Involved in the response to variation in environmental oxygen levels by targeting the hypoxia-inducible transcription factor hif-1 for proteasomal degradation when oxygen levels are normal (around 20%) (PubMed:11595184). By regulating hif-1 expression, plays a role in iron homeostasis, aging, heat acclimation and progeny size (PubMed:12686697, PubMed:19372390, PubMed:22396654). Mediates resistance to enteropathogenic E.coli (PubMed:16091039). Mediates susceptibility to B.thuringiensis pore-forming toxins (PubMed:20011506). Not involved in P.aeruginosa susceptibility (PubMed:20865124). Protein modification; protein ubiquitination. Interacts with hif-1 (hydroxylated on 'Pro-621'); the interaction induces hif-1 degradation (PubMed:11595184). May be a component of the cullin E3 ubiquitin ligase complex (By similarity). Increased mortality induced by B.thuringiensis pore-forming toxins Cry21A and Cry21B (PubMed:20011506). Increased mortality and sensitivity to paralysis induced by enteropathogenic E.coli infection (PubMed:16091039). Increased mortality upon heat stress (PubMed:12686697). RNAi-mediated knockdown causes an enhanced resistance to polyglutamine or amyloid-beta-mediated paralysis and an increase in adult life span. Belongs to the VHL family.