Signal transducer and activator of transcription 3

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Protein attributes

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Sequence annotation (Features)

Sequences

References

Web resources

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Sequence annotation (Features)

Sequences

References

Web resources

Cross-references

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#Exp.

IntAct

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P40763 (STAT3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified January 25, 2012. Version 132. History...

Clusters with 100%, 90%, 50% identity |

Documents (5) |

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Names·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·Documents Customize order

Protein names

Recommended name:
Signal transducer and activator of transcription 3

Alternative name(s):
Acute-phase response factor

Gene names

Name:	STAT3
Synonyms:	APRF

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Sequence length	770 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

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. Ref.9 Ref.13 Ref.16
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. Ref.8 Ref.9 Ref.10 Ref.11 Ref.12 Ref.13 Ref.16 Ref.18 Ref.19 Ref.20 Ref.21 Ref.25 Ref.28 Ref.33
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.20 Ref.26 Ref.33
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 leads to an increase of its transcriptional activity. Ref.7 Ref.9 Ref.14 Ref.17 Ref.20 Ref.22 Ref.23 Ref.24 Ref.25 Ref.27 Ref.29 Ref.30 Ref.31 Ref.33 Ref.34 Ref.35 Ref.36 Ref.37 Ref.39
Involvement in disease	Defects in STAT3 are the cause of hyperimmunoglobulin E recurrent infection syndrome autosomal dominant (AD-HIES) [MIM:147060]; also known as hyper-IgE syndrome or Job syndrome. AD-HIES is 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. Ref.40 Ref.41
Miscellaneous	Involved in the gp130-mediated signaling pathway.
Sequence similarities	Belongs to the transcription factor STAT family. Contains 1 SH2 domain.

Keywords
Biological process	Host-virus interaction Transcription Transcription regulation
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Disease mutation
Domain	SH2 domain
Ligand	DNA-binding
Molecular function	Activator
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Uncategorized	ligand-regulated transcription factor activity Inferred from direct assay. Source: BHF-UCL
Biological process	JAK-STAT cascade involved in growth hormone signaling pathway Inferred from sequence or structural similarity. Source: UniProtKB astrocyte differentiation Inferred from sequence or structural similarity. Source: UniProtKB cellular component movement Traceable author statement. 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. Source: BHF-UCL interspecies interaction between organisms Inferred from electronic annotation. Source: UniProtKB-KW negative regulation of transcription from RNA polymerase II promoter Traceable author statement. Source: ProtInc nerve growth factor receptor signaling pathway Traceable author statement. Source: Reactome 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. Source: BHF-UCL protein import into nucleus Inferred from direct assay Ref.33. Source: UniProtKB radial glial cell differentiation Inferred from sequence or structural similarity. Source: UniProtKB response to estradiol stimulus Inferred from direct assay. Source: BHF-UCL sexual reproduction Inferred from sequence or structural similarity. Source: UniProtKB temperature homeostasis Inferred from sequence or structural similarity. Source: UniProtKB
Cellular component	cytosol Traceable author statement. Source: Reactome nucleoplasm Traceable author statement. Source: Reactome nucleus Inferred from electronic annotation. Source: InterPro plasma membrane Inferred from sequence or structural similarity. Source: UniProtKB
Molecular function	calcium ion binding Inferred from electronic annotation. Source: InterPro non-membrane spanning protein tyrosine kinase activity Traceable author statement. Source: Reactome 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 transcription factor activity Inferred from electronic annotation. Source: InterPro signal transducer activity Inferred from electronic annotation. Source: InterPro transcription factor binding Inferred from physical interaction. Source: UniProtKB transcription regulatory region DNA binding Inferred from direct assay. Source: BHF-UCL
Complete GO annotation...

