| Type: | Family | Name: | Gigaxonin |
| Description: | Gigaxonin (also known as KLHL16) regulates microtubule-associated protein 1B (MAP1B), which is involved in maintaining the integrity of cytoskeletal structures and promoting neuronal stability []. Gigaxonin belongs to the KLHL family. Mutations in the gigaxonin gene cause giant axonal neuropathy (GAN), which is a devastating sensory and motor neuropathy []. Gigaxonin binds to the ubiquitin-activating enzyme E1 through its N-terminal BTB domain, while the carboxy-terminal kelch repeat domain interacts directly with the light chain (LC) of MAP1B. It may serve as an ubiquitin substrate adaptor protein that controls MAP1B-LC degradation [, ].The KLHL (Kelch-like) proteins generally have a BTB/POZ domain, a BACK domain, and five to six Kelch motifs. They constitute a subgroup at the intersection between the BTB/POZ domain and Kelch domain superfamilies. The BTB/POZ domain facilitates protein binding [], while the Kelch domain (repeats) form beta-propellers. The Kelch superfamily of proteins can be subdivided into five groups: (1) N-propeller, C-dimer proteins, (2) N-propeller proteins, (3) propeller proteins, (4) N-dimer, C-propeller proteins, and (5) C-propeller proteins. KLHL family members belong to the N-dimer, C-propeller subclass of Kelch repeat proteins []. In addition to BTB/POZ and Kelch domains, the KLHL family members contain a BACK domain, first described as a 130-residue region of conservation observed amongst BTB-Kelch proteins []. Many of the Kelch-like proteins have been identified as adaptors for the recruitment of substrates to Cul3-based E3 ubiquitin ligases [, ]. | Short Name: | KLHL16 |
