SecF is a multi-pass inner membrane protein that forms the SecDF accessory complex together with SecD. As part of the Sec protein translocase, SecDF uses the proton motive force (PMF) to enhance protein translocation across the cytoplasmic membrane after the ATP-dependent function of SecA. SecDF undergoes PMF-driven conformational cycles that pull preproteins through the SecYEG channel into the periplasm, functioning as a membrane-integrated chaperone that works independently of ATP. In P. aeruginosa, the SecD-SecF complex has been directly demonstrated by in vivo cross-linking mass spectrometry.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005886 plasma membrane | IBA GO_REF:0000033 | ACCEPT | Summary: IBA annotation for plasma membrane localization inferred from phylogenetic analysis (PANTHER PTN000763987). SecF is an integral inner membrane protein in bacteria, and in P. aeruginosa the inner membrane corresponds to the plasma membrane. Reason: SecF is an integral inner membrane protein with six transmembrane helices. Plasma membrane localization is conserved across bacterial SecDF complexes and supported by experimental characterization of E. coli SecD/SecF (P0AG90, P0AG93), the T. thermophilus SecDF crystal structure, and in vivo cross-linking of the P. aeruginosa SecD-SecF complex. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000763987 · PANTHER:PTN000763987 SUPPORTS TRANSFER Ancestral bacterial SecDF transmembrane node conserved across SecD/SecF inner-membrane subunits. UniProtKB:P0AG93 · secF SUPPORTS TRANSFER Direct E. coli SecF ortholog with experimentally established six-transmembrane inner-membrane topology. UniProtKB:P0AG90 · secD SUPPORTS TRANSFER E. coli SecD subunit of the heterodimeric SecDF inner-membrane complex, sharing the ancestral RND-superfamily 6-TM inner-membrane topology at PTN000763987. Supporting Evidence: PMID:21562494 Here, we determined the crystal structure of Thermus thermophilus SecDF at 3.3 Å resolution, revealing a pseudo-symmetrical, 12-helix transmembrane domain belonging to the RND superfamily and two major periplasmic domains, P1 and P4 PMID:7507921 TnphoA fusions have been used to analyze the topology of SecD in the inner membrane; the protein contains six transmembrane stretches and a large periplasmic domain |
| GO:0015031 protein transport | IBA GO_REF:0000033 | MODIFY | Summary: IBA annotation for involvement in protein transport inferred from PANTHER node PTN000763987. While SecF participates in protein export across the bacterial inner membrane, this parent term is overly general relative to the Sec-complex-specific process GO:0043952 already annotated on the gene. Reason: SecF functions specifically as part of the SecDF accessory complex of the bacterial Sec translocase rather than in generic protein transport. Per GO review guidelines, a true but overly general parent term is refined with MODIFY to the specific supported descendant GO:0043952 (protein transport by the Sec complex), which is already accepted on this gene. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: PANTHER:PTN000763987 · PANTHER:PTN000763987 SUPPORTS TRANSFER PAINT node PTN000763987 stops at the generic parent term GO:0015031 rather than the Sec-complex-specific descendant GO:0043952. UniProtKB:P0AG93 · secF SUPPORTS TRANSFER Direct E. coli SecF ortholog experimentally shown to function as a PMF-driven accessory subunit of the Sec protein translocase (GO:0043952). UniProtKB:P0AG90 · secD SUPPORTS TRANSFER E. coli SecD heterodimeric partner in the SecDF translocase accessory complex; both SecD and SecF specifically mediate protein transport by the Sec complex (GO:0043952). Proposed replacements: protein transport by the Sec complex Supporting Evidence: PMID:29718185 The bacterial membrane protein SecDF enhances protein translocation across the membrane driven by the complex of SecA ATPase and SecYEG |
| GO:0005886 plasma membrane | IEA GO_REF:0000120 | ACCEPT | Summary: IEA annotation for plasma membrane from combined automated methods (UniProt subcellular location mapping). Correct and consistent with the IBA annotation above. Reason: Redundant with the IBA annotation but independently correct. SecF is an integral inner membrane protein confirmed by topology studies and crystal structures. Supporting Evidence: PMID:21562494 Here, we determined the crystal structure of Thermus thermophilus SecDF at 3.3 Å resolution, revealing a pseudo-symmetrical, 12-helix transmembrane domain belonging to the RND superfamily and two major periplasmic domains, P1 and P4 |
