Alternative titles; symbols
HGNC Approved Gene Symbol: CETN2
Cytogenetic location: Xq28 Genomic coordinates (GRCh38): X:152,826,994-152,830,757 (from NCBI)
Caltractin, a 20-kD calcium-binding protein (also known as centrin), was purified and cloned at the DNA level from the unicellular green alga Chlamydomonas. It showed a strong amino acid sequence relatedness (50%) to the CDC31 gene product from Saccharomyces cerevisiae. Examination of mutants in Chlamydomonas caltractin and yeast CDC31 indicated that these proteins are required for the proper duplication and segregation of the centrosome (major microtubule-organizing center; MTOC) in these cells. Using the coding region of Chlamydomonas caltractin to screen a human umbilical vein endothelial cDNA library, Lee and Huang (1993) isolated a partial human homolog. The full-length human cDNA, which they isolated from a T-cell lymphoblastic leukemia cDNA library, encodes a deduced 72-amino acid protein with 4 potential EF-hand calcium-binding domains. The protein shares 70% sequence identity with its algal counterpart. Northern blot analysis indicated ubiquitous expression of a single-sized RNA species. In both HeLa and BHK cells, Lee and Huang (1993) identified caltractin as a 21-kD polypeptide specifically localized to the centrosome of interphase and mitotic cells. The high level of conservation from algae to humans and its association with the centrosome suggested that caltractin plays a fundamental role in the structure and function of the microtubule-organizing center.
Tanaka et al. (1994) demonstrated by fluorescence in situ hybridization that the CALT gene is located on Xq28. By PCR and southern analysis on YACs from the Xq28 region, Chatterjee et al. (1995) refined the assignment of the CALT gene to a region between loci DXS1104 and DXS52. In the mouse, they showed that it is located likewise between these markers on the X chromosome.
Ying et al. (2014) found that Cetn2-knockout mice were born at mendelian ratios and appeared normal at birth. The mice developed a syndromic ciliopathy composed of dysosmia and hydrocephalus; however, they did not display a retinal phenotype. Ying et al. (2019) generated Cetn3 (602907) -/- mice, which were born in a mendelian ratio, were viable and fertile, and did not have syndromic ciliopathy. Retinal morphology and function were normal in Cetn3 -/- mice. However, Cetn2/Cetn3 double-knockout mice were born in nonmendelian ratios and exhibited syndromic ciliopathy as well as progressive retina degeneration. Quantification of scotopic electroretinography revealed that retinas of Cetn2 +/- Cetn3 -/- mice had responses to light intermediate to Cetn2/Cetn3 double-knockout mice and wildtype or Cetn3 -/- mice, suggesting haploinsufficiency. Loss of Cetn2 and Cetn3 reduced Rp1 (180100)-responsive axoneme length, and resulted in accumulation of Cetn1 at the connecting cilium (CC) center, with variable depletion at the distal and proximal ends. Photoreceptors of double-knockout mice displayed a gradual deacetylation of CC microtubules, but hyperacetylation of proximal outer segment (OS) axoneme microtubules. In addition, OS discs were misaligned and CC/axonemes were dilated. The distal CC dilation of Cetn2- and Cetn3-deficient photoreceptors correlated with gradual depletion of Spata7 (609868) from CC.
Chatterjee, A., Tanaka, T., Parrish, J. E., Herman, G. E. Refined mapping of caltractin in human Xq28 and in the homologous region of the mouse X chromosome places the gene with the bare patches (Bpa) and striated (Str) critical regions. Mammalian Genome 6: 802-804, 1995. [PubMed: 8597638] [Full Text: https://doi.org/10.1007/BF00539008]
Lee, V. D., Huang, B. Molecular cloning and centrosomal localization of human caltractin. Proc. Nat. Acad. Sci. 90: 11039-11043, 1993. [PubMed: 8248209] [Full Text: https://doi.org/10.1073/pnas.90.23.11039]
Tanaka, T., Okui, K., Nakamura, Y. Assignment of the human caltractin gene (CALT) to Xq28 by fluorescence in situ hybridization. Genomics 24: 609-610, 1994. [PubMed: 7713520]
Ying, G., Avasthi, P., Irwin, M., Gerstner, C. D., Frederick, J. M., Lucero, M. T., Baehr, W. Centrin 2 is required for mouse olfactory ciliary trafficking and development of ependymal cilia planar polarity. J. Neurosci. 34: 6377-6388, 2014. [PubMed: 24790208] [Full Text: https://doi.org/10.1523/JNEUROSCI.0067-14.2014]
Ying, G., Frederick, J. M., Baehr, W. Deletion of both centrin 2 (CETN2) and CETN3 destabilizes the distal connecting cilium of mouse photoreceptors. J. Biol. Chem. 294: 3957-3973, 2019. [PubMed: 30647131] [Full Text: https://doi.org/10.1074/jbc.RA118.006371]