FTSH12

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0004176 ATP-dependent peptidase activity	IEA GO_REF:0000002	MARK AS OVER ANNOTATED	Summary: ATP-dependent peptidase activity, inferred from the FtsH (M41) domain architecture via InterPro Reason: FTSH12 is the only subunit of the Ycf2/FtsHi motor that retains the M41 zinc site (HEAGH 769-773 plus D849), so peptidase activity is sequence-compatible, but it has never been measured for FTSH12 and no substrate is known. The H769Y zinc-site mutant fully complements the embryo-lethal knockout, and FTSH12 lacks the hydrophobic pore-loop residues that FtsH proteases use to grip substrates. The essential role is as a motor subunit, not as a protease. Marked as an over-annotation rather than removed, because the catalytic motif is intact and a minor or conditional activity cannot be excluded; it is an inferred-only activity and should not be transferred as an experimentally established function. This matches the verdict on the same rows in the A0A1P8ARD2 gene-model review (genes/ARATH/FTSH12). Supporting Evidence: PMID:30309901 These components are each essential for plant viability and retain the AAA-type ATPase domain, but only FtsH12 contains the zinc binding active site generally conserved among FtsH-type metalloproteases. file:ARATH/FTSH12__Q9SAJ3/FTSH12__Q9SAJ3-bioinformatics/RESULTS.md The M41 protease domain retains the HEAGH zinc motif at 769-773 and the third zinc PMID:30309901 We therefore concluded that, although FtsH12 retains the zinc binding motif, the motif is dispensable for its essential function. PMID:30309901 The absence of conserved hydrophobic residues in the anticipated substrate binding pore loop region of FtsH12 ( Figure 1A ) and the observed relatively weak cross-linking to translocating preprotein ( Supplemental Figure 6C ) suggest a different contribution of FtsH12 compared with the other FtsHi members in the Ycf2/FtsHi complex. PMID:33216923 N-terminome analyses further demonstrated normal proteolytic maturation of plastid-imported proteins irrespective of FTSH12 abundance.
GO:0004176 ATP-dependent peptidase activity	ISS PMID:14630971 Coordinated regulation and complex formation of yellow varie...	MARK AS OVER ANNOTATED	Summary: ATP-dependent peptidase activity, inferred from the FtsH (M41) domain architecture by sequence similarity Reason: FTSH12 is the only subunit of the Ycf2/FtsHi motor that retains the M41 zinc site (HEAGH 769-773 plus D849), so peptidase activity is sequence-compatible, but it has never been measured for FTSH12 and no substrate is known. The H769Y zinc-site mutant fully complements the embryo-lethal knockout, and FTSH12 lacks the hydrophobic pore-loop residues that FtsH proteases use to grip substrates. The essential role is as a motor subunit, not as a protease. Marked as an over-annotation rather than removed, because the catalytic motif is intact and a minor or conditional activity cannot be excluded; it is an inferred-only activity and should not be transferred as an experimentally established function. This matches the verdict on the same rows in the A0A1P8ARD2 gene-model review (genes/ARATH/FTSH12). Supporting Evidence: PMID:30309901 These components are each essential for plant viability and retain the AAA-type ATPase domain, but only FtsH12 contains the zinc binding active site generally conserved among FtsH-type metalloproteases. file:ARATH/FTSH12__Q9SAJ3/FTSH12__Q9SAJ3-bioinformatics/RESULTS.md The M41 protease domain retains the HEAGH zinc motif at 769-773 and the third zinc PMID:30309901 We therefore concluded that, although FtsH12 retains the zinc binding motif, the motif is dispensable for its essential function. PMID:30309901 The absence of conserved hydrophobic residues in the anticipated substrate binding pore loop region of FtsH12 ( Figure 1A ) and the observed relatively weak cross-linking to translocating preprotein ( Supplemental Figure 6C ) suggest a different contribution of FtsH12 compared with the other FtsHi members in the Ycf2/FtsHi complex. PMID:33216923 N-terminome analyses further demonstrated normal proteolytic maturation of plastid-imported proteins irrespective of FTSH12 abundance.
