DTL Q9NZJ0

Denticleless蛋白同源物 (DDB1和CUL4相关因子2) (Lethal(2) denticleless蛋白同源物) (视黄酸调节核基质相关蛋白)

功能描述

DCX (DDB1-CUL4-X-box) E3泛素-蛋白连接酶复合物的底物特异性适配器，该复合物是细胞周期控制、DNA损伤反应和跨损伤DNA合成所必需的。DCX(DTL)复合物，也称为CRL4(CDT2)复合物，介导CDT1、CDKN1A/p21(CIP1)、FBH1、KMT5A和SDE2的多聚泛素化及随后的降解 (PubMed:16861906, PubMed:16949367, PubMed:16964240, PubMed:17085480, PubMed:18703516, PubMed:18794347, PubMed:18794348, PubMed:19332548, PubMed:20129063, PubMed:23478441, PubMed:23478445, PubMed:23677613, PubMed:27906959)。响应DNA损伤的CDT1降解对于确保DNA复制的正确细胞周期调控是必要的 (PubMed:16861906, PubMed:16949367, PubMed:17085480)。S期或UV照射后的CDKN1A/p21(CIP1)降解对于控制复制许可至关重要 (PubMed:18794348, PubMed:19332548)。KMT5A的降解对于TGF-beta信号传导、细胞周期进程、DNA修复和细胞迁移等机制的适当调控也很重要 (PubMed:23478445)。大多数底物需要与PCNA相互作用才能进行多聚泛素化：底物通过其PIP-box与PCNA相互作用，而那些在PIP box中含有'K+4'基序的底物会招募DCX(DTL)复合物，导致其降解。在未受损的增殖细胞中，DCX(DTL)复合物还促进PCNA的'Lys-164'单泛素化，从而参与PCNA依赖的跨损伤DNA合成 (PubMed:20129063, PubMed:23478441, PubMed:23478445, PubMed:23677613)。DDB1-CUL4A-DTL E3连接酶复合物通过介导CRY1的泛素化和降解来调控生物钟功能 (PubMed:26431207)。 {ECO:0000269|PubMed:16861906, ECO:0000269|PubMed:16949367, ECO:0000269|PubMed:16964240, ECO:0000269|PubMed:17085480, ECO:0000269|PubMed:18703516, ECO:0000269|PubMed:18794347, ECO:0000269|PubMed:18794348, ECO:0000269|PubMed:19332548, ECO:0000269|PubMed:20129063, ECO:0000269|PubMed:23478441, ECO:0000269|PubMed:23478445, ECO:0000269|PubMed:23677613, ECO:0000269|PubMed:26431207, ECO:0000269|PubMed:27906959}。

组织特异性

Expressed in placenta and testis, very low expression seen in skeletal muscle. Detected in all hematopoietic tissues examined, with highest expression in thymus and bone marrow. A low level detected in the spleen and lymph node, and barely detectable level in the peripheral leukocytes. RA treatment down-regulated the expression in NT2 cell.

亚细胞定位

Nucleus