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:
The dimeric fly 14-3-3zeta protein of 248 aas modulates as a negative regulator to control the activity of the Slowpoke calcium-dependent potassium channel (dSlo) by interacting with the dSlo binding protein, Slob (Zhou et al. 2003).
14.3.3zeta of Drosophila melanogaster (Fruit fly)
14-3-3 protein epsilon , 14-3-3ε, of 255 aas and 0 TMSs. It positively regulates phosphorylated protein HSF1 (Q00613; 529 aas, 0 TMSs) nuclear export to the cytoplasm (Wang et al. 2003). A mitochondrial stress-specific form of HSF1 (heat shock factor 1) protects against age-related proteostasis collapse (Williams et al. 2020).
14-3-3ε adaptor protein of Homo sapiens
14-3-3 protein gamma, 14-3-3γ or YWHAG, of 247 aas and 0 TMSs. It is an adapter protein implicated in the regulation of a large spectrum of both general and specialized signaling pathways. It binds to a large number of partners, usually by recognition of a phosphoserine or phosphothreonine motif. Binding generally results in the modulation of the activity of the binding partner (Jin et al. 2006). The 14-3-3gamma isoform binds to and regulates the localization of endoplasmic reticulum (ER) membrane protein TMCC3 for the reticular network of the ER (Suhda et al. 2023).
14-3-3γ of Homo sapiens
14-3-3zeta/delta protein of 245 aas, an adapter protein implicated in the regulation of a large number of signaling systems and transport proteins. It binds to its partners, often by recognition of a phosphoserine or phosphothreonine motif. Binding generally results in the modulation of the activity of the target partner protein (Tsuruta et al. 2004; Gu et al. 2006).
14-3-3 of Homo sapiens
14-3-3 protein of 262 aas.
14-3-3 of Plasmodium falciparum
14-3-3ε protein of 169 aas
14-3-3ε of Tetrahymena thermophila
Uncharacterized protein of 212 aas.
UP of Ascaris suum (Pig roundworm) (Ascaris lumbricoides)
14-3-3 protein of 363 aas.
14-3-3 protein of Glarea lozoyensis
14-3-3 homologue of 233 aas.
14-3-3 of Reticulomyxa filosa
14-3-3 protein, GF14λ, ATF1, RCI2, of 248 aas
14-3-3 protein of Arabidopsis thaliana
14-3-3 theta (YWHAQ) of 245 aas and 0 TMSs. It is an adapter protein implicated in the regulation of several general and specialized signaling pathways. It binds
to a large number of partners, usually by recognition of a
phosphoserine or phosphothreonine motif. Binding generally results in
the modulation of the activity of the binding partner (Asih et al. 2022).
YWHAQ of Homo sapiens
Uncharacterized protein of 294 aas and 1 N-terminal TMS.
UP of Streptococcus iniae