# CCDC74A

## Overview
CCDC74A is a gene that encodes the protein coiled-coil domain containing 74A, which plays a critical role in cell division, particularly during mitosis. The protein is primarily involved in the organization and stabilization of kinetochore fibers, essential components for the proper alignment and segregation of chromosomes. CCDC74A, along with its paralog CCDC74B, interacts directly with microtubules, facilitating the bundling of these structures, which is crucial for the formation of bipolar spindles and chromosome alignment. The proteins encoded by these genes are localized to the mitotic spindles and are integral to maintaining spindle integrity and promoting efficient mitotic progression (Zhou2019CCDC74A/B).

## Function
CCDC74A, along with its paralog CCDC74B, encodes proteins that are integral to the structure and function of the mitotic spindle during cell division. These proteins are specifically involved in the organization and stabilization of kinetochore fibers (K-fibers), which are essential for the proper alignment and segregation of chromosomes during mitosis. CCDC74A and CCDC74B bind directly to microtubules through distinct domains and are capable of bundling these microtubules both in vivo and in vitro. This bundling activity is vital for the formation of bipolar spindles and the alignment of chromosomes (Zhou2019CCDC74A/B).

The proteins are localized at the spindles and central spindles in mitotic cells, playing a crucial role in mitotic spindle integrity and chromosomal alignment. Functional studies have shown that depletion of these proteins leads to increased mitotic index, prolonged prometaphase, and reduced cell viability. Specifically, knockdown of CCDC74A/B results in shorter and misoriented spindles, increased percentages of cells in G2/M phase, and defects in mitotic progression (Zhou2019CCDC74A/B).

Moreover, CCDC74A/B proteins bind to microtubules at two separate regions rich in positively charged amino acids, facilitating their interaction with the negatively charged C-terminal tail of tubulin dimers. This interaction is essential for their function in bundling microtubules, particularly the kinetochore fibers (K-fibers), which are critical for proper chromosome alignment and stability of the spindle structure (Zhou2019CCDC74A/B).

## Interactions
CCDC74A, along with its closely related counterpart CCDC74B, participates in crucial protein-protein interactions that are essential for the proper organization and function of the mitotic spindle during cell division. These proteins directly bind to and bundle microtubules, a process that is vital for the formation and maintenance of kinetochore fibers (K-fibers) and the overall stability of the spindle apparatus. The bundling activity of CCDC74A/B is mediated through two distinct microtubule-binding regions within each protein, which interact with the negatively charged C-terminal tail of tubulin dimers (Zhou2019CCDC74A/B). 

Moreover, CCDC74A/B proteins are capable of self-association, forming homodimers or potentially larger oligomers. This self-association is critical for their function in microtubule bundling and stabilization (Zhou2019CCDC74A/B). The interaction between CCDC74A/B proteins and other spindle-associated proteins, such as NuMA and HURP, has also been suggested, although the specific mechanisms and outcomes of these interactions require further investigation (Zhou2019CCDC74A/B). These interactions highlight the role of CCDC74A/B in the dynamic and complex environment of the mitotic spindle, underscoring their importance in maintaining cellular division integrity.


## References


[1. (Zhou2019CCDC74A/B) Haining Zhou, Tao Zheng, Tianning Wang, Qi Li, Fulin Wang, Xin Liang, Jianguo Chen, and Junlin Teng. Ccdc74a/b are k-fiber crosslinkers required for chromosomal alignment. BMC Biology, September 2019. URL: http://dx.doi.org/10.1186/s12915-019-0694-9, doi:10.1186/s12915-019-0694-9. (10 citations) 10.1186/s12915-019-0694-9](https://doi.org/10.1186/s12915-019-0694-9)