SecA is the essential ATP-driven motor protein of the bacterial Sec translocase (EC 7.4.2.8) that powers post-translational protein secretion through the SecYEG channel. As a P-type polypeptide translocase ATPase, SecA couples ATP binding and hydrolysis to mechanical translocation of preproteins bearing N-terminal signal peptides across the cytoplasmic membrane. The protein cycles between cytoplasmic and membrane-associated states, interacting with the SecYEG preprotein-conducting channel to drive stepwise translocation of polypeptide chains. SecA undergoes conformational changes upon nucleotide binding and hydrolysis that push polypeptide segments through SecYEG. In B. subtilis, SecA localizes to discrete membrane-proximal "secretion zones" during high-level secretion of proteins like alpha-amylase. The protein functions as part of the holotranslocon complex comprising SecYEG with SecDF-YajC and YidC, and cooperates with TerC family proteins (MeeF/MeeY) for co-translocational metalation of secreted enzymes. SecA binds zinc as a cofactor through a C-terminal SEC-C motif and contains helicase-like ATP-binding domains characteristic of the superfamily 2 helicases. The protein can exist as both monomers and various homodimeric forms, with a single SecA monomer interacting with SecY in the functional translocation channel. SecA is essential for bacterial viability and has been proposed as an antibiotic target.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005886 plasma membrane | IBA GO_REF:0000033 | ACCEPT | Summary: SecA is a peripheral membrane protein that associates with the plasma membrane on the cytoplasmic side during active protein translocation. UniProt states SecA is localized to Cell membrane as a Peripheral membrane protein on the Cytoplasmic side with experimental evidence from PMID:27362352. The deep research confirms SecA binds to the inner leaflet and SecYEG at the cytoplasmic membrane and cycles into a membrane-inserted state during active translocation. Reason: Plasma membrane localization is well-established for SecA as part of its core function in protein translocation. SecA cycles between cytoplasm and membrane, associating with the membrane during translocation via SecYEG interaction. IBA annotation is appropriate and consistent with experimental evidence. Supporting Evidence: file:BACSU/secA/secA-deep-research-falcon.md SecA is cytosolic but binds to the inner leaflet and SecYEG at the cytoplasmic membrane; it cycles into a membrane-inserted state during active translocation and interacts with anionic phospholipids |
| GO:0005524 ATP binding | IBA GO_REF:0000033 | ACCEPT | Summary: ATP binding is a core molecular function of SecA. The protein contains well-characterized ATP-binding sites with multiple residues directly involved in nucleotide coordination. Mutagenesis of K106 abolishes activity (PMID:8440733). Crystal structures demonstrate ADP/ATP binding. Reason: ATP binding is fundamental to SecA function as an ATPase motor. The protein belongs to the superfamily 2 helicases with helicase-like ATP-binding domains (IPR014001, IPR001650). UniProt records multiple ATP binding residues with structural evidence. This is a core function annotation. Supporting Evidence: UniProt:P28366 Has a central role in coupling the hydrolysis of ATP to the transfer of proteins into and across the cell membrane file:BACSU/secA/secA-deep-research-falcon.md ATP binding/hydrolysis by SecA produces conformational changes that push polypeptide segments through SecYEG PMID:12242434 We have determined the crystal structure of SecA with and without magnesium-adenosine diphosphate bound to the high-affinity ATPase site at 3.0 and 2.7 angstrom resolution, respectively |
| GO:0031522 cell envelope Sec protein transport complex | IBA GO_REF:0000033 | ACCEPT | Summary: SecA is an integral component of the Sec protein transport complex. UniProt states SecA is Part of the essential Sec protein translocation apparatus which comprises SecA, SecYEG and auxiliary proteins SecDF. The deep research confirms SecA operates within the holotranslocon as a dynamic secretion machine. Reason: SecA is definitionally a component of the Sec protein transport complex. This cellular component annotation accurately captures SecA's localization as part of the functional translocase machinery at the membrane. The IBA annotation is appropriate. Supporting Evidence: UniProt:P28366 Part of the essential Sec protein translocation apparatus which comprises SecA, SecYEG and auxiliary proteins SecDF file:BACSU/secA/secA-deep-research-falcon.md The functional secretion unit in Gram-positive bacteria (holotranslocon) comprises SecYEG with SecDF-YajC and YidC; SecA powers translocation into/through SecYEG |
