Signal recognition particle (SRP) receptor FtsY is a membrane-associated GTPase (EC 3.6.5.4) that functions as the bacterial receptor for the SRP-ribosome-nascent chain complex. FtsY contains an NG module (N-terminal regulatory subdomain fused to a Ras-like G GTPase subdomain) and an acidic A-domain that mediates membrane association. Upon interaction with SRP-bound ribosome-nascent chain complexes, FtsY facilitates transfer of nascent membrane proteins to the SecYEG translocon for co-translational insertion. Both FtsY and its SRP partner Ffh hydrolyze GTP to drive the targeting cycle.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000166 nucleotide binding | IEA GO_REF:0000043 | MODIFY | Summary: FtsY is indeed a nucleotide-binding protein, specifically binding GTP via its NG domain. However, this annotation is too general and redundant with the more specific GO:0005525 (GTP binding) annotation. The UniProt record confirms GTP binding sites at residues 297-304, 379-383, and 443-446 (HAMAP-Rule:MF_00920). Reason: The annotation is directionally correct but too broad. Replace it with GO:0005525, which names the nucleotide bound by the FtsY G domain and is already present in the annotation set. Proposed replacements: GTP binding Supporting Evidence: UniProt:Q88CR9 Belongs to the GTP-binding SRP family. FtsY subfamily. |
| GO:0003924 GTPase activity | IEA GO_REF:0000120 | ACCEPT | Summary: GTPase activity is a core molecular function of FtsY. The exact record assigns EC 3.6.5.4 and places hydrolysis by Ffh and FtsY during transfer to Sec and dissociation of the targeting complex. Reason: This is a well-established core function of FtsY. The catalytic reaction (GTP + H2O = GDP + phosphate + H+) is documented in UniProt with HAMAP-Rule evidence, and the function statement places hydrolysis directly in the SRP targeting cycle. Supporting Evidence: UniProt:Q88CR9 Reaction=GTP + H2O = GDP + phosphate + H(+); Xref=Rhea:RHEA:19669 |
| GO:0005047 signal recognition particle binding | IEA GO_REF:0000118 | ACCEPT | Summary: SRP binding is a core molecular function of FtsY. The exact UniProt function statement identifies FtsY as the receptor for the SRP-RNC complex. Reason: This annotation accurately describes one of the core molecular functions of FtsY. Receptor engagement of SRP-RNC is the defining interaction that precedes transfer of the RNC to Sec. Supporting Evidence: UniProt:Q88CR9 Acts as a receptor for the complex formed by the signal recognition particle (SRP) and the ribosome-nascent chain (RNC) |
| GO:0005525 GTP binding | IEA GO_REF:0000120 | ACCEPT | Summary: GTP binding is a core molecular function of FtsY. The protein contains a P-loop NTPase domain with specific GTP binding sites. UniProt documents three GTP binding regions at residues 297-304, 379-383, and 443-446. The G domain of FtsY adopts a Ras-like fold characteristic of GTPases. Reason: This annotation correctly describes a fundamental molecular function of FtsY. GTP binding is required for the SRP-FtsY interaction and subsequent targeting cycle. Multiple domain annotations (IPR000897, IPR013822) and feature annotations in UniProt confirm the presence of GTP binding sites. Supporting Evidence: UniProt:Q88CR9 Belongs to the GTP-binding SRP family. FtsY subfamily. |
| GO:0005737 cytoplasm | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: FtsY is indeed found in the cytoplasm as part of its functional cycle. UniProt documents cytoplasmic localization (HAMAP-Rule:MF_00920). However, FtsY dynamically associates with the plasma membrane via its acidic A-domain, and its primary function occurs at the membrane-cytoplasm interface. Reason: UniProt explicitly assigns both cytoplasm and peripheral association with the cytoplasmic face of the inner membrane. These are dynamic FtsY states rather than redundant alternative annotations. Supporting Evidence: UniProt:Q88CR9 Cytoplasm {ECO:0000256|HAMAP-Rule:MF_00920} |
| GO:0005886 plasma membrane | IEA GO_REF:0000120 | ACCEPT | Summary: Plasma membrane localization is accurate. UniProt places FtsY at the cell inner membrane as a peripheral protein on the cytoplasmic side. Reason: This is the primary cellular localization where FtsY carries out its function. As a peripheral membrane protein, FtsY associates with the cytoplasmic face of the plasma membrane to receive SRP-RNC complexes and transfer them to the Sec translocase. Supporting Evidence: UniProt:Q88CR9 Cell inner membrane {ECO:0000256|HAMAP-Rule:MF_00920} |