GO:0004222 metalloendopeptidase activity	IBA GO_REF:0000033	MARK AS OVER ANNOTATED	Summary: IBA from PTN008683692, an FtsH-family metalloprotease node seeded by human AFG3L2 and SPG7. Reason: FTSH12 is the only subunit of the Ycf2/FtsHi motor that retains the M41 zinc site (HEAGH 769-773 plus D849), so peptidase activity is sequence-compatible, but it has never been measured for FTSH12 and no substrate is known. The H769Y zinc-site mutant fully complements the embryo-lethal knockout, and FTSH12 lacks the hydrophobic pore-loop residues that FtsH proteases use to grip substrates. The essential role is as a motor subunit, not as a protease. Marked as an over-annotation rather than removed, because the catalytic motif is intact and a minor or conditional activity cannot be excluded; it is an inferred-only activity and should not be transferred as an experimentally established function. This matches the verdict on the same rows in the A0A1P8ARD2 gene-model review (genes/ARATH/FTSH12). The PAINT node placement is reasonable at the level of retained catalytic machinery, which FTSH12 does keep; no target-specific loss of the zinc site has occurred, so the IBA is not removed, only flagged. Propagation Review Root cause: UNRESOLVED Failure modes: FUNCTIONAL DIVERGENCE Sources checked: PANTHER:PTN008683692 UNRESOLVED FtsH-family metalloprotease node seeded by the mitochondrial m-AAA proteases AFG3L2 and SPG7. FTSH12 keeps the HEAGH zinc site and Asp849, so the catalytic machinery the node asserts is present, but the lineage was recruited into the chloroplast import motor, the zinc site is dispensable (H769Y complements) and no FTSH12 protease activity has been measured. Whether the activity was retained cannot be decided from current evidence. Supporting Evidence: PMID:30309901 These components are each essential for plant viability and retain the AAA-type ATPase domain, but only FtsH12 contains the zinc binding active site generally conserved among FtsH-type metalloproteases. file:ARATH/FTSH12__Q9SAJ3/FTSH12__Q9SAJ3-bioinformatics/RESULTS.md The M41 protease domain retains the HEAGH zinc motif at 769-773 and the third zinc PMID:30309901 We therefore concluded that, although FtsH12 retains the zinc binding motif, the motif is dispensable for its essential function. PMID:30309901 The absence of conserved hydrophobic residues in the anticipated substrate binding pore loop region of FtsH12 ( Figure 1A ) and the observed relatively weak cross-linking to translocating preprotein ( Supplemental Figure 6C ) suggest a different contribution of FtsH12 compared with the other FtsHi members in the Ycf2/FtsHi complex. PMID:33216923 N-terminome analyses further demonstrated normal proteolytic maturation of plastid-imported proteins irrespective of FTSH12 abundance.
GO:0004222 metalloendopeptidase activity	IEA GO_REF:0000002	MARK AS OVER ANNOTATED	Summary: Metalloendopeptidase activity from InterPro Peptidase_M41 signatures. Reason: FTSH12 is the only subunit of the Ycf2/FtsHi motor that retains the M41 zinc site (HEAGH 769-773 plus D849), so peptidase activity is sequence-compatible, but it has never been measured for FTSH12 and no substrate is known. The H769Y zinc-site mutant fully complements the embryo-lethal knockout, and FTSH12 lacks the hydrophobic pore-loop residues that FtsH proteases use to grip substrates. The essential role is as a motor subunit, not as a protease. Marked as an over-annotation rather than removed, because the catalytic motif is intact and a minor or conditional activity cannot be excluded; it is an inferred-only activity and should not be transferred as an experimentally established function. This matches the verdict on the same rows in the A0A1P8ARD2 gene-model review (genes/ARATH/FTSH12). Supporting Evidence: PMID:30309901 These components are each essential for plant viability and retain the AAA-type ATPase domain, but only FtsH12 contains the zinc binding active site generally conserved among FtsH-type metalloproteases. file:ARATH/FTSH12__Q9SAJ3/FTSH12__Q9SAJ3-bioinformatics/RESULTS.md The M41 protease domain retains the HEAGH zinc motif at 769-773 and the third zinc PMID:30309901 We therefore concluded that, although FtsH12 retains the zinc binding motif, the motif is dispensable for its essential function. PMID:30309901 The absence of conserved hydrophobic residues in the anticipated substrate binding pore loop region of FtsH12 ( Figure 1A ) and the observed relatively weak cross-linking to translocating preprotein ( Supplemental Figure 6C ) suggest a different contribution of FtsH12 compared with the other FtsHi members in the Ycf2/FtsHi complex. PMID:33216923 N-terminome analyses further demonstrated normal proteolytic maturation of plastid-imported proteins irrespective of FTSH12 abundance.
