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Protein

WW domain-containing transcription regulator protein 1

Gene

WWTR1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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.4 Publications

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionActivator
Biological processTranscription, Transcription regulation

Enzyme and pathway databases

ReactomeiR-HSA-2028269 Signaling by Hippo
R-HSA-2032785 YAP1- and WWTR1 (TAZ)-stimulated gene expression
R-HSA-2173796 SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription
R-HSA-5578768 Physiological factors
R-HSA-8940973 RUNX2 regulates osteoblast differentiation
R-HSA-8951671 RUNX3 regulates YAP1-mediated transcription
SignaLinkiQ9GZV5
SIGNORiQ9GZV5

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
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 3

Organism-specific databases

EuPathDBiHostDB:ENSG00000018408.14
HGNCiHGNC:24042 WWTR1
MIMi607392 gene
neXtProtiNX_Q9GZV5

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi51S → A or D: Loss of interaction with TEAD4. 1 Publication1
Mutagenesisi89S → A: Significant resistance to inhibition by STK3/MST2 and LATS2. 1 Publication1
Mutagenesisi311S → A: Partial resistance to inhibition by MST2 and LATS2. 1 Publication1

Keywords - Diseasei

Proto-oncogene

Organism-specific databases

DisGeNETi25937
MalaCardsiWWTR1
OpenTargetsiENSG00000018408
PharmGKBiPA134899667

Polymorphism and mutation databases

BioMutaiWWTR1
DMDMi67462080

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000760691 – 400WW domain-containing transcription regulator protein 1Add BLAST400

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei62PhosphoserineCombined sources1
Modified residuei89Phosphoserine; by LATS21 Publication1
Modified residuei105PhosphoserineCombined sources1
Modified residuei295PhosphoserineCombined sources1
Modified residuei311Phosphoserine; by LATS21 Publication1

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. Phosphorylation results in the inhibition of transcriptional coactivation through YWHAZ-mediated nuclear export.1 Publication

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ9GZV5
MaxQBiQ9GZV5
PaxDbiQ9GZV5
PeptideAtlasiQ9GZV5
PRIDEiQ9GZV5
ProteomicsDBi80157

PTM databases

iPTMnetiQ9GZV5
PhosphoSitePlusiQ9GZV5

Expressioni

Tissue specificityi

Highly expressed in kidney, heart, placenta and lung. Expressed in the thyroid tissue.2 Publications

Gene expression databases

BgeeiENSG00000018408 Expressed in 238 organ(s), highest expression level in pigmented layer of retina
CleanExiHS_TAZ
HS_WWTR1
ExpressionAtlasiQ9GZV5 baseline and differential
GenevisibleiQ9GZV5 HS

Organism-specific databases

HPAiCAB017483
CAB068248
HPA007415

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 (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.By similarity3 Publications

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi117434, 27 interactors
CORUMiQ9GZV5
ELMiQ9GZV5
IntActiQ9GZV5, 39 interactors
MINTiQ9GZV5
STRINGi9606.ENSP00000353847

Structurei

3D structure databases

ProteinModelPortaliQ9GZV5
SMRiQ9GZV5
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini124 – 157WWPROSITE-ProRule annotationAdd BLAST34

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili225 – 259Sequence analysisAdd BLAST35

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi394 – 400PDZ-binding7

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi194 – 241Gln-richAdd BLAST48

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 (By similarity).By similarity
Binds to transcription factors via its WW domain.

Keywords - Domaini

Coiled coil

Phylogenomic databases

eggNOGiENOG410INUC Eukaryota
ENOG4111U1C LUCA
GeneTreeiENSGT00510000046760
HOGENOMiHOG000007854
HOVERGENiHBG002748
InParanoidiQ9GZV5
KOiK16820
OMAiAMSQPNL
OrthoDBiEOG091G095A
PhylomeDBiQ9GZV5
TreeFamiTF326941

Family and domain databases

CDDicd00201 WW, 1 hit
InterProiView protein in InterPro
IPR001202 WW_dom
IPR036020 WW_dom_sf
PfamiView protein in Pfam
PF00397 WW, 1 hit
SMARTiView protein in SMART
SM00456 WW, 1 hit
SUPFAMiSSF51045 SSF51045, 1 hit
PROSITEiView protein in PROSITE
PS01159 WW_DOMAIN_1, 1 hit
PS50020 WW_DOMAIN_2, 1 hit

Sequence (1+)i

Sequence statusi: Complete.

