Betacellulin is a protein that in humans is encoded by the BTCgene located on chromosome 4 at locus 4q13-q21. Betacellulin is a member of the EGF family of growth factors. It is synthesized primarily as a transmembrane precursor, which is then processed to mature molecule by proteolytic events. This protein is a ligand for the EGF receptor.
BTC is a polymer of about 62-111 amino acid residues. Secondary Structure: 6% helical (1 helices; 3 residues) 36% beta sheet (5 strands; 18 residues)
BTC was originally identified as a growth-promoting factor in mouse pancreatic β-cell carcinoma cell line and has since been identified in humans. Mouse BTC (mBTC) is expressed as a 178-amino acid precursor. The membrane-bound precursor is cleaved to yield mature secreted mBTC. BTC is synthesized in a wide range of adult tissues and in many cultured cells, including smooth muscle cells and epithelial cells. The amino acid sequence of mature mBTC is 82.5%, identical with that of human BTC (hBTC), and both exhibit significant overall similarity with other members of the EGF family.
The structure for the small protein Betacellulin that is shown was determined by two-dimensional nuclear magnetic resonance spectroscopy. The species that BTC was taken from was Homo sapiens.This particular molecule of BTC has a formula weight of 5916.9 and its sequence was determined to be RKGHFSRCPKQYKHYCIKGRCRFVVAEQTPSCVCDEGYIGARCERVDLFY (if you would like to see an image of what parts of the sequence code for the secondary structures observed in the image, click here). Also, a Ramachandran plot can be found here.
Kim HS, Shin HS, Kwak HJ, Cho CH, Lee CO, Koh GY (February 2003). "Betacellulin induces angiogenesis through activation of mitogen-activated protein kinase and phosphatidylinositol 3'-kinase in endothelial cell". FASEB J.17 (2): 318–20. doi:10.1096/fj.02-0570fje. PMID12475887.
Yamamoto T, Akisue T, Marui T et al. (2004). "Expression of betacellulin, heparin-binding epidermal growth factor and epiregulin in human malignant fibrous histiocytoma.". Anticancer Res.24 (3b): 2007–10. PMID15274392.
Nakagawa T, Furuta H, Sanke T et al. (2005). "Molecular scanning of the betacellulin gene for mutations in type 2 diabetic patients.". Diabetes Res. Clin. Pract.68 (3): 188–92. doi:10.1016/j.diabres.2004.09.019. PMID15936459.
Silver K, Tolea M, Wang J et al. (2005). "The exon 1 Cys7Gly polymorphism within the betacellulin gene is associated with type 2 diabetes in African Americans.". Diabetes54 (4): 1179–84. doi:10.2337/diabetes.54.4.1179. PMID15793259.
Tanimura K, Nakago S, Murakoshi H et al. (2004). "Changes in the expression and cytological localization of betacellulin and its receptors (ErbB-1 and ErbB-4) in the trophoblasts in human placenta over the course of pregnancy.". Eur. J. Endocrinol.151 (1): 93–101. doi:10.1530/eje.0.1510093. PMID15248827.
Saito T, Okada S, Ohshima K et al. (2004). "Differential activation of epidermal growth factor (EGF) receptor downstream signaling pathways by betacellulin and EGF.". Endocrinology145 (9): 4232–43. doi:10.1210/en.2004-0401. PMID15192046.
Moss ML, Bomar M, Liu Q et al. (2007). "The ADAM10 prodomain is a specific inhibitor of ADAM10 proteolytic activity and inhibits cellular shedding events.". J. Biol. Chem.282 (49): 35712–21. doi:10.1074/jbc.M703231200. PMID17895248.
Nagaoka T, Fukuda T, Hashizume T et al. (2008). "A betacellulin mutant promotes differentiation of pancreatic acinar AR42J cells into insulin-producing cells with low affinity of binding to ErbB1.". J. Mol. Biol.380 (1): 83–94. doi:10.1016/j.jmb.2008.03.054. PMID18508082.
Nakano Y, Furuta H, Doi A et al. (2005). "A functional variant in the human betacellulin gene promoter is associated with type 2 diabetes.". Diabetes54 (12): 3560–6. doi:10.2337/diabetes.54.12.3560. PMID16306376.
Sanderson MP, Erickson SN, Gough PJ et al. (2005). "ADAM10 mediates ectodomain shedding of the betacellulin precursor activated by p-aminophenylmercuric acetate and extracellular calcium influx.". J. Biol. Chem.280 (3): 1826–37. doi:10.1074/jbc.M408804200. PMID15507448.
Silver KD, Magnuson VL, Tolea M et al. (2006). "Association of a polymorphism in the betacellulin gene with type 1 diabetes mellitus in two populations.". J. Mol. Med.84 (7): 616–23. doi:10.1007/s00109-006-0052-6. PMID16683131.