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STAT3

Summary: 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].

Name	OMIM ID	Ensembl ID	HGNC ID	PHARMGKB ID	Map Location
signal transducer and activator of transcription 3	MIM:102582	Ensembl:ENSG00000168610	HGNC:HGNC:11364	PA337	17q21.2

Gene Categories:

PROTEASE TUMOR SUPPRESSOR TRANSCRIPTION FACTOR BINDING TRANSCRIPTION FACTOR COMPLEX DRUG RESISTANCE NEUTRAL ZINC METALLOPEPTIDASE DRUGGABLE GENOME NUCLEAR HORMONE RECEPTOR

GO terms in STAT3

Term Type	Evidence Type	GO Term ID	GO Des.
MF	IDA	GO:0000978	RNA polymerase II proximal promoter sequence-specific DNA binding
MF	ISA	GO:0000981	RNA polymerase II transcription factor activity, sequence-specific DNA binding
MF	ISM	GO:0000981	RNA polymerase II transcription factor activity, sequence-specific DNA binding
MF	NAS	GO:0000981	RNA polymerase II transcription factor activity, sequence-specific DNA binding
MF	IMP	GO:0001077	transcriptional activator activity, RNA polymerase II proximal promoter sequence-specific DNA binding
MF	IPI	GO:0001103	RNA polymerase II repressing transcription factor binding
MF	IDA	GO:0001228	transcriptional activator activity, RNA polymerase II transcription regulatory region sequence-specific DNA binding
MF	ISS	GO:0003677	DNA binding
MF	IDA	GO:0003700	DNA-binding transcription factor activity
MF	IDA	GO:0004879	nuclear receptor activity
MF	IPI	GO:0005515	protein binding
MF	IPI	GO:0008134	transcription factor binding
MF	ISS	GO:0019901	protein kinase binding
MF	IPI	GO:0019903	protein phosphatase binding
MF	IDA	GO:0031490	chromatin DNA binding
MF	IEA	GO:0031730	CCR5 chemokine receptor binding
MF	IEA	GO:0035259	glucocorticoid receptor binding
MF	IPI	GO:0042802	identical protein binding
MF	ISS	GO:0042803	protein homodimerization activity
MF	IDA	GO:0044212	transcription regulatory region DNA binding
MF	ISS	GO:0046983	protein dimerization activity
BP	TAS	GO:0000122	negative regulation of transcription by RNA polymerase II
BP	ISS	GO:0001659	temperature homeostasis
BP	ISS	GO:0001754	eye photoreceptor cell differentiation
BP	IDA	GO:0006355	regulation of transcription, DNA-templated
BP	ISS	GO:0006357	regulation of transcription by RNA polymerase II
BP	IDA	GO:0006606	protein import into nucleus
BP	IEA	GO:0006953	acute-phase response
BP	ISS	GO:0006954	inflammatory response
BP	TAS	GO:0007165	signal transduction
BP	TAS	GO:0007259	JAK-STAT cascade
BP	TAS	GO:0007399	nervous system development
BP	IEA	GO:0007568	aging
BP	IEA	GO:0008283	cell proliferation
BP	IEA	GO:0008285	negative regulation of cell proliferation
BP	IDA	GO:0010628	positive regulation of gene expression
BP	IMP	GO:0010628	positive regulation of gene expression
BP	IEA	GO:0010730	negative regulation of hydrogen peroxide biosynthetic process
BP	IEA	GO:0016032	viral process
BP	ISS	GO:0016310	phosphorylation
BP	NAS	GO:0019221	cytokine-mediated signaling pathway
BP	TAS	GO:0019221	cytokine-mediated signaling pathway
BP	ISS	GO:0019953	sexual reproduction
BP	IDA	GO:0030522	intracellular receptor signaling pathway
BP	IDA	GO:0032355	response to estradiol
BP	IDA	GO:0032870	cellular response to hormone stimulus
BP	IDA	GO:0033210	leptin-mediated signaling pathway
BP	TAS	GO:0035019	somatic stem cell population maintenance
BP	IDA	GO:0035278	miRNA mediated inhibition of translation
BP	TAS	GO:0035723	interleukin-15-mediated signaling pathway
BP	TAS	GO:0038111	interleukin-7-mediated signaling pathway
