ftsY

UniProt ID: Q88CR9
Organism: Pseudomonas putida (strain ATCC 47054 / DSM 6125 / CFBP 8728 / NCIMB 11950 / KT2440)
Review Status: DRAFT
Aliases:
PP_5111 SRP receptor signal recognition particle receptor
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Gene Description

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.

Existing Annotations Review

GO Term Evidence Action Reason
GO:0000166 nucleotide binding
IEA
GO_REF:0000043
MARK AS OVER ANNOTATED
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: While technically correct, 'nucleotide binding' is a very general term that provides little functional insight. FtsY specifically binds GTP, not nucleotides in general. The annotation GO:0005525 (GTP binding) is already present and provides the appropriate level of specificity for this GTPase. The nucleotide binding annotation is redundant and should be superseded by the more informative GTP binding annotation.
Supporting Evidence:
file:PSEPK/ftsY/ftsY-deep-research-falcon.md
FtsY is an SRP-type P-loop NTPase whose catalytic core comprises an NG module (N-terminal regulatory "N" subdomain fused to a Ras-like "G" GTPase subdomain)
GO:0003924 GTPase activity
IEA
GO_REF:0000120
ACCEPT
Summary: GTPase activity is a core molecular function of FtsY. The protein catalyzes GTP hydrolysis (EC 3.6.5.4) as part of the SRP targeting cycle. Cryo-EM structures demonstrate that FtsY and Ffh form a GTP-dependent heterodimer, and GTP hydrolysis by both proteins drives disassembly of the SRP-FtsY complex after nascent chain handover to SecYEG (Jomaa et al., 2016; Jomaa et al., 2017).
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. Structural studies confirm that GTPase activity is essential for the SRP targeting cycle, driving both assembly and disassembly of SRP-FtsY complexes during co-translational protein targeting.
Supporting Evidence:
UniProt:Q88CR9
Reaction=GTP + H2O = GDP + phosphate + H(+); Xref=Rhea:RHEA:19669
file:PSEPK/ftsY/ftsY-deep-research-falcon.md
The SRP-SR (Ffh-FtsY) NG domains heterodimerize in a GTP-dependent manner to form functional early/closed/activated complexes
GO:0005047 signal recognition particle binding
IEA
GO_REF:0000118
ACCEPT
Summary: SRP binding is a core molecular function of FtsY. As the SRP receptor, FtsY directly binds to SRP (comprising Ffh protein and 4.5S RNA) through its NG domain. Cryo-EM structures captured multiple states of the RNC-SRP-FtsY complex, demonstrating the physical interaction between FtsY and SRP components (Jomaa et al., 2016; Jomaa et al., 2017).
Reason: This annotation accurately describes one of the core molecular functions of FtsY. The protein functions specifically as the receptor for SRP, and structural studies have characterized the SRP-FtsY interface in detail. The NG domain heterodimer formation between FtsY and Ffh (the SRP protein component) is central to the co-translational protein targeting mechanism.
Supporting Evidence:
UniProt:Q88CR9
Acts as a receptor for the complex formed by the signal recognition particle (SRP) and the ribosome-nascent chain (RNC)
file:PSEPK/ftsY/ftsY-deep-research-falcon.md
Cryo-EM reconstructions in Escherichia coli captured sequential states of the RNC-SRP-FtsY complexes, including "early," "closed," and "activated" NG-domain arrangements
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.
file:PSEPK/ftsY/ftsY-deep-research-falcon.md
FtsY is an SRP-type P-loop NTPase whose catalytic core comprises an NG module (N-terminal regulatory "N" subdomain fused to a Ras-like "G" GTPase subdomain)
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: While FtsY does cycle through the cytoplasm and can be found there, its primary site of action is at the plasma membrane where it receives SRP-RNC complexes and delivers them to SecYEG. The cytoplasmic localization is accurate but represents a transitional state rather than the primary site of function.
Supporting Evidence:
UniProt:Q88CR9
Cytoplasm {ECO:0000256|ARBA:ARBA00022490, ECO:0000256|HAMAP-Rule:MF_00920}
GO:0005886 plasma membrane
IEA
GO_REF:0000120
ACCEPT
Summary: Plasma membrane localization is accurate and represents the primary site of FtsY function. FtsY associates with the inner membrane as a peripheral membrane protein on the cytoplasmic side. The acidic A-domain mediates membrane association. Cryo-EM structures show FtsY positioned at the membrane-ribosome interface near SecYEG (Jomaa et al., 2016; Jomaa et al., 2017).
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 nascent chains to the SecYEG translocon. UniProt and structural studies confirm this localization.
Supporting Evidence:
UniProt:Q88CR9
Cell inner membrane {ECO:0000256|HAMAP-Rule:MF_00920}
file:PSEPK/ftsY/ftsY-deep-research-falcon.md
density for the A/N of FtsY is weak/flexible, consistent with a dynamic peripheral domain
GO:0006605 protein targeting
IEA
GO_REF:0000118
MARK AS OVER ANNOTATED
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: While technically correct, 'protein targeting' is a high-level parent term that provides minimal functional specificity. The annotation GO:0006614 (SRP-dependent cotranslational protein targeting to membrane) precisely describes the biological process in which FtsY participates. Retaining this annotation adds redundancy without additional information.
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
KEEP AS NON CORE
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: This annotation is not incorrect, as FtsY does function in targeting proteins to membranes. However, GO:0006614 provides the specific mechanism (SRP-dependent, cotranslational) that accurately describes FtsY's role. This more general term can be retained as it may be useful for broader queries, but it is redundant given the presence of the more specific annotation.
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 and accurate biological process annotation for FtsY. The protein functions as the membrane-associated receptor in the SRP pathway, specifically for co-translational targeting of nascent proteins. Cryo-EM structures captured the complete pathway including SRP-FtsY-RNC-SecYEG quaternary complexes (Jomaa et al., 2016; Jomaa et al., 2017).
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.
file:PSEPK/ftsY/ftsY-deep-research-falcon.md
SRP recognizes exposed hydrophobic signal sequences emerging from the ribosome tunnel, stabilizes the ribosome-nascent chain complex (RNC), and then engages FtsY at the membrane
GO:0016020 membrane
IEA
GO_REF:0000120
MARK AS OVER ANNOTATED
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: 'Membrane' is a very general cellular component term that provides minimal localization information. Since GO:0005886 (plasma membrane) is already annotated and accurately describes where FtsY functions, this general membrane annotation is redundant and uninformative.
Supporting Evidence:
UniProt:Q88CR9
Membrane {ECO:0000256|ARBA:ARBA00023136, ECO:0000256|HAMAP-Rule:MF_00920}
GO:0016787 hydrolase activity
IEA
GO_REF:0000043
MARK AS OVER ANNOTATED
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: 'Hydrolase activity' is a very broad enzymatic classification that includes thousands of enzymes acting on diverse substrates. FtsY specifically has GTPase activity (EC 3.6.5.4), and this specific annotation is already present (GO:0003924). The general hydrolase annotation provides no useful functional insight beyond what is already captured by the GTPase activity annotation.
Supporting Evidence:
UniProt:Q88CR9
Hydrolase {ECO:0000256|ARBA:ARBA00022801, ECO:0000256|HAMAP-Rule:MF_00920}