GO:0005515 protein binding	IPI PMID:30309901 A Ycf2-FtsHi Heteromeric AAA-ATPase Complex Is Required for ...	REMOVE	Summary: IPI with FtsHi5 from the Ycf2/FtsHi complex purification (Kikuchi et al. 2018). Reason: Bare protein binding is uninformative. The interaction itself is real and is captured informatively by part_of GO:0062091 Ycf2/FtsHi complex (IDA, same paper); removal does not mean the reported interaction is false. Supporting Evidence: PMID:30309901 The inner envelope-localized Ycf2, FtsHi1, FtsHi2, FtsHi4, FtsHi5, FtsH12, and pdNAD-MDH proteins therefore form a stable 2-MD complex (the Ycf2/FtsHi complex), which interacts with the translocating preproteins.
GO:0005515 protein binding	IPI PMID:30309901 A Ycf2-FtsHi Heteromeric AAA-ATPase Complex Is Required for ...	REMOVE	Summary: IPI with FtsHi2 from the Ycf2/FtsHi complex purification (Kikuchi et al. 2018). Reason: Bare protein binding is uninformative. The interaction itself is real and is captured informatively by part_of GO:0062091 Ycf2/FtsHi complex (IDA, same paper); removal does not mean the reported interaction is false. Supporting Evidence: PMID:30309901 The inner envelope-localized Ycf2, FtsHi1, FtsHi2, FtsHi4, FtsHi5, FtsH12, and pdNAD-MDH proteins therefore form a stable 2-MD complex (the Ycf2/FtsHi complex), which interacts with the translocating preproteins.
GO:0005515 protein binding	IPI PMID:30309901 A Ycf2-FtsHi Heteromeric AAA-ATPase Complex Is Required for ...	REMOVE	Summary: IPI with pdNAD-MDH from the Ycf2/FtsHi complex purification (Kikuchi et al. 2018). Reason: Bare protein binding is uninformative. The interaction itself is real and is captured informatively by part_of GO:0062091 Ycf2/FtsHi complex (IDA, same paper); removal does not mean the reported interaction is false. Supporting Evidence: PMID:30309901 The inner envelope-localized Ycf2, FtsHi1, FtsHi2, FtsHi4, FtsHi5, FtsH12, and pdNAD-MDH proteins therefore form a stable 2-MD complex (the Ycf2/FtsHi complex), which interacts with the translocating preproteins.
GO:0005515 protein binding	IPI PMID:30309901 A Ycf2-FtsHi Heteromeric AAA-ATPase Complex Is Required for ...	REMOVE	Summary: IPI with FtsHi1 from the Ycf2/FtsHi complex purification (Kikuchi et al. 2018). Reason: Bare protein binding is uninformative. The interaction itself is real and is captured informatively by part_of GO:0062091 Ycf2/FtsHi complex (IDA, same paper); removal does not mean the reported interaction is false. Supporting Evidence: PMID:30309901 The inner envelope-localized Ycf2, FtsHi1, FtsHi2, FtsHi4, FtsHi5, FtsH12, and pdNAD-MDH proteins therefore form a stable 2-MD complex (the Ycf2/FtsHi complex), which interacts with the translocating preproteins.
GO:0005515 protein binding	IPI PMID:30309901 A Ycf2-FtsHi Heteromeric AAA-ATPase Complex Is Required for ...	REMOVE	Summary: IPI with FtsHi4 from the Ycf2/FtsHi complex purification (Kikuchi et al. 2018). Reason: Bare protein binding is uninformative. The interaction itself is real and is captured informatively by part_of GO:0062091 Ycf2/FtsHi complex (IDA, same paper); removal does not mean the reported interaction is false. Supporting Evidence: PMID:30309901 The inner envelope-localized Ycf2, FtsHi1, FtsHi2, FtsHi4, FtsHi5, FtsH12, and pdNAD-MDH proteins therefore form a stable 2-MD complex (the Ycf2/FtsHi complex), which interacts with the translocating preproteins.
