cDNA cloning, sequencing and chromosome mapping of a non-erythroid spectrin, human alpha-fodrin.
Several overlapping cDNA clones encompassing 2760 nucleotides of the alpha-subunit of a human non-erythroid spectrin (termed fodrin) were isolated from a human lung fibroblast cDNA library. DNA and RNA blot analyses indicated that a single copy alpha-fodrin gene encodes a 9-kb transcript. The cDNA clones were sequenced, and all were found to contain long open reading frames. The overlapping regions were identical except for a 60-nucleotide inframe insertion at position 1133 in the composite sequence. This result suggests that at least two distinct transcripts exist in fibroblast cells. The chromosomal location of human alpha-fodrin was assigned to 1p34-1p36.1 by hybridization to somatic cell hybrids, and it is thus distinct from that of human alpha-spectrin which has been mapped to 1q22-1q25. Alignment of the composite 919 amino acids of the predicted protein sequence of human alpha-fodrin with that of human alpha-spectrin indicated that alpha-fodrin has a similar 106-amino-acid repeating structure, which is homologous with alpha-spectrin repeats 7-15. Repeats 10 and 11 are anomalous in sequence and structure from other repeats. A comparison of nucleic acid and amino acid homologies between alpha-spectrin and the alpha-fodrin of several vertebrates indicated that human non-erythroid alpha-fodrin and the common alpha-subunit of erythroid and non-erythroid cells of non-mammalian vertebrates are closely related (90%-96% amino acid homology), whereas alpha-fodrin is only distantly related to the erythroid-specific alpha-spectrin subunit of mammals (55%-59% amino acid homology). These data suggest that mammalian erythroid alpha-spectrin evolved by duplication and rapid divergence from an ancestral alpha-fodrin-like gene.
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics*; D002460:Cell Line; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D004247:DNA / Q000378:metabolism*; D004262:DNA Restriction Enzymes; D006801:Humans; D008840:Microfilament Proteins / Q000235:genetics*; D009693:Nucleic Acid Hybridization; D012689:Sequence Homology, Nucleic Acid; D013049:Spectrin / Q000235:genetics*
D002352:Carrier Proteins; D004247:DNA; D004262:DNA Restriction Enzymes; D008840:Microfilament Proteins; D013049:Spectrin