id: A0A9L0R9P8
gene_symbol: OMA1
taxon:
  id: NCBITaxon:9796
  label: Equus caballus
status: COMPLETE
description: Assessment of 1 ProtNLM GO predictions for the selected horse OMA1 protein, using mammalian
  experimental findings and an explicit comparison of the horse sequence.
source_documents:
- genes/human/OMA1/OMA1-uniprot.txt
- genes/HORSE/OMA1/OMA1-bioinformatics/RESULTS.md
- projects/PROTNLM_EVALUATION/mammal-benchmark/horse40-predictions.csv
predictions:
- source_method: ProtNLM2
  source_version: UniProt API snapshot 2026-09-08
  predicted_term:
    id: GO:0006508
    label: proteolysis
  predicted_term_type: GO_BP
  review:
    assessment: CNN
    confidence_score: 2
    summary: Human-cell experiments establish OMA1-dependent proteolytic cleavage of OPA1 (PMID:20038677).
      The horse sequence retains the HExxH catalytic motif and third zinc ligand, despite more variable
      terminal regions and 66.47% overall paired identity. The broad proteolysis prediction is a justified
      transfer of the conserved metalloprotease mechanism and exactly overlaps horse GOA. Specific substrate
      or stress-response claims would require their own assessment. Training-set membership is unknown.
    supported_by:
    - reference_id: file:human/OMA1/OMA1-uniprot.txt
      supporting_text: 'CC   -!- FUNCTION: Metalloprotease that is part of the quality control system
        in

        CC       the inner membrane of mitochondria (PubMed:20038677, PubMed:25605331,

        CC       PubMed:32132706, PubMed:32132707). Activated in response to various

        CC       mitochondrial stress, leading to the proteolytic cleavage of target

        CC       proteins, such as OPA1, UQCC3 and DELE1 (PubMed:20038677,

        CC       PubMed:25275009, PubMed:32132706, PubMed:32132707). Involved in the

        CC       fusion of the mitochondrial inner membranes by mediating cleavage of

        CC       OPA1 at S1 position, generating the soluble OPA1 (S-OPA1), which

        CC       cooperates with the membrane form (L-OPA1) to coordinate the fusion of

        CC       mitochondrial inner membranes (PubMed:31922487). Following stress

        CC       conditions that induce loss of mitochondrial membrane potential,

        CC       mediates cleavage of OPA1, leading to excess production of soluble OPA1

        CC       (S-OPA1) and negative regulation of mitochondrial fusion

        CC       (PubMed:20038677, PubMed:25275009). Involved in mitochondrial safeguard

        CC       in response to transient mitochondrial membrane depolarization

        CC       (flickering) by catalyzing cleavage of OPA1, leading to excess

        CC       production of S-OPA1, preventing mitochondrial hyperfusion (By

        CC       similarity). Also acts as a regulator of apoptosis: upon BAK and BAX

        CC       aggregation, mediates cleavage of OPA1, leading to the remodeling of

        CC       mitochondrial cristae and allowing the release of cytochrome c from

        CC       mitochondrial cristae (PubMed:25275009). In depolarized mitochondria,

        CC       may also act as a backup protease for PINK1 by mediating PINK1 cleavage

        CC       and promoting its subsequent degradation by the proteasome

        CC       (PubMed:30733118). May also cleave UQCC3 in response to mitochondrial

        CC       depolarization (PubMed:25605331). Also acts as an activator of the

        CC       integrated stress response (ISR): in response to mitochondrial stress,

        CC       mediates cleavage of DELE1 to generate the processed form of DELE1 (S-

        CC       DELE1), which translocates to the cytosol and activates EIF2AK1/HRI to

        CC       trigger the ISR (PubMed:32132706, PubMed:32132707). Its role in

        CC       mitochondrial quality control is essential for regulating lipid

        CC       metabolism as well as to maintain body temperature and energy

        CC       expenditure under cold-stress conditions (By similarity). Binds

        CC       cardiolipin, possibly regulating its protein turnover (By similarity).

        CC       Required for the stability of the respiratory supercomplexes (By

        CC       similarity). {ECO:0000250|UniProtKB:Q9D8H7,

        CC       ECO:0000269|PubMed:20038677, ECO:0000269|PubMed:25275009,

        CC       ECO:0000269|PubMed:25605331, ECO:0000269|PubMed:30733118,

        CC       ECO:0000269|PubMed:31922487, ECO:0000269|PubMed:32132706,

        CC       ECO:0000269|PubMed:32132707}.'
    - reference_id: file:HORSE/OMA1/OMA1-bioinformatics/RESULTS.md
      supporting_text: The horse sequence A0A9L0R9P8 (513 residues) aligns to human Q96E52 (524 residues)
        with 66.47% identity across 498 paired residues. Paired coverage is 95.04% of the human sequence
        and 97.08% of the horse sequence.
    - reference_id: PMID:20038677
      supporting_text: 'In this study, we show that this inducible cleavage is

        mediated by a zinc metalloprotease called OMA1. We find that OMA1 small

        interfering RNA inhibits inducible cleavage, helps retain fusion competence, and

        slows the onset of apoptosis, showing that OMA1 controls OPA1 cleavage and

        function.'
references:
- id: file:human/OMA1/OMA1-uniprot.txt
  title: UniProt record for human OMA1
  findings: []
- id: file:HORSE/OMA1/OMA1-bioinformatics/RESULTS.md
  title: "OMA1: horse\u2013human sequence comparison"
  findings: []
- id: PMID:20038677
  title: Inducible proteolytic inactivation of OPA1 mediated by the OMA1 protease in mammalian cells.
  findings: []