dbPTM

WWTR1_HUMAN - PTM Information in dbPTM

Basic Information of Protein

Overview of Protein Modification Sites with Functional and Structural Information
UniProt ID	WWTR1_HUMAN
UniProt AC	Q9GZV5
Protein Name	WW domain-containing transcription regulator protein 1
Gene Name	WWTR1
Organism	Homo sapiens (Human).
Sequence Length	400
Subcellular Localization	Nucleus. Cytoplasm. Concentrates along specific portions of the plasma membrane, and accumulates in punctate nuclear bodies. When phosphorylated, is retained in cytoplasm by YWHAZ. Can be retained in the nucleus by MED15.
Protein Description	Transcriptional coactivator which acts as a 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. WWTR1 enhances PAX8 and NKX2-1/TTF1-dependent gene activation. Regulates the nuclear accumulation of SMADS and has a key role in coupling them to the transcriptional machinery such as the mediator complex. Regulates embryonic stem-cell self-renewal, promotes cell proliferation and epithelial-mesenchymal transition..
Protein Sequence	MNPASAPPPLPPPGQQVIHVTQDLDTDLEALFNSVMNPKPSSWRKKILPESFFKEPDSGSHSRQSSTDSSGGHPGPRLAGGAQHVRSHSSPASLQLGTGAGAAGSPAQQHAHLRQQSYDVTDELPLPPGWEMTFTATGQRYFLNHIEKITTWQDPRKAMNQPLNHMNLHPAVSSTPVPQRSMAVSQPNLVMNHQHQQQMAPSTLSQQNHPTQNPPAGLMSMPNALTTQQQQQQKLRLQRIQMERERIRMRQEELMRQEAALCRQLPMEAETLAPVQAAVNPPTMTPDMRSITNNSSDPFLNGGPYHSREQSTDSGLGLGCYSVPTTPEDFLSNVDEMDTGENAGQTPMNINPQQTRFPDFLDCLPGTNVDLGTLESEDLIPLFNDVESALNKSEPFLTWL

