The N-terminal EF-hand calcium-binding proteins 1–3(NECAB1–3) constitute a family of predominantly neuronal proteins characterized by the presence of at least one EF-hand calcium-binding domain and a functionally le...The N-terminal EF-hand calcium-binding proteins 1–3(NECAB1–3) constitute a family of predominantly neuronal proteins characterized by the presence of at least one EF-hand calcium-binding domain and a functionally less well characterized C-terminal antibiotic biosynthesis monooxygenase domain. All three family members were initially discovered due to their interactions with other proteins. NECAB1 associates with synaptotagmin-1, a critical neuronal protein involved in membrane trafficking and synaptic vesicle exocytosis. NECAB2 interacts with predominantly striatal G-protein-coupled receptors, while NECAB3 partners with amyloid-β A4 precursor protein-binding family A members 2 and 3, key regulators of amyloid-β production. This demonstrates the capacity of the family for interactions with various classes of proteins. NECAB proteins exhibit distinct subcellular localizations: NECAB1 is found in the nucleus and cytosol, NECAB2 resides in endosomes and the plasma membrane, and NECAB3 is present in the endoplasmic reticulum and Golgi apparatus. The antibiotic biosynthesis monooxygenase domain, an evolutionarily ancient component, is akin to atypical heme oxygenases in prokaryotes but is not wellcharacterized in vertebrates. Prokaryotic antibiotic biosynthesis monooxygenase domains typically form dimers, suggesting that calcium-mediated conformational changes in NECAB proteins may induce antibiotic biosynthesis monooxygenase domain dimerization, potentially activating some enzymatic properties. However, the substrate for this enzymatic activity remains uncertain. Alternatively, calcium-mediated conformational changes might influence protein interactions or the subcellular localization of NECAB proteins by controlling the availability of protein–protein interaction domains situated between the EF hands and the antibiotic biosynthesis monooxygenase domain. This review summarizes what is known about genomic organization, tissue expression, intracellular localization, interaction partners, and the physiological and pathophysiological role of the NECAB family.展开更多
目的:观察亮氨酸拉链EF-hand结构域跨膜蛋白1(leucine zipper/EF-hand-containing transmembrane protein 1,LETM1)在结肠癌中的表达情况,探讨LETM1蛋白是否能够成为判断结肠癌患者预后的新的生物学指标.方法:利用免疫组织化学法检测73...目的:观察亮氨酸拉链EF-hand结构域跨膜蛋白1(leucine zipper/EF-hand-containing transmembrane protein 1,LETM1)在结肠癌中的表达情况,探讨LETM1蛋白是否能够成为判断结肠癌患者预后的新的生物学指标.方法:利用免疫组织化学法检测73例结肠癌患者组织中LETM1蛋白的表达水平和蛋白激酶B(protein kinase B,PKB)/Akt的丝氨酸473(Ser473)、苏氨酸308(Thr308)两个磷酸化位点及葡萄糖合成激酶3β(glycogen synthase k i n a s e 3β,G S K3β)的磷酸化水平,并根据LETM1蛋白表达水平进行高表达和低表达分组;采用Kaplan-Meier法分析各组无疾病生存期;采用χ2检验进行组间单因素分析.结果:在结肠癌患者中LETM1蛋白高表达率为54.8%,LETM1蛋白在结肠癌浸润深度、分化及淋巴结转移中低表达和高表达率分别为27.3%/72.7%、38.3%/61.7%和22.7%/77.3%,其差异均有统计学意义(P<0.05),而与年龄、性别、肿瘤大小未见统计学意义(P>0.05).LETM1蛋白在结肠癌组织中可以激活磷脂酰肌醇3激酶(phosphatidylinositol 3 kinase,PI-3K)/A k t信号传导通路.L ETM1高表达患者无疾病生存期显著低于LETM1低表达患者(P<0.05).结论:LETM1蛋白在结肠癌中高表达,可能参与结肠癌的发生、发展与复发.LETM1蛋白可以作为预测结肠癌患者预后的新的生物学指标.展开更多
基金supported by the Deutsche Forschungsgemeinschaft (ME1922/14-1) to AM。
文摘The N-terminal EF-hand calcium-binding proteins 1–3(NECAB1–3) constitute a family of predominantly neuronal proteins characterized by the presence of at least one EF-hand calcium-binding domain and a functionally less well characterized C-terminal antibiotic biosynthesis monooxygenase domain. All three family members were initially discovered due to their interactions with other proteins. NECAB1 associates with synaptotagmin-1, a critical neuronal protein involved in membrane trafficking and synaptic vesicle exocytosis. NECAB2 interacts with predominantly striatal G-protein-coupled receptors, while NECAB3 partners with amyloid-β A4 precursor protein-binding family A members 2 and 3, key regulators of amyloid-β production. This demonstrates the capacity of the family for interactions with various classes of proteins. NECAB proteins exhibit distinct subcellular localizations: NECAB1 is found in the nucleus and cytosol, NECAB2 resides in endosomes and the plasma membrane, and NECAB3 is present in the endoplasmic reticulum and Golgi apparatus. The antibiotic biosynthesis monooxygenase domain, an evolutionarily ancient component, is akin to atypical heme oxygenases in prokaryotes but is not wellcharacterized in vertebrates. Prokaryotic antibiotic biosynthesis monooxygenase domains typically form dimers, suggesting that calcium-mediated conformational changes in NECAB proteins may induce antibiotic biosynthesis monooxygenase domain dimerization, potentially activating some enzymatic properties. However, the substrate for this enzymatic activity remains uncertain. Alternatively, calcium-mediated conformational changes might influence protein interactions or the subcellular localization of NECAB proteins by controlling the availability of protein–protein interaction domains situated between the EF hands and the antibiotic biosynthesis monooxygenase domain. This review summarizes what is known about genomic organization, tissue expression, intracellular localization, interaction partners, and the physiological and pathophysiological role of the NECAB family.
文摘目的:观察亮氨酸拉链EF-hand结构域跨膜蛋白1(leucine zipper/EF-hand-containing transmembrane protein 1,LETM1)在结肠癌中的表达情况,探讨LETM1蛋白是否能够成为判断结肠癌患者预后的新的生物学指标.方法:利用免疫组织化学法检测73例结肠癌患者组织中LETM1蛋白的表达水平和蛋白激酶B(protein kinase B,PKB)/Akt的丝氨酸473(Ser473)、苏氨酸308(Thr308)两个磷酸化位点及葡萄糖合成激酶3β(glycogen synthase k i n a s e 3β,G S K3β)的磷酸化水平,并根据LETM1蛋白表达水平进行高表达和低表达分组;采用Kaplan-Meier法分析各组无疾病生存期;采用χ2检验进行组间单因素分析.结果:在结肠癌患者中LETM1蛋白高表达率为54.8%,LETM1蛋白在结肠癌浸润深度、分化及淋巴结转移中低表达和高表达率分别为27.3%/72.7%、38.3%/61.7%和22.7%/77.3%,其差异均有统计学意义(P<0.05),而与年龄、性别、肿瘤大小未见统计学意义(P>0.05).LETM1蛋白在结肠癌组织中可以激活磷脂酰肌醇3激酶(phosphatidylinositol 3 kinase,PI-3K)/A k t信号传导通路.L ETM1高表达患者无疾病生存期显著低于LETM1低表达患者(P<0.05).结论:LETM1蛋白在结肠癌中高表达,可能参与结肠癌的发生、发展与复发.LETM1蛋白可以作为预测结肠癌患者预后的新的生物学指标.
