Alternative titles; symbols
HGNC Approved Gene Symbol: S100G
Cytogenetic location: Xp22.2 Genomic coordinates (GRCh38) : X:16,650,158-16,654,670 (from NCBI)
Calbindin D9K, the vitamin D-dependent calcium-binding protein (CaBP9K), was first described in rat intestine. It is a cytosolic protein of molecular weight 9,000 and belongs to a family of calcium-binding proteins that includes calmodulin (CALM1, 114180; CALM2, 114182), parvalbumin (PVALB, 168890), troponin C (191039, 191040), and S100 protein (S100A, 176940; S100B, 176990). This calbindin is found in the mammalian intestine, placenta, uterus, and kidney. The intestinal protein is vitamin D-dependent and its expression correlates with calcium transport activity. In keeping with its role in calcium absorption, concentrations of CaBP9K are highest in duodenal villus enterocytes. A vitamin D-independent role in calcium transport in placenta and kidney has been postulated. Using RT-PCR methodology with rat- and bovine-derived primers and intestinal RNA, Jeung et al. (1992) cloned the full-length cDNA encoding human calbindin-D(9k). The clones included a coding region of 79 amino acids, 57-nucleotide 5-prime- and 159-nucleotide 3-prime noncoding regions, and a poly(A) tail. The deduced protein sequence is homologous to other mammalian calbindins. Northern analysis revealed the mRNA in human duodenum to be about 600 nucleotides long. Expression levels in adult human tissue were substantially lower than in child, rat, or porcine intestine.
Howard et al. (1992) cloned and sequenced the human CALB3 gene. A single abundant mRNA transcript was detectable in proximal small intestine, but not in kidney, uterus, or placenta.
Jeung et al. (1994) determined that the CALB3 gene spans 5.5 kb and contains 3 exons. They characterized the promoter and 1,300 basepairs of the 5-prime flanking region. Besides a TATA box and 2 CAAT-like motifs, a sequence related to a vitamin D response element was detected about 1.1 kb upstream from the promoter. A sequence 50 nucleotides downstream from the promoter showed extensive homology to the estrogen response element at the same location within the rat gene. However, 2 essential nucleotides within this region differ between the rat and human sequences, and the human element failed to bind estrogen receptor (ESR1; 133430). Jeung et al. (1994) proposed that the 2-nucleotide change within this region causes lack of expression in human uterus and possibly placenta.
By probing DNA from human-rodent somatic cell hybrids, Howard et al. (1992) mapped the CALB3 gene to the short arm of the X chromosome.
Jeung et al. (1994) showed that the CALB3 gene is on the X chromosome by PCR analyses of human/hamster somatic cell hybrid DNAs. They quoted C. Oudet as suggesting that the location of the CALB3 gene is between Xp22.2 and the telomere.
Luu et al. (2004) found that Calb3 and Calb1 expression increased in mouse endometrial epithelium just before implantation but disappeared at implantation sites after attachment. By injecting morpholino oligonucleotides against Calb3 into wildtype and Calb1-null mice just before implantation, Luu et al. (2004) eliminated 1 or both proteins from the uterine epithelium. Implantation was blocked only when both Calb3 and Calb1 were absent: treated wildtype mice and untreated Calb1-null mice were fertile. Furthermore, the effect on implantation was highly dependent on the timing of morpholino oligonucleotide injection.
Kutuzova et al. (2006) found that Calb3-null mice were viable and fertile and had serum calcium levels indistinguishable from wildtype mice, regardless of age or gender. They concluded that CALB3 is not required for calcium homeostasis.
Howard, A., Legon, S., Spurr, N. K., Walters, J. R. F. Molecular cloning and chromosomal assignment of human calbindin-D9K. Biochem. Biophys. Res. Commun. 185: 663-669, 1992. [PubMed: 1610358] [Full Text: https://doi.org/10.1016/0006-291x(92)91676-h]
Jeung, E.-B., Krisinger, J., Dann, J. L., Leung, P. C. K. Molecular cloning of the full-length cDNA encoding the human calbindin-D(9k). FEBS Lett. 307: 224-228, 1992. [PubMed: 1379540] [Full Text: https://doi.org/10.1016/0014-5793(92)80772-9]
Jeung, E.-B., Leung, P. C. K., Krisinger, J. The human calbindin-D(9k) gene: complete structure and implications on steroid hormone regulation. J. Molec. Biol. 235: 1231-1238, 1994. [PubMed: 8308886] [Full Text: https://doi.org/10.1006/jmbi.1994.1076]
Kutuzova, G. D., Akhter, S., Christakos, S., Vanhooke, J., Kimmel-Jehan, C., DeLuca, H. F. Calbindin D(9k) knockout mice are indistinguishable from wild-type mice in phenotype and serum calcium level. Proc. Nat. Acad. Sci. 103: 12377-12381, 2006. [PubMed: 16895982] [Full Text: https://doi.org/10.1073/pnas.0605252103]
Luu, K. C., Nie, G. Y., Salamonsen, L. A. Endometrial calbindins are critical for embryo implantation: evidence from in vivo use of morpholino antisense oligonucleotides. Proc. Nat. Acad. Sci. 101: 8028-8033, 2004. [PubMed: 15138301] [Full Text: https://doi.org/10.1073/pnas.0401069101]