SecB
      cytosolic localization.
    action: ACCEPT
    reason: SecB was originally purified as a cytosolic factor, providing direct evidence
      for cytosol localization.
    supported_by:
    - reference_id: PMID:2649892
      supporting_text: We have purified to homogeneity a cytosolic factor from Escherichia
        coli that is required for the translocation of a preprotein into inverted
        vesicles of the E. coli plasma membrane.
- term:
    id: GO:0006605
    label: protein targeting
  evidence_type: IMP
  original_reference_id: PMID:6403503
  review:
    summary: SecB mutations cause defective protein targeting/localization. The original
      secB mutants showed pleiotropic defects in secretion of envelope proteins (PMID:6403503).
    action: ACCEPT
    reason: SecB is essential for targeting a subset of preproteins to the Sec translocon.
      The GO:0006605 definition ("targeting specific proteins to particular regions
      of the cell") accurately describes SecB's role in directing preproteins to the
      inner membrane for translocation. This is consistent with but slightly different
      from the protein transport annotations.
    supported_by:
    - reference_id: PMID:6403503
      supporting_text: We isolated a new class of Escherichia coli mutants with pleiotropic
        defects in protein secretion. ... the selection also yielded mutants with
        mutations in a new locus, which was designated secB.
- term:
    id: GO:0015031
    label: protein transport
  evidence_type: IMP
  original_reference_id: PMID:6403503
  review:
    summary: SecB mutations cause defective protein transport across the inner membrane
      (PMID:6403503). This is a broader term that encompasses the Sec-complex-specific
      annotation.
    action: ACCEPT
    reason: Accurate but broad. SecB is clearly involved in protein transport as shown
      by the secB mutant phenotype. The more specific GO:0043952 (protein transport
      by the Sec complex) is also present.
    supported_by:
    - reference_id: PMID:6403503
      supporting_text: These secB mutants were defective in the localization of maltose-binding
        protein and, in at least one case, OmpF protein.
- term:
    id: GO:0043952
    label: protein transport by the Sec complex
  evidence_type: IMP
  original_reference_id: PMID:6403503
  review:
    summary: The original secB mutant identification showed defective protein secretion,
      placing SecB in the Sec-dependent export pathway (PMID:6403503). Later work
      confirmed SecB functions specifically in the Sec pathway.
    action: ACCEPT
    reason: The original paper identifies secB as a gene required for protein secretion
      alongside secA. While the original paper did not explicitly name the "Sec complex,"
      subsequent work established SecB as a dedicated component of the Sec pathway.
      The IMP annotation from EcoliWiki is appropriate.
    supported_by:
    - reference_id: PMID:6403503
      supporting_text: The properties of secB mutants suggest that the secB product
        could be a component of the E. coli secretory apparatus.
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: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:14643199
  title: Crystal structure of SecB from Escherichia coli.
  findings:
  - statement: SecB forms a homotetramer (dimer of dimers) as shown by X-ray crystallography
      at 2.35 angstrom resolution.
    supporting_text: The chaperone SecB from Escherichia coli is primarily involved
      in passing precursor proteins into the Sec system via specific interactions
      with SecA. The crystal structure of SecB from E. coli has been solved to 2.35
      A resolution.
- id: PMID:15690043
  title: Interaction network containing conserved and essential protein complexes
    in Escherichia coli.
  findings:
  - statement: Large-scale affinity purification/mass spectrometry identified SecB
      interactions with CpxR and SecA.
    supporting_text: A total of 857 proteins, including 198 of the most highly conserved,
      soluble non-ribosomal proteins essential in at least one bacterial species,
      were tagged successfully, whereas 648 could be purified to homogeneity and their
      interacting protein partners identified by mass spectrometry.
- id: PMID:15811382
  title: 'Asymmetric binding between SecA and SecB two symmetric proteins: implications
    for function in export.'
  findings:
  - statement: SecB C-terminal alpha-helices bind in the interfacial region of the
      SecA dimer, and this asymmetric binding facilitates conformational changes for
      precursor transfer.
    supporting_text: unexpectedly, the binding between the two symmetric molecules
      is asymmetric and that the C-terminal alpha-helices of SecB bind in the interfacial
      region of the SecA dimer.
- id: PMID:16352602
  title: Defining the role of the Escherichia coli chaperone SecB using comparative
    proteomics.
  findings:
  - statement: Comparative proteomics identified the full set of SecB substrates including
      DegP, FhuA, FkpA, GBP, LamB, MalE, OmpA, OmpF, OmpT, OmpX, OppA, PhoE, TolB,
      TolC, YbgF, YcgK, YgiW and YncE.
    supporting_text: The SecB/A dependence of 12 secretory proteins affected by the
      secB null mutation (DegP, FhuA, FkpA, OmpT, OmpX, OppA, TolB, TolC, YbgF, YcgK,
      YgiW, and YncE) was confirmed by "classical" pulse-labeling experiments. Our
      study more than triples the number of known SecB-dependent secretory proteins
      and shows that the primary role of SecB is to facilitate the targeting of secretory
      proteins to the Sec-translocase.
- id: PMID:16962134
  title: Sites of interaction of a precursor polypeptide on the export chaperone SecB
    mapped by site-directed spin labeling.
  findings:
  - statement: Site-directed spin labeling and EPR mapped the binding sites of unfolded
      precursor galactose-binding protein on SecB surface, showing contact with a
      large portion of the small chaperone surface. A model for transfer of the ligand
      from SecB to SecA was proposed.
    supporting_text: Capture of the precursor polypeptides before they fold is achieved
      by the promiscuous binding to the chaperone SecB. SecB delivers its ligand to
      export sites through its specific binding to SecA
- id: PMID:18048690
  title: Direct observation of chaperone-induced changes in a protein folding pathway.
  findings:
  - statement: Single-molecule optical tweezers and MD simulations showed SecB completely
      prevents stable tertiary contacts in MBP, retaining it in a molten-globule-like
      state.
    supporting_text: Interactions with SecB completely prevent stable tertiary contacts
      in the core structure but have no detectable effect on the folding of the external
      alpha helices.
- id: PMID:18304323
  title: Protein abundance profiling of the Escherichia coli cytosol.
