Nidogen/entactin is a ubiquitous 150-kDa multidomain basement membrane
protein. Since in vitro binding studies indicated that nidogen may fu
nction as a major mediator in basement membrane organization and assem
bly, analysis of gene structure and regulation of gene expression will
help us to understand many biological processes that involve degradat
ion and reorganization of the basement membrane zone. An approximately
100-kb region of genomic DNA encoding the human nidogen gene (NID) in
cluding 5' and 3' flanking sequences has been cloned and characterized
by restriction mapping and sequencing. The entire gene is more than 9
0 kb in length and contains 20 exons. All introns interrupt protein co
ding sequences. The size of individual introns varies significantly, r
anging from 0.6 to 18 kb. Its exon/intron structure revealed that the
protein domains of human nidogen are organized in a domain-specific ma
nner with various subdomains being encoded by individual exons, indica
ting that exon duplication and shuffling have played an important role
in determining the present structure of the protein. Comparison of th
e exon organization with the recently published ascidian nidogen amino
acid sequence strongly suggests that vertebrate nidogen might have ev
olved from a common ancestral precursor resembling ascidian nidogen. (
C) 1995 Academic Press, Inc.