Conklin D, Gilbertson D, Taft D W, Maurer M F, Whitmore T E, Smith D L, Walker K M, Chen L H, Wattler S, Nehls M, Lewis K B
ZymoGenetics, Inc., 1201 Eastlake Avenue East, Seattle, Washington 98012, USA.
Genomics. 1999 Dec 15;62(3):477-82. doi: 10.1006/geno.1999.6041.
Based on searches of EST databases for signal sequences and amphipathic helices, we have identified and cloned an angiopoietin-like gene, ANGPTL3. Multiple tissue Northern blots show that ANGPTL3 is expressed principally in the liver. ANGPTL3 is expressed early during liver development, and expression is maintained in adult liver. Human ANGPTL3 is a 460-amino-acid polypeptide with the characteristic structure of angiopoietins: a signal peptide, an extended helical domain predicted to form dimeric or trimeric coiled-coils, a short linker peptide, and a globular fibrinogen homology domain (FHD). Murine ANGPTL3 is a 455-acid polypeptide encoded by seven exons on mouse chromosome 4, spanning about 11 kb of DNA. ANGPTL3 contains the four conserved cysteines implicated in the intramolecular disulfide bonds within the FHD, but it does not contain two other cysteines that are found within the FHD of angiopoietins 1, 2, and 4. ANGPTL3 also does not contain the characteristic calcium binding motif found in the other angiopoietins. By radiation hybrid mapping and the use of surrounding genes, human ANGPTL3 maps to the 1p31 region.
通过搜索EST数据库中的信号序列和两亲性螺旋，我们鉴定并克隆了一个血管生成素样基因ANGPTL3。多种组织的Northern杂交结果显示，ANGPTL3主要在肝脏中表达。ANGPTL3在肝脏发育早期即开始表达，并在成年肝脏中持续表达。人ANGPTL3是一种由460个氨基酸组成的多肽，具有血管生成素的特征性结构：一个信号肽、一个预测可形成二聚体或三聚体卷曲螺旋的延伸螺旋结构域、一个短连接肽和一个球状纤维蛋白原同源结构域（FHD）。小鼠ANGPTL3是一种由455个氨基酸组成的多肽，由小鼠4号染色体上的7个外显子编码，跨越约11kb的DNA。ANGPTL3在FHD内含有参与分子内二硫键形成的4个保守半胱氨酸，但不含有血管生成素1、2和4的FHD中存在的另外两个半胱氨酸。ANGPTL3也不含有其他血管生成素中发现的特征性钙结合基序。通过辐射杂种图谱分析和使用周围基因，人ANGPTL3定位于1p31区域。