BP	TAS	GO:0038114	interleukin-21-mediated signaling pathway
BP	TAS	GO:0038155	interleukin-23-mediated signaling pathway
BP	IEA	GO:0040014	regulation of multicellular organism growth
BP	TAS	GO:0042531	positive regulation of tyrosine phosphorylation of STAT protein
BP	ISS	GO:0042593	glucose homeostasis
BP	ISS	GO:0042755	eating behavior
BP	IEA	GO:0042789	mRNA transcription by RNA polymerase II
BP	IMP	GO:0043066	negative regulation of apoptotic process
BP	IDA	GO:0044320	cellular response to leptin stimulus
BP	IDA	GO:0044321	response to leptin
BP	IEA	GO:0045471	response to ethanol
BP	IMP	GO:0045648	positive regulation of erythrocyte differentiation
BP	ISS	GO:0045747	positive regulation of Notch signaling pathway
BP	IEA	GO:0045766	positive regulation of angiogenesis
BP	IEA	GO:0045820	negative regulation of glycolytic process
BP	IDA	GO:0045893	positive regulation of transcription, DNA-templated
BP	IMP	GO:0045893	positive regulation of transcription, DNA-templated
BP	ISS	GO:0045893	positive regulation of transcription, DNA-templated
BP	IDA	GO:0045944	positive regulation of transcription by RNA polymerase II
BP	IGI	GO:0045944	positive regulation of transcription by RNA polymerase II
BP	IMP	GO:0045944	positive regulation of transcription by RNA polymerase II
BP	IEA	GO:0046902	regulation of mitochondrial membrane permeability
BP	ISS	GO:0048708	astrocyte differentiation
BP	IDA	GO:0051726	regulation of cell cycle
BP	ISS	GO:0060019	radial glial cell differentiation
BP	ISS	GO:0060259	regulation of feeding behavior
BP	IDA	GO:0060396	growth hormone receptor signaling pathway
BP	IDA	GO:0060397	JAK-STAT cascade involved in growth hormone signaling pathway
BP	ISS	GO:0060397	JAK-STAT cascade involved in growth hormone signaling pathway
BP	IDA	GO:0070102	interleukin-6-mediated signaling pathway
BP	IMP	GO:0070102	interleukin-6-mediated signaling pathway
BP	TAS	GO:0070102	interleukin-6-mediated signaling pathway
BP	TAS	GO:0070106	interleukin-27-mediated signaling pathway
BP	TAS	GO:0070757	interleukin-35-mediated signaling pathway
BP	TAS	GO:0071345	cellular response to cytokine stimulus
BP	IEA	GO:0071407	cellular response to organic cyclic compound
BP	ISS	GO:0072540	T-helper 17 cell lineage commitment
BP	ISS	GO:0097009	energy homeostasis
BP	IEA	GO:1901215	negative regulation of neuron death
BP	IEA	GO:1902728	positive regulation of growth factor dependent skeletal muscle satellite cell proliferation
BP	IDA	GO:1902895	positive regulation of pri-miRNA transcription by RNA polymerase II
BP	IGI	GO:1904685	positive regulation of metalloendopeptidase activity
BP	IEA	GO:1905564	positive regulation of vascular endothelial cell proliferation
BP	IDA	GO:2000637	positive regulation of gene silencing by miRNA
BP	IEA	GO:2000737	negative regulation of stem cell differentiation
BP	IEA	GO:2001171	positive regulation of ATP biosynthetic process
BP	IEA	GO:2001223	negative regulation of neuron migration
CC	IDA	GO:0000790	nuclear chromatin
CC	IDA	GO:0005634	nucleus
CC	ISS	GO:0005634	nucleus
CC	IDA	GO:0005654	nucleoplasm
CC	TAS	GO:0005654	nucleoplasm
CC	IDA	GO:0005737	cytoplasm
CC	ISS	GO:0005737	cytoplasm
CC	IEA	GO:0005743	mitochondrial inner membrane
CC	IDA	GO:0005829	cytosol
CC	TAS	GO:0005829	cytosol
CC	ISS	GO:0005886	plasma membrane
CC	IC	GO:0090575	RNA polymerase II transcription factor complex
CC	IMP	GO:0090575	RNA polymerase II transcription factor complex