Core Functions

FtsY hydrolyzes GTP (EC 3.6.5.4) as part of the SRP targeting cycle. GTP hydrolysis by both FtsY and Ffh drives dissociation of the SRP-FtsY complex after nascent chain handover to SecYEG.

Supporting Evidence:
  • UniProt:Q88CR9
    Reaction=GTP + H2O = GDP + phosphate + H(+); Xref=Rhea:RHEA:19669
  • file:PSEPK/ftsY/ftsY-deep-research-falcon.md
    The SRP-SR (Ffh-FtsY) NG domains heterodimerize in a GTP-dependent manner

FtsY directly binds SRP through NG domain heterodimerization with Ffh. This interaction is central to its function as the SRP receptor and enables transfer of ribosome-nascent chain complexes to the membrane.

Supporting Evidence:
  • UniProt:Q88CR9
    Acts as a receptor for the complex formed by the signal recognition particle (SRP) and the ribosome-nascent chain (RNC)
  • file:PSEPK/ftsY/ftsY-deep-research-falcon.md
    Cryo-EM reconstructions in Escherichia coli captured sequential states of the RNC-SRP-FtsY complexes

References

Gene Ontology annotation through association of InterPro records with GO terms
Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword mapping
Electronic Gene Ontology annotations created by transferring manual GO annotations between related proteins based on shared sequence features
TreeGrafter-generated GO annotations
Combined Automated Annotation using Multiple IEA Methods
file:PSEPK/ftsY/ftsY-deep-research-falcon.md
Deep research summary for ftsY
  • FtsY is the membrane-associated SR receptor that partners with SRP to drive co-translational targeting
  • FtsY contains an NG module and an acidic A-domain for membrane association
  • Cryo-EM structures captured sequential states of RNC-SRP-FtsY complexes at near-atomic resolution
  • GTP hydrolysis by both Ffh and FtsY drives disassembly of the SRP-FtsY complex

Suggested Questions for Experts

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?

Suggested Experiments

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.

Deep Research

Falcon

(ftsY-deep-research-falcon.md)
this with annotations you find in gene/protein databases, but these can be outdated or inaccurate. Falcon Edison Scientific Literature 15 citations 2025-12-19T19:31:15.594347

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.

Research plan status. We verified the identity (ftsY, UniProt Q88CR9, PP_5111) and gathered primary structural and mechanistic evidence for the bacterial SRP receptor FtsY, together with recent insights on SRP pathway adaptations relevant to function, localization, and potential applications.

Comprehensive research report: ftsY (Q88CR9) in Pseudomonas putida KT2440

1) Key concepts and definitions
- Gene/protein identity and family: ftsY encodes the bacterial signal recognition particle (SRP) receptor FtsY, the membrane-associated SR (EC 3.6.5.4) that partners with SRP (Ffh protein + 4.5S RNA) to drive co‑translational targeting of nascent membrane and secretory proteins. FtsY is an SRP-type P-loop NTPase whose catalytic core comprises an NG module (N-terminal regulatory “N” subdomain fused to a Ras-like “G” GTPase subdomain). Bacterial FtsY also contains an acidic A-domain implicated in membrane association and receptor function; in ribosome-bound cryo‑EM reconstructions, the A/N regions are flexibly disposed, consistent with a peripheral, dynamic association at the membrane–ribosome interface (Nature Communications 2016; Nature Communications 2017). URLs: 2016, https://doi.org/10.1038/ncomms10471 (published Jan 2016); 2017, https://doi.org/10.1038/ncomms15470 (published May 2017). (jomaa2016structuresofthe pages 1-2, jomaa2016structuresofthe pages 7-8, ahmad2017structureofthe pages 7-8)
- Core pathway: In bacteria, SRP recognizes exposed hydrophobic signal sequences emerging from the ribosome tunnel, stabilizes the ribosome–nascent chain complex (RNC), and then engages FtsY at the membrane. The SRP–SR (Ffh–FtsY) NG domains heterodimerize in a GTP-dependent manner to form functional early/closed/activated complexes that position the nascent chain for handover to the SecYEG translocon for insertion/translocation (Nature Communications 2016; Nature Communications 2017). URLs: 2016, https://doi.org/10.1038/ncomms10471; 2017, https://doi.org/10.1038/ncomms15470. (jomaa2016structuresofthe pages 1-2, ahmad2017structureofthe pages 7-8)

