STAT3 Gene (Protein Coding)

Signal Transducer And Activator Of Transcription 3

GC17M042313
GIFtS:
53
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 vario... See more...

Aliases for STAT3 Gene

Aliases for STAT3 Gene

  • Signal Transducer And Activator Of Transcription 3 2 3 4 5
  • APRF 2 3 4
  • Acute-Phase Response Factor 3 4
  • Signal Transducer And Activator Of Transcription 3 (Acute-Phase Response Factor) 2
  • DNA-Binding Protein APRF 3
  • ADMIO1 3
  • ADMIO 3
  • STAT3 5
  • HIES 3

External Ids for STAT3 Gene

Previous GeneCards Identifiers for STAT3 Gene

  • GC17M040032
  • GC17M042622
  • GC17M040375
  • GC17M040840
  • GC17M037718
  • GC17M040465
  • GC17M036231

Summaries for STAT3 Gene

Entrez Gene Summary for STAT3 Gene

  • 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. This gene also plays a role in regulating host response to viral and bacterial infections. Mutations in this gene are associated with infantile-onset multisystem autoimmune disease and hyper-immunoglobulin E syndrome. [provided by RefSeq, Aug 2020]

CIViC Summary for STAT3 Gene

GeneCards Summary for STAT3 Gene

STAT3 (Signal Transducer And Activator Of Transcription 3) is a Protein Coding gene. Diseases associated with STAT3 include Hyper-Ige Recurrent Infection Syndrome 1, Autosomal Dominant and Autoimmune Disease, Multisystem, Infantile-Onset, 1. Among its related pathways are Immune response IL-23 signaling pathway and IL-6 signaling pathway. Gene Ontology (GO) annotations related to this gene include DNA-binding transcription factor activity and sequence-specific DNA binding. An important paralog of this gene is STAT1.

UniProtKB/Swiss-Prot Summary for STAT3 Gene

  • 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). Upon activation of IL6ST/gp130 signaling by interleukin-6 (IL6), binds to the IL6-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).

Tocris Summary for STAT3 Gene

  • STATs (signal transducers and activators of transcription) are a family of seven transcription factors that form part of the JAK-STAT signaling cascade, the basis of the signal transduction mechanism for many cytokine receptors. STATs are activated by phosphorylation by JAKs.

Gene Wiki entry for STAT3 Gene

Additional gene information for STAT3 Gene

No data available for PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for STAT3 Gene

Genomics for STAT3 Gene

GeneHancer (GH) Regulatory Elements Pubs

Download GeneHancer 2017 data
Promoters and enhancers for STAT3 Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around STAT3 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for STAT3

Top Transcription factor binding sites by QIAGEN in the STAT3 gene promoter:
  • CREB
  • deltaCREB

Genomic Locations for STAT3 Gene

Latest Assembly
chr17:42,313,324-42,388,540
(GRCh38/hg38)
Size:
75,217 bases
Orientation:
Minus strand

Previous Assembly
chr17:40,465,342-40,540,460
(GRCh37/hg19 by Entrez Gene)
Size:
75,119 bases
Orientation:
Minus strand

chr17:40,465,342-40,540,586
(GRCh37/hg19 by Ensembl)
Size:
75,245 bases
Orientation:
Minus strand

Genomic View for STAT3 Gene

Genes around STAT3 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
STAT3 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for STAT3 Gene
GeneLoc Logo Genomic Neighborhood • Exon Structure • Gene Density

RefSeq DNA sequence for STAT3 Gene

Proteins for STAT3 Gene

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  • Protein details for STAT3 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P40763-STAT3_HUMAN
    Recommended name:
    Signal transducer and activator of transcription 3
    Protein Accession:
    P40763
    Secondary Accessions:
    • A8K7B8
    • K7ENL3
    • O14916
    • Q9BW54

