FtsI (PBP3) is the inner-membrane-anchored class-B penicillin-binding protein that cross-links septal peptidoglycan in Escherichia coli. Its catalytic domain faces the periplasm and forms D,D peptide cross-links while its partner FtsW polymerizes glycan strands. This coordinated synthesis builds the division septum and shapes new cell poles. Beta-lactam antibiotics acylate its active site and inhibit division. Purified anchor-free FtsI also hydrolyzes synthetic thioesters and transfers their acyl groups to amino acceptors; these model-substrate reactions are distinct from its physiological septal cross-linking role.
Definition: Catalysis of peptide crosslink formation in peptidoglycan by a serine-dependent D,D-transpeptidase: transfer of the donor D-Ala4 acyl group from a pentapeptide stem to an amino acceptor on another stem or its peptide bridge, with release of terminal D-Ala5. This forms a D,D (4-to-3) crosslink rather than an L,D (3-to-3) crosslink; the acceptor amino group and bridge depend on the organism.
Justification: The current GO search contains peptidoglycan L,D-transpeptidase activity but no exact D,D-transpeptidase term. GO:0009002 specifies net hydrolysis with water, not merely the first half of a cross-linking reaction. A peptide amino acceptor instead resolves the FtsI acyl-enzyme to form a D,D cross-link. The synthetic-thioester assays support transfer chemistry, while cellular septal peptidoglycan analysis supports the physiological role; these evidence levels are distinguished. Round-1 QuickGO search found no exact D,D-specific peptidoglycan transpeptidase term; GO:0016755 is the verified aminoacyl-transfer parent. The shared definition does not standardize the organism-specific acceptor chemistry or upgrade inferential linkage evidence.
Parent term: aminoacyltransferase activity
Supporting Evidence:
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005886 plasma membrane | IBA GO_REF:0000033 | ACCEPT | Summary: FtsI is anchored in the inner membrane with its catalytic region exposed to the periplasm. Reason: Beta-lactamase fusions and side-specific proteolysis in PMID:2677607 establish the N-terminal membrane anchor and periplasmic topology. This independent target evidence supports both the inferred and literature-synthesis rows; paint-losses found no IRD/IKR on the target lineage. Supporting Evidence: PMID:2677607 PBP3 therefore appeared to have a simple membrane topology with residues 36 to the carboxy-terminus exposed on the periplasmic side of the cytoplasmic membrane. |
| GO:0008658 penicillin binding | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Beta-lactams bind and acylate the FtsI/PBP3 active site. Reason: The penicillin-binding claim is experimentally supported, including preferential binding of division-inhibiting beta-lactams in PMID:1103132 and the acylation kinetics of the soluble PBP3 construct in PMID:9324244. Retain this specific antibiotic-target property outside the physiological core, which is septal peptide cross-linking. This is not antibiotic resistance or drug detoxification. Supporting Evidence: PMID:1103132 beta-Lactams that specifically inhibit cell division bind preferentially to penicillin binding protein 3 (molecular weight 60,000) |
| GO:0071555 cell wall organization | IBA GO_REF:0000033 | ACCEPT | Summary: FtsI organizes the septal cell wall by forming peptide cross-links. Reason: The transpeptidase directly organizes the peptidoglycan network at the growing septum; this is supported by cellular cross-link analysis, not merely a requirement for viability. Retain the organizational process alongside biosynthesis: current ontology ancestry does not make peptidoglycan biosynthesis a descendant of GO:0071555, so substituting that term would not be a specificity refinement. Supporting Evidence: PMID:3531167 The peptidoglycan transpeptidase activity of penicillin-binding protein 3 appears to use either nascent or exogenously added UDP-N-acetylmuramyl tripeptide-derived substrates as acceptors. |
| GO:0000917 division septum assembly | IEA GO_REF:0000043 | ACCEPT | Summary: FtsI cross-links the peptidoglycan framework of the division septum. Reason: FtsI performs the cross-linking work within the septal synthase pair. Cellular peptidoglycan analysis supports cross-link formation, and target localization places it at the developing septum. These independent lines support the septum-assembly claim beyond the divisome review cited by the original NAS row. Supporting Evidence: PMID:3531167 The peptidoglycan transpeptidase activity of penicillin-binding protein 3 appears to use either nascent or exogenously added UDP-N-acetylmuramyl tripeptide-derived substrates as acceptors. PMID:9603865 The localization of FtsI was not observed in ftsZ or ftsA mutants, indicating that it was dependent on the prior localization of these proteins. |