2) Biochemical mechanism and structural snapshots (emphasis on recent, authoritative sources)
- SRP–FtsY GTPase cycle: Cryo‑EM reconstructions in Escherichia coli captured sequential states of the RNC–SRP–FtsY complexes, including “early,” “closed,” and “activated” NG-domain arrangements that couple GTP binding/dimerization to conformational changes in the SRP M domain and fingerloop that engage the signal sequence at the tunnel exit (uL24/H59), and to approach of the SecYEG translocon. These structures provide near‑atomic details of how SRP–FtsY primes and delivers the nascent chain to SecYEG, and how activation positions the signal sequence for handover (Nature Communications 2016; Nature Communications 2017). URLs: 2016, https://doi.org/10.1038/ncomms10471; 2017, https://doi.org/10.1038/ncomms15470. (jomaa2016structuresofthe pages 1-2, ahmad2017structureofthe pages 7-8, jomaa2016structuresofthe pages 5-6)
- Quaternary assembly with translocon: A cryo‑EM “activated” quaternary complex of RNC–SRP–FtsY–translocon shows a kinked, untwisted SRP RNA that repositions the NG heterodimer and places the translocon near the ribosomal exit, while the signal sequence extends beyond the SRP M‑domain groove towards SecYEG; density for the A/N of FtsY is weak/flexible, consistent with a dynamic peripheral domain. PDB/EMD: 5NCO/EMD‑3617. Published May 2017 (Nature Communications). URL: https://doi.org/10.1038/ncomms15470. (ahmad2017structureofthe pages 7-8, jomaa2016structuresofthe pages 7-8)
- Role of 4.5S RNA: The bacterial SRP RNA accelerates both assembly and disassembly of the Ffh–FtsY NG heterodimer, thereby “catalyzing” the targeting cycle for efficient membrane protein biogenesis. Genetic perturbations of SRP RNA or its partners disrupt competence and virulence pathways in Streptococcus pneumoniae, underscoring the centrality of a fast SRP cycle in vivo (Journal of Bacteriology, Sep 2024). URL: https://doi.org/10.1128/jb.00004-24. (lin2024signalrecognitionparticle pages 14-16)

3) Subcellular localization and membrane association
- Membrane-proximal action: Structural snapshots of translating ribosomes bound by SRP and FtsY demonstrate that the NG core binds on the ribosome, while the SRP RNA and M domain coordinate the signal sequence and the approach of SecYEG at the membrane. The A/N regions of FtsY are flexibly disposed and incompletely resolved, consistent with a membrane‑associated, dynamic receptor whose acidic A-domain contributes to membrane engagement. These data collectively indicate that FtsY functions at the inner membrane, coupling the RNC to SecYEG during co‑translational targeting (Nature Communications 2016; Nature Communications 2017). URLs: 2016, https://doi.org/10.1038/ncomms10471; 2017, https://doi.org/10.1038/ncomms15470. (jomaa2016structuresofthe pages 1-2, jomaa2016structuresofthe pages 7-8, ahmad2017structureofthe pages 7-8)

4) Essentiality/fitness and organism-specific considerations
- Essentiality context and physiological effects: In streptococci, mutants lacking SRP components (scRNA, ffh, ftsY) show major growth and functional defects, including impaired competence pili production and DNA uptake; some phenotypes are partially rescued by nutritional supplementation. These findings highlight that SRP (and by implication FtsY) is central for membrane protein targeting and cellular fitness across bacteria, even though organismal dependence can vary (Journal of Bacteriology, Sep 2024). URL: https://doi.org/10.1128/jb.00004-24. (lin2024signalrecognitionparticle pages 14-16)
- Pseudomonas putida KT2440 (PP_5111; Q88CR9): The gene symbol and locus assignment identify the SRP receptor FtsY in KT2440. While species‑specific essentiality scores from KT2440 genome-wide fitness screens were not found in the retrieved corpus, the structural and mechanistic conservation of SRP–FtsY argues that ftsY underpins co-translational targeting to SecYEG in P. putida. Pending KT2440-specific essentiality datasets, FtsY should be presumed critical for robust growth and secretion of inner‑membrane proteins in this chassis organism, by analogy to conserved SRP function (Nature Communications 2016; Nature Communications 2017; Journal of Bacteriology 2024). URLs: 2016, https://doi.org/10.1038/ncomms10471; 2017, https://doi.org/10.1038/ncomms15470; 2024, https://doi.org/10.1128/jb.00004-24. (jomaa2016structuresofthe pages 1-2, ahmad2017structureofthe pages 7-8, lin2024signalrecognitionparticle pages 14-16)

5) Pathway context and interactions
- SecYEG handover: High‑resolution SRP–FtsY structures on the ribosome show the M-domain and fingerloop docking the signal helix and contacting rRNA near the exit site, and the spatial proximity required for SecYEG engagement. SecYEG contacts uL23/uL29 on the ribosome, and steric considerations show how the fingerloop and M‑domain C‑terminus vacate to allow Sec loop 6/7 to occupy the site as the signal sequence is transferred. These provide a mechanistic framework for the FtsY‑mediated coupling of cargo delivery to SecYEG (Nature Communications 2016). URL: https://doi.org/10.1038/ncomms10471. (jomaa2016structuresofthe pages 5-6)
- YidC interplay: Bacteria can vary in their reliance on the SRP–Sec pathway versus YidC insertase. In S. pneumoniae, YidC2 does not fully compensate for SRP loss in competence, yet species may shift the balance between SRP‑dependent Sec insertion and YidC‑mediated insertion of particular substrates. This illustrates how FtsY’s central role in SRP targeting integrates with alternative insertases in a species‑specific manner (Journal of Bacteriology, Sep 2024). URL: https://doi.org/10.1128/jb.00004-24. (lin2024signalrecognitionparticle pages 14-16)

