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Aliases for STAT3 Gene

Aliases for STAT3 Gene

  • Signal Transducer And Activator Of Transcription 3 (Acute-Phase Response Factor) 2 3
  • APRF 3 4 6
  • Acute-Phase Response Factor 3 4
  • HIES 3 6
  • Signal Transducer And Activator Of Transcription 3 3
  • DNA-Binding Protein APRF 3
  • ADMIO 3

External Ids for STAT3 Gene

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. Three alternatively spliced transcript variants encoding distinct isoforms have been described. [provided by RefSeq, Jul 2008]

GeneCards Summary for STAT3 Gene

STAT3 (Signal Transducer And Activator Of Transcription 3 (Acute-Phase Response Factor)) is a Protein Coding gene. Diseases associated with STAT3 include hyper ige syndrome and autoimmune disease, multisystem, infantile-onset. Among its related pathways are PI-3K cascade and Signaling by FGFR. GO annotations related to this gene include sequence-specific DNA binding transcription factor activity and sequence-specific DNA binding. An important paralog of this gene is STAT1.

UniProtKB/Swiss-Prot for STAT3 Gene

  • Signal transducer and transcription activator that mediates cellular responses to interleukins, KITLG/SCF and other growth factors. May mediate cellular responses to activated FGFR1, FGFR2, FGFR3 and FGFR4. Binds to the interleukin-6 (IL-6)-responsive elements identified in the promoters of various acute-phase protein genes. Activated by IL31 through IL31RA. Cytoplasmic STAT3 represses macroautophagy by inhibiting EIF2AK2/PKR activity. Plays an important role in host defense in methicillin-resistant S.aureus lung infection by regulating the expression of the antimicrobial lectin REG3G (By similarity).

Tocris Summary for STAT3 Gene

  • STATs (signal transducers and activators of transcription) are a family of 7 transcription factors that form part of the JAK-STAT signaling cascade. This cascade is the basis of the signal transduction mechanism for many cytokine receptors. Once activated by phosphorylation by JAKs, STATs translocate to the nucleus. Accumulation of STATs in the nucleus is both rapid and tightly controlled. A number of factors regulate the JAK-STAT pathway including STAT dephosphorylation by phosphatases, altered nuclear import-export dynamics of STAT, and STAT gene activation antagonists such as SOCS (suppressors of cytokine signaling) and PIAS (Protein Inhibitors of Activated STATs).

Gene Wiki entry for STAT3 Gene

No data available for PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for STAT3 Gene

Genomics for STAT3 Gene

Genomic Location for STAT3 Gene

Start:
42,313,324 bp from pter
End:
42,388,568 bp from pter
Size:
75,245 bases
Orientation:
Minus strand

Genomic View for STAT3 Gene

UCSC Golden Path with GeneCards custom track
Cytogenetic band:
Genomic Location for STAT3 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for STAT3 Gene

Regulatory Elements for STAT3 Gene

Transcription factor binding sites by QIAGEN in the STAT3 gene promoter:

Proteins for STAT3 Gene

  • 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). Interacts with IL31RA, NCOA1, PELP1, SIPAR, SOCS7, STATIP1 and TMF1. Interacts with HCV core protein. Interacts with IL23R in presence of IL23. 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. Interacts with NEK6 (By similarity). Binds to CDK9 when activated and nuclear. Interacts with BMX. Interacts with ZIPK/DAPK3. Interacts with PIAS3; the interaction occurs on stimulation by IL6, CNTF or OSM and inhibits the DNA binding activity of STAT3. In prostate cancer cells, interacts with STAT3 and promotes DNA binding activity of STAT3. Interacts with STMN3, antagonizing its microtubule-destabilizing activity. Interacts with the Lys-129 acetylated form of BIRC5/survivin. Interacts with FER. Interacts (via SH2 domain) with EIF2AK2/PKR (via the kinase catalytic domain).
    Miscellaneous:
    • Involved in the gp130-mediated signaling pathway

    Alternative splice isoforms for STAT3 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for STAT3 Gene

Proteomics data for STAT3 Gene at MOPED

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 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. Phosphoryation at Tyr-705 by PTK6 or FER leads to an increase of its transcriptional activity. Dephosphorylation on tyrosine residues by PTPN2 negatively regulates IL6/interleukin-6 signaling.
  • Modification sites at PhosphoSitePlus
  • Ubiquitination at Lys87, Lys97, Lys177, Lys180, Lys244, Lys294, and Lys709