| GO:0004180 carboxypeptidase activity | IEA GO_REF:0000043 | MODIFY | Summary: FtsI performs D,D-transpeptidation; the hydrolytic peptidase mapping does not express that net reaction. Reason: This is a reaction-class correction, not an is_a refinement. GO:0009002 specifies water-dependent hydrolysis of an acetylated Lys-D-Ala-D-Ala substrate; carboxypeptidase and peptidase parents also require hydrolysis. The retrieved full PMID:9324244 postprint reports no detectable activity of anchor-free G57-V577 PBP3 on that peptide, but demonstrates synthetic-thioester hydrolysis and aminolysis. The latter does not prove peptide-bond hydrolysis. Cellular cross-linking evidence supports D,D acyl transfer to an amino acceptor (PMID:3531167). Replace the historical EC-derived hydrolytic proxy with the existing proposed D,D-transpeptidase term, without claiming a universal absence of all hydrolytic side reactions or treating the truncated assay as intact native FtsI. Proposed replacements: serine-type peptidoglycan D,D-transpeptidase activity Supporting Evidence: file:ECOLI/ftsI/ftsI-source-analysis/catalytic-specificity.md PBP3p has no detectable activity on the tripeptide (acetyl)2-L-lysyl-D-alanyl-D-alanine PMID:3531167 The peptidoglycan transpeptidase activity of penicillin-binding protein 3 appears to use either nascent or exogenously added UDP-N-acetylmuramyl tripeptide-derived substrates as acceptors. |
| GO:0005886 plasma membrane | IEA GO_REF:0000120 | ACCEPT | Summary: FtsI is anchored in the inner membrane with its catalytic region exposed to the periplasm. Reason: Beta-lactamase fusions and side-specific proteolysis in PMID:2677607 establish the N-terminal membrane anchor and periplasmic topology. This independent target evidence supports both the inferred and literature-synthesis rows; paint-losses found no IRD/IKR on the target lineage. Supporting Evidence: PMID:2677607 PBP3 therefore appeared to have a simple membrane topology with residues 36 to the carboxy-terminus exposed on the periplasmic side of the cytoplasmic membrane. |
| GO:0006508 proteolysis | IEA GO_REF:0000043 | REMOVE | Summary: Septal peptide cross-linking is not protein degradation. Reason: GO:0006508 denotes hydrolysis of proteins into smaller polypeptides or amino acids. FtsI transfers a peptidyl acyl group between peptidoglycan stems to build cross-links; transient donor-bond cleavage during that transfer does not establish proteolysis. The electronic keyword mapping conflates an acyl-transfer mechanism with protein hydrolysis. Synthetic-thioester hydrolysis likewise does not supply evidence of proteolysis. Supporting Evidence: PMID:3531167 The peptidoglycan transpeptidase activity of penicillin-binding protein 3 appears to use either nascent or exogenously added UDP-N-acetylmuramyl tripeptide-derived substrates as acceptors. file:ECOLI/ftsI/ftsI-source-analysis/catalytic-specificity.md PBP3p has no detectable activity on the tripeptide (acetyl)2-L-lysyl-D-alanyl-D-alanine |
| GO:0008233 peptidase activity | IEA GO_REF:0000043 | MODIFY | Summary: FtsI performs D,D-transpeptidation; the hydrolytic peptidase mapping does not express that net reaction. Reason: This is a reaction-class correction, not an is_a refinement. GO:0009002 specifies water-dependent hydrolysis of an acetylated Lys-D-Ala-D-Ala substrate; carboxypeptidase and peptidase parents also require hydrolysis. The retrieved full PMID:9324244 postprint reports no detectable activity of anchor-free G57-V577 PBP3 on that peptide, but demonstrates synthetic-thioester hydrolysis and aminolysis. The latter does not prove peptide-bond hydrolysis. Cellular cross-linking evidence supports D,D acyl transfer to an amino acceptor (PMID:3531167). Replace the historical EC-derived hydrolytic proxy with the existing proposed D,D-transpeptidase term, without claiming a universal absence of all hydrolytic side reactions or treating the truncated assay as intact native FtsI. Proposed replacements: serine-type peptidoglycan D,D-transpeptidase activity Supporting Evidence: file:ECOLI/ftsI/ftsI-source-analysis/catalytic-specificity.md PBP3p has no detectable activity on the tripeptide (acetyl)2-L-lysyl-D-alanyl-D-alanine PMID:3531167 The peptidoglycan transpeptidase activity of penicillin-binding protein 3 appears to use either nascent or exogenously added UDP-N-acetylmuramyl tripeptide-derived substrates as acceptors. |
| GO:0008360 regulation of cell shape | IEA GO_REF:0000043 | ACCEPT | Summary: FtsI septal synthesis contributes directly to the shape of new poles. Reason: The GO definition is modulation of cell surface configuration, not exclusively rod-shape maintenance during elongation. PMID:3049550 connects an FtsI substitution and partial PBP3 inhibition to pointed polar caps and altered local surface synthesis. Combined with its direct septal cross-linking function, this supports morphogenesis; the earlier argument that only PBP2 controls any cell shape was too restrictive. Supporting Evidence: PMID:3049550 Partial inactivation of PBP3 by subinhibitory concentrations of cephalexin, furazlocillin, and piperacillin resulted in the formation of slightly pointed polar caps, suggesting that the shape of the polar caps is correlated with PBP3 activity. PMID:3531167 The peptidoglycan transpeptidase activity of penicillin-binding protein 3 appears to use either nascent or exogenously added UDP-N-acetylmuramyl tripeptide-derived substrates as acceptors. |
