A novel human gene (SARM) at chromosome 17q11 encodes a protein with a SAMmotif and structural similarity to armadillo/beta-catenin that is conserved in mouse, Drosophila, and Caenorhabditis elegans

A novel human gene, SARM, encodes the orthologue of a Drosophila protein (C G7915) and contains a unique combination of the sterile alpha (SAM) and the HEAT/Armadillo motifs, The SARM gene was identified on chromosome 17q11, b etween markers D17S783 and D17S841 on BAC clone AC002094, which also includ ed a HERV repeat and keratin-18-like, MAC30, TN-PAIP1, HSPC017, and vitrone ctin genes in addition to three unknown genes. The mouse SARM gene was loca ted on a mouse chromosome 11 BAC clone (AC002324). The SARM gene is 1.8 kb centromeric to the vitronectin gene, and the two genes share a promoter reg ion that directs a high level of liver-specific expression of both the SARM and the vitronectin genes. In addition to the liver, the SARM gene was hig hly expressed in the kidney. A 0.4-kb antisense transcript was coordinately expressed with the SARM gene in the kidney and liver, while in the brain a nd malignant cell lines, it appeared independent of SARM gene transcription . The SARM gene encodes a protein of 690 amino acids. Based on amino acid s equence homology, we have identified a SAM motif within this derived protei n. Structure modeling and protein folding recognition studies confirmed the presence of alpha-alpha right-handed superhelix-like folds consistent with the structure of the Armadillo and HEAT repeats of the beta -catenin and i mportin protein families, Both motifs are known to be involved in protein-p rotein interactions promoting the formation of diverse protein complexes, W e have identified the same conserved SAM/Armadillo moth combination in the mouse, Drosophila, and Caenorhabditis elegans SARM proteins. (C) 2001 Acade mic Press.