    Protein attributes for STAT3 Gene

    Size:
    770 amino acids
    Molecular mass:
    88068 Da
    Quaternary structure:
    • Forms a homodimer or a heterodimer with a related family member (at least STAT1) (PubMed:28065600). Interacts with IL31RA, NCOA1, PELP1, SIPAR, SOCS7, STATIP1 and TMF1 (PubMed:15994929, PubMed:15194700, PubMed:17344214, PubMed:15677474, PubMed:15467733) (By similarity). Interacts with IL23R in presence of IL23 (PubMed:12023369). Interacts (via SH2 domain) with NLK. Interacts with ARL2BP; the interaction is enhanced by LIF and JAK1 expression (By similarity). Interacts with KPNA4 and KPNA5; KPNA4 may be the primary mediator of nuclear import (By similarity). Interacts with CAV2; the interaction is increased on insulin-induced tyrosine phosphorylation of CAV2 and leads to STAT3 activation (By similarity). Interacts with ARL2BP; interaction is enhanced with ARL2 (PubMed:18234692). Interacts with NEK6 (By similarity). Binds to CDK9 when activated and nuclear (PubMed:17956865). Interacts with BMX (PubMed:10688651). Interacts with ZIPK/DAPK3 (PubMed:16219639). Interacts with PIAS3; the interaction occurs on stimulation by IL6, CNTF or OSM and inhibits the DNA binding activity of STAT3 (PubMed:9388184). In prostate cancer cells, interacts with PRKCE and promotes DNA binding activity of STAT3 (PubMed:17875724). Interacts with STMN3, antagonizing its microtubule-destabilizing activity (By similarity). Interacts with the 'Lys-129' acetylated form of BIRC5/survivin (PubMed:20826784). Interacts with FER (PubMed:19147545). Interacts (via SH2 domain) with EIF2AK2/PKR (via the kinase catalytic domain) (PubMed:23084476). Interacts with INPP5F; the interaction is independent of STAT3 Tyr-705 phosphorylation status (PubMed:25476455). Interacts with FGFR4 (PubMed:26675719). Interacts with OCAD1 (By similarity). Interacts (unphosphorylated or phosphorylated at Ser-727) with PHB (PubMed:31899195). Interacts and may form heterodimers with NHLH1 (By similarity).
    • (Microbial infection) Interacts with HCV core protein.
    • (Microbial infection) Interacts with S.typhimurium SarA.
    Miscellaneous:
    • Involved in the gp130-mediated signaling pathway.

    Three dimensional structures from OCA and Proteopedia for STAT3 Gene

    Alternative splice isoforms for STAT3 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for STAT3 Gene

Protein Expression for STAT3 Gene

See protein expression from ProteomicsDB, MOPED, PaxDb, and MaxQB

Post-translational modifications for STAT3 Gene

  • Tyrosine phosphorylated upon stimulation with EGF. Tyrosine phosphorylated in response to constitutively activated FGFR1, FGFR2, FGFR3 and FGFR4 (By similarity). Activated through tyrosine phosphorylation by BMX. Tyrosine phosphorylated in response to IL6, IL11, LIF, CNTF, KITLG/SCF, CSF1, EGF, PDGF, IFN-alpha, LEP and OSM. Activated KIT promotes phosphorylation on tyrosine residues and subsequent translocation to the nucleus. Phosphorylated on serine upon DNA damage, probably by ATM or ATR. Serine phosphorylation is important for the formation of stable DNA-binding STAT3 homodimers and maximal transcriptional activity. ARL2BP may participate in keeping the phosphorylated state of STAT3 within the nucleus. Upon LPS challenge, phosphorylated within the nucleus by IRAK1. Upon erythropoietin treatment, phosphorylated on Ser-727 by RPS6KA5. Phosphorylation at Tyr-705 by PTK6 or FER leads to an increase of its transcriptional activity (PubMed:12763138, PubMed:16568091, PubMed:21135090). Dephosphorylation on tyrosine residues by PTPN2 negatively regulates IL6/interleukin-6 signaling.
  • Acetylated on lysine residues by CREBBP. Deacetylation by LOXL3 leads to disrupt STAT3 dimerization and inhibit STAT3 transcription activity (PubMed:28065600). Oxidation of lysine residues to allysine on STAT3 preferentially takes place on lysine residues that are acetylated (PubMed:28065600).
  • Some lysine residues are oxidized to allysine by LOXL3, leading to disrupt STAT3 dimerization and inhibit STAT3 transcription activity (PubMed:28065600). Oxidation of lysine residues to allysine on STAT3 preferentially takes place on lysine residues that are acetylated (PubMed:28065600).
  • (Microbial infection) Phosphorylated on Tyr-705 in the presence of S.typhimurium SarA.
  • Ubiquitination at Lys87, Lys97, Lys177, Lys180, Lys244, Lys294, and Lys709
  • Modification sites at PhosphoSitePlus

Other Protein References for STAT3 Gene

ENSEMBL proteins:
REFSEQ proteins:

Antibodies for research

  • Abcam antibodies for STAT3

No data available for DME Specific Peptides for STAT3 Gene

Domains & Families for STAT3 Gene

Gene Families for STAT3 Gene

HGNC:
Human Protein Atlas (HPA):
  • Cancer-related genes
  • Disease related genes
  • Plasma proteins
  • Predicted intracellular proteins
  • Transcription factors

Protein Domains for STAT3 Gene

InterPro:
Blocks:
  • STAT protein

Suggested Antigen Peptide Sequences for STAT3 Gene

GenScript: Design optimal peptide antigens:
  • Signal transducer and activator of transcription 3 isoform 2 (B5BTZ6_HUMAN)
  • STAT3 (Q9BXH2_HUMAN)
  • Acute-phase response factor (STAT3_HUMAN)