| GO:0043952 protein transport by the Sec complex | IBA GO_REF:0000033 | ACCEPT | Summary: SecA drives protein transport through the Sec complex as the ATP-dependent motor. The deep research states SecA has a central role in coupling the hydrolysis of ATP to the transfer of proteins into and across the cell membrane, serving as an ATP-driven molecular motor driving the stepwise translocation of polypeptide chains across the membrane. Reason: This biological process annotation accurately captures the primary function of SecA - driving protein transport through the Sec translocase. SecA is the motor that powers Sec-dependent translocation. This is a core function. Supporting Evidence: UniProt:P28366 Has a central role in coupling the hydrolysis of ATP to the transfer of proteins into and across the cell membrane, serving as an ATP-driven molecular motor driving the stepwise translocation of polypeptide chains across the membrane file:BACSU/secA/secA-deep-research-falcon.md SecA is the ATP-driven motor of the bacterial Sec translocase that post-translationally drives preprotein movement through the SecYEG channel PMID:12242434 The SecA adenosine triphosphatase (ATPase) mediates extrusion of the amino termini of secreted proteins from the eubacterial cytosol based on cycles of reversible binding to the SecYEG translocon |
| GO:0000166 nucleotide binding | IEA GO_REF:0000043 | ACCEPT | Summary: SecA binds nucleotides (ATP/ADP) as part of its catalytic cycle. This IEA annotation from UniProtKB keyword mapping is accurate but too general compared to the more specific GO:0005524 (ATP binding) annotations also present. Reason: While this annotation is correct, it is broader than the ATP binding annotations already present. Since duplicates with different evidence codes are acceptable and this IEA provides complementary computational evidence, it can be retained. The annotation is not wrong, just less specific than the IBA ATP binding annotation. Supporting Evidence: UniProt:P28366 Has a central role in coupling the hydrolysis of ATP to the transfer of proteins into and across the cell membrane PMID:12242434 We have determined the crystal structure of SecA with and without magnesium-adenosine diphosphate bound to the high-affinity ATPase site at 3.0 and 2.7 angstrom resolution, respectively |
| GO:0005524 ATP binding | IEA GO_REF:0000120 | ACCEPT | Summary: This is a duplicate ATP binding annotation with IEA evidence from combined automated annotation. The IBA annotation with the same GO ID provides phylogenetically-based evidence for the same function. Reason: Duplicate annotations with different evidence codes are acceptable. This IEA annotation provides complementary computational support for the core ATP binding function of SecA. Supporting Evidence: UniProt:P28366 Has a central role in coupling the hydrolysis of ATP to the transfer of proteins into and across the cell membrane, serving as an ATP-driven molecular motor |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | ACCEPT | Summary: SecA is a cytoplasmic protein that cycles to the membrane during active translocation. UniProt states subcellular location includes Cytoplasm with the note Distribution is 50-50 between cytoplasm and membrane. The deep research confirms SecA is cytosolic but binds to the inner leaflet and SecYEG at the cytoplasmic membrane. Reason: Cytoplasmic localization is accurate - SecA exists in equilibrium between cytoplasm and membrane. The protein is soluble in the cytoplasm and peripherally associates with the membrane during translocation. Supporting Evidence: UniProt:P28366 Note=Distribution is 50-50 file:BACSU/secA/secA-deep-research-falcon.md SecA is cytosolic but binds to the inner leaflet and SecYEG at the cytoplasmic membrane; it cycles into a membrane-inserted state during active translocation |
| GO:0005886 plasma membrane | IEA GO_REF:0000120 | ACCEPT | Summary: This is a duplicate plasma membrane annotation with IEA evidence. The IBA annotation with the same GO ID is also present with phylogenetic evidence. Reason: Duplicate annotations with different evidence codes are acceptable. Both IBA and IEA evidence support plasma membrane localization as a core aspect of SecA function. Supporting Evidence: file:BACSU/secA/secA-deep-research-falcon.md SecA is cytosolic but binds to the inner leaflet and SecYEG at the cytoplasmic membrane |
