Q9GZV5 · WWTR1_HUMAN
- ProteinWW domain-containing transcription regulator protein 1
- GeneWWTR1
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids400 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
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, PubMed:23911299).
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).
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).
GO annotations
all annotations | all molecular function | virus receptor activity | dna binding | rna binding | cytoskeletal motor activity | catalytic activity | gtpase activity | structural molecule activity | transporter activity | cytoskeletal protein binding | lipid binding | cyclase activity | antioxidant activity | oxidoreductase activity | transferase activity | hydrolase activity | lyase activity | isomerase activity | ligase activity | protein tag activity | cargo receptor activity | histone binding | protein folding chaperone | translation regulator activity | nutrient reservoir activity | receptor ligand activity | molecular transducer activity | molecular adaptor activity | toxin activity | cell adhesion mediator activity | molecular function regulator activity | virus coreceptor activity | catalytic activity, acting on a protein | catalytic activity, acting on dna | catalytic activity, acting on rna | molecular carrier activity | transcription regulator activity | general transcription initiation factor activity | molecular sensor activity | molecular sequestering activity | atp-dependent activity | other molecular function | all biological process | mitotic cell cycle | cytokinesis | cytoplasmic translation | immune system process | muscle system process | circulatory system process | renal system process | respiratory system process | carbohydrate metabolic process | generation of precursor metabolites and energy | dna replication | dna repair | dna recombination | chromatin organization | dna-templated transcription | regulation of dna-templated transcription | trna metabolic process | protein folding | protein glycosylation | amino acid metabolic process | modified amino acid metabolic process | lipid metabolic process | vitamin metabolic process | sulfur compound metabolic process | intracellular protein transport | nucleocytoplasmic transport | autophagy | inflammatory response | mitochondrion organization | cytoskeleton organization | microtubule-based movement | peroxisome organization | lysosome organization | chromosome segregation | cell adhesion | establishment or maintenance of cell polarity | programmed cell death | photosynthesis | mrna metabolic process | snrna metabolic process | vesicle-mediated transport | reproductive process | digestive system process | signaling | cell differentiation | protein catabolic process | extracellular matrix organization | regulatory ncrna-mediated gene silencing | telomere organization | cell junction organization | wound healing | ribosome biogenesis | cilium organization | anatomical structure development | cell motility | nervous system process | endocrine process | protein maturation | transmembrane transport | nucleobase-containing small molecule metabolic process | hepaticobiliary system process | membrane organization | protein-containing complex assembly | cell wall organization or biogenesis | nitrogen cycle metabolic process | protein localization to plasma membrane | defense response to other organism | detoxification | meiotic nuclear division | mitotic nuclear division | mitochondrial gene expression | carbohydrate derivative metabolic process | other biological process | all cellular component | nuclear chromosome | extracellular region | extracellular space | cell wall | nucleus | nuclear envelope | nucleoplasm | chromosome | nucleolus | mitochondrion | lysosome | endosome | vacuole | peroxisome | endoplasmic reticulum | golgi apparatus | lipid droplet | microtubule organizing center | cytosol | ribosome | cytoskeleton | plasma membrane | cilium | plastid | thylakoid | external encapsulating structure | extracellular matrix | cytoplasmic vesicle | organelle | other cellular component | |||
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Keywords
- Molecular function
- Biological process
Enzyme and pathway databases
The subsequence GAAGSPAQQHAHLRQQSYDVTDELPLPPGWEMTFTATGQRYFLNHIEKITTWQDPRKAMNQPLNHMNLHPAVSSTPVPQR, which contains the WW domain, shows transcriptional activator activity in a high-throughput recruitment assay.
Names & Taxonomy
Protein names
- Recommended nameWW domain-containing transcription regulator protein 1
- Alternative names
Gene names
- Community suggested namesWWTR1
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionQ9GZV5
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Note: Concentrates along specific portions of the plasma membrane, and accumulates in punctate nuclear bodies (By similarity).
When phosphorylated, is retained in the cytoplasm by YWHAZ (By similarity).
Can be retained in the nucleus by MED15 (PubMed:18568018).
Localized in the cytoplasm in areas of epithelial cell high density (PubMed:21145499).
At blastocyst stage expressed in the nucleus in trophectodermal cells, however expressed in the cytoplasm in the inner cell mass (By similarity).
In the nucleus, phosphorylation by PRP4K induces nuclear exclusion (PubMed:29695716).
Interaction with AMOTL2 results in localization to the cytoplasm and tight junctions (PubMed:23911299).
When phosphorylated, is retained in the cytoplasm by YWHAZ (By similarity).
Can be retained in the nucleus by MED15 (PubMed:18568018).
Localized in the cytoplasm in areas of epithelial cell high density (PubMed:21145499).
At blastocyst stage expressed in the nucleus in trophectodermal cells, however expressed in the cytoplasm in the inner cell mass (By similarity).
In the nucleus, phosphorylation by PRP4K induces nuclear exclusion (PubMed:29695716).
Interaction with AMOTL2 results in localization to the cytoplasm and tight junctions (PubMed:23911299).
Keywords
- Cellular component
Disease & Variants
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 51 | Loss of interaction with TEAD4. | ||||
Sequence: S → A or D | ||||||
Mutagenesis | 89 | Significant resistance to inhibition by STK3/MST2 and LATS2. No effect on binding to PRRG4. | ||||
Sequence: S → A | ||||||
Mutagenesis | 111-158 | Reduced binding to PRRG4. | ||||
Sequence: Missing | ||||||
Mutagenesis | 311 | Partial resistance to inhibition by MST2 and LATS2. | ||||
Sequence: S → A | ||||||
Mutagenesis | 394-400 | No effect on binding to PRRG4. | ||||
Sequence: Missing |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 481 variants from UniProt as well as other sources including ClinVar and dbSNP.
Keywords
- Disease
Organism-specific databases
Miscellaneous
Genetic variation databases
PTM/Processing
Features
Showing features for chain, modified residue (large scale data), cross-link, modified residue.
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Chain | PRO_0000076069 | 1-400 | UniProt | WW domain-containing transcription regulator protein 1 | |||
Sequence: MNPASAPPPLPPPGQQVIHVTQDLDTDLEALFNSVMNPKPSSWRKKILPESFFKEPDSGSHSRQSSTDSSGGHPGPRLAGGAQHVRSHSSPASLQLGTGAGAAGSPAQQHAHLRQQSYDVTDELPLPPGWEMTFTATGQRYFLNHIEKITTWQDPRKAMNQPLNHMNLHPAVSSTPVPQRSMAVSQPNLVMNHQHQQQMAPSTLSQQNHPTQNPPAGLMSMPNALTTQQQQQQKLRLQRIQMERERIRMRQEELMRQEAALCRQLPMEAETLAPVQAAVNPPTMTPDMRSITNNSSDPFLNGGPYHSREQSTDSGLGLGCYSVPTTPEDFLSNVDEMDTGENAGQTPMNINPQQTRFPDFLDCLPGTNVDLGTLESEDLIPLFNDVESALNKSEPFLTWL | |||||||
Modified residue (large scale data) | 21 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Cross-link | 46 | UniProt | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) | ||||
Sequence: K | |||||||
Modified residue | 62 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 62 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 66 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 87 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 89 | UniProt | Phosphoserine; by LATS2 | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 89 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 90 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 93 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 105 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 105 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 117 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 175 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue | 295 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 295 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 296 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 307 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 311 | UniProt | Phosphoserine; by LATS2 | ||||
Sequence: S |
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. Phosphorylation results in the inhibition of transcriptional coactivation through YWHAZ-mediated nuclear export. Phosphorylated in the nucleus by PRP4K; phosphorylation leads to nuclear exclusion (PubMed:29695716).
Ubiquitinated at Lys-46; leading to proteasomal degradation. Deubiquitinated and stabilized by UCHL1 at Lys-46; leading to inhibition of osteoclastogenesis.
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Highly expressed in kidney, heart, placenta and lung. Expressed in the thyroid tissue.
Gene expression databases
Organism-specific databases
Interaction
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).
Interacts (via WW domain) with AMOTL2 (via PPXY motif); the interaction promotes WWTR1/TAZ localization to the cytoplasm and tight junctions, thereby inhibiting its transcriptional coactivator properties (PubMed:23911299).
Interacts (via WW domain) with AMOT isoform 1; the interaction facilitates translocation of WWTR1/TAZ to the cytoplasm (PubMed:21205866).
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).
Interacts (via WW domain) with AMOTL2 (via PPXY motif); the interaction promotes WWTR1/TAZ localization to the cytoplasm and tight junctions, thereby inhibiting its transcriptional coactivator properties (PubMed:23911299).
Interacts (via WW domain) with AMOT isoform 1; the interaction facilitates translocation of WWTR1/TAZ to the cytoplasm (PubMed:21205866).
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | Q9GZV5 | BTRC Q9Y297 | 2 | EBI-747743, EBI-307461 | |
BINARY | Q9GZV5 | C1orf74 Q96LT6 | 3 | EBI-747743, EBI-12049899 | |
BINARY | Q9GZV5 | CCAR1 Q8IX12 | 2 | EBI-747743, EBI-356265 | |
BINARY | Q9GZV5 | CTNNB1 P35222 | 4 | EBI-747743, EBI-491549 | |
BINARY | Q9GZV5 | DVL1 O14640 | 2 | EBI-747743, EBI-723489 | |
BINARY | Q9GZV5 | DVL2 O14641 | 4 | EBI-747743, EBI-740850 | |
BINARY | Q9GZV5 | IL16 Q14005-2 | 3 | EBI-747743, EBI-17178971 | |
BINARY | Q9GZV5 | LATS1 O95835 | 5 | EBI-747743, EBI-444209 | |
BINARY | Q9GZV5 | PRRG4 Q9BZD6 | 4 | EBI-747743, EBI-3918643 | |
BINARY | Q9GZV5 | RTN4IP1 Q8WWV3 | 3 | EBI-747743, EBI-743502 | |
BINARY | Q9GZV5 | SCRIB Q14160 | 3 | EBI-747743, EBI-357345 | |
BINARY | Q9GZV5 | TCP11L1 Q9NUJ3 | 3 | EBI-747743, EBI-2555179 | |
BINARY | Q9GZV5 | TEAD1 P28347-2 | 3 | EBI-747743, EBI-12151837 | |
BINARY | Q9GZV5 | TEAD2 Q15562-2 | 3 | EBI-747743, EBI-9370956 | |
BINARY | Q9GZV5 | TEAD3 Q99594 | 5 | EBI-747743, EBI-746720 | |
BINARY | Q9GZV5 | TEAD4 Q15561 | 11 | EBI-747743, EBI-747736 | |
BINARY | Q9GZV5 | WBP2 Q969T9 | 6 | EBI-747743, EBI-727055 | |
BINARY | Q9GZV5 | YWHAE P62258 | 4 | EBI-747743, EBI-356498 | |
BINARY | Q9GZV5 | YWHAG P61981 | 5 | EBI-747743, EBI-359832 |
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for region, compositional bias, domain, coiled coil, motif.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 52-117 | Disordered | ||||
Sequence: FFKEPDSGSHSRQSSTDSSGGHPGPRLAGGAQHVRSHSSPASLQLGTGAGAAGSPAQQHAHLRQQS | ||||||
Compositional bias | 58-72 | Polar residues | ||||
Sequence: SGSHSRQSSTDSSGG | ||||||
Domain | 124-157 | WW | ||||
Sequence: LPLPPGWEMTFTATGQRYFLNHIEKITTWQDPRK | ||||||
Region | 222-400 | Required for interaction with PALS1 | ||||
Sequence: PNALTTQQQQQQKLRLQRIQMERERIRMRQEELMRQEAALCRQLPMEAETLAPVQAAVNPPTMTPDMRSITNNSSDPFLNGGPYHSREQSTDSGLGLGCYSVPTTPEDFLSNVDEMDTGENAGQTPMNINPQQTRFPDFLDCLPGTNVDLGTLESEDLIPLFNDVESALNKSEPFLTWL | ||||||
Coiled coil | 225-259 | |||||
Sequence: LTTQQQQQQKLRLQRIQMERERIRMRQEELMRQEA | ||||||
Motif | 394-400 | PDZ-binding | ||||
Sequence: EPFLTWL |
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.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length400
- Mass (Da)44,101
- Last updated2001-03-01 v1
- Checksum630B50F46FB74C60
Computationally mapped potential isoform sequences
There are 7 potential isoforms mapped to this entry
Features
Showing features for compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Compositional bias | 58-72 | Polar residues | ||||
Sequence: SGSHSRQSSTDSSGG |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AJ299431 EMBL· GenBank· DDBJ | CAC17722.1 EMBL· GenBank· DDBJ | mRNA | ||
AK022036 EMBL· GenBank· DDBJ | BAB13957.1 EMBL· GenBank· DDBJ | mRNA | ||
CH471052 EMBL· GenBank· DDBJ | EAW78868.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
CH471052 EMBL· GenBank· DDBJ | EAW78869.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BC014052 EMBL· GenBank· DDBJ | AAH14052.1 EMBL· GenBank· DDBJ | mRNA | ||
AL050107 EMBL· GenBank· DDBJ | CAB43275.1 EMBL· GenBank· DDBJ | mRNA | ||
AL833852 EMBL· GenBank· DDBJ | CAD38711.1 EMBL· GenBank· DDBJ | mRNA |