General Information of Drug Therapeutic Target (DTT) (ID: TT8UN2D)

DTT Name Yes-associated protein 1 (YAP1)
Synonyms Yorkie homolog; Yes-associated protein YAP65 homolog; YAP65; Transcriptional coactivator YAP1; Protein yorkie homolog; 65 kDa Yes-associated protein
Gene Name YAP1
DTT Type
Literature-reported target
[1]
UniProt ID
YAP1_HUMAN
TTD ID
T94048
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Sequence
MDPGQQPPPQPAPQGQGQPPSQPPQGQGPPSGPGQPAPAATQAAPQAPPAGHQIVHVRGD
SETDLEALFNAVMNPKTANVPQTVPMRLRKLPDSFFKPPEPKSHSRQASTDAGTAGALTP
QHVRAHSSPASLQLGAVSPGTLTPTGVVSGPAATPTAQHLRQSSFEIPDDVPLPAGWEMA
KTSSGQRYFLNHIDQTTTWQDPRKAMLSQMNVTAPTSPPVQQNMMNSASGPLPDGWEQAM
TQDGEIYYINHKNKTTSWLDPRLDPRFAMNQRISQSAPVKQPPPLAPQSPQGGVMGGSNS
NQQQQMRLQQLQMEKERLRLKQQELLRQAMRNINPSTANSPKCQELALRSQLPTLEQDGG
TQNPVSSPGMSQELRTMTTNSSDPFLNSGTYHSRDESTDSGLSMSSYSVPRTPDDFLNSV
DEMDTGDTINQSTLPSQQNRFPDYLEAIPGTNVDLGTLEGDGMNIEGEELMPSLQEALSS
DILNDMESVLAATKLDKESFLTWL
Function
The core of this pathway is composed of a kinase cascade wherein STK3/MST2 and STK4/MST1, in complex with its regulatory protein SAV1, phosphorylates and activates LATS1/2 in complex with its regulatory protein MOB1, which in turn phosphorylates and inactivates YAP1 oncoprotein and WWTR1/TAZ. Plays a key role in tissue tension and 3D tissue shape by regulating cortical actomyosin network formation. Acts via ARHGAP18, a Rho GTPase activating protein that suppresses F-actin polymerization. Plays a key role to control cell proliferation in response to cell contact. Phosphorylation of YAP1 by LATS1/2 inhibits its translocation into the nucleus to regulate cellular genes important for cell proliferation, cell death, and cell migration. The presence of TEAD transcription factors are required for it to stimulate gene expression, cell growth, anchorage-independent growth, and epithelial mesenchymal transition (EMT) induction. Transcriptional regulator which can act both as a coactivator and a corepressor and is the critical 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.
KEGG Pathway
Hippo signaling pathway (hsa04390 )
Hippo signaling pathway - multiple species (hsa04392 )
Reactome Pathway
Signaling by Hippo (R-HSA-2028269 )
YAP1- and WWTR1 (TAZ)-stimulated gene expression (R-HSA-2032785 )
RUNX1 regulates transcription of genes involved in differentiation of HSCs (R-HSA-8939236 )
RUNX2 regulates osteoblast differentiation (R-HSA-8940973 )
RUNX3 regulates YAP1-mediated transcription (R-HSA-8951671 )
EGR2 and SOX10-mediated initiation of Schwann cell myelination (R-HSA-9619665 )
Nuclear signaling by ERBB4 (R-HSA-1251985 )

References

1 YAP1 is essential for tumor growth and is a potential therapeutic target for EGFR-dependent lung adenocarcinomas. Oncotarget. 2017 Jul 27;8(52):89539-89551.