YWHAZ

Description

The YWHAZ (tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein zeta) is a protein-coding gene located on chromosome 8.

14-3-3 protein zeta/delta (14-3-3ζ) is a protein that in humans is encoded by the YWHAZ gene on chromosome 8. The protein encoded by this gene is a member of the 14-3-3 protein family and a central hub protein for many signal transduction pathways. 14-3-3ζ is a major regulator of apoptotic pathways critical to cell survival and plays a key role in a number of cancers and neurodegenerative diseases.

== Structure == 14-3-3 proteins generally form ~30 kDa-long homo- or heterodimers. Each of the monomers are composed of 9 antiparallel alpha helices. Four alpha-helices (αC, αE, αG, and αI) form an amphipathic groove that serves as the ligand binding site, which can recognize three types of consensus binding motifs: RXX(pS/pT)XP, RXXX(pS/pT)XP, and (pS/pT)X1-2-COOH (where pS/pT represents phosphorylated serine/threonine). In addition to these primary interactions, the target protein can also bind outside the groove via secondary interactions. In particular, the crystallized structure of 14-3-3ζ forms a cup-shaped dimer when complexed with CBY. The YWHAZ gene encodes two transcript variants which differ in the 5' UTR but produce the same protein.

== Function == 14-3-3ζ is one of 7 members of the 14-3-3 protein family, which is ubiquitously expressed and highly conserved among plants and mammals. This protein family is known for regulating signal transduction pathways primarily through binding phosphoserine proteins, though it can also bind phosphothreonine proteins and unphosphorylated proteins.

YWHAZ, also known as 14-3-3 protein zeta/delta, plays a central role in regulating a wide range of signaling pathways, both general and specialized. It interacts with a large number of protein partners, often through recognition of phosphorylated serine or threonine residues. This binding typically results in modulation of the partner protein's activity. For example, YWHAZ promotes the retention and inactivation of the TFEB transcription factor by binding to its phosphorylated form. Additionally, YWHAZ stimulates the activity of ARHGEF7 on RAC1, leading to lamellipodia and membrane ruffle formation. In neurons, YWHAZ regulates spine maturation by modulating ARHGEF7 activity.

YWHAZ is also known as 14-3-3-zeta, HEL-S-3, HEL-S-93, HEL4, KCIP-1, POPCHAS, YWHAD.

Associated Diseases

WES Whole Exome Sequencing