GO:0005515 protein binding	IPI PMID:30309901 A Ycf2-FtsHi Heteromeric AAA-ATPase Complex Is Required for ...	REMOVE	Summary: IPI with Ycf2 from the Ycf2/FtsHi complex purification (Kikuchi et al. 2018). Reason: Bare protein binding is uninformative. The interaction itself is real and is captured informatively by part_of GO:0062091 Ycf2/FtsHi complex (IDA, same paper); removal does not mean the reported interaction is false. Supporting Evidence: PMID:30309901 The inner envelope-localized Ycf2, FtsHi1, FtsHi2, FtsHi4, FtsHi5, FtsH12, and pdNAD-MDH proteins therefore form a stable 2-MD complex (the Ycf2/FtsHi complex), which interacts with the translocating preproteins.
GO:0005524 ATP binding	IEA GO_REF:0000002	ACCEPT	Summary: ATP binding inferred from the AAA+ P-loop domain. Reason: FTSH12 retains intact Walker A (GPPGTGKT) and Walker B (FVFVDE) motifs, and the Ycf2/FtsHi motor was resolved by cryo-EM as a heterohexameric AAA+ ATPase. Nucleotide binding by the FTSH12 subunit is well supported by sequence; direct binding measurements on FTSH12 alone are lacking. Supporting Evidence: file:ARATH/FTSH12__Q9SAJ3/FTSH12__Q9SAJ3-bioinformatics/RESULTS.md The AAA+ module retains a canonical Walker A motif (GPPGTGKT, 533-540) and Walker B PMID:39197452 The Ycf2-FtsHi structure reveals a heterohexameric AAA+ ATPase motor module with characteristic features.
GO:0005737 cytoplasm	IEA GO_REF:0000117	MODIFY	Summary: ARBA-predicted cytoplasm. Reason: Not wrong in the broad sense (plastids are within the cytoplasm), but uninformative; experiments place FTSH12 in the chloroplast inner envelope membrane. Proposed replacements: chloroplast inner membrane Supporting Evidence: PMID:33216923 Sub-cellular fractionation and in organello protease protection assays confirmed localization of FtsH12 in the inner envelope of the chloroplast. PMID:33216923 Together, this confirms that FtsH12 is located in the inner chloroplast envelope, with the C-terminal part containing the AAA-type domain and the catalytic domain facing the stroma
GO:0005739 mitochondrion	HDA PMID:28887381 Global Analysis of Membrane-associated Protein Oligomerizati...	MARK AS OVER ANNOTATED	Summary: Mitochondrion from a high-throughput membrane-protein correlation-profiling study. Reason: FTSH12 has a cleaved chloroplast transit peptide (mature N-terminus at Ser51), is immunodetected in chloroplast envelope fractions and is a subunit of the chloroplast Ycf2/FtsHi import motor. No targeted study reports a mitochondrial pool; the HDA call most likely reflects co-fractionation of envelope membranes. The cached paper does not name FTSH12 in its text, so the specific data were not inspected; the row is demoted rather than removed. Supporting Evidence: PMID:33216923 Sub-cellular fractionation and in organello protease protection assays confirmed localization of FtsH12 in the inner envelope of the chloroplast. PMID:30309901 The inner envelope-localized Ycf2, FtsHi1, FtsHi2, FtsHi4, FtsHi5, FtsH12, and pdNAD-MDH proteins therefore form a stable 2-MD complex (the Ycf2/FtsHi complex), which interacts with the translocating preproteins.
