Description: Homo sapiens signal transducer and activator of transcription 3 (acute-phase response factor) (STAT3), transcript variant 1, mRNA. RefSeq Summary (NM_139276): 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. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Jul 2020]. Transcript (Including UTRs) Position: hg19 chr17:40,465,343-40,540,513 Size: 75,171 Total Exon Count: 24 Strand: - Coding Region Position: hg19 chr17:40,467,763-40,500,534 Size: 32,772 Coding Exon Count: 23
ID:STAT3_HUMAN DESCRIPTION: RecName: Full=Signal transducer and activator of transcription 3; AltName: Full=Acute-phase response factor; 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. SUBUNIT: 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. INTERACTION: O14874:BCKDK; NbExp=2; IntAct=EBI-518675, EBI-1046765; Q96G01:BICD1; NbExp=2; IntAct=EBI-518675, EBI-1104509; P07384:CAPN1; NbExp=2; IntAct=EBI-518675, EBI-1542113; P31146:CORO1A; NbExp=2; IntAct=EBI-518675, EBI-1046676; Q9UER7:DAXX; NbExp=4; IntAct=EBI-518675, EBI-77321; O95661:DIRAS3; NbExp=3; IntAct=EBI-518675, EBI-6139214; Q13011:ECH1; NbExp=2; IntAct=EBI-518675, EBI-711968; Q9BVP2:GNL3; NbExp=2; IntAct=EBI-518675, EBI-641642; Q07666:KHDRBS1; NbExp=2; IntAct=EBI-518675, EBI-1364; O43318:MAP3K7; NbExp=4; IntAct=EBI-518675, EBI-358684; P45984:MAPK9; NbExp=2; IntAct=EBI-518675, EBI-713568; P45984-1:MAPK9; NbExp=3; IntAct=EBI-518675, EBI-713586; Q8TE76:MORC4; NbExp=2; IntAct=EBI-518675, EBI-3940432; Q92665:MRPS31; NbExp=2; IntAct=EBI-518675, EBI-720602; P22736:NR4A1; NbExp=3; IntAct=EBI-518675, EBI-721550; Q9ULD0:OGDHL; NbExp=2; IntAct=EBI-518675, EBI-3940481; P06401:PGR; NbExp=3; IntAct=EBI-518675, EBI-78539; Q04206:RELA; NbExp=4; IntAct=EBI-518675, EBI-73886; P46781:RPS9; NbExp=2; IntAct=EBI-518675, EBI-351206; O00570:SOX1; NbExp=2; IntAct=EBI-518675, EBI-2935583; P30626:SRI; NbExp=2; IntAct=EBI-518675, EBI-750459; Q06520:SULT2A1; NbExp=2; IntAct=EBI-518675, EBI-3921363; SUBCELLULAR LOCATION: 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. TISSUE SPECIFICITY: Heart, brain, placenta, lung, liver, skeletal muscle, kidney and pancreas. PTM: 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. DISEASE: Defects in STAT3 are the cause of hyperimmunoglobulin E recurrent infection syndrome autosomal dominant (AD-HIES) [MIM:147060]; also known as hyper-IgE syndrome or Job syndrome. AD-HIES is 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. MISCELLANEOUS: Involved in the gp130-mediated signaling pathway. SIMILARITY: Belongs to the transcription factor STAT family. SIMILARITY: Contains 1 SH2 domain. WEB RESOURCE: Name=Wikipedia; Note=STAT3 entry; URL="http://en.wikipedia.org/wiki/STAT3"; WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/STAT3ID444.html"; WEB RESOURCE: Name=STAT3base; Note=STAT3 mutation db; URL="http://bioinf.uta.fi/STAT3base/"; WEB RESOURCE: Name=SeattleSNPs; URL="http://pga.gs.washington.edu/data/stat3/";
asthma Litonjua, A. A. et al. 2005, Polymorphisms in signal transducer and activator of transcription 3 and lung function in asthma., Respiratory research. 2005 Jun;6(1):52.
[PubMed 15935090]
Our results indicate that genetic variants in STAT3, independent of asthma treatment, are determinants of FEV1 in both adults and children with asthma, and suggest that STAT3 may participate in inflammatory pathways that have an impact on level of lung function.
Crohn Disease Jeffrey C Barrett et al. Nature genetics 2008, Genome-wide association defines more than 30 distinct susceptibility loci for Crohn's disease., Nature genetics.
[PubMed 18587394]
Crohn's disease Barrett ,et al. 2008, Genome-wide assocation defines more than 30 distinct susceptibility loci for Crohn's disease, Nature genetics 2008 40- 8 : 955-62.
[PubMed 18587394]
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on P40763
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.