LIV-1 breast cancer protein belongs to new family of histidine-rich membrane proteins with potential to control intracellular Zn2+ homeostasis.
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.
Taylor
K M
KM
Tenovus Cancer Research Centre, Welsh School of Pharmacy, Cardiff University, UK. taylorkm@cf.ac.uk
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D017360:Arabidopsis / Q000235:genetics; D017173:Caenorhabditis elegans / Q000235:genetics; D027682:Cation Transport Proteins; D002462:Cell Membrane / Q000378:metabolism; D017124:Conserved Sequence; D006639:Histidine / Q000737:chemistry; D006801:Humans; D007477:Ions; D008565:Membrane Proteins / Q000737:chemistry* / Q000235:genetics*; D051379:Mice; D008954:Models, Biological; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000737:chemistry* / Q000235:genetics*; D051381:Rats; D017386:Sequence Homology, Amino Acid; D015003:Yeasts / Q000235:genetics; D015027:Zebrafish / Q000235:genetics; D015032:Zinc / Q000378:metabolism*
D027682:Cation Transport Proteins; D007477:Ions; D008565:Membrane Proteins; D009363:Neoplasm Proteins; C418627:SLC39A6 protein, human; D006639:Histidine; D015032:Zinc