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P40763 (STAT3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified March 19, 2014. Version 156. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Signal transducer and activator of transcription 3
Alternative name(s):
Acute-phase response factor
Gene names
Name:STAT3
Synonyms:APRF
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

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. 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. Ref.9 Ref.10 Ref.14 Ref.17 Ref.39

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 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). Ref.8 Ref.9 Ref.11 Ref.12 Ref.13 Ref.14 Ref.17 Ref.19 Ref.20 Ref.21 Ref.22 Ref.25 Ref.27 Ref.29 Ref.30 Ref.34 Ref.35 Ref.39

Subcellular location

Cytoplasm. 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. Ref.21 Ref.26 Ref.30

Tissue specificity

Heart, brain, placenta, lung, liver, skeletal muscle, kidney and pancreas.

Post-translational modification

Tyrosine 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. Ref.7 Ref.9 Ref.10 Ref.15 Ref.18 Ref.21 Ref.24 Ref.25 Ref.28 Ref.30 Ref.34 Ref.38

Involvement in disease

Hyperimmunoglobulin 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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.42 Ref.43

Miscellaneous

Involved in the gp130-mediated signaling pathway.

Sequence similarities

Belongs to the transcription factor STAT family.

Contains 1 SH2 domain.

Ontologies

Keywords
   Biological processHost-virus interaction
Transcription
Transcription regulation
   Cellular componentCytoplasm
Nucleus
   Coding sequence diversityAlternative splicing
Polymorphism
   DiseaseDisease mutation
   DomainSH2 domain
   LigandDNA-binding
   Molecular functionActivator
   PTMAcetylation
Phosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processJAK-STAT cascade involved in growth hormone signaling pathway

Inferred from sequence or structural similarity. Source: UniProtKB

acute-phase response

Inferred from electronic annotation. Source: Ensembl

astrocyte differentiation

Inferred from sequence or structural similarity. Source: UniProtKB

cell proliferation

Inferred from electronic annotation. Source: Ensembl

cellular component movement

Traceable author statement PubMed 9670957. Source: ProtInc

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 direct assay Ref.10. Source: UniProtKB

negative regulation of cell death

Inferred from electronic annotation. Source: Ensembl

negative regulation of neuron migration

Inferred from electronic annotation. Source: Ensembl

negative regulation of transcription from RNA polymerase II promoter

Traceable author statement PubMed 8675499. Source: ProtInc

neurotrophin TRK receptor signaling pathway

Traceable author statement. Source: Reactome

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 direct assay PubMed 17324931. Source: BHF-UCL

protein import into nucleus

Inferred from direct assay Ref.30. 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

response to drug

Inferred from electronic annotation. Source: Ensembl

response to estradiol

Inferred from direct assay PubMed 12552091. Source: BHF-UCL

response to ethanol

Inferred from electronic annotation. Source: Ensembl

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

viral process

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentcytosol

Traceable author statement. Source: Reactome

nucleoplasm

Traceable author statement. Source: Reactome

plasma membrane

Inferred from sequence or structural similarity. Source: UniProtKB

   Molecular_functioncalcium ion binding

Inferred from electronic annotation. Source: InterPro

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

Inferred from direct assay PubMed 17324931. Source: BHF-UCL

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 electronic annotation. Source: Ensembl

signal transducer activity

Traceable author statement Ref.1. Source: ProtInc

transcription regulatory region DNA binding

Inferred from direct assay PubMed 17324931. Source: BHF-UCL

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P40763-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform Del-701 (identifier: P40763-2)

The sequence of this isoform differs from the canonical sequence as follows:
     701-701: Missing.
Note: Contains a phosphotyrosine at position 704.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed
Chain2 – 770769Signal transducer and activator of transcription 3
PRO_0000182417

Regions

Domain580 – 67091SH2
Motif150 – 16213Essential for nuclear import

Amino acid modifications

Modified residue21N-acetylalanine
Modified residue7051Phosphotyrosine; by FER and PTK6 Ref.7 Ref.15 Ref.23 Ref.24 Ref.30 Ref.38
Modified residue7271Phosphoserine; by DYRK2, NLK, NEK6, IRAK1, RPS6KA5, ZIPK/DAPK3 and PKC/PRKCE Ref.7 Ref.15 Ref.18 Ref.21 Ref.25 Ref.28 Ref.30 Ref.31 Ref.32 Ref.36 Ref.38

