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Protein

WW domain-containing transcription regulator protein 1

Gene

Wwtr1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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 (By similarity).By similarity1 Publication

GO - Molecular functioni

  • protein homodimerization activity Source: UniProtKB
  • transcription coactivator activity Source: UniProtKB
  • transcription corepressor activity Source: MGI

GO - Biological processi

  • cilium morphogenesis Source: MGI
  • glomerulus development Source: MGI
  • hippo signaling Source: MGI
  • kidney morphogenesis Source: MGI
  • mesenchymal cell differentiation Source: MGI
  • multicellular organism growth Source: MGI
  • negative regulation of canonical Wnt signaling pathway Source: MGI
  • negative regulation of catenin import into nucleus Source: MGI
  • negative regulation of fat cell differentiation Source: MGI
  • negative regulation of protein kinase activity Source: MGI
  • negative regulation of protein phosphorylation Source: MGI
  • negative regulation of transcription from RNA polymerase II promoter Source: MGI
  • osteoblast differentiation Source: MGI
  • positive regulation of cell proliferation Source: MGI
  • positive regulation of epithelial to mesenchymal transition Source: MGI
  • positive regulation of transcription from RNA polymerase II promoter Source: MGI
  • protein ubiquitination Source: MGI
  • regulation of canonical Wnt signaling pathway Source: MGI
  • regulation of metanephric nephron tubule epithelial cell differentiation Source: MGI
  • regulation of SMAD protein import into nucleus Source: MGI
  • regulation of transcription, DNA-templated Source: MGI
  • SCF-dependent proteasomal ubiquitin-dependent protein catabolic process Source: MGI
  • stem cell division Source: MGI
  • transcription, DNA-templated Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Activator

Keywords - Biological processi

Transcription, Transcription regulation

Enzyme and pathway databases

ReactomeiR-MMU-2028269. Signaling by Hippo.
R-MMU-2032785. YAP1- and WWTR1 (TAZ)-stimulated gene expression.
R-MMU-2173796. SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription.

Names & Taxonomyi

Protein namesi
Recommended name:
WW domain-containing transcription regulator protein 1
Alternative name(s):
Transcriptional coactivator with PDZ-binding motif
Gene namesi
Name:Wwtr1
Synonyms:Taz
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 3

Organism-specific databases

MGIiMGI:1917649. Wwtr1.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: MGI
  • nucleoplasm Source: MGI
  • nucleus Source: MGI
  • transcription factor complex Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi89 – 891S → A: Loss of YWHAZ binding with increased nuclear localization. Partial recovery of nuclear accumulation; when associated with deletion of 392-L--L-395. 1 Publication
Mutagenesisi392 – 3954Missing : Loss of SLC9A3R2 binding and reduced nuclear localization. Partial recovery of nuclear accumulation; when associated with A-89. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 395395WW domain-containing transcription regulator protein 1PRO_0000076070Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei89 – 891PhosphoserineCombined sources
Modified residuei89 – 891Phosphoserine; by LATS2By similarity
Modified residuei306 – 3061Phosphoserine; by LATS2By similarity

Post-translational modificationi

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 (By similarity). Phosphorylation results in the inhibition of transcriptional coactivation through YWHAZ-mediated nuclear export.By similarity1 Publication

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiQ9EPK5.
PaxDbiQ9EPK5.
PRIDEiQ9EPK5.

PTM databases

iPTMnetiQ9EPK5.
PhosphoSiteiQ9EPK5.

Expressioni

Tissue specificityi

Highly expressed in kidney, heart, placenta and lung.1 Publication

Gene expression databases

BgeeiQ9EPK5.
CleanExiMM_WWTR1.
GenevisibleiQ9EPK5. MM.

Interactioni

Subunit structurei

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. 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 (By similarity).By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
Axin1O356254EBI-1211920,EBI-2365912
CCAR1Q8IX125EBI-1211920,EBI-356265From a different organism.
CTNNB1P352222EBI-1211920,EBI-491549From a different organism.
Nkx2-1P234413EBI-1211920,EBI-1223127From a different organism.
TJP1Q071574EBI-1211920,EBI-79553From a different organism.
TJP2Q951684EBI-1211920,EBI-8304003From a different organism.

GO - Molecular functioni

  • protein homodimerization activity Source: UniProtKB

Protein-protein interaction databases

BioGridi220584. 43 interactions.
DIPiDIP-39476N.
IntActiQ9EPK5. 16 interactions.
MINTiMINT-4123841.
STRINGi10090.ENSMUSP00000113040.

