• Purity

  >95%, by SDS-PAGE visualized with Silver Staining and quantitative densitometry by Coomassie? Blue Staining.

• Endotoxin Level

  <0.01 EU per 1 μg of the protein by the LAL method.  

• Activity

  Measured by its ability to enhance neurite outgrowth of E16-E18 rat embryonic cortical neurons. Recombinant Human Progranulin/PGRN, immobilized at 10-40 μg/mL on a nitrocellulose coated plate, is able to significantly enhance neurite outgrowth.

• Source

  Mouse myeloma cell line, NS0-derived Thr18-Leu593, with a C-terminal 6-His tag

• Accession #

• N-terminal Sequence    
  Analysis

  Thr18

• Predicted Molecular Mass

  62.6 kDa

• SDS-PAGE

  90-95 kDa    
   

Background: Progranulin/PGRN

Progranulin, also known as acrogranin, PC cell-derived growth factor (PCDGF) and epithelin/granulin precursor, is a ubiquitously expressed, 88 kDa, secreted glycoprotein (1 - 3). Structurally, it does not belong to any of the well-established growth factor families (4). Human Progranulin is 593 amino acids (aa) in length and contains a 17 aa signal sequence and 5 potential sites for N-linked glycosylation (Swiss Prot # P28799). It has a highly repetitive organization, containing seven tandem copies of a 55 - 57 aa consensus motif that contains 12 conserved cysteine residues: VXCX5-6CX5CCX8CCX6CCXDX2HCCPX4CX5-6CX2 (1). There is one alternate splice form for human Progranulin. This has a deletion of aa corresponding to aa 377 - 531 of the standard form. Progranulin is secreted as a full length form (2, 4), and may undergo proteolysis leading to the release of numerous peptides made from the seven tandem repeats, called the granulins (5 - 7). Human Progranulin shares 75% aa sequence identity with mouse and rat Progranulin. Progranulin is involved in the regulation of cellular proliferation, as well as differentiation, development, and pathological processes (4). It has been isolated as a differentially expressed gene during mesothelial differentiation (8), macrophage development (9), the development of rheumatoid arthritis and osteoarthritis (10), sexual differentiation of the brain (11), and has also been shown to be a mediator of cartilage proliferation and of wound response and tissue repair (4, 12 13). High levels of Progranulin expression have been found to be associated with several human cancers and are believed to contribute to tumorigenesis in breast cancer, clear cell renal carcinoma, invasive ovarian carcinoma, glioblastoma, adipocyte teratoma, and multiple myeloma (4 - 5, 12, 14 - 19). In addition, mutations in the Progranulin gene are a cause of frontotemporal dementia, and increased expression of Progranulin is seen in activated microglia in many neurodegenerative diseases including Creutzfeldt-Jakob disease, motor neuron disease and Alzheimer's disease (20). Mutations in Progranulin causing neurodegenerative disease indicate that Progranulin is important for neuronal survival (20).

• References:

1. Plowman, G.D. et al. (1992) J. Biol. Chem. 267:13073.

2. Zhou, J. et al. (1993) J. Biol. Chem. 268:10863.

3. Liu, Y. et al. (2007) BMC Cancer 7:22.

4. Xu, K. et al. (2007) J. Biol. Chem. 282:11347.

5. Davidson, B. et al. (2004) Cancer 100:2139.

6. Zanocco-Marani, T. et al. (1999) Cancer Res. 59:5331.

7. Lu, R. and G. Serrero (2000) Proc. Natl. Acad. Sci. U.S.A. 97:3993.

8. Sun, X. et al. (2004) Am. J. Respir. Cell Mol. Biol. 30:510.

9. Barreda, D.R. et al. (2004) Dev. Comp. Immunol. 28:727.

10. Justen, H.P. et al. (2000) Mol. Cell Biol. Res. Commun. 3:165.

11. Suzuki, M. and M. Nishiahara (2002) Mol. Genet. Metab. 75:31.

12. He, Z. et al. (2003) Nat. Med. 9:225.

13. Zhu, J. et al. (2002) Cell 111:867.

14. He, Z. and A. Bateman (2003) J. Mol. Med. 81:600.

15. Bateman, A. et al. (1990) Biochem. Biophys. Res. Commun. 173:1161.

16. Gonzalez, E.M. et al. (2003) J. Biol. Chem. 278:38113.

17. Jones, M.B. et al. (2003) Gynecol. Oncol. 88:S136.

18. Wang, W. et al. (2003) Clin. Cancer Res. 9:2221.

19. Zhang, H. and G. Serrero (1998) Proc. Natl. Acad. Sci. U.S.A. 95:14202.

20. Baker, M. et al. (2006) Nature 442:916.

• Entrez Gene IDs:

  2896 (Human); 14824 (Mouse)

• Alternate Names:

  Acrogranin; GEP; GP88; GRN; PCDGF; PEPI; PGRN; Proepithelin; Progranulin