Transcellular calcium transport occurs in many epithelial tissues including intestine, kidney, and placenta. We identified the human ortholog (hCaT1) of a recently cloned rat calcium transport protein, CAT1, that mediates intestinal calcium uptake, hCaT1 messenger RNA is present in the gastrointestinal tract, including esophagus, stomach, duodenum, jejunum, ileum, and colon. High levels of hCaT1 transcripts are also present in pancreas, placenta, prostate, and salivary gland, while moderate levels are present in liver, kidney, and testis. hCaT1 mRNA is also expressed in the colorectal cancer cell line, SW480, and the chronic myelogenous leukemia cell line, K-562. The hCaT1 gene was assigned to the long arm of chromosome 7, bands q33-34, by fluorescence in situ hybridization. When expressed in Xenopus laevis oocytes, hCaT1 promotes saturable Ca2+ uptake with a Michaelis constant of 0.25 mM. Our studies suggest a role for hCaT1 in cellular calcium uptake in a variety of tissues, including the transcellular calcium transport pathway in intestine. (C) 2000 Academic Press.