The structure of cell adhesion molecule uvomorulin. Insights into the molecular mechanism of Ca2+-dependent cell adhesion.

Abstract

We have determined the amino acid sequence of the Ca2+‐dependent cell adhesion molecule uvomorulin as it appears on the cell surface. The extracellular part of the molecule exhibits three internally repeated domains of 112 residues which are most likely generated by gene duplication. Each of the repeated domains contains two highly conserved units which could represent putative Ca2+‐binding sites. Secondary structure predictions suggest that the putative Ca2+‐binding units are located in external loops at the surface of the protein. The protein sequence exhibits a single membrane‐spanning region and a cytoplasmic domain. Sequence comparison reveals extensive homology to the chicken L‐CAM. Both uvomorulin and L‐CAM are identical in 65% of their entire amino acid sequence suggesting a common origin for both CAMs.

Cadherin Adhesion: Mechanisms and Molecular Interactions

“…The authors, however, did not comment on Ca ++ binding sites. Nevertheless, sequence alignment of the known cadherins shows conservation in each of the five internal repeats of the putative Ca ++ -binding sites proposed by Ringwald et al (1987).…”

“…However, the mechanism remains unclear. After solving the protein sequence of uvomorulin (E-cadherin), Ringwald et al (1987) identified three internal repeats in the extracellular domain. Within these domains they identified two distinct putative Ca ++ -binding loops based on sequence homology to known Ca ++ -binding regions.…”

Cloning and sequence analysis of desmosomal glycoproteins 2 and 3 (desmocollins): cadherin-like desmosomal adhesion molecules with heterogeneous cytoplasmic domains.

“…Four conserved cysteines in EC5 are also boxed. Putative Ca 2+ binding sites are ovedined and labeled a or b after Ringwald et al (1987). Sequence of the cytoplasmic domain of dg3 that is known to be identical in dg2 is underlined.…”

“…5). (e) Several putative calcium binding sites (Ringwald et al, 1987) are conserved between the three molecules (Fig. 5, overlined).…”

“…Derived amino acid sequences of these proteins reveal a homologous family of transmembrane glycoproteins with a single membrane spanning domain, and a highly conserved cytoplasmic domain (Ringwald et al, 1987;Gallin et al, 1987;Nose et al, 1987;Nagafuchi et al, 1987;Hatta et al, 1988;Miyatani et al, 1989;Shimoyama et al, 1989;Walsh et al, 1990;Liaw et ai., 1990).…”