• Purity

  >90%, by SDS-PAGE visualized with Silver Staining and quantitative densitometry by Coomassie? Blue Staining.

• Endotoxin Level

  <1.0 EU per 1 μg of the protein by the LAL method.  

• Activity

  Measured by its ability to induce clustering of Caki?2 human clear cell carcinoma epithelial cells. Schwochau, G.     et al. (1998) Kidney Int.     53:1647.

• Source

  Mouse myeloma cell line, NS0-derived Asp23-Arg227 (beta) & Ser228-Glu449 (alpha) with a C-terminal 6-His tag

• Accession #

• N-terminal Sequence    
  Analysis

  Ser228 ( alpha chain) & Asp23 ( beta chain)

• Structure / Form

  Disulfide-linked heterodimer

• Predicted Molecular Mass

  26.7 kDa ( alpha chain) and 24.2 kDa ( beta chain)

• SDS-PAGE

  40 kDa and 39 kDa, under reducing conditions

Background: Clusterin

Clusterin, also known as Apolipoprotein J, Sulfated Glycoprotein 2 (SGP-2), TRPM-2, and SP-40,40, is a secreted multifunctional protein that was named for its ability to induce cellular clustering. It binds a wide range of molecules and may function as a chaperone of misfolded extracellular proteins. It also participates in the control of cell proliferation, apoptosis, and carcinogenesis (1, 2). Clusterin is predominantly expressed in adult testis, ovary, adrenal gland, liver, heart, and brain and in many epithelial tissues during embryonic development (3). Human Clusterin is synthesized as a precursor that contains two coiled coil domains, three nuclear localization signals (NLS), and one heparin binding domain (4-6). Intracellular cleavages of the precursor remove the signal peptide and generate comparably sized alpha  and beta  chains which are secreted as an 80 kDa N-glycosylated disulfide-linked heterodimer (7, 8). Mature human Clusterin shares 77% amino acid sequence identity with mouse and rat Clusterin. High μg/mL concentrations of Clusterin circulate predominantly as a component of high density lipoprotein particles, and these are internalized and degraded through interactions with LRP-2/Megalin (9, 10). In human, an alternately spliced 50 kDa isoform of Clusterin (nCLU) lacks the signal peptide and remains intracellular (5,  11). This molecule is neither glycosylated nor cleaved into alpha and beta chains (11). In the cytoplasm, nCLU destabilizes the actin cytoskeleton and inhibits NF kappa B activation (12, 13). Cellular exposure to ionizing radiation promotes the translocation of nCLU to the nucleus where it interacts with Ku70 and promotes apoptosis (5, 11). This function contrasts with the cytoprotective effect of secreted Clusterin (14). During colon cancer tumor progression there is a down?regulation of the intracellular form and an up?regulation of the glycosylated secreted form (11).

• References:

1. Carver, J.A. et al. (2003) IUBMB Life 55:661.

2. Shannan, B. et al. (2006) Cell Death Differ. 13:12.

3. French, L.E. et al. (1993) J. Cell Biol. 122:1119.

4. Kirszbaum, L. et al. (1989) EMBO J. 8:711.

5. Leskov, K.S. et al. (2003) J. Biol. Chem. 278:11590.

6. Pankhurst, G.J. et al. (1998) Biochemistry 37:4823.

7. Burkey, B.F. et al. (1991) J. Lipid. Res. 32:1039.

8. de Silva, H.V. et al. (1990) J. Biol. Chem. 265:14292.

9. Jenne, D.E.         et al. (1991) J. Biol. Chem.         266:11030.

10. Kounnas, M.Z.         et al. (1995) J. Biol. Chem.         270:13070.

11. Pucci, S.         et al. (2004) Oncogene         23:2298.

12. Moretti, R. M.         et al. (2007) Cancer Res.         67:10325.

13. Santilli, G.         et al. (2003) J. Biol. Chem.         278:38214.

14. Trougakos, I.P.         et al. (2004) Cancer Res.         64:1834.

• Entrez Gene IDs:

  1191 (Human); 12759 (Mouse)

• Alternate Names:

  40; 40, sulfated glycoprotein 2; Aging-associated gene 4 protein; aging-associated protein 4; APOJ; apo-J; Apolipoprotein J; CLI; CLIclusterin (complement lysis inhibitor, SP-40; CLU; Clusterin; Complement cytolysis inhibitor; complement lysis inhibitor; Complement-associated protein SP-40; Ku70-binding protein 1; KUB1SGP2; MGC24903; NA1/NA2; SGP-2; SP-40; sulfated glycoprotein 2; Testosterone-repressed prostate message 2; testosterone-repressed prostate message 2, apolipoprotein J); TRPM-2; TRPM-2TRPM2