Recombinant Human Progranulin Protein, CF

• Reactivity: Hu
• Applications: Bioactivity
• Format: Carrier-Free

Recombinant Human Progranulin Protein, CF Summary

• Details of Functionality: 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 human Progranulin/PGRN protein
  Thr18-Leu593, with a C-terminal 6-His tag
• Accession #: P28799
• N-terminal Sequence: Thr18
• Protein/Peptide Type: Recombinant Proteins
• Gene: GRN
• Purity: >95%, by SDS-PAGE visualized with Silver Staining and quantitative densitometry by Coomassie® Blue Staining.
• Endotoxin Note: <0.01 EU per 1 μg of the protein by the LAL method.

Applications/Dilutions

• Dilutions:
  • Bioactivity
• Theoretical MW: 62.6 kDa.
  Disclaimer note: The observed molecular weight of the protein may vary from the listed predicted molecular weight due to post translational modifications, post translation cleavages, relative charges, and other experimental factors.
• SDS-PAGE: 90-95 kDa

Packaging, Storage & Formulations

• Storage: Use a manual defrost freezer and avoid repeated freeze-thaw cycles.
  • 12 months from date of receipt, -20 to -70 °C as supplied.
  • 1 month, 2 to 8 °C under sterile conditions after reconstitution.
  • 3 months, -20 to -70 °C under sterile conditions after reconstitution.
• Buffer: Lyophilized from a 0.2 μm filtered solution in PBS.
• Purity: >95%, by SDS-PAGE visualized with Silver Staining and quantitative densitometry by Coomassie® Blue Staining.
• Reconstitution Instructions: Reconstitute at 200 μg/mL in sterile PBS.

Notes

This product is produced by and ships from R&D Systems, Inc., a Bio-Techne brand.

Alternate Names for Recombinant Human Progranulin Protein, CF

• Acrogranin
• CLN11
• GEP
• GP88
• granulin precursor
• GRN
• PCDGF
• PEPI
• PGRN
• Proepithelin
• Progranulin

Background

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).

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.

Publications for Progranulin/PGRN (2420-PG)(19)