Graphical View of Domain Structure for InterPro Entry

P40763

UniProtKB/Swiss-Prot:

STAT3_HUMAN :
  • Belongs to the transcription factor STAT family.
Family:
  • Belongs to the transcription factor STAT family.
genes like me logo Genes that share domains with STAT3: view

Function for STAT3 Gene

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Molecular function for STAT3 Gene

UniProtKB/Swiss-Prot Function:
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). Upon activation of IL6ST/gp130 signaling by interleukin-6 (IL6), binds to the IL6-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).
GENATLAS Biochemistry:
signal transducer and activator of transcription 3,homologous to p91,component of the interferon stimulated gene factor 3 complexes,involved in IL6 and related cytokines induced signal transduction by JAK kinases,also involved in the G1 to S cell cycle transition,induced by IL6ST (GP130),playing a critical role in the maintenance of an undifferentiated ES phenotype,widely expressed,located in the cytoplasm and translocated to the nucleus after tyrosine phosphorylation,inhibited by protein phosphatase 2D,persistently activated in many cancers and transformed cell lines and required in cell culture for transformation and blocking of apoptosis

Phenotypes From GWAS Catalog for STAT3 Gene

Gene Ontology (GO) - Molecular Function for STAT3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000976 transcription regulatory region sequence-specific DNA binding IDA 17324931
GO:0000978 RNA polymerase II proximal promoter sequence-specific DNA binding IDA 19390056
GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific ISA --
GO:0001103 RNA polymerase II repressing transcription factor binding IPI 22783022
GO:0001228 DNA-binding transcription activator activity, RNA polymerase II-specific IMP 16946298
genes like me logo Genes that share ontologies with STAT3: view
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Human Phenotype Ontology for STAT3 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for STAT3 Gene

MGI Knock Outs for STAT3:

Animal Models for research

miRNA for STAT3 Gene

miRTarBase miRNAs that target STAT3

Transcription Factor Targets for STAT3 Gene

Selected GeneGlobe predicted Target genes for STAT3
Targeted motifs for STAT3 Gene
HOMER Transcription Factor Regulatory Elements motif STAT3
  • Consensus sequence: CTTCCGGGAA Submotif: canonical Cell Type: mES GEO ID: GSE11431

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for STAT3

Clone products for research

  • Addgene plasmids for STAT3

No data available for Enzyme Numbers (IUBMB) for STAT3 Gene

Localization for STAT3 Gene

Subcellular locations from UniProtKB/Swiss-Prot for STAT3 Gene

Cytoplasm. Nucleus. Note=Shuttles between the nucleus and the cytoplasm. Translocated into the nucleus upon tyrosine phosphorylation and dimerization, in response to signaling by activated FGFR1, FGFR2, FGFR3 or FGFR4. Constitutive nuclear presence is independent of tyrosine phosphorylation. Predominantly present in the cytoplasm without stimuli. Upon leukemia inhibitory factor (LIF) stimulation, accumulates in the nucleus. The complex composed of BART and ARL2 plays an important role in the nuclear translocation and retention of STAT3. Identified in a complex with LYN and PAG1.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for STAT3 gene
Compartment Confidence
plasma membrane 5
nucleus 5
cytosol 5
extracellular 4
cytoskeleton 3
mitochondrion 3
endoplasmic reticulum 3
lysosome 3
golgi apparatus 3
peroxisome 2
endosome 2

Subcellular locations from the

Human Protein Atlas (HPA)
  • Cytosol (3)
  • Nucleoplasm (3)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for STAT3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000785 chromatin IDA,ISA --
GO:0005634 nucleus ISS --
GO:0005654 nucleoplasm TAS --
GO:0005667 transcription factor complex IDA 24429361
GO:0005737 cytoplasm TAS,ISS --
genes like me logo Genes that share ontologies with STAT3: view