Structurei

3D structure databases

ProteinModelPortaliQ9EPK5.
SMRiQ9EPK5. Positions 14-57, 123-157.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini124 – 15734WWPROSITE-ProRule annotationAdd
BLAST

Coiled coil

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Coiled coili224 – 25835Sequence analysisAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi389 – 3957PDZ-bindingBy similarity

Domaini

The PDZ-binding motif is essential for stimulated gene transcription. It localizes the protein into both punctate nuclear foci and plasma membrane-associated complexes.
Binds to transcription factors via its WW domain.

Sequence similaritiesi

Contains 1 WW domain.PROSITE-ProRule annotation

Keywords - Domaini

Coiled coil

Phylogenomic databases

eggNOGiENOG410KCVW. Eukaryota.
ENOG4111U1C. LUCA.
GeneTreeiENSGT00510000046760.
HOGENOMiHOG000007854.
HOVERGENiHBG002748.
InParanoidiQ9EPK5.
KOiK16820.
OMAiSQQNHPP.
OrthoDBiEOG75MVW6.
PhylomeDBiQ9EPK5.
TreeFamiTF326941.

Family and domain databases

InterProiIPR001202. WW_dom.
[Graphical view]
PfamiPF00397. WW. 1 hit.
[Graphical view]
SMARTiSM00456. WW. 1 hit.
[Graphical view]
SUPFAMiSSF51045. SSF51045. 1 hit.
PROSITEiPS01159. WW_DOMAIN_1. 1 hit.
PS50020. WW_DOMAIN_2. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9EPK5-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MNPSSVPHPL PPPGQQVIHV TQDLDTDLEA LFNSVMNPKP SSWRKKILPE
60 70 80 90 100
SFFKEPDSGS HSRQSSTDSS GGHPGPRLAG GAQHVRSHSS PASLQLGTGA
110 120 130 140 150
GAAGGPAQQH AHLRQQSYDV TDELPLPPGW EMTFTATGQR YFLNHIEKIT
160 170 180 190 200
TWQDPRKVMN QPLNHVNLHP SITSTSVPQR SMAVSQPNLA MNHQHQQVVA
210 220 230 240 250
TSLSPQNHPT QNQPTGLMSV PNALTTQQQQ QQKLRLQRIQ MERERIRMRQ
260 270 280 290 300
EELMRQEAAL CRQLPMETET MAPVNTPAMS TDMRSVTNSS SDPFLNGGPY
310 320 330 340 350
HSREQSTDSG LGLGCYSVPT TPEDFLSNMD EMDTGENSGQ TPMTVNPQQT
360 370 380 390
RFPDFLDCLP GTNVDLGTLE SEDLIPLFND VESALNKSEP FLTWL
Length:395
Mass (Da):43,620
Last modified:June 7, 2005 - v2
Checksum:i1B8A7487D4CA341C
GO
Isoform 2 (identifier: Q9EPK5-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MHNSTAPLSARLFPKGGSLLQTLFMGQSGSRGGCARLRLLCRLLAQWERPRPVPGIKM

Note: No experimental confirmation available.
Show »
Length:452
Mass (Da):49,834
Checksum:i6A8D7114823BA29F
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti384 – 3841A → V in CAC17733 (PubMed:11118213).Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 11M → MHNSTAPLSARLFPKGGSLL QTLFMGQSGSRGGCARLRLL CRLLAQWERPRPVPGIKM in isoform 2. 1 PublicationVSP_026137

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ299430 mRNA. Translation: CAC17733.1.
AK142299 mRNA. Translation: BAE25019.1.
AK142720 mRNA. Translation: BAE25174.1.
BC004640 mRNA. Translation: AAH04640.1.
BC014727 mRNA. Translation: AAH14727.1.
CCDSiCCDS38434.1. [Q9EPK5-1]
CCDS50912.1. [Q9EPK5-2]
RefSeqiNP_001161753.1. NM_001168281.1. [Q9EPK5-2]
NP_598545.2. NM_133784.3. [Q9EPK5-1]
UniGeneiMm.405029.