Publications using 2420-PG

• L�tge, M;De Martin, A;Gil-Cruz, C;Perez-Shibayama, C;Stanossek, Y;Onder, L;Cheng, HW;Kurz, L;Cadosch, N;Soneson, C;Robinson, MD;Stoeckli, SJ;Ludewig, B;Pikor, NB; Conserved stromal-immune cell circuits secure B cell homeostasis and function Nature immunology 2023-05-18 [PMID: 37202489] (Bioassay, Human)
• LH Tran, GJ Graulus, C Vincke, N Smiejkowsk, A Kindt, N Devoogdt, S Muylderman, P Adriaensen, W Guedens Nanobodies for the Early Detection of Ovarian Cancer International Journal of Molecular Sciences, 2022-11-08;23(22):. 2022-11-08 [PMID: 36430166] (ELISA Capture, Human)
• A Zambusi, KT Novoselc, S Hutten, S Kalpazidou, C Koupourtid, R Schieweck, S Aschenbroi, L Silva, AS Yazgili, F van Bebber, B Schmid, G Möller, C Tritscher, C Stigloher, C Delbridge, S Sirko, ZI Günes, S Liebscher, J Schlegel, H Aliee, F Theis, S Meiners, M Kiebler, D Dormann, J Ninkovic TDP-43 condensates and lipid droplets regulate the reactivity of microglia and regeneration after traumatic brain injury Nature Neuroscience, 2022-11-24;25(12):1608-1625. 2022-11-24 [PMID: 36424432] (Bioassay, In Vivo, Human, Zebrafish)
• J Liu, X Lai, R Yu, H Ding, H Bai, Z Yang, Y Yin, F Xu, J Cao Progranulin aggravates lethal Candida albicans sepsis by regulating inflammatory response and antifungal immunity PloS Pathogens, 2022-09-19;18(9):e1010873. 2022-09-19 [PMID: 36121866] (Bioassay, Human)
• AM Monteys, AA Hundley, PT Ranum, L Tecedor, A Muehlmatt, E Lim, D Lukashev, R Sivasankar, BL Davidson Regulated control of gene therapies by drug-induced splicing Nature, 2021-07-28;0(0):. 2021-07-28 [PMID: 34321659] (Mouse)
• D Tian, Q Qin, M Li, X Li, Q Xu, Q Lv Homocysteine Impairs Endothelial Cell Barrier Function and Angiogenic Potential via the Progranulin/EphA2 Pathway Frontiers in Pharmacology, 2021-01-08;11(0):614760. 2021-01-08 [PMID: 33510642] (Bioassay, Human)
• S Gururaj, PJ Sampognaro, AR Argouarch, AW Kao Progranulin Adsorbs to Polypropylene Tubes and Disrupts Functional Assays: Implications for Research, Biomarker Studies, and Therapeutics Frontiers in Neuroscience, 2020-12-14;14(0):602235. 2020-12-14 [PMID: 33381010] (Cell Culture, Human)
• D Feng, X Kang, R Wang, H Chen, K Zhang, W Feng, H Li, Y Zhu, S Wu Progranulin modulates cartilage-specific gene expression via sirtuin 1-mediated deacetylation of the transcription factors SOX9 and P65 J. Biol. Chem., 2020-08-03;0(0):. 2020-08-03 [PMID: 32747445] (Cell Culture, Rat)
• W Yoo, J Lee, KH Noh, S Lee, D Jung, MH Kabir, D Park, C Lee, KS Kwon, JS Kim, S Kim Progranulin attenuates liver fibrosis by downregulating the inflammatory response Cell Death Dis, 2019-10-07;10(10):758. 2019-10-07 [PMID: 31591383] (Bioassay, Human)
• M Maeno, T Mizutani, H Tsuyoshi, S Yamada, S Ishikane, S Kawabe, K Nishimura, M Yamada, K Miyamoto, Y Yoshida Development of a novel and rapid measurement system for growth differentiation factor-15, progranulin, and osteopontin in uterine sarcoma Endocr. J., 2019-09-18;0(0):. 2019-09-18 [PMID: 31534059] (Standard, Human)
• L Schulze-Ed, C Dürr, S Öztürk, M Zucknick, A Benner, V Kalter, S Ohl, V Close, P Wuchter, S Stilgenbau, P Lichter, M Seiffert Dissecting the Prognostic Significance and Functional Role of Progranulin in Chronic Lymphocytic Leukemia Cancers (Basel), 2019-06-13;11(6):. 2019-06-13 [PMID: 31200555] (Bioassay, Human)
• K Fujita, X Chen, H Homma, K Tagawa, M Amano, A Saito, S Imoto, H Akatsu, Y Hashizume, K Kaibuchi, S Miyano, H Okazawa Targeting Tyro3 ameliorates a model of PGRN-mutant FTLD-TDP via tau-mediated synaptic pathology Nat Commun, 2018-01-30;9(1):433. 2018-01-30 [PMID: 29382817] (Bioassay)
• Progranulin promotes peripheral nerve regeneration and reinnervation: role of notch signaling Mol Neurodegener, 2016-10-22;11(1):69. 2016-10-22 [PMID: 27770818] (Bioassay, Rat)
• Abdiche , Yasmina, Miles , Adam, Eckman , Josh, Foletti , Davide, Van Blarcom , Thomas J, Yeung , Yik Andy, Pons , Jaume, Rajpal , Arvind High-throughput epitope binning assays on label-free array-based biosensors can yield exquisite epitope discrimination that facilitates the selection of monoclonal antibodies with functional activity. PLoS ONE, 2014-03-20;9(3):e92451. 2014-03-20 [PMID: 24651868] (Bioassay)
• Wilson TR, Fridlyand J, Yan Y, Penuel E, Burton L, Chan E, Peng J, Lin E, Wang Y, Sosman J, Ribas A, Li J, Moffat J, Sutherlin DP, Koeppen H, Merchant M, Neve R, Settleman J Widespread potential for growth-factor-driven resistance to anticancer kinase inhibitors. Nature, 2012-07-26;487(7408):505-9. 2012-07-26 [PMID: 22763448] (Bioassay, Human)
• Suh HS, Choi N, Tarassishin L, Lee SC Regulation of progranulin expression in human microglia and proteolysis of progranulin by matrix metalloproteinase-12 (MMP-12). PLoS ONE, 2012-04-11;7(4):e35115. 2012-04-11 [PMID: 22509390] (Bioassay, Human)
• Elkabets M, Gifford AM, Scheel C, Nilsson B, Reinhardt F, Bray MA, Carpenter AE, Jirstrom K, Magnusson K, Ebert BL, Ponten F, Weinberg RA, McAllister SS Human tumors instigate granulin-expressing hematopoietic cells that promote malignancy by activating stromal fibroblasts in mice. J. Clin. Invest., 2011-01-25;121(2):784-99. 2011-01-25 [PMID: 21266779] (Bioassay, Human)
• Sleegers K, Brouwers N, Van Damme P, Engelborghs S, Gijselinck I, van der Zee J, Peeters K, Mattheijssens M, Cruts M, Vandenberghe R, De Deyn PP, Robberecht W, Van Broeckhoven C Serum biomarker for progranulin-associated frontotemporal lobar degeneration. Ann. Neurol., 2009-05-01;65(5):603-9. 2009-05-01 [PMID: 19288468] (ELISA (Standard))
• Van Damme P, Van Hoecke A, Lambrechts D, Vanacker P, Bogaert E, van Swieten J, Carmeliet P, Van Den Bosch L, Robberecht W Progranulin functions as a neurotrophic factor to regulate neurite outgrowth and enhance neuronal survival. J. Cell Biol., 2008-03-31;181(1):37-41. 2008-03-31 [PMID: 18378771] (ELISA (Standard))

Bioinformatics

• Gene Symbol: GRN
• Uniprot:
  • P28799(Human)