P46937 (YAP1_HUMAN) 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:	YAP65

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	504 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. Isoform 2 and isoform 3 can activate the C-terminal fragment (CTF) of ERBB4 (isoform 3). Ref.2 Ref.12 Ref.14 Ref.15 Ref.17 Ref.20
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 By similarity. The phosphorylated form interacts with YWHAB. Interacts (via WW domains) with LATS1 (via PPxY motif 2). Interacts with LATS2. Isoform 2 and isoform 3 interact (via WW domain 1) with isoform 3 of ERBB4 (via PPxY motif 2). Interacts with TEAD1, TEAD2, TEAD3 and TEAD4. Interacts with TP73. Interacts with RUNX1. Interacts with HCK. Ref.2 Ref.6 Ref.11 Ref.12 Ref.14 Ref.15 Ref.17 Ref.22 Ref.23
Subcellular location	Cytoplasm. Nucleus. 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. Ref.12 Ref.15 Ref.17 Ref.21
Tissue specificity	Increased expression seen in some liver and prostate cancers. Isoforms lacking the transactivation domain found in striatal neurons of patients with Huntington disease (at protein level). Ref.9 Ref.12
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-400 and Ser-403 by CK1 is triggered by previous phosphorylation at Ser-397 by LATS proteins and leads to YAP1 ubiquitination by SCF(beta-TRCP) E3 ubiquitin ligase and subsequent degradation. Phosphorylated at Thr-119, Ser-138, Thr-154, Ser-367 and Thr-412 by MAPK8/JNK1 and MAPK9/JNK2, which is required for the regukation of apoptosis by YAP1. Ref.7 Ref.8 Ref.10 Ref.12 Ref.13 Ref.15 Ref.16 Ref.17 Ref.18 Ref.19 Ref.20 Ref.21 Ubiquitinated by SCF(beta-TRCP) E3 ubiquitin ligase. Ref.21
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	cell proliferation Inferred from direct assay Ref.12. Source: UniProtKB cellular response to gamma radiation Inferred from direct assay Ref.17. Source: UniProtKB contact inhibition Inferred from direct assay Ref.12. Source: UniProtKB hippo signaling cascade Traceable author statement Ref.15. Source: UniProtKB regulation of transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW response to DNA damage stimulus Inferred from direct assay Ref.17. Source: UniProtKB transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	cytoplasm Inferred from direct assay Ref.12Ref.15. Source: UniProtKB nucleus Inferred from direct assay Ref.12Ref.15Ref.17. Source: UniProtKB
Molecular function	protein binding Inferred from physical interaction Ref.12Ref.15Ref.17Ref.14. Source: UniProtKB transcription coactivator activity Inferred from direct assay Ref.15Ref.17. Source: UniProtKB transcription corepressor activity Inferred from direct assay Ref.15. Source: UniProtKB transcription regulatory region DNA binding Inferred from direct assay Ref.17. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
SMAD1	Q15797	3	EBI-1044059,EBI-1567153

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Note: Additional isoforms lacking the transactivation domain exist.

Isoform 1 (identifier: P46937-1)

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: P46937-2)

Also known as: YAP2;

The sequence of this isoform differs from the canonical sequence as follows:
     328-343: Missing.

Isoform 3 (identifier: P46937-3)

Also known as: YAP1;

The sequence of this isoform differs from the canonical sequence as follows:
     230-267: Missing.
     329-343: AMRNINPSTANSPKC → VRP

