HUMAN PLECTIN - ORGANIZATION OF THE GENE, SEQUENCE-ANALYSIS, AND CHROMOSOME LOCALIZATION (8Q24)

Plectin, a 500-kDa intermediate filament binding protein, has;been pro posed to provide mechanical strength to cells and tissues by acting as a cross-linking element of the cytoskeleton. To set the basis for fut ure studies on gene regulation, tissue-specific expression, and pathol ogical conditions involving this protein, we have cloned the human ple ctin gene, determined its coding sequence, and established its genomic organization. The coding sequence contains 32 exons that extend over 32 kb of the human genome. Most of the introns reside within a region encoding the globular N-terminal domain of the molecule, whereas the e ntire central rod domain and the entire C-terminal globular domain wer e found to be encoded by single exons of remarkable length, > 3 kb and > 6 kb, respectively. Overall, the organization of the human plectin gene was strikingly similar to that of human bullous pemphigoid antige n I (BPAG1), confirming that both proteins belong to the same gene fam ily. Comparison of the deduced protein sequences for human and rat ple ctin revealed that they were 93% identical, By using fluorescence in s itu hybridization, we have mapped the plectin gene to the long arm of chromosome 8 within the telomeric region. This gene locus (8q24) has p reviously been implicated in the human blistering skin disease epiderm olysis bullosa simplex Ogna, Detailed knowledge of the structure of th e plectin gene and its chromosome localization will aid in the elucida tion of whether this or any other pathological conditions are linked t o alterations in the plectin gene.