ZYX gene

The ZYX gene (ZYX stands for: Zyxin) is a protein-coding gene located on chromosome 7q34. An important paralog of this gene is TRIP6. Alternative splicing results in several transcript variants that code for the same isoform.

The ZYX gene encodes an adhesion platelet protein (Zyxin). This binds alpha-actinin and the CRP protein. Important for the targeting of members of the TES and ENA/VASP family to focal adhesions and for the formation of actin-rich structures. Possibly part of a signal transduction pathway that mediates adhesion-stimulated changes in gene expression.

Focal adhesions are actin-rich structures that allow cells to adhere to the extracellular matrix and where protein complexes involved in signal transduction assemble. Zyxin is a zinc-binding phosphoprotein that concentrates at focal adhesions and along the actin cytoskeleton. Zyxin has an N-terminal proline-rich domain and three LIM domains in its C-terminal half. The proline-rich domain may interact with SH3 domains of proteins involved in signal transduction pathways, while the LIM domains are likely involved in protein-protein binding. Zyxin may act as a messenger in the signal transduction pathway, mediating adhesion-stimulated changes in gene expression and modulating the cytoskeletal organization of actin bundles. Alternative splicing results in multiple transcript variants encoding the same isoform.

Skin fibrosis is a common pathology in systemic sclerosis (SSc), keloids in morphea, which is characterized by fibroblast activation and excessive deposition of extracellular matrix (ECM). Recent results show that the focal adhesion pathway is upregulated and that zyxin appears to be the primary focal adhesion protein involved in skin fibrosis. Inhibition of zyxin significantly inhibits skin fibrosis. It is possible that zyxin is a potential therapeutic target in skin fibrosis (Huang Y et al. (2023).

Androgenetic alopecia (AGA): In androgenetic alopecia, it is shown that the expression of ZYX was increased in the affected frontal RFs of individuals with AGA compared to unaffected occipital RFs. ZYX knockout mice show increased hair growth and anagen onset compared to wild-type mice. Reduction of ZYX expression in ex vivo cultured HFs by siRNA resulted in increased hair shaft production, delayed catagen onset of hair follicles, increased proliferation of dermal papilla cells (DPCs), and regulated the expression of stem cell-related proteins. These results suggest that ZYX plays an important role in the pathogenesis of AGA and the stem cell properties of DPCs, and can potentially be used as a therapeutic target in AGA (Liu Q et al. (2021)

Diseases associated with ZYX include:

• Lipomatosis, familial multiple
• and
• Ewing's sarcoma.

1. Huang Y et al. (2023) Enhancement of Zyxin Promotes Skin Fibrosis by Regulating FAK/PI3K/AKT and TGF-β Signaling Pathways via Integrins. Int J Biol Sci 19:2394-2408.

2. Liu Q et al. (2021) Increased Expression of Zyxin and Its Potential Function in Androgenetic Alopecia. Front Cell Dev Biol 8:582282.