Identification and cloning of two isoforms of human high-temperature requirement factor A3 (HtrA3), characterization of its genomic structure and comparison of its tissue distribution with HtrA1 and HtrA2
Identification and cloning of two isoforms of human high-temperature requirement factor A3 (HtrA3), characterization of its genomic structure and comparison of its tissue distribution with HtrA1 and HtrA2
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DOI：
10.1042/bj20021569
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发表时间：
2003-04-01
影响因子：
4.1
通讯作者：
Salamonsen, LA
中科院分区：
文献类型：
--
作者：
Nie, GY;Hampton, A;Salamonsen, LA
在目前的研究中，我们发现了人类高温需求因子A(HtrA)蛋白家族的另一个成员，称为妊娠相关丝氨酸蛋白酶或HtrA3，它在心脏和胎盘中表达最高。我们克隆了人HtrA3mRNA的两种形式(长和短)的全长序列，将该基因定位在染色体4p16.1上，确定了它的基因组结构，并揭示了这两种mRNA变体是如何通过选择性剪接产生的。Northern blotting也验证了选择性剪接。长型HtrA3蛋白有四个不同的结构域：(I)胰岛素/胰岛素样生长因子结合结构域，(Ii)Kazal型S蛋白酶抑制器域，(Iii)胰蛋白酶结构域和(Iv)PDZ结构域。除了缺少PDZ结构域之外，短形式与长形式相同。对人类HtrA蛋白的所有成员及其异构体的比较表明，HtrA3的两种异构体都代表活性丝氨酸蛋白酶，它们可能具有不同的底物特异性，HtrA3可能具有与HtrA1相似的功能。这三个HtrA家族成员在76个人类组织中表现出非常不同的mRNA表达模式，表明每个成员都有特定的功能。有趣的是，HtrA1和HtrA3都在胎盘中高表达。确定每个HtrA家族成员的组织特异性功能显然是重要的。
In the present study, we identified an additional member of the human high-temperature requirement factor A (HtrA) protein family, called pregnancy-related serine protease or HtrA3, which was most highly expressed in the heart and placenta. We cloned the full-length sequences of two forms (long and short) of human HtrA3 mRNA, located the gene on chromosome 4p16.1, determined its genomic structure and revealed how the two mRNA variants are produced through alternative splicing. The alternative splicing was also verified by Northern blotting. Four distinct domains were found for the long form HtrA3 protein: (i) an insulin/insulin-like growth factor binding domain, (ii) a Kazaltype S protease-inhibitor domain, (iii) a trypsin protease domain and (iv) a PDZ domain. The short form is identical to the long form except it lacks the PDZ domain. Comparison of all members of human HtrA proteins, including their isoforms, suggests that both isoforms of HtrA3 represent active serine proteases, that they may have different substrate specificities and that HtrA3 may have similar functions to HtrA1. All three HtrA family members showed very different mRNA-expression patterns in 76 human tissues, indicating a specific function for each. Interestingly, both HtrA1 and HtrA3 are highly expressed in the placenta. Identification of the tissue-specific function of each HtrA family member is clearly of importance.