Skp

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0006457 protein folding	IBA GO_REF:0000033	ACCEPT	Summary: IBA annotation for protein folding. Skp is involved in the biogenesis pathway of outer membrane proteins, but its primary role is as a holdase/carrier rather than a classical foldase. Skp maintains OMP substrates in an unfolded state during periplasmic transit (PMID:19181847). The OmpA beta-barrel domain remains unfolded while bound to Skp (PMID:19181847). Folding and insertion into the outer membrane only occurs after release from Skp at the BAM complex, often requiring LPS (PMID:12509434). While Skp participates in the broader folding pathway, a more accurate description would be that Skp prevents premature folding/aggregation and escorts OMPs to the site of folding. The IBA annotation is reasonable at a high level given its role in the OMP biogenesis pathway. Reason: Protein folding is a biological-process annotation: it records Skp's participation in the pathway that produces folded OMPs, not direct foldase catalytic activity. Current PAINT places this inherited role at PTN002170712, and Skp's experimental IDA and IMP annotations independently support that placement. Its carrier-holdase mechanism is captured separately by GO:0140309, while GO:0043165 records the associated assembly pathway. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN002170712 · PANTHER:PTN002170712 SUPPORTS TRANSFER Current PTHR35089 PAINT retains GO:0006457 at this ancestral node. UniProtKB:P0AEU7 · UniProtKB:P0AEU7 SUPPORTS TRANSFER Skp itself is the experimentally grounded descendant seed; its presence in the IBA trace is expected and is not circular. Supporting Evidence: PMID:19181847 while bound to Skp, the beta-barrel domain of OmpA is maintained in an unfolded state, whereas the periplasmic domain is folded in its native conformation PMID:12509434 Skp alone was not sufficient to facilitate membrane insertion and folding of OmpA. In addition, lipopolysaccharide (LPS) was required. OmpA remained unfolded when bound to Skp and LPS in solution.
GO:0050821 protein stabilization	IBA GO_REF:0000033	ACCEPT	Summary: IBA annotation for protein stabilization. This is well-supported by multiple experimental studies. Skp prevents aggregation of unfolded OMP intermediates in the periplasm (PMID:10455120, PMID:15304217, PMID:23796519). In skp null mutants combined with degP deletion, protein aggregates accumulate in the periplasm (PMID:10455120). Skp protects substrates from aggregation in a cavity-dependent manner (PMID:19181847). Reason: Core function of Skp as a holdase chaperone. IBA annotation is strongly supported by experimental evidence from multiple laboratories. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN002170712 · PANTHER:PTN002170712 SUPPORTS TRANSFER Current PTHR35089 PAINT retains GO:0050821 at this ancestral node. UniProtKB:P0AEU7 · UniProtKB:P0AEU7 SUPPORTS TRANSFER Skp itself provides direct descendant evidence for protein stabilization; its presence in the trace is expected and is not circular. Supporting Evidence: PMID:10455120 in the absence of an active DegP, a lack of Skp leads to the accumulation of protein aggregates in the periplasm PMID:15304217 The ability of Skp to prevent the aggregation of model substrates in vitro is independent of ATP
GO:0042597 periplasmic space	IEA GO_REF:0000044	MODIFY	Summary: IEA annotation based on UniProt subcellular location mapping. Consistent with extensive experimental evidence for periplasmic localization (PMID:1838129, PMID:8730870, PMID:10455120). The more specific term GO:0030288 (outer membrane-bounded periplasmic space) is also annotated with IDA evidence. This broader IEA annotation is acceptable as it does not conflict with the more specific experimental evidence. Reason: Correct but less specific than the directly supported bacterial periplasm term. Replace the broad mapping with GO:0030288. Proposed replacements: outer membrane-bounded periplasmic space Supporting Evidence: PMID:1838129 Skp partitions with beta-lactamase into the fraction of soluble, periplasmic proteins
