Horse MIC26 (apolipoprotein O, APOO) is a 198-residue integral protein of the mitochondrial inner membrane and a subunit of the mitochondrial contact site and cristae organising system (MICOS). MICOS is the inner-membrane complex that forms and maintains crista junctions, the narrow necks that join each crista to the inner boundary membrane. The protein is the one-to-one orthologue of human MIC26, to which it is 91% identical over its full length. It has the single ApoO (MIC26/MIC27) domain and one transmembrane helix (residues 110-128). In human cells MIC26 belongs, with its paralogue MIC27 and with MIC10 and MIC13, to the MIC10 subcomplex of MICOS. It joins the complex late in assembly and is not needed to stabilise the other subunits, but loss of MIC26 reduces the number of crista junctions, loss of MIC26 together with MIC27 collapses the cristae, and pathogenic variants of human APOO disrupt cristae. These functions are inferred for the horse protein from the human orthologue; no experiment has been reported on horse MIC26. Despite its historical name, MIC26 is a mitochondrial protein and not a secreted apolipoprotein.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005739 mitochondrion | IEA GO_REF:0000117 | MODIFY | Summary: ARBA rule assigns the mitochondrion to this MIC26/MIC27-family protein. Reason: Correct, but less specific than the evidence supports. The human orthologue spans the inner membrane, and the horse protein keeps the single transmembrane helix at the equivalent position. The specific term, mitochondrial inner membrane, is already on this gene through the SubCell row. Proposed replacements: mitochondrial inner membrane Supporting Evidence: PMID:25764979 The latter isoform spans the mitochondrial inner membrane and physically interacts with several MICOS complex subunits such as MIC60, MIC27, and MIC10. PMID:37279200 we conclude that both MIC26 and MIC27 are exclusively localized in mitochondria and that the observed phenotypes reported previously are exclusively due to their mitochondrial function file:HORSE/SAT1/SAT1-bioinformatics/RESULTS.md PANTHER v19 places A0A5F5PNJ9 in PTHR14564:SF2 "MICOS COMPLEX SUBUNIT MIC26", the same subfamily as human APOO (Q9BUR5) |
| GO:0005743 mitochondrial inner membrane | IEA GO_REF:0000044 | ACCEPT | Summary: UniRule-derived subcellular location 'Mitochondrion inner membrane' mapped to GO. Reason: The most specific location supported. The human orthologue is an integral inner-membrane MICOS subunit, and the horse sequence has its single predicted transmembrane helix at residues 110-128, equivalent to human 108-128. Supporting Evidence: PMID:25764979 The latter isoform spans the mitochondrial inner membrane and physically interacts with several MICOS complex subunits such as MIC60, MIC27, and MIC10. file:HORSE/SAT1/SAT1-uniprot.txt FT TRANSMEM 110..128 |
| GO:0031966 mitochondrial membrane | IEA GO_REF:0000044 | MODIFY | Summary: ARBA-derived generic 'Mitochondrion membrane' location mapped to GO. Reason: Correct but not specific enough. Which membrane is known from the orthologue, the inner membrane, and that term is already on the gene. Proposed replacements: mitochondrial inner membrane Supporting Evidence: PMID:25764979 The latter isoform spans the mitochondrial inner membrane and physically interacts with several MICOS complex subunits such as MIC60, MIC27, and MIC10. |
| GO:0042407 cristae formation | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT family-node inference seeded by human MIC26, whose single and double knockouts reduce crista junction number. Reason: Core process. The horse protein is the one-to-one orthologue of the seed and sits in the same PANTHER subfamily (SF2), so it is inside the clade that inherited the function. MIC26 does part of the work itself as a structural MICOS subunit at the crista junction. Its own deletion costs crista junctions, so this is more than a requirement for the process. A single donor is enough for a small, homogeneous family. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN001803267 · PTHR14564 MIC26/MIC27 IBD node SUPPORTS TRANSFER The node carries only two IBDs, MICOS complex and cristae formation. The horse protein is in SF2 with the human seed. UniProtKB:Q9BUR5 · APOO/MIC26 (Homo sapiens) SUPPORTS TRANSFER Experimental seed (IMP, PMID:25764979; CRISPR knockout, PMID:32788226). Ensembl Compara one-to-one orthologue of the horse gene, 91% identical. Supporting Evidence: PMID:32788226 SKOs and DKO cells have significant reduction in CJs per mitochondrial section. PMID:25764979 MIC26 depletion led to alterations in mitochondrial ultrastructure and caused a significant reduction in the number of crista junctions. file:HORSE/SAT1/SAT1-bioinformatics/RESULTS.md PANTHER v19 places A0A5F5PNJ9 in PTHR14564:SF2 "MICOS COMPLEX SUBUNIT MIC26", the same subfamily as human APOO (Q9BUR5) |
| GO:0042407 cristae formation | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro2GO mapping from the MIC26/MIC27 family entries. Reason: Same claim as the IBA row. Correct family and correct term. Supporting Evidence: file:HORSE/SAT1/SAT1-uniprot.txt DR InterPro; IPR033182; MIC26/MIC27_animal. PMID:32788226 SKOs and DKO cells have significant reduction in CJs per mitochondrial section. |
| GO:0061617 MICOS complex | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT family-node inference seeded by human MIC26 and MIC27 and Drosophila Mic26-27, all of which are MICOS subunits. Reason: MICOS membership is the defining property of every characterised member of PTHR14564. It is shown for the human orthologue by co-immunoprecipitation, radiolabelled import and complexome profiling. The horse protein is in subfamily SF2 with the human MIC26 seed. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN001803267 · PTHR14564 MIC26/MIC27 IBD node SUPPORTS TRANSFER The family-level node. Both mammalian paralogues and the fly protein are MICOS subunits. UniProtKB:Q9BUR5 · APOO/MIC26 (Homo sapiens) SUPPORTS TRANSFER Direct orthologue of the target (same PANTHER subfamily, Compara one-to-one). UniProtKB:Q6UXV4 · APOOL/MIC27 (Homo sapiens) SUPPORTS TRANSFER Paralogue in SF3. Supports the complex-membership term, which is shared across the family. Its cardiolipin binding is not transferred. FB:FBgn0038400 · Mic26-27 (Drosophila melanogaster) SUPPORTS TRANSFER Invertebrate family member. Supports a family-wide MICOS role. Supporting Evidence: PMID:25781180 we show that ApoO is detected in the >1 MDa MIB complex after radiolabelled import into mitochondria and co-immunoprecipitates with Mic60/Mitofilin PMID:25764979 The latter isoform spans the mitochondrial inner membrane and physically interacts with several MICOS complex subunits such as MIC60, MIC27, and MIC10. |
| GO:0061617 MICOS complex | IEA GO_REF:0000120 | ACCEPT | Summary: Combined InterPro/UniRule inference of MICOS complex membership. Reason: Same claim as the IBA row, and correct. Supporting Evidence: PMID:25781180 we show that ApoO is detected in the >1 MDa MIB complex after radiolabelled import into mitochondria and co-immunoprecipitates with Mic60/Mitofilin file:HORSE/SAT1/SAT1-uniprot.txt DR InterPro; IPR033182; MIC26/MIC27_animal. |
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Download this section (compressed HTML)Q: Should the UniProt gene name of A0A5F5PNJ9 be corrected from SAT1 to APOO? Its VGNC (VGNC:22698) and Bgee cross-references belong to the horse SAT1 gene, which overlaps APOO on the opposite strand of chromosome X.
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