With	Entry	#Exp.	IntAct
BCKDK	O14874	2	EBI-518675,EBI-1046765
BICD1	Q96G01	2	EBI-518675,EBI-1104509
CAPN1	P07384	2	EBI-518675,EBI-1542113
CORO1A	P31146	2	EBI-518675,EBI-1046676
DAXX	Q9UER7	4	EBI-518675,EBI-77321
ECH1	Q13011	2	EBI-518675,EBI-711968
GNL3	Q9BVP2	2	EBI-518675,EBI-641642
KHDRBS1	Q07666	2	EBI-518675,EBI-1364
MAP3K7	O43318	4	EBI-518675,EBI-358684
MAPK9	P45984	2	EBI-518675,EBI-713568
MAPK9	P45984-1	3	EBI-518675,EBI-713586
MORC4	Q8TE76	2	EBI-518675,EBI-3940432
MRPS31	Q92665	2	EBI-518675,EBI-720602
NR4A1	P22736	3	EBI-518675,EBI-721550
OGDHL	Q9ULD0	2	EBI-518675,EBI-3940481
RELA	Q04206	4	EBI-518675,EBI-73886
RPS9	P46781	2	EBI-518675,EBI-351206
SOX1	O00570	2	EBI-518675,EBI-2935583
SRI	P30626	2	EBI-518675,EBI-750459
SULT2A1	Q06520	2	EBI-518675,EBI-3921363

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Chain

1 – 770

770

Signal transducer and activator of transcription 3

PRO_0000182417

Domain

580 – 670

SH2

Motif

150 – 162

Essential for nuclear import

Modified residue

539

Phosphotyrosine Ref.7 Ref.33 Ref.37

Modified residue

691

Phosphoserine Ref.7 Ref.30 Ref.33

Modified residue

705

Phosphotyrosine; by PTK6 Ref.7 Ref.14 Ref.22 Ref.23 Ref.24 Ref.27 Ref.29 Ref.33 Ref.37

Modified residue

714

Phosphothreonine Ref.7 Ref.33 Ref.34 Ref.35

Modified residue

727

Phosphoserine; by DYRK2, NLK, NEK6, IRAK1, RPS6KA5, ZIPK/DAPK3 and PKC/PRKCE Ref.7 Ref.14 Ref.17 Ref.20 Ref.25 Ref.31 Ref.33 Ref.34 Ref.35 Ref.36

Alternative sequence

701

Missing in isoform Del-701.

VSP_010474

Natural variant

Q → K.
Corresponds to variant rs1803125 [ dbSNP | Ensembl ].

VAR_018683

Natural variant

143

M → I. Ref.3
Corresponds to variant rs17878478 [ dbSNP | Ensembl ].

VAR_018679

Natural variant

382

R → L in AD-HIES. Ref.40

VAR_037365

Natural variant

382

R → Q in AD-HIES; loss of function. Ref.40 Ref.41

VAR_037366

Natural variant

382

R → W in AD-HIES; loss of function. Ref.40 Ref.41

VAR_037367

Natural variant

384

F → L in AD-HIES. Ref.40

VAR_037368

Natural variant

384

F → S in AD-HIES. Ref.40

VAR_037369

Natural variant

389

T → I in AD-HIES; loss of function. Ref.41

VAR_037370

Natural variant

423

R → Q in AD-HIES. Ref.40

VAR_037371

Natural variant

437

H → Y in AD-HIES; loss of function. Ref.41

VAR_037372

Natural variant

463

Missing in AD-HIES; loss of function.

VAR_037373

Natural variant

561

F → Y. Ref.1
Corresponds to variant rs1064116 [ dbSNP | Ensembl ].

VAR_037374

Natural variant

611

S → N in AD-HIES. Ref.40

VAR_037375

Natural variant

621

F → V in AD-HIES. Ref.40

VAR_037376

Natural variant

622

T → I in AD-HIES. Ref.40

VAR_037377

Natural variant

637

V → L in AD-HIES. Ref.40

VAR_037378

Natural variant

637

V → M in AD-HIES. Ref.40

VAR_037379

Natural variant

644

Missing in AD-HIES.

