Cubam, is the term used to refer to a multi-ligand receptor located in the terminal

ileum The ileum () is the final section of the small intestine in most higher vertebrates, including mammals, reptiles, and birds. In fish, the divisions of the small intestine are not as clear and the terms posterior intestine or distal intestine m ...

, specializing in absorption of

vitamin B12 Vitamin B12, also known as cobalamin, is a water-soluble vitamin involved in metabolism. It is one of eight B vitamins. It is required by animals, which use it as a cofactor in DNA synthesis, in both fatty acid and amino acid metabolism. It ...

. Cubam is essentially composed of amnionless (AMN), and

cubilin Cubilin is a protein that in humans is encoded by the ''CUBN'' gene. Function Cubilin (CUBN) acts as a receptor for intrinsic factor-vitamin B12 complexes. The role of receptor is supported by the presence of 27 CUB domains. Cubilin shows a re ...

. Cubilin is essential as a cell receptor recognizing the "vitamin B12-intrinsic factor" complex, whereas amnionless is more involved in the receptor mediated endocytosis of the complex.

Clinical significance

Vitamin B12 is an essential water-soluble vitamin, the absorption of which relies on a functional secretion of salivary

haptocorrin Haptocorrin also known as transcobalamin-1 (TC-1) or cobalophilin is a transcobalamin protein that in humans is encoded by the gene. The essential function of haptocorrin is protection of the acid-sensitive vitamin B12 while it moves through the ...

, functional secretion of gastric

intrinsic factor Intrinsic factor (IF), cobalamin binding intrinsic factor, also known as gastric intrinsic factor (GIF), is a glycoprotein produced by the parietal cells (in humans) or chief cells (in rodents) of the stomach. It is necessary for the absorption o ...

, functional cleavage of the haptocorrin via pancreatic

protease A protease (also called a peptidase, proteinase, or proteolytic enzyme) is an enzyme that catalyzes (increases reaction rate or "speeds up") proteolysis, breaking down proteins into smaller polypeptides or single amino acids, and spurring the form ...

, and a functional absorption via the Cubam at terminal ileum. As expected, a defect at any point of the aforementioned list, can cause malabsorption of vitamin B12, and subsequent macrocytic anemia. The most common cause of Vitamin B12 deficiency is deficiency of the intrinsic factor (IF) usually due to

atrophic gastritis Atrophic gastritis is a process of chronic inflammation of the gastric mucosa of the stomach, leading to a loss of gastric glandular cells and their eventual replacement by intestinal and fibrous tissues. As a result, the stomach's secretion of ...

, which reduces the number of

parietal cell Parietal cells (also known as oxyntic cells) are epithelial cells in the stomach that secrete hydrochloric acid (HCl) and intrinsic factor. These cells are located in the gastric glands found in the lining of the fundus and body regions of ...

s secreting intrinsic factor. This can lead to

pernicious anemia Pernicious anemia is a type of vitamin B12 deficiency anemia, a disease in which not enough red blood cells are produced due to the malabsorption of vitamin B12. Malabsorption in pernicious anemia results from the lack or loss of intrinsic fac ...

. However, a rare abnormality of AMN can also cause vitamin B12 anemia; this condition is referred to as " Imerslund-Gräsbeck syndrome (IGS)." Autosomal recessive mutations in both components of Cubam (AMN, and cubilin) is responsible for Imerslund-Gräsbeck syndrome, which manifests as macrocytic,

megaloblastic anemia Megaloblastic anemia is a type of macrocytic anemia. An anemia is a red blood cell defect that can lead to an undersupply of oxygen. Megaloblastic anemia results from inhibition of DNA synthesis during red blood cell production. When DNA synthe ...

. Severe vitamin B12 deficiency is most commonly caused by an autoimmune mediated deficiency in

. Rarely, a mutations in the gene CUBN, coding for cubilin, or AMN, coding for amnionless cause an autosomal recessive form of vitamin B12 deficiency, known as the Imerslund-Gräsbeck syndrome. Cubilin and amnionless also play a role in renal tubular function. Cubilin is essential for embryonic development in rodents, but appears not to be essential for normal human embryonic development.

References

{{Reflist Receptors