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P46938 (YAP1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 113. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Yorkie homolog
Alternative name(s):
65 kDa Yes-associated protein
Short name=YAP65
Gene names
Name:Yap1
Synonyms:Yap, Yap65
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length488 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

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. 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 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.

Subunit structure

Binds to the SH3 domain of the YES kinase. Binds to WBP1 and WBP2. Binds, in vitro, through the WW1 domain, to neural isoforms of ENAH that contain the PPSY motif. The phosphorylated form interacts with YWHAB. Interacts (via WW domains) with LATS1 (via PPxY motif 2). Interacts with LATS2. Interacts (via WW domain 1) with isoform JM-Aof ERBB4 (via PPxY motif 2). Interacts with TEAD1, TEAD2 and TEAD3 By similarity. Interacts with TP73 and HCK By similarity. Interacts with RUNX1 By similarity. Interacts with TEAD4. 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. Ref.5 Ref.6 Ref.12

Subcellular location

Cytoplasm By similarity. Nucleus By similarity. 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 By similarity.

Tissue specificity

Isoforms lacking the transactivation domain seen in striatal neurons (at protein level). Ubiquitous. Isoform 2 is expressed at higher levels in the neural tissues. Ref.2 Ref.8

Domain

The first coiled-coil region mediates most of the interaction with TEAD transcription factors By similarity. Ref.8

Post-translational modification

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 regukation of apoptosis by YAP1 By similarity.

Ubiquitinated by SCF(beta-TRCP) E3 ubiquitin ligase By similarity.

Sequence similarities

Belongs to the YORKIE family.

Contains 2 WW domains.

Ontologies

Keywords
   Biological processTranscription
Transcription regulation
   Cellular componentCytoplasm
Nucleus
   Coding sequence diversityAlternative splicing
   DiseaseProto-oncogene
   DomainCoiled coil
Repeat
   Molecular functionActivator
Repressor
   PTMPhosphoprotein
Ubl conjugation
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processDNA damage induced protein phosphorylation

Inferred from sequence or structural similarity. Source: UniProtKB

cell proliferation

Inferred from electronic annotation. Source: Ensembl

cellular response to gamma radiation

Inferred from sequence or structural similarity. Source: UniProtKB

contact inhibition

Inferred from electronic annotation. Source: Ensembl

embryonic heart tube morphogenesis

Inferred from genetic interaction PubMed 18332127. Source: MGI

hippo signaling

Inferred from genetic interaction PubMed 18369314. Source: MGI

keratinocyte differentiation

Inferred from mutant phenotype PubMed 18369314. Source: MGI

lateral mesoderm development

Inferred from genetic interaction PubMed 18332127. Source: MGI

negative regulation of epithelial cell differentiation

Inferred from direct assay PubMed 17980593. Source: MGI

negative regulation of extrinsic apoptotic signaling pathway

Inferred from genetic interaction PubMed 17980593. Source: MGI

notochord development

Inferred from genetic interaction PubMed 18332127. Source: MGI

paraxial mesoderm development

Inferred from genetic interaction PubMed 18332127. Source: MGI

positive regulation of canonical Wnt signaling pathway

Inferred from direct assay PubMed 17980593. Source: MGI

positive regulation of cell proliferation

Inferred from direct assay PubMed 17980593PubMed 19952108. Source: MGI

positive regulation of organ growth

Inferred from direct assay PubMed 17980593. Source: MGI

positive regulation of transcription from RNA polymerase II promoter

Inferred from genetic interaction PubMed 16207754. Source: MGI

regulation of canonical Wnt signaling pathway

Inferred from genetic interaction PubMed 23974041. Source: MGI

regulation of cell proliferation

Inferred from genetic interaction PubMed 19004856. Source: MGI

regulation of keratinocyte proliferation

Inferred from mutant phenotype PubMed 18369314. Source: MGI

regulation of metanephric nephron tubule epithelial cell differentiation

Inferred from genetic interaction PubMed 23974041. Source: MGI

regulation of stem cell proliferation

Inferred from direct assay PubMed 19952108. Source: MGI

somatic stem cell maintenance

Inferred from direct assay PubMed 17980593. Source: MGI

transcription from RNA polymerase II promoter

Inferred from physical interaction PubMed 19952108. Source: GOC

vasculogenesis

Inferred from mutant phenotype PubMed 16354681. Source: MGI

   Cellular_componentcytoplasm

Inferred from direct assay PubMed 18369314PubMed 19289085PubMed 22232070PubMed 23974041. Source: MGI

nucleus

Inferred from direct assay PubMed 18369314PubMed 19004856PubMed 19289085PubMed 19952108PubMed 22232070PubMed 23974041. Source: MGI

transcription factor complex

Inferred from genetic interaction PubMed 16207754. Source: MGI

   Molecular_functionRNA polymerase II transcription factor binding transcription factor activity

