Proline-rich and Gla domain 4 (PRRG4)

Proline-rich and Gla domain 4 (PRRG4) is a transmembrane protein encoded by the PRRG4 gene. It contains a Gla domain (gamma-carboxyglutamic acid), a post-translationally modified region involved in calcium ion binding, and multiple proline-rich motifs (PPxY, LPxY), which serve as binding sites for WW domain-containing proteins[2][5]. PRRG4 is localized to the plasma membrane and has been observed in neural tissues such as the spinal cord and brain, where it likely plays a role in axon guidance by regulating the cell surface delivery of ROBO1 and potentially other membrane targets[5][6]. PRRG4 may modulate various intracellular signaling pathways through interactions involving its proline-rich domains. Recent research shows PRRG4 promotes mitochondrial function and breast cancer cell migration via the Src-STAT3-POLG signaling axis, supporting its role in cancer progression[4]. It is also linked by association studies to Wilms tumor, aniridia, and other developmental disorders[5][8]. Though PRRG4 possesses domains often found in proteins with coagulation functions, its main known roles are outside the coagulation cascade, with implications for neural development and cancer biology[2][5]. There are currently no known drug interactions or established mechanisms of pharmacological targeting, and it is not generally considered a classical therapeutic target such as a receptor or enzyme.

Other names

Transmembrane gamma-carboxyglutamic acid protein 4TMG4Proline-rich Gla protein 4Proline-rich gamma-carboxyglutamic acid protein 4PRGP4