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 504

504

Yorkie homolog

PRO_0000076071

Regions

Domain

171 – 204

34

WW 1

Domain

230 – 263

34

WW 2

Region

291 – 504

214

Transactivation domain

Compositional bias

3 – 49

47

Pro-rich

Amino acid modifications

Modified residue

61

1

Phosphoserine; by LATS1 and LATS2 Ref.12 Ref.15 Ref.18

Modified residue

109

1

Phosphoserine; by LATS1 and LATS2 Ref.7 Ref.12 Ref.15 Ref.16

Modified residue

110

1

Phosphothreonine Ref.7 Ref.8

Modified residue

119

1

Phosphothreonine; by MAPK8 and MAPK9 Ref.20

Modified residue

127

1

Phosphoserine; by LATS1 and LATS2 Ref.12 Ref.15 Ref.18 Ref.21

Modified residue

128

1

Phosphoserine Ref.18

Modified residue

131

1

Phosphoserine Ref.18

Modified residue

138

1

Phosphoserine; by MAPK8 and MAPK9 Ref.18 Ref.20

Modified residue

143

1

Phosphothreonine Ref.8 Ref.18

Modified residue

149

1

Phosphoserine Ref.18

Modified residue

154

1

Phosphothreonine; by MAPK8 and MAPK9 Ref.8 Ref.18 Ref.20

Modified residue

164

1

Phosphoserine; by LATS1 and LATS2 Ref.12 Ref.15

Modified residue

274

1

Phosphoserine Ref.18

Modified residue

276

1

Phosphoserine Ref.10

Modified residue

289

1

Phosphoserine Ref.18

Modified residue

367

1

Phosphoserine; by MAPK8 and MAPK9 Ref.18 Ref.20

Modified residue

371

1

Phosphoserine Ref.13 Ref.19

Modified residue

397

1

Phosphoserine; by LATS1 and LATS2 Ref.12 Ref.15 Ref.21

Modified residue

400

1

Phosphoserine; by CK1 Ref.21

Modified residue

403

1

Phosphoserine; by CK1 Ref.21

Modified residue

407

1

Phosphotyrosine; by ABL1 Ref.17

Modified residue

412

1

Phosphothreonine; by MAPK8 and MAPK9 Ref.20

Natural variations

Alternative sequence

230 – 267

38

Missing in isoform 3.

VSP_039053

Alternative sequence

328 – 343

16

Missing in isoform 2.

VSP_039054

Alternative sequence

329 – 343

15

AMRNI…NSPKC → VRP in isoform 3.

VSP_039055

Experimental info

Mutagenesis

80

1

V → A: No change in interaction with TEAD4. Reduced interaction with TEAD4 and transforming ability; when associated with A-84 and A-85. Ref.23

Mutagenesis

84

1

V → A: Reduced interaction with TEAD4 and transforming ability; when associated with A-80 and A-85. Ref.23

Mutagenesis

85

1

P → A: Reduced interaction with TEAD4 and transforming ability; when associated with A-80 and A-84. Ref.23

Mutagenesis

86

1

M → A: Complete loss of interaction with TEAD1. Ref.22

Mutagenesis

89

1

R → A: Complete loss of interaction with TEAD1. Ref.22

Mutagenesis

91

1

L → A: Complete loss of interaction with TEAD1. Ref.22

Mutagenesis

94

1

S → A: Loss of interaction with TEAD1, TEAD2, TEAD3 and TEAD4. Loss of transcriptional coactivation activity towards TEAD1, TEAD2, TEAD3 and TEAD4 but no effect on its activity towards RUNX2 and ERBB4. Ref.14 Ref.22

Mutagenesis

95

1

F → A: Complete loss of interaction with TEAD1. Ref.22

Mutagenesis

96

1

F → A: Loss of interaction with TEAD1. Ref.22

Mutagenesis

122

1

H → A, R, N or K: Loss of phosphorylation by LATS1. Ref.12 Ref.15

Mutagenesis

122

1

H → L or Y: Significantly decreased phosphorylation at S-127 and decreased interaction with YWHAB. Ref.12 Ref.15

Mutagenesis

124

1

R → A: Loss of phosphorylation by LATS1. Ref.15

Mutagenesis

127

1

S → A: Reduced phosphorylation by LATS2, loss of phosphorylation by LATS1, loss of interaction with YWHAB, decreased interaction with ERBB4 and increased nuclear localization and transcriptional coactivation activity toward ERBB4. Ref.2 Ref.12 Ref.15

Mutagenesis

129

1

P → D: No effect on phosphorylation but loss of interaction with YWHAB. Ref.12

Mutagenesis

199

1

W → A: Loss of interaction with ERBB4 and loss of transcriptional coactivation function toward CTF; when associated with A-202. Ref.2

