DegronMD - P46937(YAP1)

FUNCTION: 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 (PubMed:17974916, PubMed:18280240, PubMed:18579750, PubMed:21364637, PubMed:30447097). 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 (PubMed:18158288). 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 (PubMed:25778702). Plays a key role in controlling 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 (PubMed:18158288). 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 (PubMed:18579750). Suppresses ciliogenesis via acting as a transcriptional corepressor of the TEAD4 target genes AURKA and PLK1 (PubMed:25849865). In conjunction with WWTR1, involved in the regulation of TGFB1-dependent SMAD2 and SMAD3 nuclear accumulation (By similarity). {ECO:0000250|UniProtKB:P46938, ECO:0000269|PubMed:17974916, ECO:0000269|PubMed:18158288, ECO:0000269|PubMed:18280240, ECO:0000269|PubMed:18579750, ECO:0000269|PubMed:21364637, ECO:0000269|PubMed:25778702, ECO:0000269|PubMed:25849865, ECO:0000269|PubMed:30447097}.; FUNCTION: [Isoform 2]: Activates the C-terminal fragment (CTF) of ERBB4 (isoform 3). {ECO:0000269|PubMed:12807903}.; FUNCTION: [Isoform 3]: Activates the C-terminal fragment (CTF) of ERBB4 (isoform 3). {ECO:0000269|PubMed:12807903}. View more >>

GO - Biological processes (BP): bud elongation involved in lung branching [GO:0060449]; cardiac muscle tissue regeneration [GO:0061026]; cell morphogenesis [GO:0000902]; cell population proliferation [GO:0008283]; cellular response to DNA damage stimulus [GO:0006974]; cellular response to gamma radiation [GO:0071480]; cellular response to retinoic acid [GO:0071300]; contact inhibition [GO:0060242]; embryonic heart tube morphogenesis [GO:0003143]; heart process [GO:0003015]; hippo signaling [GO:0035329]; interleukin-6-mediated signaling pathway [GO:0070102]; intestinal epithelial cell development [GO:0060576]; keratinocyte differentiation [GO:0030216]; lateral mesoderm development [GO:0048368]; lung epithelial cell differentiation [GO:0060487]; negative regulation of cilium assembly [GO:1902018]; negative regulation of epithelial cell apoptotic process [GO:1904036]; negative regulation of epithelial cell differentiation [GO:0030857]; negative regulation of extrinsic apoptotic signaling pathway [GO:2001237]; negative regulation of fat cell differentiation [GO:0045599]; negative regulation of gene expression [GO:0010629]; negative regulation of stem cell differentiation [GO:2000737]; negative regulation of transcription by RNA polymerase II [GO:0000122]; notochord development [GO:0030903]; paraxial mesoderm development [GO:0048339]; positive regulation of canonical Wnt signaling pathway [GO:0090263]; positive regulation of cardiac muscle cell proliferation [GO:0060045]; positive regulation of cell growth [GO:0030307]; positive regulation of epithelial cell proliferation [GO:0050679]; positive regulation of gene expression [GO:0010628]; positive regulation of intracellular estrogen receptor signaling pathway [GO:0033148]; positive regulation of Notch signaling pathway [GO:0045747]; positive regulation of osteoblast differentiation [GO:0045669]; positive regulation of protein localization to nucleus [GO:1900182]; positive regulation of stem cell population maintenance [GO:1902459]; positive regulation of transcription, DNA-templated [GO:0045893]; positive regulation of transcription by RNA polymerase II [GO:0045944]; progesterone receptor signaling pathway [GO:0050847]; protein-containing complex assembly [GO:0065003]; regulation of keratinocyte proliferation [GO:0010837]; regulation of metanephric nephron tubule epithelial cell differentiation [GO:0072307]; regulation of neurogenesis [GO:0050767]; regulation of stem cell proliferation [GO:0072091]; response to progesterone [GO:0032570]; somatic stem cell population maintenance [GO:0035019]; tissue homeostasis [GO:0001894]; trophectodermal cell differentiation [GO:0001829]; vasculogenesis [GO:0001570]; wound healing [GO:0042060] View more >>

GO - Molecular function (MF): View more >>

GO - Cellular component (CC): View more >>

Choose a PDB ID:
Open in full screen with detailed sequence annotations

Data table is loading....

