WW domain-containing transcription regulator protein

kinase cascade wherein STK3/MST2 and STK4/MST1, in complex with its regulatory protein SAV1, phosphorylates and activates LATS1/2 in complex with its regulatory protein MOB1, which in turn phosphorylates and inactivates YAP1 oncoprotein and WWTR1/TAZ. WWTR1 enhances PAX8 and NKX2-1/TTF1-dependent gene activation. Regulates the nuclear accumulation of SMADS and has a key role in coupling them to the transcriptional machinery such as the mediator complex. Regulates embryonic stem-cell self-renewal, promotes cell proliferation and epithelial-mesenchymal transition. Binds to SLC9A3R2 via the PDZ motif at the plasma membrane. Binds to YWHAZ in vivo and in vitro through the phosphoserine-binding motif RSHSSP. Interacts (via coiled-coil domain) with SMAD2 (via MH1 domain), SMAD3 and SMAD4. Interacts with MED15, PAX8 and NKX2-1. Interacts with TEAD1, TEAD2, TEAD3 and TEAD4. Highly expressed in kidney, heart, placenta and lung. Expressed in the thyroid tissue.

Protein type: Oncoprotein; Transcription, coactivator/corepressor

Chromosomal Location of Human Ortholog: 3q23-q24

Cellular Component: cytoplasm; cytosol; nucleoplasm; nucleus

Molecular Function: protein binding; transcription coactivator activity

Biological Process: negative regulation of protein amino acid phosphorylation; negative regulation of protein kinase activity; positive regulation of cell proliferation; positive regulation of transcription from RNA polymerase II promoter; stem cell division; transcription initiation from RNA polymerase II promoter