P52631 (STAT3_RAT) Reviewed, UniProtKB/Swiss-Prot
Last modified May 14, 2014. Version 127. History...
Names and origin
|Protein names||Recommended name:|
Signal transducer and activator of transcription 3
|Organism||Rattus norvegicus (Rat) [Reference proteome]|
|Taxonomic identifier||10116 [NCBI]|
|Taxonomic lineage||Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus|
|Sequence length||770 AA.|
|Sequence processing||The displayed sequence is further processed into a mature form.|
|Protein existence||Evidence at protein level|
General annotation (Comments)
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 By similarity. Cytoplasmic STAT3 represses macroautophagy by inhibiting EIF2AK2/PKR activity By similarity. 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.
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 IL23R in presence of IL23. Interacts (via SH2 domain) with NLK. Interacts with KPNA4 and KPNA5; KPNA4 may be the primary mediator of nuclear import By similarity. Interacts with ARL2BP; interaction is enhanced with ARL2. Interacts with ARL2BP; the interaction is enhanced by LIF and JAK1 expression By similarity. Interacts with CAV2; the interaction is increased on insulin-induced tyrosine phosphorylation of CAV2 and leads to STAT3 activation. Interacts with NEK6. Binds to CDK9 when activated and nuclear By similarity. Interacts with BMX By similarity. Interacts with ZIPK/DAPK3 By similarity. Interacts with STMN3, antagonizing its microtubule-destabilizing activity By similarity. Interacts with the 'Lys-129' acetylated form of BIRC5/survivin. Interacts with FER By similarity. Interacts (via SH2 domain) with EIF2AK2/PKR (via the kinase catalytic domain) By similarity. Ref.3
Cytoplasm By similarity. Nucleus By similarity. 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 By similarity.
Detected in lung, heart, oviduct, ovary, uterus and kidney (at protein level). Detected in ovary, oviduct, and at lower levels in uterus and lung.
Activated through tyrosine phosphorylation by BMX. Tyrosine phosphorylated in response to IL6, IL11, CNTF, LIF, KITLG/SCF, CSF1, EGF, PDGF, IFN-alpha 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. Phosphorylated on Ser-727 by RPS6KA5 By similarity. Phosphoryation at Tyr-705 by FER or PTK6 leads to an increase of its transcriptional activity. Dephosphorylation on tyrosine residues by PTPN2 negatively regulates IL6/interleukin-6 signaling By similarity.
Involved in the gp130-mediated signaling pathway.
Belongs to the transcription factor STAT family.
Contains 1 SH2 domain.
Sequence annotation (Features)
|Feature key||Position(s)||Length||Description||Graphical view||Feature identifier|
|Initiator methionine||1||1||Removed By similarity|
|Chain||2 – 770||769||Signal transducer and activator of transcription 3||PRO_0000182419|
|Domain||580 – 670||91||SH2|
|Motif||150 – 162||13||Essential for nuclear import By similarity|
Amino acid modifications
|Modified residue||2||1||N-acetylalanine By similarity|
|Modified residue||705||1||Phosphotyrosine; by FER and PTK6 By similarity|
|Modified residue||727||1||Phosphoserine; by DYRK2, NLK, NEK6, IRAK1, RPS6KA5, ZIPK/DAPK3 and PKC/PRKCE By similarity|
|||"Transcription factors Stat3 and Stat5b are present in rat liver nuclei late in an acute phase response and bind interleukin-6 response elements."|
Ripperger J.A., Fritz S., Richter K., Hocke G.M., Lottspeich F., Fey G.H.
J. Biol. Chem. 270:29998-30006(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
|||"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."|
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
|||"Caveolin-2 regulation of STAT3 transcriptional activation in response to insulin."|
Kwon H., Jeong K., Hwang E.M., Park J.-Y., Hong S.-G., Choi W.-S., Pak Y.
Biochim. Biophys. Acta 1793:1325-1333(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH CAV2.
|+||Additional computationally mapped references.|
|X91810 mRNA. Translation: CAA62920.1.|
BC087025 mRNA. Translation: AAH87025.1.
|RefSeq||NP_036879.1. NM_012747.2. |
3D structure databases
|SMR||P52631. Positions 136-715. |
Protein-protein interaction databases
|BioGrid||247196. 2 interactions.|
Protocols and materials databases
Genome annotation databases
|Ensembl||ENSRNOT00000026760; ENSRNOP00000026760; ENSRNOG00000019742. |
|RGD||3772. Stat3. |
Enzyme and pathway databases
|Reactome||REACT_212996. Signal Transduction. |
Gene expression databases
Family and domain databases
|Gene3D||18.104.22.168. 1 hit. |
1.10.532.10. 1 hit.
1.20.1050.20. 1 hit.
22.214.171.1240. 1 hit.
3.30.505.10. 1 hit.
|InterPro||IPR011992. EF-hand-dom_pair. |
|PANTHER||PTHR11801. PTHR11801. 1 hit. |
|Pfam||PF00017. SH2. 1 hit. |
PF01017. STAT_alpha. 1 hit.
PF02864. STAT_bind. 1 hit.
PF02865. STAT_int. 1 hit.
|SMART||SM00252. SH2. 1 hit. |
SM00964. STAT_int. 1 hit.
|SUPFAM||SSF47655. SSF47655. 1 hit. |
SSF48092. SSF48092. 1 hit.
SSF49417. SSF49417. 1 hit.
SSF55550. SSF55550. 1 hit.
|PROSITE||PS50001. SH2. 1 hit. |
|Accession||Primary (citable) accession number: P52631|
|Entry status||Reviewed (UniProtKB/Swiss-Prot)|
|Annotation program||Chordata Protein Annotation Program|
Index of protein domains and families