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Description

Protein salvador homolog 1 (UniProt: Q9H4B6, also known as 45 kDa WW domain protein, hWW45) is encoded by the SAV1 (also known as WW45) gene (Gene ID: 60485) in human. SAV1, a homodimeric protein is ubiquitously expressed in adult tissues with highest expression observed in the pancreas, aorta, and interventricular septum and lowest expression in skeletal muscle. SAV1 protein contains two WW domains (aa 199-232 and 234-267) and one SARAH domain (aa 321-368). SAV1 is phosphorylated by STK3/MST2 and STK4/MST1, but phosphorylation is not required for its stability. However, it increases the number of protein binding sites on the scaffold molecule. SAV1 is also required for STK3/MST2 and STK4/MST1 activation and promotes cell-cycle exit and terminal differentiation in developing epithelial tissues. SAV1 regulates their activity in the Hippo signaling pathway, which plays a pivotal role in organ size control and tumor suppression by restricting proliferation and promoting apoptosis. STK3/MST2 and STK4/MST1- SAV1 complex is also shown to phosphorylate and activate LATS1/2 in complex with its regulatory protein MOB1, which in turn phosphorylates and inactivates YAP1 oncoprotein and WWTR1/TAZ. Phosphorylation of YAP1 inhibits its translocation into the nucleus.