LIV‐1 Breast Cancer Protein Belongs to New Family of Histidine‐Rich Membrane Proteins with Potential to Control Intracellular Zn2+ Homeostasis

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Abstract
Investigation of the protein product of the oestrogen‐regulated gene LIV‐1, implicated in metastatic breast cancer, has revealed 10 protein sequences of unknown function that belong to a new family with potential to control intracellular Zn2+ homeostasis. Sequence alignment highlights the similarity in transmembrane domains and extramembrane charged residues, indicating potential ion‐transport ability. This family has a novel highly conserved motif of 66 residues, including a transmembrane domain and a catalytic zinc‐binding sequence of zinc metalloproteases, containing conserved (indicated in bold type) proline and glutamine residues, HEXPHEXGD. These proteins contain more plentiful histidine‐rich repeats than zinc transporters, suggesting an ability to bind or transport zinc across membranes. I propose that these 11 proteins form a new family with the potential to control intracellular Zn2+ homeostasis.

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