There was some confusion in the nomenclature of the human BEX genes. The BEX1 referred in the publications (Quentmeier et al., 2005; Yang et al., 2002) is actually BEX2. BEX2, represented by the Genbank accession number AF220189, was called BEX1 by Yang et al. and others (Quentmeier et al., 2005; Yang et al., 2002). Later on, Alvarez et al. found that AF220189 is more similar to mouse Bex2 than to mouse Bex1 (74% and 68% identical, respectively) and that its chromosomal localization matches that of mouse Bex2 (Alvarez et al., 2005). Therefore, AF220189 is considered the human homologue of mouse Bex2, and is human BEX2.

BEX1 encodes a gene belonging to the brain expressed X-linked gene family. It is a putative tumor suppressor as it is silenced in human glioma (Foltz et al., 2006). The BEX1 gene contains three exons, but the coding region is contained in one single exon.

Interacts with neurotrophin receptor p75NTR/NGFR (Naderi et al., 2007). Interacts with olfactory marker protein (OMP) (Koo et al., 2004).

The BEX1 protein (NP_060946.3) has 125 amino acid residues.

Koo et al. assessed the expression pattern of Bex proteins in several different mouse tissues by western blot analysis (Koo et al., 2004). They used a polyclonal chicken antibody directed against a peptide common to the C-terminal region of mouse Bex1 and -2, which are 87% identical and 90% similar in amino acid sequences. They found that Bex1 and -2 proteins are expressed in mouse whole brain without olfactory bulb, olfactory bulb, olfactory epithelium and at a lower level in the heart, kidney, and liver but, not in the lung (Koo et al., 2004).

Nucleus and cytoplasm (Koo et al., 2004).

BEX1 plays a role in cell cycle progression as Bex1 levels oscillated during the cell cycle (Vilar et al., 2006). BEX1 also participates in neuronal differentiation (Vilar et al., 2006). Nerve growth factor (NGF) is a member of the neurotrophin family proteins that mediate survival, growth and differentiation of neuronal and glial cells by binding to two different types of cell surface receptors, the Trk tyrosine kinases - TrkA, TrkB and TrkC - and the p75 neurotrophin receptor (p75NTR). Vilar et al. showed that Bex1 competed with RIP2 (receptor-interacting serine-threonine kinase 2) for binding to the p75NTR intracellular domain, and elevating RIP2 levels restored the ability of cells overexpressing Bex1 to differentiate in response to NGF (Vilar et al., 2006). They further demonstrated that, in PC12 cells, Bex1 overexpression inhibited the induction of NF-kappaB activity by NGF without affecting activation of Erk1/Erk2 and AKT, while Bex1 knockdown accelerated neuronal differentiation and potentiated NF-kappaB activity in response to NGF (Vilar et al., 2006).

Five BEX members have been identified in human. They are BEX1, BEX2, NGFRAP1 (nerve growth factor receptor (TNFRSF16) associated protein 1, BEX3), BEX4, and BEX5. They are all clustered on the X chromosome at Xq22.1-2 (Alvarez et al., 2005).

None identified.