| GO:0006605 protein targeting | IEA GO_REF:0000104 | MODIFY | Summary: IEA annotation from UniRule (MF_01464) for involvement in protein targeting. SecDF acts during the PMF-driven polypeptide translocation step at the SecYEG channel rather than in preprotein signal recognition or membrane targeting. Reason: Protein targeting encompasses preprotein recognition and delivery to the membrane, whereas SecDF acts at the SecYEG channel after targeting to pull the translocating polypeptide into the periplasm using the proton motive force. This UniRule mapping is therefore corrected laterally with MODIFY to GO:0043952 (protein transport by the Sec complex), which is already accepted on this gene and accurately captures SecF's biological process. Proposed replacements: protein transport by the Sec complex Supporting Evidence: PMID:29718185 SecDF is proposed to undergo repeated conformational transitions to pull out the precursor protein from the SecYEG channel into the periplasm |
| GO:0006886 intracellular protein transport | IEA GO_REF:0000002 | MODIFY | Summary: IEA annotation from InterPro2GO mapping (IPR005665 SecF bacterial family). SecF facilitates preprotein export across the bacterial inner membrane via the Sec translocase rather than generic intracellular protein transport. Reason: This InterPro2GO mapping assigns the broad term GO:0006886 (intracellular protein transport), which fails to specify the Sec translocase pathway. Refining with MODIFY to the specific supported term GO:0043952 (protein transport by the Sec complex), already accepted on this gene, accurately reflects SecF function. Proposed replacements: protein transport by the Sec complex Supporting Evidence: PMID:21562494 Protein translocation across the bacterial membrane, mediated by the secretory translocon SecYEG and the SecA ATPase, is enhanced by proton motive force and membrane-integrated SecDF |
| GO:0015450 protein-transporting ATPase activity | IEA GO_REF:0000002 | MODIFY | Summary: IEA annotation from InterPro2GO mapping (IPR005665). This is an incorrect annotation for SecF. SecF does not have ATPase activity. The ATPase function in the Sec translocase belongs to SecA. SecDF instead uses the proton motive force to drive conformational changes that enhance translocation. Reason: SecF/SecDF is explicitly not an ATPase. Multiple structural and biochemical studies demonstrate that SecDF uses the proton motive force, not ATP hydrolysis, to enhance translocation. Tsukazaki et al. (2011) identified an ATP-independent translocation step requiring SecDF and PMF. The appropriate MF term is GO:0009977 (proton motive force dependent protein transmembrane transporter activity), as SecDF conducts protons coupled to polypeptide movement. SecF contributes to the translocase complex activity but does not independently enable ATPase activity. Proposed replacements: proton motive force dependent protein transmembrane transporter activity Supporting Evidence: PMID:21562494 we propose that SecDF functions as a membrane-integrated chaperone, powered by proton motive force, to achieve ATP-independent protein translocation PMID:29718185 Once SecDF captures the precursor protein on the periplasmic surface, SecDF can complete protein translocation even if SecA function is inactivated by ATP depletion, implying that SecDF is a protein-translocation motor that works independent of SecA PMID:28467902 SecDF in I form can generate a tunnel that penetrates the transmembrane region and functions as a proton pathway regulated by a conserved Asp residue |