| GO:0006605 protein targeting | IEA GO_REF:0000118 | MODIFY | Summary: FtsY is involved in protein targeting, specifically the targeting of nascent membrane and secretory proteins to the plasma membrane. However, this term is very general and redundant with the more specific annotations for 'protein targeting to membrane' (GO:0006612) and 'SRP-dependent cotranslational protein targeting to membrane' (GO:0006614). Reason: This parent term is correct but too broad. Replace it with GO:0006614, which captures the SRP-dependent cotranslational mechanism documented for FtsY. Proposed replacements: SRP-dependent cotranslational protein targeting to membrane Supporting Evidence: UniProt:Q88CR9 Involved in targeting and insertion of nascent membrane proteins into the cytoplasmic membrane |
| GO:0006612 protein targeting to membrane | IEA GO_REF:0000104 | MODIFY | Summary: FtsY is indeed involved in protein targeting to membrane. This annotation is accurate but less specific than GO:0006614 (SRP-dependent cotranslational protein targeting to membrane). FtsY specifically functions in the SRP-dependent co-translational pathway, not in post-translational targeting mechanisms. Reason: The membrane-targeting statement is correct, but GO:0006614 provides the known SRP-dependent cotranslational mechanism and should replace this parent. Proposed replacements: SRP-dependent cotranslational protein targeting to membrane Supporting Evidence: UniProt:Q88CR9 Involved in targeting and insertion of nascent membrane proteins into the cytoplasmic membrane |
| GO:0006614 SRP-dependent cotranslational protein targeting to membrane | IEA GO_REF:0000002 | ACCEPT | Summary: This is the most specific existing biological-process annotation for FtsY. UniProt identifies FtsY as the receptor that transfers SRP-bound RNCs to the Sec translocase. Reason: This annotation precisely describes the core biological process in which FtsY participates. FtsY is the bacterial SRP receptor that, together with SRP (Ffh + 4.5S RNA), mediates co-translational targeting of nascent membrane and secretory proteins to the SecYEG translocon. This is the primary and defining function of FtsY across bacteria. Supporting Evidence: UniProt:Q88CR9 Part of the signal recognition particle protein translocation system, which is composed of SRP and FtsY. SRP is a ribonucleoprotein composed of Ffh and a 4.5S RNA molecule. |
| GO:0016020 membrane | IEA GO_REF:0000120 | MODIFY | Summary: While FtsY is membrane-associated, this annotation is too general. The protein is a peripheral membrane protein specifically associated with the plasma membrane (inner membrane in bacteria). GO:0005886 (plasma membrane) provides the appropriate level of specificity. Reason: The parent localization is correct but underspecified. Replace it with GO:0005886, which corresponds to the bacterial inner/cell membrane localization stated by UniProt. Proposed replacements: plasma membrane Supporting Evidence: UniProt:Q88CR9 Cell inner membrane {ECO:0000256|HAMAP-Rule:MF_00920} |
| GO:0016787 hydrolase activity | IEA GO_REF:0000043 | MODIFY | Summary: FtsY does have hydrolase activity as it hydrolyzes GTP. However, this annotation is far too general. The specific hydrolase activity is GTPase activity (GO:0003924), which is already annotated and provides the appropriate mechanistic information. Reason: The hydrolase classification is correct but too broad. Replace it with GO:0003924, which names the exact GTPase activity and matches the documented Rhea reaction. Proposed replacements: GTPase activity Supporting Evidence: UniProt:Q88CR9 Reaction=GTP + H2O = GDP + phosphate + H(+); Xref=Rhea:RHEA:19669 |
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Download this section (compressed HTML)Q: What is the essentiality of ftsY in Pseudomonas putida KT2440, and are there fitness defects under specific growth conditions?
Q: Does P. putida FtsY interact with YidC insertase pathway components, and what is the relative contribution of SRP-Sec vs YidC pathways for membrane protein insertion in this organism?
Experiment: Conditional depletion or CRISPRi knockdown of ftsY in P. putida KT2440 to assess growth phenotypes and membrane protein biogenesis defects. This would confirm essentiality and provide organism-specific phenotypic data.
Experiment: Co-immunoprecipitation or proximity labeling (BioID/APEX) to identify FtsY interactors in P. putida, including potential organism-specific partners. This would confirm conserved interactions with SRP components and SecYEG while potentially identifying novel interaction partners.
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