WWTR1_HUMAN
ID WWTR1_HUMAN Reviewed; 400 AA.
AC Q9GZV5; D3DNH7; Q8N3P2; Q9Y3W6;
DT 07-JUN-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 03-AUG-2022, entry version 172.
DE RecName: Full=WW domain-containing transcription regulator protein 1;
DE AltName: Full=Transcriptional coactivator with PDZ-binding motif;
GN Name=WWTR1; Synonyms=TAZ;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, AND TISSUE
RP SPECIFICITY.
RX PubMed=11118213; DOI=10.1093/emboj/19.24.6778;
RA Kanai F., Marignani P.A., Sarbassova D., Yagi R., Hall R.A., Donowitz M.,
RA Hisaminato A., Fujiwara T., Ito Y., Cantley L.C., Yaffe M.B.;
RT "TAZ: a novel transcriptional co-activator regulated by interactions with
RT 14-3-3 and PDZ domain proteins.";
RL EMBO J. 19:6778-6791(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Embryo;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Placenta;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 3-400.
RC TISSUE=Amygdala, and Uterus;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling
RT networks.";
RL Cell 127:635-648(2006).
RN [7]
RP FUNCTION, PHOSPHORYLATION AT SER-89 AND SER-311, AND MUTAGENESIS OF SER-89
RP AND SER-311.
RX PubMed=18227151; DOI=10.1128/mcb.01874-07;
RA Lei Q.Y., Zhang H., Zhao B., Zha Z.Y., Bai F., Pei X.H., Zhao S., Xiong Y.,
RA Guan K.L.;
RT "TAZ promotes cell proliferation and epithelial-mesenchymal transition and
RT is inhibited by the hippo pathway.";
RL Mol. Cell. Biol. 28:2426-2436(2008).
RN [8]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH SMAD2; SMAD3; SMAD4
RP AND MED15.
RX PubMed=18568018; DOI=10.1038/ncb1748;
RA Varelas X., Sakuma R., Samavarchi-Tehrani P., Peerani R., Rao B.M.,
RA Dembowy J., Yaffe M.B., Zandstra P.W., Wrana J.L.;
RT "TAZ controls Smad nucleocytoplasmic shuttling and regulates human
RT embryonic stem-cell self-renewal.";
RL Nat. Cell Biol. 10:837-848(2008).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-105, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [10]
RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH PAX8 AND NKX2-1, AND
RP TISSUE SPECIFICITY.
RX PubMed=19010321; DOI=10.1016/j.yexcr.2008.10.016;
RA Di Palma T., D'Andrea B., Liguori G.L., Liguoro A., de Cristofaro T.,
RA Del Prete D., Pappalardo A., Mascia A., Zannini M.;
RT "TAZ is a coactivator for Pax8 and TTF-1, two transcription factors
RT involved in thyroid differentiation.";
RL Exp. Cell Res. 315:162-175(2009).
RN [11]
RP INTERACTION WITH TEAD1; TEAD2; TEAD3 AND TEAD4, AND MUTAGENESIS OF SER-51.
RX PubMed=19324877; DOI=10.1074/jbc.m900843200;
RA Zhang H., Liu C.Y., Zha Z.Y., Zhao B., Yao J., Zhao S., Xiong Y., Lei Q.Y.,
RA Guan K.L.;
RT "TEAD transcription factors mediate the function of TAZ in cell growth and
RT epithelial-mesenchymal transition.";
RL J. Biol. Chem. 284:13355-13362(2009).
RN [12]
RP INTERACTION WITH PALS1, AND SUBCELLULAR LOCATION.
RX PubMed=21145499; DOI=10.1016/j.devcel.2010.11.012;
RA Varelas X., Samavarchi-Tehrani P., Narimatsu M., Weiss A., Cockburn K.,
RA Larsen B.G., Rossant J., Wrana J.L.;
RT "The Crumbs complex couples cell density sensing to Hippo-dependent control
RT of the TGF-beta-SMAD pathway.";
RL Dev. Cell 19:831-844(2010).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-105, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [14]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [15]
RP INTERACTION WITH PRRG4, AND MUTAGENESIS OF SER-89; 111-ALA--ALA-158 AND
RP 394-GLU--LEU-400.
