| Category | Evidence summary | Key citations |
|---|---|---|
| Protein identity/synonyms | GLMN in the cited literature refers to human glomulin, the glomuvenous malformation protein; a foundational mechanistic study explicitly notes the aliases FAP68 and FAP48 and uses human cell lines and a human GLMN clone, matching UniProt Q92990. | (pqac-00000001, pqac-00000005) |
| Molecular function | GLMN is a negative regulator of RBX1-containing cullin-RING E3 ubiquitin ligases rather than an enzyme with its own catalytic activity. It inhibits CRL/SCF ubiquitination reactions and stabilizes selected regulators such as FBW7 by restraining CRL-dependent turnover. | (pqac-00000010, pqac-00000013, pqac-00000015) |
| Mechanism | Structural and biochemical work shows GLMN binds the RBX1 RING domain and masks the E2-binding surface, outcompeting the E2 enzyme CDC34 and blocking ubiquitin chain synthesis. A minimal RBX1-binding region spanning GLMN residues 300–594 was sufficient for this inhibitory interaction. | (pqac-00000010, pqac-00000012) |
| Key binding partners/complexes | Direct and selective interaction with RBX1 is strongly supported, with little or no binding to RBX2 in the cited studies. GLMN associates with CUL1-containing SCF/CRL1 complexes and also with other cullins (including CUL3 and CUL4A in coprecipitation assays), and in innate immunity it binds cIAP1 and cIAP2 via their RING domains. | (pqac-00000001, pqac-00000012, pqac-00000013, pqac-00000009) |
| Pathways | The best-supported pathway assignment is ubiquitin-proteasome regulation through CRL/SCF complexes, especially CRL1/SCF^FBW7. Additional evidence places GLMN in a GLMN–cIAP–inflammasome axis, where it negatively regulates cIAP-mediated inflammasome activation and thereby modulates pyroptosis. | (pqac-00000009, pqac-00000010, pqac-00000011, pqac-00000013) |
| Subcellular localization | Specific steady-state compartment annotation is limited in the gathered evidence. In macrophages, GLMN formed puncta after LPS/ATP stimulation that colocalized with active caspase-1, and it colocalized with cIAP2 after Shigella infection, supporting stimulus-dependent localization near inflammasome-related structures. | (pqac-00000009) |
| Disease relevance | Loss-of-function GLMN mutations are causally linked to glomuvenous malformation (GVM), and mechanistic studies connect disease to disruption of the RBX1-binding/inhibitory function of GLMN. GVM patient samples also showed accumulation of FBW7 substrates such as Cyclin E and c-Myc, consistent with altered CRL regulation in disease tissue. | (pqac-00000001, pqac-00000010, pqac-00000013, pqac-00000000) |
| Key quantitative data | Reported quantitative measurements include high-affinity GLMN–RBX1 binding with Kd ~38.6 nM and mapping of a minimal RBX1-binding fragment to GLMN residues 300–594. Open Targets evidence also lists GLMN associations with glomuvenous malformation and venous malformation, each supported by 5 evidence items in the retrieved dataset. | (pqac-00000012, pqac-00000000) |


*Table: This table summarizes the best-supported functional annotation for human GLMN/glomulin from the gathered mechanistic and disease evidence. It highlights identity, molecular mechanism, pathway placement, localization evidence, disease links, and key quantitative findings relevant to UniProt Q92990.*