Product Specifications
Source
E. coli-derived human Activin A protein
Gly311-Ser426
Produced using non-animal reagents in an animal-free laboratory.Manufactured and tested under cGMP guidelines.
Purity
>97%, by SDS-PAGE with quantitative densitometry by Coomassie® Blue Staining. The molecular weight by mass spectrometry is 25917 Da ± 5 Da.
Endotoxin Level
<0.10 EU per 1 μg of the protein by the LAL method.
N-terminal Sequence Analysis
Gly311-Leu-Glu-(Cys)-Asp-Gly-Lys-Val-Asn-Ile
Predicted Molecular Mass
13 kDa (monomer)
SDS-PAGE
13 kDa, under reducing conditions.
23 kDa, under non-reducing conditions.
Activity
Measured by its ability to induce cytotoxicity using MPC-11 mouse B lymphocyte cells.
The ED50 for this effect is <10.0
ng/mL.
The specific activity of Recombinant Human Activin A is >1000 units/mg, which is calibrated against
the human Activin A WHO reference standard (NIBSC code: 91/626).
Host Cell Protein
<0.500 ng per μg of protein when tested by ELISA.
Mycoplasma
Negative for Mycoplasma.
Host Cell DNA
<0.00150 ng per µg of protein when tested by PCR.
Background: Activin A
Activin and Inhibin are members of the TGF-beta superfamily of cytokines and are involved in a wide range of biological processes including tissue morphogenesis and repair, fibrosis, inflammation, neural development, hematopoiesis, reproductive system function, and carcinogenesis (1‑7). Activin and Inhibin are produced as precursor proteins. Their amino terminal propeptides are proteolytically cleaved and facilitate formation of disulfide-linked dimers of the bioactive proteins (8, 9). Activins are nonglycosylated homodimers or heterodimers of various beta subunits ( beta A, beta B, beta C, and beta E in mammals), while Inhibins are heterodimers of a unique alpha subunit and one of the beta subunits. Activin A is a widely expressed homodimer of two beta A chains. The beta A subunit can also heterodimerize with a beta B or beta C subunit to form Activin AB and Activin AC, respectively (10). The 14 kDa mature human beta A chain shares 100% amino acid sequence identity with bovine, feline, mouse, porcine, and rat beta A.
Activin A exerts its biological activities by binding to the type 2 serine/threonine kinase Activin RIIA which then noncovalently associates with the type 1 serine/threonine kinase Activin RIB/ALK-4 (7, 11). Signaling through this receptor complex leads to Smad activation and regulation of activin-responsive gene transcription (7, 11). The bioactivity of Activin A is regulated by a variety of mechanisms (11). BAMBI, Betaglycan, and Cripto are cell‑associated molecules that function as decoy receptors or limit the ability of Activin A to induce receptor complex assembly (12‑14). The intracellular formation of Activin A can be prevented by the incorporation of the beta A subunit into Activin AC or Inhibin A (3, 10). And the bioavailability of Activin A is restricted by its incorporation into inactive complexes with alpha 2-Macroglobulin, Follistatin, and FLRG (15, 16).
Activin A is involved in the differentiation of various cell
and tissue types. The induction of definitive endoderm by Activin A is required
in differentiation protocols of induced pluripotent stem cells (iPSCs) (17, 18).
In vitro models of human gametogenesis use prolonged Activin A supplementation
to human embryonic stem cells for differentiation into human primordial germ
cell-like cells (19). Activin A can also be used to maintain cells in vitro, as
is the case for iPSC-derived nephron cells that can then be used in disease
modeling, drug screening and in regenerative medicine (20).
Activin A is an
important factor for tumor cells to evade the immune system as Activin A can
act on surrounding immune cells to decrease their antitumor activity (21).
Activin A also promotes migration and growth of tumors, making it a target for
cancer therapies (22). Specifically, research has shown that interfering with
Activin A activity can assist in overcoming CD8 T-cell exclusion and
immunotherapy resistance (23). In bone marrow-derived stem cell transplants for
treatment of diabetes, Activin A enhances migration and homing of stem cells
towards pancreatic lineage (24).
References
- Kumanov, P. et al. (2005) Reprod. Biomed. Online 10:786.
- Maeshima, A. et al. (2008) Endocr. J. 55:1.
- Rodgarkia-Dara, C. et al. (2006) Mutat. Res. 613:123.
- Werner, S. and C. Alzheimer (2006) Cytokine Growth Factor Rev. 17:157.
- Xu, P. and A.K. Hall (2006) Dev. Biol. 299:303.
- Shav-Tal, Y. and D. Zipori (2002) Stem Cells 20:493.