GO:0005745 m-AAA complex	IBA GO_REF:0000033	REMOVE	Summary: IBA m-AAA complex from PTN000554085, a eukaryotic mitochondrial m-AAA protease node (AFG3L2, SPG7, Yta10/Yta12 and orthologs). Reason: FTSH12 is not a mitochondrial protein: it resides in the chloroplast inner envelope and is a stable subunit of the 2-MDa Ycf2/FtsHi import motor, and its lineage derives from the plastid (cyanobacterial) FtsH, not from the mitochondrial m-AAA clade. The m-AAA complex is a mitochondrial inner-membrane AFG3L2/SPG7-type assembly; propagating it to a plastid envelope motor subunit is a node-placement/localization overreach with target-specific evidence against it. Propagation Review Root cause: PROPAGATION BAD Failure modes: COMPARTMENT OR COMPLEX MISMATCH Sources checked: PANTHER:PTN000554085 SUPPORTS SOURCE BUT NOT TARGET Mitochondrial m-AAA node; donors are metazoan/yeast mitochondrial proteases. FTSH12 is a plastid-derived chloroplast inner-envelope motor subunit. Supporting Evidence: PMID:33216923 Together, this confirms that FtsH12 is located in the inner chloroplast envelope, with the C-terminal part containing the AAA-type domain and the catalytic domain facing the stroma PMID:30309901 The inner envelope-localized Ycf2, FtsHi1, FtsHi2, FtsHi4, FtsHi5, FtsH12, and pdNAD-MDH proteins therefore form a stable 2-MD complex (the Ycf2/FtsHi complex), which interacts with the translocating preproteins. PMID:30309901 Ycf2, FtsHi1, FtsHi2, FtsHi4, FtsHi5, and FtsH12 are all derived from the chloroplast genome-encoded FtsH in the ancestral cyanobacterial endosymbiont
GO:0005886 plasma membrane	ISM GO_REF:0000122	REMOVE	Summary: AtSubP-predicted plasma membrane. Reason: Computational prediction contradicted by fractionation and protease-protection data placing FTSH12 in the chloroplast inner envelope with a cleaved transit peptide. Supporting Evidence: PMID:33216923 Sub-cellular fractionation and in organello protease protection assays confirmed localization of FtsH12 in the inner envelope of the chloroplast. PMID:33216923 Together, this confirms that FtsH12 is located in the inner chloroplast envelope, with the C-terminal part containing the AAA-type domain and the catalytic domain facing the stroma
GO:0006508 proteolysis	IEA GO_REF:0000002	MARK AS OVER ANNOTATED	Summary: Proteolysis inferred from Peptidase_M41 signatures. Reason: FTSH12 is the only subunit of the Ycf2/FtsHi motor that retains the M41 zinc site (HEAGH 769-773 plus D849), so peptidase activity is sequence-compatible, but it has never been measured for FTSH12 and no substrate is known. The H769Y zinc-site mutant fully complements the embryo-lethal knockout, and FTSH12 lacks the hydrophobic pore-loop residues that FtsH proteases use to grip substrates. The essential role is as a motor subunit, not as a protease. Marked as an over-annotation rather than removed, because the catalytic motif is intact and a minor or conditional activity cannot be excluded; it is an inferred-only activity and should not be transferred as an experimentally established function. This matches the verdict on the same rows in the A0A1P8ARD2 gene-model review (genes/ARATH/FTSH12). Supporting Evidence: PMID:30309901 These components are each essential for plant viability and retain the AAA-type ATPase domain, but only FtsH12 contains the zinc binding active site generally conserved among FtsH-type metalloproteases. file:ARATH/FTSH12__Q9SAJ3/FTSH12__Q9SAJ3-bioinformatics/RESULTS.md The M41 protease domain retains the HEAGH zinc motif at 769-773 and the third zinc PMID:30309901 We therefore concluded that, although FtsH12 retains the zinc binding motif, the motif is dispensable for its essential function. PMID:30309901 The absence of conserved hydrophobic residues in the anticipated substrate binding pore loop region of FtsH12 ( Figure 1A ) and the observed relatively weak cross-linking to translocating preprotein ( Supplemental Figure 6C ) suggest a different contribution of FtsH12 compared with the other FtsHi members in the Ycf2/FtsHi complex. PMID:33216923 N-terminome analyses further demonstrated normal proteolytic maturation of plastid-imported proteins irrespective of FTSH12 abundance.
