title: A novel human gene (SARM) at chromosome 17q11 encodes a protein with a SAM motif and structural similarity to Armadillo/beta-catenin that is conserved in mouse, Drosophila, and Caenorhabditis elegans.
abstract: A novel human gene, SARM, encodes the orthologue of a Drosophila protein (CG7915) and contains a unique combination of the sterile alpha (SAM) and the HEAT/Armadillo motifs. The SARM gene was identified on chromosome 17q11, between markers D17S783 and D17S841 on BAC clone AC002094, which also included a HERV repeat and keratin-18-like, MAC30, TNFAIP1, HSPC017, and vitronectin genes in addition to three unknown genes. The mouse SARM gene was located 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 region 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 highly 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 and malignant cell lines, it appeared independent of SARM gene transcription. The SARM gene encodes a protein of 690 amino acids. Based on amino acid sequence homology, we have identified a SAM motif within this derived protein. 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 importin protein families. Both motifs are known to be involved in protein-protein interactions promoting the formation of diverse protein complexes. We have identified the same conserved SAM/Armadillo motif combination in the mouse, Drosophila, and Caenorhabditis elegans SARM proteins.
authors.affiliation: Pacific Biomedical Research Center, University of Hawaii, 1993 East-West Road, Honolulu, Hawaii, 96822
authors.forename: M
authors.initials: M
authors.lastname: Mink
authors.forename: B
authors.initials: B
authors.lastname: Fogelgren
authors.forename: K
authors.initials: K
authors.lastname: Olszewski
authors.forename: P
authors.initials: P
authors.lastname: Maroy
authors.forename: K
authors.initials: K
authors.lastname: Csiszar
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D051186:Armadillo Domain Proteins; D015152:Blotting, Northern; D001921:Brain / Q000378:metabolism; D017173:Caenorhabditis elegans; D002874:Chromosome Mapping; D002886:Chromosomes, Human, Pair 17; D017124:Conserved Sequence; D003598:Cytoskeletal Proteins / Q000096:biosynthesis / Q000737:chemistry* / Q000235:genetics*; D004330:Drosophila; D029721:Drosophila Proteins; D019143:Evolution, Molecular; D005091:Exons; D020224:Expressed Sequence Tags; D005819:Genetic Markers; D006801:Humans; D007231:Infant, Newborn; D019476:Insect Proteins / Q000235:genetics*; D007438:Introns; D051379:Mice; D008957:Models, Genetic; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D014018:Tissue Distribution; D015534:Trans-Activators; D014157:Transcription Factors; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured; D051176:beta Catenin
chemical_list: C495305:ARM protein, Drosophila; D051186:Armadillo Domain Proteins; C495270:CTNNB1 protein, human; C495267:CTNNB1 protein, mouse; D003598:Cytoskeletal Proteins; D029721:Drosophila Proteins; D005819:Genetic Markers; D019476:Insect Proteins; C435689:SARM1 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; D051176:beta Catenin