Seroussi E, Kedra D, Kost-Alimova M, Sandberg-Nordqvist A C, Fransson I, Jacobs J F, Fu Y, Pan H Q, Roe B A, Imreh S, Dumanski J P
Department of Molecular Medicine, Karolinska Hospital, CMM Building, L8:00, Stockholm, S-171 76, Sweden.
Genomics. 1999 May 1;57(3):380-8. doi: 10.1006/geno.1998.5739.
The avian tom1 (target of myb 1) gene has been previously characterized from v-myb-transformed cells. We report here cloning of the human and mouse tom1 orthologs. Both genes are expressed ubiquitously, with the highest levels in skeletal muscle, brain, and intestines, as assessed by Northern blot and mRNA in situ hybridization. The N-terminal domain of the TOM1 protein shares similarity with HGS (hepatocyte growth factor-regulated tyrosine kinase substrate) and STAM (signal-transducing adaptor molecule), which are associated with vesicular trafficking at the endosome. A putative coiled-coil domain was also detected in the central part of the TOM1 protein. This domain structure suggests that TOM1 is another member of a family of genes implicated in the trafficking regulation of growth-factor-receptor complexes that are destined for degradation in the lysosome. We also show that a human paralog of TOM1 (TOM1-like gene 1) exists. Furthermore, we provide a transcription map over a 190-kb contig of the TOM1 region. This map includes its distal neighbors HMOX1 and MCM5 and two proximal novel genes, one of which is a HMG-box-containing gene (HMG2L1), and the other of unknown function. Using a genomic PAC clone, we demonstrate that the mouse Tom1 and Hmox1 genes are part of an as yet undescribed syntenic group between mouse chromosome 8C1 and human chromosome 22q13.1.
禽源tom1(myb 1的靶标)基因先前已从v-myb转化细胞中得到鉴定。我们在此报告人类和小鼠tom1直系同源基因的克隆。通过Northern印迹和mRNA原位杂交评估发现,这两个基因均在全身表达,在骨骼肌、脑和肠道中表达水平最高。TOM1蛋白的N端结构域与HGS(肝细胞生长因子调节的酪氨酸激酶底物)和STAM(信号转导衔接分子)具有相似性,它们与内体的囊泡运输相关。在TOM1蛋白的中央部分还检测到一个假定的卷曲螺旋结构域。这种结构域结构表明,TOM1是参与生长因子受体复合物运输调节的基因家族的另一个成员,这些复合物将在溶酶体中降解。我们还表明存在TOM1的人类旁系同源基因(TOM1样基因1)。此外,我们提供了TOM1区域190 kb重叠群的转录图谱。该图谱包括其远端邻居HMOX1和MCM5以及两个近端新基因,其中一个是含HMG盒的基因(HMG2L1),另一个功能未知。使用基因组PAC克隆,我们证明小鼠Tom1和Hmox1基因是小鼠8号染色体C1区和人类22号染色体q13.1之间一个尚未描述的同线群的一部分。