Identity of Human Normal Counterpart (MmTRA1b) of Mouse Leukemogenesis-Associated Gene (MmTRA1a) Product as Plasma Membrane Phospholipid Scramblase and Chromosome Mapping of the Human MmTRA1b/Phospholipid Scramblase Gene

Abstract

We recently cloned a new leukemogenesis-associated gene MmTRA1a (Mm-1 cell derivedtransplantability-associated gene1a,former name “TRA1′’) from a mouse leukemogenic and monocytic Mm-P cell cDNA library and also cloned its normal counterpart MmTRA1b (former name “NOR1′’) from a normal mouse kidney cDNA library. The mouse MmTRA1a is a truncated form of mouse MmTRA1b. Here we report the cloning of a cDNA (human MmTRA1b) homologous to the mouse MmTRA1b from a human monocytic U937 cell cDNA library. The human MmTRA1b cDNA predicts a peptide containing 318 amino acids with a calculated molecular weight of 35,047 Da. The predicted human MmTRA1b protein sequence shared 78% amino acid identity with the mouse counterpart (328 amino acids). Both the human homologue and mouse MmTRA1b protein but not MmTRA1a protein possess a proline-rich domain at the N-terminal end. The human MmTRA1b gene was mapped to chromosome 3q23. Expression of the human homologue was increased during differentiation of U937 cells induced by most typical differentiation inducers. Moreover, predicted amino acid sequence analysis of human MmTRA1b cDNA revealed perfect identity with the human plasma membrane phospholipid scramblase that is required for transbilayer movement of membrane phospholipids. These results provide new information on the possible roles of MmTRA1b/phospholipid scramblase and the truncated MmTRA1a in the leukemogenesis and differentiation of monocytic leukemia cells.