NOMENCLATURE CONFLICT NOTE

PMR1 encodes the major Golgi membrane P-type ATPase ion pump responsible for transporting calcium [Ca(2+)] and manganese [Mn(2+)] ions into the Golgi apparatus (8, 9, 3, 10). Both ions are necessary for proper processing and trafficking of polypeptides through the secretory pathway, but each plays a distinct role. Ca(2+) is required to sustain protein sorting while Mn(2+) is required for protein glycosylation. In addition, Pmr1p provides a major route for cellular detoxification of Mn(2+). Excess levels of cytosolic Mn(2+) are transported into the Golgi and then exit the cell via secretory pathway vesicles (9, 11, 12 and references therein).

Two different regions in this protein have been demonstrated to play important roles in Pmr1p selectivity and function, an N-terminal EF hand-like motif is necessary for ion binding and transport activity in vitro. Single point mutations in this motif can change the affinity of the protein for Ca(2+), Mn(2+), or both. (13). Second, putative cation translocating regions have been localized to transmembrane helices 4 and 6. Specific mutations in these regions can also alter the ion selectivity of Pmr1p (9). A null mutation of the HUR1 gene, which overlaps PMR1, was reported to cause sensitivity to hydroxyurea (14); however, a precise deletion within PMR1 that does not include any of the HUR1 coding sequence confers hydroxyurea sensitivity (15).

Pmr1p is the prototype of a family of transporters known as SPCA (Secretory Pathway Ca2+-ATPases) with members found in fungi, C. elegans, D. melanogaster, and mammals (12 and refereneces therein). Defects in the human ortholog of PMR1, ATP2C1, are associated with Hailey-Hailey disease (aka benign familial pemphigus), a severe blistering skin disorder (reviewed in 16). Although hSPCA1 (the protein encoded by ATP2C1) and Pmr1p are only 49% homologous, when expressed in yeast, ATP2C1 fully complements the pmr1 mutant phenotype (17).

Last updated: 2006-11-21