Mutation	Sample	Cancer	Dataset	Degron hit	Class	Location	Type	Impact score
p.S184F	TCGA-14-1451	GBM	TCGA	QRYFLNHID	DEG_APCC_DBOX_1	186:194	Mutation rewiring degron network	0.2778
p.S184F	DO13384	GBM	ICGC	QRYFLNHID	DEG_APCC_DBOX_1	186:194	Mutation rewiring degron network	0.2778
p.Q344K	TCGA-66-2765	LUSC	TCGA	LRSQLPTLE	DEG_APCC_DBOX_1	348:356	Mutation rewiring degron network	0.2222
p.Q344K	DO26761	LUSC	ICGC	LRSQLPTLE	DEG_APCC_DBOX_1	348:356	Mutation rewiring degron network	0.2222
p.T398A	TCGA-AP-A051	UCEC	TCGA	DSGLSMS	DEG_SCF_TRCP1_1	399:405	Mutation blocking phosphorylation signal	0.75
p.T398A	DO42673	UCEC	ICGC	DSGLSMS	DEG_SCF_TRCP1_1	399:405	Mutation blocking phosphorylation signal	0.75
p.N339H	TCGA-DF-A2KV	UCEC	TCGA	LRSQLPTLE	DEG_APCC_DBOX_1	348:356	Mutation rewiring degron network	0.0833
p.N339H	DO219771	UCEC	ICGC	LRSQLPTLE	DEG_APCC_DBOX_1	348:356	Mutation rewiring degron network	0.0833
p.H392N	TCGA-EE-A2GT	SKCM	TCGA	DSGLSMS	DEG_SCF_TRCP1_1	399:405	Mutation rewiring degron network	0.1389
p.H392N	DO37946	SKCM	ICGC	DSGLSMS	DEG_SCF_TRCP1_1	399:405	Mutation rewiring degron network	0.1389
p.P341A	TCGA-HE-7130	KIRP	TCGA	LRSQLPTLE	DEG_APCC_DBOX_1	348:356	Mutation rewiring degron network	0.1389
p.P341A	DO20776	KIRP	ICGC	LRSQLPTLE	DEG_APCC_DBOX_1	348:356	Mutation rewiring degron network	0.1389
p.E396D	TCGA-HE-7130	KIRP	TCGA	DSGLSMS	DEG_SCF_TRCP1_1	399:405	Mutation rewiring degron network	0.25
p.E396D	DO20776	KIRP	ICGC	DSGLSMS	DEG_SCF_TRCP1_1	399:405	Mutation rewiring degron network	0.25
p.S366C	TCGA-IG-A3Y9	ESCA	TCGA	LRSQLPTLE	DEG_APCC_DBOX_1	348:356	Mutation blocking phosphorylation signal	0.5
p.T196I	TCGA-J7-A8I2	KIRP	TCGA	QRYFLNHID	DEG_APCC_DBOX_1	186:194	Mutation rewiring degron network	0.2778
p.T196I	DO223958	KIRP	ICGC	QRYFLNHID	DEG_APCC_DBOX_1	186:194	Mutation rewiring degron network	0.2778
p.P413Q	TCGA-KO-8408	KICH	TCGA	DSGLSMS	DEG_SCF_TRCP1_1	399:405	Mutation rewiring degron network	0.1111
p.P413Q	DO220562	KICH	ICGC	DSGLSMS	DEG_SCF_TRCP1_1	399:405	Mutation rewiring degron network	0.1111
p.L402P	DO223566	CLLE	ICGC	DSGLSMS	DEG_SCF_TRCP1_1	399:405	Mutation altering degron motif	0.6471
p.R394Q	DO234263	ESAD	ICGC	DSGLSMS	DEG_SCF_TRCP1_1	399:405	Mutation rewiring degron network	0.1944
p.G359C	DO228976	LICA	ICGC	LRSQLPTLE	DEG_APCC_DBOX_1	348:356	Mutation rewiring degron network	0.25
p.V409F	DO229019	LICA	ICGC	DSGLSMS	DEG_SCF_TRCP1_1	399:405	Mutation rewiring degron network	0.2222
