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Details on Person UniProt:P42227 Stat3
| Class:Id | ReferenceGeneProduct:102393 |
|---|---|
| _chainChangeLog | initiator methionine:1 added on Sat February 7 2015;chain:2-770 added on Sat February 7 2015;initiator methionine:1 for 102393 removed on Fri Nov 03 2023;initiator methionine: for 102393 added on Fri Nov 03 2023;initiator methionine: for 102393 removed on Fri Aug 15 2025;initiator methionine:1 for 102393 added on Fri Aug 15 2025 |
| _displayName | UniProt:P42227 Stat3 |
| _timestamp | 2026-02-20 21:44:45 |
| chain | initiator methionine:1 chain:2-770 |
| checksum | 6C00626711C8012D |
| comment | FUNCTION Signal transducer and transcription activator that mediates cellular responses to interleukins, KITLG/SCF, LEP and other growth factors (PubMed:23917203, PubMed:26026268). Once activated, recruits coactivators, such as NCOA1 or MED1, to the promoter region of the target gene (By similarity). May mediate cellular responses to activated FGFR1, FGFR2, FGFR3 and FGFR4 (By similarity). 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 (By similarity). Activated by IL31 through IL31RA (By similarity). Acts as a regulator of inflammatory response by regulating differentiation of naive CD4(+) T-cells into T-helper Th17 or regulatory T-cells (Treg): acetylation promotes its transcription activity and cell differentiation while deacetylation and oxidation of lysine residues by LOXL3 inhibits differentiation (By similarity). Involved in cell cycle regulation by inducing the expression of key genes for the progression from G1 to S phase, such as CCND1 (By similarity). Mediates the effects of LEP on melanocortin production, body energy homeostasis and lactation (PubMed:12594516). May play an apoptotic role by transctivating BIRC5 expression under LEP activation (PubMed:16825198). Cytoplasmic STAT3 represses macroautophagy by inhibiting EIF2AK2/PKR activity (By similarity). Plays a crucial role in basal beta cell functions, such as regulation of insulin secretion (PubMed:20215569). Following JAK/STAT signaling activation and as part of a complex with NFATC3 and NFATC4, binds to the alpha-beta E4 promoter region of CRYAB and activates transcription in cardiomyocytes (PubMed:19538478). Plays an important role in host defense in methicillin-resistant S.aureus lung infection by regulating the expression of the antimicrobial lectin REG3G (PubMed:23401489).SUBUNIT Forms a homodimer or a heterodimer with a related family member (at least STAT1). Component of a promoter-binding complex composed of STAT3, NFATC3 and NFATC4; complex formation is enhanced by calcineurin (PubMed:19538478). Interacts with IL31RA, NCOA1, PELP1, SIPAR, SOCS7, STATIP1 and TMF1. 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 PRKCE 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) (By similarity). Interacts with FGFR4 (By similarity). Interacts with INPP5F; the interaction is independent of STAT3 Tyr-705 phosphorylation status (By similarity). Interacts with OCIAD1 (PubMed:23972987). Interacts with OCIAD2 (By similarity). Interacts (unphosphorylated or phosphorylated at Ser-727) with PHB1 (By similarity). Interacts and may form heterodimers with NHLH1 (PubMed:18356286). Found in a complex with SLC39A6, SLC39A10 and with the 'Ser-727' phosphorylated form of STAT3 throughout mitosis (By similarity). Interacts (when acetylated) with EP300 (via bromo domain); interaction takes place following STAT3 acetylation by EP300 and promotes enhanceosome assembly (By similarity). Interacts (when acetylated) with BRD2 (via bromo domain); interaction promotes STAT3 recruitment to chromatin and T-helper Th17 cell differentiation (By similarity). Interacts with FAM220A/SIPAR; the interaction occurs in both the nucleus and the cytoplasm, is enhanced by IL6 and promotes STAT3 dephosphorylation (PubMed:23917203). Interacts in both unphosphorylated and phosphorylated forms with FAM220A but interacts preferentially in the phosphorylated form in the nucleus (PubMed:23917203, PubMed:26026268). Interacts with PTPN2; the interaction is promoted by FAM220A and leads to STAT3 dephosphorylation which negatively regulates STAT3 transcriptional activator activity (PubMed:26026268).INTERACTION 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 (By similarity). 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. Translocates to the nucleus in the presence of EDN1 (By similarity).ALTERNATIVE PRODUCTS Expressed in ventricular cardiomyocytes (at protein level) (PubMed:19538478). Expressed in the lung (at protein level) (PubMed:23401489). Expressed in the liver, spleen and kidney (PubMed:7512451).TISSUE SPECIFICITY Expressed in the liver.INDUCTION Induced by methicillin-resistant S.aureus infection in the lung.PTM Activated through tyrosine phosphorylation by BMX. Tyrosine phosphorylated in response to IL6, IL11, CNTF, LIF, KITLG/SCF, CSF1, EGF, PDGF, IFN-alpha, LEP and OSM. Activated KIT promotes phosphorylation on tyrosine residues and subsequent translocation to the nucleus. Tyrosine phosphorylated in response to constitutively activated FGFR1, FGFR2, FGFR3 and FGFR4. 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. Tyrosine phosphorylated upon stimulation with EGF. Upon LPS challenge, phosphorylated within the nucleus by IRAK1 (By similarity). Upon UV-A treatment, phosphorylated on Ser-727 by RPS6KA5 (By similarity). Dephosphorylation on tyrosine residues by PTPN2 negatively regulates IL6/interleukin-6 signaling (By similarity). Phosphorylation at Tyr-705 by PTK6, isoform M2 of PKM (PKM2) or FER leads to an increase of its transcriptional activity (By similarity). Phosphorylation at Tyr-705 is increased in the presence of calcineurin (PubMed:19538478). Phosphorylation at Tyr-640 by TYK2 negatively regulates transcriptional activity (By similarity).PTM Acetylated on lysine residues by EP300/p300, promoting its activation (By similarity). Acetylation at Lys-49 and Lys-87 by EP300/p300 promotes its activation (By similarity). Acetylation at Lys-87 by EP300/p300 promotes its association with BRD2 and recruitment to chromatin (By similarity). Deacetylated at Lys-49 and Lys-87 by HDAC1 (By similarity). Acetylation at Lys-685 by EP300/p300 promotes its homodimerization and activation (By similarity). Deacetylated at Lys-685 by HDAC3 (By similarity). Acetylated on lysine residues by CREBBP (By similarity). Deacetylation by LOXL3 leads to disrupt STAT3 dimerization and inhibit STAT3 transcription activity (By similarity). Oxidation of lysine residues to allysine on STAT3 preferentially takes place on lysine residues that are acetylated (By similarity).PTM Some lysine residues are oxidized to allysine by LOXL3, leading to disrupt STAT3 dimerization and inhibit STAT3 transcription activity. Oxidation of lysine residues to allysine on STAT3 preferentially takes place on lysine residues that are acetylated.PTM Methylated at Lys-140. Demethylation at Lys-140 by Jmjd1c facilitates its dephosphorylation by Ptpn6.PTM (Microbial infection) Phosphorylated on Tyr-705 in the presence of S.typhimurium SarA.DISRUPTION PHENOTYPE Early embryonic lethality, day 6.5-7.5. Conditional, tissue specific mutants are variably viable and show diverse defects including obesity, diabetes, thermal dysregulation and infertility.MISCELLANEOUS Involved in the gp130-mediated signaling pathway.SIMILARITY Belongs to the transcription factor STAT family. |