| GO:0006605 protein targeting | IEA GO_REF:0000120 | ACCEPT | Summary: SecA is involved in targeting preproteins to the translocation apparatus. The protein recognizes signal peptide-bearing preproteins and delivers them to SecYEG for translocation. This is part of the broader Sec-dependent secretion pathway. Reason: Protein targeting is a valid biological process for SecA, as it recognizes and directs preproteins to the SecYEG channel. This is broader than but consistent with the more specific "protein transport by the Sec complex" annotation. Supporting Evidence: file:BACSU/secA/secA-deep-research-falcon.md SecA recognizes preproteins with N-terminal signal peptides that engage the lateral gate of SecY |
| GO:0006886 intracellular protein transport | IEA GO_REF:0000002 | ACCEPT | Summary: SecA participates in intracellular protein transport by moving preproteins from the cytoplasm to the membrane/extracellular space via SecYEG. This InterPro-derived annotation captures the transport function. Reason: This annotation is accurate but very general. SecA does participate in intracellular protein transport as part of the Sec pathway. The more specific annotation "protein transport by the Sec complex" (GO:0043952) better captures the specificity of SecA function, but this broader term is not incorrect. Supporting Evidence: UniProt:P28366 Has a central role in coupling the hydrolysis of ATP to the transfer of proteins into and across the cell membrane |
| GO:0008564 protein-exporting ATPase activity | IEA GO_REF:0000003 | ACCEPT | Summary: This is the most specific and accurate molecular function annotation for SecA. EC 7.4.2.8 maps to protein-exporting ATPase activity. UniProt records the catalytic activity with experimental evidence from PMID:8440733. Reason: This is the core molecular function of SecA. The EC number 7.4.2.8 corresponds to protein-translocating ATPase activity. SecA couples ATP hydrolysis to the mechanical work of pushing polypeptides through SecYEG. This annotation should be retained as a core function. Supporting Evidence: UniProt:P28366 Reaction=ATP + H2O + cellular proteinSide 1 = ADP + phosphate + cellular proteinSide 2.; EC=7.4.2.8 file:BACSU/secA/secA-deep-research-falcon.md SecA is a P-type polypeptide translocase ATPase (EC 7.4.2.8) that couples ATP hydrolysis to mechanical translocation of mostly unfolded preproteins bearing N-terminal signal peptides across the cytoplasmic membrane via SecYEG PMID:12242434 The SecA adenosine triphosphatase (ATPase) mediates extrusion of the amino termini of secreted proteins from the eubacterial cytosol based on cycles of reversible binding to the SecYEG translocon |
| GO:0016887 ATP hydrolysis activity | IDA PMID:12242434 Nucleotide control of interdomain interactions in the confor... | NEW | Summary: The 2002 crystal structures of B. subtilis SecA (PDB 1M6N apo and 1M74 with Mg-ADP) resolved the high-affinity ATPase site occupied by magnesium-ADP, the product of ATP hydrolysis, and defined SecA as an ATPase whose tandem motor (DEAD-box helicase-like) domains are modulated by nucleotide binding. This structure is the first experimental-grade evidence for SecA in this file (no experimental GO annotation of any aspect previously existed; all prior annotations are IBA/IEA), so ATP hydrolysis activity is added as a NEW annotation directly supported by the structure. Reason: SecA is the ATPase motor of the Sec translocase; the crystal structures capture magnesium-ADP (the hydrolysis product) bound at the high-affinity ATPase site and identify SecA's helicase-like motor domains, providing direct structural evidence for ATP hydrolysis activity (GO:0016887). No existing annotation in this file captures ATP hydrolysis activity per se (GO:0008564 protein-exporting ATPase activity is the coupled-transport enzyme term), so this MF term is added. Supporting Evidence: PMID:12242434 The SecA adenosine triphosphatase (ATPase) mediates extrusion of the amino termini of secreted proteins from the eubacterial cytosol based on cycles of reversible binding to the SecYEG translocon PMID:12242434 We have determined the crystal structure of SecA with and without magnesium-adenosine diphosphate bound to the high-affinity ATPase site at 3.0 and 2.7 angstrom resolution, respectively |