Other Protein References for STAT3 Gene

No data available for DME Specific Peptides for STAT3 Gene

Domains for STAT3 Gene

Gene Families for STAT3 Gene

HGNC:
  • SH2D :SH2 domain containing

UniProtKB/Swiss-Prot:

STAT3_HUMAN
Domain:
  • Contains 1 SH2 domain.:
    • P40763
Family:
  • Belongs to the transcription factor STAT family.:
    • P40763
genes like me logo Genes that share domains with STAT3: view

Function for STAT3 Gene

Molecular function for STAT3 Gene

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
UniProtKB/Swiss-Prot Function: Signal transducer and transcription activator that mediates cellular responses to interleukins, KITLG/SCF and other growth factors. May mediate cellular responses to activated FGFR1, FGFR2, FGFR3 and FGFR4. Binds to the interleukin-6 (IL-6)-responsive elements identified in the promoters of various acute-phase protein genes. Activated by IL31 through IL31RA. Cytoplasmic STAT3 represses macroautophagy by inhibiting EIF2AK2/PKR activity. Plays an important role in host defense in methicillin-resistant S.aureus lung infection by regulating the expression of the antimicrobial lectin REG3G (By similarity).

Gene Ontology (GO) - Molecular Function for STAT3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000978 RNA polymerase II core promoter proximal region sequence-specific DNA binding IDA 16835372
GO:0000981 sequence-specific DNA binding RNA polymerase II transcription factor activity --
GO:0001103 RNA polymerase II repressing transcription factor binding IPI 22783022
GO:0001228 RNA polymerase II transcription regulatory region sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription IDA 16835372
GO:0003677 DNA binding ISS --
genes like me logo Genes that share ontologies with STAT3: view
genes like me logo Genes that share phenotypes with STAT3: view

Animal Models for STAT3 Gene

MGI Knock Outs for STAT3:
Targeting motifs for STAT3 Gene
HOMER Transcription Factor Regulatory Elements motif STAT3
  • Consensus sequence: CTTCCGGGAA Submotif: canonical Cell Type: mES GeoId: GSE11431

No data available for Enzyme Numbers (IUBMB) and Transcription Factor Targeting 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
Jensen Localization Image for STAT3 Gene COMPARTMENTS Subcellular localization image for STAT3 gene
Compartment Confidence
nucleus 5
cytosol 4
plasma membrane 4
extracellular 3
cytoskeleton 2
endoplasmic reticulum 2
mitochondrion 2
golgi apparatus 1
lysosome 1
peroxisome 1
vacuole 1

Gene Ontology (GO) - Cellular Components for STAT3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000790 nuclear chromatin IDA 16835372
GO:0005634 nucleus ISS --
GO:0005654 nucleoplasm TAS --
GO:0005737 cytoplasm ISS --
GO:0005743 mitochondrial inner membrane IEA --
genes like me logo Genes that share ontologies with STAT3: view

Pathways for STAT3 Gene

genes like me logo Genes that share pathways with STAT3: view

Gene Ontology (GO) - Biological Process for STAT3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000122 negative regulation of transcription from RNA polymerase II promoter 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 from RNA polymerase II promoter ISS --
genes like me logo Genes that share ontologies with STAT3: view

Compounds for STAT3 Gene

(5) ApexBio Compounds for STAT3 Gene

Compound Action Cas Number
Fludarabine Chemotherapy agent [21679-14-1]
NSC 74859 STAT3 inhibitor, binds to STAT3 SH2 domain, inhibits STAT3-DNA binding [501919-59-1]
SD 1008 JAK2/STAT3 signaling pathway inhibitor. [960201-81-4]
Stattic Small molecule inhibitor of STAT3 [19983-44-9]
WP1066 Cell permeable STAT3 inhibitor [857064-38-1]

(5) Tocris Compounds for STAT3 Gene

Compound Action Cas Number
Cucurbitacin I Selective inhibitor of STAT3/JAK2 signaling [2222-07-3]
Niclosamide STAT3 inhibitor; also inhibits mTORC1 signaling [50-65-7]
NSC 74859 Selective STAT3 inhibitor [501919-59-1]
SD 1008 JAK2/STAT3 signaling pathway inhibitor [960201-81-4]
Stattic Selective STAT3 inhibitor [19983-44-9]

