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Gene Review

YAP1  -  Yes-associated protein 1

Homo sapiens

Synonyms: COB1, Protein yorkie homolog, Transcriptional coactivator YAP1, YAP, YAP2, ...
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Disease relevance of YAP1


High impact information on YAP1

  • A non-conserved isoleucine in the amino-terminal flanking region covers a hydrophobic patch and stabilizes the WW domain of human YAP65 in vitro [6].
  • The transcriptional coactivator Yes-associated protein (YAP) has been shown to interact with and to enhance p73-dependent apoptosis in response to DNA damage [7].
  • Altogether, our findings identify YAP as a key determinant of p73 gene targeting in response to DNA damage [7].
  • We also found that YAP contributes to the DNA damage-induced accumulation of p73 and potentiates the p300-mediated acetylation of p73 [7].
  • Endogenous p73, YAP, and p300 proteins are concomitantly recruited onto the regulatory regions of the apoptotic target gene p53AIP1 only when cells are exposed to apoptotic conditions [7].

Biological context of YAP1


Anatomical context of YAP1

  • In conclusion, YAP65 is expressed mainly in centroacinar and small ductal cells in the normal pancreas [1].
  • YAP65 mRNA expression levels in human pancreatic tissue samples and cell lines were analyzed by Northern blotting and quantitative RT-PCR [1].
  • In the normal pancreas, YAP65 was absent in acinar cells, large ducts and islet cells, but exhibited moderate to strong immunoreactivity in centroacinar cells and ductules [1].
  • NHERF also recruits non-membrane proteins such as the c-Yes/YAP-65 complex, members of the phospholipase Cbeta family and the GRK6A protein kinase to apical surface of polarized epithelial cells where they regulate or respond to membrane signals [13].
  • We propose that TAZ, as well as a highly related molecule YAP, are functionally, though not structurally, similar to beta-catenin and integrate extracellular, membrane, and cytoskeletal-derived signals to influence mesenchymal stem cell fate [14].

Associations of YAP1 with chemical compounds

  • In addition, we show that the nonreceptor tyrosine kinase c-Yes is contained within EBP50 protein complexes by association with YAP65 [15].
  • A constitutively active form of c-Yes was observed to decrease the binding affinity between YAP and p53BP-2 using chloramphenicol acetyltransferase/enzyme-linked immunosorbent assay, whereas the overexpression of c-Yes did not modify this interaction [16].
  • One protein that associates with 14-3-3 in an Akt-dependent manner is shown here to be the Yes-associated protein (YAP), which is phosphorylated by Akt at serine 127, leading to binding to 14-3-3 [12].
  • Treatment of cells with cisplatin leads to an increase in p73 accumulation and induction of apoptosis, but both were dramatically reduced in the presence of Yap1 siRNA [17].

Physical interactions of YAP1

  • Here, we report that Yes-associated protein 65 (YAP65) binds with high affinity to the second EBP50 PDZ domain [15].
  • Binding assays and site-specific mutagenesis have shown that the proline-rich motif binds with relatively high affinity and specificity to the WW domain of YAP, with a preliminary consensus that is different from the SH3-binding PXXP motif [18].

Regulatory relationships of YAP1

  • In contrast, hnRNP U has no effect when co-expressed with a truncated YAP protein lacking the hnRNP U-binding site [10].
  • In addition, our results show that interaction of WWOX and ErbB-4 suppresses transcriptional coactivation of CTF by YAP in a dose-dependent manner [19].
  • The mutation is in a conserved amino acid sequence in the C terminal of the protein, a potential binding site for YAP65 one of TEAD1's cofactors that is expressed in human retina as well as TEAD1 based on RT-PCR experiments [20].

Other interactions of YAP1

  • The COOH terminus of YAP65 is necessary and sufficient to mediate association with EBP50 [15].
  • Furthermore, hnRNP U and YAP only interact in the nucleus, suggesting that the association between the two proteins is regulated [10].
  • In summary, our data indicate that WWOX antagonizes the function of YAP by competing for interaction with ErbB-4 and other targets and thus affect its transcriptional activity [19].
  • TGF-beta1 strongly induced Smad7 mRNA in Colo-357 and in Panc-1 cells, but only slightly induced YAP65 mRNA in Colo-357 cells [1].
  • Like YAP65, TAZ interacted with all four TEF-1 family members [21].

