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 homologs for the alpha 2 and beta subunits of chicken Cap Z. The derived human alpha subunit shares 95% amino acid identity with the chicken alpha 2 subunit; the beta subunit is 99% identical to the chicken subunit residues 1-243. The remaining portion of the human beta subunit (244-272) diverges significantly with only 8 out of 29 C-terminal amino acids 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 Cap Z binds actin with an affinity equal that of chicken Cap Z. These results point to the eight shared amino acids as critical for actin binding, three of which are regularly spaced leucines. These apolar residues and one outside the region of divergence align well with those residues of the actin-binding alpha-helix proposed for gelsolin segment 1. The apolar residues as well as three polar amino acids are also conserved in other capping, capping and severing, and monomer-binding proteins. Amino acid substitutions in the chicken beta subunit of the two most highly conserved leucines result in significant decreases in F-actin binding activity. The human alpha 2 gene (CAPZA2) has been mapped to chromosome 7 position q31.2-q31.3 and the beta gene (CAPZB) to chromosome 1 region p36.1.
Barron-Casella
E A
EA
Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Torres
M A
MA
Scherer
S W
SW
Heng
H H
HH
Tsui
L C
LC
Casella
J F
JF
D000199:Actins / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D017173:Caenorhabditis elegans / Q000378:metabolism; D051347:CapZ Actin Capping Protein; D002645:Chickens; D002874:Chromosome Mapping; D018244:Chromosomes, Artificial, Yeast; D002878:Chromosomes, Human, Pair 1; D002897:Chromosomes, Human, Pair 7; D017124:Conserved Sequence; D017931:DNA Primers; D004023:Dictyostelium / Q000378:metabolism; D015723:Gene Library; D017781:Genes, Immediate-Early; D015186:Hominidae / Q000235:genetics*; D006801:Humans; D046911:Macromolecular Substances; D051379:Mice; D008840:Microfilament Proteins; D008969:Molecular Sequence Data; D009124:Muscle Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D017433:Protein Structure, Secondary; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism; D012160:Retina / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D017386:Sequence Homology, Amino Acid
D000199:Actins; C495842:CAPZA1 protein, human; C495845:CAPZA2 protein, human; D051347:CapZ Actin Capping Protein; D017931:DNA Primers; D046911:Macromolecular Substances; D008840:Microfilament Proteins; D009124:Muscle Proteins; D011994:Recombinant Proteins