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Protein

Signal transducer and activator of transcription 3

Gene

Stat3

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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).By similarity

GO - Molecular functioni

  1. CCR5 chemokine receptor binding Source: RGD
  2. DNA binding Source: UniProtKB
  3. glucocorticoid receptor binding Source: RGD
  4. ligand-activated sequence-specific DNA binding RNA polymerase II transcription factor activity Source: Ensembl
  5. protein dimerization activity Source: UniProtKB
  6. protein kinase binding Source: UniProtKB
  7. sequence-specific DNA binding Source: RGD
  8. sequence-specific DNA binding transcription factor activity Source: RGD
  9. signal transducer activity Source: InterPro
  10. transcription factor binding Source: RGD
  11. transcription regulatory region DNA binding Source: Ensembl

GO - Biological processi

  1. acute-phase response Source: RGD
  2. aging Source: RGD
  3. astrocyte differentiation Source: UniProtKB
  4. cell proliferation Source: Ensembl
  5. eating behavior Source: UniProtKB
  6. eye photoreceptor cell differentiation Source: UniProtKB
  7. glucose homeostasis Source: UniProtKB
  8. interleukin-6-mediated signaling pathway Source: UniProtKB
  9. JAK-STAT cascade Source: RGD
  10. JAK-STAT cascade involved in growth hormone signaling pathway Source: UniProtKB
  11. negative regulation of cell death Source: RGD
  12. negative regulation of cell proliferation Source: Ensembl
  13. negative regulation of glycolytic process Source: Ensembl
  14. negative regulation of hydrogen peroxide biosynthetic process Source: RGD
  15. negative regulation of neuron death Source: RGD
  16. negative regulation of neuron migration Source: Ensembl
  17. phosphorylation Source: UniProtKB
  18. positive regulation of ATP biosynthetic process Source: RGD
  19. positive regulation of growth factor dependent skeletal muscle satellite cell proliferation Source: RGD
  20. positive regulation of Notch signaling pathway Source: UniProtKB
  21. positive regulation of transcription, DNA-templated Source: UniProtKB
  22. positive regulation of transcription from RNA polymerase II promoter Source: Ensembl
  23. protein import into nucleus Source: UniProtKB
  24. radial glial cell differentiation Source: UniProtKB
  25. regulation of mitochondrial membrane permeability Source: RGD
  26. regulation of multicellular organism growth Source: Ensembl
  27. regulation of transcription from RNA polymerase II promoter Source: UniProtKB
  28. response to cytokine Source: RGD
  29. response to drug Source: RGD
  30. response to estradiol Source: RGD
  31. response to ethanol Source: RGD
  32. response to organic cyclic compound Source: RGD
  33. response to organic substance Source: RGD
  34. response to peptide hormone Source: RGD
  35. sexual reproduction Source: UniProtKB
  36. stem cell maintenance Source: Ensembl
  37. temperature homeostasis Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Activator

Keywords - Biological processi

Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding

Enzyme and pathway databases

ReactomeiREACT_285987. Signalling to STAT3.
REACT_295726. Signaling by Leptin.
REACT_301200. Downstream signal transduction.
REACT_314415. Growth hormone receptor signaling.
REACT_319332. Interleukin-6 signaling.
REACT_325355. Signaling by FGFR1 fusion mutants.
REACT_335137. Signaling by SCF-KIT.

Names & Taxonomyi

Protein namesi
Recommended name:
Signal transducer and activator of transcription 3
Gene namesi
Name:Stat3
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
ProteomesiUP000002494 Componenti: Chromosome 10

Organism-specific databases

RGDi3772. Stat3.

