Cloning and characterization of a close homologue of human UDP-N-acetyl-α-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase-T3, designated GalNAc-T6 -: Evidence for genetic but not functional redundancy
Cloning and characterization of a close homologue of human UDP-N-acetyl-α-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase-T3, designated GalNAc-T6 -: Evidence for genetic but not functional redundancy
复制标题
DOI：
10.1074/jbc.274.36.25362
复制
发表时间：
1999-09-03
影响因子：
4.8
通讯作者：
Clausen, H
中科院分区：
文献类型：
--
作者：
Bennett, EP;Hassan, H;Clausen, H
UDP-GalAc：多肽N-乙酰半乳糖胺转移酶，命名为GalNAc-T3，具有独特的功能，其特定的受体底物被GalNAc-T3所利用，而不被其他GalNAc-转移酶所利用。GalNAc-T3的表达模式受到限制，表达缺失是低分化胰腺肿瘤的特征。在本研究中，我们鉴定了第六个人UDP-GalNAc：多肽N-乙酰半乳糖胺转移酶，命名为GalNAc-T6，与GalNAc-T3有很高的相似性。GalNAc-T6在整个编码区与GalNAc-T3有很高的序列相似性，而同源糖基转移酶基因之间的相似性有限，通常局限于假定的催化区域。GALNT3和GALNT6的基因组结构与位于10个外显子的编码区相同，但分别定位在2q31和12q13。GalNAc-T3和-T6的受体底物特异性与其他GalNAc-转移酶相似，但又不同。Northern分析显示了不同的表达模式，这一点得到了使用单抗的免疫细胞学的证实。与GalNAc-T3相比，GalNAc-T6在WI38成纤维细胞中表达，表明GalNAc-T6是癌胎儿纤维连接蛋白合成的候选基因，这一结果证明了多肽GalNAc-T6存在遗传冗余，并不提供完全的功能冗余。
The UDP-GalAc:polypeptide N-acetylgalactosaminyltransferase, designated GalNAc-T3, exhibits unique functions, Specific acceptor substrates are used by GalNAc-T3 and not by other GalNAc-transferases. The expression pattern of GalNAc-T3 is restricted, and loss of expression is a characteristic feature of poorly differentiated pancreatic tumors. In the present study, a sixth human UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferase, designated GalNAc-T6, with high similarity to GalNAc-T3, was characterized. GalNAc-T6 exhibited high sequence similarity to GalNAc-T3 throughout the coding region, in contrast to the limited similarity that exists between homologous glycosyltransferase genes, which is usually restricted to the putative catalytic domain. The genomic organizations of GALNT3 and GALNT6 are identical with the coding regions placed in 10 exons, but the genes are localized differently at 2q31 and 12q13, respectively. Acceptor substrate specificities of GalNAc-T3 and -T6 were similar and different from other GalNAc-transferases. Northern analysis revealed distinct expression patterns, which were confirmed by immunocytology using monoclonal antibodies. In contrast to GalNAc-T3, GalNAc-T6 was expressed in WI38 fibroblast cells, indicating that GalNAc-T6 represents a candidate for synthesis of oncofetal fibronectin, The results demonstrate the existence of genetic redundancy of a polypeptide GalNAc-transferase that does not provide full functional redundancy.