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).