WWP2

From Proteopedia

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Contents 1 Thoughts & Notes 2 Introduction 3 Structure 4 Function 5 Disease 6 Relevance 7 Structural highlights 8 References

Thoughts & Notes

Should we link this page to 5tjq (2,3-linker)? It also has a proteopedia page.

Introduction

WWP2 is a type of ubiquitin protein ligase and belongs to the NEDD4 family. More specifically, it is a member of the Homologous to the E6-AP Carboxyl Terminus (HECT) E3 Ligases class which accept a ubiquitin molecule from an enzyme upstream in the ubiquitination pathway and transfer the ubiquitin to a Lysine residue in the target signaling molecule or transcription factor. The thioester bond formation between an active site Cystine on HECT E3 Ligases and ubiquitin differentiates this family of enzymes from the more abundant RING family of ubiquitin ligases which mediate ubiquitin transfer through non-covalent interactions. Within HECT E3 Ligases, WWP2 falls into the NEDD4 family. NEDD4 E3 Ligases consist of an N-terminal C2 Domain, between 2-4 WW domains, and a C-terminal HECT domain.

Structure

spinqualitylabelsall models WWP2 Ubiquitin Ligase Full-length Structure (PDB entry 5TJ8) Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image WWP2 is a consisting of a C2 domain, four WW domains (labeled WW1-WW4), two lobes labeled N and C, and a HECT domain. WWP2 has a 2,3-linker connecting WW2 and WW2 domains, this linker plays an autoinhibitory role. Upon phosphorylation the 2,3-linker changes conformation, this change into a more active form that allows the protein to bind ubiquitin in the E2 binding site. This binding will further open the protein up to bind possible substrates.

Function

Disease

Relevance

Structural highlights

References

1. A Tunable Brake for HECT Ubiquitin Ligases.,Chen Z, Jiang H, Xu W, Li X, Dempsey DR, Zhang X, Devreotes P, Wolberger C, Amzel LM, Gabelli SB, Cole PA Mol Cell. 2017 May 4;66(3):345-357.e6. doi: 10.1016/j.molcel.2017.03.020. PMID:2847587