WWTR1

WW domain-containing transcription regulator protein 1 is a protein that in humans is encoded by the WWTR1 gene.[5][6][7]

WWTR1
Identifiers
Aliases	WWTR1, TAZ, WW domain containing transcription regulator 1
External IDs	OMIM: 607392 MGI: 1917649 HomoloGene: 9159 GeneCards: WWTR1
Gene location (Human) Chr. Chromosome 3 (human)[1] Band 3q25.1 Start 149,517,235 bp[1] End 149,736,714 bp[1]
Gene location (Mouse) Chr. Chromosome 3 (mouse)[2] Band 3|3 D Start 57,455,649 bp[2] End 57,575,910 bp[2]
RNA expression pattern More reference expression data
Gene ontology Molecular function • protein homodimerization activity • GO:0001106 transcription corepressor activity • GO:0001105 transcription coactivator activity • GO:0001948 protein binding Cellular component • cytoplasm • transcription regulator complex • nucleoplasm • cell nucleus • cytosol • nuclear body Biological process • negative regulation of protein phosphorylation • cilium morphogenesis • regulation of metanephric nephron tubule epithelial cell differentiation • negative regulation of fat cell differentiation • regulation of transcription, DNA-templated • negative regulation of protein kinase activity • multicellular organism growth • regulation of canonical Wnt signaling pathway • glomerulus development • negative regulation of transcription from RNA polymerase II promoter • Hippo signaling pathway • positive regulation of epithelial to mesenchymal transition • regulation of SMAD protein import into nucleus • SCF-dependent proteasomal ubiquitin-dependent protein catabolic process • mesenchymal cell differentiation • stem cell division • protein ubiquitination • osteoblast differentiation • kidney morphogenesis • positive regulation of cell proliferation • transcription initiation from RNA polymerase II promoter • negative regulation of canonical Wnt signaling pathway • positive regulation of transcription from RNA polymerase II promoter • transcription, DNA-templated • tissue homeostasis • heart process Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	25937	97064
Ensembl	ENSG00000018408	ENSMUSG00000027803
UniProt	Q9GZV5	Q9EPK5
RefSeq (mRNA)	NM_001168278 NM_001168280 NM_015472 NM_001348362	NM_001168281 NM_133784
RefSeq (protein)	NP_001161750 NP_001161752 NP_056287 NP_001335291	NP_001161753 NP_598545
Location (UCSC)	Chr 3: 149.52 – 149.74 Mb	Chr 3: 57.46 – 57.58 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

Structure

WWTR1 contains WW domain, coiled coil region, and PDZ domain-binding motif.

Function

WWTR1 It is a 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)/STK4(MST1), in complex with its regulatory protein SAV1, phosphorylates and activates LATS1/LATS2 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.

Using the human SHSY5Y cell line as a model of neuronal differentiation, human FAT1 was shown to regulate the nucleocytoplasmic relocation of WWTR1/TAZ and enhanced transcription of the Hippo target gene CTGF. The same study also showed FAT1 was able to regulate TGF-beta signalling [8]

Nomenclature

Note that this gene is often confused with tafazzin, which has the official gene symbol TAZ. TAZ (the gene) is unrelated to the Hippo pathway. WWTR1 is often referred to as TAZ in research publications due to the first publication describing this gene called it TAZ, even though TAZ (tafazzin) was already named.

References

1. GRCh38: Ensembl release 89: ENSG00000018408 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000027803 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Kanai F, Marignani PA, Sarbassova D, Yagi R, Hall RA, Donowitz M, Hisaminato A, Fujiwara T, Ito Y, Cantley LC, Yaffe MB (Dec 2000). "TAZ: a novel transcriptional co-activator regulated by interactions with 14-3-3 and PDZ domain proteins". The EMBO Journal. 19 (24): 6778–91. doi:10.1093/emboj/19.24.6778. PMC 305881. PMID 11118213.
6. Howell M, Borchers C, Milgram SL (Jun 2004). "Heterogeneous nuclear ribonuclear protein U associates with YAP and regulates its co-activation of Bax transcription". The Journal of Biological Chemistry. 279 (25): 26300–6. doi:10.1074/jbc.M401070200. PMID 15096513.
7. "Entrez Gene: WWTR1 WW domain containing transcription regulator 1".
8. Ahmed AF, de Bock CE, Lincz LF, Pundavela J, Zouikr I, Sontag E, Hondermarck H, Thorne RF (Jun 2015). "FAT1 cadherin acts upstream of Hippo signalling through TAZ to regulate neuronal differentiation". Cellular and Molecular Life Sciences. 72 (23): 4653–69. doi:10.1007/s00018-015-1955-6. PMID 26104008. S2CID 15861327.

Further reading

• Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, Berriz GF, Gibbons FD, Dreze M, Ayivi-Guedehoussou N, Klitgord N, Simon C, Boxem M, Milstein S, Rosenberg J, Goldberg DS, Zhang LV, Wong SL, Franklin G, Li S, Albala JS, Lim J, Fraughton C, Llamosas E, Cevik S, Bex C, Lamesch P, Sikorski RS, Vandenhaute J, Zoghbi HY, Smolyar A, Bosak S, Sequerra R, Doucette-Stamm L, Cusick ME, Hill DE, Roth FP, Vidal M (Oct 2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature. 437 (7062): 1173–8. doi:10.1038/nature04209. PMID 16189514. S2CID 4427026.
• Hong JH, Hwang ES, McManus MT, Amsterdam A, Tian Y, Kalmukova R, Mueller E, Benjamin T, Spiegelman BM, Sharp PA, Hopkins N, Yaffe MB (Aug 2005). "TAZ, a transcriptional modulator of mesenchymal stem cell differentiation". Science. 309 (5737): 1074–8. doi:10.1126/science.1110955. PMID 16099986. S2CID 1958224.
• Park KS, Whitsett JA, Di Palma T, Hong JH, Yaffe MB, Zannini M (Apr 2004). "TAZ interacts with TTF-1 and regulates expression of surfactant protein-C". The Journal of Biological Chemistry. 279 (17): 17384–90. doi:10.1074/jbc.M312569200. PMID 14970209.