Mutagenesis

202

1

P → A: Loss of interaction with ERBB4 and loss of transcriptional coactivation function toward CTF; when associated with A-199. Ref.2

Mutagenesis

397

1

S → A: Loss of phosphorylation by LATS1. Ref.15

Mutagenesis

407

1

Y → E: Enhanced interaction with TP73. Ref.17

Mutagenesis

407

1

Y → F: No phosphorylation by ABL1 and partial loss of binding to TP73. Ref.17

Secondary structure

1

.

.

.

.

.

.

.

.

504

Helix Strand Turn

Details...

Beta strand

188 – 191

4

Turn

192 – 195

4

Beta strand

196 – 200

5

Turn

202 – 204

3

Beta strand

205 – 207

3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (YAP2L) [UniParc]. Last modified April 20, 2010. Version 2. Checksum: 6145F7049ED338AE	FASTA	504	54,462
	10 20 30 40 50 60 MDPGQQPPPQ PAPQGQGQPP SQPPQGQGPP SGPGQPAPAA TQAAPQAPPA GHQIVHVRGD 70 80 90 100 110 120 SETDLEALFN AVMNPKTANV PQTVPMRLRK LPDSFFKPPE PKSHSRQAST DAGTAGALTP 130 140 150 160 170 180 QHVRAHSSPA SLQLGAVSPG TLTPTGVVSG PAATPTAQHL RQSSFEIPDD VPLPAGWEMA 190 200 210 220 230 240 KTSSGQRYFL NHIDQTTTWQ DPRKAMLSQM NVTAPTSPPV QQNMMNSASG PLPDGWEQAM 250 260 270 280 290 300 TQDGEIYYIN HKNKTTSWLD PRLDPRFAMN QRISQSAPVK QPPPLAPQSP QGGVMGGSNS 310 320 330 340 350 360 NQQQQMRLQQ LQMEKERLRL KQQELLRQAM RNINPSTANS PKCQELALRS QLPTLEQDGG 370 380 390 400 410 420 TQNPVSSPGM SQELRTMTTN SSDPFLNSGT YHSRDESTDS GLSMSSYSVP RTPDDFLNSV 430 440 450 460 470 480 DEMDTGDTIN QSTLPSQQNR FPDYLEAIPG TNVDLGTLEG DGMNIEGEEL MPSLQEALSS 490 500 DILNDMESVL AATKLDKESF LTWL
	Isoform 2 (YAP2) [UniParc]. Checksum: 675CC207C83A311E	FASTA	488	52,748
	10 20 30 40 50 60 MDPGQQPPPQ PAPQGQGQPP SQPPQGQGPP SGPGQPAPAA TQAAPQAPPA GHQIVHVRGD 70 80 90 100 110 120 SETDLEALFN AVMNPKTANV PQTVPMRLRK LPDSFFKPPE PKSHSRQAST DAGTAGALTP 130 140 150 160 170 180 QHVRAHSSPA SLQLGAVSPG TLTPTGVVSG PAATPTAQHL RQSSFEIPDD VPLPAGWEMA 190 200 210 220 230 240 KTSSGQRYFL NHIDQTTTWQ DPRKAMLSQM NVTAPTSPPV QQNMMNSASG PLPDGWEQAM 250 260 270 280 290 300 TQDGEIYYIN HKNKTTSWLD PRLDPRFAMN QRISQSAPVK QPPPLAPQSP QGGVMGGSNS 310 320 330 340 350 360 NQQQQMRLQQ LQMEKERLRL KQQELLRQEL ALRSQLPTLE QDGGTQNPVS SPGMSQELRT 370 380 390 400 410 420 MTTNSSDPFL NSGTYHSRDE STDSGLSMSS YSVPRTPDDF LNSVDEMDTG DTINQSTLPS 430 440 450 460 470 480 QQNRFPDYLE AIPGTNVDLG TLEGDGMNIE GEELMPSLQE ALSSDILNDM ESVLAATKLD KESFLTWL
	Isoform 3 (YAP1) [UniParc]. Checksum: 87CB840D3393EFC0	FASTA	454	48,755
	10 20 30 40 50 60 MDPGQQPPPQ PAPQGQGQPP SQPPQGQGPP SGPGQPAPAA TQAAPQAPPA GHQIVHVRGD 70 80 90 100 110 120 SETDLEALFN AVMNPKTANV PQTVPMRLRK LPDSFFKPPE PKSHSRQAST DAGTAGALTP 130 140 150 160 170 180 QHVRAHSSPA SLQLGAVSPG TLTPTGVVSG PAATPTAQHL RQSSFEIPDD VPLPAGWEMA 190 200 210 220 230 240 KTSSGQRYFL NHIDQTTTWQ DPRKAMLSQM NVTAPTSPPV QQNMMNSASA MNQRISQSAP 250 260 270 280 290 300 VKQPPPLAPQ SPQGGVMGGS NSNQQQQMRL QQLQMEKERL RLKQQELLRQ VRPQELALRS 310 320 330 340 350 360 QLPTLEQDGG TQNPVSSPGM SQELRTMTTN SSDPFLNSGT YHSRDESTDS GLSMSSYSVP 370 380 390 400 410 420 RTPDDFLNSV DEMDTGDTIN QSTLPSQQNR FPDYLEAIPG TNVDLGTLEG DGMNIEGEEL 430 440 450 MPSLQEALSS DILNDMESVL AATKLDKESF LTWL