GO:0051082 unfolded protein binding	IEA GO_REF:0000002	MODIFY	Summary: IEA annotation from InterPro (IPR005632, Chaperone_Skp). While Skp does bind unfolded proteins, GO:0051082 is now formally obsolete as it is overly broad and fails to distinguish between different modes of chaperone action. Skp is a true carrier chaperone that escorts unfolded OMPs from the Sec translocon/inner membrane to the BAM complex in the outer membrane (PMID:10455120, PMID:19181847). The term GO:0140309 (unfolded protein holdase activity) precisely captures this escort/carrier function. Reason: GO:0051082 is now formally obsolete. Skp functions as an unfolded protein carrier -- it binds unfolded OMPs at the inner membrane and escorts them across the periplasm to the BAM complex for outer membrane insertion. This is a carrier/escort function, not merely binding. Proposed replacements: unfolded protein holdase activity Supporting Evidence: PMID:10455120 Skp is a molecular chaperone involved in generating and maintaining the solubility of early folding intermediates of outer membrane proteins in the periplasmic space of Gram-negative bacteria PMID:19181847 This domain-based chaperoning mechanism allows the transport of beta-barrels across the periplasm in an unfolded state, which may be important for efficient insertion into the outer membrane file:ECOLI/Skp/Skp-deep-research-falcon.md Skp is an ATP-independent periplasmic holdase chaperone
GO:0005515 protein binding	IPI PMID:19181847 The cavity-chaperone Skp protects its substrate from aggrega...	MODIFY	Summary: IPI annotation for protein binding based on Skp interaction with OmpA (with/from UniProtKB:P0A910). This study demonstrated by NMR and crosslinking that the OmpA beta-barrel is bound within the Skp cavity while the periplasmic domain protrudes outside (PMID:19181847). However, GO:0005515 (protein binding) is uninformative. The interaction is better captured by the more specific GO:0140309 (unfolded protein holdase activity) or GO:0042802 (identical protein binding) for the homotrimerization. Reason: Protein binding is too vague and uninformative for curation purposes. The specific interaction with unfolded OMPs is the functional essence, which is better represented by GO:0140309 (unfolded protein holdase activity). Proposed replacements: unfolded protein holdase activity Supporting Evidence: PMID:19181847 the OmpA beta-barrel is bound deep within the Skp cavity, whereas the folded periplasmic domain protrudes outside of the cavity where it tumbles independently from the rest of the complex
GO:0005515 protein binding	IPI PMID:24077225 Conformation and dynamics of the periplasmic membrane-protei...	MODIFY	Summary: IPI annotation for protein binding based on Skp interaction with OmpA (with/from UniProtKB:P0A910) and OmpX (UniProtKB:P0A917). This study used high-resolution NMR to characterize Skp complexes with OmpX and tOmpA, showing that OMP substrates populate a dynamic conformational ensemble while bound to Skp (PMID:24077225). As with the other protein binding annotations, GO:0005515 is uninformative. Note: the GOA file shows two rows for this PMID with different with/from values (P0A910 and P0A917). Reason: Protein binding is too vague. The specific interaction with unfolded OMPs is better represented by GO:0140309 (unfolded protein holdase activity). Proposed replacements: unfolded protein holdase activity Supporting Evidence: PMID:24077225 The Skp trimer constitutes a flexible architectural scaffold that becomes more rigid upon substrate binding. The OMP substrates populate a dynamic conformational ensemble
GO:0042802 identical protein binding	IPI PMID:16858726 A complexomic study of Escherichia coli using two-dimensiona...	KEEP AS NON CORE	Summary: IPI annotation for identical protein binding (homotrimerization) from a complexomic study using 2D blue native/SDS-PAGE. Skp was identified as a homomultimeric complex (PMID:16858726). Skp is a well-established homotrimer (PMID:15304217). The trimerization is essential for its chaperone function as the three subunits form the cavity that captures OMPs. Reason: Homotrimerization is a valid structural prerequisite for the functional Skp cavity, but identical protein binding is not itself the core holdase activity. Supporting Evidence: PMID:16858726 50 heteromultimeric and 256 homomultimeric protein complexes were found PMID:15304217 The structure of the Skp trimer resembles a jellyfish with alpha-helical tentacles protruding from a beta barrel body defining a central cavity
