|calbindin 1, 28kDa|
NMR solution structure of Ca2+-loaded calbindin D28K.
|Locus||Chr. 8 p11|
|calbindin 2, 29kDa (calretinin)|
|Locus||Chr. 16 q22.1|
Calbindin refers to several calcium-binding proteins. They were originally described as vitamin D-dependent calcium-binding proteins in the intestine and kidney in the chick and mammals. They are now classified in different sub-families as they differ in the number of Ca2+ binding EF-hand sites.
Calbindin-D28k was first shown to be present in the intestine in birds and then found in the mammalian kidney. It is also expressed in a number of neuroendocrine cells, particularly in the cerebellum. It is encoded in humans by the CALB1 gene.
Calbindin-D28k contains 4 active calcium-binding domains, and 2 modified domains that have lost their calcium-binding capacity. Calbindin-D28k acts as a calcium buffer and calcium sensor and can hold four Ca2+ in the EF-hands of loops EF1, EF3, EF4 and EF5. The structure was solved using high-resolution NMR and which was one of the largest proteins then to be determined. The sequence of Calbindin is 263 residues in length and has only one chain. The sequence consists mostly of alpha helicies but beta sheets are not absent. According to the PDB it is 44% helical with 14 helices containing 117 residues, and 4% beta sheet with 9 strands containing 13 residues.
Calbindin-D28k is a vitamin D responsive gene in many tissues, in particular the chick intestine, where it has a clear function in mediating calcium absorption. In the brain, its synthesis is independent of vitamin-D.
Calretinin is a 29kDa protein with 58% homology to calbindin-D28k and principally found in nervous tissues. It is encoded in humans by the CALB2 gene.
Calbindin-D9k is present in mammalian intestinal epithelial cells (enterocytes). Calbindin-D9k can also be found in the kidney and uterus in some mammalian species. It in encoded in humans by the S100G gene which has also been termed CALB3.
Calbindin-D9k mediates the transport of calcium across the enterocytes from the apical side, where entry is regulated by the calcium channel TRPV6, to the basolateral side, where calcium pumps such as PMCA1 utilize intracellular adenosine triphosphate to pump calcium into the blood. The transport of calcium across the enterocyte cytoplasm appears to be rate-limiting for calcium absorption in the intestine; the presence of calbindin increases the amount of calcium crossing the cell without raising the free concentration. Calbindin-D9k may also stimulate the basolateral calcium-pumping ATPases. Expression of calbindin-D9k, like that of calbindin-D28k, is stimulated by the active vitamin D metabolite, calcitriol although the precise mechanisms are still controversial. In mice in which the receptor for vitamin D is not expressed, calbindin-D9k is reduced, but not absent.
- PDB 2G9B; Kojetin DJ, Venters RA, Kordys DR, Thompson RJ, Kumar R, Cavanagh J (2006). "Structure, binding interface and hydrophobic transitions of Ca2+-loaded calbindin-D(28K)". Nat. Struct. Mol. Biol. 13 (7): 641–7. doi:10.1038/nsmb1112. PMID 16799559.
- Wasserman, RH; Fullmer, CS (1989). "On the molecular mechanism of intestinal calcium transport.". Advances in experimental medicine and biology 249: 45–65. doi:10.1007/978-1-4684-9111-1_5. PMID 2543194.
- Rogers, JH (1987). "Calretinin: a gene for a novel calcium-binding protein expressed principally in neurons.". The Journal of Cell Biology 105 (3): 1343–53. doi:10.1083/jcb.105.3.1343. PMC 2114790. PMID 3654755.
- Wasserman, RH; Chandler, JS, Meyer, SA, Smith, CA, Brindak, ME, Fullmer, CS, Penniston, JT, Kumar, R (1992). "Intestinal calcium transport and calcium extrusion processes at the basolateral membrane". The Journal of nutrition 122 (3 Suppl): 662–71. PMID 1311756.
- Feher, JJ; Fullmer, CS, Wasserman, RH (1992). "Role of facilitated diffusion of calcium by calbindin in intestinal calcium absorption". The American journal of physiology 262 (2 Pt 1): C517–26. PMID 1539638.
- Barley, NF; Prathalingam, SR, Zhi, P, Legon, S, Howard, A, Walters, JR (1999). "Factors involved in the duodenal expression of the human calbindin-D9k gene". The Biochemical journal 341 (3): 491–500. doi:10.1042/0264-6021:3410491. PMC 1220384. PMID 10417310.