Five members of a novel Ca2+-binding protein (CABP) subfamily with similarity to calmodulin

Five members of a novel Ca2+-binding protein (CABP) subfamily with similarity to calmodulin
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DOI:
10.1074/jbc.275.2.1247
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发表时间:
2000-01-14
影响因子:
4.8
通讯作者:
Palczewski, K
Palczewski, K
中科院分区:
生物学2区
文献类型:
--
作者:
Haeseleer, F;Sokal, I;Palczewski, K

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在脊椎动物视网膜中鉴定出一个新的钙结合蛋白亚家族(CABP)的5个成员,其序列与钙调蛋白(CaM)有46-58%的相似性。这些钙结合蛋白和CaM之间的重要区别包括它们的第二个EF-手环的变化,使这些基序在钙离子配位中不活跃,以及它们的中心α-螺旋延长了一个α-螺旋。CaBP1和CaBP2含有一个共同的N-末端肉豆蔻酰化序列,类似于Recoverin亚家族的成员,在体外是脂肪酸酰化的。对于每个不同的成员,表达模式都不同。例如,CaBP5的表达仅限于视网膜视杆和视锥双极细胞。相反,CaBP1有更广泛的表达模式。在大脑中,CaBP1存在于大脑皮层和海马体中,而在视网膜中,该蛋白存在于视锥双极细胞和无长突细胞中。CaBP1和CaBP2以多种选择性剪接变异体的形式表达,在异源表达系统中,这些形式表现出不同的亚细胞定位模式。在重组实验中,CaBPs可以在功能上替代CaM。这些数据表明,这些新的CaBPs是中枢神经系统中钙离子介导的细胞信号转导的重要组成部分,它们可能是CaM的补充或替代。
Five members of a novel Ca2+-binding protein subfamily (CaBP), with 46-58% sequence similarity to calmodulin (CaM), were identified in the vertebrate retina. Important differences between these Ca2+-binding proteins and CaM include alterations within their second EF-hand loop that render these motifs inactive in Ca2+ coordination and the fact that their central alpha-helixes are extended by one alpha-helical turn. CaBP1 and CaBP2 contain a consensus sequence for N-terminal myristoylation, similar to members of the recoverin subfamily and are fatty acid acylated in vitro. The patterns of expression differ for each of the various members. Expression of CaBP5, for example, is restricted to retinal rod and cone bipolar cells. In contrast, CaBP1 has a more widespread pattern of expression. In the brain, CaBP1 is found in the cerebral cortex and hippocampus, and in the retina this protein is found in cone bipolar and amacrine cells. CaBP1 and CaBP2 are expressed as multiple, alternatively spliced variants, and in heterologous expression systems these forms show different patterns of subcellular localization. In reconstitution assays, CaBPs are able to substitute functionally for CaM. These data suggest that these novel CaBPs are an important component of Ca2+-mediated cellular signal transduction in the central nervous system where they may augment or substitute for CaM.