Analytical, diagnostic and therapeutic context of YAP1


  1. Yes-associated protein (YAP65) in relation to Smad7 expression in human pancreatic ductal adenocarcinoma. Guo, J., Kleeff, J., Zhao, Y., Li, J., Giese, T., Esposito, I., Büchler, M.W., Korc, M., Friess, H. Int. J. Mol. Med. (2006) [Pubmed]
  2. Identification of tumor-specific molecular signatures in intracranial ependymoma and association with clinical characteristics. Modena, P., Lualdi, E., Facchinetti, F., Veltman, J., Reid, J.F., Minardi, S., Janssen, I., Giangaspero, F., Forni, M., Finocchiaro, G., Genitori, L., Giordano, F., Riccardi, R., Schoenmakers, E.F., Massimino, M., Sozzi, G. J. Clin. Oncol. (2006) [Pubmed]
  3. Evolution of binding affinity in a WW domain probed by phage display. Dalby, P.A., Hoess, R.H., DeGrado, W.F. Protein Sci. (2000) [Pubmed]
  4. Inactivation of YAP oncoprotein by the Hippo pathway is involved in cell contact inhibition and tissue growth control. Zhao, B., Wei, X., Li, W., Udan, R.S., Yang, Q., Kim, J., Xie, J., Ikenoue, T., Yu, J., Li, L., Zheng, P., Ye, K., Chinnaiyan, A., Halder, G., Lai, Z.C., Guan, K.L. Genes Dev. (2007) [Pubmed]
  5. Yes-associated protein 1 exhibits oncogenic property in gastric cancer and its nuclear accumulation associates with poor prognosis. Kang, W., Tong, J.H., Chan, A.W., Lee, T.L., Lung, R.W., Leung, P.P., So, K.K., Wu, K., Fan, D., Yu, J., Sung, J.J., To, K.F. Clin. Cancer Res. (2011) [Pubmed]
  6. Structure of the WW domain of a kinase-associated protein complexed with a proline-rich peptide. Macias, M.J., Hyvönen, M., Baraldi, E., Schultz, J., Sudol, M., Saraste, M., Oschkinat, H. Nature (1996) [Pubmed]
  7. The transcriptional coactivator Yes-associated protein drives p73 gene-target specificity in response to DNA Damage. Strano, S., Monti, O., Pediconi, N., Baccarini, A., Fontemaggi, G., Lapi, E., Mantovani, F., Damalas, A., Citro, G., Sacchi, A., Del Sal, G., Levrero, M., Blandino, G. Mol. Cell (2005) [Pubmed]
  8. WW domain-containing protein YAP associates with ErbB-4 and acts as a co-transcriptional activator for the carboxyl-terminal fragment of ErbB-4 that translocates to the nucleus. Komuro, A., Nagai, M., Navin, N.E., Sudol, M. J. Biol. Chem. (2003) [Pubmed]
  9. Saccharomyces cerevisiae Hsp31p, a stress response protein conferring protection against reactive oxygen species. Skoneczna, A., Miciałkiewicz, A., Skoneczny, M. Free Radic. Biol. Med. (2007) [Pubmed]
  10. Heterogeneous nuclear ribonuclear protein U associates with YAP and regulates its co-activation of Bax transcription. Howell, M., Borchers, C., Milgram, S.L. J. Biol. Chem. (2004) [Pubmed]
  11. Selection of suitable reference genes for accurate normalization of gene expression profile studies in non-small cell lung cancer. Silvia, S., Francesca, C., Marco, L.I., Silvia, N., Giorgio V, S., Raffaele, C.A. BMC Cancer (2006) [Pubmed]
  12. Akt phosphorylates the Yes-associated protein, YAP, to induce interaction with 14-3-3 and attenuation of p73-mediated apoptosis. Basu, S., Totty, N.F., Irwin, M.S., Sudol, M., Downward, J. Mol. Cell (2003) [Pubmed]
  13. Expanding the role of NHERF, a PDZ-domain containing protein adapter, to growth regulation. Voltz, J.W., Weinman, E.J., Shenolikar, S. Oncogene (2001) [Pubmed]
  14. TAZ: a beta-catenin-like molecule that regulates mesenchymal stem cell differentiation. Hong, J.H., Yaffe, M.B. Cell Cycle (2006) [Pubmed]
  15. Yes-associated protein 65 localizes p62(c-Yes) to the apical compartment of airway epithelia by association with EBP50. Mohler, P.J., Kreda, S.M., Boucher, R.C., Sudol, M., Stutts, M.J., Milgram, S.L. J. Cell Biol. (1999) [Pubmed]
  16. Yes-associated protein and p53-binding protein-2 interact through their WW and SH3 domains. Espanel, X., Sudol, M. J. Biol. Chem. (2001) [Pubmed]
  17. The Yes-associated protein 1 stabilizes p73 by preventing Itch-mediated ubiquitination of p73. Levy, D., Adamovich, Y., Reuven, N., Shaul, Y. Cell Death Differ. (2007) [Pubmed]
  18. Characterization of a novel protein-binding module--the WW domain. Sudol, M., Chen, H.I., Bougeret, C., Einbond, A., Bork, P. FEBS Lett. (1995) [Pubmed]
  19. WW domain-containing proteins, WWOX and YAP, compete for interaction with ErbB-4 and modulate its transcriptional function. Aqeilan, R.I., Donati, V., Palamarchuk, A., Trapasso, F., Kaou, M., Pekarsky, Y., Sudol, M., Croce, C.M. Cancer Res. (2005) [Pubmed]
  20. A novel TEAD1 mutation is the causative allele in Sveinsson's chorioretinal atrophy (helicoid peripapillary chorioretinal degeneration). Fossdal, R., Jonasson, F., Kristjansdottir, G.T., Kong, A., Stefansson, H., Gosh, S., Gulcher, J.R., Stefansson, K. Hum. Mol. Genet. (2004) [Pubmed]
  21. The transcriptional co-activator TAZ interacts differentially with transcriptional enhancer factor-1 (TEF-1) family members. Mahoney, W.M., Hong, J.H., Yaffe, M.B., Farrance, I.K. Biochem. J. (2005) [Pubmed]
  22. The WW domain of Yes-associated protein binds a proline-rich ligand that differs from the consensus established for Src homology 3-binding modules. Chen, H.I., Sudol, M. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  23. Characterization of the mammalian YAP (Yes-associated protein) gene and its role in defining a novel protein module, the WW domain. Sudol, M., Bork, P., Einbond, A., Kastury, K., Druck, T., Negrini, M., Huebner, K., Lehman, D. J. Biol. Chem. (1995) [Pubmed]
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