CG34117 encodes a small (101 aa) mitochondrial protein of the animal FMC1 family (PANTHER PTHR31716:SF1), the Drosophila ortholog of human FMC1 (C7orf55). It is a non-catalytic assembly factor for mitochondrial ATP synthase (complex V). Human FMC1 is in the same PANTHER subfamily and aligns collinearly with the fly protein over its whole length. It localizes to mitochondria and binds the F1-assembly chaperone ATPAF2. Its loss destabilizes the F1 alpha and beta subunits and lowers the amount and activity of assembled complex V. The fly protein is therefore expected to support assembly of the F1 catalytic sector inside mitochondria. Yeast Fmc1 is a functional analog in a separate PANTHER family, with no detectable sequence homology. No fly-specific localization, interaction or assembly experiment has been reported.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0003674 molecular_function | ND GO_REF:0000015 | ACCEPT | Summary: No specific molecular-function term can yet be assigned. The only characterized subfamily member, human FMC1, is known to bind the F1-assembly factor ATPAF2, which supports no informative MF term beyond protein binding. Reason: A literature search found no study of CG34117 itself. The human ortholog's known molecular property, co-immunoprecipitation with ATPAF2, would map only to bare protein binding, which repo policy treats as uninformative. FMC1 is not a catalytic subunit, so no enzymatic activity is implied. Keeping the ND root is correct until a specific activity is defined. Supporting Evidence: file:DROME/CG34117/CG34117-deep-research-falcon.md Searches using the exact accession and gene symbol identified **no peer-reviewed study directly characterizing CG34117/Q0KI97** PMID:28719601 In two replicates, we observed only a single high-abundance endogenous binding partner: ATPAF2, a known assembly factor the F1 ATP synthase |
| GO:0005739 mitochondrion | IBA GO_REF:0000033 | ACCEPT | Summary: Mitochondrial residence is inherited from PAINT node PTN001271866, which is grounded on human FMC1 (Q96HJ9) in the same PANTHER subfamily. Reason: CG34117 and human FMC1 are both in PTHR31716:SF1 and align collinearly at about 41% identity. Human FMC1 was shown to be mitochondrial by immunostaining of the endogenous protein. The IBA donor is the right one, an in-subfamily ortholog with direct experimental localization. This is unlike the yeast-based ISS rows, whose donor sits in a different PANTHER family. No fly localization assay exists. Supporting Evidence: PMID:28719601 First, we confirmed mitochondrial localization (Fig 6A) by immunostaining with antibodies to endogenous C7orf55 file:DROME/CG34117/CG34117-bioinformatics/RESULTS-rereview.md CG34117 and human FMC1 are in the same PANTHER family and subfamily. |
| GO:0005759 mitochondrial matrix | ISS GO_REF:0000024 | UNDECIDED | Summary: The matrix sub-compartment is plausible, but the only basis for it is yeast Fmc1 (P40491). Yeast Fmc1 is in a different PANTHER family and shows no detectable sequence homology to the animal FMC1 proteins. Reason: The ISS donor P40491 is classified in PANTHER PTHR28015, whereas CG34117 and human FMC1 are in PTHR31716. The paper that characterized human FMC1 states that the human and yeast proteins have no BLASTP-detectable homology. They share only an LYRM-type Pfam assignment, so the similarity-based transfer has no sequence basis. Yeast Fmc1 is a soluble matrix protein. Human FMC1 binds ATPAF2, and the F1 assembly that ATPAF2 assists takes place on the matrix side. Matrix localization of CG34117 is therefore likely. However, no experiment places any PTHR31716 member in the matrix rather than at the matrix face of the inner membrane. The location is kept as UNDECIDED rather than accepted, and the with/from is flagged for the source to check. Supporting Evidence: PMID:28719601 these short human and yeast proteins have no sequence homology detectable via BLASTP file:DROME/CG34117/CG34117-bioinformatics/RESULTS-rereview.md Yeast Fmc1 is in a different PANTHER family (PTHR28015). PMID:11096112 Fmc1p is a soluble protein located in the mitochondrial matrix. |
| GO:0033615 mitochondrial proton-transporting ATP synthase complex assembly | IBA GO_REF:0000033 | ACCEPT | Summary: Complex V assembly is the core process. It is inherited from PAINT node PTN001271866 and grounded on human FMC1 knockout and rescue data together with FMC1 binding to the F1 assembly factor ATPAF2. Reason: Human FMC1 (Q96HJ9) is in the same PANTHER subfamily as CG34117 and aligns with it over its whole length. FMC1 knockout specifically destabilized complex V, reducing F1 alpha and beta subunit levels, assembled complex V and in-gel ATPase activity. Re-expression rescued every defect. FMC1 also co-immunoprecipitates with ATPAF2, a dedicated F1 assembly factor. FMC1 is therefore part of the assembly machinery itself, not a downstream requirement. That meets the participation bar for an assembly process. The yeast temperature dependence is not transferred, because yeast Fmc1 is a separate-family analog. Supporting Evidence: PMID:28719601 in the absence of C7orf55 we observed a specific destabilization of the mitochondrial complex V using three assays PMID:28719601 All the defects in complex V were entirely rescued by the reintroduction of a CRISPR-resistant version of C7orf55 file:DROME/CG34117/CG34117-bioinformatics/RESULTS-rereview.md CG34117 and human FMC1 are in the same PANTHER family and subfamily. |
| GO:0033615 mitochondrial proton-transporting ATP synthase complex assembly | ISS GO_REF:0000024 | ACCEPT | Summary: This is the same claim as the IBA row. The ISS donor is the in-subfamily human ortholog FMC1. Reason: Like the IBA, this FlyBase ISS uses human FMC1 (Q96HJ9) as its donor. Q96HJ9 is in the same PANTHER subfamily and has direct knockout, rescue and ATPAF2-binding evidence for complex V assembly. The two rows reinforce each other. Supporting Evidence: PMID:28719601 in the absence of C7orf55 we observed a specific destabilization of the mitochondrial complex V using three assays PMID:28719601 specifically that C7orf55 binds a known assembly factor of this complex |
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Download this section (compressed HTML)Q: Does CG34117 bind the fly ATPAF2 ortholog, as human FMC1 binds ATPAF2, and does it sit in the soluble matrix or at the matrix face of the inner membrane?
Q: Do animal FMC1 (PTHR31716) and yeast Fmc1 (PTHR28015) share LYRM ancestry, or did they converge on similar roles? Should yeast-based transfers to animal FMC1 proteins be withdrawn?
Experiment: Knock down CG34117 by RNAi in fly tissue or S2 cells, then assess complex V by blue-native PAGE with in-gel ATPase activity and measure ATP5A/ATP5B levels, rescuing with an RNAi-resistant transgene.
Experiment: Tag CG34117 at its endogenous locus and use mitochondrial subfractionation with protease protection to place it in the matrix or at the inner membrane. Co-immunoprecipitate it to test binding to the fly ATPAF2 ortholog.
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