Tissue interactions that take place in early embryos are required for normal eye development (Spemann 1901; Lewis 1904). Without a lens placode, the optic vesicle remains rudimentary, and the optic cup with well-defined neuroretinal and pigmented layers is not formed (Hyer et al. 1998). Ablation of the developing lens using a toxin transgene inhibits the formation of the iris, the ciliary body, the vitreous body, and the retina (Breitman et al. 1989; Harrington et al. 1991). Therefore, the lens is an important source of signals that influence eye development, and a variety of genes expressed by the lens have been identified. Mu et al. 2003; used signal sequence trap screens (Klein et al. 1996) to isolate molecule(s) from a chick E6 lens cDNA library. A novel clone was found in the lens equatorial region and was therefore designated ‘Equarin’.
Two forms of Equarin were isolated from a chick E6 lens cDNA library. Equarin-L consists of 592 amino acid residues, the N-terminal regions of which are identical to those of Equarin-S as well as an extra 366 amino acid residues in the C-terminal region. In mammals, this gene and its encoded protein have been renamed CCDC80 (coiled-coil domain containing 80, also known as DRO1 and URB). Murine and human CCDC80 have high homology (murine 65.6% and human 66.4%) to Equarin (Aoki et al. 2002; Mu et al. 2003). Rat, murine and human CCDC80 have a wide tissue distribution (e.g., fat, lung, ovary, uterus, mammary gland, testis, liver, spleen, pancreas, kidney, heart, stomach, bladder, skeletal muscle, skin, and brain) (Aoki et al. 2002; Okada et al. 2008; Tremblay et al. 2009). Three repeat regions of Equarin-L and mouse CCDC80 display similarity to a C-terminal region of SRPX (sushi-repeat-containing protein encoded on the X chromosome)/drs (downregulated by Src) and SRPX2 (sushi-repeat protein upregulated in leukemia)/SRPUL proteins (Dry et al. 1995; Meindl et al. 1995; Pan et al. 1996; Inoue et al. 1998; Kurosawa et al. 1999; Marcantonio et al. 2001; Mu et al. 2003; Liu et al. 2004) (Fig. 1A). Pawłowski et al. has described not only vertebrate examples of this domain, which was named DUDES (DRO1-URB-DRS-Equarin-SRPUL) (Bommer et al. 2005), but also the many prokaryotic homologues. Therefore, they decided to rename the domain to P-DUDES (Prokaryotes-DUDES) (Pawłowski et al. 2010). Although the sequence similarity of the DUDES domains in CCDC80, SRPX and SRPX2 has been discussed on many occasions, the functional relativity between them has been rarely discussed. Roles for CCDC80 in tumor suppression, energy metabolism, embryonic development and skeletal formation have been suggested. However, the role of CCDC80 and its regulation at the cellular level are only just beginning to be understood.