- Chen, Y.G. et al. (2006) Exp. Biol. Med. 231:534.
- Gray, A.M. and A.J. Mason (1990) Science 247:1328.
- Mason, A.J. et al. (1996) Mol. Endocrinol. 10:1055.
- Thompson, T.B. et al. (2004) Mol. Cell. Endocrinol. 225:9.
- Harrison, C.A. et al. (2005) Trends Endocrinol. Metab. 16:73.
- Onichtchouk, D. et al. (1999) Nature 401:480.
- Gray, P.C. et al. (2002) Mol. Cell. Endocrinol. 188:254.
- Kelber, J.A. et al. (2008) J. Biol. Chem. 283:4490.
- Phillips, D.J. et al. (1997) J. Endocrinol. 155:65.
- Schneyer, A. et al. (2003) Endocrinology 144:1671.
- Ghorbani-Dalini, S. et
al. (2020) 3 Biotech. 10:215.
- Mennen, R. H. et al. (2022) Reprod Toxicol. 107:44.
- Mishra, S. et al. (2021) Stem Cells. 39:551.
- Tanigawa, S. et al. (2019) Stem Cell Reports 13:322.
- Cangkrama, M. et al. (2020) Trends Mol. Med. 26:1107.
- Ries, A. et al. (2020) Expert
Opin. Ther. Targets. 24:985.
- Pinjusic, K. et al. (2022) J. Immunother. Cancer. 10:e004533.
- Dadheech, N. et al. (2020) Stem Cell Res. Ther. 11:327.
Alternate Names
activin AB alpha polypeptide, Activin beta-A chain, erythroid differentiation factor, Erythroid differentiation protein, follicle-stimulating hormone-releasing protein, FSH-releasing protein, inhibin beta A chain, inhibin beta A subunit, Inhibin, beta-1
Additional Activin A Products
Manufacturing Specifications
GMP Proteins
R&D Systems, a Bio-Techne Brand's GMP proteins are produced according to relevant sections of the following documents: USP Chapter 1043, Ancillary Materials for Cell, Gene and Tissue-Engineered Products and Eu. Ph. 5.2.12, Raw Materials of Biological Origin for the Production of Cell-based and Gene Therapy Medicinal Products.
R&D Systems' quality focus includes:
- Designed, manufactured and tested under an ISO 9001:2015 and ISO 13485:2016 certified quality system
- Documented and controlled manufacturing process
- Control of documentation and process changes by QA
- Personnel training programs
- Raw material inspection and vendor qualification/monitoring program
- Validated equipment, processes and test methods
- Equipment calibration and maintenance schedules using a Regulatory Asset Manager
- Facility/Utilities maintenance, contamination controls, safety and pest control programs
- Material review process for variances
- Robust product stability program following relevant ICH guidelines
R&D Systems strives to provide our customers with the analytical characteristics of each product so that customers may determine whether our products are appropriate for their application. Each product is provided with a lot-specific Certificate of Analysis that contains the product's specifications and test results. Quality control testing may include, but is not limited to:
- N-terminal amino acid analysis
- SDS-PAGE purity analysis
- Molecular weight analysis via mass spectrometry
- Endotoxin assessment per USP <85> and Ph. Eur. 2.6.14 guidelines
- Bioassay analysis
- Microbial testing per USP <71> and Ph. Eur. 2.6.1 guidelines
- Host cell protein assessment
- Host cell DNA assessment
- Mycoplasma assessment
Additional testing and documentation requested by the customer can be arranged at an additional cost.
Production records and facilities are available for examination by appropriate personnel on-site at R&D Systems in Minneapolis and St. Paul, Minnesota USA.
R&D Systems sells GMP grade products for preclinical or clinical
ex vivo use. They are not for
in vivo use. Please read the following End User Terms prior to using this product.
Animal-Free Manufacturing Conditions
Our dedicated controlled-access animal-free laboratories ensure that at no point in production are the products exposed to potential contamination by animal components or byproducts. Every stage of manufacturing is conducted in compliance with R&D Systems' stringent Standard Operating Procedures (SOPs). Production and purification procedures use equipment and media that are confirmed animal-free.
Production
- All molecular biology procedures use animal-free media and dedicated labware.
- Dedicated fermentors are utilized in committed animal-free areas.
Purification
- Protein purification columns are animal-free.
- Bulk proteins are filtered using animal-free filters.
- Purified proteins are stored in animal-free containers.
Please read our complete Animal-Free Statement
Product Specific Notices for Recombinant Human Activin A GMP Protein, CF
Full terms and conditions of sale can be found online in the Protein Sciences Segment T&Cs at: Terms & Conditions.
For preclinical, or clinical ex vivo use