RX PubMed=23873930; DOI=10.1074/jbc.m113.484683;
RA Yazicioglu M.N., Monaldini L., Chu K., Khazi F.R., Murphy S.L., Huang H.,
RA Margaritis P., High K.A.;
RT "Cellular localization and characterization of cytosolic binding partners
RT for Gla domain-containing proteins PRRG4 and PRRG2.";
RL J. Biol. Chem. 288:25908-25914(2013).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-62 AND SER-295, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [17]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [18]
RP SUBCELLULAR LOCATION.
RX PubMed=25849865; DOI=10.1038/ncomms7781;
RA Kim J., Jo H., Hong H., Kim M.H., Kim J.M., Lee J.K., Heo W.D., Kim J.;
RT "Actin remodelling factors control ciliogenesis by regulating YAP/TAZ
RT activity and vesicle trafficking.";
RL Nat. Commun. 6:6781-6781(2015).
CC -!- FUNCTION: Transcriptional coactivator which acts as a downstream
CC regulatory target in the Hippo signaling pathway that plays a pivotal
CC role in organ size control and tumor suppression by restricting
CC proliferation and promoting apoptosis (PubMed:11118213,
CC PubMed:18227151). The core of this pathway is composed of a kinase
CC cascade wherein STK3/MST2 and STK4/MST1, in complex with its regulatory
CC protein SAV1, phosphorylates and activates LATS1/2 in complex with its
CC regulatory protein MOB1, which in turn phosphorylates and inactivates
CC YAP1 oncoprotein and WWTR1/TAZ (PubMed:18227151). WWTR1 enhances PAX8
CC and NKX2-1/TTF1-dependent gene activation (PubMed:19010321). In
CC conjunction with YAP1, involved in the regulation of TGFB1-dependent
CC SMAD2 and SMAD3 nuclear accumulation (PubMed:18568018). Plays a key
CC role in coupling SMADs to the transcriptional machinery such as the
CC mediator complex (PubMed:18568018). Regulates embryonic stem-cell self-
CC renewal, promotes cell proliferation and epithelial-mesenchymal
CC transition (PubMed:18227151, PubMed:18568018).
CC {ECO:0000269|PubMed:11118213, ECO:0000269|PubMed:18227151,
CC ECO:0000269|PubMed:18568018, ECO:0000269|PubMed:19010321}.
CC -!- SUBUNIT: Binds to SLC9A3R2 via the PDZ motif at the plasma membrane (By
CC similarity). Binds to YWHAZ in vivo and in vitro through the
CC phosphoserine-binding motif RSHSSP (By similarity). Interacts (via
CC coiled-coil domain) with SMAD2 (via MH1 domain), SMAD3 and SMAD4
CC (PubMed:18568018). Interacts with MED15 (PubMed:18568018). Interacts
CC with PAX8 and NKX2-1 (PubMed:19010321). Interacts with TEAD1, TEAD2,
CC TEAD3 and TEAD4 (PubMed:19324877). Interacts (via WW domain) with PALS1
CC (PubMed:21145499). Interacts with LATS1 (By similarity). Interacts with
CC YAP1 (when phosphorylated at 'Ser-127') (By similarity). Interacts (via
CC WW domain) with PRRG4 (via cytoplasmic domain) (PubMed:23873930).
CC {ECO:0000250|UniProtKB:Q9EPK5, ECO:0000269|PubMed:18568018,
CC ECO:0000269|PubMed:19010321, ECO:0000269|PubMed:19324877,
CC ECO:0000269|PubMed:21145499, ECO:0000269|PubMed:23873930}.