Pathways & Interactions for STAT3 Gene

PathCards logo

SuperPathways for STAT3 Gene

SuperPathway Contained pathways
1 Common Cytokine Receptor Gamma-Chain Family Signaling Pathways
IL-21 Signaling Pathways
.90
IL-7 Signaling Pathways
.90
IL-9 Signaling Pathways
.90
Common Cytokine Receptor Gamma-Chain Family Signaling Pathways
.90
IL-15 Signaling Pathways
.88
IL-2 Signaling Pathways
.88
Immune response IL-9 signaling pathway
.42
IL-9 Pathway
.36
2 Immune response IL-23 signaling pathway
Development PDGF signaling via STATs and NF-kB
.44
Immune response IL-23 signaling pathway
.44
Development Angiopoietin - Tie2 signaling
.38
Angiopoietin-TIE2 Signaling
.36
Immune response IL-10 signaling pathway
.36
IL23-mediated signaling events
.35
Rac1/Pak1/p38/MMP-2 pathway
.35
3 RET signaling
Signaling by Leptin
.95
Downstream signal transduction
.94
Signaling by PDGF
.94
NGF signalling via TRKA from the plasma membrane
.87
Signaling by SCF-KIT
.85
Signalling by NGF
.81
4 Th17 cell differentiation
Th17 cell differentiation
.55
Inflammatory bowel disease
.37
Immune response IL-22 signaling pathway
.36
IL-22 Pathway
.01
5 Prolactin Signaling Pathway
Development Prolactin receptor signaling
.38
Prolactin Signaling Pathway
.38
Prolactin signaling pathway
.34
Leptin signaling pathway
.33
genes like me logo Genes that share pathways with STAT3: view

Pathways by source for STAT3 Gene

24 GeneGo (Thomson Reuters) pathways for STAT3 Gene
  • Chemotaxis CXCR4 signaling pathway
  • Cytokine production by Th17 cells in CF
  • Cytokine production by Th17 cells in CF (Mouse model)
  • Development A3 receptor signaling
  • Development Angiopoietin - Tie2 signaling
1 Tocris pathway for STAT3 Gene
34 Qiagen pathways for STAT3 Gene
  • Angiopoietin-TIE2 Signaling
  • BMP Pathway
  • CD40 Signaling
  • CNTF Signaling
  • Colorectal Cancer Metastasis
1 Cell Signaling Technology pathway for STAT3 Gene
1 GeneTex pathway for STAT3 Gene

SIGNOR curated interactions for STAT3 Gene

Activates:
Inactivates:
Is activated by:
Is inactivated by:

Gene Ontology (GO) - Biological Process for STAT3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000122 negative regulation of transcription by RNA polymerase II TAS 8675499
GO:0001659 temperature homeostasis ISS --
GO:0001754 eye photoreceptor cell differentiation ISS --
GO:0006355 regulation of transcription, DNA-templated IDA 15664994
GO:0006357 regulation of transcription by RNA polymerase II TAS,ISS --
genes like me logo Genes that share ontologies with STAT3: view

Drugs & Compounds for STAT3 Gene

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  1. Drug products for research

(112) Drugs for STAT3 Gene - From: DrugBank, PharmGKB, ClinicalTrials, ApexBio, DGIdb, Tocris, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Niclosamide Approved, Investigational, Vet_approved Pharma STAT3 inhibitor; also inhibits mTORC1 signaling 26
rituximab Approved Pharma Therapeutic Antibodies 2114
Amphotericin B Approved, Investigational Pharma 154
Clotrimazole Approved, Vet_approved Pharma 3164
Durvalumab Approved, Investigational Pharma 543

(51) Additional Compounds for STAT3 Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs

(4) Tocris Compounds for STAT3 Gene

Compound Action Cas Number
Cryptotanshinone STAT3 inhibitor. Also displays multiple other activities 35825-57-1
Napabucasin STAT3 inhibitor; also blocks cancer stem cell self-renewal 83280-65-3
Niclosamide STAT3 inhibitor; also inhibits mTORC1 signaling 50-65-7
SD 1008 JAK2/STAT3 signaling pathway inhibitor 960201-81-4

(12) ApexBio Compounds for STAT3 Gene

Compound Action Cas Number
Corylifol A 775351-88-7
Cryptotanshinone STAT3/AChE inhibitor 35825-57-1
Cucurbitacin I STAT3/JAK2 signaling inhibitor 2222-07-3
FLLL32 STAT3 inhibitor 1226895-15-3
HO-3867 STAT3 inhibitor, selective 1172133-28-6
Niclosamide 50-65-7
Nifuroxazide Antidiarrheal agent 965-52-6
NSC 74859 Stat3 inhibitor 501919-59-1
SD 1008 Inhibitor of JAK2/STAT3 signaling pathway,apoptosis inducer 960201-81-4
SH-4-54 STAT inhibitor, potent 1456632-40-8
Stattic STAT3 inhibitor,small-molecule and potent 19983-44-9
WP1066 JAK2/STAT3 inhibitor,cell-permeable 857064-38-1
genes like me logo Genes that share compounds with STAT3: view

Drug products for research

Transcripts for STAT3 Gene

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mRNA/cDNA for STAT3 Gene

21 REFSEQ mRNAs :
21 NCBI additional mRNA sequence :
50 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for STAT3

Clone products for research

  • Addgene plasmids for STAT3