Skip Header

Contribute Send feedback
Read comments (?) or add your own

Q9EPK5 (WWTR1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified May 29, 2013. Version 91. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
WW domain-containing transcription regulator protein 1
Alternative name(s):
Transcriptional coactivator with PDZ-binding motif
Gene names
Name:Wwtr1
Synonyms:Taz
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length395 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

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 By similarity. Ref.1

Subunit structure

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. Ref.1

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 By similarity. Ref.1

Tissue specificity

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

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.

Binds to transcription factors via its WW domain.

Post-translational modification

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. Ref.1

Sequence similarities

Contains 1 WW domain.

Ontologies

Keywords
   Biological processTranscription
Transcription regulation
   Cellular componentCytoplasm
Nucleus
   Coding sequence diversityAlternative splicing
   DomainCoiled coil
   Molecular functionActivator
   PTMPhosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcilium morphogenesis

Inferred from mutant phenotype PubMed 17251353. Source: MGI

glomerulus development

Inferred from mutant phenotype PubMed 18172001. Source: MGI

hippo signaling cascade

Inferred from electronic annotation. Source: Compara

negative regulation of canonical Wnt receptor signaling pathway

Inferred from electronic annotation. Source: Compara

negative regulation of catenin import into nucleus

Inferred from electronic annotation. Source: Compara

negative regulation of fat cell differentiation

Inferred from genetic interaction PubMed 16099986. Source: MGI

negative regulation of protein kinase activity

Inferred from electronic annotation. Source: Compara

negative regulation of transcription from RNA polymerase II promoter

Inferred from genetic interaction PubMed 16099986. Source: MGI

osteoblast differentiation

Inferred from mutant phenotype PubMed 16099986. Source: MGI

positive regulation of cell proliferation

Inferred from electronic annotation. Source: Compara

positive regulation of epithelial to mesenchymal transition

Inferred from electronic annotation. Source: Compara

positive regulation of transcription from RNA polymerase II promoter

Inferred from direct assay PubMed 14970209. Source: MGI

regulation of SMAD protein import into nucleus

Inferred from electronic annotation. Source: Compara

stem cell division

Inferred from electronic annotation. Source: Compara

transcription, DNA-dependent

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentcytoplasm

Inferred from direct assay Ref.1PubMed 16099986. Source: MGI

transcription factor complex

Inferred from direct assay PubMed 14970209. Source: MGI

   Molecular_functionprotein homodimerization activity

Inferred from direct assay PubMed 16332960. Source: UniProtKB

transcription coactivator activity

Inferred from direct assay PubMed 16332960. Source: UniProtKB

transcription corepressor activity

Inferred from genetic interaction PubMed 16099986. Source: MGI

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

CCAR1Q8IX125EBI-1211920,EBI-356265From a different organism.
CTNNB1P352222EBI-1211920,EBI-491549From a different organism.
Nkx2-1P234413EBI-1211920,EBI-1223127From a different organism.

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q9EPK5-1)

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.
Isoform 2 (identifier: Q9EPK5-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MHNSTAPLSARLFPKGGSLLQTLFMGQSGSRGGCARLRLLCRLLAQWERPRPVPGIKM
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 395395WW domain-containing transcription regulator protein 1
PRO_0000076070

Regions

Domain124 – 15734WW
Coiled coil224 – 25835 Potential
Motif389 – 3957PDZ-binding By similarity

Amino acid modifications

Modified residue891Phosphoserine; by LATS2 By similarity
Modified residue931Phosphoserine Ref.4
Modified residue3061Phosphoserine; by LATS2 By similarity

Natural variations

Alternative sequence11M → MHNSTAPLSARLFPKGGSLL QTLFMGQSGSRGGCARLRLL CRLLAQWERPRPVPGIKM in isoform 2.
VSP_026137

Experimental info

Mutagenesis891S → A: Loss of YWHAZ binding with increased nuclear localization. Partial recovery of nuclear accumulation; when associated with deletion of 392-L--L-395. Ref.1
Mutagenesis392 – 3954Missing: Loss of SLC9A3R2 binding and reduced nuclear localization. Partial recovery of nuclear accumulation; when associated with A-89. Ref.1
Sequence conflict3841A → V in CAC17733. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified June 7, 2005. Version 2.
Checksum: 1B8A7487D4CA341C