| GO:0008658 penicillin binding | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Beta-lactams bind and acylate the FtsI/PBP3 active site. Reason: The penicillin-binding claim is experimentally supported, including preferential binding of division-inhibiting beta-lactams in PMID:1103132 and the acylation kinetics of the soluble PBP3 construct in PMID:9324244. Retain this specific antibiotic-target property outside the physiological core, which is septal peptide cross-linking. This is not antibiotic resistance or drug detoxification. |
| GO:0008955 peptidoglycan glycosyltransferase activity | IEA GO_REF:0000002 | REMOVE | Summary: FtsI is the peptide-cross-linking component of the FtsWI pair, not its glycan polymerase. Reason: The 1981 PMID:7030331 paper historically assigned both activities; its full text could not be obtained here, so no contaminant or misidentified gene is alleged. The independently retrieved primary PMID:9324244 tested radiolabeled lipid II in two protocols with active PBP1b controls and detected no polymerization by folded anchor-free PBP3; the construct limitation is explicit. The followup synthesis PMID:9614966, the distinct class-B domain architecture, the curated UniProt caution and the later assignment of polymerization to FtsW converge against intrinsic FtsI glycosyltransferase activity. PMID:6450748 measured septal murein incorporation after PBP3 inhibition, which does not distinguish glycan polymerization from cross-linking. FtsI-dependent activation or coordination of a partner polymerase is not possession of that partner's catalytic activity. This rejects the common function claim consistently across IEA, IMP and IDA rather than rejecting an assay merely because it is old. Supporting Evidence: PMID:9614966 It has no detectable transglycosylase activity with lipid II as substrate. PMID:3531167 The peptidoglycan transpeptidase activity of penicillin-binding protein 3 appears to use either nascent or exogenously added UDP-N-acetylmuramyl tripeptide-derived substrates as acceptors. file:ECOLI/ftsI/ftsI-source-analysis/catalytic-specificity.md |
| GO:0009002 serine-type D-Ala-D-Ala carboxypeptidase activity | IEA GO_REF:0000120 | MODIFY | Summary: FtsI performs D,D-transpeptidation; the hydrolytic peptidase mapping does not express that net reaction. Reason: This is a reaction-class correction, not an is_a refinement. GO:0009002 specifies water-dependent hydrolysis of an acetylated Lys-D-Ala-D-Ala substrate; carboxypeptidase and peptidase parents also require hydrolysis. The retrieved full PMID:9324244 postprint reports no detectable activity of anchor-free G57-V577 PBP3 on that peptide, but demonstrates synthetic-thioester hydrolysis and aminolysis. The latter does not prove peptide-bond hydrolysis. Cellular cross-linking evidence supports D,D acyl transfer to an amino acceptor (PMID:3531167). Replace the historical EC-derived hydrolytic proxy with the existing proposed D,D-transpeptidase term, without claiming a universal absence of all hydrolytic side reactions or treating the truncated assay as intact native FtsI. Proposed replacements: serine-type peptidoglycan D,D-transpeptidase activity Supporting Evidence: file:ECOLI/ftsI/ftsI-source-analysis/catalytic-specificity.md PBP3p has no detectable activity on the tripeptide (acetyl)2-L-lysyl-D-alanyl-D-alanine PMID:3531167 The peptidoglycan transpeptidase activity of penicillin-binding protein 3 appears to use either nascent or exogenously added UDP-N-acetylmuramyl tripeptide-derived substrates as acceptors. |
| GO:0009252 peptidoglycan biosynthetic process | IEA GO_REF:0000120 | ACCEPT | Summary: FtsI makes peptide cross-links during peptidoglycan biosynthesis. Reason: Cellular and ether-permeabilized-cell experiments in PMID:3531167 assign a peptide-cross-linking contribution to PBP3. PMID:6450748 independently restricts its major synthetic role to septation. The original SEDS-polymerase reference PMID:27525505 is contextual evidence for the partner system, not proof that FtsI polymerizes glycans. Direct cross-link formation suffices for participation in this biosynthetic process. Supporting Evidence: PMID:3531167 The peptidoglycan transpeptidase activity of penicillin-binding protein 3 appears to use either nascent or exogenously added UDP-N-acetylmuramyl tripeptide-derived substrates as acceptors. |
| GO:0016787 hydrolase activity | IEA GO_REF:0000043 | MODIFY | Summary: Purified anchor-free FtsI hydrolyzes synthetic thioesters. Reason: Hydrolase activity has independent biochemical support in PMID:9324244, but GO:0016790 thiolester hydrolase activity is its verified descendant and describes the assayed bond. Refine to that term. The model-substrate capacity remains outside core_functions; it does not establish hydrolysis of peptidoglycan peptide bonds or a native thioester-metabolic role. Proposed replacements: thiolester hydrolase activity Supporting Evidence: PMID:9324244 The truncated PBP3 functions as a thiolesterase. |
