Recombinant Human Crossveinless-2 Protein, CF

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

Recombinant Human Crossveinless-2 Protein, CF Summary

• Details of Functionality: Measured by its ability to inhibit rhBMP-4-induced alkaline phosphatase production by ATDC5 mouse chondrogenic cells. Binnerts, M.E. et al. (2004) Biochem. Biophys. Res. Commun. 315:272. The ED₅₀ for this effect is 0.2-1.6 µg/mL in the presence of 30 ng/mL of Recombinant Human BMP-4 (Catalog # 314-BP).
• Source: Mouse myeloma cell line, NS0-derived human Crossveinless-2/CV-2 protein
  Val34-Asp369, with an N-terminal 7-His tag & Ala39-Asp369 (N-terminal fragments) & Pro370-Arg685 (C-terminal fragment)
• Accession #: Q8N8U9
• N-terminal Sequence: His & Ala39 (N-terminal fragments) & Pro370 (C-terminal fragment)
• Structure / Form: Disulfide-linked heterodimer
• Protein/Peptide Type: Recombinant Proteins
• Gene: BMPER
• Purity: >95%, by SDS-PAGE under reducing conditions and visualized by silver stain.
• Endotoxin Note: <0.10 EU per 1 μg of the protein by the LAL method.

Applications/Dilutions

• Dilutions:
  • Bioactivity
• SDS-PAGE: 50-55 kDa doublet and 39 kDa, reducing conditions

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 under reducing conditions and visualized by silver stain.
• 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 Crossveinless-2 Protein, CF

• BMP binding endothelial regulator
• BMP-binding endothelial regulator precursor protein
• BMP-binding endothelial regulator protein
• BMPER
• Bone morphogenetic protein-binding endothelial cell precursor-derived regulator
• CRIM3
• crossveinless 2
• Crossveinless-2
• CV2
• CV-2
• hCV2
• KIAA1965
• Protein crossveinless-2

Background

Crossveinless-2 (CV-2), also known as bone morphogenetic protein-binding endothelial cell precursor-derived regulator (BMPER), is a secreted chordin-like protein that modulates the BMP signaling pathway (1 - 3). Human CV-2 is synthesized as a 685 amino acid (aa) residue precursor protein with a putative 39 aa signal peptide, five tandem chordin-like cysteine-rich (CR) domains, a partial von Willebrand factor type D domain (vWD), and a carboxyl trypsin inhibitor-like cysteine-rich domain (TIL) (1, 4). Secreted CV-2 is reported to be proteolytically cleaved to generate two fragments that are disulfide-linked (1, 2). The cleavage site of R&D Systems’ recombinant CV-2 is found to be between asp³⁶⁹ and pro³⁷⁰ in the GDPH sequence within the vWD domain. This cleavage is likely due to an autocatalytic mechanism triggered by low pH comparable to that of the late secretory pathway (5). The GDPH sequence is conserved in CV-2 from other species. It is also found in multiple proteins that undergo a similar type of cleavage (5). Human CV-2 message is detected in many tissues, with the highest expression detected in adult brain and adult and fetal lung (1). It is also expressed in flk-1⁺ endothelial cell precursors and in primary chondrocytes (2). During embryonic development, CV-2 is expressed in regions of high BMP signaling, such as the posterior primitive streak and the ventral tail bud (4). Human CV-2 shares 92% and 34% aa sequence identity with the mouse and Drosophila homologs, respectively (1, 4). Results from biochemical experiments using recombinant CV-2 show that CV-2 directly interacts with BMP-2, -4, and -6 to antagonize BMP signaling, which can regulate a wide range of differentiation processes (1, 2). In contrast, genetic data from Drosophila suggest that CV-2 potentiates BMP-signaling (6). It is possible that like TSG, CV-2 can positively and negatively modulate BMP signal transduction depending on the cell context (7).

1. Binnerts, M.E. et al. (2004) Biochem Biophys Res Commun. 315:272.
2. Moser, M. et al. (2003) Mol Cell Biol. 23:5664. 
3. Garcia-Abreu, J. et al. (2002) Gene, 287: 39. 
4. Coffinier, C. et al. (2002) Mech Dev. 119:S179.
5. Lidell, M.E. et al. (2003) J. Biol. Chem. 278:13944.
6. Conley, C.A. et al. (2000) Development 127:3947.
7. Kamimura, M. et al. (2004) Developmental Dynamics 230:434.

Publications for Crossveinless-2/CV-2/BMPER (1956-CV/CF)(6)

Publications using 1956-CV/CF

• JS Esser, RE Steiner, M Deckler, H Schmitt, B Engert, S Link, A Charlet, C Patterson, C Bode, Q Zhou, M Moser Extracellular bone morphogenetic protein modulator BMPER and twisted gastrulation homolog 1 preserve arterial-venous specification in zebrafish blood vessel development and regulate Notch signaling in endothelial cells FEBS J., 2018-03-09;0(0):. 2018-03-09 [PMID: 29473997] (Bioassay, Human)
• Bulk cell density and Wnt/TGFbeta signalling regulate mesendodermal patterning of human pluripotent stem cells Nat Commun, 2016-12-09;7(0):13602. 2016-12-09 [PMID: 27934856] (Bioassay, Human)
• 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 Bone morphogenetic protein-9 suppresses growth of myeloma cells by signaling through ALK2 but is inhibited by endoglin. Blood Cancer J, 2014-03-21;4(0):e196. 2014-03-21 [PMID: 24658374] (Bioassay, Human)
• Satomi-Kobayashi S, Kinugasa M, Kobayashi R, Hatakeyama K, Kurogane Y, Ishida T, Emoto N, Asada Y, Takai Y, Hirata K, Rikitake Y Osteoblast-like differentiation of cultured human coronary artery smooth muscle cells by bone morphogenetic protein endothelial cell precursor-derived regulator (BMPER). J Biol Chem, 2012-07-09;287(36):30336-45. 2012-07-09 [PMID: 22778264] (Bioassay, Human)
• Yao Y, Jumabay M, Ly A, Radparvar M, Wang AH, Abdmaulen R, Bostrom KI Crossveinless 2 regulates bone morphogenetic protein 9 in human and mouse vascular endothelium. Blood, 2012-04-03;119(21):5037-47. 2012-04-03 [PMID: 22474252] (Bioassay, Human)
• Helbing T, Rothweiler R, Ketterer E, Goetz L, Heinke J, Grundmann S, Duerschmied D, Patterson C, Bode C, Moser M BMP activity controlled by BMPER regulates the proinflammatory phenotype of endothelium. Blood, 2011-09-07;118(18):5040-9. 2011-09-07 [PMID: 21900199] (Bioassay, In Vivo, Human, Mouse)

Bioinformatics

• Gene Symbol: BMPER
• Uniprot:
  • Q8N8U9()