| GO:0015031 protein transport | IEA GO_REF:0000043 | ACCEPT | Summary: SecA is involved in protein transport as the motor driving secretion through SecYEG. This annotation is accurate but very general compared to the more specific "protein transport by the Sec complex" (GO:0043952). Reason: This general protein transport annotation is accurate. SecA mediates protein transport across membranes. While less specific than GO:0043952, it is not incorrect and provides keyword-based evidence. Supporting Evidence: UniProt:P28366 Has a central role in coupling the hydrolysis of ATP to the transfer of proteins into and across the cell membrane, serving as an ATP-driven molecular motor driving the stepwise translocation of polypeptide chains across the membrane |
| GO:0016020 membrane | IEA GO_REF:0000002 | ACCEPT | Summary: SecA associates with membranes as a peripheral membrane protein. This InterPro-derived annotation is accurate but very general - the more specific GO:0005886 (plasma membrane) annotations are also present. Reason: This general membrane annotation is technically correct but less informative than the specific plasma membrane annotations. It can be retained as complementary evidence from InterPro. Supporting Evidence: file:BACSU/secA/secA-deep-research-falcon.md SecA is cytosolic but binds to the inner leaflet and SecYEG at the cytoplasmic membrane |
| GO:0017038 protein import | IEA GO_REF:0000002 | REMOVE | Summary: This annotation appears to be an error or overly generic mapping from InterPro. SecA is involved in protein EXPORT (secretion) not import. The Sec pathway translocates proteins from the cytoplasm to the periplasm/extracellular space, which is export, not import. Reason: SecA is a protein EXPORTER, not importer. The Sec translocase moves preproteins from the cytoplasm out through the membrane. "Protein import" implies movement into the cytoplasm, which is the opposite of SecA's function. This annotation should be removed as it is misleading. Supporting Evidence: UniProt:P28366 Reaction=ATP + H2O + cellular proteinSide 1 = ADP + phosphate + cellular proteinSide 2.; EC=7.4.2.8 file:BACSU/secA/secA-deep-research-falcon.md SecA is a P-type polypeptide translocase ATPase that couples ATP hydrolysis to mechanical translocation of mostly unfolded preproteins bearing N-terminal signal peptides across the cytoplasmic membrane |
| GO:0045121 membrane raft | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: UniProt records membrane raft localization based on PMID:27362352, which studied flotillin-associated membrane microdomains in B. subtilis. However, the UniProt subunit comment notes SecA only shows some colocalization with FloA or FloT membrane assemblies suggesting limited association with lipid rafts. Reason: The annotation is based on experimental evidence from PMID:27362352, but the evidence indicates only partial colocalization with membrane rafts. This is not a core localization for SecA function - the primary functional location is at SecYEG translocon sites. The membrane raft association may represent a subset of SecA molecules or a regulatory aspect. Supporting Evidence: UniProt:P28366 Only shows some colocalization with FloA or FloT membrane assemblies (PubMed:27362352) |
| GO:0046872 metal ion binding | IEA GO_REF:0000043 | ACCEPT | Summary: SecA binds zinc through its C-terminal SEC-C motif. UniProt records that SecA may bind 1 zinc ion per subunit through conserved cysteine residues. Reason: Metal ion binding (specifically zinc) is a documented property of SecA. The SEC-C motif at the C-terminus contains conserved cysteines that coordinate zinc. While the precise functional role of zinc binding is less clear than the ATPase activity, this is a legitimate molecular function annotation based on structural and sequence evidence. Supporting Evidence: UniProt:P28366 May bind 1 zinc ion per subunit |
| GO:0065002 intracellular protein transmembrane transport | IEA GO_REF:0000104 | ACCEPT | Summary: SecA drives transmembrane transport of proteins through SecYEG. This annotation captures the essence of SecA function - moving proteins across the membrane. The term is appropriate for SecA's role in translocation. Reason: This annotation accurately describes SecA's function in driving protein transport across the cytoplasmic membrane. SecA powers the movement of preproteins through the SecYEG channel, which is intracellular protein transmembrane transport. Supporting Evidence: UniProt:P28366 Has a central role in coupling the hydrolysis of ATP to the transfer of proteins into and across the cell membrane file:BACSU/secA/secA-deep-research-falcon.md SecA couples ATP hydrolysis to mechanical translocation of mostly unfolded preproteins bearing N-terminal signal peptides across the cytoplasmic membrane via SecYEG |
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