| GO:0043093 FtsZ-dependent cytokinesis | IEA GO_REF:0000104 | ACCEPT | Summary: FtsI supplies septal peptide cross-linking in the FtsZ-organized cytokinetic machinery. Reason: The target participates catalytically in septum synthesis and is recruited after FtsZ/FtsA. The combination of actual wall-building activity and FtsZ-dependent organization supports this process, rather than inferring participation from localization dependence alone. Supporting Evidence: PMID:3531167 The peptidoglycan transpeptidase activity of penicillin-binding protein 3 appears to use either nascent or exogenously added UDP-N-acetylmuramyl tripeptide-derived substrates as acceptors. PMID:9603865 The localization of FtsI was not observed in ftsZ or ftsA mutants, indicating that it was dependent on the prior localization of these proteins. |
| GO:0051301 cell division | IEA GO_REF:0000120 | MODIFY | Summary: FtsI cross-links septal peptidoglycan during FtsZ-dependent cytokinesis. Reason: GO:0043093 is a verified descendant of cell division, already present in this review. FtsI performs the septal cross-linking work, and its localization depends on prior FtsZ/FtsA assembly (PMID:9603865). Use the more specific supported division process consistently across the three original rows. Proposed replacements: FtsZ-dependent cytokinesis Supporting Evidence: PMID:3531167 The peptidoglycan transpeptidase activity of penicillin-binding protein 3 appears to use either nascent or exogenously added UDP-N-acetylmuramyl tripeptide-derived substrates as acceptors. PMID:9603865 The localization of FtsI (PBP3), a penicillin-binding protein specifically required for cell division in Escherichia coli, was investigated by immunofluorescence microscopy and found to localize to the septum. |
| GO:0071555 cell wall organization | IEA GO_REF:0000043 | ACCEPT | Summary: FtsI organizes the septal cell wall by forming peptide cross-links. Reason: The transpeptidase directly organizes the peptidoglycan network at the growing septum; this is supported by cellular cross-link analysis, not merely a requirement for viability. Retain the organizational process alongside biosynthesis: current ontology ancestry does not make peptidoglycan biosynthesis a descendant of GO:0071555, so substituting that term would not be a specificity refinement. Supporting Evidence: PMID:3531167 The peptidoglycan transpeptidase activity of penicillin-binding protein 3 appears to use either nascent or exogenously added UDP-N-acetylmuramyl tripeptide-derived substrates as acceptors. |
| GO:0005515 protein binding | IPI PMID:15774864 Interaction network among Escherichia coli membrane proteins... | REMOVE | Summary: FtsI interacts with FtsQ (P06136) as shown by bacterial two-hybrid analysis [PMID:15774864]. FtsQ is an essential divisome protein. Reason: The FtsQ interaction is well-documented, but GO:0005515 is a generic binding parent that does not describe FtsI's D,D-transpeptidase activity or its role in septal peptidoglycan synthesis. No more specific molecular-function term is supported by this interaction evidence alone. |
| GO:0005515 protein binding | IPI PMID:15774864 Interaction network among Escherichia coli membrane proteins... | REMOVE | Summary: FtsI interacts with FtsW (P0ABG4) as shown by bacterial two-hybrid analysis [PMID:15774864]. FtsW-FtsI form a core subcomplex of the divisome. Reason: The FtsI-FtsW contact is central to septal peptidoglycan synthesis, but the bare GO:0005515 term is not an informative molecular-function annotation. The interaction evidence supports the divisome and peptidoglycan-synthesis process rows rather than a standalone binding function for FtsI. Supporting Evidence: PMID:20847002 The integral membrane FtsW protein and peptidoglycan synthase PBP3 form a subcomplex in Escherichia coli |
| GO:0005515 protein binding | IPI PMID:15774864 Interaction network among Escherichia coli membrane proteins... | REMOVE | Summary: FtsI interacts with FtsL (P0AEN4) per bacterial two-hybrid [PMID:15774864]. Reason: This row captures a real divisome contact, but GO:0005515 is too generic to represent a function of FtsI. The evidence does not by itself justify a more specific molecular-function replacement. |
| GO:0005515 protein binding | IPI PMID:15774864 Interaction network among Escherichia coli membrane proteins... | REMOVE | Summary: FtsI interacts with FtsN (P29131) per bacterial two-hybrid [PMID:15774864]. FtsI is required for FtsN localization to the septum. Reason: FtsI-FtsN binding is functionally relevant to divisome assembly, but GO:0005515 itself is uninformative and should not be kept as the functional annotation; the cell-division and septal-localization rows capture the supported biology more precisely. Supporting Evidence: PMID:9282742 FtsN, a late recruit to the septum in Escherichia coli |
| GO:0005515 protein binding | IPI PMID:15774864 Interaction network among Escherichia coli membrane proteins... | UNDECIDED | Summary: The source supports an interaction study, but this precise original target-partner claim has not been resolved from the accessible material. Reason: The available evidence does not justify the earlier partner-specific summary with confidence. The source is retained without asserting wrong-gene attribution. Independent FtsI interactions are well established, but they do not verify the particular edge underlying this row. The standing bare-binding policy would remove an adjudicated generic interaction as uninformative; the access/source-level uncertainty here instead warrants UNDECIDED, not an invented functional replacement. |