GO:0042802 identical protein binding	IPI PMID:19181847 The cavity-chaperone Skp protects its substrate from aggrega...	KEEP AS NON CORE	Summary: IPI annotation for identical protein binding from Walton et al. 2009, which used NMR and crosslinking to study the Skp trimer-OmpA complex. The Skp trimer is integral to the cavity chaperone mechanism (PMID:19181847). Duplicate of the GO:0042802 annotation from PMID:16858726 in terms of GO term, but valid with different evidence. Reason: Valid additional evidence for homotrimerization, retained as a non-core structural property rather than a core molecular function. Supporting Evidence: PMID:19181847 The 17-kDa protein (Skp) is a periplasmic chaperone that assists the folding and insertion of many OMPs
GO:0042802 identical protein binding	IPI PMID:24077225 Conformation and dynamics of the periplasmic membrane-protei...	KEEP AS NON CORE	Summary: IPI annotation for identical protein binding from Burmann et al. 2013 NMR study of Skp-OMP complexes. Confirms the trimeric nature of Skp (PMID:24077225). Reason: Valid additional evidence for homotrimerization, retained as a non-core structural property rather than a core molecular function. Supporting Evidence: PMID:24077225 The Skp trimer constitutes a flexible architectural scaffold that becomes more rigid upon substrate binding
GO:0006457 protein folding	IDA PMID:12509434 Folding and insertion of the outer membrane protein OmpA is ...	ACCEPT	Summary: IDA annotation for protein folding from Bulieris et al. 2003. This study demonstrated that Skp, together with LPS, assists the folding and insertion of OmpA into phospholipid bilayers in vitro (PMID:12509434). Importantly, Skp alone was not sufficient -- LPS was also required. OmpA remained unfolded when bound to Skp. Thus Skp acts as a carrier/holdase in the folding pathway rather than directly catalyzing folding. The protein folding annotation is acceptable in the broader sense that Skp participates in the pathway leading to OMP folding. Reason: The assay directly shows that Skp participates in the biological process leading to OmpA folding and insertion. GO:0006457 does not assert that Skp catalyzes folding; the carrier-holdase mechanism and the outer-membrane-assembly context are represented by separate annotations. Supporting Evidence: PMID:12509434 Skp alone was not sufficient to facilitate membrane insertion and folding of OmpA. In addition, lipopolysaccharide (LPS) was required PMID:12509434 unfolded OmpA in complex with Skp and LPS folded faster into phospholipid bilayers than urea-unfolded OmpA
GO:0043165 Gram-negative-bacterium-type cell outer membrane assembly	IDA PMID:8730870 A periplasmic protein (Skp) of Escherichia coli selectively ...	ACCEPT	Summary: IDA annotation from Chen and Henning 1996, the foundational paper identifying Skp as a periplasmic chaperone for OMPs. They showed Skp selectively binds OMPs (OmpA, OmpC, OmpF, LamB) and that skp deletion mutants have much-reduced concentrations of outer membrane proteins (PMID:8730870). This is a core biological process annotation for Skp. Reason: Core function. Skp is directly involved in outer membrane assembly by escorting OMPs across the periplasm to the outer membrane. Supporting Evidence: PMID:8730870 The mutant was viable but possessed much-reduced concentrations of outer membrane proteins. This defect was fully restored by a plasmid-borne skp gene