6) Recent developments and latest research (2023–2024)
- SRP cycle adaptations, physiology, and virulence: 2024 work in pneumococcus demonstrates that SRP components, including FtsY, drive essential physiological programs such as genetic competence, with mutants exhibiting broad stress and nutrient‑acquisition defects. These data emphasize the speed/efficiency requirement of the SRP cycle (accelerated by SRP RNA) and highlight SRP components as potential intervention points for antimicrobial strategies that impair membrane protein targeting (Journal of Bacteriology, Sep 2024). URL: https://doi.org/10.1128/jb.00004-24. (lin2024signalrecognitionparticle pages 14-16)
- Structural mechanism reinforced: The cryo‑EM framework for SRP–FtsY engagement, activation, and Sec handover remains the authoritative structural basis for interpreting new organism‑specific observations and for the design of mechanistic probes or inhibitors that target the NG dimerization/hydrolysis steps (Nature Communications 2016; Nature Communications 2017). URLs: 2016, https://doi.org/10.1038/ncomms10471; 2017, https://doi.org/10.1038/ncomms15470. (jomaa2016structuresofthe pages 1-2, ahmad2017structureofthe pages 7-8)

7) Applications, expert views, and quantitative data
- Applications and implementations: The SRP receptor FtsY is a conserved GTPase central to membrane protein biogenesis and thus a conceptual antimicrobial target. Recent physiological studies linking SRP disruption to virulence impairments support this view; any applied design should account for the conserved NG interface and the SRP RNA–accelerated assembly/disassembly kinetics that tune the targeting cycle (Journal of Bacteriology, Sep 2024; Nature Communications 2016/2017). URLs as above. (lin2024signalrecognitionparticle pages 14-16, jomaa2016structuresofthe pages 1-2, ahmad2017structureofthe pages 7-8)
- Quantitative/structural statistics: Cryo‑EM map resolutions and deposited entries exemplify the structural basis. RNC–SRP–FtsY complexes solved at ~3.4–4.3 Å overall, with local filtering for NG domains/SRP RNA (~6 Å) and SecYEG (~4.8 Å) in specific states; quaternary complex deposited as PDB 5NCO/EMD‑3617 (Nature Communications 2017) and multiple ribosome‑bound states documented in 2016 (Nature Communications). URLs: 2016, https://doi.org/10.1038/ncomms10471; 2017, https://doi.org/10.1038/ncomms15470. (jomaa2016structuresofthe pages 5-6, ahmad2017structureofthe pages 7-8)

Expert analysis
- Structural biogenesis experts have established a coherent model in which Ffh’s M‑domain fingerloop and the NG dimer act as a coordinated switch to couple signal sequence capture to FtsY‑mediated docking and GTPase activation, after which GTP hydrolysis and SRP RNA remodeling drive timely disassembly and handover to Sec. The dynamic, weakly resolved N/A regions of FtsY in cryo‑EM reflect a functional flexibility at the membrane, matching a receptor that must engage both ribosome and translocon while sampling membrane contacts (Nature Communications 2016; Nature Communications 2017). URLs: 2016, https://doi.org/10.1038/ncomms10471; 2017, https://doi.org/10.1038/ncomms15470. (jomaa2016structuresofthe pages 1-2, jomaa2016structuresofthe pages 7-8, ahmad2017structureofthe pages 7-8)

Notes on identity verification and ambiguity
- The symbol “ftsY” is used consistently for the bacterial SRP receptor across organisms. The target here is Pseudomonas putida KT2440 ftsY (PP_5111; UniProt Q88CR9). The domain/family description (SRP GTPase; P‑loop NTPase/AAA+‑like fold in the G domain; NG module; acidic A‑domain) aligns with current structural literature (Nature Communications 2016; Nature Communications 2017). (jomaa2016structuresofthe pages 1-2, ahmad2017structureofthe pages 7-8)

Gaps and recommendations
- Species‑specific essentiality/fitness data for ftsY in P. putida KT2440 were not present in the retrieved evidence set. Given SRP’s conserved role and strong phenotypes in bacteria, ftsY is likely critical for growth and membrane protein biogenesis in KT2440; targeted KT2440 RB‑TnSeq/TraDIS datasets should be consulted to quantify essentiality/fitness precisely. Structural/biochemical insights from E. coli SRP–FtsY provide a robust framework for interpreting Pseudomonas data as they become available (Nature Communications 2016; Nature Communications 2017; Journal of Bacteriology 2024). URLs as above. (jomaa2016structuresofthe pages 1-2, ahmad2017structureofthe pages 7-8, lin2024signalrecognitionparticle pages 14-16)

References

  1. (jomaa2016structuresofthe pages 1-2): Ahmad Jomaa, Daniel Boehringer, Marc Leibundgut, and Nenad Ban. Structures of the e. coli translating ribosome with srp and its receptor and with the translocon. Nature Communications, Jan 2016. URL: https://doi.org/10.1038/ncomms10471, doi:10.1038/ncomms10471. This article has 128 citations and is from a highest quality peer-reviewed journal.

  2. (jomaa2016structuresofthe pages 7-8): Ahmad Jomaa, Daniel Boehringer, Marc Leibundgut, and Nenad Ban. Structures of the e. coli translating ribosome with srp and its receptor and with the translocon. Nature Communications, Jan 2016. URL: https://doi.org/10.1038/ncomms10471, doi:10.1038/ncomms10471. This article has 128 citations and is from a highest quality peer-reviewed journal.

  3. (ahmad2017structureofthe pages 7-8): Ahmad Jomaa, Yu-Hsien Hwang Fu, Daniel Boehringer, Marc Leibundgut, Shu-ou Shan, and Nenad Ban. Structure of the quaternary complex between srp, sr, and translocon bound to the translating ribosome. Nature Communications, May 2017. URL: https://doi.org/10.1038/ncomms15470, doi:10.1038/ncomms15470. This article has 79 citations and is from a highest quality peer-reviewed journal.

