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FLASH GENE
Symbol YAP1 contributors: mct/npt/pgu - updated : 12-09-2019
HGNC name Yes-associated protein 1
HGNC id 16262
Corresponding disease
CLBMS2 colobomatous microphthalmia syndromic 2
Location 11q22.1      Physical location : 101.981.191 - 102.104.154
Synonym name
  • Yes-associated protein 1, 65kDa
  • yes-associated protein 2
  • homolog of yorkie
  • Synonym symbol(s) YAP65, YAP, YAP2, YKI
    DNA
    TYPE functioning gene
    STRUCTURE 123.04 kb     9 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    regionally located in a region to which the multiple endocrine neoplasia type 1 gene has been mapped
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    9 - 5386 - 504 - 2010 20153295
  • isoform 1
  • 7 - 5236 - 454 - 2010 20153295
  • isoform 2
  • 8 - 5348 - 488 - -
    - - 4993 - 326 - -
    - - 5282 - 466 - -
    - - 5246 - 454 - -
    - - 5294 - 470 - -
    - - 5360 - 492 - -
    - - 5408 - 508 - -
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart     Mus musculusFetal
     heart     Mus musculusAdult
    Nervousbrain     Mus musculus
    Reproductivefemale systemovary  highly
     male systemtestis  highly
    Urinarykidneynephronrenal capsuleglomerulushighly Homo sapiens
    Visualeye   highly Mus musculus
     eyeretina    Homo sapiens
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Muscularstriatumcardiacmyocardium  Mus musculusFetal
    Nervouscentral   
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Muscularmyocyte Mus musculusFetal
    Urinarypodocyte Homo sapiens
    VisualMuller cell Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period pregnancy
    Text placenta highly
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • N-terminal region folded into two short helices with an extended loop containing the PXXphiP motif in between, while the C-terminal domain of TEAD4 has an immunoglobulin-like fold
  • WW domains, which are important protein-protein interaction modules that mediate interaction with proline-rich motifs, most commonly PPXY
  • a PDZ-binding motif at its C-terminus, motif necessary for its localization in the nucleus and for promoting cell detachment and apoptosis
  • conjugated PhosphoP
    HOMOLOGY
    interspecies homolog to murine Yap1 (91.7pc)
    homolog to yeast S.pombe Spbc 16e9.11cp
    homolog to drosophila Yorkie
    intraspecies paralog to TAZ
    Homologene
    FAMILY
  • YORKIE family
  • CATEGORY protooncogene
    SUBCELLULAR LOCALIZATION     plasma membrane,junction,tight
        intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus,nucleoplasm
    text
  • TJP2 and YAP1 proteins co-localize in the nucleus
  • LATS2, AMOTL2, and YAP1 all localize to tight junctions, raising the possibility that clustering of Hippo pathway components at tight junctions might function to trigger LATS2 activation and growth inhibition in response to increased cell density
  • basic FUNCTION
  • may be involved in protein-protein interactions
  • inducing epithelial-to-mesenchymal transition, suppression of apoptosis, growth factor-independent proliferation, and anchorage-independent growth
  • playing a role in different growth and differentiation regulating pathways, and may play a role in the normal and diseased pancreas
  • role of WBP2 and YAP1 as coactivators for progesterone receptor (PR) and estrogen receptor (ER) transactivation pathways
  • oncogene in breast and liver tumorigenesis
  • mediating cell contact inhibition
  • regulating C2C12 myogenesis
  • transcriptional coactivator and stimulate gene expression by promoting the activity of their cognate transcription factors
  • WW domain-containing transcriptional co-activator that acts as the effector of the Hippo pathway in mammalian cells
  • encode protein that is a cofactor of the TEAD family of transcription factors
  • downstream effector of the Hippo signaling pathway, which controls organ expansion and tissue development
