The reference OMIM entry for this protein is 615944

C2 calcium-dependent domain-containing protein 3; c2cd3

DESCRIPTION

Based on experiments in mice, C2CD3 is predicted to be an essential regulator of cilia formation, hedgehog signaling (see SHH, 600725), and embryonic patterning (Hoover et al., 2008). C2CD3 is also a positive regulator of centriole length (Thauvin-Robinet et al., 2014).

CLONING

Hoover et al. (2008) cloned mouse C2cd3. The deduced 2,322-amino acid protein has a calculated molecular mass of approximately 250 kD. It has 5 C2 domains predicted to mediate interactions with proteins and membrane lipids. C2cd3 was expressed ubiquitously in mouse embryos between embryonic day 8.5 (E8.5) and E10.5. Fluorescence-tagged C2cd3 localized to the ciliary basal body in transfected mouse embryonic fibroblasts (MEFs). Orthologs of C2cd3 were detected in vertebrates, including human, but not in invertebrates. Thauvin-Robinet et al. (2014) reported that C2CD3 contains a C2-like N-terminal domain, followed by 6 canonical C2 domains predicted to bind calcium and phospholipid headgroups. Fluorescence-tagged mouse C2cd3 localized to centriolar satellites and to the distal lumen of mature centrioles and procentrioles, near the distal tip. Database analysis revealed orthologs of C2CD3 in organisms that assemble centrioles or cilia.

MAPPING

By genomic sequence analysis, Hoover et al. (2008) mapped the C2CD3 gene to human chromosome 11q13.4 and mouse chromosome 7.

GENE FUNCTION

Using coimmunoprecipitation analysis, Thauvin-Robinet et al. (2014) found that endogenous C2CD3 interacted with OFD1 (300170) in human RPE cells. Epitope-tagged human OFD1 also interacted with fluorescence-tagged mouse C2cd3 in vitro. RPE cells overexpressing fluorescence-tagged mouse C2cd3 developed hyperelongated centrioles and centriole-like microtubular rods in various regions of the cytoplasm. Coexpression of mouse Ofd1 with C2cd3 reduced the frequency of hyperelongated centrioles in transfected U2OS cells. Using wildtype and C2cd3-null MEFs, Ye et al. (2014) determined that localization of C2cd3 to centriolar satellites depended on Pcm1 (600299) and dynein (see 600112)-mediated retrograde transport. Localization of C2cd3 to distal ends of the mother and daughter centrioles was required for recruitment of the distal appendage proteins Ccdc41 (CEP83; 615847), Sclt1 (611399), Cep89 (615470), Fbf1, and Cep164 (614848) and for the intraflagellar transport B proteins Ift88 (600595) and Ift52. In the absence of C2cd3, Ttbk2 (611695) was not recruited to the distal end of the mother centriole, and Cp110 (609544) was not removed. C2cd3 was also required for docking of ciliary vesicles to the mother centriole. Ye et al. (2014) concluded that C2CD3 regulates initiation of ciliogenesis through centriolar maturation, ciliogenic protein recruitment, and ciliary vesicle docking.

MOLECULAR GENETICS

In a 4-year-old boy with orofaciodigital syndrome (OFD14; 615948), Thauvin-Robinet et al. (2014) identified a homozygous truncating mutation in the C2CD3 gene (R62X; 615944.0001). The mutation was found by whole-exome sequencing and segregated with the disorder in the family. Sequencing of the coding exons of C2CD3 in 34 patients with OFD identified 1 fetus who was compound heterozygous for 2 mutations in the C2CD3 gene (615944.0002 and 615944.0003). Functional studies of the 3 variants were not performed, but Thauvin-Robinet et al. (2014) demonstrated that C2CD3 is required for cilium assembly and function, consistent with OFD being a cili ... More on the omim web site

Subscribe to this protein entry history

June 30, 2020: Protein entry updated
Automatic update: OMIM entry 615944 was added.

Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).