Natural variations

Alternative sequence7011Missing in isoform Del-701.
VSP_010474
Natural variant321Q → K.
Corresponds to variant rs1803125 [ dbSNP | Ensembl ].
VAR_018683
Natural variant1431M → I. Ref.3
Corresponds to variant rs17878478 [ dbSNP | Ensembl ].
VAR_018679
Natural variant3821R → L in AD-HIES. Ref.42
VAR_037365
Natural variant3821R → Q in AD-HIES; loss of function. Ref.42 Ref.43
VAR_037366
Natural variant3821R → W in AD-HIES; loss of function. Ref.42 Ref.43
VAR_037367
Natural variant3841F → L in AD-HIES. Ref.42
VAR_037368
Natural variant3841F → S in AD-HIES. Ref.42
VAR_037369
Natural variant3891T → I in AD-HIES; loss of function. Ref.43
VAR_037370
Natural variant4231R → Q in AD-HIES. Ref.42
VAR_037371
Natural variant4371H → Y in AD-HIES; loss of function. Ref.43
VAR_037372
Natural variant4631Missing in AD-HIES; loss of function. Ref.42 Ref.43
VAR_037373
Natural variant5611F → Y. Ref.1
Corresponds to variant rs1064116 [ dbSNP | Ensembl ].
VAR_037374
Natural variant6111S → N in AD-HIES. Ref.42
VAR_037375
Natural variant6211F → V in AD-HIES. Ref.42
VAR_037376
Natural variant6221T → I in AD-HIES. Ref.42
VAR_037377
Natural variant6371V → L in AD-HIES. Ref.42
VAR_037378
Natural variant6371V → M in AD-HIES. Ref.42
VAR_037379
Natural variant6441Missing in AD-HIES. Ref.42
VAR_037380
Natural variant6571Y → C in AD-HIES. Ref.42
VAR_037381

Experimental info

Sequence conflict1331T → A in BAF84622. Ref.4
Sequence conflict2881Q → H in AAA58374. Ref.1
Sequence conflict4601P → S in AAA58374. Ref.1
Sequence conflict5481K → N in AAA58374. Ref.1
Sequence conflict6521E → V in BAF84622. Ref.4
Sequence conflict6671V → L in AAA58374. Ref.1
Sequence conflict7301T → A in AAA58374. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified June 7, 2004. Version 2.
Checksum: 6C00632211C8012D

FASTA77088,068
        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 ELFRNLMKSA 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 QFESLTFDME LTSECATSPM 

« Hide

Isoform Del-701 [UniParc].

Checksum: A374A32AB9D28077
Show »

