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 may ...

, specializing in absorption of

vitamin B12 Vitamin B12, also known as cobalamin, is a water-soluble vitamin involved in metabolism. One of eight B vitamins, it serves as a vital cofactor (biochemistry), cofactor in DNA synthesis and both fatty acid metabolism, fatty acid and amino a ...

. 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 r ...

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

, functional secretion of gastric

intrinsic factor Intrinsic factor (IF), also known as cobalamin binding intrinsic factor, or 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 absorp ...

, functional cleavage of the haptocorrin via pancreatic

protease A protease (also called a peptidase, proteinase, or proteolytic enzyme) is an enzyme that catalysis, catalyzes proteolysis, breaking down proteins into smaller polypeptides or single amino acids, and spurring the formation of new protein products ...

, 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 Macrocytic anemia is a condition and blood disorder characterized by the presence of predominantly larger-than-normal erythrocytes (red blood cells, or ''RBCs'') accompanied by low numbers of RBC, which often carry an insufficient amount of hemogl ...

. 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 gland, gastric glandular cells and their eventual replacement by Intestinal metaplasia, intestinal and fibrous tissues. As ...

, 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 o ...

s secreting intrinsic factor. This can lead to

pernicious anemia Pernicious anemia is a disease where not enough red blood cells are produced due to a deficiency of Vitamin B12, vitamin B12. Those affected often have a gradual onset. The most common initial symptoms are Fatigue, feeling tired and weak. Other ...

. 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 replication, DNA synthesis during red blood cell production. ...

. 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