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P52631 (STAT3_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified May 14, 2014. Version 127. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (1) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Signal transducer and activator of transcription 3
Gene names
Name:Stat3
OrganismRattus norvegicus (Rat) [Reference proteome]
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus

Protein attributes

Sequence length770 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

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 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.

Subunit 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 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

Subcellular location

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.

Tissue specificity

Detected in lung, heart, oviduct, ovary, uterus and kidney (at protein level). Detected in ovary, oviduct, and at lower levels in uterus and lung.

Post-translational modification

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.

Miscellaneous

Involved in the gp130-mediated signaling pathway.

Sequence similarities

Belongs to the transcription factor STAT family.

Contains 1 SH2 domain.

Ontologies

Keywords
   Biological processTranscription
Transcription regulation
   Cellular componentCytoplasm
Nucleus
   DomainSH2 domain
   LigandDNA-binding
   Molecular functionActivator
   PTMAcetylation
Phosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processJAK-STAT cascade

Traceable author statement Ref.1. Source: RGD

JAK-STAT cascade involved in growth hormone signaling pathway

Inferred from sequence or structural similarity. Source: UniProtKB

acute-phase response

Inferred from expression pattern Ref.1. Source: RGD

astrocyte differentiation

Inferred from sequence or structural similarity. Source: UniProtKB

cell proliferation

Inferred from electronic annotation. Source: Ensembl

eating behavior

Inferred from sequence or structural similarity. Source: UniProtKB

eye photoreceptor cell differentiation

Inferred from sequence or structural similarity. Source: UniProtKB

glucose homeostasis

Inferred from sequence or structural similarity. Source: UniProtKB

interleukin-6-mediated signaling pathway

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of cell death

Inferred from mutant phenotype PubMed 19450559. Source: RGD

negative regulation of neuron migration

Inferred from electronic annotation. Source: Ensembl

phosphorylation

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of Notch signaling pathway

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of transcription from RNA polymerase II promoter

Inferred from electronic annotation. Source: Ensembl

positive regulation of transcription, DNA-templated

Inferred from sequence or structural similarity. Source: UniProtKB

protein import into nucleus

Inferred from sequence or structural similarity. Source: UniProtKB

radial glial cell differentiation

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of multicellular organism growth

Inferred from electronic annotation. Source: Ensembl

regulation of transcription from RNA polymerase II promoter

Inferred from sequence or structural similarity. Source: UniProtKB

response to cytokine

Inferred from direct assay PubMed 18270592. Source: RGD

response to drug

Inferred from expression pattern PubMed 18031608. Source: RGD

response to estradiol

Inferred from expression pattern PubMed 17916759. Source: RGD

response to ethanol

Inferred from expression pattern PubMed 17916759. Source: RGD

response to organic cyclic compound

Inferred from expression pattern PubMed 18339648. Source: RGD

response to organic substance

Inferred from expression pattern PubMed 17916759. Source: RGD

response to peptide hormone

Inferred from expression pattern PubMed 17911393. Source: RGD

sexual reproduction

Inferred from sequence or structural similarity. Source: UniProtKB

stem cell maintenance

Inferred from electronic annotation. Source: Ensembl

temperature homeostasis

Inferred from sequence or structural similarity. Source: UniProtKB

   Cellular_componentcytoplasm

Inferred from sequence or structural similarity. Source: UniProtKB

cytosol

Traceable author statement. Source: Reactome

mitochondrial inner membrane

Inferred from direct assay PubMed 23271731. Source: UniProtKB

nucleus

Inferred from sequence or structural similarity. Source: UniProtKB

plasma membrane

Inferred from sequence or structural similarity. Source: UniProtKB

   Molecular_functionCCR5 chemokine receptor binding

Inferred from physical interaction PubMed 14674010. Source: RGD

DNA binding

Inferred from sequence or structural similarity. Source: UniProtKB

calcium ion binding

Inferred from electronic annotation. Source: InterPro

glucocorticoid receptor binding

Inferred from physical interaction PubMed 20155810. Source: RGD

ligand-activated sequence-specific DNA binding RNA polymerase II transcription factor activity

Inferred from electronic annotation. Source: Ensembl

protein dimerization activity

Inferred from sequence or structural similarity. Source: UniProtKB

protein kinase binding

Inferred from sequence or structural similarity. Source: UniProtKB

sequence-specific DNA binding

Inferred from direct assay PubMed 16648019. Source: RGD

sequence-specific DNA binding transcription factor activity

Traceable author statement Ref.1. Source: RGD

signal transducer activity

Inferred from electronic annotation. Source: InterPro

transcription factor binding

Inferred from physical interaction PubMed 19289167. Source: RGD

transcription regulatory region DNA binding

Inferred from electronic annotation. Source: Ensembl

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed By similarity
Chain2 – 770769Signal transducer and activator of transcription 3
PRO_0000182419

Regions

Domain580 – 67091SH2
Motif150 – 16213Essential for nuclear import By similarity

Amino acid modifications

Modified residue21N-acetylalanine By similarity
Modified residue7051Phosphotyrosine; by FER and PTK6 By similarity
Modified residue7271Phosphoserine; by DYRK2, NLK, NEK6, IRAK1, RPS6KA5, ZIPK/DAPK3 and PKC/PRKCE By similarity

Sequences

Sequence LengthMass (Da)Tools
P52631 [UniParc].

