The genomic size is 122863 bases and the gene is located on plus strand. YAP1 gene is composed of 7 exons. The open reading frame of the coding region is 1364 bp. No polymorphisms of YAP1 is known.
SNP: 1590 single nucleotide polymorphisms are present in the human gene according to NCBI database.

The human YAP1 coding sequence consists of 1364 bp from the start codon to the stop codon. A differentially spliced isoform of YAP1 (9 exons), with two WW domains known as YAP2 also exists (Sudol et al., 1995).

No pseudogene of YAP1 is known.

The Yes-associated protein (YAP), a critical mediator of p73 function, binds p73 to regulate its transcriptional activity (Strano et al., 2001) and subsequent cell-death induction (Basu et al., 2003). This binding is negatively regulated by AKT-mediated YAP phosphorylation (Basu et al., 2003) and enhanced by DNA damage (Strano et al., 2005). In addition to increase p73 transcriptional activity via the p300 acetyltansferase (Strano et al., 2005), YAP can stabilize p73 protein in a posttranslational manner by competing with the ITCH E3-ligase for binding to p73 (Levy et al., 2007).

Structure: YAP protein consists of 454 amino acids, with a molecular weight of 65 kDa. It was identified as a protein that interacted with the non receptor tyrosine kinase c-Yes, which is a member of the Src family (Sudol, 1994). In fact, Yap is able to interact with the SH3 domain of c-Yes (and also c-Src), through a stretch of proline residues; this proline-rich region is able to interact with SH3 domains of many other proteins. In addition Yap contains another binding domain of a different nature. Due to the presence of two tryptophan residues, which appear to be conserved along evolution and that play an important role in the domain structure and function, it was named WW domain (Sudol et al., 1995; Sudol and Hunter, 2000).
The WW domain binds to short stretches of prolines (PY motif), and therefore mediating the interaction between proteins. The WW domain of Yap belongs to the first of four different classes that differ in terms of the sequence of the interacting motif, a PPxY in the case of WW type I. Yap has been found to interact with many proteins, whose function often is quite substantially different, and the majority of these interactions are mostly mediated by the WW domain (Bertini et al., 2009).
The interaction with PEBP2 (a RunX transcription factor) was the first example of Yap1 as a co-activator of transcription. The WW domain of Yap1 interacts with the PY motif present in the transcription activation domain of PEBP2 and in this occasion Yap1 was reported for the first time to have a strong intrinsic transactivation activity (Yagi et al., 1999). The transcriptional coactivator Yes-associated protein (YAP) was shown to interact with and to enhance p73-dependent apoptosis in response to DNA damage (Strano et al., 2001; Strano et al., 2005).

Interactors of YAP	Reference
YES	Sudol et al., 1995
WBP1 and WBP2	Chen and Sudol, 1995
NFE2	Gavva et al., 1997
RUNX1 and RUNX2	Yagi et al., 1999
EBP50	Mohler et al., 1999
TP53BP2	Espanel and Sudol, 2001
TP73	Strano et al., 2001
TEAD1, 2, 3, 4	Vassilev et al., 2001
SMAD7	Ferrigno et al., 2002
AKT	Basu et al., 2003
ERBB4	Komuro et al., 2003
HNRNPU	Howell et al., 2004
LATS1	Hao et al., 2008
ABL1	Levy et al., 2008
PML	Lapi et al., 2008
EGR1	Zagurovskaya et al., 2009

Table 1: Modified by Bertini et al., 2009.

By Northern blot analysis YAP1 expression shows a major transcript of approximately 5 kb in several human tissues. High expression was found in placenta, prostate, testis, ovary, and small intestine, and lower expression was found in brain, liver, and spleen. No expression was found in peripheral blood leukocytes (Sudol et al., 1995).
YAP1 is the predominant isoform and is ubiquitously expressed in the major part of tissues for twelve normal human tissues (out of 28 tissues shown) hybridized against Affymetrix GeneChips HG-U95A-E (GeneNote data) and for 22 normal human tissues hybridized against HG-U133A (GNF Symatlas data) (Su et al., 2004).

