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Calbindin

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calbindin 1, 28kDa
NMR solution structure of Ca2+-loaded calbindin D28K.[1]
Identifiers
SymbolCALB1
Alt. symbolsCALB
NCBI gene793
HGNC1434
OMIM114050
RefSeqNM_004929
UniProtP05937
Other data
LocusChr. 8p11
Search for
StructuresSwiss-model
DomainsInterPro
calbindin 2, 29kDa (calretinin)
Identifiers
SymbolCALB2
NCBI gene794
HGNC1435
OMIM114051
RefSeqNM_001740
UniProtP22676
Other data
LocusChr. 16q22.1
Search for
StructuresSwiss-model
DomainsInterPro

Calbindinsare three differentcalcium-binding proteins:calbindin,calretininandS100G.They were originally described asvitamin D-dependent calcium-binding proteinsin the intestine and kidney of chicks and mammals. They are now classified in differentsubfamiliesas they differ in the number of Ca2+bindingEF hands.

Calbindin 1

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Main article:Calbindin 1

Calbindin 1 or simply calbindin 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 neuronal and endocrine cells, particularly in thecerebellum.It is a 28 kDa protein encoded in humans by theCALB1gene.

Calbindin contains 4 active calcium-bindingdomains,and 2 modified domains that have lost their calcium-binding capacity. Calbindin acts as a calcium buffer and calcium sensor and can hold four Ca2+in theEF-handsof loops EF1, EF3, EF4 and EF5. The structure of rat calbindin was originally solved by nuclear magnetic resonance and was one of the largest proteins then to be determined by this technique.[1]The sequence of calbindin is 263 residues in length and has only one chain. The sequence consists mostly of alpha helices but beta sheets are not absent. According to the NMR PDB (PDB entry 2G9B)[2]it is 44% helical with 14 helices containing 117 residues, and 4% beta sheet with 9 strands containing 13 residues. In 2018 the X-ray crystal structure of human calbindin was published (PDB entry 6FIE).[3][4]There were differences observed between the nuclear magnetic resonance and crystal structure despite 98% sequence identity between the rat and human isoforms. Small angle X-ray scattering indicates that the crystal structure better predicts the properties of calbindin in solution compared with the structure determined by nuclear magnetic resonance.

Calbindin is avitamin D–responsive gene in many tissues, in particular the chick intestine, where it has a clear function in mediating calcium absorption.[5]In the brain, its synthesis is independent of vitamin-D.

Calbindin 2 (Calretinin)

[edit]
Main article:Calretinin

Calretinin, also known as calbindin 2, is a 29 kDa protein with 58% homology to calbindin 1 and principally found in nervous tissues.[6]It is encoded in humans by theCALB2gene and was formerly known ascalbindin-D29k.

Calbindin 3 (S100G)

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See also:S100G

S100G, formerlycalbindin 3andcalbindin-D9k,is present in mammalianenterocytes(epithelial cells of the intestine). S100G can also be found in the kidney anduterusin some mammalian species. It is encoded in humans by theS100Ggene which has also been termedCALB3.Nonetheless, there is nohomologybetween calbindin 1 and S100G, apart from their calcium binding domains (EF-hands): S100G has two EF-hands, and calbindin 1 has six. Unlike calbindin 1 and 2, S100G is a member of theS100family ofcalcium-binding proteins.

S100G mediates the transport of calcium across the enterocytes from the apical side, where entry is regulated by thecalcium channelTRPV6,to the basolateral side, wherecalcium pumpssuch asPMCA1 utilize intracellularadenosine triphosphateto pump calcium into the blood.[7]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.[8]S100G may also stimulate the basolateral calcium-pumpingATPases.Expressionof S100G, like that of calbindin 1, is stimulated by the active vitamin Dmetabolite,calcitriolalthough the precise mechanisms are still controversial.[9]In mice in which thevitamin D receptoris not expressed, S100G is less abundant, but not absent.[citation needed]

Discovery

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Vitamin D-dependent calcium binding proteins were discovered in the cytosolic fractions of chickenintestine,and later in mammalian intestine and kidney, by researchers including Robert Wasserman ofCornell University.[10][11]Such proteins boundcalciumin the micromolar range and were greatly reduced invitamin D-deficient animals. Expression could be induced by treating these animals withvitamin Dmetabolites such ascalcitriol.