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: 7782338] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Tissue: Lung.
[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: 12807903] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION, INTERACTION WITH ERBB4, MUTAGENESIS OF SER-127; TRP-199 AND PRO-202.
[3]	"Human chromosome 11 DNA sequence and analysis including novel gene identification." Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K., Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T., Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G. , Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C., Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A., Hattori M., Rogers J., Lander E.S., Sakaki Y. Nature 440:497-500(2006) [PubMed: 16554811] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Pancreas.
[6]	"Characterization of the WW domain of human Yes-associated protein and its polyproline containing ligands." Chen H.I., Einbond A., Kwak S.-J., Linn H., Koepf E., Peterson S., Kelly J.W., Sudol M. J. Biol. Chem. 272:17070-17077(1997) [PubMed: 9202023] [Abstract] Cited for: INTERACTION WITH WBP1 AND WBP2.
[7]	"Large-scale characterization of HeLa cell nuclear phosphoproteins." Beausoleil S.A., Jedrychowski M., Schwartz D., Elias J.E., Villen J., Li J., Cohn M.A., Cantley L.C., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 101:12130-12135(2004) [PubMed: 15302935] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-109 AND THR-110, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[8]	"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed: 17081983] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-110; THR-143 AND THR-154, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[9]	"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: 16461361] [Abstract] Cited for: IDENTIFICATION OF ISOFORMS LACKING THE TRANSCRIPTIONAL ACTIVATION DOMAIN, TISSUE SPECIFICITY.
[10]	"A probability-based approach for high-throughput protein phosphorylation analysis and site localization." Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P. Nat. Biotechnol. 24:1285-1292(2006) [PubMed: 16964243] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-276, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[11]	"Regulation of p73 by Hck through kinase-dependent and independent mechanisms." Paliwal P., Radha V., Swarup G. BMC Mol. Biol. 8:45-45(2007) [PubMed: 17535448] [Abstract] Cited for: INTERACTION WITH HCK.
[12]	"Inactivation of YAP oncoprotein by the Hippo pathway is involved in cell contact inhibition and tissue growth control." Zhao B., Wei X., Li W., Udan R.S., Yang Q., Kim J., Xie J., Ikenoue T., Yu J., Li L., Zheng P., Ye K., Chinnaiyan A., Halder G., Lai Z.C., Guan K.L. Genes Dev. 21:2747-2761(2007) [PubMed: 17974916] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH YWHAB, PHOSPHORYLATION AT SER-61; SER-109; SER-127; SER-164 AND SER-397, MUTAGENESIS OF HIS-122; SER-127 AND PRO-129, TISSUE SPECIFICITY.
[13]	"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: 17525332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-371, MASS SPECTROMETRY. Tissue: Embryonic kidney.
[14]	"TEAD mediates YAP-dependent gene induction and growth control." Zhao B., Ye X., Yu J., Li L., Li W., Li S., Yu J., Lin J.D., Wang C.Y., Chinnaiyan A.M., Lai Z.C., Guan K.L. Genes Dev. 22:1962-1971(2008) [PubMed: 18579750] [Abstract] Cited for: FUNCTION, INTERACTION WITH TEAD1; TEAD2; TEAD3 AND TEAD4, MUTAGENESIS OF SER-94.
