opa1

Summary: Opa1 performs GTP-dependent mitochondrial membrane fusion.

Reason: Opa1 is the conserved inner-membrane fusion GTPase. The zebrafish depletion study supports mitochondrial remodeling, and ortholog biochemistry supplies the molecular mechanism; broad membrane/mitochondrial fusion terms remain valid alongside the inner-membrane-specific term.

Summary: Mitochondrial membrane is a valid broader localization for Opa1.

Reason: The inner mitochondrial membrane is within the scope of mitochondrial membrane. Specific localization does not invalidate its parent; PAINT places this localization at the OPA1-family node PTN007514526.

Summary: The ancestral peroxisome fission inference remains unresolved for zebrafish Opa1.

Reason: Independent PANTHER v19 tree retrieval places Q5U3A7 below PTN008520527 and OPA1 node PTN007514526. Current PAINT has the corresponding IBD at PTN008520527; this is an ancestral claim, not a pairwise transfer invalidated by a different donor name. The shared EAT-3 OpenScientist report identifies native IMS topology and domain divergence as mechanistic concerns. These are relevant biological arguments, but the report does not resolve loss of this ancestrally placed function in OPA1. A negative assay is not required to reject an IBA; here the lineage and domain premises offered for rejection did not withstand independent checks. Preserve uncertainty pending adjudication of inheritance or loss in the OPA1 clade. Moreover, PMID:32228866 Fig. 1A explicitly identifies an OPA1 middle domain and GED, contradicting the report's inference of GED loss from missing database domain labels.

Summary: The Opa1 catalytic machinery acts in the mitochondrial intermembrane space.

Reason: The soluble processed form occupies the intermembrane space and cooperates with inner-membrane-anchored Opa1. This inherited OPA1 localization is supported by the target record and PTN007514526; the long form does not exclude the soluble form.

Summary: The ancestral microtubule binding inference remains unresolved for zebrafish Opa1.

Reason: Independent PANTHER v19 tree retrieval places Q5U3A7 below PTN000170013 and OPA1 node PTN007514526. Current PAINT has the corresponding IBD at PTN000170013; this is an ancestral claim, not a pairwise transfer invalidated by a different donor name. The shared EAT-3 OpenScientist report identifies native IMS topology and domain divergence as mechanistic concerns. These are relevant biological arguments, but the report does not resolve loss of this ancestrally placed function in OPA1. A negative assay is not required to reject an IBA; here the lineage and domain premises offered for rejection did not withstand independent checks. Preserve uncertainty pending adjudication of inheritance or loss in the OPA1 clade. Moreover, PMID:32228866 Fig. 1A explicitly identifies an OPA1 middle domain and GED, contradicting the report's inference of GED loss from missing database domain labels.

Summary: GTP hydrolysis is part of the core Opa1 membrane-remodeling mechanism.

Reason: Opa1 itself consumes GTP by hydrolysis while driving membrane fusion. GTPase activity and GTP metabolic process are valid broader descriptions of work performed by the protein; a more specific fusogenic term does not make them over-annotations.

Summary: Opa1 binds GTP as the substrate of its dynamin-like GTPase domain.

Reason: Nucleotide binding is intrinsic to the conserved hydrolytic fusion mechanism, not a secondary developmental effect.

Summary: Long Opa1 is anchored in the mitochondrial inner membrane.

Reason: The long/short processing system positions Opa1 at the inner membrane and adjacent intermembrane space, matching the membrane-fusion machinery.

Summary: The Opa1 catalytic machinery acts in the mitochondrial intermembrane space.

Reason: The soluble processed form occupies the intermembrane space and cooperates with inner-membrane-anchored Opa1. This inherited OPA1 localization is supported by the target record and PTN007514526; the long form does not exclude the soluble form.

Summary: Opa1 performs GTP-dependent mitochondrial membrane fusion.

Reason: Opa1 is the conserved inner-membrane fusion GTPase. The zebrafish depletion study supports mitochondrial remodeling, and ortholog biochemistry supplies the molecular mechanism; broad membrane/mitochondrial fusion terms remain valid alongside the inner-membrane-specific term.

Summary: GTP hydrolysis is part of the core Opa1 membrane-remodeling mechanism.

Reason: Opa1 itself consumes GTP by hydrolysis while driving membrane fusion. GTPase activity and GTP metabolic process are valid broader descriptions of work performed by the protein; a more specific fusogenic term does not make them over-annotations.

Summary: Long Opa1 is anchored in the mitochondrial inner membrane.

Reason: The long/short processing system positions Opa1 at the inner membrane and adjacent intermembrane space, matching the membrane-fusion machinery.

Summary: The Opa1 catalytic machinery acts in the mitochondrial intermembrane space.

Reason: The soluble processed form occupies the intermembrane space and cooperates with inner-membrane-anchored Opa1. This inherited OPA1 localization is supported by the target record and PTN007514526; the long form does not exclude the soluble form.