FASTA39543,620
        10         20         30         40         50         60 
MNPSSVPHPL PPPGQQVIHV TQDLDTDLEA LFNSVMNPKP SSWRKKILPE SFFKEPDSGS 

        70         80         90        100        110        120 
HSRQSSTDSS GGHPGPRLAG GAQHVRSHSS PASLQLGTGA GAAGGPAQQH AHLRQQSYDV 

       130        140        150        160        170        180 
TDELPLPPGW EMTFTATGQR YFLNHIEKIT TWQDPRKVMN QPLNHVNLHP SITSTSVPQR 

       190        200        210        220        230        240 
SMAVSQPNLA MNHQHQQVVA TSLSPQNHPT QNQPTGLMSV PNALTTQQQQ QQKLRLQRIQ 

       250        260        270        280        290        300 
MERERIRMRQ EELMRQEAAL CRQLPMETET MAPVNTPAMS TDMRSVTNSS SDPFLNGGPY 

       310        320        330        340        350        360 
HSREQSTDSG LGLGCYSVPT TPEDFLSNMD EMDTGENSGQ TPMTVNPQQT RFPDFLDCLP 

       370        380        390 
GTNVDLGTLE SEDLIPLFND VESALNKSEP FLTWL 

« Hide

Isoform 2 [UniParc].

Checksum: 6A8D7114823BA29F
Show »

FASTA45249,834

References

« Hide 'large scale' references
[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. expand/collapse author list , 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]"Large-scale phosphorylation analysis of mouse liver."
Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-93, MASS SPECTROMETRY.
Tissue: Liver.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
IPIIPI00320121.
IPI00848891.
RefSeqNP_001161753.1. NM_001168281.1.
NP_598545.2. NM_133784.3.
UniGeneMm.405029.

3D structure databases

ProteinModelPortalQ9EPK5.
SMRQ9EPK5. Positions 14-57, 123-157.
ModBaseSearch...

Protein-protein interaction databases

IntActQ9EPK5. 9 interactions.
MINTMINT-4123841.

PTM databases

PhosphoSiteQ9EPK5.

Proteomic databases

PaxDbQ9EPK5.
PRIDEQ9EPK5.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000029380; ENSMUSP00000029380; ENSMUSG00000027803.
ENSMUST00000120977; ENSMUSP00000113040; ENSMUSG00000027803.
GeneID97064.
KEGGmmu:97064.
UCSCuc008phb.2. mouse.
uc012cpt.1. mouse.

Organism-specific databases

CTD25937.
MGIMGI:1917649. Wwtr1.

Phylogenomic databases

eggNOGNOG247722.
GeneTreeENSGT00510000046760.
HOGENOMHOG000007854.
HOVERGENHBG002748.
InParanoidQ9EPK5.
KOK16820.
OMAMAMSQPN.
OrthoDBEOG4MSCZC.

Enzyme and pathway databases

ReactomeREACT_78136. Gene Expression.

Gene expression databases

BgeeQ9EPK5.
CleanExMM_WWTR1.
GenevestigatorQ9EPK5.
GermOnlineENSMUSG00000027803. Mus musculus.

Family and domain databases

InterProIPR001202. WW_dom.
[Graphical view]
PfamPF00397. WW. 1 hit.
[Graphical view]
SMARTSM00456. WW. 1 hit.
[Graphical view]
SUPFAMSSF51045. WW_Rsp5_WWP. 1 hit.
PROSITEPS01159. WW_DOMAIN_1. 1 hit.
PS50020. WW_DOMAIN_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio352477.
SOURCESearch...

Entry information

Entry nameWWTR1_MOUSE
AccessionPrimary (citable) accession number: Q9EPK5
Secondary accession number(s): Q3UQ69, Q3UQM0, Q99KI4
Entry history
Integrated into UniProtKB/Swiss-Prot: June 7, 2005
Last sequence update: June 7, 2005
Last modified: May 29, 2013
This is version 91 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot

SIMILARITY comments

Index of protein domains and families