CC -!- INTERACTION:
CC Q9GZV5; Q96LT6: C1orf74; NbExp=3; IntAct=EBI-747743, EBI-12049899;
CC Q9GZV5; Q8IX12: CCAR1; NbExp=2; IntAct=EBI-747743, EBI-356265;
CC Q9GZV5; P35222: CTNNB1; NbExp=4; IntAct=EBI-747743, EBI-491549;
CC Q9GZV5; O14640: DVL1; NbExp=2; IntAct=EBI-747743, EBI-723489;
CC Q9GZV5; O14641: DVL2; NbExp=4; IntAct=EBI-747743, EBI-740850;
CC Q9GZV5; Q14005-2: IL16; NbExp=3; IntAct=EBI-747743, EBI-17178971;
CC Q9GZV5; O95835: LATS1; NbExp=5; IntAct=EBI-747743, EBI-444209;
CC Q9GZV5; Q9BZD6: PRRG4; NbExp=4; IntAct=EBI-747743, EBI-3918643;
CC Q9GZV5; Q8WWV3: RTN4IP1; NbExp=3; IntAct=EBI-747743, EBI-743502;
CC Q9GZV5; Q14160: SCRIB; NbExp=3; IntAct=EBI-747743, EBI-357345;
CC Q9GZV5; Q9NUJ3: TCP11L1; NbExp=3; IntAct=EBI-747743, EBI-2555179;
CC Q9GZV5; P28347-2: TEAD1; NbExp=3; IntAct=EBI-747743, EBI-12151837;
CC Q9GZV5; Q15562-2: TEAD2; NbExp=3; IntAct=EBI-747743, EBI-9370956;
CC Q9GZV5; Q99594: TEAD3; NbExp=3; IntAct=EBI-747743, EBI-746720;
CC Q9GZV5; Q15561: TEAD4; NbExp=9; IntAct=EBI-747743, EBI-747736;
CC Q9GZV5; Q969T9: WBP2; NbExp=6; IntAct=EBI-747743, EBI-727055;
CC Q9GZV5; P62258: YWHAE; NbExp=3; IntAct=EBI-747743, EBI-356498;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:11118213,
CC ECO:0000269|PubMed:18568018, ECO:0000269|PubMed:19010321,
CC ECO:0000269|PubMed:21145499, ECO:0000269|PubMed:25849865}. Cytoplasm
CC {ECO:0000269|PubMed:18568018, ECO:0000269|PubMed:25849865}. Cell
CC membrane {ECO:0000269|PubMed:11118213}. Note=Concentrates along
CC specific portions of the plasma membrane, and accumulates in punctate
CC nuclear bodies (By similarity). When phosphorylated, is retained in the
CC cytoplasm by YWHAZ (By similarity). Can be retained in the nucleus by
CC MED15 (PubMed:18568018). Localized in the cytoplasm in areas of
CC epithelial cell high density (PubMed:21145499). At blastocyst stage
CC expressed in the nucleus in trophectodermal cells, however expressed in
CC the cytoplasm in the inner cell mass (By similarity).
CC {ECO:0000250|UniProtKB:Q9EPK5, ECO:0000269|PubMed:18568018,
CC ECO:0000269|PubMed:21145499}.
CC -!- TISSUE SPECIFICITY: Highly expressed in kidney, heart, placenta and
CC lung. Expressed in the thyroid tissue. {ECO:0000269|PubMed:11118213,
CC ECO:0000269|PubMed:19010321}.
CC -!- DOMAIN: The PDZ-binding motif is essential for stimulated gene
CC transcription. It localizes the protein into both punctate nuclear foci
CC and plasma membrane-associated complexes (By similarity).
CC {ECO:0000250}.
CC -!- DOMAIN: Binds to transcription factors via its WW domain.
CC -!- PTM: Phosphorylated by LATS2 and STK3/MST2. Phosphorylation by LATS2
CC results in creation of 14-3-3 binding sites, retention in the
CC cytoplasm, and functional inactivation. Phosphorylation results in the
CC inhibition of transcriptional coactivation through YWHAZ-mediated
CC nuclear export. {ECO:0000269|PubMed:18227151}.
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DR EMBL; AJ299431; CAC17722.1; -; mRNA.
DR EMBL; AK022036; BAB13957.1; -; mRNA.
