Alternative titles; symbols
HGNC Approved Gene Symbol: HAUS1
Cytogenetic location: 18q21.1 Genomic coordinates (GRCh38): 18:46,104,385-46,128,333 (from NCBI)
HAUS1 is 1 of 8 subunits of the 390-kD human augmin complex, or HAUS complex. The augmin complex was first identified in Drosophila, and its name comes from the Latin verb 'augmentare,' meaning 'to increase.' The augmin complex is a microtubule-binding complex involved in microtubule generation within the mitotic spindle and is vital to mitotic spindle assembly (Goshima et al., 2008; Uehara et al., 2009).
By screening a HeLa cell cDNA library for genes that induced agar invasion in S. cerevisiae, Einarson et al. (2004) cloned CCDC5, which they designated HEIC. The deduced 278-amino acid protein contains 3 potential coiled-coil domains and a C-terminal leucine-rich nuclear exclusion sequence. CCDC5 shares 89%, 84%, and 54% amino acid identity with cow, mouse, and frog Ccdc5, respectively. No closely related proteins were identified in Drosophila or C. elegans. Northern blot analysis detected a transcript of about 1.2 to 1.3 kb in all tissues examined, with highest abundance in pancreas, heart, liver, kidney, and muscle. Western blot analysis detected a single CCDC5 protein of about 32 kD in human, dog, and monkey cells.
Using mass spectrometry to identify proteins immunoprecipitated with the augmin complex subunit DGT6 (HAUS6; 613433) from HeLa cell mitotic extracts, Uehara et al. (2009) identified CCDC5. The deduced 277-amino acid protein has a calculated molecular mass of 31.8 kD.
Einarson et al. (2004) found that CCDC5-depleted HeLa cells formed metaphase plates with normal timing after G2/M transition, but many cells had disorganized mitotic spindles. Subsequently, severe defects occurred at the metaphase-anaphase transition that were characterized by a significant delay at this stage or, more commonly, cellular disintegration accompanied by the display of classic biochemical markers of apoptosis. The mitotic defects occurred in spite of functional cell cycle checkpoints.
Uehara et al. (2009) found that epitope-tagged CCDC5 immunoprecipitated endogenous DGT6 from HeLa cells. Like other augmin subunits, fluorescence-tagged CCDC5 localized to the metaphase spindle and accumulated at centrosomes during interphase. Knockdown of CCDC5 via RNA interference reduced the signals for gamma-tubulin (TUBG1; 191135) and microtubules at mitotic spindles.
Using RNA interference, Lawo et al. (2009) independently showed that HAUS1 is a critical component of the human augmin complex, and they confirmed interaction of HAUS1 with the other 7 augmin subunits by coimmunoprecipitation analysis. Knockdown of HAUS1 or any of the other augmin subunits resulted in destabilization of kinetochore microtubules, formation of multipolar spindles, fragmentation of centrosomes, and increased centrosome size. These severe mitotic defects were alleviated by codepletion of the nuclear mitotic apparatus (NUMA; see 164009), suggesting that augmin and NUMA regulate opposing activities.
Einarson et al. (2004) determined that the CCDC5 gene contains 10 exons.
By genomic sequence analysis, Einarson et al. (2004) mapped the CCDC5 gene to chromosome 18q21.1. There are 3 CCDC5 pseudogenes on chromosomes 5, 8, and X.
Einarson, M. B., Cukierman, E., Compton, D. A., Golemis, E. A. Human enhancer of invasion-cluster, a coiled-coil protein required for passage through mitosis. Molec. Cell. Biol. 24: 3957-3971, 2004. [PubMed: 15082789] [Full Text: https://doi.org/10.1128/MCB.24.9.3957-3971.2004]
Goshima, G., Mayer, M., Zhang, N., Stuurman, N., Vale, R. D. Augmin: a protein complex required for centrosome-independent microtubule generation within the spindle. J. Cell Biol. 181: 421-429, 2008. [PubMed: 18443220] [Full Text: https://doi.org/10.1083/jcb.200711053]
Lawo, S., Bashkurov, M., Mullin, M., Gomez Ferreria, M., Kittler, R., Habermann, B., Tagliaferro, A., Poser, I., Hutchins, J. R. A., Hegemann, B., Pinchev, D., Buchholz, F., Peters, J.-M., Hyman, A. A., Gingras, A.-C., Pelletier, L. HAUS, the 8-subunit human augmin complex, regulates centrosome and spindle integrity. Curr. Biol. 19: 816-826, 2009. [PubMed: 19427217] [Full Text: https://doi.org/10.1016/j.cub.2009.04.033]
Uehara, R., Nozawa, R., Tomioka, A., Petry, S., Vale, R. D., Obuse, C., Goshima, G. The augmin complex plays a critical role in spindle microtubule generation for mitotic progression and cytokinesis in human cells. Proc. Nat. Acad. Sci. 106: 6998-7003, 2009. [PubMed: 19369198] [Full Text: https://doi.org/10.1073/pnas.0901587106]