• Purity

  >95%, by SDS-PAGE under reducing conditions and visualized by silver stain.

• Endotoxin Level

  <0.10 EU per 1 μg of the protein by the LAL method.  

• Activity

  Measured by its binding ability in a functional ELISA. When recombinant human VEGF R1 is coated at 5 μg/mL (100 μL/well), the concentration of Recombinant Human Endorepellin/Perlecan that produces 50% of the optimal binding response is approximately 2-10 μg/mL

• Source

  Mouse myeloma cell line, NS0-derived Arg3684-Ser4391 (Ser4004Thr), with a C-terminal 10-His tag

• Accession #

• N-terminal Sequence    
  Analysis

  Arg3684

• Predicted Molecular Mass

  76.7 kDa

• SDS-PAGE

  90-95 kDa, reducing conditions

Background: Endorepellin/Perlecan

Endorepellin is an 80 kDa glycoprotein that is derived from the C-terminal end of the heparan sulfate proteoglycan, Perlecan. Perlecan itself is an approximately 850 kDa modular protein that contains multiple LDLR, EGF-like, Laminin-like, and immunoglobulin-like domains. Mouse Perlecan lacks several of the Ig-like domains found in the human protein (1-3). Endorepellin corresponds to domain V of Perlecan and consists of three Laminin G domains separated by four EGF-like domains (4). Human Endorepellin shares 89% amino acid sequence identity with mouse Endorepellin. A 26 kDa fragment of Endorepellin is known as LG3 and contains the third Laminin G-like domain of Endorepellin. LG3 can be released by Cathepsin L or BMP-1/Tolloid family mediated cleavage (4-6). Endorepellin binds to Integrin alpha 2/ beta 1, preventing the integrin-dependent adhesion of vascular endothelial cells (EC) to fibronectin and collagen I (7, 8). In contrast, this interaction enhances platelet adhesion to collagen as well as platelet aggregation and activation (9). Endorepellin additionally binds to VEGF R1 and VEGF R2 on EC (10). Its binding to VEGF R2 and Integrin alpha 2/ beta 1 on EC induces the association and down‑regulation of both proteins, followed by the inhibition of EC migration, tubulogenesis, secretion of VEGF, and the activation of multiple receptors involved in angiogenesis (4, 7, 8, 10, 11). Endorepellin also binds to Endostatin, resulting in a reduction of the anti-angiogenic activity of both proteins (4). It preferentially interacts with tumor vasculature and inhibits tumor growth and angiogenesis (8, 12).

• References:

1. Whitelock, J.M. et al. (2008) Biochemistry 47:11174.

2. Murdoch, A.D. et al. (1992) J. Biol. Chem. 267:8544.

3. Noonan, D.M. et al. (1991) J. Biol. Chem. 266:22939.

4. Mongiat, M. et al. (2003) J. Biol. Chem. 278:4238.

5. Cailhier, J.-F. et al. (2008) J. Biol. Chem. 283:27220.

6. Gonzalez, E.M. et al. (2005) J. Biol. Chem. 280:7080.

7. Bix, G. et al. (2004) J. Cell Biol. 166:97.

8. Woodall, B.P. et al. (2008) J. Biol. Chem. 283:2335.

9. Bix, G. et al. (2007) Blood 109:3745.

10. Goyal, A. et al. (2011) J. Biol. Chem. 286:25947.

11. Nystrom, A. et al. (2009) Blood 114:4897.

12. Bix, G. et al. (2006) J. Natl. Cancer Inst. 98:1634.

• Entrez Gene IDs:

  3339 (Human)

• Alternate Names:

  basement membrane-specific heparan sulfate proteoglycan core protein; endorepellin (domain V region); Endorepellin; heparan sulfate proteoglycan 2; HSPG; HSPG2; perlecan proteoglycan; Perlecan; PLCSchwartz-Jampel syndrome 1 (chondrodystrophic myotonia); PRCAN; SJA; SJS; SJS1