P46938 (YAP1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Yorkie homolog

Alternative name(s):
65 kDa Yes-associated protein
Short name=YAP65

Gene names

Name:	Yap1
Synonyms:	Yap, Yap65

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	488 AA.
Sequence status	Complete.
Protein existence	Evidence 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-A of 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.11
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.7
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 process	Transcription Transcription regulation
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Alternative splicing
Disease	Proto-oncogene
Domain	Repeat
Molecular function	Activator Repressor
PTM	Phosphoprotein Ubl conjugation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	DNA damage induced protein phosphorylation Inferred from sequence or structural similarity. Source: UniProtKB cell proliferation Inferred from electronic annotation. Source: Compara cellular response to gamma radiation Inferred from sequence or structural similarity. Source: UniProtKB contact inhibition Inferred from electronic annotation. Source: Compara embryonic heart tube morphogenesis Inferred from genetic interaction PubMed 18332127. Source: MGI hippo signaling cascade 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 apoptotic process Inferred from genetic interaction PubMed 17980593. Source: MGI negative regulation of epithelial cell differentiation Inferred from direct assay 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 receptor 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 keratinocyte proliferation Inferred from mutant phenotype PubMed 18369314. 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 vasculogenesis Inferred from mutant phenotype PubMed 16354681. Source: MGI
Cellular_component	cytoplasm Inferred from direct assay PubMed 18369314PubMed 19289085. Source: MGI transcription factor complex Inferred from genetic interaction PubMed 16207754. Source: MGI
Molecular_function	RNA 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 transcription coactivator activity Inferred from direct assay PubMed 16332960. Source: UniProtKB transcription corepressor activity Inferred from electronic annotation. Source: Compara transcription regulatory region DNA binding Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

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 key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 488

488

Yorkie homolog

PRO_0000076072

Regions

Domain

156 – 189

34

WW 1

Domain

215 – 248

34

WW 2

Region

276 – 488

213

Transactivation domain

Compositional bias

3 – 34

32

Pro-rich

Amino acid modifications

Modified residue

46

1

Phosphoserine; by LATS1 and LATS2 By similarity

Modified residue

48

1

Phosphothreonine By similarity

Modified residue

94

1

Phosphoserine; by LATS1 and LATS2 By similarity

Modified residue

104

1

Phosphothreonine; by MAPK8 and MAPK9 By similarity

Modified residue

112

1

Phosphoserine; by LATS1 and LATS2 By similarity

Modified residue

113

1

Phosphoserine Ref.8

Modified residue

116

1

Phosphoserine By similarity

Modified residue

123

1

Phosphoserine; by MAPK8 and MAPK9 By similarity

Modified residue

149

1

Phosphoserine; by LATS1 and LATS2 By similarity

Modified residue

274

1

Phosphoserine By similarity

Modified residue

352

1

Phosphoserine; by MAPK8 and MAPK9 By similarity

Modified residue

356

1

Phosphoserine Ref.9

Modified residue

382

1

Phosphoserine; by LATS1 and LATS2 By similarity

Modified residue

385

1

Phosphoserine; by CK1 By similarity

Modified residue

388

1

Phosphoserine; by CK1 By similarity

Modified residue

392

1

Phosphotyrosine; by ABL1 By similarity

Modified residue

397

1

Phosphothreonine; by MAPK8 and MAPK9 By similarity

Natural variations

Alternative sequence

313 – 328

16

Missing in isoform 2.

VSP_039056

Secondary structure

1

.

.

.

.

.

.

.

.

.

488

Helix Strand Turn

Details...

Helix

51 – 58

8

Beta strand

61 – 63

3

Helix

71 – 73

3

Helix

79 – 81

3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (YAP2L) [UniParc]. Last modified April 20, 2010. Version 2. Checksum: 5A2221B74B1400F9	FASTA	488	52,383
	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
	Isoform 2 (YAP2) [UniParc]. Checksum: 174FD33E0381126C	FASTA	472	50,703
	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 FRQELALRSQ LPTLEQDGGT PNAVSSPGMS QELRTMTTNS SDPFLNSGTY 370 380 390 400 410 420 HSRDESTDSG LSMSSYSIPR TPDDFLNSVD EMDTGDTISQ STLPSQQSRF PDYLEALPGT 430 440 450 460 470 NVDLGTLEGD AMNIEGEELM PSLQEALSSE ILDVESVLAA TKLDKESFLT WL

References

	« Hide 'large scale' referencesShow '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]	"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.
[8]	"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: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-112 AND SER-113, MASS SPECTROMETRY. Tissue: Liver.
[9]	"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, MASS SPECTROMETRY. Tissue: Embryonic kidney.
[10]	"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, MASS SPECTROMETRY. Tissue: Embryonic fibroblast.
[11]	"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.

IPI

IPI00108989.
IPI00621717.

PIR

B56954.

RefSeq

NP_001164618.1. NM_001171147.1.
NP_033560.1. NM_009534.3.

UniGene

Mm.221992.
Mm.486262.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3JUA	X-ray	3.00	B/D/F/H	47-85	[»]

ProteinModelPortal

P46938.

SMR

P46938. Positions 47-85, 150-250.

ModBase

Search...

Protein-protein interaction databases

IntAct

P46938. 2 interactions.

MINT

MINT-85211.

PTM databases

PhosphoSite

P46938.

Proteomic databases

PaxDb

P46938.

PRIDE

P46938.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENSMUST00000065353; ENSMUSP00000069554; ENSMUSG00000053110.
ENSMUST00000086580; ENSMUSP00000083772; ENSMUSG00000053110.

GeneID

22601.

KEGG

mmu:22601.

UCSC

uc009ode.2. mouse.
uc009odf.2. mouse.

Organism-specific databases

CTD

10413.

MGI

MGI:103262. Yap1.

Phylogenomic databases

eggNOG

COG5021.

GeneTree

ENSGT00510000046760.

HOGENOM

HOG000007854.

HOVERGEN

HBG002748.

InParanoid

Q91WL1.

KO

K16687.

OMA

QSSYEIP.

Gene expression databases

ArrayExpress

P46938.

Bgee

P46938.

CleanEx

MM_YAP1.

Genevestigator

P46938.

GermOnline

ENSMUSG00000053110. Mus musculus.

Family and domain databases

InterPro

IPR001202. WW_dom.
[Graphical view]

Pfam

PF00397. WW. 2 hits.
[Graphical view]

SMART

SM00456. WW. 2 hits.
[Graphical view]

SUPFAM

SSF51045. WW_Rsp5_WWP. 2 hits.

PROSITE

PS01159. WW_DOMAIN_1. 2 hits.
PS50020. WW_DOMAIN_2. 2 hits.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

P46938.

NextBio

302957.

SOURCE

Search...

Entry information

Entry name

YAP1_MOUSE

Accession

Primary (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:	May 1, 2013
This is version 104 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program