Transcriptional coactivator which acts as a downstream regulatory target in the Hippo signaling pathway that plays a pivotal role in organ size control and tumor suppression by restricting proliferation and promoting apoptosis (PubMed:11118213). The core of this pathway is composed of a 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 (By similarity). WWTR1 enhances PAX8 and NKX2-1/TTF1-dependent gene activation (By similarity). In conjunction with YAP1, involved in the regulation of TGFB1-dependent SMAD2 and SMAD3 nuclear accumulation (PubMed:21145499). Plays a key role in coupling SMADs to the transcriptional machinery such as the mediator complex (By similarity). Regulates embryonic stem-cell self-renewal, promotes cell proliferation and epithelial-mesenchymal transition (By similarity). Binds to SLC9A3R2 via the PDZ motif at the plasma membrane (PubMed:11118213). Binds to YWHAZ in vivo and in vitro through the phosphoserine-binding motif RSHSSP (PubMed:11118213). Interacts (via coiled-coil domain) with SMAD2 (via MH1 domain), SMAD3 and SMAD4 (By similarity). Interacts with MED15 (By similarity). Interacts with PAX8 and NKX2-1 (By similarity). Interacts with TEAD1, TEAD2, TEAD3 and TEAD4 (By similarity). Interacts (via WW domain) with PALS1 (PubMed:21145499). Interacts with LATS1 (PubMed:21145499). Interacts with YAP1 (when phosphorylated at 'Ser-112') (PubMed:21145499). Interacts (via WW domain) with PRRG4 (via cytoplasmic domain) (By similarity). Concentrates along specific portions of the plasma membrane, and accumulates in punctate nuclear bodies (PubMed:11118213). When phosphorylated is retained in the cytoplasm by YWHAZ (PubMed:11118213). Can be retained in the nucleus by MED15 (By similarity). Localized in the cytoplasm in areas of epithelial cell high density (PubMed:21145499). At blastocyst stage expressed in the nucleus in trophectodermal cells, however expressed in the cytoplasm in the inner cell mass (PubMed:21145499). Highly expressed in kidney, heart, placenta and lung. The PDZ-binding motif is essential for stimulated gene transcription. It localizes the protein into both punctate nuclear foci and plasma membrane-associated complexes. Binds to transcription factors via its WW domain. Phosphorylated by LATS2 and STK3/MST2. Phosphorylation by LATS2 results in creation of 14-3-3 binding sites, retention in the cytoplasm, and functional inactivation (By similarity). Phosphorylation results in the inhibition of transcriptional coactivation through YWHAZ-mediated nuclear export.