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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). These proteins also regulate sucrose/glucose/fructose:H+ symporters of the SLC49 family (TC#2.A.2.4) (Vitavska et al. 2018).

References associated with 8.A.98 family:

Asih, P.R., A. Poljak, M. Kassiou, Y.D. Ke, and L.M. Ittner. (2022). Differential mitochondrial protein interaction profile between human translocator protein and its A147T polymorphism variant. PLoS One 17: e0254296. 35522669
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
Jin, Y., M.S. Dai, S.Z. Lu, Y. Xu, Z. Luo, Y. Zhao, and H. Lu. (2006). 14-3-3gamma binds to MDMX that is phosphorylated by UV-activated Chk1, resulting in p53 activation. EMBO. J. 25: 1207-1218. 16511572
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
Suhda, S., Y. Yamamoto, S. Wisesa, R. Sada, and T. Sakisaka. (2023). The 14-3-3γ isoform binds to and regulates the localization of endoplasmic reticulum (ER) membrane protein TMCC3 for the reticular network of the ER. J. Biol. Chem. 299: 102813. 36549645
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
Vitavska, O., R. Bartölke, K. Tabke, J.J. Heinisch, and H. Wieczorek. (2018). Interaction of mammalian and plant H/sucrose transporters with 14-3-3 proteins. Biochem. J. 475: 3239-3254. 30237153
Wang, X., N. Grammatikakis, A. Siganou, and S.K. Calderwood. (2003). Regulation of molecular chaperone gene transcription involves the serine phosphorylation, 14-3-3 epsilon binding, and cytoplasmic sequestration of heat shock factor 1. Mol. Cell Biol. 23: 6013-6026. 12917326
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