FASTA76987,981

References

« Hide 'large scale' references
[1]"Molecular cloning of APRF, a novel IFN-stimulated gene factor 3 p91-related transcription factor involved in the gp130-mediated signaling pathway."
Akira S., Nishio Y., Inoue M., Wang X.-J., Wei S., Matsusaka T., Yoshida K., Sudo T., Naruto M., Kishimoto T.
Cell 77:63-71(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT TYR-561.
Tissue: Placenta.
[2]"Highly conserved amino-acid sequence between murine STAT3 and a revised human STAT3 sequence."
Della Pietra L., Bressan A., Pezzotti A., Serlupi-Crescenzi O.
Gene 213:119-124(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[3]SeattleSNPs variation discovery resource
Submitted (MAR-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT ILE-143.
[4]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[5]"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] (ISOFORMS 1 AND DEL-701).
Tissue: Kidney and Pancreas.
[6]Della Pietra L., Bressan A., Pezzotti A.R., Serlupi-Crescenzi O.
Submitted (OCT-1997) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 564-704.
Tissue: Liver.
[7]"Requirement of serine phosphorylation for formation of STAT-promoter complexes."
Zhang X., Blenis J., Li H.-C., Schindler C., Chen-Kiang S.
Science 267:1990-1994(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SERINE RESIDUES.
[8]"Specific inhibition of Stat3 signal transduction by PIAS3."
Chung C.D., Liao J., Liu B., Rao X., Jay P., Berta P., Shuai K.
Science 278:1803-1805(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH PIAS3.
[9]"Etk, a Btk family tyrosine kinase, mediates cellular transformation by linking Src to STAT3 activation."
Tsai Y.T., Su Y.H., Fang S.S., Huang T.N., Qiu Y., Jou Y.S., Shih H.M., Kung H.J., Chen R.H.
Mol. Cell. Biol. 20:2043-2054(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION BY BMX, INTERACTION WITH BMX, FUNCTION.
[10]"The nuclear isoform of protein-tyrosine phosphatase TC-PTP regulates interleukin-6-mediated signaling pathway through STAT3 dephosphorylation."
Yamamoto T., Sekine Y., Kashima K., Kubota A., Sato N., Aoki N., Matsuda T.
Biochem. Biophys. Res. Commun. 297:811-817(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN IL6 SIGNALING, PHOSPHORYLATION, DEPHOSPHORYLATION BY PTPN2.
[11]"Functional interaction of STAT3 transcription factor with the coactivator NcoA/SRC1a."
Giraud S., Bienvenu F., Avril S., Gascan H., Heery D.M., Coqueret O.
J. Biol. Chem. 277:8004-8011(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH NCOA1.
[12]"Activation of STAT3 by the hepatitis C virus core protein leads to cellular transformation."
Yoshida T., Hanada T., Tokuhisa T., Kosai K., Sata M., Kohara M., Yoshimura A.
J. Exp. Med. 196:641-653(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH HCV CORE PROTEIN.
[13]"A receptor for the heterodimeric cytokine IL-23 is composed of IL-12Rbeta1 and a novel cytokine receptor subunit, IL-23R."
Parham C., Chirica M., Timans J., Vaisberg E., Travis M., Cheung J., Pflanz S., Zhang R., Singh K.P., Vega F., To W., Wagner J., O'Farrell A.-M., McClanahan T.K., Zurawski S., Hannum C., Gorman D., Rennick D.M. expand/collapse author list , Kastelein R.A., de Waal Malefyt R., Moore K.W.
J. Immunol. 168:5699-5708(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH IL23R.
[14]"Identification and characterization of signal transducer and activator of transcription 3 recruitment sites within the epidermal growth factor receptor."
Shao H., Cheng H.Y., Cook R.G., Tweardy D.J.
Cancer Res. 63:3923-3930(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN EGFR SIGNALING, INTERACTION WITH EGFR.
[15]"Erythropoietin-induced serine 727 phosphorylation of STAT3 in erythroid cells is mediated by a MEK-, ERK-, and MSK1-dependent pathway."
Wierenga A.T., Vogelzang I., Eggen B.J., Vellenga E.
Exp. Hematol. 31:398-405(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT TYR-705 AND SER-727.
[16]"Signal transduction via the stem cell factor receptor/c-Kit."
Ronnstrand L.
Cell. Mol. Life Sci. 61:2535-2548(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW ON ROLE IN KIT SIGNALING.
[17]"Characterization of the signaling capacities of the novel gp130-like cytokine receptor."
Dreuw A., Radtke S., Pflanz S., Lippok B.E., Heinrich P.C., Hermanns H.M.
J. Biol. Chem. 279:36112-36120(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH IL31RA.
[18]"IRAK1 serves as a novel regulator essential for lipopolysaccharide-induced interleukin-10 gene expression."
Huang Y., Li T., Sane D.C., Li L.
J. Biol. Chem. 279:51697-51703(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-727 BY IRAK1.
[19]"TMF/ARA160 is a BC-box-containing protein that mediates the degradation of Stat3."
Perry E., Tsruya R., Levitsky P., Pomp O., Taller M., Weisberg S., Parris W., Kulkarni S., Malovani H., Pawson T., Shpungin S., Nir U.
Oncogene 23:8908-8919(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH TMF1.
[20]"Proline-, glutamic acid-, and leucine-rich protein-1 is essential in growth factor regulation of signal transducers and activators of transcription 3 activation."
Manavathi B., Nair S.S., Wang R.-A., Kumar R., Vadlamudi R.K.
Cancer Res. 65:5571-5577(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH PELP1.
[21]"Physical and functional interactions between STAT3 and ZIP kinase."
Sato N., Kawai T., Sugiyama K., Muromoto R., Imoto S., Sekine Y., Ishida M., Akira S., Matsuda T.
Int. Immunol. 17:1543-1552(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-727 BY ZIPK/DAPK3, INTERACTION WITH ZIPK/DAPK3, SUBCELLULAR LOCATION.
[22]"Suppressor of cytokine signaling 7 inhibits prolactin, growth hormone, and leptin signaling by interacting with STAT5 or STAT3 and attenuating their nuclear translocation."
Martens N., Uzan G., Wery M., Hooghe R., Hooghe-Peters E.L., Gertler A.
J. Biol. Chem. 280:13817-13823(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH SOCS7.
[23]"Immunoaffinity profiling of tyrosine phosphorylation in cancer cells."
Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H., Zha X.-M., Polakiewicz R.D., Comb M.J.
