Lasserre C, Simon M T, Ishikawa H, Diriong S, Nguyen V C, Christa L, Vernier P, Brechot C
INSERM U 370 CHU Necker, Paris, France.
Eur J Biochem. 1994 Aug 15;224(1):29-38. doi: 10.1111/j.1432-1033.1994.tb19991.x.
We previously identified, through differential screening of a human primary liver cancer library, a novel gene (named HIP) the expression of which is markedly increased in 25% of human primary liver cancers. HIP mRNA expression is tissue specific since it is restricted to pancreas and small intestine. HIP protein consists in a signal peptide linked to a carbohydrate-recognition domain (CRD), typical of C-type lectins without other binding domains. We have proposed that HIP and related proteins belong to a new family of C-type lectins. Drickamer [Drickamer, K. (1993) Curr. Opin. Struct. Biol. 3,393-400] included this group of proteins in his classification of C-type lectins as the free CRD (group VII) lectins. In the present report we describe the genomic organization and the chromosomal localization of HIP. We have shown that HIP is in fact the pancreatitis-associated protein (PAP) and provided a phylogenetic analysis of the free CRD lectins. Furthermore, the analysis of HIP/PAP gene indicates that the HIP/PAP CRD is encoded by four exons, a pattern shared with all members of this group of proteins. This common intron-exon organization indicates an ancient divergence of the free CRD-lectin group from other groups of C-type lectins. We provide evidence for the localization of HIP/PAP on chromosome 2, suggesting previous duplication of HIP/PAP and the related reg I alpha and reg I beta genes from the same ancestral gene. Finally, the sequence of the 5' upstream region of the HIP gene shows several potential regulatory elements which might account for the enhanced expression of the gene during pancreatic inflammation and liver carcinogenesis.
我们先前通过对人原发性肝癌文库进行差异筛选，鉴定出一个新基因（命名为HIP），其在25%的人原发性肝癌中表达显著增加。HIP mRNA表达具有组织特异性，因为它仅限于胰腺和小肠。HIP蛋白由一个与碳水化合物识别结构域（CRD）相连的信号肽组成，这是C型凝集素的典型特征，没有其他结合结构域。我们提出HIP及相关蛋白属于一个新的C型凝集素家族。Drickamer [Drickamer, K. (1993) Curr. Opin. Struct. Biol. 3,393 - 400] 将这组蛋白纳入他对C型凝集素的分类中，作为游离CRD（第VII组）凝集素。在本报告中，我们描述了HIP的基因组结构和染色体定位。我们已经表明HIP实际上是胰腺炎相关蛋白（PAP），并对游离CRD凝集素进行了系统发育分析。此外，对HIP/PAP基因的分析表明，HIP/PAP CRD由四个外显子编码，这是该组蛋白所有成员共有的模式。这种共同的内含子 - 外显子结构表明游离CRD凝集素组与其他C型凝集素组在远古时期就发生了分化。我们提供了HIP/PAP定位于2号染色体的证据，表明HIP/PAP以及相关的reg I alpha和reg I beta基因是由同一个祖先基因先前复制而来的。最后，HIP基因5'上游区域的序列显示出几个潜在的调控元件，这可能解释了该基因在胰腺炎症和肝癌发生过程中表达增强的原因。
