CUL7 Q14999

Cullin-7 (CUL-7)

功能描述

3M和Cul7-RING(FBXW8)复合物的核心组分，这些复合物介导靶蛋白的泛素化及随后的蛋白酶体降解 (PubMed:12481031, PubMed:12904573, PubMed:21572988, PubMed:21737058, PubMed:24793695, PubMed:35982156)。3M复合物的核心组分，该复合物是调节微管动力学和基因组完整性所必需的 (PubMed:21572988, PubMed:21737058, PubMed:24793695)。目前尚不清楚3M复合物如何调节微管，它可能通过控制微管稳定因子的水平来发挥作用 (PubMed:24793695)。Cul7-RING(FBXW8)复合物本身缺乏泛素化活性，不促进p53/TP53的多聚泛素化和蛋白酶体降解 (PubMed:16547496, PubMed:17332328, PubMed:35982156)。然而，它介导p53/TP53的招募，以便被neddylated CUL1-RBX1泛素化 (PubMed:35982156)。与CUL9的相互作用是抑制CUL9活性和BIRC5泛素化所必需的 (PubMed:24793696)。Cul7-RING(FBXW8)复合物还介导靶蛋白（如GORASP1、IRS1和MAP4K1/HPK1）的泛素化及随后的降解 (PubMed:21572988, PubMed:24362026)。GORASP1的泛素化调节大脑中的高尔基体形态发生和树突模式形成 (PubMed:21572988)。以mTOR依赖的方式介导IRS1的泛素化和降解：Cul7-RING(FBXW8)复合物识别并结合先前被S6激酶 (RPS6KB1或RPS6KB2) 磷酸化的IRS1 (PubMed:18498745)。Cul7-RING(FBXW8)复合物还介导MAP4K1/HPK1的泛素化：识别并结合自磷酸化的MAP4K1/HPK1，导致其降解，从而影响细胞增殖和分化 (PubMed:24362026)。作为滋养层细胞上皮-间质转化和胎盘发育的调节因子发挥作用 (PubMed:20139075)。虽然Cul7-RING(FBXW8)和3M复合物相关联并参与共同的过程，但CUL7和Cul7-RING(FBXW8)复合物可能具有额外的功能。可能在涉及内皮增殖和/或分化的蛋白降解中发挥作用。 {ECO:0000269|PubMed:12481031, ECO:0000269|PubMed:12904573, ECO:0000269|PubMed:16547496, ECO:0000269|PubMed:17332328, ECO:0000269|PubMed:18498745, ECO:0000269|PubMed:20139075, ECO:0000269|PubMed:21572988, ECO:0000269|PubMed:21737058, ECO:0000269|PubMed:24362026, ECO:0000269|PubMed:24793695, ECO:0000269|PubMed:24793696, ECO:0000269|PubMed:35982156}。

组织特异性

Highly expressed in fetal kidney and adult skeletal muscle. Also abundant in fetal brain, as well as in adult pancreas, kidney, placenta and heart. Detected in trophoblasts, lymphoblasts, osteoblasts, chondrocytes and skin fibroblasts.

亚细胞定位

Cytoplasm. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome. Cytoplasm, perinuclear region. Golgi apparatus. Note=Colocalizes with FBXW8 at the Golgi apparatus in neurons; localization to Golgi is mediated by OBSL1. During mitosis, localizes to the mitotic apparatus (PubMed:24793695). CCDC8 is required for centrosomal location (PubMed:24793695).