SMT3A, A HUMAN HOMOLOG OF THE S-CEREVISIAE-SMT3 GENE, MAPS TO CHROMOSOME-21QTER AND DEFINES A NOVEL GENE FAMILY

cDNA selection was used to isolate coding sequences from cosmids mappi ng to the gene-rich telomeric region of human chromosome 21q. A novel cDNA, termed SMT3A, was isolated and mapped between the loci PFKL and D21S171, about 2.2 Mb proximal to the telomere, The predicted protein of 103 amino acids appears to be a homologue of the Saccharomyces cere visiae SMT3 protein, whose gene was previously isolated as a suppresso r of mutations in the MIF2 gene, The yeast MIF2 gene encodes an essent ial centromeric protein and shows homology to mammalian CENP-C, an int egral component of active kinetochores. SMT3A was found to be highly h omologous to two other recently isolated human genes, suggesting the p resence of a new gene family. Homologous sequences were also found in protozoa, metazoa, and plants, Moreover, all predicted proteins show s ignificant homology to ubiquitin. The proposed role of yeast SMT3 as c entromeric protein and the strong evolutionary conservation of the SMT 3A gene suggest an involvement of the encoded protein in the function and/or structure of the eukaryotic kinetochore. (C) 1997 Academic Pres s.