  findings:
  - statement: SecB identified in the cytosolic proteome of E. coli MC4100.
    supporting_text: we identified 1103 proteins from the cytosolic fraction of the
      Escherichia coli strain MC4100
- id: PMID:19402753
  title: Global functional atlas of Escherichia coli encompassing previously uncharacterized
    proteins.
  findings:
  - statement: Large-scale functional atlas showing SecB-CpxR interaction.
    supporting_text: we performed an extensive proteomic survey using affinity-tagged
      E. coli strains and generated comprehensive genomic context inferences to derive
      a high-confidence compendium for virtually the entire proteome consisting of
      5,993 putative physical interactions
- id: PMID:21037004
  title: Orientation of SecA and SecB in complex, derived from disulfide cross-linking.
  findings:
  - statement: Disulfide cross-linking defined the relative orientation of SecA and
      SecB within the complex. Two SecA protomers bind one SecB tetramer.
    supporting_text: The tetrameric cytoplasmic chaperone SecB binds to precursors
      of exported proteins before they can become stably folded and delivers them
      to SecA.
- id: PMID:2170023
  title: The binding cascade of SecB to SecA to SecY/E mediates preprotein targeting
    to the E. coli plasma membrane.
  findings:
  - statement: SecB has a dual function in stabilizing precursors and delivering them
      to membrane-bound SecA. The SecB-SecA-SecYEG binding cascade was characterized
      with binding affinities.
    supporting_text: SecB has a dual function in stabilizing the precursor and in
      passing it on to membrane-bound SecA, the next step in the pathway.
- id: PMID:2649892
  title: Cytosolic factor purified from Escherichia coli is necessary and sufficient
    for the export of a preprotein and is a homotetramer of SecB.
  findings:
  - statement: SecB purified as a 64-kDa homotetramer of identical 16-kDa subunits
      from the cytosol. It is necessary and sufficient for translocation of preproteins
      into inverted membrane vesicles.
    supporting_text: The purified factor amounts to 0.08% of the cytosolic proteins
      and is a 64-kDa tetramer consisting of four identical 16-kDa subunits.
- id: PMID:2664780
  title: Escherichia coli SecB protein associates with exported protein precursors
    in vivo.
  findings:
  - statement: SecB associates with precursor forms of exported proteins (MBP, LamB,
      OmpA) in vivo. The SecB-precursor complex is short-lived, consistent with an
      export intermediate.
    supporting_text: in wild-type growing cells, SecB protein associates with precursor
      forms of exported proteins, such as the periplasmic maltose-binding protein
      (MBP) and the outer-membrane proteins LamB and OmpA.
- id: PMID:27501151
  title: Structural basis for the antifolding activity of a molecular chaperone.
  findings:
  - statement: NMR structures of SecB in complex with substrates showed that precursor
      proteins wrap around the SecB homotetramer, providing the structural basis for
      antifolding activity.
    supporting_text: The most remarkable feature is that PhoA wraps around SecB in
      an overall arrangement that maximizes the interacting surface between the client
      protein, which is held in an unfolded conformation, and the chaperone.
- id: PMID:2834066
  title: The antifolding activity of SecB promotes the export of the E. coli maltose-binding
    protein.
  findings:
  - statement: SecB prevents premature folding of newly synthesized MBP precursor,
      promoting export. The antifolding activity was demonstrated by genetic suppression
      and in vitro folding assays.
    supporting_text: 'The antifolding activity of SecB was demonstrated by the following:
      the defect in MBP export in SecB- cells was suppressed by mutational alterations
      affecting MBP folding'
- id: PMID:2848249
  title: Purified secB protein of Escherichia coli retards folding and promotes membrane
    translocation of the maltose-binding protein in vitro.
  findings:
  - statement: Purified SecB retards folding of precursor MBP and promotes its translocation
      into inverted membrane vesicles in vitro. SecB is a soluble, cytoplasmic, multimeric
      protein of identical 17-kDa subunits.
    supporting_text: The purified protein also quantitatively retarded folding of
      precursor MBP into a stable, protease-resistant conformation in the absence
      of membranes.
- id: PMID:6403503
  title: Mutations in a new gene, secB, cause defective protein localization in Escherichia
    coli.
  findings:
  - statement: SecB was identified as a new gene required for protein secretion. secB
      mutants showed defective localization of MBP and OmpF. The secB product was
      proposed as a component of the E. coli secretory apparatus.
    supporting_text: These secB mutants were defective in the localization of maltose-binding
      protein and, in at least one case, OmpF protein.
- id: PMID:9321390
  title: The molecular chaperone SecB is released from the carboxy-terminus of SecA
    during initiation of precursor protein translocation.
  findings:
  - statement: The SecB-binding site on SecA is confined to the extreme C-terminal
      22 amino acids. SecB is released from SecA upon ATP binding, at the onset of
      translocation.
    supporting_text: The chaperone SecB keeps precursor proteins in a translocation-competent
      state and targets them to SecA at the translocation sites in the cytoplasmic
      membrane of Escherichia coli.
core_functions:
- description: SecB functions as a dedicated export chaperone/carrier in the Sec-dependent
    protein translocation pathway. It binds unfolded preprotein substrates in the
    cytosol, prevents their premature folding (holdase/antifolding activity), and
    delivers them to SecA at the inner membrane translocon (carrier activity). This
    is an ATP-independent process.
  molecular_function:
    id: GO:0140309
    label: unfolded protein carrier activity
  directly_involved_in:
  - id: GO:0043952
    label: protein transport by the Sec complex
  - id: GO:0036506
    label: maintenance of unfolded protein
  locations:
  - id: GO:0005829
    label: cytosol
  supported_by:
  - reference_id: PMID:2170023
    supporting_text: SecB has a dual function in stabilizing the precursor and in
      passing it on to membrane-bound SecA, the next step in the pathway.
  - reference_id: PMID:16962134
    supporting_text: SecB delivers its ligand to export sites through its specific
      binding to SecA, a peripheral component of the membrane translocon.
  - reference_id: PMID:2848249
    supporting_text: The purified protein also quantitatively retarded folding of
      precursor MBP into a stable, protease-resistant conformation in the absence
      of membranes.

