PMADS

Id:	acc2004
Group:	2sens
Protein:	STAT3
Gene Symbol:	STAT3
Protein Id:	P40763
Protein Name:	STAT3_HUMAN
PTM:	phosphorylation
Site:	Tyr727
Site Sequence:	CSNTIDLPMSPRTLDSLMQFG
Disease Category:	Cancer
Disease:	Medulloblastoma
Disease Subtype:
Disease Cellline:	UW228
Disease Info:
Drug:	SPARC OV
Drug Info:	"Paclitaxel is a taxane chemotherapy agent that inhibits microtubule disassembly, used in the treatment of various cancers including ovarian, breast, and lung cancer. Carboplatin is a platinum-containing chemotherapy drug that cross-links DNA, disrupting cell division, commonly used in the treatment of ovarian, lung, and other solid tumors."
Effect:	modulate
Effect Info:	"SPARC regulates the Notch signaling pathway by inhibiting IL-6, thereby reducing the phosphorylation of STAT3. This mechanism enables SPARC to promote the expression of neural markers and neural-like differentiation, thus enhancing the sensitivity of medulloblastoma cells to treatment."
Note:
Score:	3.0
Pubmed(PMID):	21613407
Sentence Index:	21613407_8-9
Sentence:	"Immunohistochemical analysis of tumor sections from mice treated with Ad-DsRed-SP showed increased immunoreactivity for the neuronal markers and a decrease in Notch1 expression and phosphorylation of STAT3. Taken together, our results suggest that SPARC induces expression of neuronal markers in medulloblastoma cells through its inhibitory effect on IL-6-regulated suppression of Notch pathway-mediated STAT3 signaling, thus giving further support to the potential use of SPARC as a therapeutic candidate for medulloblastoma treatment."

Sequence & Structure:

MAQWNQLQQLDTRYLEQLHQLYSDSFPMELRQFLAPWIESQDWAYAASKESHATLVFHNLLGEIDQQYSRFLQESNVLYQHNLRRIKQFLQSRYLEKPMEIARIVARCLWEESRLLQTAATAAQQGGQANHPTAAVVTEKQQMLEQHLQDVRKRVQDLEQKMKVVENLQDDFDFNYKTLKSQGDMQDLNGNNQSVTRQKMQQLEQMLTALDQMRRSIVSELAGLLSAMEYVQKTLTDEELADWKRRQQIACIGGPPNICLDRLENWITSLAESQLQTRQQIKKLEELQQKVSYKGDPIVQHRPMLEERIVELFRNLMKSAFVVERQPCMPMHPDRPLVIKTGVQFTTKVRLLVKFPELNYQLKIKVCIDKDSGDVAALRGSRKFNILGTNTKVMNMEESNNGSLSAEFKHLTLREQRCGNGGRANCDASLIVTEELHLITFETEVYHQGLKIDLETHSLPVVVISNICQMPNAWASILWYNMLTNNPKNVNFFTKPPIGTWDQVAEVLSWQFSSTTKRGLSIEQLTTLAEKLLGPGVNYSGCQITWAKFCKENMAGKGFSFWVWLDNIIDLVKKYILALWNEGYIMGFISKERERAILSTKPPGTFLLRFSESSKEGGVTFTWVEKDISGKTQIQSVEPYTKQQLNNMSFAEIIMGYKIMDATNILVSPLVYLYPDIPKEEAFGKYCRPESQEHPEADPGSAAPYLKTKFICVTPTTCSNTIDLPMSPRTLDSLMQFGNNGEGAEPSAGGQFESLTFDMELTSECATSPM

Select PDB:

Known Drugs:

source: Multi-Sources

(see table)