GO:0050821 protein stabilization	EXP PMID:10455120 Skp, a molecular chaperone of gram-negative bacteria, is req...	ACCEPT	Summary: EXP annotation from Schaefer et al. 1999 demonstrating Skp's role in maintaining solubility of OMP folding intermediates. In skp/degP double mutants, protein aggregates accumulate in the periplasm (PMID:10455120). Skp is required for the release of newly translocated OMPs from the plasma membrane and maintenance of their solubility. Reason: Core function of Skp. Preventing aggregation and maintaining solubility of unfolded OMPs is the essence of its holdase/carrier activity. Supporting Evidence: PMID:10455120 in the absence of an active DegP, a lack of Skp leads to the accumulation of protein aggregates in the periplasm PMID:10455120 Skp is a molecular chaperone involved in generating and maintaining the solubility of early folding intermediates of outer membrane proteins
GO:0050821 protein stabilization	IDA PMID:12509434 Folding and insertion of the outer membrane protein OmpA is ...	ACCEPT	Summary: IDA annotation from Bulieris et al. 2003. Demonstrated that Skp prevents aggregation of unfolded OmpA and maintains it in a soluble complex (PMID:12509434). OmpA remained unfolded but soluble when bound to Skp. Reason: Consistent with Skp's core holdase function of preventing aggregation. Supporting Evidence: PMID:12509434 OmpA remained unfolded when bound to Skp and LPS in solution. From this complex, OmpA folded spontaneously into lipid bilayers
GO:0050821 protein stabilization	IDA PMID:15304217 Crystal structure of Skp, a prefoldin-like chaperone that pr...	ACCEPT	Summary: IDA annotation from the Skp crystal structure paper (Walton and Sousa 2004). Demonstrated that Skp prevents aggregation of model substrates in vitro in an ATP-independent manner (PMID:15304217). The structure reveals the cavity where substrates are protected from aggregation. Reason: Structural and biochemical evidence for Skp's anti-aggregation function. Supporting Evidence: PMID:15304217 The ability of Skp to prevent the aggregation of model substrates in vitro is independent of ATP
GO:0050821 protein stabilization	IDA PMID:23796519 Dissecting the effects of periplasmic chaperones on the in v...	ACCEPT	Summary: IDA annotation from McMorran et al. 2013. Demonstrated that Skp can rescue the OMP PagP from aggregation and promote its subsequent folding and membrane insertion (PMID:23796519). Skp-mediated delivery of PagP to liposomes is influenced by electrostatic interactions between the chaperone and lipid. Reason: Additional evidence from a different OMP substrate (PagP) confirming Skp's role in preventing OMP aggregation. Supporting Evidence: PMID:23796519 folding and membrane insertion of PagP can be restored, in part, by Skp in conditions that strongly favour PagP aggregation PMID:23796519 the key role of Skp in holding aggregation-prone OMPs prior to their direct or indirect delivery to the membrane
GO:0051082 unfolded protein binding	IDA PMID:19181847 The cavity-chaperone Skp protects its substrate from aggrega...	MODIFY	Summary: IDA annotation from Walton et al. 2009. NMR experiments provided direct evidence that the OmpA beta-barrel domain is maintained in an unfolded state while bound deep within the Skp cavity (PMID:19181847). This confirms Skp binds unfolded proteins, but GO:0051082 fails to capture the carrier/escort function. GO:0140309 (unfolded protein holdase activity) is more appropriate as Skp transports unfolded OMPs from the inner membrane to the BAM complex. Reason: GO:0051082 is now formally obsolete and does not distinguish Skp's carrier function from simple binding. Skp is a cavity chaperone that physically escorts unfolded OMPs across the periplasm. Proposed replacements: unfolded protein holdase activity Supporting Evidence: PMID:19181847 while bound to Skp, the beta-barrel domain of OmpA is maintained in an unfolded state PMID:19181847 This domain-based chaperoning mechanism allows the transport of beta-barrels across the periplasm in an unfolded state
GO:0051082 unfolded protein binding	IDA PMID:24077225 Conformation and dynamics of the periplasmic membrane-protei...	MODIFY	Summary: IDA annotation from Burmann et al. 2013. High-resolution NMR showed that OMP substrates bound to Skp populate a dynamic conformational ensemble with structural interconversion rates on the submillisecond timescale (PMID:24077225). The dynamic state enables energy-independent substrate release. As with other GO:0051082 annotations, GO:0140309 is more appropriate. Reason: GO:0051082 is now formally obsolete. Skp's function is better described as unfolded protein holdase activity given the escort function across the periplasm. Proposed replacements: unfolded protein holdase activity Supporting Evidence: PMID:24077225 The dynamic state allows for energy-independent substrate release and provides a general paradigm for the conformation of OMP polypeptides bound to energy-independent chaperones
