Human and Xenopus cingulin share a modular organization of the coiled-coil rod domain: predictions for intra- and intermolecular assembly.

The complete nucleotide and derived amino acid sequences of Homo sapiens cingulin cDNA (5143 bp) were determined by sequencing two distinct EST clones that showed significant sequence homology to Xenopus laevis cingulin. Protein sequence analysis indicates that the molecule contains two chains and has a tripartite structure with N-terminal (head) domains, a coiled-coil rod domain (length, 120 nm), and short C-terminal (tail) domains. Human and Xenopus cingulin heads are only 33% identical, yet a human cingulin N-terminal fragment still interacts with canine ZO-1 and ZO-2 in vitro. The rod domain contains two A and two B subdomains, though it lacks the third B subdomain present in Xenopus cingulin. The heptad substructures of Xenopus and human cingulins were further characterized by computer analysis and indicated that the two-stranded coiled-coil structure contained chains that were parallel and in axial register. Fast Fourier transform analysis and a scoring technique designed to recognize potential interactions between different supramolecular arrangements suggests that cingulin dimers may further assemble through antiparallel interactions between the last approximately 100 amino acids of the coiled-coil region. Cingulin mRNA ( approximately 5.2 kb) was detected by Northern blotting in epithelial tissues. A human cingulin EST was mapped to chromosome 1q21 using the UniGene database. Copyright 2000 Academic Press.