YAP1

1JMQ, 1K5R, 1K9Q, 1K9R, 2LAW, 2LAX, 2LAY, 2LTV, 2LTW, 3KYS, 3MHR, 4RE1, 4REX1041322601ENSG00000137693ENSMUSG00000053110P46937P46938NM_001282099NM_001282100NM_001282101NM_006106NM_001171147NM_009534NP_001269028NP_001269029NP_001269030NP_006097NP_001164618NP_033560YAP1 (yes-associated protein 1), also known as YAP or YAP65, is a protein that acts as a transcriptional regulator by activating the transcription of genes involved in cell proliferation and suppressing apoptotic genes. YAP1 is inhibited in the Hippo signaling pathway which allows the cellular control of organ size and tumor suppression. YAP1 was first identified by virtue of its ability to associate with the SH3 domain of Yes and Src protein tyrosine kinases. YAP1 is a potent oncogene, which is amplified in various human cancers.1jmq: YAP65 (L30K mutant) WW domain in Complex with GTPPPPYTVG peptide1k5r: YAP65 WW domain S24-Amino-Ethylsulfanyl-Acetic Acid mutant1k9q: YAP65 WW domain complexed to N-(n-octyl)-GPPPY-NH21k9r: YAP65 WW domain complexed to Acetyl-PLPPY YAP1 (yes-associated protein 1), also known as YAP or YAP65, is a protein that acts as a transcriptional regulator by activating the transcription of genes involved in cell proliferation and suppressing apoptotic genes. YAP1 is inhibited in the Hippo signaling pathway which allows the cellular control of organ size and tumor suppression. YAP1 was first identified by virtue of its ability to associate with the SH3 domain of Yes and Src protein tyrosine kinases. YAP1 is a potent oncogene, which is amplified in various human cancers. Cloning of the YAP1 gene facilitated the identification of a modular protein domain, known as the WW domain. Two splice isoforms of the YAP1 gene product were initially identified, named YAP1-1 and YAP1-2, which differed by the presence of an extra 38 amino acids that encoded the WW domain. Apart from the WW domain, the modular structure of YAP1 contains a proline-rich region at the very amino terminus, which is followed by a TID (TEAD transcription factor interacting domain). Next, following a single WW domain, which is present in the YAP1-1 isoform, and two WW domains, which are present in the YAP1-2 isoform, there is the SH3-BM (Src Homology 3 binding motif). Following the SH3-BM is a TAD (transcription activation domain) and a PDZ domain-binding motif (PDZ-BM) (Figure 1). YAP1 is a transcriptional co-activator and its proliferative and oncogenic activity is driven by its association with the TEAD family of transcription factors, which up-regulate genes that promote cell growth and inhibit apoptosis. Several other functional partners of YAP1 were identified, including RUNX, SMADs, p73, ErbB4, TP53BP, LATS1/2, PTPN14, AMOTs, and ZO1/2. YAP1 and its close paralog, TAZ (WWTR1), are the main effectors of the Hippo tumor suppressor pathway. When the pathway is activated, YAP1 and TAZ are phosphorylated on a serine residue and sequestered in the cytoplasm by 14-3-3 proteins. When the Hippo pathway is not activated, YAP1/TAZ enter the nucleus and regulate gene expression.