GO:0009507 chloroplast	HDA PMID:18431481 Sorting signals, N-terminal modifications and abundance of t...	MODIFY	Summary: Chloroplast proteome identification (Zybailov et al. 2008). Reason: Correct but general. Fractionation and protease-protection assays specify the chloroplast inner envelope membrane (GO:0009706, already annotated IDA for this gene). Proposed replacements: chloroplast inner membrane Supporting Evidence: PMID:33216923 Sub-cellular fractionation and in organello protease protection assays confirmed localization of FtsH12 in the inner envelope of the chloroplast.
GO:0009507 chloroplast	IDA PMID:14630971 Coordinated regulation and complex formation of yellow varie...	MODIFY	Summary: Chloroplast localization (Sakamoto et al. 2003 chloroplast FtsH family survey). Reason: Correct but general. Fractionation and protease-protection assays specify the chloroplast inner envelope membrane (GO:0009706, already annotated IDA for this gene). Proposed replacements: chloroplast inner membrane Supporting Evidence: PMID:14630971 We show here that nine FtsH proteins are located in the chloroplasts. PMID:33216923 Sub-cellular fractionation and in organello protease protection assays confirmed localization of FtsH12 in the inner envelope of the chloroplast.
GO:0009507 chloroplast	ISM GO_REF:0000122	MODIFY	Summary: AtSubP-predicted chloroplast localization. Reason: Correct but general. Fractionation and protease-protection assays specify the chloroplast inner envelope membrane (GO:0009706, already annotated IDA for this gene). Proposed replacements: chloroplast inner membrane Supporting Evidence: PMID:33216923 Sub-cellular fractionation and in organello protease protection assays confirmed localization of FtsH12 in the inner envelope of the chloroplast.
GO:0009535 chloroplast thylakoid membrane	IEA GO_REF:0000044	REMOVE	Summary: Chloroplast thylakoid membrane from the UniProt subcellular-location mapping, which cites Sakamoto et al. 2003. Reason: Contradicted by direct evidence: FTSH12 immunosignal is enriched in envelope fractions and absent from thylakoid membranes, and it is a subunit of the inner-envelope Ycf2/FtsHi import motor. The thylakoid assignment appears to derive from the 2003 family survey of FtsH targeting. Supporting Evidence: PMID:33216923 Compared with whole chloroplast extracts, the FtsH12 immunosignal strongly increased in envelope fractions, but was absent in samples of the thylakoid membrane PMID:33216923 Sub-cellular fractionation and in organello protease protection assays confirmed localization of FtsH12 in the inner envelope of the chloroplast.
GO:0009536 plastid	HDA PMID:22923678 Putative glycosyltransferases and other plant Golgi apparatu...	MODIFY	Summary: Plastid localization from LOPIT proteomics. Reason: Correct but general; FTSH12 is an inner-envelope membrane protein, detected also in non-photosynthetic plastids. Replace with GO:0009706 chloroplast inner membrane, which the gene already carries by IDA. Proposed replacements: chloroplast inner membrane Supporting Evidence: PMID:33216923 Sub-cellular fractionation and in organello protease protection assays confirmed localization of FtsH12 in the inner envelope of the chloroplast.