DR EMBL; CH471052; EAW78868.1; -; Genomic_DNA.
DR EMBL; CH471052; EAW78869.1; -; Genomic_DNA.
DR EMBL; BC014052; AAH14052.1; -; mRNA.
DR EMBL; AL050107; CAB43275.1; -; mRNA.
DR EMBL; AL833852; CAD38711.1; -; mRNA.
DR CCDS; CCDS3144.1; -.
DR PIR; T08755; T08755.
DR RefSeq; NP_001161750.1; NM_001168278.2.
DR RefSeq; NP_001161752.1; NM_001168280.2.
DR RefSeq; NP_001335291.1; NM_001348362.1.
DR RefSeq; NP_056287.1; NM_015472.5.
DR RefSeq; XP_016861611.1; XM_017006122.1.
DR PDB; 5N5R; X-ray; 1.80 A; P=87-95.
DR PDB; 5N5T; X-ray; 1.80 A; P=87-94.
DR PDB; 5N5W; X-ray; 1.37 A; P=86-95.
DR PDB; 5N75; X-ray; 1.80 A; P=86-95.
DR PDB; 6RHC; X-ray; 1.20 A; P=86-98.
DR PDB; 6RJL; X-ray; 1.28 A; P=86-98.
DR PDB; 6RJQ; X-ray; 1.89 A; P=86-98.
DR PDB; 6RP6; X-ray; 1.89 A; P=86-98.
DR PDB; 6SLW; X-ray; 2.00 A; P=86-98.
DR PDB; 6SLX; X-ray; 1.80 A; P=86-98.
DR PDBsum; 5N5R; -.
DR PDBsum; 5N5T; -.
DR PDBsum; 5N5W; -.
DR PDBsum; 5N75; -.
DR PDBsum; 6RHC; -.
DR PDBsum; 6RJL; -.
DR PDBsum; 6RJQ; -.
DR PDBsum; 6RP6; -.
DR PDBsum; 6SLW; -.
DR PDBsum; 6SLX; -.
DR AlphaFoldDB; Q9GZV5; -.
DR SMR; Q9GZV5; -.
DR BioGRID; 117434; 52.
DR CORUM; Q9GZV5; -.
DR ELM; Q9GZV5; -.
DR IntAct; Q9GZV5; 45.
DR MINT; Q9GZV5; -.
DR STRING; 9606.ENSP00000419465; -.
DR iPTMnet; Q9GZV5; -.
DR PhosphoSitePlus; Q9GZV5; -.
DR BioMuta; WWTR1; -.
DR DMDM; 67462080; -.
DR EPD; Q9GZV5; -.
DR jPOST; Q9GZV5; -.
DR MassIVE; Q9GZV5; -.
DR MaxQB; Q9GZV5; -.
DR PaxDb; Q9GZV5; -.
DR PeptideAtlas; Q9GZV5; -.
DR PRIDE; Q9GZV5; -.
DR ProteomicsDB; 80157; -.
DR Antibodypedia; 1743; 377 antibodies from 36 providers.
DR DNASU; 25937; -.
DR Ensembl; ENST00000360632.8; ENSP00000353847.3; ENSG00000018408.15.
DR Ensembl; ENST00000465804.5; ENSP00000419465.1; ENSG00000018408.15.
DR Ensembl; ENST00000467467.5; ENSP00000419234.1; ENSG00000018408.15.
DR GeneID; 25937; -.
DR KEGG; hsa:25937; -.
DR MANE-Select; ENST00000360632.8; ENSP00000353847.3; NM_015472.6; NP_056287.1.
DR UCSC; uc003exf.4; human.
DR CTD; 25937; -.
DR DisGeNET; 25937; -.
DR GeneCards; WWTR1; -.
DR HGNC; HGNC:24042; WWTR1.
DR HPA; ENSG00000018408; Low tissue specificity.
DR MalaCards; WWTR1; -.
DR MIM; 607392; gene.
DR neXtProt; NX_Q9GZV5; -.
DR OpenTargets; ENSG00000018408; -.
