HtrA2 (Omi; Q9VFJ3) notes
Identity
- HtrA-family mitochondrial serine protease (trypsin-like protease domain + PDZ), fly orthologue of HTRA2/Omi (PARK13).
Literature journal
- Mitochondrial; translocates on apoptotic stimuli; cleaves DIAP1 PMID:17397804; stays near mitochondria PMID:17397804.
- IMS protein with IAP-binding motifs; released to cytosol; degrades DIAP1 [PMID:17557079 "a developmentally regulated mitochondrial intermembrane space protein that undergoes processive cleavage, in situ, to generate two distinct inhibitor of apoptosis (IAP) binding motifs"; "dOmi alleviates DIAP1 inhibition of all caspases by proteolytically degrading DIAP1"].
- DIAP1 binds both mature isoforms and ubiquitinates dOmi [PMID:18259196 "DIAP1 was able to bind to both isoforms via its BIR1 and BIR2 domains"; "The binding of DIAP1 to dOmi also resulted in DIAP1-mediated polyubiquitination of dOmi"].
- Rhomboid-7 cleaves Omi precursor; Omi acts downstream of Pink1 (overexpression assays) PMID:19048081.
- Loss of function: dispensable for apoptosis PMID:19282869; mitochondrial integrity role debated - null mutants lack mitochondrial morphology defects PMID:19118185.
- Germ cell death in testis, catalytic not IAP-antagonist PMID:23523076. This GCD is spontaneous elimination of male germ cells in the testis, not death of ectopic/migratory germ cells.
- ABPP serine hydrolase atlas detected HtrA2 activity PMID:33827210.
- Deep research (falcon) failed on the first attempt (OOM / fallback provider unavailable); retried.
Curation thoughts
- Core: IMS serine endopeptidase; on release, IAP antagonist by binding/cleaving DIAP1 (shown mostly by overexpression); physiologically required for spermatogonial germ cell death.
- "ectopic germ cell programmed cell death" does not match the paper (spontaneous testis GCD) -> MODIFY to programmed cell death.
- DIAP1-binding protein-binding rows modified to BIR domain binding (GO:1990525); GO has no term for IAP antagonism itself.
- Generic ancestors (peptidase activity, serine hydrolase activity, regulation of apoptotic process) kept as non-core; specific children carry the core functions.
- ectopic germ cell programmed cell death (PMID:23523076) modified to programmed cell death: the paper concerns pre-meiotic germ cell elimination in the testis, not ectopic germ cells; Dronc row treated identically.
Deep research (falcon) additions
- Retry produced HtrA2-deep-research-falcon.md. It agrees on serine endopeptidase activity with DIAP1 as a direct substrate ["DIAP1 is a directly demonstrated fly substrate."], cleavage between DIAP1 Ile165/Gly166, catalytic Ser266 required, and the catalytic (not IAP-antagonist) role in spermatogonial germ cell death.