Chow V T, Quek H H
Department of Microbiology, Faculty of Medicine, National University of Singapore, Singapore.
Ann Hum Genet. 1997 Jul;61(Pt 4):369-73. doi: 10.1046/j.1469-1809.1997.6140369.x.
We previously sequenced the 4333-nucleotide cDNA of the COPA (HEP-COP) gene which encodes the human homologue of the alpha-subunit of the coatomer protein complex, involved in intracellular protein transport. Within the 3' untranslated region at nucleotides 4049-4333 was observed an Alu repeat containing conserved A and B block elements, and showing high homology to the human Alu-Sx subfamily consensus sequence. Upstream of the Alu repeat were noted a TATA box, a CAAT motif and two activating transcription factor (ATF)-like binding sites, which represent putative regulatory elements directing Alu transcription. In addition, the 25 and 35 N-terminal amino acid residues of COPA and its bovine homologue were identical to xenin-25 and proxenin, respectively. Xenin-25 is a gastrointestinal hormone that stimulates exocrine pancreatic secretion. This peptide is related to xenopsin, neurotensin and neuromedin N which are bioactive peptides derived from larger precursors via proteolytic cleavage by cathepsin E at processing sites determined by conserved C-terminal sequences, i.e. proline/valine-X-X-hydrophobic amino acid. Given the conformity of the C-terminal residues of xenin-25 (PWIL) and of its progenitor molecule, proxenin (VIQL), it is proposed that these peptides are generated by a similar mechanism of post-translational modification involving a parent precursor represented by the alpha-subunit of coatomer.
我们之前对COPA(HEP-COP)基因的4333个核苷酸的cDNA进行了测序,该基因编码参与细胞内蛋白质运输的外套膜蛋白复合物α亚基的人类同源物。在核苷酸4049 - 4333的3'非翻译区内,观察到一个含有保守A和B框元件的Alu重复序列,并且与人类Alu-Sx亚家族共有序列具有高度同源性。在Alu重复序列上游,发现了一个TATA框、一个CAAT基序和两个激活转录因子(ATF)样结合位点,它们代表指导Alu转录的假定调控元件。此外,COPA及其牛同源物的25个和35个N端氨基酸残基分别与xenin-25和proxenin相同。Xenin-25是一种刺激胰腺外分泌的胃肠激素。该肽与xenopsin、神经降压素和神经介素N相关,它们是通过组织蛋白酶E在由保守C端序列(即脯氨酸/缬氨酸-X-X-疏水氨基酸)确定的加工位点进行蛋白水解切割,从较大的前体衍生而来的生物活性肽。鉴于xenin-25(PWIL)及其前体分子proxenin(VIQL)的C端残基一致,有人提出这些肽是通过类似的翻译后修饰机制产生的,该机制涉及以外套膜蛋白α亚基为代表的亲本前体。