2ppi

Structural highlights

Disease

[GAN_HUMAN] Defects in GAN are the cause of giant axonal neuropathy (GAN) [MIM:256850]. GAN is a severe autosomal recessive sensorimotor neuropathy affecting both the peripheral nerves and the central nervous system. It is characterized by neurofilament accumulation, leading to segmental distention of axons.^{[1] [2] [3] [4] [5] [6]}

Function

[GAN_HUMAN] Probable cytoskeletal component that directly or indirectly plays an important role in neurofilament architecture. Substrate-specific adapter of an E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins. Controls degradation of TBCB. Controls degradation of MAP1B and MAP1S, and is critical for neuronal maintenance and survival.^{[7] [8] [9] [10] [11]}

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

References

1. ↑ Wang W, Ding J, Allen E, Zhu P, Zhang L, Vogel H, Yang Y. Gigaxonin interacts with tubulin folding cofactor B and controls its degradation through the ubiquitin-proteasome pathway. Curr Biol. 2005 Nov 22;15(22):2050-5. PMID:16303566 doi:S0960-9822(05)01305-9
2. ↑ Bomont P, Cavalier L, Blondeau F, Ben Hamida C, Belal S, Tazir M, Demir E, Topaloglu H, Korinthenberg R, Tuysuz B, Landrieu P, Hentati F, Koenig M. The gene encoding gigaxonin, a new member of the cytoskeletal BTB/kelch repeat family, is mutated in giant axonal neuropathy. Nat Genet. 2000 Nov;26(3):370-4. PMID:11062483 doi:10.1038/81701
3. ↑ Kuhlenbaumer G, Young P, Oberwittler C, Hunermund G, Schirmacher A, Domschke K, Ringelstein B, Stogbauer F. Giant axonal neuropathy (GAN): case report and two novel mutations in the gigaxonin gene. Neurology. 2002 Apr 23;58(8):1273-6. PMID:11971098
4. ↑ Bomont P, Ioos C, Yalcinkaya C, Korinthenberg R, Vallat JM, Assami S, Munnich A, Chabrol B, Kurlemann G, Tazir M, Koenig M. Identification of seven novel mutations in the GAN gene. Hum Mutat. 2003 Apr;21(4):446. PMID:12655563 doi:10.1002/humu.9122
5. ↑ Houlden H, Groves M, Miedzybrodzka Z, Roper H, Willis T, Winer J, Cole G, Reilly MM. New mutations, genotype phenotype studies and manifesting carriers in giant axonal neuropathy. J Neurol Neurosurg Psychiatry. 2007 Nov;78(11):1267-70. Epub 2007 Jun 19. PMID:17578852 doi:10.1136/jnnp.2007.118968
6. ↑ Koop O, Schirmacher A, Nelis E, Timmerman V, De Jonghe P, Ringelstein B, Rasic VM, Evrard P, Gartner J, Claeys KG, Appenzeller S, Rautenstrauss B, Huhne K, Ramos-Arroyo MA, Worle H, Moilanen JS, Hammans S, Kuhlenbaumer G. Genotype-phenotype analysis in patients with giant axonal neuropathy (GAN). Neuromuscul Disord. 2007 Aug;17(8):624-30. Epub 2007 Jun 22. PMID:17587580 doi:S0960-8966(07)00114-9
7. ↑ Ding J, Liu JJ, Kowal AS, Nardine T, Bhattacharya P, Lee A, Yang Y. Microtubule-associated protein 1B: a neuronal binding partner for gigaxonin. J Cell Biol. 2002 Aug 5;158(3):427-33. Epub 2002 Jul 29. PMID:12147674 doi:10.1083/jcb.200202055
8. ↑ Furukawa M, He YJ, Borchers C, Xiong Y. Targeting of protein ubiquitination by BTB-Cullin 3-Roc1 ubiquitin ligases. Nat Cell Biol. 2003 Nov;5(11):1001-7. Epub 2003 Oct 5. PMID:14528312 doi:10.1038/ncb1056
9. ↑ Wang W, Ding J, Allen E, Zhu P, Zhang L, Vogel H, Yang Y. Gigaxonin interacts with tubulin folding cofactor B and controls its degradation through the ubiquitin-proteasome pathway. Curr Biol. 2005 Nov 22;15(22):2050-5. PMID:16303566 doi:S0960-9822(05)01305-9
10. ↑ Zhang DD, Lo SC, Sun Z, Habib GM, Lieberman MW, Hannink M. Ubiquitination of Keap1, a BTB-Kelch substrate adaptor protein for Cul3, targets Keap1 for degradation by a proteasome-independent pathway. J Biol Chem. 2005 Aug 26;280(34):30091-9. Epub 2005 Jun 27. PMID:15983046 doi:10.1074/jbc.M501279200
11. ↑ Allen E, Ding J, Wang W, Pramanik S, Chou J, Yau V, Yang Y. Gigaxonin-controlled degradation of MAP1B light chain is critical to neuronal survival. Nature. 2005 Nov 10;438(7065):224-8. Epub 2005 Oct 16. PMID:16227972 doi:nature04256