There is an SOX2OT (SOX2 overlapping transcript) that encodes a non-coding RNA. SOX2OT contains at least five exons and is transcribed into a mRNA of about 3.4 kb from the same strand as SOX2.

SOX2 is a single exon gene that encodes a member of the SRY-related HMG-box (SOX) family of transcription factors. The SOX2 single exon contains the 5 untranslated region, CDS region and the 3 untranslated region (427 bp, 954 bp, 1122 bp). The HMG box is a DNA binding domain that is highly conserved throughout eukaryotic species.

The 2503 bases of human SOX2 mRNA contains an open reading frame of 954 bases, resulting in a protein of 318 amino acid residues.

The SOX2 protein binds to DNA. The 3D structure for the ternary complex of the DNA binding domains of the Oct1 and Sox2 transcription factors with a 19mer oligonucleotide was solved (Williams et al., 2004; http://oca.weizmann.ac.il).

SOX2 is overexpressed in stem cells and many different kinds of cancer cells, including glioma, breast cancer, colorectal cancer and etc.

Nucleus and cytoplasm.

SOX2 is involved in the regulation of embryonic development and in the determination of cell fate. SOX2 is one of the four transcription factors (SOX2, KLF4, OCT4 and c-Myc), whose over expression can induce pluripotency in both mice and human somatic cells (Takahashi and Yamanaka, 2006; Takahashi et al., 2007). Again, SOX2 is one of the genes in another set of four factors (OCT4, SOX2, NANOG and LIN28) that were able to reprogram human somatic cells to pluripotent stem cells and that exhibit the essential characteristics of embryonic stem (ES) cells (Yu et al., 2007). SOX2 is one of the two factors (SOX2 and OCT4) that were sufficient to generate induced pluripotent stem cells from human cord blood cells (Giorgetti et al., 2010).

So far, twenty SOX genes have been identified in humans and mice and they can be divided into 10 subgroups on the basis of sequence similarity and genomic organization (Bowles et al., 2000; Schepers et al., 2002). SOX genes bind to the minor groove in DNA to control diverse developmental processes (Wegner, 1999). Three genes, SOX1, SOX2 and SOX3, show the closest homology to SRY and share the maximum homology within the HMG domain. These genes also share significant homology outside the HMG box and are highly conserved throughout their evolution.

Mutations in SOX2 cause anophthalmia (no eye), microphthalmia (small eye) and associated ocular developmental anomalies. Fantes identified two nonsense amino-acid changes (S83X and E93X) in the HMG box (high-mobility group DNA-binding domain), which could lead to ablate DNA binding (Fantes et al., 2003). They also observed a recurrent de novo nonsense mutation (529C->T resulting in the amino-acid change Q177X) (Fantes et al., 2003). Additional mutations were later reported for new cases (Bakrania et al., 2007; Pedace et al., 2009; Williamson et al., 2006). SOX2 mutation also caused hearing loss, and brain anomalies (Hagstrom et al., 2005), hypogonadotropic hypogonadism (Sato et al., 2007), ocular coloboma (Wang et al., 2008).