BUB1 O43683

有丝分裂检查点丝氨酸/苏氨酸蛋白激酶BUB1 (hBUB1) (EC 2.7.11.1) (BUB1A)

功能描述

丝氨酸/苏氨酸蛋白激酶，在有丝分裂过程中执行2项关键功能：对纺锤体组装检查点信号传导和正确的染色体排列至关重要。在检查点蛋白组装到动粒上起关键作用，是CENPF、BUB1B、CENPE和MAD2L1随后定位所必需的。PLK1动粒定位所必需。前中期AUKRB着丝粒富集所必需。在确定SGO1定位方面起重要作用，从而影响姐妹染色单体黏附。促进TOP2A的着丝粒定位 (PubMed:35044816)。作为后期促进复合物或环体 (APC/C) 与其激活剂CDH1复合物 (APC/C-Cdh1) 的底物。对于确保正确的染色体分离是必需的，且与BUB3结合对于此功能至关重要。可以不依赖动粒的方式调节染色体分离。可以磷酸化BUB3。当纺锤体组装检查点被激活时，BUB1-BUB3复合物在抑制APC/C方面起作用，并通过磷酸化其激活剂CDC20来抑制APC/C的泛素连接酶活性。该复合物也可以磷酸化MAD1L1。激酶活性对于抑制APC/CCDC20和染色体排列至关重要，但在纺锤体组装检查点活性中不起主要作用。介导染色体错误分离引起的细胞死亡，并起到抑制自发肿瘤发生的作用。 {ECO:0000269|PubMed:10198256, ECO:0000269|PubMed:15020684, ECO:0000269|PubMed:15525512, ECO:0000269|PubMed:15723797, ECO:0000269|PubMed:16760428, ECO:0000269|PubMed:17158872, ECO:0000269|PubMed:19487456, ECO:0000269|PubMed:20739936, ECO:0000269|PubMed:35044816}.

组织特异性

High expression in testis and thymus, less in colon, spleen, lung and small intestine. Expressed in fetal thymus, bone marrow, heart, liver, spleen and thymus. Expression is associated with cells/tissues with a high mitotic index.

亚细胞定位

Nucleus. Chromosome, centromere, kinetochore. Note=Nuclear in interphase cells. Accumulates gradually during G1 and S phase of the cell cycle, peaks at G2/M, and drops dramatically after mitosis. Localizes to the outer kinetochore. Kinetochore localization is required for normal mitotic timing and checkpoint response to spindle damage and occurs very early in prophase. AURKB, KNL1 and INCENP are required for kinetochore localization (By similarity).