Gene expression in normal tissue: STAT3

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Gene-model tissue-cancer distribution: Bubble Plot

Gene-drug pathway distribution

Pathways in STAT3

Database	Pathway ID	Pathway Des.
wikipathways	WP127	IL-5 Signaling Pathway
wikipathways	WP138	Androgen receptor signaling pathway
wikipathways	WP1528	Physiological and Pathological Hypertrophy of the Heart
wikipathways	WP1544	MicroRNAs in cardiomyocyte hypertrophy
wikipathways	WP1559	TFs Regulate miRNAs related to cardiac hypertrophy
wikipathways	WP2023	Cell Differentiation - Index expanded
wikipathways	WP2029	Cell Differentiation - Index
wikipathways	WP2032	Human Thyroid Stimulating Hormone (TSH) signaling pathway
wikipathways	WP2034	Leptin signaling pathway
wikipathways	WP2037	Prolactin Signaling Pathway
wikipathways	WP2038	Regulation of Microtubule Cytoskeleton
wikipathways	WP205	IL-7 Signaling Pathway
wikipathways	WP2112	IL17 signaling pathway
wikipathways	WP22	IL-9 Signaling Pathway
wikipathways	WP2203	Thymic Stromal LymphoPoietin (TSLP) Signaling Pathway
wikipathways	WP2263	Androgen Receptor Network in Prostate Cancer
wikipathways	WP2324	AGE-RAGE pathway
wikipathways	WP2332	Interleukin-11 Signaling Pathway
wikipathways	WP236	Adipogenesis
wikipathways	WP2374	Oncostatin M Signaling Pathway
wikipathways	WP2380	Brain-Derived Neurotrophic Factor (BDNF) signaling pathway
wikipathways	WP2593	JAK-STAT
wikipathways	WP2815	Mammary gland development pathway - Involution (Stage 4 of 4)
wikipathways	WP2855	Dopaminergic Neurogenesis
wikipathways	WP286	IL-3 Signaling Pathway
wikipathways	WP2868	TCA Cycle Nutrient Utilization and Invasiveness of Ovarian Cancer
wikipathways	WP2881	Estrogen Receptor Pathway
wikipathways	WP2882	Nuclear Receptors Meta-Pathway
wikipathways	WP304	Kit receptor signaling pathway
wikipathways	WP313	Signaling of Hepatocyte Growth Factor Receptor
wikipathways	WP3303	Rac1-Pak1-p38-MMP-2 pathway
wikipathways	WP3333	POU5F1 (OCT4), SOX2, NANOG activate genes related to proliferation
wikipathways	WP364	IL-6 signaling pathway
wikipathways	WP3646	Hepatitis C and Hepatocellular Carcinoma
wikipathways	WP3888	VEGFA-VEGFR2 Signaling Pathway
wikipathways	WP3892	Development of pulmonary dendritic cells and macrophage subsets
wikipathways	WP3929	Chemokine signaling pathway
wikipathways	WP3931	ESC Pluripotency Pathways
wikipathways	WP3935	Leptin Insulin Overlap
wikipathways	WP395	IL-4 Signaling Pathway
wikipathways	WP3972	PDGFR-beta pathway
wikipathways	WP3987	HDAC6 interactions
wikipathways	WP3995	Prion disease pathway
wikipathways	WP4018	Pathways in clear cell renal cell carcinoma
wikipathways	WP4205	MET in type 1 papillary renal cell carcinoma
wikipathways	WP437	EGF-EGFR Signaling Pathway
wikipathways	WP49	IL-2 Signaling Pathway
wikipathways	WP560	TGF-beta Receptor Signaling
wikipathways	WP581	EPO Receptor Signaling
wikipathways	WP585	Interferon type I signaling pathways
wikipathways	WP61	Notch Signaling Pathway
wikipathways	WP733	Serotonin Receptor 2 and STAT3 Signaling
pharmgkb	PA162356267	EGFR Inhibitor Pathway, Pharmacodynamics
pharmgkb	PA165374494	Busulfan Pathway, Pharmacodynamics
pid	cxcr4_pathway	CXCR4-mediated signaling events
pid	erbb1_downstream_pathway	ErbB1 downstream signaling
pid	erbb2erbb3pathway	ErbB2/ErbB3 signaling events
pid	fgf_pathway	FGF signaling pathway
pid	gmcsf_pathway	GMCSF-mediated signaling events
pid	hdac_classi_pathway	Signaling events mediated by HDAC Class I
pid	hes_heypathway	Notch-mediated HES/HEY network
pid	il12_2pathway	IL12-mediated signaling events
pid	il12_stat4pathway	IL12 signaling mediated by STAT4
pid	il23pathway	IL23-mediated signaling events
pid	il27pathway	IL27-mediated signaling events
pid	il2_1pathway	IL2-mediated signaling events
pid	il6_7pathway	IL6-mediated signaling events
pid	kitpathway	Signaling events mediated by Stem cell factor receptor (c-Kit)
pid	pdgfrbpathway	PDGFR-beta signaling pathway
pid	ptp1bpathway	Signaling events mediated by PTP1B
pid	rac1_pathway	RAC1 signaling pathway
pid	tcptp_pathway	Signaling events mediated by TCPTP
pid	trkrpathway	Neurotrophic factor-mediated Trk receptor signaling
kegg	hsa04062	Chemokine signaling pathway - Homo sapiens (human)
kegg	hsa04066	HIF-1 signaling pathway - Homo sapiens (human)
kegg	hsa04068	FoxO signaling pathway - Homo sapiens (human)
kegg	hsa04217	Necroptosis - Homo sapiens (human)
kegg	hsa04550	Signaling pathways regulating pluripotency of stem cells - Homo sapiens (human)
kegg	hsa04630	Jak-STAT signaling pathway - Homo sapiens (human)
kegg	hsa04659	Th17 cell differentiation - Homo sapiens (human)
kegg	hsa04917	Prolactin signaling pathway - Homo sapiens (human)
kegg	hsa04920	Adipocytokine signaling pathway - Homo sapiens (human)
kegg	hsa04931	Insulin resistance - Homo sapiens (human)
kegg	hsa04933	AGE-RAGE signaling pathway in diabetic complications - Homo sapiens (human)
kegg	hsa05145	Toxoplasmosis - Homo sapiens (human)
kegg	hsa05160	Hepatitis C - Homo sapiens (human)
kegg	hsa05161	Hepatitis B - Homo sapiens (human)
kegg	hsa05162	Measles - Homo sapiens (human)
kegg	hsa05167	Kaposi,s sarcoma-associated herpesvirus infection - Homo sapiens (human)
kegg	hsa05169	Epstein-Barr virus infection - Homo sapiens (human)
kegg	hsa05200	Pathways in cancer - Homo sapiens (human)
kegg	hsa05203	Viral carcinogenesis - Homo sapiens (human)
kegg	hsa05205	Proteoglycans in cancer - Homo sapiens (human)
kegg	hsa05206	MicroRNAs in cancer - Homo sapiens (human)
kegg	hsa05212	Pancreatic cancer - Homo sapiens (human)
kegg	hsa05221	Acute myeloid leukemia - Homo sapiens (human)
kegg	hsa05223	Non-small cell lung cancer - Homo sapiens (human)
kegg	hsa05321	Inflammatory bowel disease (IBD) - Homo sapiens (human)
netpath	Pathway_AndrogenReceptor	AndrogenReceptor
netpath	Pathway_BCR	BCR
netpath	Pathway_EGFR1	EGFR1
netpath	Pathway_Fibroblast__growth__factor-1	Fibroblast growth factor-1
netpath	Pathway_Gastrin	Gastrin
netpath	Pathway_IL-7	IL-7
netpath	Pathway_IL11	IL11
netpath	Pathway_IL2	IL2
netpath	Pathway_IL4	IL4
netpath	Pathway_IL5	IL5
netpath	Pathway_IL6	IL6
netpath	Pathway_IL9	IL9
netpath	Pathway_KitReceptor	KitReceptor
netpath	Pathway_Leptin	Leptin
netpath	Pathway_Notch	Notch
netpath	Pathway_Oncostatin_M	Oncostatin_M
netpath	Pathway_Prolactin	Prolactin
netpath	Pathway_RAGE	RAGE
netpath	Pathway_TSLP	TSLP
biocarta	biopeptidespathway	bioactive peptide induced signaling pathway
biocarta	egfpathway	egf signaling pathway
biocarta	erkpathway	erk1/erk2 mapk signaling pathway
biocarta	her2pathway	role of erbb2 in signal transduction and oncology
biocarta	il22bppathway	il22 soluble receptor signaling pathway
biocarta	il6pathway	il 6 signaling pathway
biocarta	pdgfpathway	pdgf signaling pathway
biocarta	stat3pathway	stat3 signaling pathway
biocarta	tpopathway	tpo signaling pathway
reactome	R-HSA-1059683	Interleukin-6 signaling
reactome	R-HSA-109581	Apoptosis
reactome	R-HSA-109606	Intrinsic Pathway for Apoptosis
reactome	R-HSA-111453	BH3-only proteins associate with and inactivate anti-apoptotic BCL-2 members
reactome	R-HSA-1226099	Signaling by FGFR in disease
reactome	R-HSA-1266695	Interleukin-7 signaling
reactome	R-HSA-1266695	Interleukin-7 signaling
reactome	R-HSA-1266738	Developmental Biology
reactome	R-HSA-1280215	Cytokine Signaling in Immune system
reactome	R-HSA-1280215	Cytokine Signaling in Immune system
reactome	R-HSA-1433557	Signaling by SCF-KIT
reactome	R-HSA-162582	Signal Transduction
reactome	R-HSA-162582	Signal Transduction
reactome	R-HSA-1643685	Disease
reactome	R-HSA-166520	Signaling by NTRKs
reactome	R-HSA-168256	Immune System
reactome	R-HSA-168256	Immune System
reactome	R-HSA-1839117	Signaling by cytosolic FGFR1 fusion mutants
reactome	R-HSA-1839124	FGFR1 mutant receptor activation
reactome	R-HSA-186763	Downstream signal transduction
reactome	R-HSA-186797	Signaling by PDGF
reactome	R-HSA-187037	Signaling by NTRK1 (TRKA)
reactome	R-HSA-198745	Signalling to STAT3
reactome	R-HSA-2262752	Cellular responses to stress
reactome	R-HSA-2559582	Senescence-Associated Secretory Phenotype (SASP)
reactome	R-HSA-2559583	Cellular Senescence
reactome	R-HSA-2586552	Signaling by Leptin
reactome	R-HSA-2892247	POU5F1 (OCT4), SOX2, NANOG activate genes related to proliferation
reactome	R-HSA-390466	Chaperonin-mediated protein folding
reactome	R-HSA-390471	Association of TriC/CCT with target proteins during biosynthesis
reactome	R-HSA-391251	Protein folding
reactome	R-HSA-392499	Metabolism of proteins
reactome	R-HSA-446652	Interleukin-1 family signaling
reactome	R-HSA-447115	Interleukin-12 family signaling
reactome	R-HSA-447115	Interleukin-12 family signaling
reactome	R-HSA-449147	Signaling by Interleukins
reactome	R-HSA-449147	Signaling by Interleukins
reactome	R-HSA-451927	Interleukin-2 family signaling
reactome	R-HSA-452723	Transcriptional regulation of pluripotent stem cells
reactome	R-HSA-5357801	Programmed Cell Death
reactome	R-HSA-5655302	Signaling by FGFR1 in disease
reactome	R-HSA-5663202	Diseases of signal transduction
reactome	R-HSA-6783589	Interleukin-6 family signaling
reactome	R-HSA-6783783	Interleukin-10 signaling
reactome	R-HSA-6785807	Interleukin-4 and Interleukin-13 signaling
reactome	R-HSA-6806834	Signaling by MET
reactome	R-HSA-6806834	Signaling by MET
reactome	R-HSA-8848021	Signaling by PTK6
reactome	R-HSA-8848021	Signaling by PTK6
reactome	R-HSA-8849474	PTK6 Activates STAT3
reactome	R-HSA-8849474	PTK6 Activates STAT3
reactome	R-HSA-8854691	Interleukin-20 family signaling
reactome	R-HSA-8875791	MET activates STAT3
reactome	R-HSA-8875791	MET activates STAT3
reactome	R-HSA-8953897	Cellular responses to external stimuli
reactome	R-HSA-8983432	Interleukin-15 signaling
reactome	R-HSA-8984722	Interleukin-35 Signalling
reactome	R-HSA-8985947	Interleukin-9 signaling
reactome	R-HSA-9006927	Signaling by Non-Receptor Tyrosine Kinases
reactome	R-HSA-9006927	Signaling by Non-Receptor Tyrosine Kinases
reactome	R-HSA-9006934	Signaling by Receptor Tyrosine Kinases
reactome	R-HSA-9006934	Signaling by Receptor Tyrosine Kinases
reactome	R-HSA-9008059	Interleukin-37 signaling
reactome	R-HSA-9020933	Interleukin-23 signaling
reactome	R-HSA-9020933	Interleukin-23 signaling
reactome	R-HSA-9020956	Interleukin-27 signaling
reactome	R-HSA-9020958	Interleukin-21 signaling
reactome	R-HSA-982772	Growth hormone receptor signaling

Gene-Drug: Aster Plot

Drug ID	Drug Name	Model Num.
iGMDRD201	SKI II	3
iGMDRD280	CYTOCHALASIN B	4
iGMDRD394	BX-795	1
iGMDRD634	SCHEMBL2608041	3
iGMDRD126	Tipifarnib	9
iGMDRD554	CHEMBL1434137	3
iGMDRD772	BRD4770	2
iGMDRD546	BMS-754807	6
iGMDRD779	PRL-3 Inhibitor I	3
iGMDRD781	Sirolimus	6
iGMDRD354	Midostaurin	1
iGMDRD506	Fedratinib	2
iGMDRD562	Navitoclax	3
iGMDRD60	Quinoclamine	2
iGMDRD23	Gossypol	3
iGMDRD356	PNU-74654	3
iGMDRD270	Ciclosporin	2
iGMDRD474	Avrainvillamide	2
iGMDRD138	PX 12	3
iGMDRD255	SB225002	2
iGMDRD318	PAC-1	2
iGMDRD57	Chloropentafluorobenzene	3
iGMDRD219	Bax channel blocker	2
iGMDRD84	Lovastatin acid	3
iGMDRD116	CD437	2
iGMDRD424	Tamatinib	2
iGMDRD286	Nsc 632839	3
iGMDRD871	BRD6368	3
iGMDRD872	BRD7137	2
iGMDRD505	Pevonedistat	4
iGMDRD300	Tozasertib	5
iGMDRD552	AZD-1775	3
iGMDRD82	Quiflapon	3
iGMDRD137	Indisulam	3
iGMDRD6	AM-580	3
iGMDRD221	Tamoxifen	3
iGMDRD434	BMS-536924	2
iGMDRD267	Oligomycin A	1

Gene in drug-gene network: Network Plot

Gene-drug targets distribution

Gene Structure: PDB

Models in STAT3

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DATATYPES

CLASSFICATION

Disclaimer: iGMDR is intended for research purposes only. Its information cannot be used for emergencies or medical or professional advice.