GO:0001530 lipopolysaccharide binding	RCA PMID:15304217 Crystal structure of Skp, a prefoldin-like chaperone that pr...	ACCEPT	Summary: RCA annotation for LPS binding from the crystal structure paper. Walton and Sousa 2004 identified a putative LPS binding site on the outer surface of Skp (residues 97-108) and showed that Skp can interact directly with LPS (PMID:15304217). LPS binding is functionally important because LPS is required together with Skp for efficient OMP folding and membrane insertion (PMID:12509434). The annotation is supported by the structural identification of the binding site and functional studies. Reason: LPS binding is a functionally relevant interaction for Skp's chaperone activity. Structural and functional evidence support this annotation, even though the evidence code is RCA. Supporting Evidence: PMID:15304217 Skp can interact directly with membrane lipids and lipopolysaccharide (LPS). These interactions are needed for efficient Skp-assisted folding of membrane proteins. We have identified a putative LPS binding site on the outer surface of Skp
GO:0030288 outer membrane-bounded periplasmic space	IDA PMID:8730870 A periplasmic protein (Skp) of Escherichia coli selectively ...	ACCEPT	Summary: IDA annotation from Chen and Henning 1996. Skp was identified as a periplasmic protein by subcellular fractionation and affinity chromatography with OmpF-bound sepharose (PMID:8730870). The periplasmic localization is consistent with Skp's role in escorting OMPs across the periplasm. Reason: Core localization annotation. Periplasmic space is where Skp functions as an OMP carrier. Supporting Evidence: PMID:8730870 Proteins of the periplasmic space were fractionated on an affinity column with sepharose-bound outer membrane porin OmpF. A 17 kDa polypeptide was the predominant protein retained by this column
GO:0030288 outer membrane-bounded periplasmic space	IDA PMID:1838129 Skp is a periplasmic Escherichia coli protein requiring SecA...	ACCEPT	Summary: IDA annotation from Thome and Mueller 1991, one of the earliest papers establishing Skp's periplasmic localization. Using subcellular fractionation with precautions to avoid non-specific electrostatic interactions, Skp partitioned with beta-lactamase into the soluble periplasmic fraction (PMID:1838129). Reason: Early definitive evidence for periplasmic localization using careful fractionation methods. Supporting Evidence: PMID:1838129 Upon cellular subfractionation (avoiding non-specific electrostatic interactions) Skp partitions with beta-lactamase into the fraction of soluble, periplasmic proteins
GO:0043165 Gram-negative-bacterium-type cell outer membrane assembly	EXP PMID:11698367 Genetic evidence for parallel pathways of chaperone activity...	ACCEPT	Summary: EXP annotation from Rizzitello et al. 2001. This genetic study demonstrated synthetic lethality between skp and surA mutations, establishing that Skp and SurA function in parallel chaperone pathways for OMP biogenesis (PMID:11698367). Loss of both pathways results in severely reduced envelope protein levels and bacteriostatic/bactericidal effects. Reason: Key genetic evidence establishing Skp's role in outer membrane assembly through a parallel chaperone pathway with SurA. Supporting Evidence: PMID:11698367 null mutations in skp and surA, as well as in degP and surA, result in synthetic phenotypes, suggesting that Skp, SurA, and DegP are functionally redundant PMID:11698367 we propose that Skp and DegP are components of the same pathway and that SurA is a component of a separate pathway
