Cubam
Encyclopedia
Cubam, is the term used to refer to a multi-ligand receptor located in the terminal ileum
, specializing in absorption of vitamin B12
. Cubam is essentially composed of amnionless
(AMN) , and cubilin
. 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.
, functional secretion of gastric intrinsic factor
, functional cleavage of the haptocorrin via pancreatic protease
, and a functional absorption via the Cubam at terminal ileum. As expected, a defect at any point of the aforementioned list, can cause malabsoption 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 pernicious anemia
, or atrophic gastritis
, 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 component of Cubam (AMN, and cubilin) is responsible for Imerslund-Gräsbeck syndrome, which manifests as macrycytic, megaloblastic anemia
.
Severe vitamin B12 deficiency is most commonly caused by an autoimmune mediated deficiency in intrinsic factor
. Rarely, a mutations in the gene CUBN, coding for cubilin, or AMN, coding for amnionless
cause an autosomal reccessive 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.
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 be used instead of ileum.The ileum follows the duodenum...
, specializing in absorption of vitamin B12
Vitamin B12
Vitamin B12, vitamin B12 or vitamin B-12, also called cobalamin, is a water-soluble vitamin with a key role in the normal functioning of the brain and nervous system, and for the formation of blood. It is one of the eight B vitamins...
. Cubam is essentially composed of amnionless
Amnionless
Amnionless is a protein that in humans is encoded by the AMN gene.- Function :A complex of amnionless and cubilin forms the cubam receptor....
(AMN) , and cubilin
Cubilin
Cubilin is a protein that in humans is encoded by the CUBN gene.- Function :Cubilin acts as a receptor for intrinsic factor-vitamin B12 complexes. The role of receptor is supported by the presence of 27 CUB domains. Cubulin is located within the epithelium of intestine and kidney. Mutations in...
. 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 haptocorrinHaptocorrin
Haptocorrin also known as transcobalamin-1 is a protein that in humans is encoded by the TCN1 gene. The essential function of haptocorrin is protection of the acid-sensitive vitamin B12 while it moves through the stomach.- Function :...
, functional secretion of gastric intrinsic factor
Intrinsic factor
Intrinsic factor also known as gastric intrinsic factor is a glycoprotein produced by the parietal cells of the stomach. It is necessary for the absorption of vitamin B12 later on in the small intestine...
, functional cleavage of the haptocorrin via pancreatic protease
Protease
A protease is any enzyme that conducts proteolysis, that is, begins protein catabolism by hydrolysis of the peptide bonds that link amino acids together in the polypeptide chain forming the protein....
, and a functional absorption via the Cubam at terminal ileum. As expected, a defect at any point of the aforementioned list, can cause malabsoption 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 pernicious anemia
Pernicious anemia
Pernicious anemia is one of many types of the larger family of megaloblastic anemias...
, or atrophic gastritis
Atrophic gastritis
Atrophic gastritis is a process of chronic inflammation of the stomach mucosa, leading to loss of gastric glandular cells and their eventual replacement by intestinal and fibrous tissues...
, however a rare abnormality of AMN can also cause vitamin B12 anemia; this condition is referred to as "Imerslund-Gräsbeck syndrome
Imerslund-Gräsbeck syndrome
Imerslund-Grasbeck syndrome or Imerslund-Najman-Grasbeck syndrome or Imerslund-Grasbeck disease is an autosomal recessive, familial form of vitamin B12 deficiency caused by malfunction of the receptor located in the terminal ileum. This receptor is referred to as "Cubam", and is composed of two...
(IGS)." Autosomal recessive mutations in both component of Cubam (AMN, and cubilin) is responsible for Imerslund-Gräsbeck syndrome, which manifests as macrycytic, megaloblastic anemia
Megaloblastic anemia
Megaloblastic anemia is an anemia that results from inhibition of DNA synthesis in red blood cell production. When DNA synthesis is impaired, the cell cycle cannot progress from the G2 growth stage to the mitosis stage...
.
Severe vitamin B12 deficiency is most commonly caused by an autoimmune mediated deficiency in intrinsic factor
Intrinsic factor
Intrinsic factor also known as gastric intrinsic factor is a glycoprotein produced by the parietal cells of the stomach. It is necessary for the absorption of vitamin B12 later on in the small intestine...
. Rarely, a mutations in the gene CUBN, coding for cubilin, or AMN, coding for amnionless
Amnionless
Amnionless is a protein that in humans is encoded by the AMN gene.- Function :A complex of amnionless and cubilin forms the cubam receptor....
cause an autosomal reccessive form of vitamin B12 deficiency, known as the Imerslund-Gräsbeck syndrome
Imerslund-Gräsbeck syndrome
Imerslund-Grasbeck syndrome or Imerslund-Najman-Grasbeck syndrome or Imerslund-Grasbeck disease is an autosomal recessive, familial form of vitamin B12 deficiency caused by malfunction of the receptor located in the terminal ileum. This receptor is referred to as "Cubam", and is composed of two...
. 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.