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Protein

Transcriptional coactivator YAP1

Gene

Yap1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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. 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.By similarity

GO - Molecular functioni

  • activating transcription factor binding Source: MGI
  • chromatin binding Source: MGI
  • proline-rich region binding Source: MGI
  • protein C-terminus binding Source: MGI
  • protein heterodimerization activity Source: MGI
  • RNA polymerase II core promoter sequence-specific DNA binding Source: MGI
  • transcription coactivator activity Source: UniProtKB
  • transcription corepressor activity Source: MGI
  • transcription factor activity, RNA polymerase II transcription factor binding Source: MGI
  • transcription regulatory region DNA binding Source: UniProtKB

GO - Biological processi

  • bud elongation involved in lung branching Source: MGI
  • cell morphogenesis Source: MGI
  • cell proliferation Source: MGI
  • cellular response to DNA damage stimulus Source: MGI
  • cellular response to gamma radiation Source: UniProtKB
  • cellular response to retinoic acid Source: MGI
  • contact inhibition Source: MGI
  • DNA damage induced protein phosphorylation Source: UniProtKB
  • embryonic heart tube morphogenesis Source: MGI
  • hippo signaling Source: MGI
  • keratinocyte differentiation Source: MGI
  • lateral mesoderm development Source: MGI
  • lung epithelial cell differentiation Source: MGI
  • negative regulation of epithelial cell differentiation Source: MGI
  • negative regulation of extrinsic apoptotic signaling pathway Source: MGI
  • negative regulation of stem cell differentiation Source: MGI
  • notochord development Source: MGI
  • paraxial mesoderm development Source: MGI
  • positive regulation of canonical Wnt signaling pathway Source: MGI
  • positive regulation of cell proliferation Source: MGI
  • positive regulation of organ growth Source: MGI
  • positive regulation of stem cell population maintenance Source: MGI
  • positive regulation of transcription, DNA-templated Source: MGI
  • positive regulation of transcription from RNA polymerase II promoter Source: MGI
  • protein complex assembly Source: MGI
  • regulation of canonical Wnt signaling pathway Source: MGI
  • regulation of cell proliferation Source: MGI
  • regulation of keratinocyte proliferation Source: MGI
  • regulation of metanephric nephron tubule epithelial cell differentiation Source: MGI
  • regulation of neurogenesis Source: MGI
  • regulation of stem cell proliferation Source: MGI
  • somatic stem cell population maintenance Source: MGI
  • transcription, DNA-templated Source: UniProtKB-KW
  • vasculogenesis Source: MGI

Keywordsi

Molecular functionActivator, Repressor
Biological processTranscription, Transcription regulation

Enzyme and pathway databases

ReactomeiR-MMU-1251985. Nuclear signaling by ERBB4.
R-MMU-2028269. Signaling by Hippo.
R-MMU-2032785. YAP1- and WWTR1 (TAZ)-stimulated gene expression.
R-MMU-8951671. RUNX3 regulates YAP1-mediated transcription.

Names & Taxonomyi

Protein namesi
Recommended name:
Transcriptional coactivator YAP1
Short name:
Yes-associated protein 1
Alternative name(s):
Protein yorkie homolog
Yes-associated protein YAP65 homolog
Gene namesi
Name:Yap1
Synonyms:Yap, Yap65
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 9

Organism-specific databases

MGIiMGI:103262. Yap1.

Subcellular locationi

  • Cytoplasm By similarity
  • Nucleus 1 Publication

  • Note: Both phosphorylation and cell density can regulate its subcellular localization. Phosphorylation sequesters it in the cytoplasm by inhibiting its translocation into the nucleus. At low density, predominantly nuclear and is translocated to the cytoplasm at high density. PTPN14 induces translocation from the nucleus to the cytoplasm.By similarity

GO - Cellular componenti

  • cytoplasm Source: MGI
  • cytosol Source: MGI
  • membrane Source: MGI
  • nucleus Source: UniProtKB
  • TEAD-1-YAP complex Source: MGI
  • TEAD-2-YAP complex Source: MGI
  • transcription factor complex Source: MGI

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Keywords - Diseasei

Proto-oncogene

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000760721 – 488Transcriptional coactivator YAP1Add BLAST488

