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HGNC Approved Gene Symbol: ODF2
Cytogenetic location: 9q34.11 Genomic coordinates (GRCh38): 9:128,455,185-128,501,292 (from NCBI)
ODF2 encodes multiple protein isoforms that have roles in the formation of primary cilia and sperm flagella and in coordinating ciliary beating (Kunimoto et al., 2012).
See ODF1 (182878). Brohmann et al. (1997) used antibodies against Odf proteins to screen a rat testis expression library and isolated the rat Odf2 gene. Sequence analysis revealed that the protein has an overall alpha-helical structure with 2 regions identical to the dimerization region of a leucine zipper motif. Brohmann et al. (1997) documented Odf2 cDNAs with 3 different 5-prime end sequences, presumed to be the result of alternative splicing. They found expression of the rat gene only in testis.
The EST database contains several human cDNA sequences which are closely related to rat Odf2, suggesting that a human homolog exists (Scott, 1997). These human cDNA sequences were derived from testis, epididymis, and fetal brain libraries.
Shao et al. (1997) used a yeast 2-hybrid screening with the leucine zipper region of ODF1 (ODF27; Shao and van der Hoorn, 1996) as bait to isolate rat testis-specific proteins that could interact with ODF27. They demonstrated that one of the novel genes isolated encoded the 84-kD ODF protein ODF2.
Soung et al. (2006) stated that the deduced 638-amino acid ODF2 protein has 2 leucine zipper motifs in its C-terminal half. Using an inactive mutant of the mitotic kinase PLK1 (602098) as bait in a yeast 2-hybrid screen of a human testis cDNA library, followed by RT-PCR of HeLa cell RNA, they identified 2 splice variants of ODF2 that they called cenexin-1 and cenexin-1 variant-1. Cenexin-1 and cenexin-1 variant-1 encode proteins of 805 and 824 amino acids, respectively. Both isoforms contain a C-terminal extension compared with ODF2, and cenexin-1 variant-1 also has a 19-amino acid insertion near its N-terminal end. Northern blot analysis of synchronized HeLa cells detected a single transcript of about 4.0 kb, representing cenexin-1. Cenexin-1 localized at the microtubule-organizing center in interphase and at spindle poles in mitosis, suggesting that cenexin-1 is a centrosomal protein. Fluorescence-tagged cenexin-1 primarily localized to the mother centrosome in interphase and to both mother and daughter centrosomes in mitosis.
Using real-time RT-PCR with a probe for the 3-prime region of mouse Odf2/cenexin, Kunimoto et al. (2012) detected highest expression in mouse trachea and lung, with much lower expression in brain, and little to no expression in heart, liver, and kidney. Western blot analysis using an antibody against the N-terminal region of Odf2/cenexin detected an apparent 75-kD protein in mouse testis and an apparent 90-kD protein in mouse trachea, lung, kidney, brain, and oviduct.
Soung et al. (2006) determined that the ODF2 gene contains 21 exons and spans 44.8 kb.
By FISH, Shao et al. (1998) mapped the human ODF2 gene to chromosome 9q34. Soung et al. (2006) mapped the ODF2 gene to chromosome 9q34.11 by genomic sequence analysis.
Using protein pull-down and coimmunoprecipitation analyses, Soung et al. (2006) confirmed that cenexin-1 interacted directly with PLK1. Mutation analysis revealed that the C-terminal domain of cenexin-1 interacted with the polo-box domain of PLK1. The C-terminal domain of cenexin-1 was also required to recruit PLK1 to centrosomes. Depletion of cenexin-1 from HeLa cells delocalized centrosomal PLK1, diminished gamma-tubulin (see 191135) recruitment to centrosomes, and altered localization of a subset of centrosomal proteins required for microtubule nucleation and function. Depletion of cenexin-1 also resulted in severe mitotic defects, including chromosome alignment and segregation defects. A significant fraction of these cells also showed multipolar chromosomes and apoptotic cell death.
