Gigaxonin (IPR030579)

Short name: KLHL16

Overlapping homologous superfamilies

Family relationships


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 [PMID: 12147674]. Gigaxonin belongs to the KLHL family. Mutations in the gigaxonin gene cause giant axonal neuropathy (GAN), which is a devastating sensory and motor neuropathy [PMID: 16227972]. 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 [PMID: 12147674, PMID: 16227972].

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 [PMID: 23676014], 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 [PMID: 10603472]. 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 [PMID: 15544948]. Many of the Kelch-like proteins have been identified as adaptors for the recruitment of substrates to Cul3-based E3 ubiquitin ligases [PMID: 23135275, PMID: 14528312].

GO terms

Biological Process

GO:0007010 cytoskeleton organization

Molecular Function

No terms assigned in this category.

Cellular Component

No terms assigned in this category.

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.