Cubilin (CUBN)

Cubilin is a large, multi-ligand endocytic receptor that serves as the principal receptor for absorption of the intrinsic factor–vitamin B12 complex in the distal ileum of mammals. It has a unique architecture comprising 27 CUB (complement C1r/C1s, Uegf, Bmp1) domains and is anchored to the cell membrane via association with the transmembrane protein amnionless, forming the so-called "cubam" complex. Cubilin is essential for dietary vitamin B12 uptake and also mediates the reabsorption of multiple proteins from renal filtrate in the kidney. Genetic deficiencies in cubilin or amnionless result in clinical syndromes of cobalamin malabsorption (Imerslund–Gräsbeck syndrome), megaloblastic anemia, and proteinuria. Crystal structure studies have detailed its modular ligand recognition and interactions dependent on calcium binding, providing insight into its critical biological roles and the molecular basis of disease when mutated.

Other names

Intrinsic factor–cobalamin receptorIF–cobalamin receptorVitamin B12 receptorCubilin (preferred molecular/gene name)CUBN (gene symbol)Cubam (the functional heteromeric complex including cubilin and amnionless)

Receptor-mediated endocytosis: Intrinsic factor binds vitamin B12 in the gut, this complex binds cubilin on ileal enterocytes; the complex is endocytosed and B12 absorbed systemically. Calcium-dependent binding: Some CUB domains require Ca²⁺ for ligand binding and structural stability.