| Functional role | Molecular mechanism | Key domains/cofactors | Key substrates/interactions | Localization/compartment (if evidenced) | Evidence notes with citations placeholders |
|---|---|---|---|---|---|
| Iron-responsive substrate receptor in SCF E3 ubiquitin ligase | Under iron-replete conditions, FBXL5 is stabilized and recruits IRP2/IREB2 for ubiquitination and proteasomal degradation, thereby suppressing IRP2-dependent iron-starvation responses | F-box domain; leucine-rich repeat (LRR) region; N-terminal hemerythrin-like domain; diiron center; [2Fe-2S] cluster reported in LRR-associated sensing model | IRP2/IREB2 substrate; SKP1 interaction as SCF component | Nucleus explicitly mentioned in one review; broader IRP pathway acts in cytoplasmic iron-response circuitry | Human FBXL5 is described as hemerythrin-like/F-box/LRR and as the substrate-recognition component of SCF targeting IRP2 (pqac-00000002, pqac-00000005, pqac-00000007) |
| Iron/oxygen sensor controlling its own stability | Iron binding stabilizes FBXL5; low iron destabilizes FBXL5 and permits IRP2 accumulation; oxygen sensitivity has been linked to an oxygen-responsive Fe-S-based mechanism | Hemerythrin-like diiron-binding module; oxygen-responsive [2Fe-2S] cluster mechanism | Functional coupling to IRP2 turnover | Nuclear mention reported; no stronger consensus localization extracted here | Reviews and cited mechanistic work describe FBXL5 as iron- and oxygen-sensitive, with stability governed by metal cofactor occupancy (pqac-00000003, pqac-00000004, pqac-00000013, pqac-00000014) |
| Structural adapter linking metal sensing to ubiquitin machinery | F-box mediates SCF assembly through SKP1, while substrate-binding surfaces in the LRR/other conserved regions support IREB2 recognition | Central F-box (SKP1-binding hotspot); C-terminal LRR substrate-binding region; hemerythrin-like metal-sensing domain | SKP1; IREB2; diiron center visualized in structural summary | Not specifically assigned by structural summary | Structural analysis and retrieved figure summarize domain architecture and interactions with SKP1 and IREB2 (pqac-00000002, pqac-00000012) |


*Table: This table summarizes the core functional annotation of human FBXL5 (UniProt Q9UKA1) using only evidence established in the conversation. It highlights FBXL5’s role as an iron/oxygen-sensitive SCF substrate receptor for IRP2, the domains/cofactors supporting that function, and the limited localization evidence retrieved.*