ID:WWTR1_HUMAN DESCRIPTION: RecName: Full=WW domain-containing transcription regulator protein 1; AltName: Full=Transcriptional coactivator with PDZ-binding motif; FUNCTION: 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. 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. 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. SUBUNIT: 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 (By similarity). 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. INTERACTION: Q8IX12:CCAR1; NbExp=2; IntAct=EBI-747743, EBI-356265; O95835:LATS1; NbExp=4; IntAct=EBI-747743, EBI-444209; Q15561:TEAD4; NbExp=2; IntAct=EBI-747743, EBI-747736; Q969T9:WBP2; NbExp=6; IntAct=EBI-747743, EBI-727055; SUBCELLULAR LOCATION: Nucleus. Cytoplasm. Note=Concentrates along specific portions of the plasma membrane, and accumulates in punctate nuclear bodies. When phosphorylated, is retained in cytoplasm by YWHAZ. Can be retained in the nucleus by MED15. TISSUE SPECIFICITY: Highly expressed in kidney, heart, placenta and lung. Expressed in the thyroid tissue. DOMAIN: The PDZ-binding motif is essential for stimulated gene transcription. It localizes the protein into both punctate nuclear foci and plasma membrane-associated complexes (By similarity). DOMAIN: Binds to transcription factors via its WW domain. PTM: 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. Phosphorylation results in the inhibition of transcriptional coactivation through YWHAZ-mediated nuclear export. SIMILARITY: Contains 1 WW domain.
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on Q9GZV5
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
US Server
Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
