P46937

※ Protein Information

Tag	Content
UniProt Accession	YAP1_HUMAN; P46937;
Entrez ID	10413
GenBank Protein ID	NM_001130145.2; NM_001195044.1; NM_001195045.1; NM_001282097.1; NM_001282098.1; NM_001282099.1; NM_001282100.1; NM_001282101.1;
GenBank Nucleotide ID	NP_001123617.1; NP_001181973.1; NP_001181974.1; NP_001269026.1; NP_001269027.1; NP_001269028.1; NP_001269029.1; NP_001269030.1;
Protein Name	Transcriptional coactivator YAP1 (Yes-associated protein 1) (Protein yorkie homolog) (Yes-associated protein YAP65 homolog)
Gene Name	YAP1; YAP65
Organism	Homo sapiens
NCBI Taxa ID	9606
Functional Description	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). 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 regul(view all) Functional Description 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). 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 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 (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).;Isoform 2: Isoform 2 and isoform 3 can activate the C-terminal fragment (CTF) of ERBB4 (isoform 3).
Sequence (Fasta)	MDPGQQPPPQ PAPQGQGQPP SQPPQGQGPP SGPGQPAPAA TQAAPQAPPA GHQIVHVRGD 60 SETDLEALFN AVMNPKTANV PQTVPMRLRK LPDSFFKPPE PKSHSRQAST DAGTAGALTP 120 QHVRAHSSPA SLQLGAVSPG TLTPTGVVSG PAATPTAQHL RQSSFEIPDD VPLPAGWEMA 180 KTSSGQRYFL NHIDQTTTWQ DPRKAMLSQM NVTAPTSPPV QQNMMNSASG PLPDGWEQAM 240 TQDGEIYYIN HKNKTTSWLD PRLDPRFAMN QRISQSAPVK QPPPLAPQSP QGGVMGGSNS 300 NQQQQMRLQQ LQMEKERLRL KQQELLRQAM RNINPSTANS PKCQELALRS QLPTLEQDGG 360 TQNPVSSPGM SQELRTMTTN SSDPFLNSGT YHSRDESTDS GLSMSSYSVP RTPDDFLNSV 420 DEMDTGDTIN QSTLPSQQNR FPDYLEAIPG TNVDLGTLEG DGMNIEGEEL MPSLQEALSS 480 DILNDMESVL AATKLDKESF LTWL 505 Fasta Sequence >P46937\|YAP1; YAP65\|Homo sapiens (Human) MDPGQQPPPQPAPQGQGQPPSQPPQGQGPPSGPGQPAPAATQAAPQAPPAGHQIVHVRGDSETDLEALFNAVMNPKTANVPQTVPMRLRKLPDSFFKPPEPKSHSRQASTDAGTAGALTPQHVRAHSSPASLQLGAVSPGTLTPTGVVSGPAATPTAQHLRQSSFEIPDDVPLPAGWEMAKTSSGQRYFLNHIDQTTTWQDPRKAMLSQMNVTAPTSPPVQQNMMNSASGPLPDGWEQAMTQDGEIYYINHKNKTTSWLDPRLDPRFAMNQRISQSAPVKQPPPLAPQSPQGGVMGGSNSNQQQQMRLQQLQMEKERLRLKQQELLRQAMRNINPSTANSPKCQELALRSQLPTLEQDGGTQNPVSSPGMSQELRTMTTNSSDPFLNSGTYHSRDESTDSGLSMSSYSVPRTPDDFLNSVDEMDTGDTINQSTLPSQQNRFPDYLEAIPGTNVDLGTLEGDGMNIEGEELMPSLQEALSSDILNDMESVLAATKLDKESFLTWL

