|Protein Name||14-3-3 protein beta/alpha|
|Ref Sequence Id||NP_777219.2|
|Amino Acid Lenth||246|
|Protein Existence Status||Reviewed: Experimental evidence at protein level|
|Presence in other biological fluids/tissue/cells||abundant in the brain, comprising approximately 1% of its total soluble protein ; also present in almost all tissues, including testes, liver, and heart|
|Protein Function||are highly conserved dimeric proteins; involvement in vital cellular processes, such as metabolism, protein trafficking, signal transduction, apoptosis and cell-cycle regulation; 14–3–3sigma is a putative tumor suppressor that is transactivated by p53 in response to DNA damage; when up-regulated, 14–3–3s induces S–G1 and G2–M cell cycle arrests; 14-3-3γ is critical for maintaining cellular homeostasis and signal transduction; 14-3-3γ is also an important factor for intracellular phosphorylation, which participates in various pathophysiological processes; 14-3-3 maintains Raf-1 in an inactive state in the absence of activation signals but promotes Raf-1 activation and stabilizes its active conformation when such signals are received; 14- 3-3 isoforms may ensure DNA damage-induced cell cycle arrest|
|Biochemical Properties||acidic isoelectric point of 4–5; primarily binds phosphorylated ligands; also capable of interacting with unphosphorylated ligands; activation of the ExoS ADP-ribosyltransferase (12, 13) and of tryptophan hydroxylase; activator of the 43-kDa inositol polyphosphate 5-phosphatase|
|Significance in milk||14-3-3 sigma regulates epithelial polarity in mammary gland as found in humans; 14-3-3γ Regulates Lipopolysaccharide-Induced Inflammatory Responses and Lactation in Dairy Cow Mammary Epithelial Cells|
|PTMs||Phosphorylation of 14-3-3 appears to modulate the function of 14-3-3 isoforms. Three phosphorylation sites have been determined in 14-3-3eta: S58, S184, and T232; in mammalian isoforms, only 14-3-3sigma and 14-3-3eta have a phosphorylation site at the corresponding 232 position|
|Significance of PTMs||regulate ligand binding activity; phosphorylated forms of beta and eta show increased potency in the inhibition of PKC in vitro|
|Linking IDs||Bomi391 Bomi392 Bomi393 Bomi394 Bomi395|
|Bibliography||1. Liu, L., Lin, Y., Liu, L., Bian, Y., Zhang, L., Gao, X., & Li, Q. (2015). 14-3-3γ Regulates Lipopolysaccharide-Induced Inflammatory Responses and Lactation in Dairy Cow Mammary Epithelial Cells by Inhibiting NF-κB and MAPKs and Up-Regulating mTOR Signaling. International Journal of Molecular Sciences, 16(7), 16622–16641. https://doi.org/10.3390/ijms160716622. |
2. Danes, C. G., Wyszomierski, S. L., Lu, J., Neal, C. L., Yang, W., & Yu, D. (2008). 14-3-3 zeta down-regulates p53 in mammary epithelial cells and confers luminal filling. Cancer Research, 68(6), 1760–1767. https://doi.org/10.1158/0008-5472.CAN-07-3177.
3. Ling, C., Zuo, D., Xue, B., Muthuswamy, S., & Muller, W. J. (2010). A novel role for 14-3-3sigma in regulating epithelial cell polarity. Genes & Development, 24(9), 947–956. https://doi.org/10.1101/gad.1896810.
4. Megidish, T., Cooper, J., Zhang, L., Fu, H., & Hakomori, S. (1998). A novel sphingosine-dependent protein kinase (SDK1) specifically phosphorylates certain isoforms of 14-3-3 protein. The Journal of Biological Chemistry, 273(34), 21834–21845. https://doi.org/10.1074/jbc.273.34.21834.
5. Michaud, N. R., Fabian, J. R., Mathes, K. D., & Morrison, D. K. (1995). 14-3-3 is not essential for Raf-1 function: identification of Raf-1 proteins that are biologically activated in a 14-3-3- and Ras-independent manner. Molecular and Cellular Biology, 15(6), 3390–3397. https://doi.org/10.1128/mcb.15.6.3390.
6. Campbell, J. K., Gurung, R., Romero, S., Speed, C. J., Andrews, R. K., Berndt, M. C., & Mitchell, C. A. (1997). Activation of the 43 kDa inositol polyphosphate 5-phosphatase by 14-3-3zeta. Biochemistry, 36(49), 15363–15370. https://doi.org/10.1021/bi9708085.
7. Celis, J. E., Gesser, B., Rasmussen, H. H., Madsen, P., Leffers, H., Dejgaard, K., … Vandekerckhove, J. (1990). Comprehensive two‐dimensional gel protein databases offer a global approach to the analysis of human cells: The transformed amnion cells (AMA) master database and its link to genome DNA sequence data. ELECTROPHORESIS, 11(12), 989–1071. https://doi.org/10.1002/elps.1150111202.
8. Isobe, T., Ichimura, T., Sunaya, T., Okuyama, T., Takahashi, N., Kuwano, R., & Takahashi, Y. (1991). Distinct forms of the protein kinase-dependent activator of tyrosine and tryptophan hydroxylases. Journal of Molecular Biology, 217(1), 125–132. https://doi.org/10.1016/0022-2836(91)90616-e.
9. Wang, W., & Shakes, D. C. (1996). Molecular evolution of the 14-3-3 protein family. Journal of Molecular Evolution, 43(4), 384–398. https://doi.org/10.1007/bf02339012.