Weinmann Arndt, Galle Peter R, Teufel Andreas
Department of Internal Medicine I, Johannes Gutenberg University, Mainz, Germany.
Int J Mol Med. 2005 Sep;16(3):443-8.
Homeobox genes have been demonstrated to play important roles during cancer differentiation and embryonic development. The subset of Iroquois-related homeobox genes (IRXs) have furthermore been demonstrated to be involved in several embryonic developmental processes such as patterning of the anterior-posterior and dorso-ventral axis, as well as specific regions of the central nervous system, and differentiation of the otic vesicle, branchial epithelium, and limbs. We have characterized a novel homeodomain protein and corresponding gene by means of computational biology. Since the protein sequence displayed high similarity to the human IRX proteins, the newly identified homeodomain protein was named Iroquois family related homeodomain protein (IFRX). The IFRX protein sequence was found to be highly conserved in vertebrates. The corresponding IFRX gene was located on chromosome 10p12.1 and is organized in seven exons. The protein is predicted to be localized to the nucleus, supporting evidence for a functional role as a transcription factor, as suggested by the existence of a homeodomain. Preliminary expression profiling by biocomputational means predicted a rather broad expression profile with expression in the bone marrow, brain, heart, kidney, liver, lung, pancreas, prostate, skeletal muscle, spinal cord, spleen and thymus. However, expression in several tissues seemed to be low. In addition, approximately one third of all available EST sequences were obtained from embryonic tissues, suggesting that IFRX has a role in embryonic development.
同源框基因已被证明在癌症分化和胚胎发育过程中发挥重要作用。此外，已证明与易洛魁族相关的同源框基因（IRXs）子集参与了多个胚胎发育过程，如前后轴和背腹轴的模式形成、中枢神经系统的特定区域以及耳泡、鳃上皮和肢体的分化。我们通过计算生物学方法鉴定了一种新的同源结构域蛋白及其相应基因。由于该蛋白序列与人类IRX蛋白显示出高度相似性，新鉴定的同源结构域蛋白被命名为易洛魁族家族相关同源结构域蛋白（IFRX）。发现IFRX蛋白序列在脊椎动物中高度保守。相应的IFRX基因位于染色体10p12.1上，由七个外显子组成。该蛋白预计定位于细胞核，这为由同源结构域的存在所暗示的作为转录因子的功能作用提供了支持证据。通过生物计算方法进行的初步表达谱分析预测其表达谱相当广泛，在骨髓、脑、心脏、肾脏、肝脏、肺、胰腺、前列腺、骨骼肌、脊髓、脾脏和胸腺中均有表达。然而，在几种组织中的表达似乎较低。此外，所有可用EST序列中约三分之一来自胚胎组织，这表明IFRX在胚胎发育中起作用。
