Cubilin receptor (CUBN)

Cubilin receptor is a large, 460 kDa peripheral membrane protein that serves as a multi-ligand endocytic receptor, primarily localized in the apical membrane of the ileum and the renal proximal tubules (UniProt P35548). It is unique among receptors because it lacks a transmembrane domain and a cytoplasmic tail, necessitating an interaction with the transmembrane protein Amnionless to form the functional CUBAM complex for membrane anchoring and internalization (PubMed: 15190073). Its primary physiological roles include the absorption of the intrinsic factor-vitamin B12 complex in the intestine and the reabsorption of filtered proteins, such as albumin, transferrin, and vitamin-binding proteins, from the primary urine in the kidney (PubMed: 10545152). Mutations in the CUBN gene are the underlying cause of Imerslund-Gräsbeck syndrome, which presents as megaloblastic anemia due to B12 deficiency and persistent proteinuria (OMIM: 211200). While there are currently no FDA-approved drugs that specifically target cubilin for therapeutic modulation, it is a subject of intense research in nephrology for its role in albuminuria and as a potential portal for the targeted delivery of drugs to the renal proximal tubule (PubMed: 28655776).

Other names

Intrinsic factor-vitamin B12 receptorIntrinsic factor-cobalamin receptorIFCRgp280Megaloblastic anemia 1MGA1460 kDa receptor

Mediates the endocytosis of various ligands, including the intrinsic factor-vitamin B12 complex and albumin, by forming a functional heterodimeric complex (CUBAM) with the transmembrane protein Amnionless.