GO:0051082 unfolded protein binding	IPI PMID:10455120 Skp, a molecular chaperone of gram-negative bacteria, is req...	MODIFY	Summary: IPI annotation from Schaefer et al. 1999 (with/from UniProtKB:P0A910 = OmpA). Using crosslinking, they showed Skp interacts with OmpA near the plasma membrane and binds specifically to pOmpA nascent chains after release from ribosomes (PMID:10455120). This demonstrates binding to early unfolded intermediates. However, GO:0140309 better captures the carrier function. Reason: GO:0051082 is now formally obsolete. The interaction represents Skp's carrier function, capturing unfolded OMPs for periplasmic transit. Proposed replacements: unfolded protein holdase activity Supporting Evidence: PMID:10455120 Following its transmembrane translocation, OmpA interacts with Skp in close vicinity to the plasma membrane PMID:10455120 Skp was also found to bind strongly and specifically to pOmpA nascent chains after their release from the ribosome suggesting the ability of Skp to recognize early folding intermediates of outer membrane proteins
GO:0051082 unfolded protein binding	IPI PMID:12509434 Folding and insertion of the outer membrane protein OmpA is ...	MODIFY	Summary: IPI annotation from Bulieris et al. 2003 (with/from UniProtKB:P0A910 = OmpA). Demonstrated direct binding of Skp to unfolded OmpA, forming a soluble complex from which OmpA can fold into lipid bilayers when LPS is present (PMID:12509434). GO:0140309 is more appropriate. Reason: GO:0051082 is now formally obsolete. The Skp-OmpA interaction is part of Skp's carrier function. Proposed replacements: unfolded protein holdase activity Supporting Evidence: PMID:12509434 OmpA remained unfolded when bound to Skp and LPS in solution. From this complex, OmpA folded spontaneously into lipid bilayers
GO:0051604 protein maturation	IDA PMID:9914480 Affinity of the periplasmic chaperone Skp of Escherichia col...	MODIFY	Summary: IDA annotation from de Cock et al. 1999 (annotated by CACAO). This study showed Skp interacts specifically with non-native outer membrane proteins and proposed that Skp is required for efficient targeting of unfolded OMPs to the membrane (PMID:9914480). While Skp contributes to the maturation pathway of OMPs, the term protein maturation (GO:0051604) is overly generic. The more specific process annotation GO:0043165 (Gram-negative-bacterium-type cell outer membrane assembly) captures the same biology more precisely. Reason: Protein maturation is too generic. Replace it with GO:0043165, which precisely captures the OMP assembly pathway supported by this targeting assay. Proposed replacements: Gram-negative-bacterium-type cell outer membrane assembly Supporting Evidence: PMID:9914480 We propose that Skp is required in vivo for the efficient targeting of unfolded outer membrane proteins to the membrane
GO:0006457 protein folding	IMP PMID:10455120 Skp, a molecular chaperone of gram-negative bacteria, is req...	ACCEPT	Summary: IMP annotation from Schaefer et al. 1999. In skp null mutants, there is a specific defect in the release of newly translocated OMPs from the plasma membrane (PMID:10455120). The skp/degP double mutant shows protein aggregate accumulation. This mutant phenotype evidence supports Skp's role in the OMP folding pathway, though Skp itself acts as a holdase/carrier rather than a foldase. Reason: The mutant phenotype supports Skp's participation upstream in the OMP folding process. This biological-process annotation does not imply direct foldase activity; Skp's carrier-holdase mechanism is represented separately. Supporting Evidence: PMID:10455120 Pulse labeling of OmpA in spheroplasts prepared from an skp null mutant revealed a specific requirement of Skp for the release of newly translocated outer membrane proteins from the plasma membrane
GO:0030288 outer membrane-bounded periplasmic space	IDA PMID:10455120 Skp, a molecular chaperone of gram-negative bacteria, is req...	ACCEPT	Summary: IDA annotation for periplasmic localization from Schaefer et al. 1999. Crosslinking experiments showed Skp interacts with OmpA near the plasma membrane in the periplasm (PMID:10455120). Additional evidence for the well-established periplasmic localization. Reason: Additional experimental evidence for periplasmic localization, consistent with other IDA annotations. Supporting Evidence: PMID:10455120 OmpA interacts with Skp in close vicinity to the plasma membrane