GO:0009706 chloroplast inner membrane	IDA PMID:30309901 A Ycf2-FtsHi Heteromeric AAA-ATPase Complex Is Required for ...	ACCEPT	Summary: Inner envelope localization of FTSH12 as a subunit of the Ycf2/FtsHi complex (Kikuchi et al. 2018). Reason: Independently confirmed by subcellular fractionation and protease-protection assays showing the C-terminal AAA+ and protease domains face the stroma. Supporting Evidence: PMID:30309901 The inner envelope-localized Ycf2, FtsHi1, FtsHi2, FtsHi4, FtsHi5, FtsH12, and pdNAD-MDH proteins therefore form a stable 2-MD complex (the Ycf2/FtsHi complex), which interacts with the translocating preproteins. PMID:33216923 Sub-cellular fractionation and in organello protease protection assays confirmed localization of FtsH12 in the inner envelope of the chloroplast. PMID:33216923 Together, this confirms that FtsH12 is located in the inner chloroplast envelope, with the C-terminal part containing the AAA-type domain and the catalytic domain facing the stroma
GO:0009941 chloroplast envelope	HDA PMID:20061580 AT_CHLORO, a comprehensive chloroplast proteome database wit...	MODIFY	Summary: Chloroplast envelope from the AT_CHLORO proteome. Reason: Correct; the more precise supported location is the inner envelope membrane (GO:0009706, part_of chloroplast envelope). Proposed replacements: chloroplast inner membrane Supporting Evidence: PMID:33216923 Together, this confirms that FtsH12 is located in the inner chloroplast envelope, with the C-terminal part containing the AAA-type domain and the catalytic domain facing the stroma PMID:33216923 Compared with whole chloroplast extracts, the FtsH12 immunosignal strongly increased in envelope fractions, but was absent in samples of the thylakoid membrane
GO:0016464 chloroplast protein-transporting ATPase activity	IDA PMID:30309901 A Ycf2-FtsHi Heteromeric AAA-ATPase Complex Is Required for ...	ACCEPT	Summary: Chloroplast protein-transporting ATPase activity: FTSH12 is an AAA+ subunit of the Ycf2/FtsHi import motor that associates with inner-envelope translocation intermediates in an ATP-dependent manner. Reason: This is the core activity of the Ycf2/FtsHi motor, of which FTSH12 is one of six AAA+ subunits. The evidence is at the level of the complex: ATP-dependent association of FTSH12 with translocating preproteins, the ATP-hydrolysis-requiring complex-bound state, and the heterohexameric motor structure. FTSH12-specific ATPase or pulling contribution is not separately measured, and FTSH12 lacks the conserved pore-loop residues and cross-links weakly to preproteins, so its role may be partly structural (assembly). The term is accepted as the core activity. The qualifier is a separate question: because the evidence attributes the activity to the complex rather than to FTSH12 alone, contributes_to is the better relation, and the core function uses it. The imported enables qualifier is preserved here and queried upstream as a probable WRONG_QUALIFIER source defect rather than changed silently. Supporting Evidence: PMID:30309901 Using this method, we found that, depending on the presence of ATP during import reactions, Ycf2, FtsHi1, FtsHi2, FtsHi4, FtsHi5, and FtsH12 were significantly associated with the translocation intermediates of the model preprotein pFd PMID:30309901 Thus, the transient associations with Ycf2 and FtsHi/FtsH12 proteins are specific to preproteins destined to be translocated across the inner envelope membrane. PMID:30309901 These data indicate that the Ycf2/FtsHi complex-bound state is the ATP-hydrolysis-requiring step for subsequent preprotein translocation across the inner envelope membrane. PMID:39197452 The Ycf2-FtsHi structure reveals a heterohexameric AAA+ ATPase motor module with characteristic features. PMID:30309901 indicating that this protein also evolved to be a Ycf2/FtsHi complex constituent and contribute to the pulling function
GO:0016887 ATP hydrolysis activity	IEA GO_REF:0000002	KEEP AS NON CORE	Summary: ATP hydrolysis activity inferred from the AAA core domain (InterPro). Reason: FTSH12 has intact Walker A/B motifs and is a subunit of a heterohexameric AAA+ motor whose ATP-hydrolysis-dependent step drives preprotein translocation. However, ATP hydrolysis by FTSH12 itself has not been measured, and the informative description of the activity is the motor-level GO:0016464 chloroplast protein-transporting ATPase activity (not an is_a descendant of this term). Kept as a non-core, sequence-inferred activity. Supporting Evidence: file:ARATH/FTSH12__Q9SAJ3/FTSH12__Q9SAJ3-bioinformatics/RESULTS.md The AAA+ module retains a canonical Walker A motif (GPPGTGKT, 533-540) and Walker B PMID:30309901 These data indicate that the Ycf2/FtsHi complex-bound state is the ATP-hydrolysis-requiring step for subsequent preprotein translocation across the inner envelope membrane.
