Molecular cloning, expression and chromosomal localization of a novel human REG family gene, REG III
Molecular cloning, expression and chromosomal localization of a novel human REG family gene, REG III
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DOI：
10.1016/j.gene.2004.06.010
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发表时间：
2004-09-29
期刊：
影响因子：
3.5
通讯作者：
Okamoto, H
中科院分区：
文献类型：
--
作者：
Nata, K;Liu, Y;Okamoto, H
再生基因(Reg)，首次从再生胰岛cDNA文库中分离出来[J.Biol.化学。263(1988)2111]，编码一种对胰腺0细胞具有生长刺激作用的分泌蛋白，可改善90%去胰岛大鼠的糖尿病[proc.娜塔莉。阿卡德。SCI。美国91(1994)3589]和非肥胖糖尿病小鼠[糖尿病51(Supp.3)(2002)S478]。REG和REG相关基因已被发现构成一个多基因家族，该家族由四个亚型(I、II、III、IV)组成，根据基因编码蛋白的一级结构[糖尿病51(Supp1.3)(2002)S462]。在小鼠和大鼠中发现了多种III型REG基因。另一方面，在人类中只发现一个III型Reg基因，HIP/PAP(在肝细胞癌-肠-胰腺中表达的基因/编码胰腺炎相关蛋白的基因)。在本研究中，我们发现了一个新的人类III型REG基因--REG III。该基因由6个外显子组成，全长约3kb，编码175个氨基酸(AA)，与HIP/PAP有85%的同源性。REG III主要在胰腺和睾丸表达，在小肠不表达，而HIP/PAP在胰腺和小肠表达较强。IL-6反应元件存在于人REG III基因5‘-上游区域，提示人REG III基因可能在急性胰腺炎时被诱导表达。到目前为止，已发现的人类REG家族基因(Reg Ipha、Reg Ibeta、HIP/PAP、Reg III和Reg IV)都有一个由6个外显子和5个内含子组成的共同基因结构，并编码同源的158-175-AA分泌蛋白。通过数据库检索和酵母人工染色体克隆的聚合酶链式反应分析，人类2号染色体上的REG家族基因，除1号染色体上的REG IV外，都被定位到人类染色体2p12上一个连续的140kb区域。从着丝粒到端粒的基因顺序为：5‘HIP/PAP 3’-5‘RS 3’-3‘Reg Ipha5’-5‘Reg Ibeta3’-3‘Reg III 5’。这些结果表明，人类REG基因家族是由一个祖先基因通过基因复制而构成的，并在该区域形成了一个基因簇。(C)2004爱思唯尔B.V.保留所有权利。
Regenerating gene (Reg), first isolated from a regenerating islet cDNA library [J. Biol. Chem. 263 (1988) 2111], encodes a secretory protein with a growth stimulating effect on pancreatic 0 cells that ameliorates the diabetes of 90% depancreatized rats [Proc. Natl. Acad. Sci. USA 91 (1994) 3589] and non-obese diabetic mice [Diabetes 51(Suppl. 3) (2002) S478]. Reg and Reg-related genes have been revealed to constitute a multigene family, the Reg family, which consists of four subtypes (types I, II, III, IV) based on the primary structures of the encoded proteins of the genes [Diabetes 51(Suppl. 3) (2002) S462]. Plural type III Reg genes were found in mouse and rat. On the other hand, only one type III REG gene, HIP/PAP (gene expressed in hepatocellular carcinoma-intestine-pancreas/gene encoding pancreatitis-associated protein), was found in human. In the present study, we found a novel human type III REG gene, REG III. This gene is divided into six exons spanning about 3 kilobase pairs (kb), and encodes a 175 amino acid (aa) protein with 85% homology with HIP/PAP. REG III was expressed predominantly in pancreas and testis, but not in small intestine, whereas HIP/PAP was expressed strongly in pancreas and small intestine. IL-6 responsive elements existed in the 5'-upstream region of the human REG III gene indicating that the human REG III gene might be induced during acute pancreatitis. All the human REG family genes identified so far (REG Ialpha, REG Ibeta, HIP/PAP, REG III and REG IV) have a common gene structure with 6 exons and 5 introns, and encode homologous 158-175-aa secretory proteins. By database searching and PCR analysis using a yeast artificial chromosome clone, the human REG family genes on chromosome 2, except for REG IV on chromosome 1, were mapped to a contiguous 140 kb region of the human chromosome 2p12. The gene order from centromere to telomere was 5' HIP/PAP 3'-5' RS 3'-3' REG Ialpha 5'-5' REG Ibeta 3'-3' REG III 5'. These results suggest that the human REG gene family is constituted from an ancestor gene by gene duplication and forms a gene cluster on the region. (C) 2004 Elsevier B.V. All rights reserved.