GO:0051082 unfolded protein binding	IPI PMID:9914480 Affinity of the periplasmic chaperone Skp of Escherichia col...	MODIFY	Summary: IPI annotation from de Cock et al. 1999 (with/from UniProtKB:P02932 = PhoE, UniProtKB:P02943 = LamB, and UniProtKB:P0A910 = OmpA). Demonstrated specific interaction of Skp with outer membrane proteins in their non-native state (PMID:9914480). Two entries exist for this PMID with different with/from values. GO:0140309 is more appropriate. Reason: GO:0051082 is now formally obsolete. Skp's interaction with non-native OMPs is part of its carrier/escort function. Proposed replacements: unfolded protein holdase activity Supporting Evidence: PMID:9914480 it interacts specifically with outer membrane proteins that are in their non-native state
GO:0001530 lipopolysaccharide binding	IPI PMID:17928002 The trimeric periplasmic chaperone Skp of Escherichia coli f...	ACCEPT	Summary: IPI annotation from Qu et al. 2007 (with/from UniProtKB:P0A910 = OmpA). This study showed that LPS binds to OmpA-Skp complexes at low stoichiometries, and that in the ternary complex, tryptophan residues of OmpA are located closer to the surface than in binary complexes (PMID:17928002). This structural change may explain how LPS facilitates membrane insertion. The IPI evidence here reflects LPS interaction with the Skp-OMP complex, supporting Skp's LPS binding. Reason: LPS binding to Skp-OMP complexes is functionally important for the OMP biogenesis pathway. Well-supported by biophysical evidence. Supporting Evidence: PMID:17928002 Lipopolysaccharide (LPS), a major component of the outer membrane of Gram-negative bacteria, bound to OmpA.Skp(3) complexes at low stoichiometries PMID:17928002 in this ternary complex, the tryptophan residues of the transmembrane domain of OmpA were located closer to the surface than in binary OmpA.Skp(3) complexes
GO:0043165 Gram-negative-bacterium-type cell outer membrane assembly	IDA PMID:12509434 Folding and insertion of the outer membrane protein OmpA is ...	ACCEPT	Summary: IDA annotation from Bulieris et al. 2003. Demonstrated that Skp together with LPS assists the folding and insertion of OmpA into phospholipid bilayers in vitro (PMID:12509434). This reconstitution of the Skp-assisted OMP folding pathway directly supports its role in outer membrane assembly. Reason: In vitro reconstitution of Skp-assisted OMP membrane insertion provides direct evidence for its role in outer membrane assembly. Supporting Evidence: PMID:12509434 unfolded OmpA in complex with Skp and LPS folded faster into phospholipid bilayers than urea-unfolded OmpA
GO:0043165 Gram-negative-bacterium-type cell outer membrane assembly	IGI PMID:17908933 Defining the roles of the periplasmic chaperones SurA, Skp, ...	ACCEPT	Summary: IGI annotation from Sklar et al. 2007 (with/from UniProtKB:P0ABZ6 = SurA). Genetic interaction evidence showing that Skp functions in a parallel pathway with DegP to rescue OMPs that fall off the primary SurA pathway (PMID:17908933). Loss of both the SurA and Skp/DegP pathways is synthetic lethal. Reason: Genetic interaction evidence placing Skp in the OMP biogenesis pathway, parallel to SurA. Supporting Evidence: PMID:17908933 DegP/Skp function to rescue OMPs that fall off the SurA pathway PMID:17908933 SurA is the primary chaperone responsible for the periplasmic transit of the bulk mass of OMPs to the YaeT complex. The role of Skp and DegP is amplified in the absence of SurA
GO:0043165 Gram-negative-bacterium-type cell outer membrane assembly	IPI PMID:17908933 Defining the roles of the periplasmic chaperones SurA, Skp, ...	ACCEPT	Summary: IPI annotation from Sklar et al. 2007 (with/from UniProtKB:P0A940 = BamA/YaeT). This study established the relationship between Skp and the BAM complex (YaeT), showing that SurA and YaeT interact directly in vivo and that Skp functions in a parallel delivery pathway (PMID:17908933). Reason: Outer-membrane assembly is independently established for Skp by multiple experimental annotations, including the IGI row from this paper. The cached abstract explicitly reports direct SurA-YaeT interaction rather than the Skp-BamA pairing, but the curator had access to fuller evidence; retain the supported process annotation while recording that provenance limitation. Supporting Evidence: PMID:17908933 we demonstrate that SurA and YaeT interact directly in vivo PMID:17908933 Evidence presented suggests that DegP/Skp function to rescue OMPs that fall off the SurA pathway