SecB

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

BioReason Chat Export

Thinking Trace

Functional Summary

UniProt Summary

InterPro Domains

GO Terms

Deep Research Falcon

Question

Gene Research for Functional Annotation

⚠️ CRITICAL: Gene/Protein Identification Context

Target Gene/Protein Identity (from UniProt):

MANDATORY VERIFICATION STEPS:

If Gene Symbol is Ambiguous or You Cannot Find Relevant Literature:

Research Target:

Output

Gene Research for Functional Annotation

⚠️ CRITICAL: Gene/Protein Identification Context

Target Gene/Protein Identity (from UniProt):

MANDATORY VERIFICATION STEPS:

If Gene Symbol is Ambiguous or You Cannot Find Relevant Literature:

Research Target:

Research report: secB (UniProt P0AG86) functional annotation in Escherichia coli K-12

1) Identity verification (mandatory)

2) Key concepts and definitions (current understanding)

2.1. What SecB is (molecular function)

2.2. “Post-translational Sec pathway” and “translocation-competent state”

2.3. Pathway role and interaction partners

3) Cellular localization and biological processes

4) Quantitative statistics and data (mechanism-relevant)

4.1. Intracellular concentration / abundance

4.2. Binding affinities and pathway coupling

4.3. Quantitative context from recent (2023) Sec-system synthesis

5) Recent developments and latest research (prioritizing 2023–2024)

6) Current applications and real-world implementations

6.1. Biotechnology: secretion/periplasmic export engineering (conceptual lever)

6.2. Antimicrobial relevance: Sec pathway as target space (SecB as accessory)

7) Expert opinions / authoritative analysis

8) Consolidated functional annotation summary

9) Key source URLs and publication dates (as retrieved)

10) Evidence gaps and recommended next steps (for completeness)

Citations

Bioreason Rl Review

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

Functional Summary Review

Notes on thinking trace

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