Ikeda Toshiyuki, Zhang Junwei, Chano Tokuhiro, Mabuchi Akihiko, Fukuda Akira, Kawaguchi Hiroshi, Nakamura Kozo, Ikegawa Shiro
Laboratory for Bone and Joint Diseases, SNP Research Center, RIKEN (The Institute of Physical and Chemical Research), c/o Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
Gene. 2002 Sep 18;298(1):59-68. doi: 10.1016/s0378-1119(02)00927-7.
The Sox (Sry-type HMG box) group of transcription factors, which is defined by a high-mobility group (HMG) DNA-binding domain, is categorized into six subfamilies. Sox5 and Sox6 belong to the group D subfamily, which is characterized by conserved N-terminal domains including a leucine-zipper, a coiled-coil domain and a Q-box. Group D Sox genes are expressed as long and short transcripts that exhibit differential expression patterns. In mouse, the long form of Sox5, L-Sox5, is co-expressed and interacts with Sox6; together, these two proteins appear to play a key role in chondrogenesis and myogenesis. In humans, however, only the short form of Sox5 has previously been identified. To gain insight into Sox5 function, we have identified and characterized human L-SOX5. The human L-SOX5 cDNA encodes a 763-amino-acid protein that is 416 residues longer than the short form and contains all of the characteristic motifs of group D Sox proteins. The predicted L-SOX5 protein shares 97% amino acid identity with its mouse counterpart and 59% identity with human SOX6. The L-SOX5 gene contains 18 exons and shows similar genomic structure to SOX6. We have identified two transcription start sites in L-SOX5 and multiple alternatively spliced mRNA variants that are distinct from the short form. Unlike the short form, which shows testis-specific expression, L-SOX5 is expressed in multiple tissues. Like SOX6, L-SOX5 shows strong expression in chondrocytes and striated muscles, indicating a likely role in human cartilage and muscle development.
Sox（Sry型HMG盒）转录因子家族由一个高迁移率族（HMG）DNA结合域定义，分为六个亚家族。Sox5和Sox6属于D组亚家族，其特征是保守的N端结构域，包括一个亮氨酸拉链、一个卷曲螺旋结构域和一个Q盒。D组Sox基因以长转录本和短转录本的形式表达，呈现出不同的表达模式。在小鼠中，Sox5的长形式L-Sox5与Sox6共同表达并相互作用；这两种蛋白质共同作用，似乎在软骨形成和肌肉生成中起关键作用。然而，在人类中，此前仅鉴定出Sox5的短形式。为了深入了解Sox5的功能，我们鉴定并表征了人类L-SOX5。人类L-SOX5 cDNA编码一种763个氨基酸的蛋白质，比短形式长416个残基，包含D组Sox蛋白的所有特征基序。预测的L-SOX5蛋白与其小鼠对应物的氨基酸同一性为97%，与人类SOX6的同一性为59%。L-SOX5基因包含18个外显子，其基因组结构与SOX6相似。我们在L-SOX5中鉴定出两个转录起始位点和多个与短形式不同的可变剪接mRNA变体。与显示睾丸特异性表达的短形式不同，L-SOX5在多种组织中表达。与SOX6一样，L-SOX5在软骨细胞和横纹肌中表达强烈，表明其可能在人类软骨和肌肉发育中发挥作用。
