copper transporting ATPase-1; copper pump-1; Cu+2-transporting ATPase alpha polypeptide; Menke's disease-associated protein (ATP7A, MNK)

Function

• may supply copper to copper-requiring proteins within the secretory pathway, when localized in the trans-Golgi network
• under conditions of elevated extracellular copper, relocalizes to the plasma membrane where it functions in the efflux of copper from cells

ATP + H2O + Cu+2(In) <--> ADP + phosphate + Cu+2(out)

Structure

• monomer
• the C-terminal di-leucine, 1487-Leu-Leu-1488, is an endocytic targeting signal which functions in retrieving recycling from the plasma membrane to the trans-Golgi network
• mutation of the di-leucine signal results in accumulation of the protein in the plasma membrane
• belongs to the cation transport ATPase (P-type) family, type IB subfamily
• contains 6 HMA domains

Compartment

• Golgi, trans-Golgi network membrane, cell membrane
• cycles constitutively between the trans-Golgi network & the plasma membrane
• predominantly found in the TGN & relocalized to the plasma membrane in response to elevated copper levels
• isoform 3: cytoplasm, cytosol (probable)
• isoform 5: endoplasmic reticulum

Alternative splicing

named isoforms=6

Expression

• found in most tissues except liver
• isoform 3 is widely expressed including in liver cell lines
• isoform 1 is expressed in fibroblasts, choriocarcinoma, colon carcinoma & neuroblastoma cell lines
• isoform 2 is expressed in fibroblasts, colon carcinoma & neuroblastoma cell lines

Pathology

• defects in ATP7A are the cause of
  • Menkes disease
  • occipital horn syndrome

Laboratory

• ATP7A gene mutation

More general terms

• copper transporting ATPase
• transmembrane 8 protein

Additional terms

• ATP7A gene mutation; copper transporting ATPase 1 gene mutation
• Menkes disease (kinky or steely hair disease)
• X-linked cutis laxa; occipital horn syndrome

Database

• UniProt: http://www.uniprot.org/uniprot/Q04656.html
• OMIM: https://mirror.omim.org/entry/300011
• OMIM: https://mirror.omim.org/entry/309400
• OMIM: https://mirror.omim.org/entry/304150
• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:538