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Calbindin
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<h2 id="calbindin-1">Calbindin 1</h2> <p class="note">Main article: <a href="/facts/Calbindin_1/P2oHYdMT">Calbindin 1</a></p> <p>Calbindin 1 or simply calbindin was first shown to be present in the intestine in birds and then found in the <a href="/facts/Mammalian_kidney/yWHP3uEf">mammalian kidney</a>. It is also expressed in a number of neuronal and endocrine cells, particularly in the <a href="/facts/Cerebellum/kBRS2Lou">cerebellum</a>. It is a 28 kDa protein encoded in humans by the <i>CALB1</i> gene. </p><p>Calbindin contains 4 active calcium-binding <a href="/facts/Protein_domain/oUpFcSsl">domains</a>, 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 the <a href="/facts/EF-hands/UVAqabCP">EF-hands</a> of 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.<a class="footnote-ref" id="fnref:1" href="#fn:1"><sup>1</sup></a> 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)<a class="footnote-ref" id="fnref:2" href="#fn:2"><sup>2</sup></a> it is 44% helical with 14 helices containing 117 residues, and 4% beta sheet with 9 strands containing 13 residues. </p><p>In 2018 the X-ray crystal structure of human calbindin was published (PDB entry 6FIE).<a class="footnote-ref" id="fnref:3" href="#fn:3"><sup>3</sup></a><a class="footnote-ref" id="fnref:4" href="#fn:4"><sup>4</sup></a> 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. </p><p>Calbindin is a <a href="/facts/Vitamin_D/No0zQB2W">vitamin D</a>–responsive gene in many tissues, in particular the chick intestine, where it has a clear function in mediating calcium absorption.<a class="footnote-ref" id="fnref:5" href="#fn:5"><sup>5</sup></a> In the brain, its synthesis is independent of vitamin-D. </p> <h2 id="calbindin-2-calretinin">Calbindin 2 (Calretinin)</h2> <p class="note">Main article: <a href="/facts/Calretinin/2Wekf29L">Calretinin</a></p> <p>Calretinin, also known as calbindin 2, is a 29 kDa protein with 58% homology to calbindin 1 and principally found in nervous tissues.<a class="footnote-ref" id="fnref:6" href="#fn:6"><sup>6</sup></a> It is encoded in humans by the <i>CALB2</i> gene and was formerly known as calbindin-D29k. </p> <h2 id="calbindin-3-s100g">Calbindin 3 (S100G)</h2> <p class="note">See also: <a href="/facts/S100G/QAYw9wGh">S100G</a></p> <p>S100G, formerly calbindin 3 and calbindin-D9k, is present in mammalian <a href="/facts/Enterocytes/NfAsbB9s">enterocytes</a> (epithelial cells of the intestine). S100G can also be found in the kidney and <a href="/facts/Uterus/LIrApMXs">uterus</a> in some mammalian species. It is encoded in humans by the <i><a href="/facts/S100G/QAYw9wGh">S100G</a></i> gene which has also been termed <i>CALB3</i>. Nonetheless, there is no <a href="/facts/Homology_(biology)/muctKlyT">homology</a> between calbindin 1 and S100G, apart from their calcium binding domains (<a href="/facts/EF-hands/UVAqabCP">EF-hands</a>): S100G has two EF-hands, and calbindin 1 has six. Unlike calbindin 1 and 2, S100G is a member of the <a href="/facts/S100_protein/NEVdr8Ue">S100</a> family of <a href="/facts/Calcium-binding_proteins/2XmwUnFU">calcium-binding proteins</a>. </p><p>S100G mediates the transport of calcium across the enterocytes from the apical side, where entry is regulated by the <a href="/facts/Calcium_channel/4C7vusSt">calcium channel</a> <a href="/facts/TRPV6/nezovQIS">TRPV6</a>, to the basolateral side, where <a href="/facts/Calcium_pump/DWohFh2D">calcium pumps</a> such as <a href="/facts/Plasma_membrane_Ca2%2B_ATPase/L3MGt3Ce">PMCA</a>1 utilize intracellular <a href="/facts/Adenosine_triphosphate/nB9bwgcU">adenosine triphosphate</a> to pump calcium into the blood.<a class="footnote-ref" id="fnref:7" href="#fn:7"><sup>7</sup></a> 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.<a class="footnote-ref" id="fnref:8" href="#fn:8"><sup>8</sup></a> S100G may also stimulate the basolateral calcium-pumping <a href="/facts/ATPase/8aEJlNgl">ATPases</a>. <a href="/facts/Gene_expression/alCPohLR">Expression</a> of S100G, like that of calbindin 1, is stimulated by the active vitamin D <a href="/facts/Metabolite/nAyywVtA">metabolite</a>, <a href="/facts/Calcitriol/3SXesdFb">calcitriol</a> although the precise mechanisms are still controversial.