ProtNLM2 External predictions
View prediction review YAML · OMA1-protnlm-predictions-review.yaml · Review status: COMPLETE
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
Review score: 2 = concordant with evidence; 1 = uncertain; 0 = discordant with evidence. This is an assessment score, not a model probability.
LSP — Less precise than existing annotation Review score: 2/2
Prediction method: ProtNLM2 · Version: UniProt API snapshot 2026-09-08
Review rationale: Human-cell experiments establish that OMA1 is the zinc metalloprotease that cleaves OPA1 (PMID:20038677) and DELE1, and the horse sequence retains the HExxH catalytic motif and third zinc ligand at 66.47% overall paired identity, so the proteolysis claim is a justified transfer and is biologically correct. It is not novel, since GO:0006508 is already in horse GOA (InterPro2GO). It is, however, materially less specific than the gene's accepted core process GO:0034982 mitochondrial protein processing (also in horse GOA), which is_a protein processing is_a proteolysis (OLS4 ancestry). The gene review accordingly replaces GO:0006508 with GO:0034982. Training-set membership is unknown.
Supporting Evidence:
- file:human/OMA1/OMA1-uniprot.txt: "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}."
- file:HORSE/OMA1/OMA1-bioinformatics/RESULTS.md: "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."
- PMID:20038677: "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."
- PMID:25275009: "Activated OMA1 cleaved the dynamin-like GTPase, optical nerve atrophy 1, an event that is critical for remodeling of mitochondrial cristae."