Alternative titles; symbols
HGNC Approved Gene Symbol: CALML3
Cytogenetic location: 10p15.1 Genomic coordinates (GRCh38): 10:5,524,961-5,526,771 (from NCBI)
Using calmodulin (CALM1; 114180) as probe, Koller and Strehler (1988) cloned CALML3, which they designated GH6, from a leukocyte genomic library. The deduced 148-amino acid protein contains 4 helix-loop-helix Ca(2+)-binding motifs and shares 85% identity with vertebrate calmodulin. Northern blot analysis detected no expression in fibroblast, teratoma, or erythroleukemia cell lines.
By immunohistochemical staining, Rogers et al. (2001) determined the tissue distribution of CALML3, which they designated CLP. CLP was expressed exclusively in the epithelium of the tissues surveyed and was most abundant in thyroid, breast, prostate, kidney, and skin. CLP expression appeared to increase in stratified epithelium during differentiation, as illustrated in skin, where CLP staining intensified from the basal through the spinous to the granular layers.
Qian et al. (1998) determined the secondary structure of CLP complexed with Ca(2+) by multidimensional nuclear magnetic resonance spectroscopy. Overall, CLP has a 2-domain structure similar to that of calmodulin. Qian et al. (1998) identified differences between calmodulin and CLP in the lengths of several helical elements and, most importantly, in the central nonhelical flexible region. Their analysis suggested that the sum of small differences in the central regions of calmodulin and CLP plays a crucial role in target selectivity between these proteins.
Han et al. (2002) determined the 1.5-angstrom crystal structure of CLP and compared it with that of calmodulin. They verified that CLP contains 2 globular domains connected by a central 7-turn alpha helix. Each globular domain has 2 helix-loop-helix motifs that form the 4 Ca(2+)-binding sites. The central helix of CLP is less flexible than the central helix of calmodulin, and the 2 proteins differ in the orientation of the globular domains about the hinge region. Significant differences between the electric surface potentials at the target protein-binding regions of CLP and calmodulin suggested that the ranges of CLP and calmodulin target proteins do not fully overlap.
Rogers et al. (2001) examined the expression of CLP in cultured normal human keratinocytes in response to various agents known to affect keratinocyte differentiation. They found that agents that inhibit terminal differentiation, particularly epidermal growth factor (EGF; 131530), downregulate CLP expression. Using several other agents that affect the growth and differentiation of keratinocytes, Rogers et al. (2001) determined that upregulated expression of CLP mRNA is linked to initiation of terminal differentiation.
Using gel overlays and yeast 2-hybrid screens, Rogers and Strehler (2001) identified myosin X (MYO10; 601481) as a specific Ca(2+)-dependent binding partner for CLP. CLP specifically bound to motif 3 of the IQ domain of MYO10, and both proteins colocalized at the cell periphery of mammary carcinoma cells. Rogers and Strehler (2001) concluded that CLP is a specific light chain of MYO10 in vivo.
Koller and Strehler (1988) determined that the CALML3 gene contains a single exon. The upstream region has no obvious TATA box, but it does have a putative CAAT box. The promoter region has several CGAGG and CACCC repeat sequences and a putative cAMP responsive element.
Berchtold et al. (1993) mapped a functional intronless gene coding for CLP to chromosome 10pter-p13. Chromosomal assignment was performed by Southern blot analysis of DNA from human/rodent somatic cell hybrids and amplification of a gene-specific 1,090-bp DNA fragment by PCR from DNA of human/hamster cell hybrids. Chromosomal sublocalization was carried out by in situ hybridization.
Berchtold, M. W., Koller, M., Egli, R., Rhyner, J. A., Hameister, H., Strehler, E. E. Localization of the intronless gene coding for calmodulin-like protein CLP to human chromosome 10p13-ter. Hum. Genet. 90: 496-500, 1993. [PubMed: 8428750] [Full Text: https://doi.org/10.1007/BF00217447]
Han, B.-G., Han, M., Sui, H., Yaswen, P., Walian, P. J., Jap, B. K. Crystal structure of human calmodulin-like protein: insights into its functional role. FEBS Lett. 521: 24-30, 2002. [PubMed: 12067719] [Full Text: https://doi.org/10.1016/s0014-5793(02)02780-1]
Koller, M., Strehler, E. E. Characterization of an intronless human calmodulin-like pseudogene. FEBS Lett. 239: 121-128, 1988. [PubMed: 3181418] [Full Text: https://doi.org/10.1016/0014-5793(88)80558-1]
Qian, H., Rogers, M. S., Schleucher, J., Edlund, U., Strehler, E. E., Sethson, I. Sequential assignment of (1)H, (15)N, (13)C resonances and secondary structure of human calmodulin-like protein determined by NMR spectroscopy. Protein Sci. 7: 2421-2430, 1998. [PubMed: 9828009] [Full Text: https://doi.org/10.1002/pro.5560071120]
Rogers, M. S., Kobayashi, T., Pittelkow, M. R., Strehler, E. E. Human calmodulin-like protein is an epithelial-specific protein regulated during keratinocyte differentiation. Exp. Cell Res. 267: 216-224, 2001. [PubMed: 11426940] [Full Text: https://doi.org/10.1006/excr.2001.5254]
Rogers, M. S., Strehler, E. E. The tumor-sensitive calmodulin-like protein is a specific light chain of human unconventional myosin X. J. Biol. Chem. 276: 12182-12189, 2001. [PubMed: 11278607] [Full Text: https://doi.org/10.1074/jbc.M010056200]