Nat. Biotechnol. 23:94-101(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-705, PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-704 (ISOFORM DEL-701), IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[24]"Identification of STAT3 as a specific substrate of breast tumor kinase."
Liu L., Gao Y., Qiu H., Miller W.T., Poli V., Reich N.C.
Oncogene 25:4904-4912(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT TYR-705 BY PTK6.
[25]"Protein kinase Cepsilon interacts with signal transducers and activators of transcription 3 (Stat3), phosphorylates Stat3Ser727, and regulates its constitutive activation in prostate cancer."
Aziz M.H., Manoharan H.T., Church D.R., Dreckschmidt N.E., Zhong W., Oberley T.D., Wilding G., Verma A.K.
Cancer Res. 67:8828-8838(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH PRKCE, PHOSPHORYLATION AT SER-727.
[26]"STAT3 nuclear import is independent of tyrosine phosphorylation and mediated by importin-alpha3."
Liu L., McBride K.M., Reich N.C.
Proc. Natl. Acad. Sci. U.S.A. 102:8150-8155(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, NUCLEAR IMPORT MOTIF.
[27]"The functional role of an interleukin 6-inducible CDK9.STAT3 complex in human gamma-fibrinogen gene expression."
Hou T., Ray S., Brasier A.R.
J. Biol. Chem. 282:37091-37102(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH CDK9.
[28]"Role for DYRK family kinases on regulation of apoptosis."
Yoshida K.
Biochem. Pharmacol. 76:1389-1394(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-727 BY DYRK2.
[29]"Oncogenic association of the Cbp/PAG adaptor protein with the Lyn tyrosine kinase in human B-NHL rafts."
Tauzin S., Ding H., Khatib K., Ahmad I., Burdevet D., van Echten-Deckert G., Lindquist J.A., Schraven B., Din N.U., Borisch B., Hoessli D.C.
Blood 111:2310-2320(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION IN A COMPLEX WITH LYN AND PAG1.
[30]"BART is essential for nuclear retention of STAT3."
Muromoto R., Sekine Y., Imoto S., Ikeda O., Okayama T., Sato N., Matsuda T.
Int. Immunol. 20:395-403(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH ARL2BP, PHOSPHORYLATION AT SERINE RESIDUES, SUBCELLULAR LOCATION.
[31]"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle."
Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M.
Mol. Cell 31:438-448(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-727, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[32]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-727, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[33]"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.
Anal. Chem. 81:4493-4501(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[34]"The Fer tyrosine kinase cooperates with interleukin-6 to activate signal transducer and activator of transcription 3 and promote human prostate cancer cell growth."
Zoubeidi A., Rocha J., Zouanat F.Z., Hamel L., Scarlata E., Aprikian A.G., Chevalier S.
Mol. Cancer Res. 7:142-155(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH FER, PHOSPHORYLATION BY FER.
[35]"Acetylation directs survivin nuclear localization to repress STAT3 oncogenic activity."
Wang H., Holloway M.P., Ma L., Cooper Z.A., Riolo M., Samkari A., Elenitoba-Johnson K.S., Chin Y.E., Altura R.A.
J. Biol. Chem. 285:36129-36137(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH BIRC5/SURVIVIN.
[36]"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-727, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[37]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[38]"Mechanisms of STAT protein activation by oncogenic KIT mutants in neoplastic mast cells."
Chaix A., Lopez S., Voisset E., Gros L., Dubreuil P., De Sepulveda P.
J. Biol. Chem. 286:5956-5966(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT TYR-705 IN RESPONSE TO KIT SIGNALING, PHOSPHORYLATION AT SER-727.
[39]"Cytoplasmic STAT3 represses autophagy by inhibiting PKR activity."
Shen S., Niso-Santano M., Adjemian S., Takehara T., Malik S.A., Minoux H., Souquere S., Marino G., Lachkar S., Senovilla L., Galluzzi L., Kepp O., Pierron G., Maiuri M.C., Hikita H., Kroemer R., Kroemer G.
Mol. Cell 48:667-680(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH EIF2AK2.
[40]"Comparative large-scale characterisation of plant vs. mammal proteins reveals similar and idiosyncratic N-alpha acetylation features."
Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T., Giglione C.
Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS], CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS].
[41]"N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB."
Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.
Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[42]"STAT3 mutations in the hyper-IgE syndrome."
Holland S.M., DeLeo F.R., Elloumi H.Z., Hsu A.P., Uzel G., Brodsky N., Freeman A.F., Demidowich A., Davis J., Turner M.L., Anderson V.L., Darnell D.N., Welch P.A., Kuhns D.B., Frucht D.M., Malech H.L., Gallin J.I., Kobayashi S.D. expand/collapse author list , Whitney A.R., Voyich J.M., Musser J.M., Woellner C., Schaffer A.A., Puck J.M., Grimbacher B.
N. Engl. J. Med. 357:1608-1619(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS AD-HIES GLN-382; LEU-382; TRP-382; LEU-384; SER-384; GLN-423; VAL-463 DEL; ASN-611; VAL-621; ILE-622; LEU-637; MET-637; GLN-644 DEL AND CYS-657.
[43]"Dominant-negative mutations in the DNA-binding domain of STAT3 cause hyper-IgE syndrome."
Minegishi Y., Saito M., Tsuchiya S., Tsuge I., Takada H., Hara T., Kawamura N., Ariga T., Pasic S., Stojkovic O., Metin A., Karasuyama H.
Nature 448:1058-1062(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS AD-HIES GLN-382; TRP-382; ILE-389; TYR-437 AND VAL-463 DEL, CHARACTERIZATION OF VARIANTS AD-HIES GLN-382; TRP-382; ILE-389; TYR-437 AND VAL-463 DEL.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
L29277 mRNA. Translation: AAA58374.1.
AJ012463 mRNA. Translation: CAA10032.1.
AY572796 Genomic DNA. Translation: AAS66986.1.
AK291933 mRNA. Translation: BAF84622.1.
BC000627 mRNA. Translation: AAH00627.1.
BC014482 mRNA. Translation: AAH14482.1.
AF029311 mRNA. Translation: AAB84254.1.
PIRA54444.
RefSeqNP_003141.2. NM_003150.3.
NP_644805.1. NM_139276.2.
NP_998827.1. NM_213662.1.
UniGeneHs.463059.