GO:0034982 mitochondrial protein processing	IBA GO_REF:0000033	REMOVE	Summary: IBA mitochondrial protein processing from PTN000554085 (mitochondrial m-AAA protease node). Reason: Mitochondrial protein processing is a function of m-AAA proteases acting in mitochondria. FTSH12 is a chloroplast inner-envelope protein of plastid FtsH origin, has no demonstrated protease activity, its zinc site is dispensable, and N-terminome analysis showed processing of plastid-imported proteins is independent of FTSH12 abundance. Target-specific evidence argues against inheritance of this mitochondrial process. Propagation Review Root cause: PROPAGATION BAD Failure modes: COMPARTMENT OR COMPLEX MISMATCH Sources checked: PANTHER:PTN000554085 SUPPORTS SOURCE BUT NOT TARGET Mitochondrial m-AAA node; donors are metazoan/yeast mitochondrial proteases. FTSH12 is a plastid-derived chloroplast inner-envelope motor subunit. Supporting Evidence: PMID:33216923 Together, this confirms that FtsH12 is located in the inner chloroplast envelope, with the C-terminal part containing the AAA-type domain and the catalytic domain facing the stroma PMID:30309901 Ycf2, FtsHi1, FtsHi2, FtsHi4, FtsHi5, and FtsH12 are all derived from the chloroplast genome-encoded FtsH in the ancestral cyanobacterial endosymbiont PMID:30309901 We therefore concluded that, although FtsH12 retains the zinc binding motif, the motif is dispensable for its essential function. PMID:33216923 N-terminome analyses further demonstrated normal proteolytic maturation of plastid-imported proteins irrespective of FTSH12 abundance.
GO:0045037 protein import into chloroplast stroma	IMP PMID:30309901 A Ycf2-FtsHi Heteromeric AAA-ATPase Complex Is Required for ...	ACCEPT	Summary: Protein import into chloroplast stroma, from Kikuchi et al. 2018. Reason: FTSH12 is a subunit of the motor that performs the ATP-dependent step of preprotein translocation across the inner envelope, and it associates specifically with inner-envelope-destined translocation intermediates. This is participation as part of the import machinery, not only necessity; knockdown also remodels the TIC import apparatus. Supporting Evidence: PMID:30309901 Using this method, we found that, depending on the presence of ATP during import reactions, Ycf2, FtsHi1, FtsHi2, FtsHi4, FtsHi5, and FtsH12 were significantly associated with the translocation intermediates of the model preprotein pFd PMID:30309901 Thus, the transient associations with Ycf2 and FtsHi/FtsH12 proteins are specific to preproteins destined to be translocated across the inner envelope membrane. PMID:30309901 These data indicate that the Ycf2/FtsHi complex-bound state is the ATP-hydrolysis-requiring step for subsequent preprotein translocation across the inner envelope membrane. PMID:33216923 The composition of the translocon on the inner chloroplast membrane (TIC) protein import complex was altered, with coordinated reduction of the FtsH12-FtsHi complex subunits and accumulation of the 1 MDa TIC complex subunits TIC56, TIC214 and TIC22-III.
GO:0062091 Ycf2/FtsHi complex	IDA PMID:30309901 A Ycf2-FtsHi Heteromeric AAA-ATPase Complex Is Required for ...	ACCEPT	Summary: Ycf2/FtsHi complex membership by BN-PAGE co-migration and complex purification. Reason: Directly established in Arabidopsis and tobacco, independently confirmed by Myc-FtsH12 immunoprecipitation, and structurally resolved as a heterohexameric AAA+ motor. Supporting Evidence: PMID:30309901 we found that FtsHi1, FtsHi2, FtsHi4, FtsHi5, Ycf2, and FtsH12 comigrated at ∼2 MD, whereas FtsHi3 was present in a distinct ∼1-MD complex PMID:30309901 The inner envelope-localized Ycf2, FtsHi1, FtsHi2, FtsHi4, FtsHi5, FtsH12, and pdNAD-MDH proteins therefore form a stable 2-MD complex (the Ycf2/FtsHi complex), which interacts with the translocating preproteins. PMID:33216923 Expression of Myc-tagged FtsH12 under its native promotor allowed identification of FtsHi1, 2, 4, and 5, and plastidic NAD-malate dehydrogenase, five of the six interaction partners in the suggested import motor complex. PMID:39197452 The Ycf2-FtsHi structure reveals a heterohexameric AAA+ ATPase motor module with characteristic features.

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