  • functions as a transcriptional coactivator, and regulates the expression of several proliferation- and apoptosis-related genes
  • transcription coactivator that plays a crucial role in organ size control by promoting cell proliferation and inhibiting apoptosis
  • critical modulator of epidermal stem cell proliferation and tissue expansion
  • fundamental role of the transcriptional regulators YAP1 and WWTR1 as downstream elements in how cells perceive their physical microenvironment
  • critical downstream effector of the Hippo pathway in the control of cardiomyocyte proliferation and a nexus for coupling the IGF, Wnt, and Hippo signaling pathways with the developmental program for heart growth
  • crucial regulator of cardiomyocyte proliferation, cardiac morphogenesis, and myocardial trabeculation
  • not cell autonomously required for postnatal hypertrophic cardiomyocyte growth
  • YAP1 and CTNNB1 cooperate to induce transformation
  • YAP1, CTNNB1 and TBX5 form a complex that regulates the expression of genes that promote survival, including BIRC5 and BCL2L1
  • SHH signaling acts downstream of YAP1 in regulating neuronal differentiation
  • can act as an oncogene in several tissue types if its activity is increased aberrantly
  • important regulator of cardiomyocyte proliferation and embryonic heart development
  • critical role of YAP1 in the regulation of cellular senescence, providing a novel insight into a potential chemotherapeutic avenue for tumor suppression
  • antiapoptotic signaling properties of YAP1 in podocytes could hold significance in the quest for targeted therapeutics aimed at preventing podocyte loss
  • central role for TEAD1 and YAP1 as signal-responsive regulators of multipotent pancreatic progenitors
  • activation of YAP1 and CTNNB1 may represent a master regulator of mechanical strain-induced cell proliferation
  • is a transcriptional coactivator in the Hippo pathway that regulates cell proliferation, differentiation, and apoptosis
  • YAP1 promotes myogenic differentiation via the MAP2K5-MAPK7 pathway
  • VGLL4 is a candidate tumor suppressor gene which acts by selectively antagonizing YAP1-dependent tumor growth
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
  • Hippo-YAP1 pathway as a critical signaling branch downstream of GPCR, (G-protein-coupled receptor)
  • YAP1-TEAD1 signaling induces mitochondrial biogenesis in endothelial cells (ECs) and stimulates angiogenesis through PPARGC1A
  • TNKS-RNF146-AMOT axis is an upstream pathway regulating YAP1
  • YAP1-TP73 signaling as a mechanism for cancer cell resistance to chemotherapies
  • a component
  • TEAD4/YAP1 complex showing that YAP1 binds to TEAD4 through three distinct regions of its N-terminal domain
  • ANKHD1 complexes with YAP1 and is required for the full activity of YAP1
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • SH3 domain of YES tyrosine kinase and SHE domain of YES oncoprotein
  • interacting with WBP2
  • interacts with SMAD7 thereby influencing TGF-beta signaling
  • interacting with PRGP2
  • binding to WBP1
  • interacts with TEAD4 mainly through the two short helices
  • interacting with TJP2 (TJP2 uses its first PDZ domain to form a complex with YAP1)
  • AXL is a key downstream target that drives YAP1-dependent oncogenic functions
  • AMOTL1 and AMOTL2, are YAP1-associated proteins
  • AMOT interacting with YAP1 and TAZ (YAP1 and TAZ inhibition by AMOT-mediated tight junction localization)
  • the most common interaction partner of YAP1 in keratinocytes corresponded to CTNNA1, an important tumor suppressor in stratified epithelia
  • FAT4 mediates its action via the Hippo pathway mediator YAP1
  • AMOTL1 inhibits pro-apoptotic function of YAP1, whereas TJP2 enhances it
  • YAP1 stimulation of cardiomyocyte proliferation requires its interaction with TEAD(1-4)
  • YAP1 protein regulates vascular smooth muscle cell phenotypic switch by interaction with MYOCD
  • KLF5 could be an important transcription factor partner for YAP1 and may contribute to the Hippo pathway