Summary: Opa1 has a conserved, context-specific role in supporting IL-17 production.

Reason: The actual ISS donor is mouse Opa1 P58281, with IMP evidence from PMID:36171294. Its T-cell-specific deletion reduces IL-17A independently of cell division, early activation, and restored respiration; OPA1-dependent metabolic signaling therefore supports cytokine output. Ortholog transfer to zebrafish is plausible but remains an inference, and this immune context is noncore relative to membrane remodeling.

Summary: The donor study supports IL-17 effector output more clearly than Th17 lineage commitment.

Reason: Full PMID:36171294 explicitly distinguishes impaired IL-17A production from intact early lineage-specifying transcription-factor expression. Late effects on maintenance and RORgamma-t do not by themselves demonstrate the initial lineage-commitment step. Retain the biological immune effect using positive regulation of IL-17 production, also already represented by its own source annotation; no additional NEW row is proposed.

Proposed replacements: positive regulation of interleukin-17 production

Summary: Opa1 assemblies deform and tubulate mitochondrial inner membranes.

Reason: Conserved OPA1 helical assembly and membrane engagement perform physical membrane remodeling. These ISS terms describe the direct molecular mechanism underlying cristae architecture and fusion, rather than a phenotype-only inference.

Summary: Opa1 assemblies deform and tubulate mitochondrial inner membranes.

Reason: Conserved OPA1 helical assembly and membrane engagement perform physical membrane remodeling. These ISS terms describe the direct molecular mechanism underlying cristae architecture and fusion, rather than a phenotype-only inference.

Summary: Opa1 performs GTP-dependent mitochondrial membrane fusion.

Reason: Opa1 is the conserved inner-membrane fusion GTPase. The zebrafish depletion study supports mitochondrial remodeling, and ortholog biochemistry supplies the molecular mechanism; broad membrane/mitochondrial fusion terms remain valid alongside the inner-membrane-specific term.

Summary: Opa1 performs GTP-dependent mitochondrial membrane fusion.

Reason: Opa1 is the conserved inner-membrane fusion GTPase. The zebrafish depletion study supports mitochondrial remodeling, and ortholog biochemistry supplies the molecular mechanism; broad membrane/mitochondrial fusion terms remain valid alongside the inner-membrane-specific term.

Summary: Zebrafish Opa1 supports ventricular cardiomyocyte growth and morphology.

Reason: The full Tom70 paper directly tests Opa1 knockdown in zebrafish: Fig. 6H shows enlarged ventricular myocytes at 2 dpf, with fragmented mitochondria and blurred cristae. This is genuine target evidence despite the Tom70-focused title. Retain the contextual cardiac-development annotation without treating the experiment as proof of a dedicated early cardiac-lineage program.

Summary: Opa1 performs GTP-dependent mitochondrial membrane fusion.

Reason: Opa1 is the conserved inner-membrane fusion GTPase. The zebrafish depletion study supports mitochondrial remodeling, and ortholog biochemistry supplies the molecular mechanism; broad membrane/mitochondrial fusion terms remain valid alongside the inner-membrane-specific term.

Summary: GTP hydrolysis is part of the core Opa1 membrane-remodeling mechanism.

Reason: Opa1 itself consumes GTP by hydrolysis while driving membrane fusion. GTPase activity and GTP metabolic process are valid broader descriptions of work performed by the protein; a more specific fusogenic term does not make them over-annotations.

Summary: phosphatidic acid binding supports Opa1 membrane remodeling.

Reason: The actual human OPA1 donor has direct liposome-binding evidence in PMID:20185555 Fig. 2A: OPA1-S1 binds phosphatidic-acid-containing liposomes and binding stimulates GTP hydrolysis. This is a real molecular capacity despite cardiolipin being the likely predominant physiological lipid. The zebrafish ISS assertion is retained as conserved membrane-remodeling capacity; target biochemical specificity remains inferred.

Summary: cardiolipin binding supports Opa1 membrane remodeling.

Reason: The curated ISS assertion concerns lipid engagement of the conserved OPA1 membrane-remodeling machinery. Cardiolipin engagement is explicit in the target record; phosphatidic-acid specificity is transferred by curator judgment rather than measured in the zebrafish developmental paper. Neither specificity is excluded by Opa1 having a fusion role.

Summary: Opa1 maintains mitochondrial morphology in zebrafish.

Reason: The full target study reports fragmented mitochondria after opa1 depletion, consistent with direct membrane-fusion/remodeling work. Mitochondrion organization is a valid core parent process.

Summary: Opa1 function supports zebrafish embryonic development.

Reason: The target study documents growth delay, smaller eyes, edema and impaired cardiac/locomotor performance after depletion. These developmental requirements are retained as context-specific consequences of mitochondrial function; they are not added to the core molecular-function summary.