This entry has 1 described isoform and 7 potential isoforms that are computationally mapped.iShow all

Q9GZV5-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MNPASAPPPL PPPGQQVIHV TQDLDTDLEA LFNSVMNPKP SSWRKKILPE
60 70 80 90 100
SFFKEPDSGS HSRQSSTDSS GGHPGPRLAG GAQHVRSHSS PASLQLGTGA
110 120 130 140 150
GAAGSPAQQH AHLRQQSYDV TDELPLPPGW EMTFTATGQR YFLNHIEKIT
160 170 180 190 200
TWQDPRKAMN QPLNHMNLHP AVSSTPVPQR SMAVSQPNLV MNHQHQQQMA
210 220 230 240 250
PSTLSQQNHP TQNPPAGLMS MPNALTTQQQ QQQKLRLQRI QMERERIRMR
260 270 280 290 300
QEELMRQEAA LCRQLPMEAE TLAPVQAAVN PPTMTPDMRS ITNNSSDPFL
310 320 330 340 350
NGGPYHSREQ STDSGLGLGC YSVPTTPEDF LSNVDEMDTG ENAGQTPMNI
360 370 380 390 400
NPQQTRFPDF LDCLPGTNVD LGTLESEDLI PLFNDVESAL NKSEPFLTWL
Length:400
Mass (Da):44,101
Last modified:March 1, 2001 - v1
Checksum:i630B50F46FB74C60
GO

Computationally mapped potential isoform sequencesi

There are 7 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
C9J038C9J038_HUMAN
WW domain-containing transcription ...
WWTR1
189Annotation score:
C9J337C9J337_HUMAN
WW domain-containing transcription ...
WWTR1
247Annotation score:
C9JR84C9JR84_HUMAN
WW domain-containing transcription ...
WWTR1
138Annotation score:
C9JQS8C9JQS8_HUMAN
WW domain-containing transcription ...
WWTR1
109Annotation score:
C9J588C9J588_HUMAN
WW domain-containing transcription ...
WWTR1
21Annotation score:
H7C4Z7H7C4Z7_HUMAN
WW domain-containing transcription ...
WWTR1
42Annotation score:
H7C4Q0H7C4Q0_HUMAN
WW domain-containing transcription ...
WWTR1
29Annotation score:

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ299431 mRNA Translation: CAC17722.1
AK022036 mRNA Translation: BAB13957.1
CH471052 Genomic DNA Translation: EAW78868.1
CH471052 Genomic DNA Translation: EAW78869.1
BC014052 mRNA Translation: AAH14052.1
AL050107 mRNA Translation: CAB43275.1
AL833852 mRNA Translation: CAD38711.1
CCDSiCCDS3144.1
PIRiT08755
RefSeqiNP_001161750.1, NM_001168278.2
NP_001161752.1, NM_001168280.2
NP_001335291.1, NM_001348362.1
NP_056287.1, NM_015472.5
XP_016861611.1, XM_017006122.1
UniGeneiHs.477921

Genome annotation databases

EnsembliENST00000360632; ENSP00000353847; ENSG00000018408
ENST00000465804; ENSP00000419465; ENSG00000018408
ENST00000467467; ENSP00000419234; ENSG00000018408
GeneIDi25937
KEGGihsa:25937
UCSCiuc003exf.4 human

Entry informationi

Entry nameiWWTR1_HUMAN
AccessioniPrimary (citable) accession number: Q9GZV5
Secondary accession number(s): D3DNH7, Q8N3P2, Q9Y3W6
Entry historyiIntegrated into UniProtKB/Swiss-Prot: June 7, 2005
Last sequence update: March 1, 2001
Last modified: September 12, 2018
This is version 149 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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