DR Orphanet; 157791; Epithelioid hemangioendothelioma.
DR PharmGKB; PA134899667; -.
DR VEuPathDB; HostDB:ENSG00000018408; -.
DR eggNOG; KOG0940; Eukaryota.
DR GeneTree; ENSGT00510000046760; -.
DR HOGENOM; CLU_041917_0_0_1; -.
DR InParanoid; Q9GZV5; -.
DR OMA; AVNTPAM; -.
DR OrthoDB; 1006566at2759; -.
DR PhylomeDB; Q9GZV5; -.
DR TreeFam; TF326941; -.
DR PathwayCommons; Q9GZV5; -.
DR Reactome; R-HSA-2028269; Signaling by Hippo.
DR Reactome; R-HSA-2032785; YAP1- and WWTR1 (TAZ)-stimulated gene expression.
DR Reactome; R-HSA-2173795; Downregulation of SMAD2/3:SMAD4 transcriptional activity.
DR Reactome; R-HSA-2173796; SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription.
DR Reactome; R-HSA-5578768; Physiological factors.
DR Reactome; R-HSA-8940973; RUNX2 regulates osteoblast differentiation.
DR Reactome; R-HSA-8951671; RUNX3 regulates YAP1-mediated transcription.
DR Reactome; R-HSA-9619665; EGR2 and SOX10-mediated initiation of Schwann cell myelination.
DR SignaLink; Q9GZV5; -.
DR SIGNOR; Q9GZV5; -.
DR BioGRID-ORCS; 25937; 243 hits in 1074 CRISPR screens.
DR ChiTaRS; WWTR1; human.
DR GeneWiki; WWTR1; -.
DR GenomeRNAi; 25937; -.
DR Pharos; Q9GZV5; Tbio.
DR PRO; PR:Q9GZV5; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; Q9GZV5; protein.
DR Bgee; ENSG00000018408; Expressed in tibia and 216 other tissues.
DR ExpressionAtlas; Q9GZV5; baseline and differential.
DR Genevisible; Q9GZV5; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0016604; C:nuclear body; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005667; C:transcription regulator complex; IEA:Ensembl.
DR GO; GO:0042803; F:protein homodimerization activity; IEA:Ensembl.
DR GO; GO:0003713; F:transcription coactivator activity; IDA:UniProtKB.
DR GO; GO:0003714; F:transcription corepressor activity; IBA:GO_Central.
DR GO; GO:0060271; P:cilium assembly; IEA:Ensembl.
DR GO; GO:0032835; P:glomerulus development; IEA:Ensembl.
DR GO; GO:0003015; P:heart process; IEA:Ensembl.
DR GO; GO:0035329; P:hippo signaling; IDA:UniProtKB.
DR GO; GO:0060993; P:kidney morphogenesis; IEA:Ensembl.
DR GO; GO:0048762; P:mesenchymal cell differentiation; IEA:Ensembl.
DR GO; GO:0035264; P:multicellular organism growth; IEA:Ensembl.
DR GO; GO:0090090; P:negative regulation of canonical Wnt signaling pathway; IMP:BHF-UCL.
DR GO; GO:0045599; P:negative regulation of fat cell differentiation; IGI:ARUK-UCL.
DR GO; GO:0006469; P:negative regulation of protein kinase activity; IMP:BHF-UCL.
DR GO; GO:0001933; P:negative regulation of protein phosphorylation; IMP:BHF-UCL.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IEA:Ensembl.
DR GO; GO:0001649; P:osteoblast differentiation; IEA:Ensembl.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IDA:UniProtKB.
DR GO; GO:0010718; P:positive regulation of epithelial to mesenchymal transition; IDA:UniProtKB.
DR GO; GO:0045669; P:positive regulation of osteoblast differentiation; IGI:ARUK-UCL.
DR GO; GO:1900182; P:positive regulation of protein localization to nucleus; ISS:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0016567; P:protein ubiquitination; IEA:Ensembl.