| GO:0005515 protein binding | IPI PMID:17185541 Three functional subdomains of the Escherichia coli FtsQ pro... | REMOVE | Summary: FtsI interacts with FtsQ (P06136). Study mapped the FtsQ domains involved in interactions with divisome proteins [PMID:17185541]. Reason: This domain-mapping study supports an FtsI-FtsQ contact, but GO:0005515 is an uninformative molecular-function parent and has no more specific evidence-backed replacement here. Supporting Evidence: PMID:17185541 FtsQ, an essential protein for the Escherichia coli divisome assembly, is able to interact with various division proteins, namely FtsI, FtsL, FtsN, FtsB and FtsW |
| GO:0005515 protein binding | IPI PMID:17185541 Three functional subdomains of the Escherichia coli FtsQ pro... | UNDECIDED | Summary: The source supports an interaction study, but this precise original target-partner claim has not been resolved from the accessible material. Reason: The available evidence does not justify the earlier partner-specific summary with confidence. The source is retained without asserting wrong-gene attribution. Independent FtsI interactions are well established, but they do not verify the particular edge underlying this row. The standing bare-binding policy would remove an adjudicated generic interaction as uninformative; the access/source-level uncertainty here instead warrants UNDECIDED, not an invented functional replacement. |
| GO:0005515 protein binding | IPI PMID:17938168 The essential cell division protein FtsN interacts with the ... | REMOVE | Summary: FtsI interacts with FtsN per [PMID:17938168]. The study examined FtsN interactions with peptidoglycan synthases. Reason: The row records another FtsI-FtsN interaction assay, but the generic GO:0005515 term adds no functional information and the cited evidence does not support a narrower molecular-function term. Supporting Evidence: PMID:17938168 PBP3 had an affinity to immobilized FtsN |
| GO:0005515 protein binding | IPI PMID:18165305 The monofunctional glycosyltransferase of Escherichia coli l... | UNDECIDED | Summary: The source supports an interaction study, but this precise original target-partner claim has not been resolved from the accessible material. Reason: The available evidence does not justify the earlier partner-specific summary with confidence. The source is retained without asserting wrong-gene attribution. Independent FtsI interactions are well established, but they do not verify the particular edge underlying this row. The standing bare-binding policy would remove an adjudicated generic interaction as uninformative; the access/source-level uncertainty here instead warrants UNDECIDED, not an invented functional replacement. |
| GO:0005515 protein binding | IPI PMID:18165305 The monofunctional glycosyltransferase of Escherichia coli l... | REMOVE | Summary: FtsI interacts with MtgA (P46022), the monofunctional glycosyltransferase [PMID:18165305]. Reason: MtgA association is a divisome contact and possible septal peptidoglycan-synthesis link, but GO:0005515 is too generic to retain as a function of FtsI and the interaction evidence supports no specific replacement term. Supporting Evidence: PMID:18165305 is able to interact with three constituents of the divisome, PBP3, FtsW, and FtsN |
| GO:0005515 protein binding | IPI PMID:18978050 Characterization of YmgF, a 72-residue inner membrane protei... | REMOVE | Summary: FtsI interacts with FtsL. Study characterized YmgF and its association with the division machinery [PMID:18978050]. Reason: This is additional evidence for a divisome interaction, but the bare protein-binding term is not functionally informative for FtsI. Supporting Evidence: PMID:18978050 Four clones were found to harbor the same DNA fragment, encoding aa 19 to 61 of the E. coli cell division protein FtsI, fused in frame to T18. |
| GO:0005515 protein binding | IPI PMID:18978050 Characterization of YmgF, a 72-residue inner membrane protei... | REMOVE | Summary: FtsI interacts with YmgF [PMID:18978050]. Reason: YmgF's association with the cell-division machinery does not make GO:0005515 an informative annotation for FtsI, and no narrower molecular-function term is supported. Supporting Evidence: PMID:18978050 YmgF was able to efficiently interact in vivo with two other E. coli cell division proteins, FtsI and FtsQ |
| GO:0005515 protein binding | IPI PMID:19458048 Crystal structure of the membrane-bound bifunctional transgl... | UNDECIDED | Summary: The source supports an interaction study, but this precise original target-partner claim has not been resolved from the accessible material. Reason: The available evidence does not justify the earlier partner-specific summary with confidence. The source is retained without asserting wrong-gene attribution. Independent FtsI interactions are well established, but they do not verify the particular edge underlying this row. The standing bare-binding policy would remove an adjudicated generic interaction as uninformative; the access/source-level uncertainty here instead warrants UNDECIDED, not an invented functional replacement. |
