TCDB is operated by the Saier Lab Bioinformatics Group

8.A.98.  The 14-3-3 protein (14-3-3) Family

The 14-3-3 proteins comprise a family of highly conserved, multifunctional proteins that are expressed in many tissues including the brain, especially during development. The seven human 14-3-3 isoforms make up approximately 1% of total soluble brain protein. These proteins play a role in cortical development, and regulate a number of neurodevelopmental processes. 14-3-3 isoforms play different roles in the development of the cortex and in human neurodevelopmental disorders (Cornell and Toyo-Oka 2017). The urea transporter, UT-A1 (TC# 1.A.28.1.3) is regulated by 14-3-3, which blocks its removal from the membrane (Klein and Sands 2016). TASK-1 (KCNK3; TC# 1.A.1.9.2) and TASK-3 (KCNK9; TC#1.A.1.19.11) K+ channels interact with 14-3-3 proteins, interactions that may influcence  targetting of these channels to the plasma membrane (Kilisch et al. 2015).The Nedd4-2 ubiquitin ligase binds 14-3-3, blocking its interaction with Orai1 and thus its degradation (Lang et al. 2012). In fact, 14-3-3 proteins regulate several aspects of intracellular transport (Smith et al. 2011). Most interacting proteins, such as the two pore K+ channels, KCNK3 and KCNK9 (see above), have 14-3-3 motifs for binding to this protein (Mrowiec and Schwappach 2006).

References associated with 8.A.98 family:

Cornell, B. and K. Toyo-Oka. (2017). 14-3-3 Proteins in Brain Development: Neurogenesis, Migration and Neuromorphogenesis. Front Mol Neurosci 10: 318. 29075177
Gu, Y.M., Y.H. Jin, J.K. Choi, K.H. Baek, C.Y. Yeo, and K.Y. Lee. (2006). Protein kinase A phosphorylates and regulates dimerization of 14-3-3 epsilon. FEBS Lett. 580: 305-310. 16376338
Kilisch, M., O. Lytovchenko, B. Schwappach, V. Renigunta, and J. Daut. (2015). The role of protein-protein interactions in the intracellular traffic of the potassium channels TASK-1 and TASK-3. Pflugers Arch 467: 1105-1120. 25559843
Klein, J.D. and J.M. Sands. (2016). Urea transport and clinical potential of urearetics. Curr Opin Nephrol Hypertens 25: 444-451. 27367911
Lang, F., A. Eylenstein, and E. Shumilina. (2012). Regulation of Orai1/STIM1 by the kinases SGK1 and AMPK. Cell Calcium 52: 347-354. 22682960
Mrowiec, T. and B. Schwappach. (2006). 14-3-3 proteins in membrane protein transport. Biol Chem 387: 1227-1236. 16972791
Smith, A.J., J. Daut, and B. Schwappach. (2011). Membrane proteins as 14-3-3 clients in functional regulation and intracellular transport. Physiology (Bethesda) 26: 181-191. 21670164
Tsuruta, F., J. Sunayama, Y. Mori, S. Hattori, S. Shimizu, Y. Tsujimoto, K. Yoshioka, N. Masuyama, and Y. Gotoh. (2004). JNK promotes Bax translocation to mitochondria through phosphorylation of 14-3-3 proteins. EMBO. J. 23: 1889-1899. 15071501
Zhou, Y., S. Reddy, H. Murrey, H. Fei, and I.B. Levitan. (2003). Monomeric 14-3-3 protein is sufficient to modulate the activity of the Drosophila slowpoke calcium-dependent potassium channel. J. Biol. Chem. 278: 10073-10080. 12529354