βm, a Structural Member of the X,K-ATPase β Subunit Family, Resides in the ER and Does Not Associate with Any Known X,K-ATPase α Subunit

βm, a muscle-specific protein, is structurally closely related to the X,K-ATPase β subunits, but its intrinsic function is not known. In this study, we have expressed βm in Xenopus oocytes and have investigated its biosynthesis and processing as well as its putative role as a chaperone of X,K-ATPase α subunits, as a regulator of sarcoplasmic reticulum Ca2+-ATPase (SERCA), or as a Ca2+-sensing protein. Our results show that βm is stably expressed in the endoplasmic reticulum (ER) in its core glycosylated, partially trimmed form. Both full-length βm, initiated at Met1, and short βm species, initiated at Met89, are detected in in vitro translations as well as in Xenopus oocytes. βm cannot associate with and stabilize Na,K-ATPase (NK), or gastric and nongastric H,K-ATPase (HK) α isoforms. βm neither assembles stably with SERCA nor is its trypsin sensitivity or electrophoretic mobility influenced by Ca2+. A mutant, in which the distinctive Glu-rich regions in the βm N-terminus are deleted, remains stably expressed in the ER and can associate with, but not stabilize X,K-ATPase α subunits. On the other hand, a chimera in which the ectodomain of βm is replaced with that of β1 NK associates efficiently with α NK isoforms and produces functional Na,K-pumps at the plasma membrane. In conclusion, our results indicate that βm exhibits a cellular location and functional role clearly distinct from the typical X,K-ATPase β subunits.