| GO:0043952 protein transport by the Sec complex | IEA GO_REF:0000104 | ACCEPT | Summary: IEA annotation from UniRule for involvement in protein transport by the Sec complex. This is the most specific and appropriate BP term for SecF function. SecDF is an integral component of the Sec translocase that enhances protein export. Reason: This is the most specific and accurate BP annotation for SecF. SecDF is a well-characterized component of the Sec protein translocation machinery. Multiple structural and biochemical studies confirm this role across bacterial species. Supporting Evidence: PMID:21562494 Protein translocation across the bacterial membrane, mediated by the secretory translocon SecYEG and the SecA ATPase, is enhanced by proton motive force and membrane-integrated SecDF, which associates with SecYEG PMID:24550475 The SecY/61 complex forms the protein-channel component of the ubiquitous protein secretion and membrane protein insertion apparatus. The bacterial version SecYEG interacts with the highly conserved YidC and SecDF-YajC subcomplex, which facilitates translocation into and across the membrane |
| GO:0065002 intracellular protein transmembrane transport | IEA GO_REF:0000104 | MODIFY | Summary: IEA annotation from UniRule (MF_01464) for intracellular protein transmembrane transport. SecF facilitates preprotein export across the bacterial inner membrane specifically as part of the Sec translocase complex. Reason: Although SecF mediates transmembrane polypeptide transport across the bacterial inner membrane, GO:0065002 is a generic parent-level mapping that omits the Sec translocase pathway. Per GO review guidelines, this broad term is refined with MODIFY to GO:0043952 (protein transport by the Sec complex), which is already accepted on this gene. Proposed replacements: protein transport by the Sec complex Supporting Evidence: PMID:29718185 Many newly synthesized proteins in the cytoplasm are programmed to be translocated to the periplasm via the narrow channel that is formed in the center of SecYEG |
| GO:0031522 cell envelope Sec protein transport complex | ISS PMID:25800553 Probing the protein interaction network of Pseudomonas aerug... | NEW | Summary: SecF is a component of the cell envelope Sec protein transport complex. In P. aeruginosa, the SecD-SecF physical interaction has been directly demonstrated by in vivo chemical cross-linking mass spectrometry. The SecDF subcomplex associates with SecYEG to form the Sec translocon, and with YidC to form the holo-translocon. This annotation is supported by deep research findings in secF-deep-research-bioreason-sft.md which correctly identifies SecF as part of the Sec protein secretion complex. Reason: GO:0031522 (cell envelope Sec protein transport complex) is the most specific CC term for SecF and captures its role as a subunit of the Sec translocase complex. This is supported by direct cross-linking evidence in P. aeruginosa (PMID:25800553) and extensive structural evidence from E. coli and T. thermophilus. Supporting Evidence: PMID:25800553 Structures of three membrane proteins, namely, SecD-SecF, OprF, and OprI are predicted using in vivo cross-linked sites PMID:24550475 The bacterial version SecYEG interacts with the highly conserved YidC and SecDF-YajC subcomplex, which facilitates translocation into and across the membrane file:PSEAE/secF/secF-deep-research-bioreason-sft.md [BioReason SFT] A multi-pass inner-membrane component of the bacterial Sec pathway |
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Download this section (compressed HTML)Q: Has SecF or SecDF been directly studied for essentiality or translocation activity in P. aeruginosa, or is all functional evidence transferred from E. coli and T. thermophilus?
Suggested experts: James E Bruce
Q: Does the SecDF complex in P. aeruginosa interact with YidC and participate in membrane protein insertion as part of a holo-translocon, similar to E. coli?
Experiment: Construct a secF deletion mutant in P. aeruginosa PAO1 and measure protein export efficiency (e.g., secretion of alkaline phosphatase or beta-lactamase) in the presence and absence of PMF (using CCCP). Compare translocation rates to wild type and to secD mutants.
Hypothesis: SecF in P. aeruginosa forms a functional SecDF complex that enhances PMF-dependent protein translocation, analogous to E. coli and T. thermophilus.
Experiment: Generate point mutations in the conserved Asp and Arg residues of P. aeruginosa SecF (identified by alignment with T. thermophilus SecDF). Assay protein export and proton conductance in reconstituted proteoliposomes.
Hypothesis: The conserved Asp and Arg residues in the SecF transmembrane region are essential for proton-coupled translocation in P. aeruginosa.
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