Kunimoto et al. (2012) developed a line of mice with deletion of exons 6 and 7 of Odf2, which they called Odf2(delta-ex6,7) mice. Homozygous Odf2(delta-ex6,7) mice were born at the expected mendelian ratio, but only 20% survived past weaning. Surviving mice were characterized by a coughing/sneezing-like phenotype, sinusitis, otitis media, and a slight tendency to hydrocephaly, suggesting primary ciliary dyskinesia. Unlike Odf2 -/- F9 embryonic mouse carcinoma cells, homozygous Odf2(delta-ex6,7) mice were born with primary cilia and expressed low levels of N-terminally truncated Odf2/cenexin. Antibody raised against the Odf2/cenexin C-terminal region detected slight immunofluorescence at the base of cilia in homozygous Odf2(delta-ex6,7) tracheal cells, but not in Odf2 -/- F9 cells. Cilium appeared to nucleate from the basal body in Odf2(delta-ex6,7) cells, but the basal foot was completely lost, and basal bodies failed to position apically in some cells. Basal feet were also absent in oviduct epithelial cells and ependymal cells in brains of homozygous Odf2(delta-ex6,7) mice. Live imaging of isolated Odf2(delta-ex6,7) trachea preparations revealed uncoordinated ciliary beating and inefficient fluid flow across the luminal surface. Deficiency of full-length Odf2/cenexin also perturbed the polarized distribution of planar cell polarity (PCP) proteins and PCP-dependent apical organization of microtubules.
Brohmann, H., Pinnecke, S., Hoyer-Fender, S. Identification and characterization of new cDNAs encoding outer dense fiber proteins of rat sperm. J. Biol. Chem. 272: 10327-10332, 1997. [PubMed: 9092585] [Full Text: https://doi.org/10.1074/jbc.272.15.10327]
Kunimoto, K., Yamazaki, Y., Nishida, T., Shinohrara, K., Ishikawa, H., Hasegawa, T., Okanoue, T., Harnada, H., Noda, T., Tamura, A., Tsukita, S., Tsukita, S. Coordinated ciliary beating requires Odf2-mediated polarization of basal bodies via basal feet. Cell 148: 189-200, 2012. [PubMed: 22265411] [Full Text: https://doi.org/10.1016/j.cell.2011.10.052]
Scott, A. F. Personal Communication. Baltimore, Md. 9/10/1997.
Shao, X., Murthy, S., Demetrick, D. J., van der Hoorn, F. A. Human outer dense fiber gene, ODF2, localizes to chromosome 9q34. Cytogenet. Cell Genet. 83: 221-223, 1998. [PubMed: 10072582] [Full Text: https://doi.org/10.1159/000015183]
Shao, X., Tarnasky, H. A., Schalles, U., Oko, R., van der Hoorn, F. A. Interactional cloning of the 84-kDa major outer dense fiber protein Odf84: leucine zippers mediate associations of Odf84 and Odf27. J. Biol. Chem. 272: 6105-6113, 1997. [PubMed: 9045620] [Full Text: https://doi.org/10.1074/jbc.272.10.6105]
Shao, X., van der Hoorn, F. A. Self-interaction of the major 27-kilodalton outer dense fiber protein is in part mediated by a leucine zipper domain in the rat. Biol. Reprod. 55: 1343-1350, 1996. [PubMed: 8949892] [Full Text: https://doi.org/10.1095/biolreprod55.6.1343]
Soung, N.-K., Kang, Y. H., Kim, K., Kamijo, K., Yoon, H., Seong, Y.-S., Kuo, Y.-L., Miki, T., Kim, S. R., Kuriyama, R., Giam, C.-Z., Ahn, C. H., Lee, K. S. Requirement of hCenexin for proper mitotic functions of polo-like kinase 1 at the centrosomes. Molec. Cell. Biol. 26: 8316-8335, 2006. [PubMed: 16966375] [Full Text: https://doi.org/10.1128/MCB.00671-06]