YAP1

Description

The YAP1 (Yes1 associated transcriptional regulator) is a protein-coding gene located on chromosome 11.

YAP1 (yes-associated protein 1), also known as YAP or YAP65, is a protein that acts as a transcription coregulator that promotes transcription of genes involved in cellular proliferation and suppressing apoptotic genes. YAP1 is a component in the hippo signaling pathway which regulates organ size, regeneration, and tumorigenesis. 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.

== Structure ==

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 (transactivation domain) and a PDZ domain-binding motif (PDZ-BM) (Figure 1).

== Function == 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.

Transcriptional regulator that can act as both a coactivator and a corepressor, playing a crucial role as the downstream target in the Hippo signaling pathway. This pathway is essential for regulating organ size and suppressing tumors by controlling cell proliferation and promoting apoptosis. The core of the Hippo pathway involves a kinase cascade where STK3/MST2 and STK4/MST1, in complex with SAV1, phosphorylate and activate LATS1/2 (in complex with MOB1). LATS1/2 then phosphorylates and inactivates YAP1 and WWTR1/TAZ, preventing their nuclear translocation and regulating the expression of their target genes. YAP1 also plays a vital role in tissue tension and 3D tissue shape by regulating the cortical actomyosin network through ARHGAP18, a Rho GTPase activating protein that suppresses F-actin polymerization. It also functions as a transcriptional corepressor of TEAD4 target genes AURKA and PLK1, suppressing ciliogenesis.

YAP1 is also known as COB1, YAP, YAP-1, YAP2, YAP65, YKI.

Associated Diseases

WES Whole Exome Sequencing

Clinical Exome Sequencing