※ PTM-Disease Association

Num	PTM	Disease	Cell Type	Type	PTM Site	PMID
1	Phosphorylation	Gastric cancer		P		23058008
1	[Reference]: In the present study, human gastric adenocarcinoma tissues of different grades (N=78) were collected and the mRNA and protein expression of YAP and phosphorylated YAP (p-YAP) in gastric adenocarcinomas were evaluated using immunohistochemistry, Real-time PCR and Western blot assays
2	Serine Phosphorylation	Hepatocellular carcinoma/Hepatocarcinoma/Hepatoma		A	S127	22761457
2	[Reference]: Indeed, mouse models demonstrate that MST1/2 deficiency in the liver results in loss of YAP Ser127 phosphorylation, uncontrolled liver growth and development of hepatocellular carcinoma
3	Serine Phosphorylation	Lung cancer/carcinoma	A549 cell line	D	S127	21060948
3	[Reference]: Phosphoproteome?profile of human lung cancer?cell?line?A549
4	Serine Phosphorylation	Bladder cancer		D	S127	26119935
4	[Reference]: Yap phosphorylation decreased in cisplatin resistant tumors (xenograft model).
5	Serine Phosphorylation	Cervical cancer/carcinoma	Hela cell line	P	S127	23027127
5	[Reference]: LKB1 tumor suppressor regulates AMP kinase/mTOR-independent cell growth and proliferation via the phosphorylation of Yap

※ Disease Cross-ref Annotation

Database	Annotation
CTD (Curated) (count: 5)	MESH:C535575 ; Carcinoma, squamous cell of head and neck OMIM:120433 ; COLOBOMA, OCULAR, WITH OR WITHOUT HEARING IMPAIRMENT, CLEFT LIP/PALATE, AND/OR MENTAL RETARDATION MESH:D009447 ; Neuroblastoma MESH:D010051 ; Ovarian Neoplasms MESH:D012008 ; Recurrence
DisGeNet (Curated) (count: 19) (view all)	C0018784; Sensorineural Hearing Loss (disorder) C0018965; Hematuria C0025362; Mental Retardation C0026010; Microphthalmos C0027819; Neuroblastoma C0206732; Epithelioid hemangioendothelioma C0240063; Coloboma of iris C0240896; Fundus coloboma C0423903; Low intelligence C0795902; Coloboma, cleft lip-palate and mental retardation syndrome C0917816; Mental deficiency C0919267; ovarian neoplasm C1168401; Squamous cell carcinoma of the head and neck C1398522; Cleft palate and bilateral cleft lip C1843367; Poor school performance C3714756; Intellectual Disability C4020876; Dull intelligence C4280625; Decreased size of eyeball C4280808; Abnormally small eyeball
GWASdb (count: 11) (view all)	rs10895257; Matrix metalloproteinase levels; cardiovascular system disease rs11225148; Pubertal anthropometrics; Null rs11602707; Matrix metalloproteinase levels; cardiovascular system disease rs17689778; Multiple complex diseases; Null rs10501995; Hearing function; auditory system disease rs11225161; Hearing function; auditory system disease rs1894116; Hearing function; auditory system disease rs1894116; Polycystic ovary syndrome; polycystic ovary syndrome rs7131529; Multiple complex diseases; Null rs10791569; Matrix metalloproteinase levels; cardiovascular system disease rs11225166; Hearing function; auditory system disease