  • through its TEAD-interaction domain, YAP1 enhances multiple processes known to be important for tumor progression and metastasis, including cellular proliferation, transformation, migration, and invasion
  • PTPN14 interacts with yes-associated protein 1 (YAP1), a member of the hippo signaling pathway (PTPN14 acts to suppress cell proliferation by promoting cell density-dependent cytoplasmic translocation of YAP1)
  • YAP1 expression is required for the tumorigenicity of CTNNB1 active cells
  • AMOT promotes the ubiquitination of YAP1 by ITCH and prevents ITCH from binding to large tumor suppressor 1
  • YAP1 binding to dendrin is a prosurvival mechanism
  • GABPA is an activator of YAP1 gene expression and a potential therapeutic target for cancers driven by YAP1
  • regulation of NAIP by TEAD1/YAP1 is at the transcriptional level
  • AMOT acts as a YAP1 cofactor, preventing YAP1 phosphorylation and augmenting its activity toward a specific set of genes that facilitate tumorigenesis
  • AJUBA is required for MAPK8-mediated activation of YAP1 and AJUBA contributed to wing regeneration after wounding and to tumor growth
  • PTPN11 physically interacts with transcriptional coactivators YAP1 and TAZ, targets of the cell-density-sensing Hippo signal
  • LATS1/LATS2 involved in phosphorylation of AMOT130, which is a key feature that enables it to inhibit YAP1-dependent signaling and cell growth
  • NEDD4 directly interacts with LATS1, leading to ubiquitination and decreased levels of LATS1 and, thus, increased YAP1 localization in the nucleus
  • MEN1 binds to YAP1 promoter loci and up-regulates H3K4me3
  • negatively regulates YAP1 activity through the LATS family, and inactivation of AJUBA is a novel key mechanism in malignant mesothelioma cell proliferation
  • VGLL4 is a novel tumor suppressor for lung cancer through negatively regulating the YAP1-TEAD complex formation and thus the Hippo pathway
  • is a positive regulator of YAP1 and promotes cell growth and cell cycle progression through Cyclin A upregulation
  • ARHGEF7 is a key component that links the Hippo kinase cassette to YAP1/WWTR1 in response to multiple upstream Hippo pathway activators
  • actin remodelling factors LIMK2 and TESK1 are key players in the ciliogenesis control network in which YAP1/WWTR1 and directional vesicle trafficking are integral components
  • MAMDC4 competes with YAP1 for binding to AMOT proteins in subconfluent cells
  • CRB3 promotes the interaction between YAP1 and the Hippo pathway kinases LATS1/2 at apical cell junctions to induce YAP1 phosphorylation and cytoplasmic retention, which drive cell differentiation
  • EPS8, a signaling adapter regulating actin dynamics, is a novel partner of CDH5 and is able to modulate YAP1 activity 7)
  • KDM4A cooperated with ETV1 to increase expression of yes associated protein 1 (YAP1), a Hippo pathway component that itself was associated with prostate tumor aggressiveness
  • AMOT can interact with YAP1 to either stimulate or inhibit YAP1 activity, playing a potential role in cell proliferation
  • CIZ1 enhanced the interaction between YAP1 and TEAD1
  • CDC42/WASL/stress fibers/YAP1 signal pathway may potentially play an important role in regulating podocyte apoptosis
  • S100A7 is repressed by YAP1 via the Hippo pathway
  • RASSF1 limits TGFB1 induced invasion, offering a new framework on how RASSF1 affects YAP1 transcriptional output and elicits its tumor-suppressive function
  • YAP1 promotes myelin and non-myelin genes transcription while the polarity protein CRB3, localized at the tips of the myelin sheath, activates the Hippo pathway to temper YAP1 activity, therefore allowing for optimal myelin growth
  • YAP1 activates JAG2 expression in muscle fibers, which in turn regulates the pool of fetal muscle progenitors via NOTCH1 in a non-cell-autonomous manner
  • acetylation-mediated, VGLL4-dependent switch that regulates TEAD1 stability and YAP1-TEAD1 activity