<a class="footnote-ref" id="fnref:9" href="#fn:9"><sup>9</sup></a> In mice in which the <a href="/facts/Vitamin_D_receptor/G6UAEBhn">vitamin D receptor</a> is not expressed, S100G is less abundant, but not absent. </p> <h2 id="discovery">Discovery</h2> <p>Vitamin D-dependent calcium binding proteins were discovered in the cytosolic fractions of chicken <a href="/facts/Intestine/nK2zwqBS">intestine</a>, and later in mammalian intestine and kidney, by researchers including Robert Wasserman of <a href="/facts/Cornell_University/FGyXuXeI">Cornell University</a>.<a class="footnote-ref" id="fnref:10" href="#fn:10"><sup>10</sup></a><a class="footnote-ref" id="fnref:11" href="#fn:11"><sup>11</sup></a> Such proteins bound <a href="/facts/Calcium/hf252CC0">calcium</a> in the micromolar range and were greatly reduced in <a href="/facts/Vitamin_D/No0zQB2W">vitamin D</a>-deficient animals. Expression could be induced by treating these animals with <a href="/facts/Vitamin_D/No0zQB2W">vitamin D</a> metabolites such as <a href="/facts/Calcitriol/3SXesdFb">calcitriol</a>. </p><p>They were found to exist in two distinct sizes with a <a href="/facts/Molecular_weight/FWueGMed">molecular weight</a> of approximately 9 kDa and 28 kDa, and they were renamed calbindins. </p> <p><i>This article incorporates text from the <a href="/facts/United_States_National_Library_of_Medicine/Hzty0MCX">United States National Library of Medicine</a>, which is in the <a href="/facts/Public_domain/YWKMDKw4">public domain</a>.</i> </p> <h2 id="references">References</h2> <ol> <li id="fn:1"><p>PDB: 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. PMID 16799559. S2CID 29426332. <a href="/wiki/Protein_Data_Bank" target="_blank">/wiki/Protein_Data_Bank</a> <a href="#fnref:1" class="footnote-back-ref">↩</a></p></li> <li id="fn:2"><p>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. ISSN 1545-9993. PMID 16799559. S2CID 29426332. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:2" class="footnote-back-ref">↩</a></p></li> <li id="fn:3"><p>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. PMC 6173056. PMID 30289411. <a href="https://www.rcsb.org/structure/6FIE" target="_blank">https://www.rcsb.org/structure/6FIE</a> <a href="#fnref:3" class="footnote-back-ref">↩</a></p></li> <li id="fn:4"><p>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. PMC 6173056. PMID 30289411. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6173056" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6173056</a> <a href="#fnref:4" class="footnote-back-ref">↩</a></p></li> <li id="fn:5"><p>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. ISBN 978-1-4684-9113-5. PMID 2543194. <a href="978-1-4684-9113-5" target="_blank">978-1-4684-9113-5</a> <a href="#fnref:5" class="footnote-back-ref">↩</a></p></li> <li id="fn:6"><p>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. PMC 2114790. PMID 3654755. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2114790" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2114790</a> <a href="#fnref:6" class="footnote-back-ref">↩</a></p></li> <li id="fn:7"><p>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. PMID 1311756. <a href="https://doi.org/10.1093%2Fjn%2F122.suppl_3.662" target="_blank">https://doi.org/10.1093%2Fjn%2F122.suppl_3.662</a> <a href="#fnref:7" class="footnote-back-ref">↩</a></p></li> <li id="fn:8"><p>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. PMID 1539638. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:8" class="footnote-back-ref">↩</a></p></li> <li id="fn:9"><p>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. PMC 1220384. PMID 10417310. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1220384" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1220384</a> <a href="#fnref:9" class="footnote-back-ref">↩</a></p></li> <li id="fn:10"><p>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. PMID 17797460. S2CID 8221178. <a href="/wiki/Bibcode_(identifier)" target="_blank">/wiki/Bibcode_(identifier)</a> <a href="#fnref:10" class="footnote-back-ref">↩</a></p></li> <li id="fn:11"><p>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. PMC 2225897. PMID 19873640. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2225897" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2225897</a> <a href="#fnref:11" class="footnote-back-ref">↩</a></p></li> </ol>