[15]	"Tumor suppressor LATS1 is a negative regulator of oncogene YAP." Hao Y., Chun A., Cheung K., Rashidi B., Yang X. J. Biol. Chem. 283:5496-5509(2008) [PubMed: 18158288] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH LATS1 AND LATS2, PHOSPHORYLATION AT SER-61; SER-109; SER-127; SER-164 AND SER-397, MUTAGENESIS OF HIS-122; ARG-124; SER-127 AND SER-397.
[16]	"Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis." Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III J. Proteome Res. 7:1346-1351(2008) [PubMed: 18220336] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-109, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[17]	"Yap1 phosphorylation by c-Abl is a critical step in selective activation of proapoptotic genes in response to DNA damage." Levy D., Adamovich Y., Reuven N., Shaul Y. Mol. Cell 29:350-361(2008) [PubMed: 18280240] [Abstract] Cited for: FUNCTION, PHOSPHORYLATION AT TYR-407 BY ABL1, MUTAGENESIS OF TYR-407, SUBCELLULAR LOCATION, INTERACTION WITH RUNX1 AND TP73.
[18]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-61; SER-127; SER-128; SER-131; SER-138; THR-143; SER-149; THR-154; SER-274; SER-289 AND SER-367, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[19]	"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach." Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S. Anal. Chem. 81:4493-4501(2009) [PubMed: 19413330] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-371, MASS SPECTROMETRY. Tissue: Embryonic kidney.
[20]	"JNK phosphorylates Yes-associated protein (YAP) to regulate apoptosis." Tomlinson V., Gudmundsdottir K., Luong P., Leung K.Y., Knebel A., Basu S. Cell Death Dis. 1:E29-E29(2010) [PubMed: 21364637] [Abstract] Cited for: PHOSPHORYLATION AT THR-119; SER-138; THR-154; SER-367 AND THR-412 BY MAPK8/JNK1 AND MAPK9/JNK2, FUNCTION.
[21]	"A coordinated phosphorylation by Lats and CK1 regulates YAP stability through SCF(beta-TRCP)." Zhao B., Li L., Tumaneng K., Wang C.-Y., Guan K.-L. Genes Dev. 24:72-85(2010) [PubMed: 20048001] [Abstract] Cited for: PHOSPHORYLATION AT SER-400 AND SER-403 BY CSNK1D/CK1, PHOSPHORYLATION AT SER-127 AND SER-397 BY LATS PROTEINS, UBIQUITINATION BY SCF(BETA-TRCP), SUBCELLULAR LOCATION.
[22]	"Structural insights into the YAP and TEAD complex." Li Z., Zhao B., Wang P., Chen F., Dong Z., Yang H., Guan K.L., Xu Y. Genes Dev. 24:235-240(2010) [PubMed: 20123905] [Abstract] Cited for: INTERACTION WITH TEAD1, X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 50-171 IN COMPLEX WITH TEAD1, MUTAGENESIS OF MET-86; ARG-89; LEU-91; SER-94; PHE-95 AND PHE-96.
[23]	"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: 20123908] [Abstract] Cited for: INTERACTION WITH TEAD4, MUTAGENESIS OF VAL-80; VAL-84 AND PRO-85.
[24]	"Solution structures of the YAP65 WW domain and the variant L30 K in complex with the peptides GTPPPPYTVG, N-(n-octyl)-GPPPY and PLPPY and the application of peptide libraries reveal a minimal binding epitope." Pires J.R., Taha-Nejad F., Toepert F., Ast T., Hoffmueller U., Schneider-Mergener J., Kuehne R., Macias M.J., Oschkinat H. J. Mol. Biol. 314:1147-1156(2001) [PubMed: 11743730] [Abstract] Cited for: STRUCTURE BY NMR OF 165-210 OF WILD-TYPE AND MUTANT LYS-190 IN COMPLEX WITH PRO-RICH PEPTIDES.
[25]	"Using flexible loop mimetics to extend phi-value analysis to secondary structure interactions." Ferguson N., Pires J.R., Toepert F., Johnson C.M., Pan Y.P., Volkmer-Engert R., Schneider-Mergener J., Daggett V., Oschkinat H., Fersht A. Proc. Natl. Acad. Sci. U.S.A. 98:13008-13013(2001) [PubMed: 11687614] [Abstract] Cited for: STRUCTURE BY NMR OF 165-204.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

