title: Ancient conserved domain protein-1 binds copper and modifies its retention in cells.
abstract: The ancient conserved domain protein (ACDP) family are a recently identified group of homologous mammalian proteins. Some family members have been suggested to have roles in the metabolism of metals. We investigated the capacity of ACDP-1 to bind metals. Using immobilised metal affinity chromatography and isothermal titration calorimetry we determined that ACDP-1 is a high affinity copper binding protein able to bind copper at nanomolar concentrations. In addition the promoter of ACDP-1 contains metal response elements and the cellular expression of ACDP-1 alters cellular retention of copper. However, cellular expression of ACDP-1 does not alter cellular resistance to the toxicity of copper or other metals. As our findings place the subcellular localisation of ACDP-1 in the cytoplasm it is possible that ACDP-1 represent a novel copper chaperone or storage protein.
authors.affiliation: Department of Biology and Biochemistry, University of Bath, Bath, UK.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Alderton
authors.forename: Paul
authors.initials: P
authors.lastname: Davies
authors.forename: Katie
authors.initials: K
authors.lastname: Illman
authors.forename: David R
authors.initials: DR
authors.lastname: Brown
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D027682:Cation Transport Proteins; D002460:Cell Line; D002522:Chlorocebus aethiops; D003001:Cloning, Molecular; D003300:Copper / Q000378:metabolism* / Q000633:toxicity; D016213:Cyclins / Q000235:genetics / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism; D019216:Metals, Heavy / Q000633:toxicity; D051379:Mice; D008969:Molecular Sequence Data; D017386:Sequence Homology, Amino Acid
chemical_list: D002352:Carrier Proteins; D027682:Cation Transport Proteins; C523974:Cnnm1 protein, mouse; D016213:Cyclins; D019216:Metals, Heavy; D003300:Copper