A novel subfamily of mouse cytosolic carboxypeptidases
A novel subfamily of mouse cytosolic carboxypeptidases
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DOI：
10.1096/fj.06-7329com
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发表时间：
2007-03-01
期刊：
影响因子：
4.8
通讯作者：
Fricker, Lloyd D.
中科院分区：
文献类型：
--
作者：
Kalinina, Elena;Biswas, Reeta;Fricker, Lloyd D.
Nna1 是最近描述的与金属羧肽酶具有序列相似性的基因产物。在本研究中，在小鼠基因组中鉴定出另外五个 Nna1 样基因，并将其命名为胞质羧肽酶 (CCP) 2 至 6。建模表明，羧肽酶结构域折叠成类似于 M14 家族金属羧肽酶的结构，具有催化活性和广泛底物特异性所需的所有残基。所有 CCP 在睾丸中含量丰富，也在大脑、垂体、眼睛和其他小鼠组织中表达。在大脑中，Nna1/CCP1、CCP5 和 CCP6 分布广泛，而 CCP2 和 3 的表达模式受到限制。发现 Nna1/CCP1、CCP2、CCP5 和 CCP6 表现出胞质分布，其中 CCP5 在细胞核中略有积累。基于上述结果，我们假设 Nna1/CCP1 和 CCP2-6 在细胞质蛋白（例如 α-微管蛋白）的加工中发挥作用，已知α-微管蛋白是通过去除 C 末端酪氨酸而被修饰的。对缺乏 Nna1/CCP1 的小鼠嗅球中 α 微管蛋白形式的分析表明，二尖瓣细胞中不存在去酪氨酸化形式。综上所述，这些结果与 Nna1/CCP1 和相关 CCP 在微管蛋白加工中的作用一致。
Nna1 is a recently described gene product that has sequence similarity with metallocarboxypeptidases. In the present study, five additional Nna1-like genes were identified in the mouse genome and named cytosolic carboxypeptidase (CCP) 2 through 6. Modeling suggests that the carboxypeptidase domain folds into a structure that resembles metallocarboxypeptidases of the M14 family, with all necessary residues for catalytic activity and broad substrate specificity. All CCPs are abundant in testis and also expressed in brain, pituitary, eye, and other mouse tissues. In brain, Nna1/CCP1, CCP5, and CCP6 are broadly distributed, whereas CCP2 and 3 exhibit restricted patterns of expression. Nna1/CCP1, CCP2, CCP5, and CCP6 were found to exhibit a cytosolic distribution, with a slight accumulation of CCP5 in the nucleus. Based on the above results, we hypothesized that Nna1/CCP1 and CCP2-6 function in the processing of cytosolic proteins such as alpha-tubulin, which is known to be modified by the removal of a C-terminal tyrosine. Analysis of the forms of alpha tubulin in the olfactory bulb of mice lacking Nna1/CCP1 showed the absence of the detyrosinylated form in the mitral cells. Taken together, these results are consistent with a role for Nna1/CCP1 and the related CCPs in the processing of tubulin.