ALK7 Extracellular Domain (human, recombinant)

Activin receptor-like kinase 7 (ALK7) is a serine/threonine kinase and member of the type I TGF-β receptor superfamily that is encoded by ACVR1C in humans.^1,2 It is composed of an extracellular ligand-binding domain, a single transmembrane domain, an intracellular serine/threonine kinase domain, and a cytoplasmic serine/threonine-rich region.^3,4 Alternative splicing of the ACVR1C pre-mRNA produces a truncated isoform, tALK7, which lacks the first 50 amino acids of the full-length protein, and two soluble isoforms, sALK7a and sALK7b, which lack the transmembrane, kinase, and cytoplasmic domains.⁵ ALK7 is highly expressed in neuronal tissues, as well as intestinal tissues, pancreatic islets, and adipocytes.^6,7,2 It heterodimerizes with activin receptor type 2A (ACTRIIA) or ACTRIIB, and upon ligand activation by activin A, activin B, activin AB, or Nodal, induces phosphorylation of SMAD2 and SMAD3 to regulate gene expression.^6,3 ALK7-mediated signaling has roles in insulin secretion and apoptosis, as well as roles in the suppression of tumorigenesis and metastasis.^8,9 ACVR1C SNPs are associated with increased risk of metabolic syndrome in women, and adipose tissue ACVR1C expression is decreased in obese individuals.^2,7 Cayman’s ALK7 Extracellular Domain (human, recombinant) protein is a disulfide-linked homodimer. The reduced monomer, composed of ALK7 (22-113) fused to human IgG1 Fc at its C-terminus, consists of 330 amino acids, has a calculated molecular weight of 36.6 kDa, and a predicted N-terminus of Leu22 after signal peptide cleavage. By SDS-PAGE, under reducing conditions, the apparent molecular mass of the protein is greater than 36.6 kDa due to glycosylation.

WARNING This product is not for human or veterinary use.

1. Reissmann, E., Jörnvall, H., Blokzijl, A., et al. The orphan receptor ALK7 and the Activin receptor ALK4 mediate signaling by Nodal proteins during vertebrate development. Genes Dev. 15(15), 2010-2022 (2001).

2. Zhang, W., Wang, H., Zhang, W., et al. ALK7 gene polymorphism is associated with metabolic syndrome risk and cardiovascular remodeling. Arq. Bras. Cardiol. 101(2), 134-140 (2013).

3. Watanabe, R. Activin receptor-like kinase and the insulin gene. Vitamins and hormones 85, 1-27 (2011).

4. Tsuchida, K., Nakatani, M., Uezumi, A., et al. Signal transduction pathway through activin receptors as a therapeutic target of musculoskeletal diseases and cancer. Endocr. J. 55(1), 11-21 (2008).

5. Roberts, H.J., Hu, S., Qiu, Q., et al. Identification of novel isoforms of activin receptor-like kinase 7 (ALK7) generated by alternative splicing and expression of ALK7 and its ligand, Nodal, in human placenta. Biol. Reprod. 68(5), 1719-1726 (2003).

6. Tsuchida, K., Nakatani, M., Yamakawa, N., et al. Activin isoforms signal through type I receptor serine/threonine kinase ALK7. Mol. Cell. Endocrinol. 220(1-2), 59-65 (2004).

7. Carlsson, L.M.S., Jacobson, P., Walley, A., et al. ALK7 expression is specific for adipose tissue, reduced in obesity and correlates to factors implicated in metabolic disease. Biochem. Biophys. Res. Commun. 382(2), 309-314 (2009).

8. Michael, I.P., Saghafinia, S., Tichet, M., et al. ALK7 signaling manifests a homeostatic tissue barrier that is abrogated during tumorigenesis and metastasis. Dev. Cell 49(3), 409-424 (2019).

9. Zhao, F., Huang, F., Tang, M., et al. Nodal induces apoptosis through activation of the ALK7 signaling pathway in pancreatic INS-1 β-cells. Am. J. Physiol. Endocrinol. Metab. 303(1), E132-E143 (2012).