(122) Novoseek inferred chemical compound relationships for STAT3 Gene

Compound -log(P) Hits PubMed IDs
gp 130 92 145
tyrosine 83.7 254
cucurbitacin i 81.8 13
atiprimod 73.2 7
pd180970 67.5 3
genes like me logo Genes that share compounds with STAT3: view

Transcripts for STAT3 Gene

Unigene Clusters for STAT3 Gene

Signal transducer and activator of transcription 3 (acute-phase response factor):
Representative Sequences:

Alternative Splicing Database (ASD) splice patterns (SP) for STAT3 Gene

ExUns: 1a · 1b · 1c ^ 2a · 2b ^ 3 ^ 4a · 4b ^ 5 ^ 6 ^ 7 ^ 8 ^ 9 ^ 10 ^ 11 ^ 12 ^ 13 ^ 14 ^ 15 ^ 16a · 16b ^ 17 ^ 18 ^ 19a · 19b ^ 20a ·
SP1: - -
SP2: -
SP3:
SP4:
SP5:
SP6: -
SP7:
SP8:
SP9:

ExUns: 20b · 20c ^ 21 ^ 22a · 22b ^ 23a · 23b ^ 24a · 24b · 24c · 24d · 24e
SP1: -
SP2: -
SP3:
SP4: - -
SP5:
SP6:
SP7:
SP8:
SP9: -

Relevant External Links for STAT3 Gene

GeneLoc Exon Structure for
STAT3
ECgene alternative splicing isoforms for
STAT3

Expression for STAT3 Gene

mRNA expression in normal human tissues for STAT3 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Integrated Proteomics: protein expression from ProteomicsDB, PaxDb, MOPED, and MaxQB for STAT3 Gene

SOURCE GeneReport for Unigene cluster for STAT3 Gene Hs.463059

mRNA Expression by UniProt/SwissProt for STAT3 Gene

P40763-STAT3_HUMAN
Tissue specificity: Heart, brain, placenta, lung, liver, skeletal muscle, kidney and pancreas
genes like me logo Genes that share expressions with STAT3: view

Orthologs for STAT3 Gene

This gene was present in the common ancestor of chordates.

Orthologs for STAT3 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia STAT3 36
  • 99.78 (n)
  • 100 (a)
STAT3 37
  • 100 (a)
OneToOne
cow
(Bos Taurus)
Mammalia STAT3 36
  • 93.77 (n)
  • 99.74 (a)
STAT3 37
  • 100 (a)
OneToOne
dog
(Canis familiaris)
Mammalia STAT3 36
  • 93.12 (n)
  • 99.48 (a)
STAT3 37
  • 99 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Stat3 36
  • 91.39 (n)
  • 99.87 (a)
Stat3 16
Stat3 37
  • 100 (a)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia STAT3 37
  • 94 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia STAT3 37
  • 100 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Stat3 36
  • 91.34 (n)
  • 99.74 (a)
chicken
(Gallus gallus)
Aves STAT3 36
  • 83.55 (n)
  • 97.4 (a)
STAT3 37
  • 97 (a)
OneToOne
lizard
(Anolis carolinensis)
Reptilia STAT3 37
  • 96 (a)
OneToOne
African clawed frog
(Xenopus laevis)
Amphibia stat3-A 36
tropical clawed frog
(Silurana tropicalis)
Amphibia LOC100498278 36
  • 79.95 (n)
  • 93.78 (a)
rainbow trout
(Oncorhynchus mykiss)
Actinopterygii Omy.11857 36
zebrafish
(Danio rerio)
Actinopterygii stat3 36
  • 78.45 (n)
  • 89.72 (a)
stat3 37
  • 84 (a)
OneToOne
Species with no ortholog for STAT3:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • fruit fly (Drosophila melanogaster)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea squirt (Ciona intestinalis)
  • sea squirt (Ciona savignyi)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)

Evolution for STAT3 Gene

ENSEMBL:
Gene Tree for STAT3 (if available)
TreeFam:
Gene Tree for STAT3 (if available)

