The NACC1 gene is encoded by 5 exons spanning 5958 base pairs that are located on chromosome 19p13.13.

4556 bp linear mRNA. The coding sequence (1584 bp) is from 169-1752 bp.

NAC1 consists of 527 amino acids and the protein is predicted to have a molecular weight of 57258 Da (Stead et al., 2009). Comprising of a N terminal BTB/POZ domain and the C terminal BEN domain, NAC1 is missing a Zinc Finger domain unlike many members of the BTB/POZ family. The homodimerization of NAC1 mediated by the BTB domain is thought to be essential for its functional activities (Nakayama et al., 2006). The newly defined BEN domain may mediate protein-DNA interactions (Abhiman et al., 2008), however it remains to be investigated if NAC1 is indeed a DNA binding protein.

Expressed in Arabidopsis root as a transcription activator, found in nuclear accumbens of neuronal tissues and overexpressed in various human neoplastic diseases (Cha et al., 1997; Xie et al., 2002; Guo et al., 2005; Nakayama et al., 2006; Shen et al., 2007; Nakayama et al., 2007; Yeasmin et al., 2008; Mackler et al., 2008; Ishibashi et al., 2009; Korutla et al., 2009; Ishikawa et al., 2010; Yeasmin et al., 2011).

Nucleus and cytoplasm. Dynamic changes in subcellular localization of NAC1 at the different phases of cell cycle progression were documented. In non-mitotic cells, NAC1 accumulated in distinct nuclear punctate bodies. During mitosis, these punctate nuclear bodies dissolve into a diffuse pattern of distribution in the cytoplasm. NAC1 nuclear bodies reappeared once mitosis was completed and the nuclear membrane reformed. (Wu et al., 2011).

First identified as a novel transcript in the nucleus-accumbens of cocaine-addicted rats (Cha et al., 1997), NAC1 was known as a transcriptional corepressor (Korutla et al., 2009) with well defined functions in the murine neurologic physiological pathways (Shen et al., 2007; Mackler et al., 2008) and Arabidopsis root development (Xie et al., 2002; Guo et al., 2005). The role of NAC1 in human cancer was unknown. Preliminary studies of SAGE (Serial Analysis of Gene Expression) libraries were conducted to elucidate the role of NAC1 in the pathogenesis of human cancers and had revealed the higher expression levels of NAC1 in tumor samples as compared to the normal tissues in various cancer types such as pancreas, liver, and breast (Nakayama et al., 2006). Following that, detailed gene expression studies were undertaken in patient tumor samples and characterized the overexpression of NAC1 in cervical carcinoma and ovarian high-grade serous carcinoma, one of the most lethal neoplastic diseases in women (Nakayama et al., 2006; Nakayama et al., 2007; Yeasmin et al., 2008; Ishibashi et al., 2009; Jinawath et al., 2009; Nakayama et al., 2010; Ishikawa et al., 2010; Shih et al., 2011; Yeasmin et al., 2011). Amplification of NACC1 has also been recently reported in ovarian cancer, and analysis of The Cancer Genome Atlas data set revealed that NACC1 was one of the top potential "driver" genes that showed the highest correlation between DNA and RNA copy number in ovarian high-grade serous carcinomas (Shih et al., 2011). Additionally, NAC1 up-regulation is associated with disease aggressiveness and contributes to the development of chemo-resistance (Nakayama et al., 2006; Jinawath et al., 2009; Nakayama et al., 2010; Zhang et al., 2012). NAC1 enables the survival and growth of ovarian cancer cells by regulating several downstream targets including those involved in Gadd45 cell survival pathway (Nakayama et al., 2007; Jinawath et al., 2009), fatty acid metabolism (Ueda et al., 2010), and HMGB-1 mediated autophagic response (Zhang et al., 2012). NAC1 function has also been demonstrated to be essential for the migration of ovarian and melanoma cancer cells (Yamazaki et al., 2005; Nakayama et al., 2010). Mouse tumor xenograft studies illustrated the in vivo therapeutic potential of inactivating Nac1 function; as such manipulation in SKOV3 ovarian cancer cells and HeLa cervical cancer cells was demonstrated to be sufficient to inhibit the growth of tumor xenografts (Nakayama et al., 2006). Nac1 is more recently associated with maintenance of the pluripotency of mouse embryonic stem cells through its interaction with Nanog (Wang et al., 2006; Ma et al., 2009).

BEN1 domain, BTB/POZ domain.