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
5	Phosphorylation	---MNPASAPPPLPP ---CCCCCCCCCCCC	42.43	22210691
34	Phosphorylation	DLEALFNSVMNPKPS CHHHHHHHHHCCCCH	18.53	22210691
41	Phosphorylation	SVMNPKPSSWRKKIL HHHCCCCHHHHHCCC	48.97	22210691
46	Ubiquitination	KPSSWRKKILPESFF CCHHHHHCCCCHHHC	40.68	29967540
51	Phosphorylation	RKKILPESFFKEPDS HHCCCCHHHCCCCCC	33.76	30177828
58	Phosphorylation	SFFKEPDSGSHSRQS HHCCCCCCCCCCCCC	53.57	27273156
60	Phosphorylation	FKEPDSGSHSRQSST CCCCCCCCCCCCCCC	23.42	23403867
62	Phosphorylation	EPDSGSHSRQSSTDS CCCCCCCCCCCCCCC	33.44	22617229
65	Phosphorylation	SGSHSRQSSTDSSGG CCCCCCCCCCCCCCC	33.81	29255136
66	Phosphorylation	GSHSRQSSTDSSGGH CCCCCCCCCCCCCCC	28.09	27273156
67	Phosphorylation	SHSRQSSTDSSGGHP CCCCCCCCCCCCCCC	45.18	29255136
69	Phosphorylation	SRQSSTDSSGGHPGP CCCCCCCCCCCCCCC	30.85	30242111
70	Phosphorylation	RQSSTDSSGGHPGPR CCCCCCCCCCCCCCC	52.16	27273156
87	Phosphorylation	GGAQHVRSHSSPASL CCCCCCCCCCCCCCE	26.99	29255136
89	Phosphorylation	AQHVRSHSSPASLQL CCCCCCCCCCCCEEC	38.98	29255136
90	Phosphorylation	QHVRSHSSPASLQLG CCCCCCCCCCCEECC	21.04	29255136
93	Phosphorylation	RSHSSPASLQLGTGA CCCCCCCCEECCCCC	21.74	30278072
98	Phosphorylation	PASLQLGTGAGAAGS CCCEECCCCCCCCCC	32.24	29255136
105	Phosphorylation	TGAGAAGSPAQQHAH CCCCCCCCHHHHHHH	16.61	29255136
117	Phosphorylation	HAHLRQQSYDVTDEL HHHHHHCCCCCCCCC	18.24	22199227
118	Phosphorylation	AHLRQQSYDVTDELP HHHHHCCCCCCCCCC	15.30	22199227
121	Phosphorylation	RQQSYDVTDELPLPP HHCCCCCCCCCCCCC	22.36	22199227
133	Phosphorylation	LPPGWEMTFTATGQR CCCCCEEEEEECCCC	13.30	20068231
135	Phosphorylation	PGWEMTFTATGQRYF CCCEEEEEECCCCHH	17.72	20068231
137	Phosphorylation	WEMTFTATGQRYFLN CEEEEEECCCCHHHH	30.69	20068231
141	Phosphorylation	FTATGQRYFLNHIEK EEECCCCHHHHHHHH	12.44	27642862
173	Phosphorylation	MNLHPAVSSTPVPQR CCCCCCCCCCCCCCH	30.51	29214152
174	Phosphorylation	NLHPAVSSTPVPQRS CCCCCCCCCCCCCHH	30.08	25159151
175	Phosphorylation	LHPAVSSTPVPQRSM CCCCCCCCCCCCHHC	22.31	25159151
185	Phosphorylation	PQRSMAVSQPNLVMN CCHHCCCCCCCCCCC	30.31	-
283	Phosphorylation	QAAVNPPTMTPDMRS HHHCCCCCCCCCHHH	34.63	27251275
285	Phosphorylation	AVNPPTMTPDMRSIT HCCCCCCCCCHHHHH	20.72	27251275
290	Phosphorylation	TMTPDMRSITNNSSD CCCCCHHHHHCCCCC	27.42	23403867
292	Phosphorylation	TPDMRSITNNSSDPF CCCHHHHHCCCCCCC	29.60	23403867
295	Phosphorylation	MRSITNNSSDPFLNG HHHHHCCCCCCCCCC	37.88	25159151
296	Phosphorylation	RSITNNSSDPFLNGG HHHHCCCCCCCCCCC	51.96	23403867
305	Phosphorylation	PFLNGGPYHSREQST CCCCCCCCCCCCCCC	18.72	23403867
307	Phosphorylation	LNGGPYHSREQSTDS CCCCCCCCCCCCCCC	31.50	23403867
311	Phosphorylation	PYHSREQSTDSGLGL CCCCCCCCCCCCCCC	29.45	18227151
312	Phosphorylation	YHSREQSTDSGLGLG CCCCCCCCCCCCCCC	33.60	20736484
314	Phosphorylation	SREQSTDSGLGLGCY CCCCCCCCCCCCCCE	35.69	20736484
321	Phosphorylation	SGLGLGCYSVPTTPE CCCCCCCEECCCCHH	15.76	-
322	Phosphorylation	GLGLGCYSVPTTPED CCCCCCEECCCCHHH	26.20	28348404
325	Phosphorylation	LGCYSVPTTPEDFLS CCCEECCCCHHHHHH	53.48	28348404
326	Phosphorylation	GCYSVPTTPEDFLSN CCEECCCCHHHHHHC	20.72	28348404
332	Phosphorylation	TTPEDFLSNVDEMDT CCHHHHHHCCCCCCC	34.50	28348404
339	Phosphorylation	SNVDEMDTGENAGQT HCCCCCCCCCCCCCC	45.12	28348404
346	Phosphorylation	TGENAGQTPMNINPQ CCCCCCCCCCCCCCC	24.48	-
392	Sumoylation	DVESALNKSEPFLTW HHHHHHHCCCCCCCC	57.98	-
393	Phosphorylation	VESALNKSEPFLTWL HHHHHHCCCCCCCCC	49.80	20068231

Upstream regulatory proteins (kinases for phosphorylation sites, E3 ubiquitin ligases of ubiquitination sites, ...)