Inferred from physical interaction PubMed 19952108. Source: MGI

chromatin binding

Inferred from direct assay PubMed 19952108PubMed 21512031. Source: MGI

proline-rich region binding

Inferred from physical interaction PubMed 9305852. Source: MGI

transcription coactivator activity

Inferred from direct assay PubMed 16332960. Source: UniProtKB

transcription corepressor activity

Inferred from electronic annotation. Source: Ensembl

transcription regulatory region DNA binding

Inferred from sequence or structural similarity. Source: UniProtKB

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

Tp73Q9JJP22EBI-1211949,EBI-1770138

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Note: Additional isoforms lacking the transactivation domain exist.
Isoform 1 (identifier: P46938-1)

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.
Isoform 2 (identifier: P46938-2)

Also known as: YAP2;

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 488488Yorkie homolog
PRO_0000076072

Regions

Domain156 – 18934WW 1
Domain215 – 24834WW 2
Region276 – 488213Transactivation domain
Coiled coil71 – 8515 By similarity
Coiled coil283 – 34462 Potential
Compositional bias3 – 3432Pro-rich

Amino acid modifications

Modified residue461Phosphoserine; by LATS1 and LATS2 By similarity
Modified residue481Phosphothreonine By similarity
Modified residue941Phosphoserine; alternate Ref.11
Modified residue941Phosphoserine; by LATS1 and LATS2; alternate By similarity
Modified residue951Phosphothreonine By similarity
Modified residue1041Phosphothreonine; by MAPK8 and MAPK9 By similarity
Modified residue1121Phosphoserine; by LATS1 and LATS2 By similarity
Modified residue1161Phosphoserine By similarity
Modified residue1231Phosphoserine; by MAPK8 and MAPK9 By similarity
Modified residue1491Phosphoserine; by LATS1 and LATS2 By similarity
Modified residue2741Phosphoserine By similarity
Modified residue3521Phosphoserine; by MAPK8 and MAPK9 By similarity
Modified residue3561Phosphoserine Ref.10
Modified residue3821Phosphoserine; by LATS1 and LATS2 By similarity
Modified residue3851Phosphoserine; by CK1 By similarity
Modified residue3881Phosphoserine; by CK1 By similarity
Modified residue3921Phosphotyrosine; by ABL1 By similarity
Modified residue3971Phosphothreonine; by MAPK8 and MAPK9 By similarity

Natural variations

Alternative sequence313 – 32816Missing in isoform 2.
VSP_039056

Secondary structure

......... 488
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (YAP2L) [UniParc].

Last modified April 20, 2010. Version 2.
Checksum: 5A2221B74B1400F9

FASTA48852,383
        10         20         30         40         50         60 
MEPAQQPPPQ PAPQGPAPPS VSPAGTPAAP PAPPAGHQVV HVRGDSETDL EALFNAVMNP 

        70         80         90        100        110        120 
KTANVPQTVP MRLRKLPDSF FKPPEPKSHS RQASTDAGTA GALTPQHVRA HSSPASLQLG 

       130        140        150        160        170        180 
AVSPGTLTAS GVVSGPAAAP AAQHLRQSSF EIPDDVPLPA GWEMAKTSSG QRYFLNHNDQ 

       190        200        210        220        230        240 
TTTWQDPRKA MLSQLNVPAP ASPAVPQTLM NSASGPLPDG WEQAMTQDGE VYYINHKNKT 

       250        260        270        280        290        300 
TSWLDPRLDP RFAMNQRITQ SAPVKQPPPL APQSPQGGVL GGGSSNQQQQ IQLQQLQMEK 

       310        320        330        340        350        360 
ERLRLKQQEL FRQAIRNINP STANAPKCQE LALRSQLPTL EQDGGTPNAV SSPGMSQELR 

       370        380        390        400        410        420 
TMTTNSSDPF LNSGTYHSRD ESTDSGLSMS SYSIPRTPDD FLNSVDEMDT GDTISQSTLP 

       430        440        450        460        470        480 
SQQSRFPDYL EALPGTNVDL GTLEGDAMNI EGEELMPSLQ EALSSEILDV ESVLAATKLD 


KESFLTWL 

« Hide

Isoform 2 (YAP2) [UniParc].