They were found to exist in two distinct sizes with amolecular weightof approximately 9 kDa and 28 kDa, and they were renamed calbindins.

References

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  1. ^abPDB:2G9B​;Kojetin DJ, Venters RA, Kordys DR, Thompson RJ, Kumar R, Cavanagh J (July 2006). "Structure, binding interface and hydrophobic transitions of Ca2+-loaded calbindin-D(28K)".Nature Structural & Molecular Biology.13(7): 641–7.doi:10.1038/nsmb1112.PMID16799559.S2CID29426332.
  2. ^Kojetin, Douglas J; Venters, Ronald A; Kordys, David R; Thompson, Richele J; Kumar, Rajiv; Cavanagh, John (July 2006). "Structure, binding interface and hydrophobic transitions of Ca2+-loaded calbindin-D28K".Nature Structural & Molecular Biology.13(7): 641–647.doi:10.1038/nsmb1112.ISSN1545-9993.PMID16799559.S2CID29426332.
  3. ^Noble, J. W.; Almalki, R.; Roe, S. M.; Wagner, A.; Duman, R.; Atack, J. R. (2018)."The X-ray structure of human calbindin-D28K: an improved model".Acta Crystallogr D.74(Pt 10): 1008–1014.doi:10.2210/pdb6fie/pdb.PMC6173056.PMID30289411.
  4. ^Noble JW, Almalki R, Roe SM, Wagner A, Duman R, Atack JR (October 2018)."The X-ray structure of human calbindin-D28K: an improved model".Acta Crystallographica Section D.74(Pt 10): 1008–1014.Bibcode:2018AcCrD..74.1008N.doi:10.1107/S2059798318011610.PMC6173056.PMID30289411.
  5. ^Wasserman RH, Fullmer CS (1989). "On the Molecular Mechanism of Intestinal Calcium Transport".Mineral Absorption in the Monogastric GI Tract.Advances in Experimental Medicine and Biology. Vol. 249. pp. 45–65.doi:10.1007/978-1-4684-9111-1_5.ISBN978-1-4684-9113-5.PMID2543194.
  6. ^Rogers JH (September 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.PMC2114790.PMID3654755.
  7. ^Wasserman RH, Chandler JS, Meyer SA, Smith CA, Brindak ME, Fullmer CS, et al. (March 1992)."Intestinal calcium transport and calcium extrusion processes at the basolateral membrane".The Journal of Nutrition.122(3 Suppl): 662–71.doi:10.1093/jn/122.suppl_3.662.PMID1311756.
  8. ^Feher JJ, Fullmer CS, Wasserman RH (February 1992). "Role of facilitated diffusion of calcium by calbindin in intestinal calcium absorption".The American Journal of Physiology.262(2 Pt 1): C517-26.doi:10.1152/ajpcell.1992.262.2.C517.PMID1539638.
  9. ^Barley NF, Prathalingam SR, Zhi P, Legon S, Howard A, Walters JR (August 1999)."Factors involved in the duodenal expression of the human calbindin-D9k gene".The Biochemical Journal.341 ( Pt 3) (3): 491–500.doi:10.1042/0264-6021:3410491.PMC1220384.PMID10417310.
  10. ^Wasserman RH, Taylor AN (May 1966). "Vitamin d3-induced calcium-binding protein in chick intestinal mucosa".Science.152(3723): 791–3.Bibcode:1966Sci...152..791W.doi:10.1126/science.152.3723.791.PMID17797460.S2CID8221178.
  11. ^Wasserman RH, Corradino RA, Taylor AN (July 1969)."Binding proteins from animals with possible transport function".The Journal of General Physiology.54(1): 114–37.doi:10.1085/jgp.54.1.114.PMC2225897.PMID19873640.

This article incorporates text from theUnited States National Library of Medicine,which is in thepublic domain.

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