2ffx

Structural highlights

Disease

FRIL_HUMAN Defects in FTL are the cause of hereditary hyperferritinemia-cataract syndrome (HHCS) [MIM:600886. It is an autosomal dominant disease characterized by early-onset bilateral cataract. Affected patients have elevated level of circulating ferritin. HHCS is caused by mutations in the iron responsive element (IRE) of the FTL gene.^[1] Defects in FTL are the cause of neurodegeneration with brain iron accumulation type 3 (NBIA3) [MIM:606159; also known as adult-onset basal ganglia disease. It is a movement disorder with heterogeneous presentations starting in the fourth to sixth decade. It is characterized by a variety of neurological signs including parkinsonism, ataxia, corticospinal signs, mild nonprogressive cognitive deficit and episodic psychosis. It is linked with decreased serum ferritin levels.^{[2] [3]}

Function

FRIL_HUMAN Stores iron in a soluble, non-toxic, readily available form. Important for iron homeostasis. Iron is taken up in the ferrous form and deposited as ferric hydroxides after oxidation. Also plays a role in delivery of iron to cells. Mediates iron uptake in capsule cells of the developing kidney (By similarity).^{[4] [5]}

Evolutionary Conservation

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

See Also

• Ferritin 3D structures

References

1. ↑ Luscieti S, Santambrogio P, Langlois d'Estaintot B, Granier T, Cozzi A, Poli M, Gallois B, Finazzi D, Cattaneo A, Levi S, Arosio P. Mutant ferritin L-chains that cause neurodegeneration act in a dominant-negative manner to reduce ferritin iron incorporation. J Biol Chem. 2010 Apr 16;285(16):11948-57. Epub 2010 Feb 16. PMID:20159981 doi:10.1074/jbc.M109.096404
2. ↑ Luscieti S, Santambrogio P, Langlois d'Estaintot B, Granier T, Cozzi A, Poli M, Gallois B, Finazzi D, Cattaneo A, Levi S, Arosio P. Mutant ferritin L-chains that cause neurodegeneration act in a dominant-negative manner to reduce ferritin iron incorporation. J Biol Chem. 2010 Apr 16;285(16):11948-57. Epub 2010 Feb 16. PMID:20159981 doi:10.1074/jbc.M109.096404
3. ↑ Maciel P, Cruz VT, Constante M, Iniesta I, Costa MC, Gallati S, Sousa N, Sequeiros J, Coutinho P, Santos MM. Neuroferritinopathy: missense mutation in FTL causing early-onset bilateral pallidal involvement. Neurology. 2005 Aug 23;65(4):603-5. PMID:16116125 doi:10.1212/01.wnl.0000178224.81169.c2
4. ↑ Baraibar MA, Muhoberac BB, Garringer HJ, Hurley TD, Vidal R. Unraveling of the E-helices and disruption of 4-fold pores are associated with iron mishandling in a mutant ferritin causing neurodegeneration. J Biol Chem. 2010 Jan 15;285(3):1950-6. Epub 2009 Nov 18. PMID:19923220 doi:10.1074/jbc.M109.042986
5. ↑ Luscieti S, Santambrogio P, Langlois d'Estaintot B, Granier T, Cozzi A, Poli M, Gallois B, Finazzi D, Cattaneo A, Levi S, Arosio P. Mutant ferritin L-chains that cause neurodegeneration act in a dominant-negative manner to reduce ferritin iron incorporation. J Biol Chem. 2010 Apr 16;285(16):11948-57. Epub 2010 Feb 16. PMID:20159981 doi:10.1074/jbc.M109.096404