Paralogs for STAT3 Gene

Paralogs for STAT3 Gene

Selected SIMAP similar genes for STAT3 Gene using alignment to 6 proteins:

genes like me logo Genes that share paralogs with STAT3: view

Variants for STAT3 Gene

Sequence variations from dbSNP and Humsavar for STAT3 Gene

SNP ID Clin Chr 17 pos Sequence Context AA Info Type MAF
rs10775 -- 42,313,911(+) CTCCC(A/C)CTTAA utr-variant-3-prime
rs744166 -- 42,362,183(-) CGAGC(C/T)TGACA intron-variant
rs744284 -- 42,388,772(-) GGCTT(C/T)TGTGC upstream-variant-2KB
rs957970 -- 42,367,872(-) TGTTC(C/T)AGATT intron-variant
rs957971 -- 42,367,907(-) CCTAT(C/G)GTACT intron-variant

Structural Variations from Database of Genomic Variants (DGV) for STAT3 Gene

Variant ID Type Subtype PubMed ID
nsv833449 CNV Loss 17160897
nsv908249 CNV Loss 21882294
esv2561210 CNV Deletion 19546169
nsv512487 CNV Loss 21212237
esv22090 CNV Loss 19812545
nsv820731 CNV Deletion 20802225
esv2715948 CNV Deletion 23290073
esv1069815 CNV Deletion 17803354
nsv470586 CNV Gain 18288195
esv2667141 CNV Deletion 23128226

Relevant External Links for STAT3 Gene

HapMap Linkage Disequilibrium report
STAT3
Human Gene Mutation Database (HGMD)
STAT3

Disorders for STAT3 Gene

(1) OMIM Diseases for STAT3 Gene (102582)

UniProtKB/Swiss-Prot

STAT3_HUMAN
  • Hyperimmunoglobulin E recurrent infection syndrome, autosomal dominant (AD-HIES) [MIM:147060]: A rare disorder of immunity and connective tissue characterized by immunodeficiency, chronic eczema, recurrent Staphylococcal infections, increased serum IgE, eosinophilia, distinctive coarse facial appearance, abnormal dentition, hyperextensibility of the joints, and bone fractures. {ECO:0000269 PubMed:17676033, ECO:0000269 PubMed:17881745, ECO:0000269 PubMed:23342295}. Note=The disease is caused by mutations affecting the gene represented in this entry.
  • Autoimmune disease, multisystem, infantile-onset (ADMIO) [MIM:615952]: A disorder characterized by early childhood onset of a spectrum of autoimmune manifestations affecting multiple organs, including insulin-dependent diabetes mellitus and autoimmune enteropathy or celiac disease. Other features include short stature, non-specific dermatitis, hypothyroidism, autoimmune arthritis, and delayed puberty. {ECO:0000269 PubMed:25038750}. Note=The disease is caused by mutations affecting the gene represented in this entry.

(5) University of Copenhagen DISEASES for STAT3 Gene

(93) Novoseek inferred disease relationships for STAT3 Gene

Disease -log(P) Hits PubMed IDs
hyper-ige syndrome 74.6 27
tumors 67.9 263
response acute phase 66.5 37
cancer 65.7 186
leukemia 64.8 67

Relevant External Links for STAT3

Genetic Association Database (GAD)
STAT3
Human Genome Epidemiology (HuGE) Navigator
STAT3
genes like me logo Genes that share disorders with STAT3: view

Publications for STAT3 Gene

  1. Molecular cloning of APRF, a novel IFN-stimulated gene factor 3 p91- related transcription factor involved in the gp130-mediated signaling pathway. (PMID: 7512451) Akira S. … Kishimoto T. (Cell 1994) 2 3 4 23
  2. Requirement of serine phosphorylation for formation of STAT-promoter complexes. (PMID: 7701321) Zhang X. … Chen-Kiang S. (Science 1995) 3 4 23
  3. Etk, a Btk family tyrosine kinase, mediates cellular transformation by linking Src to STAT3 activation. (PMID: 10688651) Tsai Y.T. … Chen R.H. (Mol. Cell. Biol. 2000) 3 4 23
  4. Activation of STAT3 by the hepatitis C virus core protein leads to cellular transformation. (PMID: 12208879) Yoshida T. … Yoshimura A. (J. Exp. Med. 2002) 3 4 23
  5. Erythropoietin-induced serine 727 phosphorylation of STAT3 in erythroid cells is mediated by a MEK-, ERK-, and MSK1-dependent pathway. (PMID: 12763138) Wierenga A.T. … Vellenga E. (Exp. Hematol. 2003) 3 4 23

Products for STAT3 Gene

  • Addgene plasmids for STAT3

Sources for STAT3 Gene

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