SEQUENCE-ANALYSIS AND CHROMOSOMAL LOCALIZATION OF HUMAN CAP-Z - CONSERVED RESIDUES WITHIN THE ACTIN-BINDING DOMAIN MAY LINK CAP-Z TO GELSOLIN SEVERIN AND PROFILIN PROTEIN FAMILIES/

From a human retinal cDNA library, we have isolated cDNAs that are hom ologs for the alpha 2 and beta subunits of chicken Cap Z. The derived human alpha subunit shares 95% amino acid identity with the chicken al pha 2 subunit; the beta subunit is 99% identical to the chicken subuni t residues 1-243. The remaining portion of the human beta subunit (244 -272) diverges significantly with only 8 out of 29 C-terminal amino ac ids conserved between the two species, This lack of conservation is of particular interest because the chicken C terminus contains an actin- binding domain, Cosedimentation assays with F-actin show that human Ca p Z binds actin with an affinity equal that of chicken Cap Z, These re sults point to the eight shared amino acids as critical for actin bind ing, three of which are regularly spaced leucines, These apolar residu es and one outside the region of divergence align well with those resi dues of the actin-binding alpha-helix proposed for gelsolin segment 1. The apolar residues as well as three polar amino acids are also conse rved in other capping, capping and severing, and monomer-binding prote ins, Amino acid substitutions in the chicken beta subunit of the two m ost highly conserved leucines result in significant decreases in F-act in binding activity, The human alpha 2 gene (CAPZA2) has been mapped t o chromosome 7 position q31.2-q31.3 and the beta gene (CAPZB) to chrom osome 1 region p36.1.