X80507 Genomic DNA. Translation: CAA56672.1.
AY316529 mRNA. Translation: AAP92710.1.
AP000942 Genomic DNA. No translation available.
AP001527 Genomic DNA. No translation available.
AP002777 Genomic DNA. No translation available.
CH471065 Genomic DNA. Translation: EAW67011.1.
CH471065 Genomic DNA. Translation: EAW67015.1.
BC038235 mRNA. Translation: AAH38235.1.

IPI

IPI00009326.
IPI00216919.
IPI00956212.

PIR

A56954.

RefSeq

NP_001123617.1. NM_001130145.2.
NP_001181973.1. NM_001195044.1.
NP_001181974.1. NM_001195045.1.

UniGene

Hs.503692.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1JMQ	NMR	-	A	165-210	[»]
1K5R	NMR	-	A	165-204	[»]
1K9Q	NMR	-	A	165-204	[»]
1K9R	NMR	-	A	165-204	[»]
2LAW	NMR	-	A	230-263	[»]
2LAX	NMR	-	A	170-205	[»]
2LAY	NMR	-	A	170-205	[»]
3KYS	X-ray	2.80	B/D	50-171	[»]

ProteinModelPortal

P46937.

SMR

P46937. Positions 50-100, 165-265.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-40839N.

IntAct

P46937. 10 interactions.

MINT

MINT-3388819.

STRING

P46937.

PTM databases

PhosphoSite

P46937.

Polymorphism databases

DMDM

294862479.

Proteomic databases

PRIDE

P46937.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000345877; ENSP00000331023; ENSG00000137693.

GeneID

10413.

KEGG

hsa:10413.

UCSC

uc001pgs.1. human.

Organism-specific databases

CTD

10413.

GeneCards

GC11P102015.

HGNC

HGNC:16262. YAP1.

HPA

CAB009370.

MIM

606608. gene.

neXtProt

NX_P46937.

PharmGKB

PA38103.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG07700.

GeneTree

ENSGT00510000046760.

HOVERGEN

HBG002748.

OMA

QSSYEIP.

OrthoDB

EOG451DQP.

PhylomeDB

P46937.

Enzyme and pathway databases

Pathway_Interaction_DB

tgfbrpathway. TGF-beta receptor signaling.

Gene expression databases

ArrayExpress

P46937.

Bgee

P46937.

CleanEx

HS_YAP1.

Genevestigator

P46937.

GermOnline

ENSG00000137693. Homo sapiens.

Family and domain databases

InterPro

IPR001202. WW_Rsp5_WWP.
[Graphical view]

Gene3D

G3DSA:2.20.70.10. G3DSA:2.20.70.10. 2 hits.

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

NextBio

39472.

SOURCE

Search...

Entry information

Entry name

YAP1_HUMAN

Accession

Primary (citable) accession number: P46937
Secondary accession number(s): Q7Z574, Q8IUY9

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1995
Last sequence update:	April 20, 2010
Last modified:	January 25, 2012
This is version 116 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.