The carboxyl-terminal half of type VII collagen, including the non-collagenous NC-2 domain and intron/exon organization of the corresponding region of the COL7A1 gene.
The COL7A1 gene, which encodes type VII collagen, has been implicated as a candidate gene for dominantly and recessively inherited forms of dystrophic epidermolysis bullosa. In this study, hamster and human cDNA clones, which encode the previously uncharacterized carboxyl-terminal portion of type VII collagen, have been isolated and characterized. The previously uncharacterized carboxyl-terminal NC-2 non-collagenous domain is shown to be comprised of 161 amino acids in humans, 170 amino acids in hamster and to contain 8 conserved cysteines in each species. The 6 most carboxyl-terminal cysteines are contained in a conserved motif similar to domains found in Kunitz protease inhibitors, and most closely resembling a similar motif found in the carboxyl-terminal globular domain of the alpha 3 chain of type VI collagen. Also contained in the highly acidic NC-2 domain are a number of potential sites for phosphorylation by casein kinases. Human genomic clones containing 24 exons of COL7A1 were isolated and characterized. The NC-2 domain is encoded by 7 of these exons, which include a junctional exon encoding the end of the collagenous region and the beginning of the NC-2 domain and a final exon encoding the end of the NC-2 domain and 333 bp of 3' untranslated sequences. Comparison of hamster and human sequences shows the region surrounding the junction of the collagenous and NC-2 domains to be particularly conserved. This region is likely to contain residues involved in the proteolytic removal of the NC-2 domain and cysteines involved in formation of the disulfide linkages which stabilize type VII collagen dimers.
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Department of Pathology and Laboratory Medicine, University of Wisconsin, Madison 53706.
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D003094:Collagen / Q000737:chemistry / Q000235:genetics*; D006224:Cricetinae; D004247:DNA / Q000235:genetics; D016108:Epidermolysis Bullosa Dystrophica / Q000235:genetics; D005091:Exons; D006801:Humans; D007438:Introns; D008969:Molecular Sequence Data; D011347:Procollagen / Q000235:genetics; D015183:Restriction Mapping; D017386:Sequence Homology, Amino Acid
D011347:Procollagen; D003094:Collagen; D004247:DNA