Subcellular locationi

  1. Cytoplasm By similarity
  2. Nucleus By similarity

  3. 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).By similarity

GO - Cellular componenti

  1. cytoplasm Source: UniProtKB
  2. cytosol Source: Reactome
  3. mitochondrial inner membrane Source: UniProtKB
  4. mitochondrion Source: RGD
  5. nucleus Source: UniProtKB
  6. plasma membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methioninei1 – 11RemovedBy similarity
Chaini2 – 770769Signal transducer and activator of transcription 3PRO_0000182419Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei2 – 21N-acetylalanineBy similarity
Modified residuei705 – 7051Phosphotyrosine; by FER and PTK6By similarity
Modified residuei714 – 7141PhosphothreonineBy similarity
Modified residuei727 – 7271Phosphoserine; by DYRK2, NLK, NEK6, IRAK1, RPS6KA5, ZIPK/DAPK3 and PKC/PRKCEBy similarity

Post-translational modificationi

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).By similarity

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

PaxDbiP52631.
PRIDEiP52631.

PTM databases

PhosphoSiteiP52631.

Expressioni

Tissue specificityi

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

Gene expression databases

GenevestigatoriP52631.

Interactioni

Subunit structurei

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).By similarity

Protein-protein interaction databases

BioGridi247196. 2 interactions.
DIPiDIP-44909N.
MINTiMINT-1529438.
STRINGi10116.ENSRNOP00000026760.

Structurei

3D structure databases

ProteinModelPortaliP52631.
SMRiP52631. Positions 136-715.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini580 – 67091SH2PROSITE-ProRule annotationAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi150 – 16213Essential for nuclear importBy similarityAdd
BLAST

Sequence similaritiesi

Belongs to the transcription factor STAT family.Curated
Contains 1 SH2 domain.PROSITE-ProRule annotation

Keywords - Domaini

SH2 domain

Phylogenomic databases

eggNOGiNOG303257.
GeneTreeiENSGT00760000119236.
HOGENOMiHOG000220792.
HOVERGENiHBG055669.
InParanoidiP52631.
KOiK04692.
OMAiNKESHAT.
OrthoDBiEOG73JKTT.
PhylomeDBiP52631.
TreeFamiTF318648.

Family and domain databases

Gene3Di1.10.238.10. 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.
InterProiIPR011992. 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]
PANTHERiPTHR11801. PTHR11801. 1 hit.
PfamiPF00017. SH2. 1 hit.
PF01017. STAT_alpha. 1 hit.
PF02864. STAT_bind. 1 hit.
PF02865. STAT_int. 1 hit.
[Graphical view]
SMARTiSM00252. SH2. 1 hit.
SM00964. STAT_int. 1 hit.
[Graphical view]
SUPFAMiSSF47655. SSF47655. 1 hit.
SSF48092. SSF48092. 1 hit.
SSF49417. SSF49417. 1 hit.
SSF55550. SSF55550. 1 hit.
PROSITEiPS50001. SH2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P52631-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAQWNQLQQL DTRYLEQLHQ LYSDSFPMEL RQFLAPWIES QDWAYAASKE
60 70 80 90 100
SHATLVFHNL LGEIDQQYSR FLQESNVLYQ HNLRRIKQFL QSRYLEKPME
110 120 130 140 150
IARIVARCLW EESRLLQTAA TAAQQGGQAN HPTAAVVTEK QQMLEQHLQD
160 170 180 190 200
VRKRVQDLEQ KMKVVENLQD DFDFNYKTLK SQGDMQDLNG NNQSVTRQKM
210 220 230 240 250
QQLEQMLTAL DQMRRSIVSE LAGLLSAMEY VQKTLTDEEL ADWKRRQQIA
260 270 280 290 300
CIGGPPNICL DRLENWITSL AESQLQTRQQ IKKLEELQQK VSYKGDPIVQ
310 320 330 340 350
HRPMLEERIV DLFRNLMKSA FVVERQPCMP MHPDRPLVIK TGVQFTTKVR
360 370 380 390 400
LLVKFPELNY QLKIKVCIDK DSGDVAALRG SRKFNILGTN TKVMNMEESN
410 420 430 440 450
NGSLSAEFKH LTLREQRCGN GGRANCDASL IVTEELHLIT FETEVYHQGL
460 470 480 490 500
KIDLETHSLP VVVISNICQM PNAWASILWY NMLTNNPKNV NFFTKPPIGT
510 520 530 540 550
WDQVAEVLSW QFSSTTKRGL SIEQLTTLAE KLLGPGVNYS GCQITWAKFC
560 570 580 590 600
KENMAGKGFS FWVWLDNIID LVKKYILALW NEGYIMGFIS KERERAILST
610 620 630 640 650
KPPGTFLLRF SESSKEGGVT FTWVEKDISG KTQIQSVEPY TKQQLNNMSF
660 670 680 690 700
AEIIMGYKIM DATNILVSPL VYLYPDIPKE EAFGKYCRPE SQEHPEADPG
710 720 730 740 750
SAAPYLKTKF ICVTPTTCSN TIDLPMSPRT LDSLMQFGNN GEGAEPSAGG
760 770
QFESLTFDMD LTSECATSPM
Length:770
Mass (Da):88,040
Last modified:October 1, 1996 - v1
Checksum:iD74A0C76954754ED
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X91810 mRNA. Translation: CAA62920.1.
BC087025 mRNA. Translation: AAH87025.1.
RefSeqiNP_036879.1. NM_012747.2.
UniGeneiRn.10247.

