Zhang R Z, Pan T C, Zhang Z Y, Mattei M G, Timpl R, Chu M L
Department of Biochemistry and Molecular Biology, Thomas Jefferson University, Philadelphia, Pennsylvania 19107.
Genomics. 1994 Jul 15;22(2):425-30. doi: 10.1006/geno.1994.1404.
Fibulin-2 is a new extracellular matrix protein that we recently identified by characterizing mouse cDNA clones. Fibulin-2 mRNA is prominently expressed in mouse heart tissue and is present in low amounts in other tissues. In this study, we isolated and sequenced a 4.1-kb human fibulin-2 cDNA, which encoded a mature protein of 1157 amino acids preceded by a 27-residue signal sequence. The predicted polypeptide contains three consecutive anaphylatoxin-related segments (domain I) in its central region followed by 10 EGF-like repeats (domain II), 9 of which have a consensus sequence for calcium binding. The 408-residue N-terminal region consists of two separate subdomains, a cysteine-rich segment of 150 residues (Na subdomain) and a cysteine-free segment with a stretch of acidic amino acids (Nb subdomain). The 115-residue C-terminal segment (domain III) is similar to the C variant of fibulin-1. The amino acid sequences of the human and mouse fibulin-2 share approximately 90% identity in domains Na, I, II, and III but only 62% identity in domain Nb. The human cDNA lacks an EGF-like repeat, which is alternatively spliced in the mouse cDNA clones, and a potential cell-binding Arg-Gly-Asp sequence found in the Nb domain of the mouse counterpart. Northern blot analysis of mRNA from various human tissues reveals an abundant 4.5-kb transcript in heart, placenta, and ovary tissue. The expression pattern differs from that of fibulin-1. The fibulin-2 gene was localized by in situ hybridization to the p24-p25 region of human chromosome 3 and to the band D-E of mouse chromosome 6.
纤维连接蛋白-2是一种新的细胞外基质蛋白，我们最近通过对小鼠cDNA克隆进行表征而鉴定出来。纤维连接蛋白-2 mRNA在小鼠心脏组织中显著表达，在其他组织中含量较低。在本研究中，我们分离并测序了一个4.1 kb的人纤维连接蛋白-2 cDNA，其编码一个由1157个氨基酸组成的成熟蛋白，前面有一个27个残基的信号序列。预测的多肽在其中心区域包含三个连续的过敏毒素相关区段（结构域I），随后是10个表皮生长因子样重复序列（结构域II），其中9个具有钙结合的共有序列。408个残基的N端区域由两个独立的亚结构域组成，一个150个残基的富含半胱氨酸区段（Na亚结构域）和一个无半胱氨酸且有一段酸性氨基酸的区段（Nb亚结构域）。115个残基的C端区段（结构域III）与纤维连接蛋白-1的C变体相似。人和小鼠纤维连接蛋白-2的氨基酸序列在Na、I、II和III结构域中约有90%的同一性，但在Nb结构域中只有62%的同一性。人cDNA缺少一个在小鼠cDNA克隆中选择性剪接的表皮生长因子样重复序列，以及在小鼠对应物的Nb结构域中发现的一个潜在的细胞结合精氨酸-甘氨酸-天冬氨酸序列。对来自各种人类组织的mRNA进行Northern印迹分析，发现在心脏、胎盘和卵巢组织中有丰富的4.5 kb转录本。其表达模式与纤维连接蛋白-1不同。通过原位杂交将纤维连接蛋白-2基因定位到人类染色体3的p24 - p25区域和小鼠染色体6的D - E带。
