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MGP003004

UniProt Annotations

Entry Information
Gene Namesignal transducer and activator of transcription 3 (acute-phase response factor)
Protein EntrySTAT3_HUMAN
UniProt IDP40763
SpeciesHuman
Comments
Comment typeDescription
Alternative ProductsEvent=Alternative splicing; Named isoforms=3; Name=1; IsoId=P40763-1; Sequence=Displayed; Name=Del-701; IsoId=P40763-2; Sequence=VSP_010474; Note=Contains a phosphotyrosine at position 704.; Name=3; IsoId=P40763-3; Sequence=VSP_055918, VSP_055919;
DiseaseAutoimmune 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.
DiseaseHyperimmunoglobulin 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.
FunctionSignal 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). {ECO:0000250}.
InteractionQ9DUM3:- (xeno); NbExp=4; IntAct=EBI-518675, EBI-7971837; 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; Q99062:CSF3R; NbExp=4; IntAct=EBI-518675, EBI-7331284; 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; P30084:ECHS1; NbExp=3; IntAct=EBI-518675, EBI-719602; P00533:EGFR; NbExp=14; IntAct=EBI-518675, EBI-297353; P04626:ERBB2; NbExp=9; IntAct=EBI-518675, EBI-641062; Q15910:EZH2; NbExp=5; IntAct=EBI-518675, EBI-530054; Q8TAE8:GADD45GIP1; NbExp=3; IntAct=EBI-518675, EBI-372506; 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; P18031:PTPN1; NbExp=2; IntAct=EBI-518675, EBI-968788; Q04206:RELA; NbExp=4; IntAct=EBI-518675, EBI-73886; P07949:RET; NbExp=3; IntAct=EBI-518675, EBI-2480756; 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; P42224:STAT1; NbExp=2; IntAct=EBI-518675, EBI-1057697; Q06520:SULT2A1; NbExp=2; IntAct=EBI-518675, EBI-3921363;
MiscellaneousInvolved in the gp130-mediated signaling pathway.
PtmTyrosine 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. {ECO:0000250, ECO:0000269|PubMed:10688651, ECO:0000269|PubMed:12359225, ECO:0000269|PubMed:12763138, ECO:0000269|PubMed:15465816, ECO:0000269|PubMed:15592455, ECO:0000269|PubMed:16219639, ECO:0000269|PubMed:16568091, ECO:0000269|PubMed:17875724, ECO:0000269|PubMed:18234692, ECO:0000269|PubMed:18599021, ECO:0000269|PubMed:18669648, ECO:0000269|PubMed:18691976, ECO:0000269|PubMed:19147545, ECO:0000269|PubMed:20068231, ECO:0000269|PubMed:21135090, ECO:0000269|PubMed:7701321}.
SimilarityBelongs to the transcription factor STAT family. {ECO:0000305}.
SimilarityContains 1 SH2 domain. {ECO:0000255|PROSITE- ProRule:PRU00191}.
Subcellular LocationCytoplasm. 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.
SubunitForms 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). {ECO:0000250, ECO:0000269|PubMed:10688651, ECO:0000269|PubMed:11773079, ECO:0000269|PubMed:12023369, ECO:0000269|PubMed:12208879, ECO:0000269|PubMed:12873986, ECO:0000269|PubMed:15194700, ECO:0000269|PubMed:15467733, ECO:0000269|PubMed:15677474, ECO:0000269|PubMed:15994929, ECO:0000269|PubMed:16219639, ECO:0000269|PubMed:17875724, ECO:0000269|PubMed:17956865, ECO:0000269|PubMed:18070987, ECO:0000269|PubMed:18234692, ECO:0000269|PubMed:19147545, ECO:0000269|PubMed:20826784, ECO:0000269|PubMed:23084476, ECO:0000269|PubMed:9388184}.
Tissue SpecificityHeart, brain, placenta, lung, liver, skeletal muscle, kidney and pancreas.
Web ResourceName=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/STAT3ID444.html";
Web ResourceName=SeattleSNPs; URL="http://pga.gs.washington.edu/data/stat3/";
Web ResourceName=STAT3base; Note=STAT3 mutation db; URL="http://structure.bmc.lu.se/idbase/STAT3base/";
Web ResourceName=Wikipedia; Note=STAT3 entry; URL="http://en.wikipedia.org/wiki/STAT3";
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