Fig. 2

Schematic representation of the protein structure of the single (YAP1-1) and double (YAP1-2) WW domain isoforms of human YAP, and TAZ. YAP harbors a proline-rich region (Pro-rich; maroon) at its N-terminus which is lacking in TAZ. DNA-binding is primarily mediated by interaction with TEAD proteins via the TEAD-binding domain (orange), with phosphorylation on serine residue 94/51 in YAP and TAZ respectively important for this interaction. WW domains (WW1; light blue and WW2; green) mediate protein-protein interactions with PPxY containing partners including LATS and MRTFs [149] whereas the SRC homology 3 binding motif (SH3-BM; dark blue) enables YAP’s association with the SH3 domain of Yes and Src protein-tyrosine kinases. The transcriptional co-activator activity of YAP/TAZ is mediated by a strong transcriptional activation domain (TAD; red) that contains a coiled-coil (CC; yellow) motif. Nuclear localisation of YAP/TAZ is mediated by a Post-synaptic density, Discs large, Zonula occludens-1-binding motif (PDZ-BM; dark grey) [150]. Phosphorylation of serine 127/89 on YAP and TAZ respectively promotes their cytoplasmic sequestration facilitated by interaction with 14-3-3-proteins. YAP and TAZ also contain phosphodegron sequences (*) whereby phosphorylation of specific residues marks YAP and TAZ for degradation by the proteasome. The number of amino acids for each protein is indicated