Cloning and characterization of human MUC19 gene.
Cloning and characterization of human MUC19 gene.
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人MUC19基因的克隆和表征。
DOI：
10.1165/rcmb.2010-0312oc
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发表时间：
2011
影响因子：
6.4
通讯作者：
Chen,Yin
中科院分区：
文献类型：
--
作者：
Zhu,Lingxiang;Lee,Pakkei;Yu,Dongfang;Tao,Shasha;Chen,Yin
最新发现的凝胶形成粘蛋白MUC19在唾液腺和气管粘膜下腺中都有表达。我们先前克隆了MUC19的3‘−末端部分序列(AY236870)，并对其进行了全序列测定。在MUC19的5‘端发现一个高度可变区(HVR)。在HVR中总共检测到20种不同的剪接变体，其中18种变体能够与MUC19序列的其余部分一起翻译成蛋白质。MUC19基因最长的变异体由182个外显子组成，转录产物长约25kb。约12kb的中央外显子含有高度重复的序列，没有内含子中断。推导出的MUC19蛋白具有真正的凝胶形成粘蛋白结构，VWD-“苏氨酸/富含丝氨酸的重复序列”-VWC-CT。MUC19的一个不寻常的结构特征是它在第一个VWD结构域的上游有很长的氨基末端，这是其他凝胶形成粘蛋白所缺乏的。长的氨基末端主要由HVR中的序列翻译而来，含有富含丝氨酸的重复序列。为了验证MUC19序列的完整性，来自3‘端和5’端的引物被用来展示MUC19在气管和唾液腺中相似的组织表达模式。此外，针对MUC19的氨基(N)或羧基(C)末端也产生了抗体，唾液腺和气管粘膜下腺的抗体染色模式相似。综上所述，我们克隆并阐明了MUC19基因的全长，这将有助于理解这一重要但尚未被研究的粘蛋白基因在呼吸道疾病中的功能和调节。
The most recently discovered gel-forming mucin,MUC19, is expressed in both salivary glands and tracheal submucosal glands. We previously cloned the 3′−end partial sequence (AY236870), and here report the complete sequencing of the entireMUC19cDNA. One highly variable region (HVR) was discovered in the 5′ end ofMUC19. A total of 20 different splicing variants were detected in HVR, and 18 variants are able to translate into proteins along with the rest of theMUC19sequence. The longest variant ofMUC19consists of 182 exons, with a transcript of approximately 25 kb. A central exon of approximately 12 kb contains highly repetitive sequences and has no intron interruption. The deduced MUC19 protein has the bona fide gel-forming mucin structure, VWD-VWD-VWD-“threonine/serine-rich repeats”-VWC-CT. An unusual structural feature of MUC19, which is lacking in other gel-forming mucins, is its long amino terminus upstream of the first VWD domain. The long amino terminus is mostly translated from the sequences in HVR, and contains serine-rich repetitive sequences. To validate the integrity of theMUC19sequence, primers from both the 3′ and 5′ end were used to demonstrate a similar tissue expression pattern ofMUC19in trachea and salivary glands. In addition, antibodies were developed against either the amino (N) or carboxy (C) terminus of MUC19, and similar antibody staining patterns were observed in both salivary and tracheal submucosal glands. In conclusion, we have cloned and elucidated the entireMUC19gene, which will facilitate understanding of the function and regulation of this important, yet understudied, mucin gene in airway diseases.