3D structure databases

ProteinModelPortalP40763.
SMRP40763. Positions 2-715.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid112651. 153 interactions.
DIPDIP-33584N.
IntActP40763. 83 interactions.
MINTMINT-146801.
STRING9606.ENSP00000264657.

Chemistry

BindingDBP40763.
ChEMBLCHEMBL4026.

PTM databases

PhosphoSiteP40763.

Polymorphism databases

DMDM48429227.

Proteomic databases

PaxDbP40763.
PeptideAtlasP40763.
PRIDEP40763.

Protocols and materials databases

DNASU6774.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000264657; ENSP00000264657; ENSG00000168610. [P40763-1]
ENST00000404395; ENSP00000384943; ENSG00000168610. [P40763-2]
ENST00000588969; ENSP00000467985; ENSG00000168610. [P40763-1]
GeneID6774.
KEGGhsa:6774.
UCSCuc002hzk.1. human. [P40763-1]
uc002hzm.1. human. [P40763-2]

Organism-specific databases

CTD6774.
GeneCardsGC17M040465.
HGNCHGNC:11364. STAT3.
HPACAB003859.
HPA001671.
MIM102582. gene.
147060. phenotype.
neXtProtNX_P40763.
Orphanet2314. Autosomal dominant hyper-IgE syndrome.
PharmGKBPA337.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG303257.
HOGENOMHOG000220792.
HOVERGENHBG055669.
InParanoidP40763.
KOK04692.
OMANKESHAT.
OrthoDBEOG73JKTT.
TreeFamTF318648.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.
REACT_116125. Disease.
REACT_6900. Immune System.
SignaLinkP40763.

Gene expression databases

ArrayExpressP40763.
BgeeP40763.
CleanExHS_STAT3.
GenevestigatorP40763.

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.
PROSITEPS50001. SH2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSSTAT3. human.
GeneWikiSTAT3.
GenomeRNAi6774.
NextBio26438.
PMAP-CutDBP40763.
PROP40763.
SOURCESearch...

Entry information

Entry nameSTAT3_HUMAN
AccessionPrimary (citable) accession number: P40763
Secondary accession number(s): A8K7B8, O14916, Q9BW54
Entry history
Integrated into UniProtKB/Swiss-Prot: February 1, 1995
Last sequence update: June 7, 2004
Last modified: March 19, 2014
This is version 156 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 17

Human chromosome 17: entries, gene names and cross-references to MIM