| Structural highlights
Disease
ATP7B_HUMAN Defects in ATP7B are the cause of Wilson disease (WD) [MIM:277900. WD is an autosomal recessive disorder of copper metabolism in which copper cannot be incorporated into ceruloplasmin in liver, and cannot be excreted from the liver into the bile. Copper accumulates in the liver and subsequently in the brain and kidney. The disease is characterized by neurologic manifestations and signs of cirrhosis.[1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] [15] [16] [17] [18] [19] [20] [21] [22] [23] [24] [25] [26] [27] [28] [29] [30] [31] [32] [33] [34] [35] [36] [37] [38] [39] [40] [41] [42] [43] [44] [45] [46] [47] [48] [49] [50] [51]
Function
ATP7B_HUMAN Involved in the export of copper out of the cells, such as the efflux of hepatic copper into the bile.
Publication Abstract from PubMed
Copper-transporter ATP7B maintains copper homeostasis in the human cells and delivers copper to the biosynthetic pathways for incorporation into the newly synthesized copper-containing proteins. ATP7B is a target of several hundred mutations that lead to Wilson disease, a chronic copper toxicosis. ATP7B contains a chain of six cytosolic metal-binding domains (MBDs), the first four of which (MBD1-4) are believed to be regulatory, and the last two (MBD5-6) are required for enzyme activity. We report the NMR structure of MBD1, the last unsolved metal-binding domain of ATP7B. The structure reveals the disruptive mechanism of G85V mutation, one of the very few disease causing missense mutations in the MBD1-4 region of ATP7B.
The Structure of Metal Binding Domain 1 of the Copper Transporter ATP7B Reveals Mechanism of a Singular Wilson Disease Mutation.,Yu CH, Lee W, Nokhrin S, Dmitriev OY Sci Rep. 2018 Jan 12;8(1):581. doi: 10.1038/s41598-017-18951-1. PMID:29330485[52]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
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- ↑ Lee CC, Wu JY, Tsai FJ, Kodama H, Abe T, Yang CF, Tsai CH. Molecular analysis of Wilson disease in Taiwan: identification of one novel mutation and evidence of haplotype-mutation association. J Hum Genet. 2000;45(5):275-9. PMID:11043508 doi:10.1007/s100380070015
- ↑ Genschel J, Czlonkowska A, Sommer G, Buettner C, Bochow B, Lochs H, Schmidt H. Three novel mutations (P760L, L1305P, Q1351Stop) causing Wilson disease. Hum Mutat. 2001 Feb;17(2):156. PMID:11180609 doi:<156::AID-HUMU18>3.0.CO;2-0 10.1002/1098-1004(200102)17:2<156::AID-HUMU18>3.0.CO;2-0
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- ↑ Gromadzka G, Schmidt HH, Genschel J, Bochow B, Rodo M, Tarnacka B, Litwin T, Chabik G, Czlonkowska A. Frameshift and nonsense mutations in the gene for ATPase7B are associated with severe impairment of copper metabolism and with an early clinical manifestation of Wilson's disease. Clin Genet. 2005 Dec;68(6):524-32. PMID:16283883 doi:10.1111/j.1399-0004.2005.00528.x
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- ↑ Yu CH, Lee W, Nokhrin S, Dmitriev OY. The Structure of Metal Binding Domain 1 of the Copper Transporter ATP7B Reveals Mechanism of a Singular Wilson Disease Mutation. Sci Rep. 2018 Jan 12;8(1):581. doi: 10.1038/s41598-017-18951-1. PMID:29330485 doi:http://dx.doi.org/10.1038/s41598-017-18951-1
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