Entactin is an integral and ubiquitous component of the basement membrane. The amino acid sequences of the mouse and human molecules have been determined and exhibit 85% sequence identity. The molecule is organized into three structural domains, an N-terminal globule (I) is linked to a smaller C-terminal globule (III) by a rigid stalk (II) largely consisting of
cysteine-rich
EGF-like homology repeats and a
cysteine-rich
thyroglobulin homology repeat. The molecule binds
calcium ions and supports cell adhesion. However, its major function may be the assembly of the basement membrane. The carboxyl globule binds tightly to one of the short arms of
laminin at the inner rodlike segment. This same region is also believed to be responsible for the attachment of
entactin to
type IV collagen at approximately 80 nm from its carboxyl noncollagenous end.
Entactin therefore could serve as a bridge between the two most abundant molecules in the basement membrane. Supporting evidence for this role has been obtained from transfection of human
choriocarcinoma, JAR, cells with the
entactin gene. JAR cells synthesize
laminin and
type IV collagen but not
entactin. Transfection of
entactin into the cells stimulated incorporation of
laminin and
type IV collagen along with
entactin into the extracellular matrix and into structures resembling focal contacts. The
calcium-binding activity of
entactin may play a role in the matrix assembly process. The
protease sensitivity of
entactin suggests that it may be a target for proteolytic activity during tissue remodeling,
metastasis, and other events requiring the turnover of the basement membrane.