GO:0051082 unfolded protein binding	IPI PMID:11278858 The early interaction of the outer membrane protein phoe wit...	MODIFY	Summary: IPI annotation from Harms et al. 2001 (with/from UniProtKB:P02932 = PhoE). Crosslinking experiments demonstrated that Skp interacts with newly translocated PhoE at the periplasmic side of the inner membrane, even when PhoE is still in a transmembrane orientation in the translocase (PMID:11278858). This demonstrates Skp captures OMPs very early in their biogenesis. GO:0140309 is more appropriate. Reason: GO:0051082 is now formally obsolete. Early capture of OMPs at the translocon is part of Skp's carrier function. Proposed replacements: unfolded protein holdase activity Supporting Evidence: PMID:11278858 Newly translocated PhoE protein could be cross-linked to the periplasmic chaperone Skp at the periplasmic side of the inner membrane PMID:11278858 PhoE closely interacts with the chaperone when the protein is still in a transmembrane orientation in the translocase
GO:0051082 unfolded protein binding	IPI PMID:17928002 The trimeric periplasmic chaperone Skp of Escherichia coli f...	MODIFY	Summary: IPI annotation from Qu et al. 2007 (with/from UniProtKB:P0A910, P0A940, P76045). Comprehensive biophysical study showing Skp trimer forms 1:1 stable complexes with multiple bacterial OMPs (OmpA, OmpG, YaeT, NalP, FomA) with nanomolar dissociation constants (PMID:17928002). Binding is pH-dependent and requires electrostatic interactions. Skp efficiently shielded OmpA tryptophan residues from quenching. GO:0140309 is more appropriate. Reason: GO:0051082 is now formally obsolete. The stable 1:1 complex formation and shielding of OMP transmembrane domains is characteristic of carrier chaperone activity. Proposed replacements: unfolded protein holdase activity Supporting Evidence: PMID:17928002 The Skp trimer formed 1:1 complexes, OMP.Skp(3), with bacterial OMPs, independent of their size or origin. The dissociation constants of these OMP.Skp(3) complexes were all in the nanomolar range, indicating that they are stable PMID:17928002 Skp efficiently shielded tryptophan residues of the transmembrane strands of OmpA against fluorescence quenching by aqueous acrylamide
GO:0005829 cytosol	HDA PMID:16858726 A complexomic study of Escherichia coli using two-dimensiona...	UNDECIDED	Summary: HDA annotation for cytosolic localization from a complexomic study using 2D blue native/SDS-PAGE (PMID:16858726). Mature Skp is well established in the periplasm, but the abstract-only cached record does not show whether this HDA row reflects a pre-export pool, the study's fractionation scheme, or another experiment-specific observation. Reason: Skp's mature functional localization is periplasmic, but the cached complexomics record is abstract-only and does not expose the experiment-specific basis for this HDA row. Defer to the curator rather than inferring a fractionation artifact or pre-export pool from incomplete evidence. Supporting Evidence: PMID:16858726 the cytosolic and membrane protein complexes of Escherichia coli were separated

Gene Description

Existing Annotations Review

Core Functions

Unfolded protein carrier activity -- escorts unfolded outer membrane proteins (OMPs) from the Sec translocon at the inner membrane across the periplasm to the BAM complex for insertion into the outer membrane

Lipopolysaccharide binding -- Skp binds LPS which is required for efficient Skp-assisted folding and insertion of OMPs into membranes

References

Deep Research

Falcon

📚 Additional Documentation

Notes

Bioreason Rl Predictions

Bioreason Rl Review

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