BioPAX pathway converted from "WWTR1 (TAZ) binds ZO-2 (TJP2)" in the Reactome database. LEFT-TO-RIGHT WWTR1 (TAZ) binds ZO-2 (TJP2) Cytosolic ZO-2 (TJP2) binds WWTR1 (TAZ) to form a complex. This event may play a role in sequestering WWTR1 in the cytosol (Remue et al. 2010). The phosphorylation state of the WWTR1 protein involved in this interaction has not been determined experimentally; it is inferred to be unphosphorylated. Authored: D'Eustachio, P, 2012-02-03 Reviewed: Sudol, M, 2012-02-03 Edited: D'Eustachio, P, 2012-01-18 TAZ WWTR1 WW domain-containing transcription regulator protein 1 Transcriptional coactivator with PDZ-binding motif Reactome DB_ID: 1629773 cytosol GENE ONTOLOGY GO:0005829 UniProt:Q9GZV5 WWTR1 WWTR1 TAZ 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 (PubMed:11118213, PubMed:18227151). 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 (PubMed:18227151). WWTR1 enhances PAX8 and NKX2-1/TTF1-dependent gene activation (PubMed:19010321). In conjunction with YAP1, involved in the regulation of TGFB1-dependent SMAD2 and SMAD3 nuclear accumulation (PubMed:18568018). Plays a key role in coupling SMADs to the transcriptional machinery such as the mediator complex (PubMed:18568018). Regulates embryonic stem-cell self-renewal, promotes cell proliferation and epithelial-mesenchymal transition (PubMed:18227151, PubMed:18568018).SUBUNIT Binds to SLC9A3R2 via the PDZ motif at the plasma membrane (By similarity). 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 (PubMed:18568018). Interacts with MED15 (PubMed:18568018). Interacts with PAX8 and NKX2-1 (PubMed:19010321). Interacts with TEAD1, TEAD2, TEAD3 and TEAD4 (PubMed:19324877). Interacts (via WW domain) with PALS1 (PubMed:21145499). Interacts with LATS1 (By similarity). Interacts with YAP1 (when phosphorylated at 'Ser-127') (By similarity). Interacts (via WW domain) with PRRG4 (via cytoplasmic domain) (PubMed:23873930).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. Homo sapiens NCBI Taxonomy 9606 UniProt Q9GZV5 1 EQUAL 400 EQUAL Reactome Database ID Release 82 1629773 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=1629773 Reactome R-HSA-1629773 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-1629773.1 Reactome http://www.reactome.org TJP2 ZO-2 Tight junction protein 2 Zonula occludens protein 2 Reactome DB_ID: 2064412 UniProt:Q9UDY2 TJP2 TJP2 X104 ZO2 FUNCTION Plays a role in tight junctions and adherens junctions.SUBUNIT Homodimer (PubMed:17897942). Interacts with TJP1/ZO1 (PubMed:17897942). Interacts with occludin, SAFB and UBN1. Interaction with SAFB occurs in the nucleus. Interacts with SCRIB. Interacts with USP53 (via the C-terminal region) (By similarity). Interacts with claudins, including CLDN1, CLDN2, CLDN3, CLDN5 and CLDN7 (PubMed:12704386).TISSUE SPECIFICITY This protein is found in epithelial cell junctions. Isoform A1 is abundant in the heart and brain. Detected in brain and skeletal muscle. It is present almost exclusively in normal tissues. Isoform C1 is expressed at high level in the kidney, pancreas, heart and placenta. Not detected in brain and skeletal muscle. Found in normal as well as in most neoplastic tissues.SIMILARITY Belongs to the MAGUK family. UniProt Q9UDY2 1 EQUAL 1190 EQUAL Reactome Database ID Release 82 2064412 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2064412 Reactome R-HSA-2064412 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-2064412.1 TAZ:TJP2 WWTR1:TJP2 WWTR1:ZO-2 TAZ:ZO-2 Reactome DB_ID: 2064405 1 1 Reactome Database ID Release 82 2064405 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2064405 Reactome R-HSA-2064405 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-2064405.1 Reactome Database ID Release 82 2064418 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2064418 Reactome R-HSA-2064418 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-2064418.1 20850437 Pubmed 2010 TAZ interacts with zonula occludens-1 and -2 proteins in a PDZ-1 dependent manner Remue, E Meerschaert, K Oka, T Boucherie, C Vandekerckhove, J Sudol, M Gettemans, J FEBS Lett 584:4175-80