Checksum: 174FD33E0381126C
Show »

FASTA47250,703

References

« Hide 'large scale' references
[1]"Characterization of the mammalian YAP (Yes-associated protein) gene and its role in defining a novel protein module, the WW domain."
Sudol M., Bork P., Einbond A., Kastury K., Druck T., Negrini M., Huebner K., Lehman D.
J. Biol. Chem. 270:14733-14741(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
Strain: NIH Swiss.
Tissue: Embryo.
[2]"WW domain-containing protein YAP associates with ErbB-4 and acts as a co-transcriptional activator for the carboxyl-terminal fragment of ErbB-4 that translocates to the nucleus."
Komuro A., Nagai M., Navin N.E., Sudol M.
J. Biol. Chem. 278:33334-33341(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), TISSUE SPECIFICITY.
[3]Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
Strain: 129, C57BL/6 and FVB/N.
Tissue: Brain, Kidney and Mammary gland.
[5]"The WW domain of Yes-associated protein binds a proline-rich ligand that differs from the consensus established for Src homology 3-binding modules."
Chen H.I., Sudol M.
Proc. Natl. Acad. Sci. U.S.A. 92:7819-7823(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH WBP1 AND WBP2.
[6]"The WW domain of neural protein FE65 interacts with proline-rich motifs in Mena, the mammalian homolog of Drosophila enabled."
Ermekova K.S., Zambrano N., Linn H., Minopoli G., Gertler F., Russo T., Sudol M.
J. Biol. Chem. 272:32869-32877(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH ENAH.
[7]"Phosphoproteomic analysis of the developing mouse brain."
Ballif B.A., Villen J., Beausoleil S.A., Schwartz D., Gygi S.P.
Mol. Cell. Proteomics 3:1093-1101(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Embryonic brain.
[8]"Transcriptional repression induces a slowly progressive atypical neuronal death associated with changes of YAP isoforms and p73."
Hoshino M., Qi M.-L., Yoshimura N., Tagawa K., Wada Y.-I., Enokido Y., Marubuchi S., Harjes P., Arai N., Oyanagi K., Blandino G., Sudol M., Rich T., Kanazawa I., Wanker E.E., Saitoe M., Okazawa H.
J. Cell Biol. 172:589-604(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION OF ISOFORMS LACKING THE TRANSCRIPTIONAL ACTIVATION DOMAIN, TISSUE SPECIFICITY.
[9]"Large-scale phosphorylation analysis of mouse liver."
Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Liver.
[10]"ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage."
Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y., Gygi S.P., Elledge S.J.
Science 316:1160-1166(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-356, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Embryonic fibroblast.
[11]"Large scale localization of protein phosphorylation by use of electron capture dissociation mass spectrometry."
Sweet S.M., Bailey C.M., Cunningham D.L., Heath J.K., Cooper H.J.
Mol. Cell. Proteomics 8:904-912(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-94, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Embryonic fibroblast.
[12]"Structural basis of YAP recognition by TEAD4 in the hippo pathway."
Chen L., Chan S.W., Zhang X., Walsh M., Lim C.J., Hong W., Song H.
Genes Dev. 24:290-300(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH TEAD4, X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF 47-85 IN COMPLEX WITH TEAD4.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
PIRB56954.
RefSeqNP_001164618.1. NM_001171147.1.
NP_033560.1. NM_009534.3.
UniGeneMm.221992.
Mm.486262.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
3JUAX-ray3.00B/D/F/H47-85[»]
ProteinModelPortalP46938.
SMRP46938. Positions 47-85, 150-250.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid204611. 28 interactions.
DIPDIP-40015N.
IntActP46938. 8 interactions.
MINTMINT-85211.

PTM databases

PhosphoSiteP46938.

Proteomic databases

PaxDbP46938.
PRIDEP46938.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000065353; ENSMUSP00000069554; ENSMUSG00000053110. [P46938-1]
ENSMUST00000086580; ENSMUSP00000083772; ENSMUSG00000053110. [P46938-2]
GeneID22601.
KEGGmmu:22601.
UCSCuc009ode.2. mouse. [P46938-2]
uc009odf.2. mouse. [P46938-1]

Organism-specific databases

CTD10413.
MGIMGI:103262. Yap1.

Phylogenomic databases

eggNOGCOG5021.
GeneTreeENSGT00510000046760.
HOGENOMHOG000007854.
HOVERGENHBG002748.
InParanoidQ91WL1.
KOK16687.
OMALRQSSYE.
OrthoDBEOG75MVW6.
PhylomeDBP46938.
TreeFamTF326941.

Gene expression databases

ArrayExpressP46938.
BgeeP46938.
CleanExMM_YAP1.
GenevestigatorP46938.

Family and domain databases

InterProIPR001202. WW_dom.
[Graphical view]
PfamPF00397. WW. 2 hits.
[Graphical view]
SMARTSM00456. WW. 2 hits.
[Graphical view]
SUPFAMSSF51045. SSF51045. 2 hits.
PROSITEPS01159. WW_DOMAIN_1. 2 hits.
PS50020. WW_DOMAIN_2. 2 hits.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP46938.
NextBio302957.
PROP46938.
SOURCESearch...

Entry information

Entry nameYAP1_MOUSE
AccessionPrimary (citable) accession number: P46938
Secondary accession number(s): Q52KJ5, Q91WL1
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: April 20, 2010
Last modified: April 16, 2014
This is version 113 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot