Tchem STAT3 Signal transducer and activator of transcription 3

Protein Summary

Description

Signal transducer and transcription activator that mediates cellular responses to interleukins, KITLG/SCF, LEP and other growth factors (PubMed:10688651, PubMed:12359225, PubMed:12873986, PubMed:15194700, PubMed:17344214, PubMed:18242580, PubMed:23084476). Once activated, recruits coactivators, such as NCOA1 or MED1, to the promoter region of the target gene (PubMed:17344214). May mediate cellular responses to activated FGFR1, FGFR2, FGFR3 and FGFR4 (PubMed:12873986). Binds to the interleukin-6 (IL-6)-responsive elements identified in the promoters of various acute-phase protein genes (PubMed:12359225). Activated by IL31 through IL31RA (PubMed:15194700). Acts as a regulator of inflammatory response by regulating differentiation of naive CD4(+) T-cells into T-helper Th17 or regulatory T-cells (Treg): deacetylation and oxidation of lysine residues by LOXL3, leads to disrupt STAT3 dimerization and inhibit its transcription activity (PubMed:28065600). Involved in cell cycle regulation by inducing the expression of key genes for the progression from G1 to S phase, such as CCND1 (PubMed:17344214). Mediates the effects of LEP on melanocortin production, body energy homeostasis and lactation (By similarity). May play an apoptotic role by transctivating BIRC5 expression under LEP activation (PubMed:18242580). Cytoplasmic STAT3 represses macroautophagy by inhibiting EIF2AK2/PKR activity (PubMed:23084476). Plays a crucial role in basal beta cell functions, such as regulation of insulin secretion (By similarity). The protein encoded by this gene is a member of the STAT protein family. In response to cytokines and growth factors, STAT family members are phosphorylated by the receptor associated kinases, and then form homo- or heterodimers that translocate to the cell nucleus where they act as transcription activators. This protein is activated through phosphorylation in response to various cytokines and growth factors including IFNs, EGF, IL5, IL6, HGF, LIF and BMP2. This protein mediates the expression of a variety of genes in response to cell stimuli, and thus plays a key role in many cellular processes such as cell growth and apoptosis. The small GTPase Rac1 has been shown to bind and regulate the activity of this protein. PIAS3 protein is a specific inhibitor of this protein. Mutations in this gene are associated with infantile-onset multisystem autoimmune disease and hyper-immunoglobulin E syndrome. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Sep 2015]

Uniprot Accession IDs

• P40763
• A8K7B8
• K7ENL3
• O14916
• Q9BW54

Gene Name

• STAT3

Ensembl ID

• ENST00000264657
• ENSP00000264657
• ENSG00000168610
• ENST00000404395
• ENSP00000384943
• ENST00000585517
• ENSP00000467000
• ENST00000588969
• ENSP00000467985

Symbol

• APRF
• APRF
• HIES
• ADMIO
• ADMIO1

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
biological process	1
biological term	1
chemical	1
disease perturbation	1
hub protein	1

Protein Classes

PANTHER Classes

Protein / Transcription Factor / Signal Transducer And Activator Of Transcription 3

Protein / Nucleic Acid Binding / Signal Transducer And Activator Of Transcription 3

DTO Classes

Protein / Nucleic Acid Binding / Signal Transducer And Activator Of Transcription 3

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 11004.99   (req: < 5)

Gene RIFs: 2260   (req: <= 3)

Antibodies: 2254   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 11004.99   (req: >= 5)

Gene RIFs: 2260   (req: > 3)

Antibodies: 2254   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 91

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligands: 163

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drugs: 2

Expression Data (0 Tissues)

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No expression data found

Protein Sequence and Structure

Residue Counts

Protein Sequence

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Related Tools (4)

Target Illumination GWAS Analytics (TIGA)

TIGA scores and ranks GWAS discovered associations according to the quantity and quality of the evidence supporting the association.

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GENEVA

GENEVA (GENe Expression Variance Analysis) allows you to identify RNA-sequencing datasets from the Gene Expression Omnibus (GEO) that contain conditions modulating a gene or a gene signature.

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GlyGen

GlyGen is a data integration and dissemination project for carbohydrate and glycoconjugate related data.

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ARCHS4

ARCHS4 provides access to gene-function predictions based on RNA-seq co-expression, and gene expression levels across cell and tissues.

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Approved Drugs (2)

Explore Approved Drugs

1 – 2 of 2

niclosamide

STAT3Tchem TF

ACTIVATOR pEC50 : 5.54

digitoxin

STAT3Tchem TF

INHIBITOR :

Active Ligands (163)

Explore Active Ligands

1 – 10 of 163

AZD1480

STAT3Tchem TF

pIC50 : 8.52

CHEMBL4452527

STAT3Tchem TF

pKd : 6

CHEMBL4846365

STAT3Tchem TF

pKd : 7.28

CHEMBL4864495

STAT3Tchem TF

pKd : 7.2

CHEMBL3358611

STAT3Tchem TF

pKi : 6.84

CHEMBL3108909

STAT3Tchem TF

pKd : 6.33

CHEMBL4568628

STAT3Tchem TF

pKd : 7.1

CHEMBL4445234

STAT3Tchem TF

pIC50 : 7.16

CHEMBL4846078

STAT3Tchem TF

pIC50 : 6.08

CHEMBL4462450

STAT3Tchem TF

pIC50 : 7.05

Protein-Protein Interactions (958)

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1 – 10 of 958

• See Interactions on String-DB

TCEAL1

Tbio

Novelty:  0.02210924

p_int:  0.999948156

p_ni:  0.000051844

Data Source:  BioPlex

STAT1

Tchem

Family:  TF

Novelty:  0.0003383

p_int:  0.999892474

p_ni:  0.000107526

Score:  0.972

Data Source:  BioPlex,Reactome,STRINGDB

TRPV5

Tchem

Family:  IC

Novelty:  0.0055156

p_int:  0.999243042

p_ni:  0.000756958

Score:  0.201

Data Source:  BioPlex,STRINGDB

CDK15

Tchem

Family:  Kinase

Novelty:  0.3870338

p_int:  0.99893754

p_ni:  0.00106246

Score:  0.247

Data Source:  BioPlex,STRINGDB

SEMA4C

Tbio

Novelty:  0.01237067

p_int:  0.998572661

p_ni:  0.001427339

Score:  0.194

Data Source:  BioPlex,STRINGDB

LRRC32

Tbio

Novelty:  0.02644086

p_int:  0.997710607

p_ni:  0.002289391

p_wrong:  3e-9

Score:  0.25

Data Source:  BioPlex,STRINGDB

IL20RA

Tbio

Novelty:  0.02416816

p_int:  0.996430977

p_ni:  0.003569023

Score:  0.955

Data Source:  BioPlex,Reactome,STRINGDB

DDX19B

Tbio

Family:  Enzyme

Novelty:  0.0504568

p_int:  0.995698184

p_ni:  0.004301816

Data Source:  BioPlex

RP2

Tbio

Novelty:  0.12345247

p_int:  0.988967768

p_ni:  0.011032232

Data Source:  BioPlex

CACNG2

Tbio

Family:  IC

Novelty:  0.00808502

p_int:  0.986765395

p_ni:  0.013234589

p_wrong:  1.6e-8

Score:  0.193

Data Source:  BioPlex,STRINGDB

Nearest Tclin Targets (17)

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Upstream (9)

Downstream (8)

1 – 5 of 9

SRC

Tclin

Family:  Kinase

KEGG Distance:  1

Common Pathways:  8

1: EGFR tyrosine kinase inhibitor resistance

2: Kaposi sarcoma-associated herpesvirus infection

3: Chemokine signaling pathway

4: Proteoglycans in cancer

more:  4 more common pathways

JAK2

Tclin

Family:  Kinase

KEGG Distance:  1

Common Pathways:  14

1: EGFR tyrosine kinase inhibitor resistance

2: Adipocytokine signaling pathway

3: Kaposi sarcoma-associated herpesvirus infection

4: AGE-RAGE signaling pathway in diabetic complications

more:  10 more common pathways

JAK1

Tclin

Family:  Kinase

KEGG Distance:  1

Common Pathways:  16

1: EGFR tyrosine kinase inhibitor resistance

2: Kaposi sarcoma-associated herpesvirus infection

3: PD-L1 expression and PD-1 checkpoint pathway in cancer

4: JAK-STAT signaling pathway

more:  12 more common pathways

IL6R

Tclin

Family:  Other

KEGG Distance:  1

Common Pathways:  6

1: EGFR tyrosine kinase inhibitor resistance

2: HIF-1 signaling pathway

3: JAK-STAT signaling pathway

4: Th17 cell differentiation

more:  2 more common pathways

IL6

Tclin

Family:  Other

KEGG Distance:  1

Common Pathways:  14

1: EGFR tyrosine kinase inhibitor resistance

2: Inflammatory bowel disease (IBD)

3: Kaposi sarcoma-associated herpesvirus infection

4: Insulin resistance

more:  10 more common pathways

Pathways (263)

Reactome (56)

KEGG (28)

PathwayCommons (59)

WikiPathways (120)

Apoptosis (R-HSA-109581)

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Data Source	Name	Explore in Pharos	Explore in Source
Reactome	Apoptosis	177 targets	R-HSA-109581
Reactome	Association of TriC/CCT with target proteins during biosynthesis	39 targets	R-HSA-390471
Reactome	BH3-only proteins associate with and inactivate anti-apoptotic BCL-2 members	10 targets	R-HSA-111453
Reactome	Cellular Senescence	164 targets	R-HSA-2559583
Reactome	Cellular responses to external stimuli	487 targets	R-HSA-8953897

Name	Explore in Pharos	Explore in Source
Apoptosis	177 targets	R-HSA-109581
Association of TriC/CCT with target proteins during biosynthesis	39 targets	R-HSA-390471
BH3-only proteins associate with and inactivate anti-apoptotic BCL-2 members	10 targets	R-HSA-111453
Cellular Senescence	164 targets	R-HSA-2559583
Cellular responses to external stimuli	487 targets	R-HSA-8953897

Viral Interactions (0)

No viral interactions found

Gene Ontology Terms (102)

Functions (17)

Components (11)

Processes (74)

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1 – 10 of 17

GO Term	Evidence	Assigned by
chromatin DNA binding	Inferred from Direct Assay (IDA)	UniProtKB
DNA-binding transcription activator activity, RNA polymerase II-specific	Inferred from Direct Assay (IDA)	BHF-UCL
DNA-binding transcription factor activity	Inferred from Direct Assay (IDA)	UniProtKB
nuclear receptor activity	Inferred from Direct Assay (IDA)	BHF-UCL
RNA polymerase II proximal promoter sequence-specific DNA binding	Inferred from Direct Assay (IDA)	BHF-UCL
transcription regulatory region DNA binding	Inferred from Direct Assay (IDA)	BHF-UCL
identical protein binding	Inferred from Physical Interaction (IPI)	IntAct
protein phosphatase binding	Inferred from Physical Interaction (IPI)	UniProtKB
RNA polymerase II repressing transcription factor binding	Inferred from Physical Interaction (IPI)	BHF-UCL
transcription factor binding	Inferred from Physical Interaction (IPI)	UniProtKB

Disease Associations (null)

No disease associations found

GWAS Traits (29)

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1 – 5 of 29

GWAS Trait	EFO ID	Study Count	SNP Count	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
multiple sclerosis	MONDO_0005301	5	5	0	1.1	98.4
Crohn's disease	EFO_0000384	4	4	0	1.2	95.3
BMI-adjusted waist-hip ratio	EFO_0007788	3	6	9		86.4
inflammatory bowel disease	EFO_0003767	1	1	0	1.1	82.6
C-reactive protein measurement	EFO_0004458	2	2	2		79.4

• Explore on Target Illumination GWAS Analytics (TIGA)

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5

1 – 5 of 29

GWAS Trait	EFO ID	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
multiple sclerosis	MONDO_0005301	0	1.1	98.4
Crohn's disease	EFO_0000384	0	1.2	95.3
BMI-adjusted waist-hip ratio	EFO_0007788	9		86.4
inflammatory bowel disease	EFO_0003767	0	1.1	82.6
C-reactive protein measurement	EFO_0004458	2		79.4

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UniProt Keyword Find Similar Targets

No Header	No Header
3D-structure
Acetylation
Activator
Alternative splicing
Complete proteome
Cytoplasm
Diabetes mellitus
Disease mutation
DNA-binding
Dwarfism

GWAS Trait Find Similar Targets

No Header	No Header
allergic disease
apolipoprotein B measurement
asthma
BMI-adjusted hip circumference
BMI-adjusted waist-hip ratio
C-reactive protein measurement
childhood onset asthma
Crohn's disease
glomerular filtration rate
heel bone mineral density

MGI Phenotype Find Similar Targets

No Header	No Header
adipose tissue phenotype
behavior/neurological phenotype
cardiovascular system phenotype
cellular phenotype
digestive/alimentary phenotype
embryo phenotype
endocrine/exocrine gland phenotype
growth/size/body region phenotype
hematopoietic system phenotype
homeostasis/metabolism phenotype

IDG Resources

No IDG generated resources found

Orthologs (12)

1 – 5 of 12

Species	Name	Source ID	Gene ID	OMA	EggNOG	Inparanoid
Chimp	signal transducer and activator of transcription 3	VGNC:9663	454682
Macaque	signal transducer and activator of transcription 3		574128
Mouse	signal transducer and activator of transcription 3	MGI:103038	20848
Rat	signal transducer and activator of transcription 3	RGD:3772	25125
Dog	signal transducer and activator of transcription 3	VGNC:46890	490967

Species	Name	OMA	EggNOG	Inparanoid
Chimp	signal transducer and activator of transcription 3
Macaque	signal transducer and activator of transcription 3
Mouse	signal transducer and activator of transcription 3
Rat	signal transducer and activator of transcription 3
Dog	signal transducer and activator of transcription 3

Publication Statistics

PubMed Score 11004.99

PubMed score by year

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PubTator Score 5289.01

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Related Publications

Text Mined References (2440)

GeneRif Annotations (2260)

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PMID	Year	Title