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MGP004784

UniProt Annotations

Entry Information
Gene NameWW domain containing transcription regulator 1
Protein EntryWWTR1_HUMAN
UniProt IDQ9GZV5
SpeciesHuman
Comments
Comment typeDescription
DomainBinds to transcription factors via its WW domain.
DomainThe 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). {ECO:0000250}.
FunctionTranscriptional 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. {ECO:0000269|PubMed:11118213, ECO:0000269|PubMed:18227151, ECO:0000269|PubMed:18568018, ECO:0000269|PubMed:19010321}.
InteractionQ8IX12:CCAR1; NbExp=2; IntAct=EBI-747743, EBI-356265; P35222:CTNNB1; NbExp=4; IntAct=EBI-747743, EBI-491549; O14640:DVL1; NbExp=2; IntAct=EBI-747743, EBI-723489; O14641:DVL2; NbExp=4; IntAct=EBI-747743, EBI-740850; O95835:LATS1; NbExp=5; IntAct=EBI-747743, EBI-444209; Q15561:TEAD4; NbExp=2; IntAct=EBI-747743, EBI-747736; Q969T9:WBP2; NbExp=6; IntAct=EBI-747743, EBI-727055; P62258:YWHAE; NbExp=3; IntAct=EBI-747743, EBI-356498;
PtmPhosphorylated 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. {ECO:0000269|PubMed:18227151, ECO:0000269|PubMed:18669648, ECO:0000269|PubMed:20068231}.
SimilarityContains 1 WW domain. {ECO:0000255|PROSITE- ProRule:PRU00224}.
Subcellular LocationNucleus. 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.
SubunitBinds 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. {ECO:0000250, ECO:0000269|PubMed:18568018, ECO:0000269|PubMed:19010321, ECO:0000269|PubMed:19324877}.
Tissue SpecificityHighly expressed in kidney, heart, placenta and lung. Expressed in the thyroid tissue. {ECO:0000269|PubMed:11118213, ECO:0000269|PubMed:19010321}.
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