Genome annotation databases

EnsembliENSMUST00000029380; ENSMUSP00000029380; ENSMUSG00000027803. [Q9EPK5-1]
ENSMUST00000120977; ENSMUSP00000113040; ENSMUSG00000027803. [Q9EPK5-2]
GeneIDi97064.
KEGGimmu:97064.
UCSCiuc008phb.2. mouse. [Q9EPK5-1]
uc012cpt.1. mouse. [Q9EPK5-2]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ299430 mRNA. Translation: CAC17733.1.
AK142299 mRNA. Translation: BAE25019.1.
AK142720 mRNA. Translation: BAE25174.1.
BC004640 mRNA. Translation: AAH04640.1.
BC014727 mRNA. Translation: AAH14727.1.
CCDSiCCDS38434.1. [Q9EPK5-1]
CCDS50912.1. [Q9EPK5-2]
RefSeqiNP_001161753.1. NM_001168281.1. [Q9EPK5-2]
NP_598545.2. NM_133784.3. [Q9EPK5-1]
UniGeneiMm.405029.

3D structure databases

ProteinModelPortaliQ9EPK5.
SMRiQ9EPK5. Positions 14-57, 123-157.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi220584. 43 interactions.
DIPiDIP-39476N.
IntActiQ9EPK5. 16 interactions.
MINTiMINT-4123841.
STRINGi10090.ENSMUSP00000113040.

PTM databases

iPTMnetiQ9EPK5.
PhosphoSiteiQ9EPK5.

Proteomic databases

MaxQBiQ9EPK5.
PaxDbiQ9EPK5.
PRIDEiQ9EPK5.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000029380; ENSMUSP00000029380; ENSMUSG00000027803. [Q9EPK5-1]
ENSMUST00000120977; ENSMUSP00000113040; ENSMUSG00000027803. [Q9EPK5-2]
GeneIDi97064.
KEGGimmu:97064.
UCSCiuc008phb.2. mouse. [Q9EPK5-1]
uc012cpt.1. mouse. [Q9EPK5-2]

Organism-specific databases

CTDi25937.
MGIiMGI:1917649. Wwtr1.

Phylogenomic databases

eggNOGiENOG410KCVW. Eukaryota.
ENOG4111U1C. LUCA.
GeneTreeiENSGT00510000046760.
HOGENOMiHOG000007854.
HOVERGENiHBG002748.
InParanoidiQ9EPK5.
KOiK16820.
OMAiSQQNHPP.
OrthoDBiEOG75MVW6.
PhylomeDBiQ9EPK5.
TreeFamiTF326941.

Enzyme and pathway databases

ReactomeiR-MMU-2028269. Signaling by Hippo.
R-MMU-2032785. YAP1- and WWTR1 (TAZ)-stimulated gene expression.
R-MMU-2173796. SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription.

Miscellaneous databases

ChiTaRSiWwtr1. mouse.
NextBioi352477.
PROiQ9EPK5.
SOURCEiSearch...

Gene expression databases

BgeeiQ9EPK5.
CleanExiMM_WWTR1.
GenevisibleiQ9EPK5. MM.

Family and domain databases

InterProiIPR001202. WW_dom.
[Graphical view]
PfamiPF00397. WW. 1 hit.
[Graphical view]
SMARTiSM00456. WW. 1 hit.
[Graphical view]
SUPFAMiSSF51045. SSF51045. 1 hit.
PROSITEiPS01159. WW_DOMAIN_1. 1 hit.
PS50020. WW_DOMAIN_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "TAZ: a novel transcriptional co-activator regulated by interactions with 14-3-3 and PDZ domain proteins."
    Kanai F., Marignani P.A., Sarbassova D., Yagi R., Hall R.A., Donowitz M., Hisaminato A., Fujiwara T., Ito Y., Cantley L.C., Yaffe M.B.
    EMBO J. 19:6778-6791(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH SLC9A3R2 AND YWHAZ, PHOSPHORYLATION AT SER-89, TISSUE SPECIFICITY, MUTAGENESIS OF SER-89 AND 392-GLU--LEU-395.
  2. "The transcriptional landscape of the mammalian genome."
    Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
    , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
    Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
    Strain: C57BL/6J.
    Tissue: Heart.
  3. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
    Strain: FVB/N.
    Tissue: Mammary tumor.
  4. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Liver.
  5. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-89, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Brown adipose tissue, Heart, Kidney and Lung.

Entry informationi

Entry nameiWWTR1_MOUSE
AccessioniPrimary (citable) accession number: Q9EPK5
Secondary accession number(s): Q3UQ69, Q3UQM0, Q99KI4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: June 7, 2005
Last sequence update: June 7, 2005
Last modified: March 16, 2016
This is version 118 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.