Miyagi Y, Yasumitsu H, Mizushima H, Koshikawa N, Matsuda Y, Itoh H, Hori T A, Aoki I, Misugi K, Miyazaki K
Department of Pathology, Yokohama City University School of Medicine, Japan.
DNA Cell Biol. 1996 Nov;15(11):947-54. doi: 10.1089/dna.1996.15.947.
Placental protein 5 (PP5)/tissue factor pathway inhibitor-2 (TFPI-2) is a new homologue of TFPI, which contains three tandemly repeated Kunitz-type proteinase inhibitory (KPI) domains and potently inhibits the extrinsic blood coagulation cascade. In this study, mouse PP5/TFPI-2 cDNA was cloned using a human PP5/TFPI2 cDNA fragment as a probe. The characteristic three KPI domains with short spacer sequences and a basic amino acid stretch in the carboxyl-terminal region present in human PP5/TFPI-2 were well conserved in mouse PP5/TFPI-2. In general, the P1 reactive site residues of active KPI domains are basic amino acids. However, the putative P1 residues of the first, second, and third KPI domains were glutamine, aspartic acid, and serine, respectively. Mouse PP5/TFPI-2 mRNA was highly expressed in developing placenta as in humans. Adult liver and kidney also contained a significant amount of its transcripts. The mouse PP5/TFPI-2 gene was found to be located in the R-positive A2 band by the direct R-banding FISH and identified at 2.7 cM proximal to D6Mit 1 by interspecific backcross analysis.
胎盘蛋白5(PP5)/组织因子途径抑制剂-2(TFPI-2)是TFPI的一种新同源物,它含有三个串联重复的Kunitz型蛋白酶抑制(KPI)结构域,并能有效抑制外源性凝血级联反应。在本研究中,以人PP5/TFPI2 cDNA片段为探针克隆了小鼠PP5/TFPI-2 cDNA。人PP5/TFPI-2中存在的具有短间隔序列和羧基末端区域碱性氨基酸延伸的特征性三个KPI结构域在小鼠PP5/TFPI-2中高度保守。一般来说,活性KPI结构域的P1反应位点残基是碱性氨基酸。然而,第一、第二和第三KPI结构域的推定P1残基分别是谷氨酰胺、天冬氨酸和丝氨酸。与人类一样,小鼠PP5/TFPI-2 mRNA在发育中的胎盘中高度表达。成年肝脏和肾脏也含有大量其转录本。通过直接R带荧光原位杂交发现小鼠PP5/TFPI-2基因位于R阳性A2带,并通过种间回交分析确定其位于D6Mit 1近端2.7 cM处。