Alternative titles; symbols
HGNC Approved Gene Symbol: RHOXF1
Cytogenetic location: Xq24 Genomic coordinates (GRCh38): X:120,109,051-120,120,438 (from NCBI)
By searching databases for sequences similar to paired-like homeobox proteins of the PEPP subfamily, followed by PCR of ovary cDNA, Geserick et al. (2002) cloned OTEX. The deduced 184-amino acid protein contains a characteristic 60-amino acid homeobox domain (HD). The HD has a rare helix-breaking proline at position 29 and a lysine at position 50, a site essential for the DNA-binding specificity of homeobox proteins. The HD of OTEX shares 53.3% identity with that of ESXR1 (see 300154) and 45% identity with that of PEPP2 (300447). RT-PCR detected highest expression in ovary, testis, and epididymis, and weaker expression in prostate, mammary gland, and uterus. Immunofluorescence analysis revealed an exclusively nuclear localization that required a C-terminal nuclear localization signal.
The mouse Pem gene resides on the X chromosome and is expressed exclusively in testis, epididymis, ovary, and placenta. Due to the rapid evolution of Pem, it has been difficult to identify a human ortholog (Lin et al., 1994; Maiti et al., 1996; Sutton and Wilkinson, 1997). By searching databases using the sequence encoded by exon 4 of mouse Pem as bait, followed by RT-PCR of lymphocytic leukemia cell RNA, Wayne et al. (2002) cloned OTEX, which they designated PEPP1. Northern blot analysis detected a 0.8-kb transcript only in testis. RT-PCR detected expression in epididymis and in several tumor cell lines of diverse origin.
MacLean et al. (2005) identified a cluster of 12 homeobox genes on the mouse X chromosome expressed exclusively in male and female reproductive tissues. These 'reproductive homeobox X-linked' (Rhox) genes include Pem, Psx1, and Psx2, which MacLean et al. (2005) renamed Rhox5, Rhox6, and Rhox9, respectively. MacLean et al. (2005) identified human PEPP1 and PEPP2 as the likely orthologs of 1 or more Rhox genes, but extensive searching failed to identify any other human homeobox genes in the region syntenic to the mouse Rhox gene cluster.
Geserick et al. (2002) found OTEX expressed in a prostate cell line expressing androgen receptor (313700), and the expression increased following androgen treatment. OTEX was not expressed in a related cell line lacking androgen receptor.
Geserick et al. (2002) and Wayne et al. (2002) determined that the OTEX gene has 3 exons. Geserick et al. (2002) found that the promoter region does not contain a TATA box.
By genomic sequence analysis, Geserick et al. (2002) and Wayne et al. (2002) mapped the OTEX gene (RHOXF1) to chromosome Xq24. Wayne et al. (2002) noted that this region shows homology of synteny to a region of mouse chromosome X that contains Pem, Psx1, and Psx2, the 3 murine PEPP genes.
Geserick, C., Weiss, B., Schleuning, W.-D., Haendler, B. OTEX, an androgen-regulated human member of the paired-like class of homeobox genes. Biochem. J. 366: 367-375, 2002. [PubMed: 11980563] [Full Text: https://doi.org/10.1042/BJ20020399]
Lin, T.-P., Labosky, P. A., Grabel, L. B., Kozak, C. A., Pitman, J. L., Kleeman, J., MacLeod, C. L. The Pem homeobox gene is X-linked and exclusively expressed in extraembryonic tissues during early murine development. Dev. Biol. 166: 170-179, 1994. [PubMed: 7958444] [Full Text: https://doi.org/10.1006/dbio.1994.1305]
MacLean, J. A., II, Chen, M. A., Wayne, C. M., Bruce, S. R., Rao, M., Meistrich, M. L., Macleod, C., Wilkinson, M. F. Rhox: a novel homeobox gene cluster. Cell 120: 369-382, 2005. [PubMed: 15707895] [Full Text: https://doi.org/10.1016/j.cell.2004.12.022]
Maiti, S., Doskow, J., Sutton, K., Nhim, R. P., Lawlor, D. A., Levan, K., Lindsey, J. S., Wilkinson, M. F. The Pem homeobox gene: rapid evolution of the homeodomain, X chromosomal localization, and expression in reproductive tissue. Genomics 34: 304-316, 1996. [PubMed: 8786129] [Full Text: https://doi.org/10.1006/geno.1996.0291]
Sutton, K. A., Wilkinson, M. F. The rapidly evolving Pem homeobox gene and Agtr2, Ant2, and Lamp2 are closely linked in the proximal region of the mouse X chromosome. Genomics 45: 447-450, 1997. [PubMed: 9344676] [Full Text: https://doi.org/10.1006/geno.1997.4946]
Wayne, C. M., MacLean, J. A., II, Cornwall, G., Wilkinson, M. F. Two novel X-linked homeobox genes, hPEPP1 and hPEPP2, selectively expressed in the testis. Gene 301: 1-11, 2002. [PubMed: 12490318] [Full Text: https://doi.org/10.1016/s0378-1119(02)01087-9]