Modified Location	Modified Residue	Modification	Type of Upstream Proteins	Gene Name of Upstream Proteins	UniProt AC of Upstream Proteins	Sources
89	S	Phosphorylation	Kinase	LATS1	O95835	PSP
89	S	Phosphorylation	Kinase	LATS2	Q9NRM7	Uniprot
90	S	Phosphorylation	Kinase	CDK1	P06493	PSP
105	S	Phosphorylation	Kinase	CDK1	P06493	PSP
285	T	Phosphorylation	Kinase	CDK1	P06493	PSP
311	S	Phosphorylation	Kinase	LATS2	Q9NRM7	Uniprot
321	Y	Phosphorylation	Kinase	ARG	P42684	PSP
326	T	Phosphorylation	Kinase	CDK1	P06493	PSP
346	T	Phosphorylation	Kinase	CDK1	P06493	PSP
-	K	Ubiquitination	E3 ubiquitin ligase	BTRC	Q9Y297	PMID:20858893

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Function	Reference
Oops, there are no descriptions of PTM sites of WWTR1_HUMAN !!

Disease-associated PTM Sites based on SAP

* Distance = the distance between SAP position and PTM sites.

Modified Location	Modification	Variant Position (Distance <= 10)	Residue Change	SAP	Related Disease	Reference
Oops, there are no SNP-PTM records of WWTR1_HUMAN !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
NHRF2_HUMAN	SLC9A3R2	physical	11118213
KLF5_HUMAN	KLF5	physical	22045023
PP1A_HUMAN	PPP1CA	physical	21189257
ASPP2_HUMAN	TP53BP2	physical	21189257
FBW1A_HUMAN	BTRC	physical	21189257
1433E_HUMAN	YWHAE	physical	21189257
1433T_HUMAN	YWHAQ	physical	21555462
DVL2_HUMAN	DVL2	physical	20412773
FBW1A_HUMAN	BTRC	physical	20412773
AMOL1_HUMAN	AMOTL1	physical	26186194
AMOT_HUMAN	AMOT	physical	26186194
TEAD1_HUMAN	TEAD1	physical	26186194
TEAD3_HUMAN	TEAD3	physical	26186194
FBW1A_HUMAN	BTRC	physical	26186194
FBW1B_HUMAN	FBXW11	physical	26186194
1433E_HUMAN	YWHAE	physical	25961935
TEAD4_HUMAN	TEAD4	physical	25670202
FBW1A_HUMAN	BTRC	physical	26116754
TEAD4_HUMAN	TEAD4	physical	26116754
FBW1A_HUMAN	BTRC	physical	28018973
TEAD1_HUMAN	TEAD1	physical	28514442
TEAD3_HUMAN	TEAD3	physical	28514442
FBW1A_HUMAN	BTRC	physical	28514442
TEAD1_HUMAN	TEAD1	physical	25796446

Drug and Disease Associations

Kegg Disease
There are no disease associations of PTM sites.
OMIM Disease
There are no disease associations of PTM sites.
Kegg Drug
There are no disease associations of PTM sites.
DrugBank
There are no disease associations of PTM sites.

Regulatory Network of WWTR1_HUMAN

Related Literatures of Post-Translational Modification

Phosphorylation
Reference	PubMed
"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). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-87 AND SER-105, AND MASSSPECTROMETRY.	18669648 [Abstract]
"TAZ promotes cell proliferation and epithelial-mesenchymal transitionand is inhibited by the hippo pathway."; Lei Q.Y., Zhang H., Zhao B., Zha Z.Y., Bai F., Pei X.H., Zhao S.,Xiong Y., Guan K.L.; Mol. Cell. Biol. 28:2426-2436(2008). Cited for: FUNCTION, PHOSPHORYLATION AT SER-89 AND SER-311, AND MUTAGENESIS OFSER-89 AND SER-311.	18227151 [Abstract]