Tropomadulin is a newly characterized pointed end capping protein far actin filaments, It binds specifically to the N terminus of tropomyosin and blocks the elongation and, depolymerization of tropomyosin-coated actin filaments, A 1.9-kb human tropomodulin cDNA clone was used to map its gene by fluorescence in situ hybridization. The tropomodulin gene was assigned to human chromosome 9q22.2-q22.3, a region that is also known to contain several other genes and disease loci and is proximal to the loci for gelsolin and alpha-fodrin. The gene for tropomodulin is expressed in major human tissues at different levels in the following order: heart and skeletal muscle much greater than that in brain, lung, and pancreas, which is greater than that ill placenta, liver, and kidney, Human tropomodulin and a 64-kDa autoantigen in Graves disease (D-1) are related: tropomodulin has 42 and. 41% identity with the Graves protein in the N-terminal (69 residue) and C-terminal (194 residue) regions, respectively, The insertion of several homologous repeats in the midsection of the Graves protein, together with the extension of a proline-rich C terminus, accounts for the differences in length between the Graves protein (572 residues) and tropomodulin (359 residues), The significant sequence identity indicates that these two genes are evolved from a common ancestral gene. (C) 1996 Academic Press, Inc.