  4. (jomaa2016structuresofthe pages 5-6): Ahmad Jomaa, Daniel Boehringer, Marc Leibundgut, and Nenad Ban. Structures of the e. coli translating ribosome with srp and its receptor and with the translocon. Nature Communications, Jan 2016. URL: https://doi.org/10.1038/ncomms10471, doi:10.1038/ncomms10471. This article has 128 citations and is from a highest quality peer-reviewed journal.

  5. (lin2024signalrecognitionparticle pages 14-16): Jingjun Lin, Sook Yin Chong, Myung Whan Oh, Shi Qian Lew, Luchang Zhu, Xuejin Zhang, William H. Witola, and Gee W. Lau. Signal recognition particle rna is critical for genetic competence and virulence of streptococcus pneumoniae. Journal of Bacteriology, Sep 2024. URL: https://doi.org/10.1128/jb.00004-24, doi:10.1128/jb.00004-24. This article has 4 citations and is from a peer-reviewed journal.

Citations

  1. lin2024signalrecognitionparticle pages 14-16
  2. jomaa2016structuresofthe pages 5-6
  3. jomaa2016structuresofthe pages 1-2
  4. jomaa2016structuresofthe pages 7-8
  5. ahmad2017structureofthe pages 7-8
  6. https://doi.org/10.1038/ncomms10471
  7. https://doi.org/10.1038/ncomms15470
  8. https://doi.org/10.1038/ncomms10471;
  9. https://doi.org/10.1038/ncomms15470.
  10. https://doi.org/10.1128/jb.00004-24.
  11. https://doi.org/10.1038/ncomms15470;
  12. https://doi.org/10.1038/ncomms10471.
  13. https://doi.org/10.1038/ncomms10471,
  14. https://doi.org/10.1038/ncomms15470,
  15. https://doi.org/10.1128/jb.00004-24,

📚 Additional Documentation

Bioreason Rl Predictions

(ftsY-bioreason-rl-predictions.md)

BioReason Chat Export

Exported on March 22, 2026 at 02:29 AM


Organism: Pseudomonas putida

Sequence:

MFGSNDDKKAPAEAGEKKGLFSWFRKKPQPPAGAGVPAHEPPAVEQSAAAPVEGSAAEAPQAPEPVQAVAAPQLAEPQPVAAPPRPPVVEAPVPEPVASQPLQAPEPEPVASQPLVAPAPQPVASMPLQAAPVESAPVEAAAPVSNLVLPVAEEPVALVPDLEPKAPPAIPERAAPAPVAAPVEQAKPGFFARLKQGLSKTSASIGEGMASLFLGKKVIDDDLLDEIETRLLTADVGVEATSAIVQNLTQKVARKQLADADALYKSLQEELAALLRPVEQPLNVQAQNKPYVILVVGVNGAGKTTTIGKLAKKLQLEGKKVMLAAGDTFRAAAVEQLQVWGERNQIPVIAQHTGADSASVIFDAVQAAKARGVDVLIADTAGRLHTKDNLMEELKKVRRVIGKLDVEAPHEVLLVLDAGTGQNAISQAKYFNQSVELTGLALTKLDGTAKGGVIFALAKQFNIPIRFIGVGEGIDDLRTFEAEPFVKALFAERD

Thinking Trace

I begin with the InterPro architecture. The N-terminal half contains a triad of overlapping helical N-domain signatures: IPR042101 (Signal recognition particle SRP54, N-terminal domain superfamily, residues 182–279), IPR036225 (SRP/SRP receptor, N-terminal homologous superfamily, residues 189–269), and IPR013822 (Signal recognition particle SRP54, helical bundle, residues 194–275). This arrangement defines the canonical SRP/SRP-receptor N-domain that binds partner proteins and membranes rather than RNA. Immediately downstream, the C-terminal half is dominated by the FtsY/SRP54-family GTPase module: IPR004390 (Signal-recognition particle receptor FtsY family, residues 218–491) and IPR000897 (SRP54 subunit GTPase domain, residues 290–491). These are embedded within a broader P-loop NTPase scaffold—IPR027417 (P-loop containing nucleoside triphosphate hydrolase superfamily, residues 243–494)—and reinforced by IPR003593 (AAA+ ATPase domain, residues 289–442). The ordered layout—SRP-receptor N-domain followed by a P-loop/AAA+-like GTPase core—establishes a composite NTPase engine that binds and hydrolyzes GTP and forms regulated dimers with cognate partners.

This architecture causes GTP-dependent molecular function. The P-loop/AAA+-like core (IPR027417 and IPR003593) together with the SRP54-type GTPase module (IPR000897) specify GTP binding and hydrolysis as the primary chemistry, supporting GO:0005525 GTP binding and GO:0003924 GTPase activity. The N-terminal helical bundle (IPR013822; IPR042101; IPR036225) confers high-affinity protein–protein interfaces characteristic of SRP/SRP-receptor assemblies, explaining broad GO:0005515 protein binding.

From this molecular function, the biological role follows. SRP-receptor family signatures (IPR004390) and the SRP/SRP-receptor N-domain superfamily (IPR036225) anchor the protein in the SRP pathway that delivers ribosome–nascent-chain complexes to membrane targeting sites. GTP-driven cycles of assembly and disassembly coordinate handoff of secretory and membrane protein precursors, placing the protein in GO:0006614 SRP-dependent cotranslational protein targeting to membrane.

Cellular placement is dictated by the soluble helical architecture and absence of transmembrane segments: the protein is cytosolic but operates at membrane-proximal surfaces. Thus, it resides in the cytoplasm (GO:0005737 cytoplasm), transiently docking to ribosome–membrane interfaces during targeting.