VAR_037380

Natural variant

657

Y → C in AD-HIES. Ref.40

VAR_037381

Sequence conflict

133

T → A in BAF84622. Ref.4

Sequence conflict

288

Q → H in AAA58374. Ref.1

Sequence conflict

460

P → S in AAA58374. Ref.1

Sequence conflict

548

K → N in AAA58374. Ref.1

Sequence conflict

652

E → V in BAF84622. Ref.4

Sequence conflict

667

V → L in AAA58374. Ref.1

Sequence conflict

730

T → A in AAA58374. Ref.1

Sequence		Length	Mass (Da)
Isoform 1 [UniParc]. Last modified June 7, 2004. Version 2. Checksum: 6C00632211C8012D Show »	FASTA	770	88,068
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 »	FASTA	769	87,981
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 AAPYLKTKFI CVTPTTCSNT 730 740 750 760 IDLPMSPRTL DSLMQFGNNG EGAEPSAGGQ FESLTFDMEL TSECATSPM « Hide

	« Hide 'large scale' referencesShow '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: 7512451] [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: 9630560] [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. Sugano S. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [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: 15489334] [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: 7701321] [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: 9388184] [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: 10688651] [Abstract] Cited for: PHOSPHORYLATION BY BMX, INTERACTION WITH BMX, FUNCTION.
[10]	"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: 11773079] [Abstract] Cited for: INTERACTION WITH NCOA1.
[11]	"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: 12208879] [Abstract] Cited for: INTERACTION WITH HCV CORE PROTEIN.
[12]	"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. , Kastelein R.A., de Waal Malefyt R., Moore K.W. J. Immunol. 168:5699-5708(2002) [PubMed: 12023369] [Abstract] Cited for: INTERACTION WITH IL23R.
[13]	"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: 12873986] [Abstract] Cited for: FUNCTION IN EGFR SIGNALING, INTERACTION WITH EGFR.
[14]	"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: 12763138] [Abstract] Cited for: PHOSPHORYLATION AT TYR-705 AND SER-727.
[15]	"Signal transduction via the stem cell factor receptor/c-Kit." Ronnstrand L. Cell. Mol. Life Sci. 61:2535-2548(2004) [PubMed: 15526160] [Abstract] Cited for: REVIEW ON ROLE IN KIT SIGNALING.
[16]	"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: 15194700] [Abstract] Cited for: FUNCTION, INTERACTION WITH IL31RA.
[17]	"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: 15465816] [Abstract] Cited for: PHOSPHORYLATION AT SER-727 BY IRAK1.
[18]	"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: 15467733] [Abstract] Cited for: INTERACTION WITH TMF1.
[19]	"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: 15994929] [Abstract] Cited for: INTERACTION WITH PELP1.
[20]	"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: 16219639] [Abstract] Cited for: PHOSPHORYLATION AT SER-727 BY ZIPK/DAPK3, INTERACTION WITH ZIPK/DAPK3, SUBCELLULAR LOCATION.
[21]	"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: 15677474] [Abstract] Cited for: INTERACTION WITH SOCS7.
[22]	"Time-resolved mass spectrometry of tyrosine phosphorylation sites in the epidermal growth factor receptor signaling network reveals dynamic modules." Zhang Y., Wolf-Yadlin A., Ross P.L., Pappin D.J., Rush J., Lauffenburger D.A., White F.M. Mol. Cell. Proteomics 4:1240-1250(2005) [PubMed: 15951569] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-705, MASS SPECTROMETRY. Tissue: Mammary epithelium.
[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: 15592455] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-705, MASS SPECTROMETRY.
[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: 16568091] [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: 17875724] [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: 15919823] [Abstract] Cited for: SUBCELLULAR LOCATION, NUCLEAR IMPORT MOTIF.
[27]	"Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer." Rikova K., Guo A., Zeng Q., Possemato A., Yu J., Haack H., Nardone J., Lee K., Reeves C., Li Y., Hu Y., Tan Z., Stokes M., Sullivan L., Mitchell J., Wetzel R., Macneill J., Ren J.M. Comb M.J. Cell 131:1190-1203(2007) [PubMed: 18083107] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-705, MASS SPECTROMETRY. Tissue: Lung carcinoma.
[28]	"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: 17956865] [Abstract] Cited for: INTERACTION WITH CDK9.
[29]	"Multiple reaction monitoring for robust quantitative proteomic analysis of cellular signaling networks." Wolf-Yadlin A., Hautaniemi S., Lauffenburger D.A., White F.M. Proc. Natl. Acad. Sci. U.S.A. 104:5860-5865(2007) [PubMed: 17389395] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-705, MASS SPECTROMETRY. Tissue: Mammary epithelium.
[30]	"ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage." Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y., Gygi S.P., Elledge S.J. Science 316:1160-1166(2007) [PubMed: 17525332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-691, MASS SPECTROMETRY. Tissue: Embryonic kidney.
[31]	"Role for DYRK family kinases on regulation of apoptosis." Yoshida K. Biochem. Pharmacol. 76:1389-1394(2008) [PubMed: 18599021] [Abstract] Cited for: PHOSPHORYLATION AT SER-727 BY DYRK2.
[32]	"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: 18070987] [Abstract] Cited for: IDENTIFICATION IN A COMPLEX WITH LYN AND PAG1.
[33]	"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: 18234692] [Abstract] Cited for: INTERACTION WITH ARL2BP, PHOSPHORYLATION AT SERINE RESIDUES, SUBCELLULAR LOCATION.
[34]	"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: 18691976] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-714 AND SER-727, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[35]	"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: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-714 AND SER-727, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[36]	"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: 19413330] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-727, MASS SPECTROMETRY. Tissue: Embryonic kidney.
[37]	"An extensive survey of tyrosine phosphorylation revealing new sites in human mammary epithelial cells." Heibeck T.H., Ding S.-J., Opresko L.K., Zhao R., Schepmoes A.A., Yang F., Tolmachev A.V., Monroe M.E., Camp D.G. II, Smith R.D., Wiley H.S., Qian W.-J. J. Proteome Res. 8:3852-3861(2009) [PubMed: 19534553] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-539 AND TYR-705, MASS SPECTROMETRY. Tissue: Mammary epithelium.
[38]	"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: 21269460] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[39]	"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: 21135090] [Abstract] Cited for: PHOSPHORYLATION IN RESPONSE TO KIT SIGNALING.
[40]	"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. Grimbacher B. N. Engl. J. Med. 357:1608-1619(2007) [PubMed: 17881745] [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.
[41]	"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: 17676033] [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.