Last modified October 1, 1996. Version 1.
Checksum: D74A0C76954754ED

FASTA77088,040
        10         20         30         40         50         60 
MAQWNQLQQL DTRYLEQLHQ LYSDSFPMEL RQFLAPWIES QDWAYAASKE SHATLVFHNL 

        70         80         90        100        110        120 
LGEIDQQYSR FLQESNVLYQ HNLRRIKQFL QSRYLEKPME IARIVARCLW EESRLLQTAA 

       130        140        150        160        170        180 
TAAQQGGQAN HPTAAVVTEK QQMLEQHLQD VRKRVQDLEQ KMKVVENLQD DFDFNYKTLK 

       190        200        210        220        230        240 
SQGDMQDLNG NNQSVTRQKM QQLEQMLTAL DQMRRSIVSE LAGLLSAMEY VQKTLTDEEL 

       250        260        270        280        290        300 
ADWKRRQQIA CIGGPPNICL DRLENWITSL AESQLQTRQQ IKKLEELQQK VSYKGDPIVQ 

       310        320        330        340        350        360 
HRPMLEERIV DLFRNLMKSA FVVERQPCMP MHPDRPLVIK TGVQFTTKVR LLVKFPELNY 

       370        380        390        400        410        420 
QLKIKVCIDK DSGDVAALRG SRKFNILGTN TKVMNMEESN NGSLSAEFKH LTLREQRCGN 

       430        440        450        460        470        480 
GGRANCDASL IVTEELHLIT FETEVYHQGL KIDLETHSLP VVVISNICQM PNAWASILWY 

       490        500        510        520        530        540 
NMLTNNPKNV NFFTKPPIGT WDQVAEVLSW QFSSTTKRGL SIEQLTTLAE KLLGPGVNYS 

       550        560        570        580        590        600 
GCQITWAKFC KENMAGKGFS FWVWLDNIID LVKKYILALW NEGYIMGFIS KERERAILST 

       610        620        630        640        650        660 
KPPGTFLLRF SESSKEGGVT FTWVEKDISG KTQIQSVEPY TKQQLNNMSF AEIIMGYKIM 

       670        680        690        700        710        720 
DATNILVSPL VYLYPDIPKE EAFGKYCRPE SQEHPEADPG SAAPYLKTKF ICVTPTTCSN 

       730        740        750        760        770 
TIDLPMSPRT LDSLMQFGNN GEGAEPSAGG QFESLTFDMD LTSECATSPM 

« Hide

References

« Hide 'large scale' references
[1]"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].
Tissue: Liver.
[2]"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].
Tissue: Kidney.
[3]"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.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X91810 mRNA. Translation: CAA62920.1.
BC087025 mRNA. Translation: AAH87025.1.
RefSeqNP_036879.1. NM_012747.2.
UniGeneRn.10247.

3D structure databases

ProteinModelPortalP52631.
SMRP52631. Positions 136-715.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid247196. 2 interactions.
MINTMINT-1529438.
STRING10116.ENSRNOP00000026760.

Chemistry

ChEMBLCHEMBL1764933.

PTM databases

PhosphoSiteP52631.

Proteomic databases

PaxDbP52631.
PRIDEP52631.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSRNOT00000026760; ENSRNOP00000026760; ENSRNOG00000019742.
GeneID25125.
KEGGrno:25125.

Organism-specific databases

CTD6774.
RGD3772. Stat3.

Phylogenomic databases

eggNOGNOG303257.
GeneTreeENSGT00750000117596.
HOGENOMHOG000220792.
HOVERGENHBG055669.
InParanoidP52631.
KOK04692.
OMANKESHAT.
OrthoDBEOG73JKTT.
PhylomeDBP52631.
TreeFamTF318648.

Enzyme and pathway databases

ReactomeREACT_212996. Signal Transduction.

Gene expression databases

GenevestigatorP52631.

Family and domain databases

Gene3D1.10.238.10. 1 hit.
1.10.532.10. 1 hit.
1.20.1050.20. 1 hit.
2.60.40.630. 1 hit.
3.30.505.10. 1 hit.
InterProIPR011992. EF-hand-dom_pair.
IPR008967. p53-like_TF_DNA-bd.
IPR000980. SH2.
IPR001217. STAT.
IPR013800. STAT_TF_alpha.
IPR015988. STAT_TF_coiled-coil.
IPR013801. STAT_TF_DNA-bd.
IPR012345. STAT_TF_DNA-bd_sub.
IPR013799. STAT_TF_prot_interaction.
[Graphical view]
PANTHERPTHR11801. PTHR11801. 1 hit.
PfamPF00017. SH2. 1 hit.
PF01017. STAT_alpha. 1 hit.
PF02864. STAT_bind. 1 hit.
PF02865. STAT_int. 1 hit.
[Graphical view]
SMARTSM00252. SH2. 1 hit.
SM00964. STAT_int. 1 hit.
[Graphical view]
SUPFAMSSF47655. SSF47655. 1 hit.
SSF48092. SSF48092. 1 hit.
SSF49417. SSF49417. 1 hit.
SSF55550. SSF55550. 1 hit.
PROSITEPS50001. SH2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio605521.
PROP52631.

Entry information

Entry nameSTAT3_RAT
AccessionPrimary (citable) accession number: P52631
Entry history
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: October 1, 1996
Last modified: May 14, 2014
This is version 127 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families