DR GO; GO:0072307; P:regulation of metanephric nephron tubule epithelial cell differentiation; IEA:Ensembl.
DR GO; GO:0060390; P:regulation of SMAD protein signal transduction; IDA:UniProtKB.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; NAS:UniProtKB.
DR GO; GO:0031146; P:SCF-dependent proteasomal ubiquitin-dependent protein catabolic process; IEA:Ensembl.
DR GO; GO:0017145; P:stem cell division; IDA:UniProtKB.
DR GO; GO:0001894; P:tissue homeostasis; IEA:Ensembl.
DR CDD; cd00201; WW; 1.
DR InterPro; IPR001202; WW_dom.
DR InterPro; IPR036020; WW_dom_sf.
DR Pfam; PF00397; WW; 1.
DR SMART; SM00456; WW; 1.
DR SUPFAM; SSF51045; SSF51045; 1.
DR PROSITE; PS01159; WW_DOMAIN_1; 1.
DR PROSITE; PS50020; WW_DOMAIN_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Activator; Cell membrane; Coiled coil; Cytoplasm; Membrane;
KW Nucleus; Phosphoprotein; Proto-oncogene; Reference proteome; Transcription;
KW Transcription regulation.
FT CHAIN 1..400
FT /note="WW domain-containing transcription regulator protein
FT 1"
FT /id="PRO_0000076069"
FT DOMAIN 124..157
FT /note="WW"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00224"
FT REGION 52..117
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 222..400
FT /note="Required for interaction with PALS1"
FT /evidence="ECO:0000269|PubMed:21145499"
FT COILED 225..259
FT /evidence="ECO:0000255"
FT MOTIF 394..400
FT /note="PDZ-binding"
FT COMPBIAS 58..72
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 62
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 89
FT /note="Phosphoserine; by LATS2"
FT /evidence="ECO:0000269|PubMed:18227151"
FT MOD_RES 105
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231"
FT MOD_RES 295
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 311
FT /note="Phosphoserine; by LATS2"
FT /evidence="ECO:0000269|PubMed:18227151"
FT MUTAGEN 51
FT /note="S->A,D: Loss of interaction with TEAD4."
FT /evidence="ECO:0000269|PubMed:19324877"
FT MUTAGEN 89
FT /note="S->A: Significant resistance to inhibition by
FT STK3/MST2 and LATS2. No effect on binding to PRRG4."
FT /evidence="ECO:0000269|PubMed:18227151,
FT ECO:0000269|PubMed:23873930"
FT MUTAGEN 111..158
FT /note="Missing: Reduced binding to PRRG4."
FT /evidence="ECO:0000269|PubMed:23873930"
FT MUTAGEN 311
FT /note="S->A: Partial resistance to inhibition by MST2 and
FT LATS2."
FT /evidence="ECO:0000269|PubMed:18227151"
FT MUTAGEN 394..400
FT /note="Missing: No effect on binding to PRRG4."
FT /evidence="ECO:0000269|PubMed:23873930"
SQ SEQUENCE 400 AA; 44101 MW; 630B50F46FB74C60 CRC64;
MNPASAPPPL PPPGQQVIHV TQDLDTDLEA LFNSVMNPKP SSWRKKILPE SFFKEPDSGS
HSRQSSTDSS GGHPGPRLAG GAQHVRSHSS PASLQLGTGA GAAGSPAQQH AHLRQQSYDV
TDELPLPPGW EMTFTATGQR YFLNHIEKIT TWQDPRKAMN QPLNHMNLHP AVSSTPVPQR
SMAVSQPNLV MNHQHQQQMA PSTLSQQNHP TQNPPAGLMS MPNALTTQQQ QQQKLRLQRI
QMERERIRMR QEELMRQEAA LCRQLPMEAE TLAPVQAAVN PPTMTPDMRS ITNNSSDPFL
NGGPYHSREQ STDSGLGLGC YSVPTTPEDF LSNVDEMDTG ENAGQTPMNI NPQQTRFPDF
LDCLPGTNVD LGTLESEDLI PLFNDVESAL NKSEPFLTWL