Mechanistically, the N-domain mediates assembly with SRP components and ribosome-bound nascent chains, while the C-terminal GTPase domain times the targeting cycle by GTP-dependent complex formation and hydrolysis-triggered release. I therefore hypothesize partnerships with SRP components (e.g., the small and large SRP subunits), the ribosome, and membrane-targeting modules analogous to membrane receptors in bacteria. In Pseudomonas, likely partners include the bacterial SRP subunits and the membrane-associated targeting apparatus that receives signal peptide-bearing substrates; together these interactions produce a regulated GTPase cycle that ensures efficient cotranslational delivery to the membrane.

Functional Summary

A cytoplasmic SRP-receptor–type GTPase that orchestrates cotranslational targeting of nascent secretory and membrane proteins. It uses an N-terminal helical interaction module to assemble with targeting factors and a C-terminal P-loop GTPase engine to drive assembly and disassembly cycles. Through GTP-dependent timing, it receives ribosome–nascent-chain complexes and delivers them to membrane-associated pathways in bacteria, acting as a soluble cytoplasmic hub that transiently docks at membrane-proximal sites.

UniProt Summary

May be involved in protein secretion.

InterPro Domains

  • Signal recognition particle SRP54, N-terminal domain superfamily (IPR042101, homologous_superfamily) — residues 182-279
  • SRP/SRP receptor, N-terminal (IPR036225, homologous_superfamily) — residues 189-269
  • Signal recognition particle SRP54, helical bundle (IPR013822, domain) — residues 194-275
  • Signal-recognition particle receptor FtsY (IPR004390, family) — residues 218-491
  • P-loop containing nucleoside triphosphate hydrolase (IPR027417, homologous_superfamily) — residues 243-494
  • AAA+ ATPase domain (IPR003593, domain) — residues 289-442
  • Signal recognition particle, SRP54 subunit, GTPase domain (IPR000897, domain) — residues 290-491

GO Terms

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

Biological Process: biological_process (GO:0008150), cellular process (GO:0009987), localization (GO:0051179), establishment of localization (GO:0051234), cellular localization (GO:0051641), macromolecule localization (GO:0033036), cellular macromolecule localization (GO:0070727), establishment of localization in cell (GO:0051649), intracellular transport (GO:0046907), localization within membrane (GO:0051668), establishment of protein localization (GO:0045184), 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), establishment of protein localization to organelle (GO:0072594), establishment of protein localization to membrane (GO:0090150), protein localization to membrane (GO:0072657), protein localization to organelle (GO:0033365), protein targeting to membrane (GO:0006612), protein targeting (GO:0006605), establishment of protein localization to endoplasmic reticulum (GO:0072599), protein targeting to ER (GO:0045047), protein localization to endoplasmic reticulum (GO:0070972), cotranslational protein targeting to membrane (GO:0006613), SRP-dependent cotranslational protein targeting to membrane (GO:0006614)

Cellular Component: cellular_component (GO:0005575), cellular anatomical entity (GO:0110165), protein-containing complex (GO:0032991), cytosol (GO:0005829), intracellular anatomical structure (GO:0005622), cytoplasm (GO:0005737)


Generated by BioReason

Bioreason Rl Review

(ftsY-bioreason-rl-review.md)

BioReason-Pro RL Review: ftsY (P. putida)

Source: ftsY-bioreason-rl-predictions.md

  • Correctness: 4/5
  • Completeness: 4/5

Functional Summary Review

The BioReason functional summary describes ftsY as:

A cytoplasmic SRP-receptor-type GTPase that orchestrates cotranslational targeting of nascent secretory and membrane proteins. It uses an N-terminal helical interaction module to assemble with targeting factors and a C-terminal P-loop GTPase engine to drive assembly and disassembly cycles. Through GTP-dependent timing, it receives ribosome-nascent-chain complexes and delivers them to membrane-associated pathways in bacteria, acting as a soluble cytoplasmic hub that transiently docks at membrane-proximal sites.

This is a strong summary that accurately captures the core function of FtsY:
- SRP receptor function correctly identified
- GTPase activity for the targeting cycle
- Cotranslational protein targeting
- N-terminal NG domain + GTPase domain architecture
- Transient membrane association
- Role in delivering nascent chains to the membrane

Minor issues:
- The curated review specifies that FtsY contains an acidic A-domain that mediates membrane association, which is not captured in the BioReason summary
- The curated review emphasizes the specific partnership with Ffh (the SRP subunit) through NG domain heterodimerization, whereas BioReason describes generic "targeting factors"
- Does not mention the SecYEG translocon as the downstream target for nascent chain transfer
- The summary says "cytoplasmic" but FtsY is actually membrane-associated (plasma membrane localization in the curated review)

The thinking trace correctly identifies all seven InterPro domains including the SRP54 N-terminal domain, SRP receptor FtsY family, and P-loop NTPase superfamily. The AAA+ ATPase domain (IPR003593) annotation is noted but may be a superfamily-level classification rather than indicating AAA+ function per se.

Comparison with interpro2go:

The curated review's interpro2go annotations include nucleotide binding (GO:0000166, accepted as too general) and GTP binding (GO:0005525, accepted). BioReason adds significant value beyond interpro2go by correctly synthesizing the SRP targeting pathway context. The model's GO term predictions include SRP-dependent cotranslational protein targeting to membrane (GO:0006614), which is the correct specific biological process. This is a case where BioReason adds genuine insight by connecting domain architecture to pathway biology.

Notes on thinking trace

The trace demonstrates strong reasoning from InterPro domains to SRP pathway function. The identification of the N-domain/G-domain architecture and its role in the targeting cycle is accurate. The mention of "bacterial SRP subunits and the membrane-associated targeting apparatus" as partners is appropriate.

