Harvey Kieran F, Shearwin-Whyatt Linda M, Fotia Andrew, Parton Robert G, Kumar Sharad
Hanson Center for Cancer Research, Institute of Medical and Veterinary Science, Frome Road, Adelaide, South Australia 5000, Australia.
J Biol Chem. 2002 Mar 15;277(11):9307-17. doi: 10.1074/jbc.M110443200. Epub 2001 Dec 17.
Nedd4 belongs to a family of ubiquitin-protein ligases that is characterized by 2--4 WW domains, a carboxyl-terminal Hect (homologous to E6-AP Carboxyl terminus)domain and in most cases an amino-terminal C2 domain. We had previously identified a series of proteins that associates with the WW domains of Nedd4. In this paper, we demonstrate that one of the Nedd4-binding proteins, N4WBP5, belongs to a small group of evolutionarily conserved proteins with three transmembrane domains. N4WBP5 binds Nedd4 WW domains via the two PPXY motifs present in the amino terminus of the protein. In addition to Nedd4, N4WBP5 can interact with the WW domains of a number of Nedd4 family members and is ubiquitinated. Endogenous N4WBP5 localizes to the Golgi complex. Ectopic expression of the protein disrupts the structure of the Golgi, suggesting that N4WBP5 forms part of a family of integral Golgi membrane proteins. Based on previous observations in yeast, we propose that N4WBP5 may act as an adaptor for Nedd4-like proteins and their putative targets to control ubiquitin-dependent protein sorting and trafficking.
Nedd4属于泛素-蛋白连接酶家族，其特征是具有2至4个WW结构域、一个羧基末端Hect（与E6-AP羧基末端同源）结构域，并且在大多数情况下还有一个氨基末端C2结构域。我们之前已经鉴定出一系列与Nedd4的WW结构域相关的蛋白质。在本文中，我们证明了一种Nedd4结合蛋白N4WBP5属于一小类具有三个跨膜结构域的进化保守蛋白。N4WBP5通过该蛋白氨基末端存在的两个PPXY基序与Nedd4的WW结构域结合。除了Nedd4之外，N4WBP5还可以与许多Nedd4家族成员的WW结构域相互作用并被泛素化。内源性N4WBP5定位于高尔基体复合物。该蛋白的异位表达会破坏高尔基体的结构，这表明N4WBP5是完整高尔基体膜蛋白家族的一部分。基于之前在酵母中的观察结果，我们提出N4WBP5可能作为Nedd4样蛋白及其假定靶点的衔接蛋白，以控制泛素依赖性蛋白分选和运输。
