PROSITE documentation PDOC50025

Laminin G domain profile

The Laminin G or LNS domain (for Laminin-α, Neurexin and Sex hormone-binding globulin) is an around 180 amino acid long domain found in a large and diverse set of extracellular proteins [1,2]. It often occures in multiple copies probably serving as general protein interaction domains that bind the target proteins and other macromolecules, such as carbohydrates. In most proteins, the precise function of the laminin G domain is unknown. A large number of ligands in the G domain of laminin has been reported, including heparin, sulfatides, integrins, dystroglycan, nidogen, and fibulin [3,4,5]. In neurexin the G domain is known to bind neurexophilins, α-latrotoxin and neuroligins.

The crystal structure of Laminin G domain of neurexin 1-β has been solved [6]. It is composed of 14 β strands and one α helix. The 14 strands form two antiparallel seven stranded β sheets in a jelly roll fold. The α helix is located between β strand 12 and 13. The structure of the laminin G domain is similar to the lectin domain. Alignment of various LNS with neurexin 1-β reveal that only the central part (between strand 4 and 13) is conserved.

Some proteins known to contain a laminin G domain are listed below:

• Eukaryotic laminin α chains. It is a major noncollagenous components of basement membranes that mediate cell adhesion, growth migration, and differentiation.
• Mammalian neurexins.
• Sex steroid binding protein SBP/SHBG. It regulates the plasma metabolic clearance rate of steroid hormones by controlling their plasma concentration.
• Agrin, a basal lamina protein. It causes the aggregation of acetylcholine receptors on cultured muscle fibers.
• Vitamin K dependent protein S. An anticoagulant plasma protein that acts as a cofactor to activated protein C in the degradation of coagulation factors VA and VIIIA. It helps to prevent coagulation and stimulating fibrinolysis.
• Drosophila slit protein, essential for development of midline glia and commissural axon pathways. It is composed of four leucine-rich repeats, seven EGF-like domains, a laminin G-like repeat and the CTCK.

The profile we developed covers the whole domain, including the highly divergent ends. We artificially placed the threshold at 12.1 to remove matches against thrombospondin-like N-terminal domain, a structurally homologue module. Thus we also remove few real matches which have a score between 8.5 and 12.1.