📄 View Raw YAML

id: Q88CR9
gene_symbol: ftsY
product_type: PROTEIN
aliases:
  - PP_5111
  - SRP receptor
  - signal recognition particle receptor
status: DRAFT
taxon:
  id: NCBITaxon:160488
  label: Pseudomonas putida (strain ATCC 47054 / DSM 6125 / CFBP 8728 / NCIMB 11950
    / KT2440)
description: >-
  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.
existing_annotations:
- term:
    id: GO:0000166
    label: nucleotide binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000043
  review:
    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).
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      While technically correct, 'nucleotide binding' is a very general term that
      provides little functional insight. FtsY specifically binds GTP, not nucleotides
      in general. The annotation GO:0005525 (GTP binding) is already present and
      provides the appropriate level of specificity for this GTPase. The nucleotide
      binding annotation is redundant and should be superseded by the more informative
      GTP binding annotation.
    supported_by:
      - reference_id: file:PSEPK/ftsY/ftsY-deep-research-falcon.md
        supporting_text: FtsY is an SRP-type P-loop NTPase whose catalytic core comprises an NG module (N-terminal regulatory "N" subdomain fused to a Ras-like "G" GTPase subdomain)

- term:
    id: GO:0003924
    label: GTPase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: >-
      GTPase activity is a core molecular function of FtsY. The protein catalyzes
      GTP hydrolysis (EC 3.6.5.4) as part of the SRP targeting cycle. Cryo-EM structures
      demonstrate that FtsY and Ffh form a GTP-dependent heterodimer, and GTP hydrolysis
      by both proteins drives disassembly of the SRP-FtsY complex after nascent chain
      handover to SecYEG (Jomaa et al., 2016; Jomaa et al., 2017).
    action: ACCEPT
    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. Structural studies confirm that GTPase activity is essential for
      the SRP targeting cycle, driving both assembly and disassembly of SRP-FtsY
      complexes during co-translational protein targeting.
    supported_by:
      - reference_id: UniProt:Q88CR9
        supporting_text: Reaction=GTP + H2O = GDP + phosphate + H(+); Xref=Rhea:RHEA:19669
      - reference_id: file:PSEPK/ftsY/ftsY-deep-research-falcon.md
        supporting_text: The SRP-SR (Ffh-FtsY) NG domains heterodimerize in a GTP-dependent manner to form functional early/closed/activated complexes

- term:
    id: GO:0005047
    label: signal recognition particle binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000118
  review:
    summary: >-
      SRP binding is a core molecular function of FtsY. As the SRP receptor, FtsY
      directly binds to SRP (comprising Ffh protein and 4.5S RNA) through its NG
      domain. Cryo-EM structures captured multiple states of the RNC-SRP-FtsY complex,
      demonstrating the physical interaction between FtsY and SRP components
      (Jomaa et al., 2016; Jomaa et al., 2017).
    action: ACCEPT
    reason: >-
      This annotation accurately describes one of the core molecular functions of
      FtsY. The protein functions specifically as the receptor for SRP, and structural
      studies have characterized the SRP-FtsY interface in detail. The NG domain
      heterodimer formation between FtsY and Ffh (the SRP protein component) is
      central to the co-translational protein targeting mechanism.
    supported_by:
      - reference_id: UniProt:Q88CR9
        supporting_text: Acts as a receptor for the complex formed by the signal recognition particle (SRP) and the ribosome-nascent chain (RNC)
      - reference_id: file:PSEPK/ftsY/ftsY-deep-research-falcon.md
        supporting_text: Cryo-EM reconstructions in Escherichia coli captured sequential states of the RNC-SRP-FtsY complexes, including "early," "closed," and "activated" NG-domain arrangements

- term:
    id: GO:0005525
    label: GTP binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    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.
    action: ACCEPT
    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.
    supported_by:
      - reference_id: UniProt:Q88CR9
        supporting_text: Belongs to the GTP-binding SRP family. FtsY subfamily.
      - reference_id: file:PSEPK/ftsY/ftsY-deep-research-falcon.md
        supporting_text: FtsY is an SRP-type P-loop NTPase whose catalytic core comprises an NG module (N-terminal regulatory "N" subdomain fused to a Ras-like "G" GTPase subdomain)

- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    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.
    action: KEEP_AS_NON_CORE
    reason: >-
      While FtsY does cycle through the cytoplasm and can be found there, its
      primary site of action is at the plasma membrane where it receives SRP-RNC
      complexes and delivers them to SecYEG. The cytoplasmic localization is accurate
      but represents a transitional state rather than the primary site of function.
    supported_by:
      - reference_id: UniProt:Q88CR9
        supporting_text: Cytoplasm {ECO:0000256|ARBA:ARBA00022490, ECO:0000256|HAMAP-Rule:MF_00920}

- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: >-
      Plasma membrane localization is accurate and represents the primary site of
      FtsY function. FtsY associates with the inner membrane as a peripheral membrane
      protein on the cytoplasmic side. The acidic A-domain mediates membrane
      association. Cryo-EM structures show FtsY positioned at the membrane-ribosome
      interface near SecYEG (Jomaa et al., 2016; Jomaa et al., 2017).
    action: ACCEPT
    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 nascent
      chains to the SecYEG translocon. UniProt and structural studies confirm this
      localization.
    supported_by:
      - reference_id: UniProt:Q88CR9
        supporting_text: Cell inner membrane {ECO:0000256|HAMAP-Rule:MF_00920}
      - reference_id: file:PSEPK/ftsY/ftsY-deep-research-falcon.md
        supporting_text: density for the A/N of FtsY is weak/flexible, consistent with a dynamic peripheral domain