p.S397I	DO229035	LICA	ICGC	DSGLSMS	DEG_SCF_TRCP1_1	399:405	Mutation blocking phosphorylation signal	0.7222
p.S350N	DO229268	THCA	ICGC	LRSQLPTLE	DEG_APCC_DBOX_1	348:356	Mutation altering degron motif	0.5958
p.Q361P	SIDM00973	Melanoma	GDSC	LRSQLPTLE	DEG_APCC_DBOX_1	348:356	Mutation blocking phosphorylation signal	0.6389
p.Q361P	WM793B	skin	COSMIC	LRSQLPTLE	DEG_APCC_DBOX_1	348:356	Mutation blocking phosphorylation signal	0.6389
p.S344A	SIDM00845	Burkitt's Lymphoma	GDSC	LRSQLPTLE	DEG_APCC_DBOX_1	348:356	Mutation rewiring degron network	0.2222
p.S344A	SIDM00035	Thyroid Gland Carcinoma	GDSC	LRSQLPTLE	DEG_APCC_DBOX_1	348:356	Mutation rewiring degron network	0.2222
p.S344A	SIDM00461	Acute Myeloid Leukemia	GDSC	LRSQLPTLE	DEG_APCC_DBOX_1	348:356	Mutation rewiring degron network	0.2222
p.S344A	SIDM00946	T-Lymphoblastic Leukemia	GDSC	LRSQLPTLE	DEG_APCC_DBOX_1	348:356	Mutation rewiring degron network	0.2222
p.S344A	SIDM01519	Head and Neck Carcinoma	GDSC	LRSQLPTLE	DEG_APCC_DBOX_1	348:356	Mutation rewiring degron network	0.2222
p.S344A	Daudi	haematopoietic and lymphoid tissue	COSMIC	LRSQLPTLE	DEG_APCC_DBOX_1	348:356	Mutation rewiring degron network	0.2222
p.S344A	OCI-AML5	haematopoietic and lymphoid tissue	COSMIC	LRSQLPTLE	DEG_APCC_DBOX_1	348:356	Mutation rewiring degron network	0.2222
p.E360D	SIDM01044	Other Solid Cancers	GDSC	LRSQLPTLE	DEG_APCC_DBOX_1	348:356	Mutation rewiring degron network	0.2222
p.E360D	EPLC-272H	lung	COSMIC	LRSQLPTLE	DEG_APCC_DBOX_1	348:356	Mutation rewiring degron network	0.2222
p.A351S	SIDM01077	Prostate Carcinoma	GDSC	LRSQLPTLE	DEG_APCC_DBOX_1	348:356	Mutation altering degron motif	0.7588
p.A351S	VCaP	prostate	COSMIC	LRSQLPTLE	DEG_APCC_DBOX_1	348:356	Mutation altering degron motif	0.7588
p.S183F	SIDM00169	Head and Neck Carcinoma	GDSC	QRYFLNHID	DEG_APCC_DBOX_1	186:194	Mutation rewiring degron network	0.25
p.E178D	ACH-000585	Lung Cancer	CCLE	QRYFLNHID	DEG_APCC_DBOX_1	186:194	Mutation rewiring degron network	0.1111
p.E178D	EPLC-272H	lung	COSMIC	QRYFLNHID	DEG_APCC_DBOX_1	186:194	Mutation rewiring degron network	0.1111
p.M199I	ACH-000781	Lung Cancer	CCLE	QRYFLNHID	DEG_APCC_DBOX_1	186:194	Mutation rewiring degron network	0.1944
p.M199I	NCI-H2023	lung	COSMIC	QRYFLNHID	DEG_APCC_DBOX_1	186:194	Mutation rewiring degron network	0.1944
p.Q179P	ACH-000827	Skin Cancer	CCLE	QRYFLNHID	DEG_APCC_DBOX_1	186:194	Mutation rewiring degron network	0.1389