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei46PhosphoserineCombined sources1
Modified residuei48PhosphothreonineBy similarity1
Modified residuei90PhosphoserineBy similarity1
Modified residuei94PhosphoserineCombined sources1
Modified residuei95PhosphothreonineBy similarity1
Modified residuei104Phosphothreonine; by MAPK8 and MAPK9By similarity1
Modified residuei112PhosphoserineCombined sources1
Modified residuei113PhosphoserineBy similarity1
Modified residuei116PhosphoserineBy similarity1
Modified residuei123PhosphoserineCombined sources1
Modified residuei149Phosphoserine; by LATS1 and LATS2By similarity1
Modified residuei274PhosphoserineBy similarity1
Modified residuei352Phosphoserine; by MAPK8 and MAPK9By similarity1
Modified residuei356PhosphoserineCombined sources1
Modified residuei366PhosphoserineBy similarity1
Modified residuei367PhosphoserineCombined sources1
Modified residuei373PhosphoserineBy similarity1
Modified residuei382Phosphoserine; by LATS1 and LATS2By similarity1
Modified residuei385Phosphoserine; by CK1By similarity1
Modified residuei388Phosphoserine; by CK1By similarity1
Modified residuei392Phosphotyrosine; by ABL1By similarity1
Modified residuei397Phosphothreonine; by MAPK8 and MAPK9By similarity1

Post-translational modificationi

Phosphorylated by LATS1 and LATS2; leading to cytoplasmic translocation and inactivation. Phosphorylated by ABL1; leading to YAP1 stabilization, enhanced interaction with TP73 and recruitment onto proapoptotic genes; in response to DNA damage. Phosphorylation at Ser-385 and Ser-388 by CK1 is triggered by previous phosphorylation at Ser-382 by LATS proteins and leads to YAP1 ubiquitination by SCF(beta-TRCP) E3 ubiquitin ligase and subsequent degradation (By similarity). Phosphorylated at Thr-104, Ser-123, Ser-352 and Thr-397 by MAPK8/JNK1 and MAPK9/JNK2, which is required for the regulation of apoptosis by YAP1 (By similarity).By similarity
Ubiquitinated by SCF(beta-TRCP) E3 ubiquitin ligase.By similarity

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

MaxQBiP46938.
PaxDbiP46938.
PeptideAtlasiP46938.
PRIDEiP46938.

PTM databases

iPTMnetiP46938.
PhosphoSitePlusiP46938.

Expressioni

Tissue specificityi

Isoforms lacking the transactivation domain seen in striatal neurons (at protein level). Ubiquitous. Isoform 2 is expressed at higher levels in the neural tissues. In the embryo, it is expressed in brain, eye, and the maxillary and frontonasal components of the primary palate.3 Publications

Gene expression databases

BgeeiENSMUSG00000053110.
CleanExiMM_YAP1.
ExpressionAtlasiP46938. baseline and differential.
GenevisibleiP46938. MM.

Interactioni

Subunit structurei

Binds to the SH3 domain of the YES kinase (By similarity). Binds to WBP1 and WBP2 (PubMed:7644498). Binds, in vitro, through the WW1 domain, to neural isoforms of ENAH that contain the PPSY motif (PubMed:9407065). The phosphorylated form interacts with YWHAB (By similarity). Interacts (via WW domains) with LATS1 (via PPxY motif 2) (By similarity). Interacts with LATS2 (By similarity). Interacts (via WW domain 1) with isoform JM-A of ERBB4 (via PPxY motif 2) (By similarity). Interacts with TEAD1, TEAD2 and TEAD3 (By similarity). Interacts with TP73 and HCK (By similarity). Interacts with RUNX1 (By similarity). Interacts with TEAD4 (PubMed:20123908). Interacts (via WW domains) with PTPN14 (via PPxY motif 2); this interaction leads to the cytoplasmic sequestration of YAP1 and inhibits its transcriptional co-activator activity (By similarity).By similarity3 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • activating transcription factor binding Source: MGI
  • proline-rich region binding Source: MGI
  • protein C-terminus binding Source: MGI
  • protein heterodimerization activity Source: MGI

Protein-protein interaction databases

BioGridi204611. 38 interactors.
DIPiDIP-40015N.
ELMiP46938.
IntActiP46938. 31 interactors.
MINTiMINT-85211.
STRINGi10090.ENSMUSP00000069554.