Target	Drug name	MOA	Phase	Status	Disease	Source
STAT3	DANVATIRSEN	STAT-3 mRNA 3'UTR antisense inhibitor	2	Recruiting	head and neck squamous cell carcinoma	ClinicalTrials
STAT3	DANVATIRSEN	STAT-3 mRNA 3'UTR antisense inhibitor	2	Active, not recruiting	non-small cell lung carcinoma	ClinicalTrials
STAT3	DANVATIRSEN	STAT-3 mRNA 3'UTR antisense inhibitor	2	Completed	non-small cell lung carcinoma	ClinicalTrials
STAT3	DANVATIRSEN	STAT-3 mRNA 3'UTR antisense inhibitor	1	Completed	hepatocellular carcinoma	ClinicalTrials
STAT3	DANVATIRSEN	STAT-3 mRNA 3'UTR antisense inhibitor	1	Active, not recruiting	head and neck squamous cell carcinoma	ClinicalTrials
STAT3	DANVATIRSEN	STAT-3 mRNA 3'UTR antisense inhibitor	1	Completed	diffuse large B-cell lymphoma	ClinicalTrials ClinicalTrials
STAT3	DANVATIRSEN	STAT-3 mRNA 3'UTR antisense inhibitor	1	Active, not recruiting	neoplasm	ClinicalTrials
STAT3	DANVATIRSEN	STAT-3 mRNA 3'UTR antisense inhibitor	1	Active, not recruiting	non-small cell lung carcinoma	ClinicalTrials
STAT3	DANVATIRSEN	STAT-3 mRNA 3'UTR antisense inhibitor	1	Completed	non-Hodgkins lymphoma	ClinicalTrials
STAT3	DANVATIRSEN	STAT-3 mRNA 3'UTR antisense inhibitor	1	Active, not recruiting	urinary bladder cancer	ClinicalTrials
STAT3	DANVATIRSEN	STAT-3 mRNA 3'UTR antisense inhibitor	1	Completed	cancer	ClinicalTrials

Note: Only show clinically investigational or approved drugs with protein targets.

Protein Tractability:

source: Open Targets

Small molecule

Antibody

PROTAC

Other modalities

Approved Drug

Advanced Clinical

Phase 1 Clinical

Structure with Ligand

High-Quality Ligand

High-Quality Pocket

Med-Quality Pocket

Druggable Family

Approved Drug

Advanced Clinical

Phase 1 Clinical

UniProt loc high conf

GO CC high conf

UniProt loc med conf

UniProt SigP or TMHMM

GO CC med conf

Human Protein Atlas loc

Approved Drug

Advanced Clinical

Phase 1 Clinical

Literature

UniProt Ubiquitination

Database Ubiquitination

Half-life Data

Small Molecule Binder

Approved Drug

Advanced Clinical

Phase 1 Clinical

PTM Intensity:

source: CPTAC

No intensity data of this site,
show all other sites!

STAT3-Ser701
Cancer	Intensity
BRCA	0.628
COAD
HGSC
ccRCC
GBM	-0.869
HNSC
LUAD	0.536
LUSC
non_ccRCC	0.136
PDAC	-1.53
UCEC	1.097

STAT3-Ser718
Cancer	Intensity
BRCA
COAD	0.872
HGSC
ccRCC	-1.092
GBM
HNSC	0.22
LUAD
LUSC
non_ccRCC
PDAC
UCEC

STAT3-Ser719
Cancer	Intensity
BRCA
COAD
HGSC
ccRCC
GBM	0.014
HNSC
LUAD	-1.007
LUSC
non_ccRCC
PDAC
UCEC	0.993

STAT3-Ser726
Cancer	Intensity
BRCA
COAD	0.434
HGSC	-1.719
ccRCC	-0.023
GBM
HNSC	0.641
LUAD
LUSC	0.667
non_ccRCC
PDAC
UCEC

STAT3-Ser727
Cancer	Intensity
BRCA	1.74
COAD
HGSC
ccRCC
GBM	-1.099
HNSC
LUAD	-0.272
LUSC
non_ccRCC	-0.473
PDAC	0.531
UCEC	-0.428

STAT3-Thr713
Cancer	Intensity
BRCA
COAD	0.801
HGSC	-1.677
ccRCC	-0.148
GBM
HNSC	0.539
LUAD
LUSC	0.484
non_ccRCC
PDAC
UCEC