| GO:0005515 protein binding | IPI PMID:20847002 The integral membrane FtsW protein and peptidoglycan synthas... | REMOVE | Summary: FtsI forms a subcomplex with FtsW. FRET and co-immunoprecipitation experiments confirmed direct interactions [PMID:20847002]. Reason: The FtsI-FtsW subcomplex is core to the divisome, but GO:0005515 collapses that biology to a non-specific binding parent. Keep the process and complex context, not a generic binding function. Supporting Evidence: PMID:20847002 In this work we show direct interactions between FtsW and PBP3 in vivo and in vitro by FRET (FΓΆrster resonance energy transfer) and co-immunoprecipitation experiments |
| GO:0005515 protein binding | IPI PMID:22885295 The Ξ²-lactam resistance protein Blr, a small membrane polype... | UNDECIDED | Summary: The source supports an interaction study, but this precise original target-partner claim has not been resolved from the accessible material. Reason: The available evidence does not justify the earlier partner-specific summary with confidence. The source is retained without asserting wrong-gene attribution. Independent FtsI interactions are well established, but they do not verify the particular edge underlying this row. The standing bare-binding policy would remove an adjudicated generic interaction as uninformative; the access/source-level uncertainty here instead warrants UNDECIDED, not an invented functional replacement. |
| GO:0005515 protein binding | IPI PMID:24561554 The binary protein-protein interaction landscape of Escheric... | UNDECIDED | Summary: The source supports an interaction study, but this precise original target-partner claim has not been resolved from the accessible material. Reason: The available evidence does not justify the earlier partner-specific summary with confidence. The source is retained without asserting wrong-gene attribution. Independent FtsI interactions are well established, but they do not verify the particular edge underlying this row. The standing bare-binding policy would remove an adjudicated generic interaction as uninformative; the access/source-level uncertainty here instead warrants UNDECIDED, not an invented functional replacement. |
| GO:0000917 division septum assembly | NAS PMID:28419603 Assembly and activation of the Escherichia coli divisome. | ACCEPT | Summary: FtsI cross-links the peptidoglycan framework of the division septum. Reason: FtsI performs the cross-linking work within the septal synthase pair. Cellular peptidoglycan analysis supports cross-link formation, and target localization places it at the developing septum. These independent lines support the septum-assembly claim beyond the divisome review cited by the original NAS row. Supporting Evidence: PMID:3531167 The peptidoglycan transpeptidase activity of penicillin-binding protein 3 appears to use either nascent or exogenously added UDP-N-acetylmuramyl tripeptide-derived substrates as acceptors. PMID:9603865 The localization of FtsI was not observed in ftsZ or ftsA mutants, indicating that it was dependent on the prior localization of these proteins. |
| GO:0005886 plasma membrane | NAS PMID:28419603 Assembly and activation of the Escherichia coli divisome. | ACCEPT | Summary: FtsI is anchored in the inner membrane with its catalytic region exposed to the periplasm. Reason: Beta-lactamase fusions and side-specific proteolysis in PMID:2677607 establish the N-terminal membrane anchor and periplasmic topology. This independent target evidence supports both the inferred and literature-synthesis rows; paint-losses found no IRD/IKR on the target lineage. Supporting Evidence: PMID:2677607 PBP3 therefore appeared to have a simple membrane topology with residues 36 to the carboxy-terminus exposed on the periplasmic side of the cytoplasmic membrane. |
| GO:0032153 cell division site | NAS PMID:28419603 Assembly and activation of the Escherichia coli divisome. | ACCEPT | Summary: FtsI localizes to the cell division site (septum) during cell division. Reason: Appropriate cellular component annotation supported by experimental evidence [PMID:9603865]. Supporting Evidence: PMID:9603865 The localization of FtsI (PBP3), a penicillin-binding protein specifically required for cell division in Escherichia coli, was investigated by immunofluorescence microscopy and found to localize to the septum. |
| GO:0043093 FtsZ-dependent cytokinesis | NAS PMID:28419603 Assembly and activation of the Escherichia coli divisome. | ACCEPT | Summary: FtsI supplies septal peptide cross-linking in the FtsZ-organized cytokinetic machinery. Reason: The target participates catalytically in septum synthesis and is recruited after FtsZ/FtsA. The combination of actual wall-building activity and FtsZ-dependent organization supports this process, rather than inferring participation from localization dependence alone. Supporting Evidence: PMID:3531167 The peptidoglycan transpeptidase activity of penicillin-binding protein 3 appears to use either nascent or exogenously added UDP-N-acetylmuramyl tripeptide-derived substrates as acceptors. PMID:9603865 The localization of FtsI was not observed in ftsZ or ftsA mutants, indicating that it was dependent on the prior localization of these proteins. |