Posttranslational modification of YAP determines its binding and localisation. Lapi et al. (2008) have shown Akt-mediated phosphorylation promotes YAP cytoplasmic retention, demonstrating that active Akt counters cisplatin-induced increases in PML transcription via the YAP-p73 complex. Recently, Levy et al. (2008) have also shown that cisplatin induces ABL1-mediated YAP phosphorylation, resulting in YAP nuclear localization and increased p73 binding and activation of pro-apoptotic genes.
YAP binding of p73 and its coordination of other binding proteins probably depend on an integration of phosphorylation by AKT, ABL1, and other kinases. However, the shuttling of Yap between nucleus and cytoplasm has emerged as an important means for regulating the activity of this protein.

Yap is a small protein that binds to many transcription factors and modulates their activity. Yap increases the ability of p73 to induce apoptosis as a consequence of damage to the DNA, and therefore its activity was thought to favor tumor suppression. However, other studies have recently shown a role for Yap in cell differentiation, cell transformation and in the regulation of organ size. It has been demonstrated that the Drosophila Hippo pathway has a mammalian equivalent, and that Yap is part of this pathway, where it could stimulate proliferation (Pan, 2007; Harvey et al., 2007).
Apoptosis: The transcriptional coactivator Yes-associated protein (YAP) has demonstrated to interact with and to enhance p73-dependent apoptosis in response to DNA damage (Strano et al., 2001; Strano et al., 2005). It has been reported that YAP is phosphorylated by AKT, and such modification impairs YAP-nuclear translocation and attenuates p73-mediated apoptosis (Basu et al., 2003). Recently, it was demonstrated that p73 is required for the nuclear translocation of endogenous YAP in cells exposed to cisplatin and that YAP is recruited by PML into nuclear bodies to promote p73 transcriptional activity (Strano et al., 2005). It was found that YAP contributes to p73 stabilization in response to DNA damage and promotes p73-dependent apoptosis through the specific and selective coactivation of apoptotic p73 target genes and potentiation of p300-mediated acetylation of p73 (Strano et al., 2005). Then, it was described the existence of a proapoptotic autoregulatory feedback loop between p73, YAP, and the promyelocytic leukemia (PML) tumor suppressor gene (Lapi et al., 2008). PML is a direct transcriptional target of p73/YAP. PML contributes to the p73-dependent apoptotic response by regulating YAP stability. Importantly, PML and YAP physically interact through their PVPVY and WW domains, respectively, causing YAP stabilization upon cisplatin treatment, which occurs through PML mediated sumoylation (Lapi et al., 2008).
Together with this proapoptotic role, YAP recently was identified as a tumor suppressor in breast cancer (Yuan et al., 2008). The findings that YAP plays opposing roles in tissue growth/development and DNA damage/apoptosis appear at first contradictory, but this can be explained if YAP binds and activates or inactivates different transcription factors to differentially regulate either pro-growth or pro-apoptotic genes.
Organ size and cell differentiation: Yap plays an important role in controlling organ growth. The works done on Drosophila show how a disrupted Hippo signalling pathway has a negative impact on the growth of imaginal discs (Pan et al., 2007) and how the presence of mutated forms of Yap in particular has an effect on size and shape of fly wings (Zhao et al., 2007).
In addition Dong et al. (2007) reported that overexpression of Yap in mice increases liver size, and in the long term it induces nodules which present characteristics of HCC (Dong et al., 2007). This is in accordance with another important study where increased levels of Yap are shown to enlarge liver size in a reversible manner (Camargo et al., 2007).
However, many questions are unsolved. For instance, it would be interesting to check whether the Hippo pathway plays a role in choices taken by Yap during cell differentiation; to verify whether activity of Yap could be extended to a cellular context beside intestine epithelium; to find the molecular mechanism used by Yap to control transcription of those genes that are in charge of cell differentiation; and obviously, a screen for these genes.

Orthologs: YAP1 is evolutionarily principally conserved in 8 eukaryotes: Canis familiaris, Pan troglodytes, Bos taurus, Mus musculus, Galus gallus, Danio rerio, Xenopus laevis, Silurana tropicalis. Orthologies between human and Drosophyla melanogaster, Caenorabditis elegans and Saccaromyces cerevisiae are quite low. For details see: HomoloGene.

No mutations of YAP1 are known.