STAT3-Thr714
Cancer	Intensity
BRCA	0.773
COAD
HGSC
ccRCC
GBM	0.51
HNSC
LUAD	-1.5
LUSC
non_ccRCC	1.028
PDAC	-0.908
UCEC	0.096

STAT3-Thr715
Cancer	Intensity
BRCA
COAD	0.468
HGSC	-1.459
ccRCC	0.21
GBM
HNSC	0.78
LUAD
LUSC
non_ccRCC
PDAC
UCEC

STAT3-Thr716
Cancer	Intensity
BRCA
COAD	1.179
HGSC	-1.795
ccRCC	-0.306
GBM	0.781
HNSC	0.528
LUAD	-0.6
LUSC
non_ccRCC
PDAC
UCEC	0.212

STAT3-Thr717
Cancer	Intensity
BRCA
COAD
HGSC
ccRCC
GBM	1.093
HNSC
LUAD	-0.224
LUSC
non_ccRCC
PDAC
UCEC	-0.869

STAT3-Thr720
Cancer	Intensity
BRCA
COAD	0.825
HGSC
ccRCC	-1.112
GBM
HNSC	0.287
LUAD
LUSC
non_ccRCC
PDAC
UCEC

STAT3-Thr721
Cancer	Intensity
BRCA
COAD
HGSC
ccRCC
GBM	0.707
HNSC
LUAD	-0.707
LUSC
non_ccRCC
PDAC
UCEC

STAT3-Tyr704
Cancer	Intensity
BRCA
COAD	-0.089
HGSC	1.572
ccRCC	-1.101
GBM
HNSC	-0.535
LUAD
LUSC	0.153
non_ccRCC
PDAC
UCEC

STAT3-Tyr705
Cancer	Intensity
BRCA	0.868
COAD
HGSC
ccRCC
GBM	0.383
HNSC
LUAD	-0.032
LUSC
non_ccRCC	-1.398
PDAC	1.121
UCEC	-0.942

PTM-Disease Association:

source: PTMD

Residue	Position	State	Disease	Class	PMID
S	727	D	Oral squamous epithelial carcinoma	Phosphorylation	23733313
S	727	D	Triple-negative breast cancer	Phosphorylation	36017196
S	727	D	Pancreatic cancer	Phosphorylation	37548811
S	727	D	Pancreatic cancer/carcinoma/adenocarcinoma	Phosphorylation	18519681
S	727	P	Prostate cancer/carcinoma/adenocarcinoma	Phosphorylation	23941877
S	727	P	Breast cancer/tumor/carcinoma	Phosphorylation	23329648 ; 23329839
S	727	P	Cancer	Phosphorylation	23145121
S	727	P	Melanoma	Phosphorylation	22418867
S	727	U	Chronic lymphocytic leukemia	Phosphorylation	35595309
S	727	U	Clear cell kidney cancer	Phosphorylation	24615012 ; 33772065 ; 37945711
S	727	U	Head and neck squamous cell carcinoma	Phosphorylation	21281788
S	727	U	Prostate cancer	Phosphorylation	18829527
S	727	U	Glioblastoma multiforme	Phosphorylation	35670018
S	727	U	B-cell acute lymphoblastic leukemia	Phosphorylation	33393494
S	727	U	Hepatocellular carcinoma	Phosphorylation	31498440
S	727	U	Thyroid cancer/carcinoma	Phosphorylation	17209045

State Note: Based on the distinct PTM states in diseases, PTMD classified all disease-associated PTMs into six classes, including whether the up-regulation (U) or down-regulation (D) of PTM levels, the absence (A) or presence (P) of PTMs, and the creation (C) or disruption (N) of PTM sites are associated with diseases.

PTM-Drug Perturbation Response:

source: DecryptM

No data.

Function score:

source: funscoR

No data.

Cross Links:

CTD
DMRdb