The secretory pathway Ca2+/Mn2+-ATPase 2 is a Golgi-localized pump with high affinity for Ca2+ ions

Accumulation of Ca2+ into the Golgi apparatus is mediated by sarco(endo) plasmic reticulum Ca2+-ATPases (SERCAs) and by secretory pathway Ca2+-ATPases (SPCAs). Mammals and birds express in addition to the housekeeping SPCA1 (human gene name ATP2C1, cytogenetic position 3q22.1) a homologous SPCA2 isoform (human gene name ATP2C2, cytogenetic position 16q24.1). We show here that both genes present an identical exon/intron layout. We confirmed that hSPCA2 has the ability to transport Ca2+, demonstrated its Mn2+-transporting activity, showed its Ca2+- and Mn2+-dependent phosphoprotein intermediate formation, and documented the insensitivity of these functional activities to thapsigargin inhibition. The mRNA encoding hSPCA2 showed a limited tissue expression pattern mainly confined to the gastrointestinal and respiratory tract, prostate, thyroid, salivary, and mammary glands. Immunocytochemical localization in human colon sections presented a typical apical juxtanuclear Golgi-like staining. The expression in COS-1 cells allowed the direct demonstration of Ca-45(2+) (K-0.5 = 0.27 mu M) or Mn-54(2+) transport into an A23187-releasable compartment.