Structurei

Secondary structure

1488
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi51 – 58Combined sources8
Beta strandi61 – 63Combined sources3
Helixi71 – 73Combined sources3
Helixi79 – 81Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3JUAX-ray3.00B/D/F/H47-85[»]
ProteinModelPortaliP46938.
SMRiP46938.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP46938.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini156 – 189WW 1PROSITE-ProRule annotationAdd BLAST34
Domaini215 – 248WW 2PROSITE-ProRule annotationAdd BLAST34

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni276 – 488Transactivation domainAdd BLAST213

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili71 – 85By similarityAdd BLAST15
Coiled coili283 – 344Sequence analysisAdd BLAST62

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi3 – 34Pro-richAdd BLAST32

Domaini

The first coiled-coil region mediates most of the interaction with TEAD transcription factors.By similarity

Sequence similaritiesi

Belongs to the YAP1 family.Curated

Keywords - Domaini

Coiled coil, Repeat

Phylogenomic databases

eggNOGiKOG0940. Eukaryota.
COG5021. LUCA.
GeneTreeiENSGT00510000046760.
HOGENOMiHOG000007854.
HOVERGENiHBG002748.
InParanoidiP46938.
KOiK16687.
OMAiDQTTTWQ.
OrthoDBiEOG091G095A.
PhylomeDBiP46938.
TreeFamiTF326941.

Family and domain databases

CDDicd00201. WW. 2 hits.
InterProiView protein in InterPro
IPR001202. WW_dom.
PfamiView protein in Pfam
PF00397. WW. 2 hits.
SMARTiView protein in SMART
SM00456. WW. 2 hits.
SUPFAMiSSF51045. SSF51045. 2 hits.
PROSITEiView protein in PROSITE
PS01159. WW_DOMAIN_1. 2 hits.
PS50020. WW_DOMAIN_2. 2 hits.

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Note: Additional isoforms lacking the transactivation domain exist.
Isoform 1 (identifier: P46938-1) [UniParc]FASTAAdd to basket
Also known as: YAP2L

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MEPAQQPPPQ PAPQGPAPPS VSPAGTPAAP PAPPAGHQVV HVRGDSETDL
60 70 80 90 100
EALFNAVMNP KTANVPQTVP MRLRKLPDSF FKPPEPKSHS RQASTDAGTA
110 120 130 140 150
GALTPQHVRA HSSPASLQLG AVSPGTLTAS GVVSGPAAAP AAQHLRQSSF
160 170 180 190 200
EIPDDVPLPA GWEMAKTSSG QRYFLNHNDQ TTTWQDPRKA MLSQLNVPAP
210 220 230 240 250
ASPAVPQTLM NSASGPLPDG WEQAMTQDGE VYYINHKNKT TSWLDPRLDP
260 270 280 290 300
RFAMNQRITQ SAPVKQPPPL APQSPQGGVL GGGSSNQQQQ IQLQQLQMEK
310 320 330 340 350
ERLRLKQQEL FRQAIRNINP STANAPKCQE LALRSQLPTL EQDGGTPNAV
360 370 380 390 400
SSPGMSQELR TMTTNSSDPF LNSGTYHSRD ESTDSGLSMS SYSIPRTPDD
410 420 430 440 450
FLNSVDEMDT GDTISQSTLP SQQSRFPDYL EALPGTNVDL GTLEGDAMNI
460 470 480
EGEELMPSLQ EALSSEILDV ESVLAATKLD KESFLTWL
Length:488
Mass (Da):52,383
Last modified:April 20, 2010 - v2
Checksum:i5A2221B74B1400F9
GO
Isoform 2 (identifier: P46938-2) [UniParc]FASTAAdd to basket
Also known as: YAP2

The sequence of this isoform differs from the canonical sequence as follows:
     313-328: Missing.

Show »
Length:472
Mass (Da):50,703
Checksum:i174FD33E0381126C
GO

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_039056313 – 328Missing in isoform 2. 3 PublicationsAdd BLAST16

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X80508 mRNA. Translation: CAA56673.1.
CH466522 Genomic DNA. Translation: EDL24950.1.
BC014733 mRNA. Translation: AAH14733.1.
BC039125 mRNA. Translation: AAH39125.1.
BC094313 mRNA. Translation: AAH94313.1.
CCDSiCCDS40533.1. [P46938-2]
CCDS52718.1. [P46938-1]
PIRiB56954.
RefSeqiNP_001164618.1. NM_001171147.1. [P46938-1]
NP_033560.1. NM_009534.3. [P46938-2]
UniGeneiMm.221992.
Mm.486262.

Genome annotation databases

EnsembliENSMUST00000065353; ENSMUSP00000069554; ENSMUSG00000053110. [P46938-1]
ENSMUST00000086580; ENSMUSP00000083772; ENSMUSG00000053110. [P46938-2]
GeneIDi22601.
KEGGimmu:22601.
UCSCiuc009ode.2. mouse. [P46938-2]
uc009odf.2. mouse. [P46938-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiYAP1_MOUSE
AccessioniPrimary (citable) accession number: P46938
Secondary accession number(s): Q52KJ5, Q91WL1
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: April 20, 2010
Last modified: August 30, 2017
This is version 147 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. SIMILARITY comments
    Index of protein domains and families