※ PTM Sites

PTM	Modification Sites
Phosphorylation (count: 52) (view all)	103 FKPPEPKSHSRQAST dbPAF 105 PPEPKSHSRQASTDA dbPAF 109 KSHSRQASTDAGTAG dbPAF 110 SHSRQASTDAGTAGA dbPAF 114 QASTDAGTAGALTPQ dbPAF 119 AGTAGALTPQHVRAH dbPAF 127 PQHVRAHSSPASLQL dbPAF 128 QHVRAHSSPASLQLG dbPAF 131 RAHSSPASLQLGAVS dbPAF 138 SLQLGAVSPGTLTPT dbPAF 141 LGAVSPGTLTPTGVV dbPAF 143 AVSPGTLTPTGVVSG dbPAF 145 SPGTLTPTGVVSGPA dbPAF 149 LTPTGVVSGPAATPT dbPAF 154 VVSGPAATPTAQHLR dbPAF 156 SGPAATPTAQHLRQS dbPAF 163 TAQHLRQSSFEIPDD dbPAF 164 AQHLRQSSFEIPDDV dbPAF 217 MNVTAPTSPPVQQNM dbPAF 274 FAMNQRISQSAPVKQ dbPAF 276 MNQRISQSAPVKQPP dbPAF 289 PPPLAPQSPQGGVMG dbPAF 298 QGGVMGGSNSNQQQQ dbPAF 300 GVMGGSNSNQQQQMR dbPAF 336 AMRNINPSTANSPKC dbPAF 337 MRNINPSTANSPKCQ dbPAF 340 INPSTANSPKCQELA dbPAF 350 CQELALRSQLPTLEQ dbPAF 366 GGTQNPVSSPGMSQE dbPAF 367 GTQNPVSSPGMSQEL dbPAF 371 PVSSPGMSQELRTMT dbPAF 379 QELRTMTTNSSDPFL dbPAF 381 LRTMTTNSSDPFLNS dbPAF 382 RTMTTNSSDPFLNSG dbPAF 388 SSDPFLNSGTYHSRD dbPAF 390 DPFLNSGTYHSRDES dbPAF 391 PFLNSGTYHSRDEST dbPAF 397 TYHSRDESTDSGLSM dbPAF 398 YHSRDESTDSGLSMS dbPAF 400 SRDESTDSGLSMSSY dbPAF 403 ESTDSGLSMSSYSVP dbPAF 405 TDSGLSMSSYSVPRT dbPAF 406 DSGLSMSSYSVPRTP dbPAF 407 SGLSMSSYSVPRTPD dbPAF 408 GLSMSSYSVPRTPDD dbPAF 412 SSYSVPRTPDDFLNS dbPAF 419 TPDDFLNSVDEMDTG dbPAF 432 TGDTINQSTLPSQQN dbPAF 499 ATKLDKESFLTWL** dbPAF 61 IVHVRGDSETDLEAL dbPAF 63 HVRGDSETDLEALFN dbPAF 94 RLRKLPDSFFKPPEP dbPAF
Acetylation (count: 4)	280 ISQSAPVKQPPPLAP PLMD 315 LQQLQMEKERLRLKQ PLMD 90 TVPMRLRKLPDSFFK PLMD 97 KLPDSFFKPPEPKSH PLMD
Ubiquitination (count: 5)	280 ISQSAPVKQPPPLAP PLMD 315 LQQLQMEKERLRLKQ PLMD 321 EKERLRLKQQELLRQ PLMD 497 LAATKLDKESFLTWL PLMD 76 FNAVMNPKTANVPQT PLMD
Sumoylation (count: 2)	280 ISQSAPVKQPPPLAP PLMD 97 KLPDSFFKPPEPKSH PLMD
Malonylation (count: 1)	315 LQQLQMEKERLRLKQ PLMD
Methylation (count: 2)	494 ESVLAATKLDKESFL PLMD 497 LAATKLDKESFLTWL PLMD

※ Protein-Protein Interaction

Network

Interaction

Source

A8MX15	P46937	MINT
O14745	P46937	HPRD; MINT
O14828	P46937	HPRD
O15105	P46937	HPRD
O15350	P46937	HPRD;MINT
O60716	P46937	IntAct
P00519	P46937	HPRD
P12830	P46937	IntAct
P22223	P46937	IntAct
P26232	P46937	IntAct
P27348	P46937	HPRD; MINT
P28347	P46937	HPRD
P31749	P46937	HPRD
P31946	P46937	DIP
P35221	P46937	IntAct
P35222	P46937	IntAct
P46937	P46940	IntAct
P46937	P61981	HPRD; IntAct; MINT
P46937	P63104	MINT
P46937	Q00839	HPRD
P46937	Q01196	HPRD
P46937	Q13625	HPRD; MINT
P46937	Q15303	HPRD
P46937	Q15561	HPRD
P46937	Q15562	HPRD; DIP
P46937	Q15599	MINT
P46937	Q15797	IntAct
P46937	Q16621	HPRD
P46937	Q4VCS5	IntAct
P46937	Q5T802	HPRD
P46937	Q969T9	HPRD; MINT
P46937	Q96G27	HPRD
P46937	Q99594	HPRD
P46937	Q9H204	MINT
P46937	Q9H3D4	MINT
P46937	Q9UKB1	MINT
P46937	Q9Y297	MINT

PTMD Annotation Information

※ Protein Information

Functional Description

Fasta Sequence

※ PTM-Disease Association

※ Disease Cross-ref Annotation

※ PTM Sites

※ Protein-Protein Interaction