  • nuclear translocation of AMOTL1 is likely accompanied by YAP1 to promote cardiomyocyte proliferation
  • specific interactions between YAP1 and proteins in the ERK5 pathway, such as MEK kinase 3 (MAP3K3) and MAPK7
  • YOD1 stabilizes ITCH and facilitates ITCH-mediated LATS1/2 ubiquitination and degradation, which results in increased YAP1/TAZ level
  • VGLL4 negatively regulates the TEAD1-YAP1 transcriptional complex and exerts its growth inhibitory control through its evolutionary conserved TDU2 domain at its C-terminus
  • functions as a transcriptional co-repressor in the Hippo-Yes-associated protein (YAP1) pathway
  • YAP1 is protective against VSMC apoptosis induced by ER stress through inhibiting CASP8/3 activation mediated in part by upregulation of ANKRD1
  • ANKRD1 is a YAP1 target gene that is induced by RASSF1
  • YAP1 repression of the WNT3 gene controls hESC differentiation along the cardiac mesoderm lineage
  • NUP37 interacted with YAP1 and activated YAP1/TEAD1 signaling by enhancing the interaction between YAP1 and TEAD1
  • RASSF1 mediates transcription factor selection of YAP1 in stem cells, thereby acting as a functional "switch" between pluripotency and initiation of differentiation 9)
  • ZYX promotes colon cancer tumorigenesis in a mitotic-phosphorylation-dependent manner and through CDK8-mediated YAP1 activation
  • VGLL4 is an important regulator of CD274 expression, suggesting a central role of VGLL4 and YAP1 in the regulation of tumor immunity
  • YAP1 is a direct target of METTL14 in acute kidney injury (AKI) progression
  • cell & other
    REGULATION
    inhibited by Hippo tumor suppressor pathway
    Phosphorylated by YES1 and SRC (both YES1 and SRC are able to phosphorylate YAP1)
    Other phosphorylated on serine residues, upon DNA damage
    phosphorylated and inhibited by LATS2
    regulation by angiomotin (AMOT) family proteins via a direct interaction
    regulated via its direct interactions with angiomotin-like proteins
    ASSOCIATED DISORDERS
    corresponding disease(s) CLBMS2
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral   amplification    
    in cancers
    tumoral   amplification    
    amplified and up-regulated in hedgehog-associated medulloblastomas and mediates Shh-driven neural precursor proliferation
    tumoral   amplification --over  
    amplified and overexpressed in a subset of soft tissue sarcomas
    constitutional       loss of function
    exacerbates injury in response to chronic myocardial ischemic injury.
    tumoral     --over  
    in pancreatic cancer tissues and potentially plays an important role in the clonogenicity and growth of pancreatic cancer cells
    tumoral fusion      
    YAP1-TFE3 fusions in epithelioid hemangioendothelioma
    constitutional       loss of function
    of YAP1- and CTNNB1-mediated transcription blocked cell cycle reentry and progression through G1 into S phase, respectively
    tumoral fusion      
    fusion YAP1-FAM118B in meningioma
    Susceptibility to polycystic ovary syndrome (PCOS)
    Variant & Polymorphism other
  • rs11225161 (A/G) was significantly associated with PCOS
  • Candidate gene
  • Shh effector that may be targeted by medulloblastomas therapies aimed at eliminating medulloblastoma recurrence
  • Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancer  
    YAP1-TJP2 complex could represent a target for cancer therapy
    cancerbrain 
    Shh effector that may be targeted by medulloblastomas therapies aimed at eliminating medulloblastoma recurrence
    cardiovascularatheromacardiac
    activation of YAP1 in postnatal cardiomyocytes may be a useful strategy to stimulate cardiomyocyte expansion in therapeutic myocardial regeneration
    cancerreproductiveprostate
    KDM4A/ETV1/YAP1 axis promoting prostate cancer initiation, may be a suitable target for therapeutic inhibition
    ANIMAL & CELL MODELS
  • complete inactivation of Yap1 in mice results in developmental arrest leading to multiple system defects, including yolk sac vasculogenesis and embryonic axis elongation