| description | recommendedName: fullName evidence="40"Signal transducer and activator of transcription 3 alternativeName: fullName evidence="32 33"Acute-phase response factor |
| geneName | Stat3 Aprf |
| identifier | P42227 |
| isSequenceChanged | FALSE |
| keyword | 3D-structure Acetylation Activator Acute phase Alternative splicing Cytoplasm Direct protein sequencing DNA-binding Methylation Nucleus Phosphoprotein Reference proteome SH2 domain Transcription Transcription regulation |
| modified | [InstanceEdit:143527] Schmidt, EE, 2004-11-12 07:45:10 [InstanceEdit:217385] Schmidt, EE, 2008-03-27 06:23:53 [InstanceEdit:354386] Schmidt, EE, 2008-06-18 04:45:12 [InstanceEdit:384350] Kanapin, AA, 2008-11-26 14:00:39 [InstanceEdit:392885] Kanapin, AA, 2009-03-09 12:07:18 [InstanceEdit:400710] Schmidt, EE, 2009-03-25 05:33:35 [InstanceEdit:423310] Kanapin, AA [InstanceEdit:435478] Kanapin, AA [InstanceEdit:435871] Kanapin, AA [InstanceEdit:447347] Kanapin, AA [InstanceEdit:525883] Kanapin, AA [InstanceEdit:613449] Kanapin, AA [InstanceEdit:797602] Kanapin, AA [InstanceEdit:937368] Yung, CK [InstanceEdit:1042053] Yung, CK [InstanceEdit:1220657] Yung, CK [InstanceEdit:1300696] Yung, CK [InstanceEdit:1301627] Yung, CK [InstanceEdit:1551960] Weiser, JD [InstanceEdit:1995863] Weiser, JD [InstanceEdit:2132304] Weiser, JD [InstanceEdit:2265580] Weiser, JD [InstanceEdit:2455454] Weiser, JD [InstanceEdit:4341137] Weiser, JD [InstanceEdit:5083144] Weiser, JD [InstanceEdit:5433710] Weiser, JD [InstanceEdit:5618415] Weiser, JD [InstanceEdit:5634237] Weiser, JD [InstanceEdit:5673015] Weiser, JD [InstanceEdit:9037114] Weiser, JD [InstanceEdit:9637257] Weiser, JD [InstanceEdit:9666080] Weiser, JD [InstanceEdit:9676415] Weiser, JD [InstanceEdit:9698430] Weiser, JD [InstanceEdit:9715482] Weiser, JD [InstanceEdit:9730071] Weiser, JD [InstanceEdit:9773244] Weiser, Joel [InstanceEdit:9796772] Weiser, Joel [InstanceEdit:9841277] Weiser, Joel [InstanceEdit:9852000] Weiser, Joel, 2023-11-03 [InstanceEdit:9909836] Weiser, Joel, 2024-05-14 [InstanceEdit:9917590] Weiser, Joel, 2024-08-09 [InstanceEdit:9939033] Weiser, Joel, 2025-02-21 [InstanceEdit:9963647] Weiser, Joel, 2025-08-15 [InstanceEdit:9983091] Weiser, Joel, 2026-02-20 |
| name | Stat3 |
| referenceDatabase | [ReferenceDatabase:2] UniProt |
| secondaryIdentifier | STAT3_MOUSE A2A5D1 B7ZC17 |
| sequenceLength | 770 |
| species | [Species:48892] Mus musculus |
| (isoformParent) | [ReferenceIsoform:154389] UniProt:P42227-2 Stat3 [Mus musculus] [ReferenceIsoform:154390] UniProt:P42227-3 Stat3 [Mus musculus] [ReferenceIsoform:404008] UniProt:P42227-1 Stat3 [Mus musculus] |
| (referenceEntity) | [EntityWithAccessionedSequence:914034] p-Y705-Stat3 [cytosol] [Mus musculus] [EntityWithAccessionedSequence:914084] Stat3 [cytosol] [Mus musculus] [EntityWithAccessionedSequence:2730582] p(Y705)-Stat3 [nucleoplasm] [Mus musculus] [EntityWithAccessionedSequence:8982832] p-Stat3 [cytosol] [Mus musculus] [EntityWithAccessionedSequence:9980218] p-S727-Stat3 [cytosol] [Mus musculus] |
| (referenceSequence) | [ModifiedResidue:8982780] phosphorylated residue at unknown position [ModifiedResidue:9980217] O-phospho-L-serine at 727 |
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No pathways have been reviewed or authored by UniProt:P42227 Stat3 (102393)
