A secreted protein, Ecm1, specific for the clonal osteogenic stromal cell line MN7 was identified by 2D-SDS-PAGE (Mathieu et al, 1994, J. Bone Miner Res, 9, 903-913). The complete cDNA of the ECM1 gene has a length of 1.9 kb and codes for a protein of 559 amino acids. The Ecm1 mRNA is differentially spliced to a 1.5 Kb transcript. The 1.9 Kb mRNA is present in different tissues such as liver, lung and heart while the 1.5Kb mRNA is present in skin and cartilage containing tissues (Bhalerao J. et al., 1995, J. Biol. Chem., 270, 16385-16394).The complete Ecm1 gene was isolated from a Balbc 3T3 genomic library using the 1.9 kb cDNA as probe. The Ecm1 gene is a single copy gene of 5.3 kb containing 11 exons and is localized to mouse chromosome 3. By comparison of the cDNA sequence with the genomic sequence it was shown that the shorter transcript (1.5 kb) is a tissue specific alternatively spliced variant of the Ecm1 gene, lacking the complete exon 8. We observe that this exon 8 contains a sequence similar to the calcium-binding loop of calpain (Aoki et al., 1986, FEBS Lett., 205, 313-317). The 5 promotor region of the gene was sequenced and revealed a consensus TATA-box (at -34) followed by a GC rich region containing a putative Sp1 binding site (at -49), a putative AP1 binding site (at -71) and the presence of a possible site for the glucocorticoid receptor (GR) (at -256). Furthermore, the region between -600 to -616 contains a CCAAT box and an additional AP1 site. The function of the Ecm1 protein is at present unknown. It is tempting to speculate that the larger isoform has the ability to bind calcium and thus would be placed in bone. The protein encoded by the splice variant may have a structural modification for an altered function in skin and cartilage. Thus, alternative splicing may serve as a mechanism for generating functional diversity in the Ecm1 gene.