Recombinant Human Gremlin Protein, CF

(8 citations)   
  • Purity
    >90%, by SDS-PAGE visualized with Silver Staining and quantitative densitometry by Coomassie® Blue Staining.
  • Endotoxin Level
    <0.10 EU per 1 μg of the protein by the LAL method.
  • Activity
    Measured by its ability to inhibit alkaline phosphatase production by MC3T3‑E1 mouse preosteoblast cells. The ED50 for this effect is 0.025-0.15 μg/mL in the presence of 30 ng/mL of Recombinant Human BMP‑4 (Catalog # 314-BP).
  • Source
    Mouse myeloma cell line, NS0-derived Lys25-Asp184, with a C-terminal 10-His tag
  • Accession #
  • N-terminal Sequence
    Analysis
    Lys25
  • Structure / Form
    Dimer
  • Predicted Molecular Mass
    19.7 kDa
  • SDS-PAGE
    25-30 kDa, under reducing conditions
5190-GR
 
Formulation Lyophilized from a 0.2 μm filtered solution in PBS and EDTA.
Reconstitution Reconstitute at 200 μg/mL in sterile PBS.
Shipping The product is shipped at ambient temperature. Upon receipt, store it immediately at the temperature recommended below.
Stability & 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.
Data Images
Recombinant Human Gremlin (Catalog # 5190‑GR) inhibits BMP-4-induced alkaline phosphatase production in the MC3T3-E1 mouse preosteoblast cell line. The ED50 for this effect is 0.025‑0.15 µg/mL in the presence of 30 ng/mL of Recombinant Human BMP-4 (Catalog # 314‑BP).

1 µg/lane of Recombinant Human Gremlin was resolved with SDS-PAGE under reducing (R) conditions and visualized by silver staining, showing major bands at 25‑30 kDa. Multiple bands in gel are due to variable glycosylation.

Background: Gremlin

Gremlin, also known as Increased in High Glucose protein 2 (IHG-2) and Down-regulated in Mos-transformed cells protein (Drm), is a 28 kDa member of the Dan family of secreted glycoproteins (1-3). Human Gremlin is synthesized as a 184 amino acid (aa) precursor that contains a 24 aa signal sequence and a 160 aa mature region (SwissProt # O60565). The mature region contains one potential site for N-linked glycosylation (Asn 42), a cysteine-rich region, and a cysteine-knot motif (aa 94‑184) whose structure is shared by members of the TGF-beta superfamily (3). Post-translational modifications include glycosylation and phosphorylation (3). Gremlin exists in both secreted and membrane-associated forms (3). There are two isoforms for human Gremlin. Isoform 1 is the standard protein, and in isoform 2, there is a deletion of aa 39‑79. Human Gremlin shares 99% and 86% aa sequence identity with mouse and chick Gremlin, respectively. Northern blot analysis shows that Gremlin mRNA is highly expressed in the small intestine, fetal brain and colon, and weakly expressed in adult brain, ovary, prostate, pancreas and skeletal muscle (4). Gremlin functions as a bone morphogenetic protein (BMP) antagonist. It acts by binding to, and forming heterodimers with, BMP-2, BMP-4, and BMP-7, thus preventing them from interacting with their cell surface receptors (1). This mechanism is thought to be responsible for the pattern-inducing activity of Gremlin during embryonic development (5) and to play a role in human diseases, such as diabetic nephropathy (6). However, intracellular BMP-independent mechanisms of action (7) may mediate the ability of Gremlin to suppress transformation and tumorigenesis under certain experimental conditions (8-9). Gremlin also interacts with Slit proteins and acts as an inhibitor of monocyte chemotaxis (10). In addition, Gremlin has been found to be a proangiogenic factor expressed by endothelium (9).

  • References:
    1. Hsu, D.R. et al. (1998) Mol. Cell 1:673.
    2. McMahon, R. et al. (2000) J. Biol. Chem. 275:9901.
    3. Wordinger, R.J. et al. (2008) Exp. Eye Res. 87:78.
    4. Topol, L.Z. et al. (2000) Cytogenet. Cell Genet. 89:79.
    5. Khokha, M.K. et al. (2003) Nat. Genet. 34:303.
    6. Lappin, D.W. et al. (2002) Nephrol. Dial. Transplant 17:65.
    7. Chen, B. et al. (2002) Biochem. Biophys. Res. Commun. 295:1135.
    8. Topol, L.Z. et al. (1997) Mol. Cell. Biol. 17:4801.
    9. Stabile, H. et al. (2007) Blood 109:1834.
    10. Chen, B. et al. (2004) J. Immunol. 173:5914.
  • Entrez Gene IDs:
    26585 (Human); 23892 (Mouse)
  • Alternate Names:
    Cell proliferation-inducing gene 2 protein; CKTSF1B1gremlin 1, cysteine knot superfamily, homolog; Cysteine knot superfamily 1, BMP antagonist 1gremlin 1, cysteine knot superfamily, homolog (Xenopus laevis); DAN domain family member 2; DAND2; DAND2GREMLIN; Down-regulated in Mos-transformed cells protein; DRM; DRMMGC126660; GREM1; gremlin 1; gremlin 1-like protein; Gremlin; gremlin-1; IHG-2; Increased in high glucose protein 2; increased in high glucose-2; proliferation-inducing gene 2
Related Research Areas
Citations:

R&D Systems personnel manually curate a database that contains references using R&D Systems products. The data collected includes not only links to publications in PubMed, but also provides information about sample types, species, and experimental conditions.

8 Citations: Showing 1 - 8
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Species
Applications
Sample Type
  1. Diverse feather shape evolution enabled by coupling anisotropic signalling modules with self-organizing branching programme
    Authors: A Li, S Figueroa, TX Jiang, P Wu, R Widelitz, Q Nie, CM Chuong
    Nat Commun, 2017;8(0):ncomms14139.
    Species: Chicken
    Sample Type: In Vivo
    Application: In Vivo
  2. Generation and Applications of a DNA Aptamer against Gremlin-1
    Authors: Q Li, Y Huo, Y Guo, X Zheng, W Sun, Z Hao
    Molecules, 2017;22(5):.
    Species: N/A
    Sample Type: ssDNA
    Application: Bioassay
  3. Interleukin-6 (IL-6) trans signaling drives a STAT3-dependent pathway that leads to hyperactive transforming growth factor-beta (TGF-beta) signaling promoting SMAD3 activation and fibrosis via Gremlin protein.
    Authors: O'Reilly S, Ciechomska M, Cant R, van Laar J
    J Biol Chem, 2014;289(14):9952-60.
    Species: Human
    Sample Type: Whole Cells
    Application: Bioassay
  4. Bone morphogenetic protein-9 suppresses growth of myeloma cells by signaling through ALK2 but is inhibited by endoglin.
    Authors: Olsen O, Wader K, Misund K, Vatsveen T, Ro T, Mylin A, Turesson I, Stordal B, Moen S, Standal T, Waage A, Sundan A, Holien T
    Blood Cancer J, 2014;4(0):e196.
    Species: Human
    Sample Type: Whole Cells
    Application: Bioassay
  5. Quantitative kinetics analysis of BMP2 uptake into cells and its modulation by BMP antagonists.
    Authors: Alborzinia H, Schmidt-Glenewinkel H, Ilkavets I, Breitkopf-Heinlein K, Cheng X, Hortschansky P, Dooley S, Wolfl S
    J Cell Sci, 2013;126(0):117-27.
    Species: Human
    Sample Type: Whole Cells
    Application: Bioassay
  6. Gremlin-1 induces BMP-independent tumor cell proliferation, migration, and invasion.
    Authors: Kim M, Yoon S, Lee S
    PLoS ONE, 2012;7(4):e35100.
    Species: Human
    Sample Type: Whole Cells
    Application: Flow
  7. Widespread potential for growth-factor-driven resistance to anticancer kinase inhibitors.
    Authors: 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
    Nature, 2012;487(7408):505-9.
    Species: Human
    Sample Type: Whole Cells
    Application: Bioassay
  8. Gremlin is a novel agonist of the major proangiogenic receptor VEGFR2.
    Authors: Mitola S, Ravelli C, Moroni E, Salvi V, Leali D, Ballmer-Hofer K, Zammataro L, Presta M
    Blood, 2010;116(18):3677-80.
    Species: Human
    Sample Type: Recombinant Protein
    Application: Surface Plasmon Resonance
Primary Antibodies
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His Tag Antibody

WB, Simple Western, Flow, AP, CyTOF-ready MAB050 26  
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His Tag HRP-conjugated Antibody

WB, Simple Western MAB050H 3  
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His Tag APC-conjugated Antibody

ICFlow IC050A  
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His Tag Biotinylated Antibody

WB BAM050 4  
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His Tag PE-conjugated Antibody

ICFlow IC050P 2  
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His Tag Antibody

WB, Flow, AP MAB050R  
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His Tag Alexa Fluor® 488-conjugated Antibody

ICFlow IC050G  
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His Tag PerCP-conjugated Antibody

ICFlow IC050C  
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His Tag Alexa Fluor® 700-conjugated Antibody

ICFlow IC050N  
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Protein Purification Kits
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Histidine-tagged Protein Purification Resin

IP999 1
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