| GO:0051301 cell division | NAS PMID:28419603 Assembly and activation of the Escherichia coli divisome. | MODIFY | Summary: FtsI cross-links septal peptidoglycan during FtsZ-dependent cytokinesis. Reason: GO:0043093 is a verified descendant of cell division, already present in this review. FtsI performs the septal cross-linking work, and its localization depends on prior FtsZ/FtsA assembly (PMID:9603865). Use the more specific supported division process consistently across the three original rows. Proposed replacements: FtsZ-dependent cytokinesis Supporting Evidence: PMID:3531167 The peptidoglycan transpeptidase activity of penicillin-binding protein 3 appears to use either nascent or exogenously added UDP-N-acetylmuramyl tripeptide-derived substrates as acceptors. PMID:9603865 The localization of FtsI (PBP3), a penicillin-binding protein specifically required for cell division in Escherichia coli, was investigated by immunofluorescence microscopy and found to localize to the septum. |
| GO:0005515 protein binding | IPI PMID:33895137 ZapG (YhcB/DUF1043), a novel cell division protein in gamma-... | REMOVE | Summary: FtsI interacts with ZapG (YhcB, P0ADW3). ZapG is a novel cell division protein linking the Z-ring to septal peptidoglycan synthesis [PMID:33895137]. Reason: The ZapG contact helps place ZapG near the divisome, but the FtsI row's term is still the generic GO:0005515 parent and has no specific molecular-function replacement. Supporting Evidence: PMID:33895137 ZapG (YhcB/DUF1043), a novel cell division protein in gamma-proteobacteria linking the Z-ring to septal peptidoglycan synthesis |
| GO:0005515 protein binding | IPI PMID:28233869 Interplay between Penicillin-binding proteins and SEDS prote... | REMOVE | Summary: FtsI (PBP3) interacts with FtsW as part of a ternary complex with PBP1b [PMID:28233869]. The study characterized the interplay between these proteins in peptidoglycan synthesis. Reason: This supports the divisome peptidoglycan-synthesis machinery, but a ternary-complex interaction should not be collapsed into a generic protein-binding molecular function for FtsI. Supporting Evidence: PMID:28233869 PBP3 forms a complex with FtsW and its specific transpeptidase activity is essential for cell division |
| GO:0009252 peptidoglycan biosynthetic process | RCA PMID:27525505 SEDS proteins are a widespread family of bacterial cell wall... | ACCEPT | Summary: FtsI makes peptide cross-links during peptidoglycan biosynthesis. Reason: Cellular and ether-permeabilized-cell experiments in PMID:3531167 assign a peptide-cross-linking contribution to PBP3. PMID:6450748 independently restricts its major synthetic role to septation. The original SEDS-polymerase reference PMID:27525505 is contextual evidence for the partner system, not proof that FtsI polymerizes glycans. Direct cross-link formation suffices for participation in this biosynthetic process. Supporting Evidence: PMID:3531167 The peptidoglycan transpeptidase activity of penicillin-binding protein 3 appears to use either nascent or exogenously added UDP-N-acetylmuramyl tripeptide-derived substrates as acceptors. |
| GO:0008955 peptidoglycan glycosyltransferase activity | IMP PMID:6450748 Evidence for involvement of penicillin-binding protein 3 in ... | REMOVE | Summary: FtsI is the peptide-cross-linking component of the FtsWI pair, not its glycan polymerase. Reason: The 1981 PMID:7030331 paper historically assigned both activities; its full text could not be obtained here, so no contaminant or misidentified gene is alleged. The independently retrieved primary PMID:9324244 tested radiolabeled lipid II in two protocols with active PBP1b controls and detected no polymerization by folded anchor-free PBP3; the construct limitation is explicit. The followup synthesis PMID:9614966, the distinct class-B domain architecture, the curated UniProt caution and the later assignment of polymerization to FtsW converge against intrinsic FtsI glycosyltransferase activity. PMID:6450748 measured septal murein incorporation after PBP3 inhibition, which does not distinguish glycan polymerization from cross-linking. FtsI-dependent activation or coordination of a partner polymerase is not possession of that partner's catalytic activity. This rejects the common function claim consistently across IEA, IMP and IDA rather than rejecting an assay merely because it is old. Supporting Evidence: PMID:9614966 It has no detectable transglycosylase activity with lipid II as substrate. PMID:3531167 The peptidoglycan transpeptidase activity of penicillin-binding protein 3 appears to use either nascent or exogenously added UDP-N-acetylmuramyl tripeptide-derived substrates as acceptors. file:ECOLI/ftsI/ftsI-source-analysis/catalytic-specificity.md |
