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Intrinsic factor-vitamin B12 receptor (Cubilin-AMN complex) (Cubilin-AMN (Cubam) receptor)

Target
Cubilin-AMN (Cubam) receptor
Molecular classification
Receptor, Endocytic receptor, Apolipoprotein receptor
01

Overview

The Intrinsic factor-vitamin B12 receptor (also known as the Cubilin-AMN complex or Cubam receptor) is a large multimeric endocytic receptor found principally on the apical surface of ileal enterocytes and renal tubular cells. It consists of the peripheral cubilin protein (comprised of multiple CUB domains and EGF-like repeats) and a transmembrane partner, amnionless (AMN). This receptor specifically mediates the uptake of vitamin B12 when complexed with intrinsic factor—a glycoprotein necessary for dietary vitamin B12 absorption. Upon binding, the receptor complex facilitates endocytosis, delivering vitamin B12 into the enterocyte for subsequent transport into the systemic circulation. Molecular defects in either component of the receptor cause selective malabsorption of vitamin B12 and often proteinuria, exemplified by Imerslund-Gräsbeck syndrome. Radiolabeled vitamin B12 analogs are often used experimentally and clinically to visualize or quantify B12 uptake, but the radiolabel itself is not a target molecule or receptor.

Other names
Cubilin-AMN complexCubam receptorIF-B12 receptorIntrinsic factor receptor
02

Mechanism of action

Vitamin B12 bound to intrinsic factor is recognized and internalized via receptor-mediated endocytosis by the cubilin-AMN complex on ileal enterocytes

03

Biological functions

Vitamin B12 (cobalamin) uptake/absorptionProtein reabsorption in kidneyEndocytosis
04

Disease associations

Imerslund-Gräsbeck syndrome (hereditary B12 malabsorption)Vitamin B12 deficiencyProteinuria (due to renal cubilin dysfunction)
05

Safety considerations

Genetic variants can cause malabsorption and deficiency syndromesLoss-of-function mutations in cubilin and AMN lead to vitamin B12 deficiency and proteinuria
06

Interacting drugs

No direct drugs known to target the cubilin-AMN complex; however, radiolabeled vitamin B12 and vitamin B12 analogs are used diagnostically
07

Biomarkers

Measurement of vitamin B12 levelsHolo-transcobalamin levels in serumGenetic testing for cubilin or AMN mutations in Imerslund-Gräsbeck syndrome

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