Kallunki P, Tryggvason K
Biocenter, University of Oulu, Finland.
J Cell Biol. 1992 Jan;116(2):559-71. doi: 10.1083/jcb.116.2.559.
The primary structure of the large human basement membrane heparan sulfate proteoglycan (HSPG) core protein was determined from cDNA clones. The cDNA sequence codes for a 467-kD protein with a 21-residue signal peptide. Analysis of the amino acid sequence showed that the protein consists of five domains. The amino-terminal domain I contains three putative heparan sulfate attachment sites; domain II has four LDL receptor-like repeats; domain III contains repeats similar to those in the short arms of laminin; domain IV has lg-like repeats resembling those in neural cell adhesion molecules; and domain V contains sequences resembling repeats in the G domain of the laminin A chain and repeats in the EGF. The domain structure of the human basement membrane HSPG core protein suggests that this mosaic protein has evolved through shuffling of at least four different functional elements previously identified in other proteins and through duplication of these elements to form the functional domains. Comparison of the human amino acid sequence with a partial amino acid sequence from the corresponding mouse protein (Noonan, D. M., E. A. Horigan, S. R. Ledbetter, G. Vogeli, M. Sasaki, Y. Yamada, and J. R. Hassell. 1988. J. Biol. Chem. 263:16379-16387) shows a major difference between the species in domain IV, which contains the Ig repeats: seven additional repeats are found in the human protein inserted in the middle of the second repeat in the mouse sequence. This suggests either alternative splicing or a very recent duplication event in evolution. The multidomain structure of the basement membrane HSPG implies a versatile role for this protein. The heparan sulfate chains presumably participate in the selective permeability of basement membranes and, additionally, the core protein may be involved in a number of biological functions such as cell binding, LDL-metabolism, basement membrane assembly, calcium binding, and growth- and neurite-promoting activities.
人类大分子量基底膜硫酸乙酰肝素蛋白聚糖（HSPG）核心蛋白的一级结构是通过cDNA克隆确定的。该cDNA序列编码一种带有21个氨基酸残基信号肽的467-kD蛋白。对氨基酸序列的分析表明，该蛋白由五个结构域组成。氨基末端的结构域I包含三个假定的硫酸乙酰肝素附着位点；结构域II有四个低密度脂蛋白受体样重复序列；结构域III包含与层粘连蛋白短臂中的重复序列相似的重复序列；结构域IV有类似于神经细胞粘附分子中的免疫球蛋白样重复序列；结构域V包含与层粘连蛋白A链G结构域中的重复序列以及表皮生长因子中的重复序列相似的序列。人类基底膜HSPG核心蛋白的结构域结构表明，这种镶嵌蛋白是通过至少四种先前在其他蛋白中鉴定出的不同功能元件的重排以及这些元件的复制以形成功能结构域而进化而来的。将人类氨基酸序列与相应小鼠蛋白的部分氨基酸序列（Noonan, D. M., E. A. Horigan, S. R. Ledbetter, G. Vogeli, M. Sasaki, Y. Yamada, and J. R. Hassell. 1988. J. Biol. Chem. 263:16379 - 16387）进行比较，发现在包含免疫球蛋白重复序列的结构域IV中，两种物种之间存在主要差异：在人类蛋白中，在小鼠序列第二个重复序列的中间插入了七个额外的重复序列。这表明可能存在选择性剪接或进化过程中非常近期的复制事件。基底膜HSPG的多结构域结构意味着该蛋白具有多种功能。硫酸乙酰肝素链可能参与基底膜的选择性通透性，此外，核心蛋白可能参与多种生物学功能，如细胞结合、低密度脂蛋白代谢、基底膜组装、钙结合以及促进生长和神经突生长的活动。
