Chromosomal localization, genomic organization and evolution of the genes encoding human phosphatidylinositol transfer protein membrane-associated (PITPNM) 1, 2 and 3
Chromosomal localization, genomic organization and evolution of the genes encoding human phosphatidylinositol transfer protein membrane-associated (PITPNM) 1, 2 and 3
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DOI：
10.1159/000081519
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发表时间：
2005-01-01
影响因子：
1.7
通讯作者：
Halford, S
中科院分区：
文献类型：
--
作者：
Ocaka, L;Spalluto, C;Halford, S
含有磷脂酰肌醇转移 (PITP) 结构域的真核蛋白可分为两组，一组由小的可溶性 35-kDa 蛋白组成，另一组与膜相关并与果蝇视网膜变性 B (rdgB) 蛋白显示序列相似性。 rdgB 蛋白由四个结构域组成：氨基端 PITP 结构域、Ca(2+) 结合结构域、跨膜结构域和与蛋白酪氨酸激酶 PYK2 相互作用的羧基端结构域。与果蝇 rdgB 同源的三种哺乳动物磷脂酰肌醇转移蛋白膜相关基因（PITPNM1、2 和 3）先前已被描述并显示在哺乳动物视网膜中表达。这些发现以及 rdgB 基因在无脊椎动物光转导途径中发挥关键作用的证明使得哺乳动物基因被认为是人类眼部疾病的候选基因。为了便于对这些基因的分析，我们使用辐射杂交作图和荧光原位杂交将PITPNM2和3基因分别定位到人类染色体12p24和17p13，并使用混合作图来确认PITPNM1到染色体11q13的定位。我们还确定了可溶性和膜相关的果蝇和人类含有 PITP 结构域的基因的基因组组织。系统发育分析表明，这两个群体是由动物进化早期发生的基因复制而产生的。版权所有 (C) 2005 S. Karger AG，巴塞尔。
Eukaryotic proteins containing a phosphatidylinositol transfer ( PITP) domain can be divided into two groups, one consisting of small soluble 35-kDa proteins and the other those that are membrane-associated and show sequence similarities to the Drosophila retinal degeneration B ( rdgB) protein. The rdgB protein consists of four domains, an amino terminal PITP domain, a Ca(2+)-binding domain, a transmembrane domain and a carboxyl terminal domain that interacts with the protein tyrosine kinase PYK2. Three mammalian phosphatidylinositol transfer protein membrane-associated genes (PITPNM1, 2 and 3) with homology to Drosophila rdgB have previously been described and shown to be expressed in the mammalian retina. These findings and the demonstration that the rdgB gene plays a critical role in the invertebrate phototransduction pathway have led to the mammalian genes being considered as candidate genes for human eye diseases. In order to facilitate the analysis of these genes we have used radiation hybrid mapping and fluorescence in situ hybridization to localize the PITPNM2 and 3 genes to human chromosomes 12p24 and 17p13 respectively and hybrid mapping to confirm the localization of PITPNM1 to chromosome 11q13. We have also determined the genomic organization of both the soluble and membrane-associated Drosophila and human PITP domain-containing genes. Phylogenetic analysis indicates that the two groups arose by gene duplication that occurred very early in animal evolution. Copyright (C) 2005 S. Karger AG, Basel.