| Note |
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. |
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| | A diagram using the UCSC genome browser showing the locations of the five BEX members in the order of BEX5-BEX1-BEX4-BEX2-NGFRAP1 (nerve growth factor receptor (TNFRSF16) associated protein 1, BEX3) on the X chromosome at Xq22.1-2, along with other genes in the region. |
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| Description | 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. |
| Note | Interacts with neurotrophin receptor p75NTR/NGFR (Naderi et al., 2007). Interacts with olfactory marker protein (OMP) (Koo et al., 2004). |
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| Description | The BEX1 protein (NP_060946.3) has 125 amino acid residues. |
| Expression | 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). |
| Localisation | Nucleus and cytoplasm (Koo et al., 2004). |
| Function | 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). |
| Homology | 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). |
| Characterization of the Bex gene family in humans, mice, and rats. |
| Alvarez E, Zhou W, Witta SE, Freed CR. |
| Gene. 2005 Aug 29;357(1):18-28. |
| PMID 15958283 |
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| The SOX2 response program in glioblastoma multiforme: an integrated ChIP-seq, expression microarray, and microRNA analysis. |
| Fang X, Yoon JG, Li L, Yu W, Shao J, Hua D, Zheng S, Hood L, Goodlett DR, Foltz G, Lin B. |
| BMC Genomics. 2011 Jan 6;12:11. |
| PMID 21211035 |
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| Genome-wide analysis of epigenetic silencing identifies BEX1 and BEX2 as candidate tumor suppressor genes in malignant glioma. |
| Foltz G, Ryu GY, Yoon JG, Nelson T, Fahey J, Frakes A, Lee H, Field L, Zander K, Sibenaller Z, Ryken TC, Vibhakar R, Hood L, Madan A. |
| Cancer Res. 2006 Jul 1;66(13):6665-74. |
| PMID 16818640 |
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| The interaction of Bex and OMP reveals a dimer of OMP with a short half-life. |
| Koo JH, Gill S, Pannell LK, Menco BP, Margolis JW, Margolis FL. |
| J Neurochem. 2004 Jul;90(1):102-16. |
| PMID 15198671 |
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| BEX2 is overexpressed in a subset of primary breast cancers and mediates nerve growth factor/nuclear factor-kappaB inhibition of apoptosis in breast cancer cell lines. |
| Naderi A, Teschendorff AE, Beigel J, Cariati M, Ellis IO, Brenton JD, Caldas C. |
| Cancer Res. 2007 Jul 15;67(14):6725-36. |
| PMID 17638883 |
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| Expression of BEX1 in acute myeloid leukemia with MLL rearrangements. |
| Quentmeier H, Tonelli R, Geffers R, Pession A, Uphoff CC, Drexler HG. |
| Leukemia. 2005 Aug;19(8):1488-9. |
| PMID 15920485 |
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| Bex1, a novel interactor of the p75 neurotrophin receptor, links neurotrophin signaling to the cell cycle. |
| Vilar M, Murillo-Carretero M, Mira H, Magnusson K, Besset V, Ibanez CF. |
| EMBO J. 2006 Mar 22;25(6):1219-30. Epub 2006 Feb 23. |
| PMID 16498402 |
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| Cloning and expression pattern of a spermatogenesis-related gene, BEX1, mapped to chromosome Xq22. |
| Yang QS, Xia F, Gu SH, Yuan HL, Chen JZ, Yang QS, Ying K, Xie Y, Mao YM. |
| Biochem Genet. 2002 Feb;40(1-2):1-12. |
| PMID 11989783 |
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