Gigaxonin (GAN)

GAN1; KLHL16; Giant Axonal Neuropathy; Kelch-like protein 16

SPN	O685
HGNC	4137
MGI	1890619
PubMed	23585478
RGD	1307766
UniProt	Q9H2C0
Wiki	GAN

GAN encodes a member of the cytoskeletal BTB/kelch (Broad-Complex, Tramtrack and Bric a brac) repeat family. (Kelch repeats are predicted to form a beta-propeller shape.) The encoded protein plays a role in neurofilament architecture and is mutated in giant axonal neuropathy.gigaxonin controls protein degradation and is essential for neuronal function and survival. gigaxonin binds to the ubiquitin-activating enzyme E1 through its amino-terminal BTB domain, while the carboxy-terminal kelch repeat domain interacts directly with the light chain (LC) of microtubule-associated protein-1B (MAP1B). Overexpression of gigaxonin leads to enhanced degradation of MAP1B-LC, which could be antagonized by proteasome inhibitors. Ablation of gigaxonin caused a substantial accumulation of MAP1B-LC in GAN-null neurons.

Reference

"The gene encoding gigaxonin, a new member of the cytoskeletal BTB/kelch repeat family, is mutated in giant axonal neuropathy."
Nat. Genet. 26:370-374(2000) [PubMed] [Europe PMC] [Abstract]

"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]

"Microtubule-associated protein 1B: a neuronal binding partner for gigaxonin."
J. Cell Biol. 158:427-433(2002) [PubMed] [Europe PMC] [Abstract]

"Targeting of protein ubiquitination by BTB-Cullin 3-Roc1 ubiquitin ligases."
Nat. Cell Biol. 5:1001-1007(2003) [PubMed] [Europe PMC] [Abstract]

"Gigaxonin interacts with tubulin folding cofactor B and controls its degradation through the ubiquitin-proteasome pathway."
Curr. Biol. 15:2050-2055(2005) [PubMed] [Europe PMC] [Abstract]

"Ubiquitination of Keap1, a BTB-Kelch substrate adaptor protein for Cul3, targets Keap1 for degradation by a proteasome-independent pathway."
J. Biol. Chem. 280:30091-30099(2005) [PubMed] [Europe PMC] [Abstract]

"Gigaxonin-controlled degradation of MAP1B light chain is critical to neuronal survival."
Nature 438:224-228(2005) [PubMed] [Europe PMC] [Abstract]

"Ectodermal-neural cortex 1 down-regulates Nrf2 at the translational level."
PLoS ONE 4:E5492-E5492(2009) [PubMed] [Europe PMC] [Abstract]

"Structures of SPOP-substrate complexes: insights into molecular architectures of BTB-Cul3 ubiquitin ligases."
Mol. Cell 36:39-50(2009) [PubMed] [Europe PMC] [Abstract]

"Structure of the BTB (tramtrack and bric a brac) domain of human gigaxonin."
Submitted (JUL-2011) to the PDB data bank

"Giant axonal neuropathy (GAN): case report and two novel mutations in the gigaxonin gene."
Neurology 58:1273-1276(2002) [PubMed] [Europe PMC] [Abstract]

Erratum
Neurology 58:1444-1444(2002)

"Identification of seven novel mutations in the GAN gene."
Hum. Mutat. 21:446-446(2003) [PubMed] [Europe PMC] [Abstract]

"New mutations, genotype phenotype studies and manifesting carriers in giant axonal neuropathy."
J. Neurol. Neurosurg. Psych. 78:1267-1270(2007) [PubMed] [Europe PMC] [Abstract]

"Genotype-phenotype analysis in patients with giant axonal neuropathy (GAN)."
Neuromuscul. Disord. 17:624-630(2007) [PubMed] [Europe PMC] [Abstract]

"Whole-exome sequencing in patients with inherited neuropathies: outcome and challenges."
J. Neurol. 261:970-982(2014) [PubMed] [Europe PMC] [Abstract]