| GO:0005515 protein binding | IPI PMID:20497333 Direct interactions of early and late assembling division pr... | REMOVE | Summary: FtsI interacts with FtsN. FRET study on divisome protein interactions [PMID:20497333]. Reason: This FRET evidence supports physical proximity between FtsI and FtsN in the divisome, but GO:0005515 is not informative enough to keep as a molecular-function annotation. Supporting Evidence: PMID:20497333 we find FtsN, one of the latest proteins in the divisome assembly, interacting with late assembling proteins FtsI and FtsW |
| GO:0032153 cell division site | IDA PMID:9603865 FtsI and FtsW are localized to the septum in Escherichia col... | ACCEPT | Summary: FtsI was shown to localize to the septum by immunofluorescence microscopy [PMID:9603865]. Reason: Core cellular component annotation. Direct experimental evidence (IDA) from immunofluorescence microscopy. Supporting Evidence: PMID:9603865 The localization of FtsI (PBP3), a penicillin-binding protein specifically required for cell division in Escherichia coli, was investigated by immunofluorescence microscopy and found to localize to the septum |
| GO:0008658 penicillin binding | IDA PMID:1103132 Distinct penicillin binding proteins involved in the divisio... | KEEP AS NON CORE | Summary: Beta-lactams bind and acylate the FtsI/PBP3 active site. Reason: The penicillin-binding claim is experimentally supported, including preferential binding of division-inhibiting beta-lactams in PMID:1103132 and the acylation kinetics of the soluble PBP3 construct in PMID:9324244. Retain this specific antibiotic-target property outside the physiological core, which is septal peptide cross-linking. This is not antibiotic resistance or drug detoxification. Supporting Evidence: PMID:1103132 Cell division: beta-Lactams that specifically inhibit cell division bind preferentially to penicillin binding protein 3 (molecular weight 60,000) |
| GO:0009410 response to xenobiotic stimulus | IMP PMID:1103132 Distinct penicillin binding proteins involved in the divisio... | KEEP AS NON CORE | Summary: FtsI binds beta-lactam antibiotics (xenobiotics), which inhibit its activity and cause cell filamentation [PMID:1103132]. Reason: While accurate that FtsI responds to beta-lactam antibiotics (xenobiotics), this is not a physiological function but rather a pharmacological property. The response is inhibition of division. Keep as non-core annotation. Supporting Evidence: PMID:1103132 beta-Lactams that specifically inhibit cell division bind preferentially to penicillin binding protein 3 |
| GO:0051301 cell division | IMP PMID:1103132 Distinct penicillin binding proteins involved in the divisio... | MODIFY | Summary: FtsI cross-links septal peptidoglycan during FtsZ-dependent cytokinesis. Reason: GO:0043093 is a verified descendant of cell division, already present in this review. FtsI performs the septal cross-linking work, and its localization depends on prior FtsZ/FtsA assembly (PMID:9603865). Use the more specific supported division process consistently across the three original rows. Proposed replacements: FtsZ-dependent cytokinesis Supporting Evidence: PMID:3531167 The peptidoglycan transpeptidase activity of penicillin-binding protein 3 appears to use either nascent or exogenously added UDP-N-acetylmuramyl tripeptide-derived substrates as acceptors. PMID:9603865 The localization of FtsI (PBP3), a penicillin-binding protein specifically required for cell division in Escherichia coli, was investigated by immunofluorescence microscopy and found to localize to the septum. |
| GO:0008955 peptidoglycan glycosyltransferase activity | IDA PMID:7030331 Peptidoglycan synthetic enzyme activities of highly purified... | REMOVE | Summary: FtsI is the peptide-cross-linking component of the FtsWI pair, not its glycan polymerase. Reason: The 1981 PMID:7030331 paper historically assigned both activities; its full text could not be obtained here, so no contaminant or misidentified gene is alleged. The independently retrieved primary PMID:9324244 tested radiolabeled lipid II in two protocols with active PBP1b controls and detected no polymerization by folded anchor-free PBP3; the construct limitation is explicit. The followup synthesis PMID:9614966, the distinct class-B domain architecture, the curated UniProt caution and the later assignment of polymerization to FtsW converge against intrinsic FtsI glycosyltransferase activity. PMID:6450748 measured septal murein incorporation after PBP3 inhibition, which does not distinguish glycan polymerization from cross-linking. FtsI-dependent activation or coordination of a partner polymerase is not possession of that partner's catalytic activity. This rejects the common function claim consistently across IEA, IMP and IDA rather than rejecting an assay merely because it is old. Supporting Evidence: PMID:9614966 It has no detectable transglycosylase activity with lipid II as substrate. PMID:3531167 The peptidoglycan transpeptidase activity of penicillin-binding protein 3 appears to use either nascent or exogenously added UDP-N-acetylmuramyl tripeptide-derived substrates as acceptors. file:ECOLI/ftsI/ftsI-source-analysis/catalytic-specificity.md |
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