The NHR domains of Neuralized and related proteins: Beyond Notch signalling

- NHR domains are highly conserved domains that regulate protein-protein interactions.
- NHR domain proteins regulate numerous cellular and developmental processes.
- Structural similarity between NHR and SPRY domains.

Neuralized Homology Repeats (NHRs) were first identified in Neuralized, an E3-ubiquitin ligase that plays a key role in the Notch signalling pathway. Since their original discovery, NHR domains have been shown to regulate protein-protein interactions in a broad range of developmental processes and in a wide variety of species from flies to humans. The NHR family of proteins can be categorized into three groups: (1) those that contain a RING finger, (2) those that contain a SOCS box and, (3) those that only have NHR domains. Here we review the structure and function of NHR domains in various cellular and developmental processes.