p.Q179P	WM793B	skin	COSMIC	QRYFLNHID	DEG_APCC_DBOX_1	186:194	Mutation rewiring degron network	0.1389
p.A347S	VCaP	prostate	COSMIC	LRSQLPTLE	DEG_APCC_DBOX_1	348:356	Mutation rewiring degron network	0.3056
p.G413A	BHY	upper aerodigestive tract	COSMIC	DSGLSMS	DEG_SCF_TRCP1_1	399:405	Mutation rewiring degron network	0.1111
p.S340A	Daudi	haematopoietic and lymphoid tissue	COSMIC	LRSQLPTLE	DEG_APCC_DBOX_1	348:356	Mutation blocking phosphorylation signal	0.5556
p.S340A	OCI-AML5	haematopoietic and lymphoid tissue	COSMIC	LRSQLPTLE	DEG_APCC_DBOX_1	348:356	Mutation blocking phosphorylation signal	0.5556
p.E340D	EPLC-272H	lung	COSMIC	LRSQLPTLE	DEG_APCC_DBOX_1	348:356	Mutation blocking phosphorylation signal	0.5556
p.E344D	EPLC-272H	lung	COSMIC	LRSQLPTLE	DEG_APCC_DBOX_1	348:356	Mutation rewiring degron network	0.2222
p.Q341P	WM793B	skin	COSMIC	LRSQLPTLE	DEG_APCC_DBOX_1	348:356	Mutation rewiring degron network	0.1389
p.Q357P	WM793B	skin	COSMIC	LRSQLPTLE	DEG_APCC_DBOX_1	348:356	Mutation rewiring degron network	0.3056
p.M361I	NCI-H2023	lung	COSMIC	LRSQLPTLE	DEG_APCC_DBOX_1	348:356	Mutation blocking phosphorylation signal	0.6389
p.M365I	NCI-H2023	lung	COSMIC	LRSQLPTLE	DEG_APCC_DBOX_1	348:356	Mutation rewiring degron network	0.0833
p.M343I	NCI-H2023	lung	COSMIC	LRSQLPTLE	DEG_APCC_DBOX_1	348:356	Mutation rewiring degron network	0.1944
p.R390C	SNU-1040	large intestine	COSMIC	DSGLSMS	DEG_SCF_TRCP1_1	399:405	Mutation blocking phosphorylation signal	0.5278
p.D349A	HCC1599	breast	COSMIC	LRSQLPTLE	DEG_APCC_DBOX_1	348:356	Mutation altering degron motif	0.7793
p.R406C	SNU-1040	large intestine	COSMIC	DSGLSMS	DEG_SCF_TRCP1_1	399:405	Mutation rewiring degron network	0.3056
p.E356D	EPLC-272H	lung	COSMIC	LRSQLPTLE	DEG_APCC_DBOX_1	348:356	Mutation altering degron motif	0.5647
p.Q345P	WM793B	skin	COSMIC	LRSQLPTLE	DEG_APCC_DBOX_1	348:356	Mutation rewiring degron network	0.25

Kaplan plot for YAP1 in

Select cancer type:
Download patient class data (Lower:Upper = 50%:50%)

*NOTE: the Kaplan plots were collected from OncoLnc

DegronMD: protein-targeted degradation, mutation and drug response to degrons

YAP1

UniProt ID: P46937

Entrez ID: 10413

Protein name: Transcriptional coactivator YAP1 (Yes-associated protein 1) (Protein yorkie homolog) (Yes-associated protein YAP65 homolog)

External links: UniprotKB HGNC RefSeq COSMIC

Data table is loading....

Kaplan plot for YAP1 in