- term:
    id: GO:0006605
    label: protein targeting
  evidence_type: IEA
  original_reference_id: GO_REF:0000118
  review:
    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).
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      While technically correct, 'protein targeting' is a high-level parent term
      that provides minimal functional specificity. The annotation GO:0006614
      (SRP-dependent cotranslational protein targeting to membrane) precisely
      describes the biological process in which FtsY participates. Retaining this
      annotation adds redundancy without additional information.
    supported_by:
      - reference_id: UniProt:Q88CR9
        supporting_text: Involved in targeting and insertion of nascent membrane proteins into the cytoplasmic membrane

- term:
    id: GO:0006612
    label: protein targeting to membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000104
  review:
    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.
    action: KEEP_AS_NON_CORE
    reason: >-
      This annotation is not incorrect, as FtsY does function in targeting proteins
      to membranes. However, GO:0006614 provides the specific mechanism (SRP-dependent,
      cotranslational) that accurately describes FtsY's role. This more general
      term can be retained as it may be useful for broader queries, but it is
      redundant given the presence of the more specific annotation.
    supported_by:
      - reference_id: UniProt:Q88CR9
        supporting_text: Involved in targeting and insertion of nascent membrane proteins into the cytoplasmic membrane

- term:
    id: GO:0006614
    label: SRP-dependent cotranslational protein targeting to membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  review:
    summary: >-
      This is the most specific and accurate biological process annotation for FtsY.
      The protein functions as the membrane-associated receptor in the SRP pathway,
      specifically for co-translational targeting of nascent proteins. Cryo-EM
      structures captured the complete pathway including SRP-FtsY-RNC-SecYEG
      quaternary complexes (Jomaa et al., 2016; Jomaa et al., 2017).
    action: ACCEPT
    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.
    supported_by:
      - reference_id: UniProt:Q88CR9
        supporting_text: 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.
      - reference_id: file:PSEPK/ftsY/ftsY-deep-research-falcon.md
        supporting_text: SRP recognizes exposed hydrophobic signal sequences emerging from the ribosome tunnel, stabilizes the ribosome-nascent chain complex (RNC), and then engages FtsY at the membrane

- term:
    id: GO:0016020
    label: membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    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.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      'Membrane' is a very general cellular component term that provides minimal
      localization information. Since GO:0005886 (plasma membrane) is already
      annotated and accurately describes where FtsY functions, this general
      membrane annotation is redundant and uninformative.
    supported_by:
      - reference_id: UniProt:Q88CR9
        supporting_text: Membrane {ECO:0000256|ARBA:ARBA00023136, ECO:0000256|HAMAP-Rule:MF_00920}

- term:
    id: GO:0016787
    label: hydrolase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000043
  review:
    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.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      'Hydrolase activity' is a very broad enzymatic classification that includes
      thousands of enzymes acting on diverse substrates. FtsY specifically has
      GTPase activity (EC 3.6.5.4), and this specific annotation is already present
      (GO:0003924). The general hydrolase annotation provides no useful functional
      insight beyond what is already captured by the GTPase activity annotation.
    supported_by:
      - reference_id: UniProt:Q88CR9
        supporting_text: Hydrolase {ECO:0000256|ARBA:ARBA00022801, ECO:0000256|HAMAP-Rule:MF_00920}

references:
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with GO
    terms
  findings: []
- id: GO_REF:0000043
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword mapping
  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:0000118
  title: TreeGrafter-generated GO annotations
  findings: []
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods
  findings: []
- id: file:PSEPK/ftsY/ftsY-deep-research-falcon.md
  title: Deep research summary for ftsY
  findings:
    - statement: FtsY is the membrane-associated SR receptor that partners with SRP to drive co-translational targeting
    - statement: FtsY contains an NG module and an acidic A-domain for membrane association
    - statement: Cryo-EM structures captured sequential states of RNC-SRP-FtsY complexes at near-atomic resolution
    - statement: GTP hydrolysis by both Ffh and FtsY drives disassembly of the SRP-FtsY complex

core_functions:
- molecular_function:
    id: GO:0003924
    label: GTPase activity
  description: >-
    FtsY hydrolyzes GTP (EC 3.6.5.4) as part of the SRP targeting cycle. GTP
    hydrolysis by both FtsY and Ffh drives dissociation of the SRP-FtsY complex
    after nascent chain handover to SecYEG.
  directly_involved_in:
    - id: GO:0006614
      label: SRP-dependent cotranslational protein targeting to membrane
  locations:
    - id: GO:0005886
      label: plasma membrane
  supported_by:
    - reference_id: UniProt:Q88CR9
      supporting_text: Reaction=GTP + H2O = GDP + phosphate + H(+); Xref=Rhea:RHEA:19669
    - reference_id: file:PSEPK/ftsY/ftsY-deep-research-falcon.md
      supporting_text: The SRP-SR (Ffh-FtsY) NG domains heterodimerize in a GTP-dependent manner
- molecular_function:
    id: GO:0005047
    label: signal recognition particle binding
  description: >-
    FtsY directly binds SRP through NG domain heterodimerization with Ffh. This
    interaction is central to its function as the SRP receptor and enables
    transfer of ribosome-nascent chain complexes to the membrane.
  directly_involved_in:
    - id: GO:0006614
      label: SRP-dependent cotranslational protein targeting to membrane
  locations:
    - id: GO:0005886
      label: plasma membrane
  supported_by:
    - reference_id: UniProt:Q88CR9
      supporting_text: Acts as a receptor for the complex formed by the signal recognition particle (SRP) and the ribosome-nascent chain (RNC)
    - reference_id: file:PSEPK/ftsY/ftsY-deep-research-falcon.md
      supporting_text: Cryo-EM reconstructions in Escherichia coli captured sequential states of the RNC-SRP-FtsY complexes

suggested_questions:
  - question: >-
      What is the essentiality of ftsY in Pseudomonas putida KT2440, and are there
      fitness defects under specific growth conditions?
  - question: >-
      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?

suggested_experiments:
  - description: >-
      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.
  - description: >-
      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.