Genome annotation databases

EnsembliENSRNOT00000026760; ENSRNOP00000026760; ENSRNOG00000019742.
GeneIDi25125.
KEGGirno:25125.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X91810 mRNA. Translation: CAA62920.1.
BC087025 mRNA. Translation: AAH87025.1.
RefSeqiNP_036879.1. NM_012747.2.
UniGeneiRn.10247.

3D structure databases

ProteinModelPortaliP52631.
SMRiP52631. Positions 136-715.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi247196. 2 interactions.
DIPiDIP-44909N.
MINTiMINT-1529438.
STRINGi10116.ENSRNOP00000026760.

Chemistry

ChEMBLiCHEMBL1764933.

PTM databases

PhosphoSiteiP52631.

Proteomic databases

PaxDbiP52631.
PRIDEiP52631.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000026760; ENSRNOP00000026760; ENSRNOG00000019742.
GeneIDi25125.
KEGGirno:25125.

Organism-specific databases

CTDi6774.
RGDi3772. Stat3.

Phylogenomic databases

eggNOGiNOG303257.
GeneTreeiENSGT00760000119236.
HOGENOMiHOG000220792.
HOVERGENiHBG055669.
InParanoidiP52631.
KOiK04692.
OMAiNKESHAT.
OrthoDBiEOG73JKTT.
PhylomeDBiP52631.
TreeFamiTF318648.

Enzyme and pathway databases

ReactomeiREACT_285987. Signalling to STAT3.
REACT_295726. Signaling by Leptin.
REACT_301200. Downstream signal transduction.
REACT_314415. Growth hormone receptor signaling.
REACT_319332. Interleukin-6 signaling.
REACT_325355. Signaling by FGFR1 fusion mutants.
REACT_335137. Signaling by SCF-KIT.

Miscellaneous databases

NextBioi605521.
PROiP52631.

Gene expression databases

GenevestigatoriP52631.

Family and domain databases

Gene3Di1.10.238.10. 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.
InterProiIPR011992. 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]
PANTHERiPTHR11801. PTHR11801. 1 hit.
PfamiPF00017. SH2. 1 hit.
PF01017. STAT_alpha. 1 hit.
PF02864. STAT_bind. 1 hit.
PF02865. STAT_int. 1 hit.
[Graphical view]
SMARTiSM00252. SH2. 1 hit.
SM00964. STAT_int. 1 hit.
[Graphical view]
SUPFAMiSSF47655. SSF47655. 1 hit.
SSF48092. SSF48092. 1 hit.
SSF49417. SSF49417. 1 hit.
SSF55550. SSF55550. 1 hit.
PROSITEiPS50001. SH2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  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.

Entry informationi

Entry nameiSTAT3_RAT
AccessioniPrimary (citable) accession number: P52631
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: October 1, 1996
Last modified: April 1, 2015
This is version 134 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Miscellaneous

Involved in the gp130-mediated signaling pathway.

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.