3sh5

Structural highlights

Disease

PGBM_HUMAN Dyssegmental dysplasia, Silverman-Handmaker type;Schwartz-Jampel syndrome. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry.

Function

PGBM_HUMAN Integral component of basement membranes. Component of the glomerular basement membrane (GBM), responsible for the fixed negative electrostatic membrane charge, and which provides a barrier which is both size- and charge-selective. It serves as an attachment substrate for cells. Plays essential roles in vascularization. Critical for normal heart development and for regulating the vascular response to injury. Also required for avascular cartilage development. Endorepellin in an anti-angiogenic and anti-tumor peptide that inhibits endothelial cell migration, collagen-induced endothelial tube morphogenesis and blood vessel growth in the chorioallantoic membrane. Blocks endothelial cell adhesion to fibronectin and type I collagen. Anti-tumor agent in neovascularization. Interaction with its ligand, integrin alpha2/beta1, is required for the anti-angiogenic properties. Evokes a reduction in phosphorylation of receptor tyrosine kinases via alpha2/beta1 integrin-mediated activation of the tyrosine phosphatase, PTPN6. The LG3 peptide has anti-angiogenic properties that require binding of calcium ions for full activity.

References

1. ↑ V Le B, Kim H, Choi J, Kim JH, Hahn MJ, Lee C, Kim KK, Hwang HY. Crystal Structure of the LG3 Domain of Endorepellin, an Angiogenesis Inhibitor. J Mol Biol. 2011 Nov 25;414(2):231-42. Epub 2011 Oct 4. PMID:21996443 doi:10.1016/j.jmb.2011.09.048