Biochemical basis of regulation of human copper-transporting ATPases.
Copper is essential for cell metabolism as a cofactor of key metabolic enzymes. The biosynthetic incorporation of copper into secreted and plasma membrane-bound proteins requires activity of the copper-transporting ATPases (Cu-ATPases) ATP7A and ATP7B. The Cu-ATPases also export excess copper from the cell and thus critically contribute to the homeostatic control of copper. The trafficking of Cu-ATPases from the trans-Golgi network to endocytic vesicles in response to various signals allows for the balance between the biosynthetic and copper exporting functions of these transporters. Although significant progress has been made towards understanding the biochemical characteristics of human Cu-ATPase, the mechanisms that control their function and intracellular localization remain poorly understood. In this review, we summarize current information on structural features and functional properties of ATP7A and ATP7B. We also describe sequence motifs unique for each Cu-ATPase and speculate about their role in regulating ATP7A and ATP7B activity and trafficking.
Lutsenko
Svetlana
S
Department of Biochemistry and Molecular Biology, Oregon Health & Science University, Portland, OR 97239, USA. lutsenko@ohsu.edu
LeShane
Erik S
ES
Shinde
Ujwal
U
D000251:Adenosine Triphosphatases / Q000737:chemistry* / Q000378:metabolism; D000595:Amino Acid Sequence; D027682:Cation Transport Proteins / Q000737:chemistry* / Q000378:metabolism; D003300:Copper / Q000378:metabolism; D000079922:Copper Transport Proteins; D000073840:Copper-Transporting ATPases; D006801:Humans; D056511:Metallochaperones; D018832:Molecular Chaperones / Q000378:metabolism; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary
C474500:ATOX1 protein, human; D027682:Cation Transport Proteins; D000079922:Copper Transport Proteins; D056511:Metallochaperones; D018832:Molecular Chaperones; D003300:Copper; D000251:Adenosine Triphosphatases; C081184:ATP7A protein, human; C000612464:ATP7B protein, human; D000073840:Copper-Transporting ATPases