We have characterized the cDNA of MZFM, the mouse homolog to the novel human putative tumor suppressor gene ZFM1. The total length of the cDNA is 2,637 nucleotides with an open reading frame for a protein of 548 amino acids containing 4.7% methionine and 17.2% proline. The predicted molecular mass of 59 kD fits the 62-kD band experimentally determined by NaDodSO4-PAGE from in vitro translation products of in vitro-transcribed MZFM cDNA. The MZFM cDNA best matches to that ZFM1-isoform without the so-called 0.25-kb E-domain and to the L49345 cDNA recently identified in a human leukemia cell line. Northern analysis reveals expression of MZFM only in spleen macrophages. Reverse transcription polymerase chain reaction (RT-PCR) in combination with Southern analysis also detects a low basal expression in splenic T cells and B cells, as well as in other tissues such as heart, kidney, brain, liver, testis, bone marrow, adrenal gland, lymph nodes, pancreas, and thymus. In splenic macrophages, MZFM mRNA is alternatively spliced yielding a 3.6-kb transcript with E-domain, a 3.0-kb transcript without E-domain, and a 2.7-kb transcript with E-domain. The predicted MZFM protein contains diverse functional domains, i.e., a nuclear localization signal, a metal binding motif, a glutamine/proline stretch, proline-clusters, a CGA-motif, and a QUA1-KH-QUA2 region, thus indicating multiple functions of MZFM. Presumably, MZFM is a new member of those proteins combining features of signal transduction and RNA activation (STAR-proteins). The different MZFM-isoforms may be part of a macrophage-inherent program of transduction of environmental signals into different activational states of macrophages.