Wikipedia

STAT3 entry

Atlas of Genetics and Cytogenetics in Oncology and Haematology

STAT3base

STAT3 mutation db

SeattleSNPs

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.
IPI	IPI00306436. IPI00784414.
PIR	A54444.
RefSeq	NP_003141.2. NM_003150.3. NP_644805.1. NM_139276.2. NP_998827.1. NM_213662.1.
UniGene	Hs.463059.
3D structure databases
ProteinModelPortal	P40763.
SMR	P40763. Positions 2-715.
ModBase	Search...
Protein-protein interaction databases
IntAct	P40763. 64 interactions.
MINT	MINT-146801.
STRING	P40763.
PTM databases
PhosphoSite	P40763.
Polymorphism databases
DMDM	48429227.
Proteomic databases
PeptideAtlas	P40763.
PRIDE	P40763.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000264657; ENSP00000264657; ENSG00000168610.
GeneID	6774.
KEGG	hsa:6774.
UCSC	uc002hzl.1. human. uc002hzm.1. human.
Organism-specific databases
CTD	6774.
GeneCards	GC17M040465.
H-InvDB	HIX0013840.
HGNC	HGNC:11364. STAT3.
HPA	CAB003859. HPA001671.
MIM	102582. gene. 147060. phenotype.
neXtProt	NX_P40763.
Orphanet	2314. Autosomal dominant hyper IgE syndrome.
PharmGKB	PA337.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG07164.
HOGENOM	HBG446644.
HOVERGEN	HBG055669.
InParanoid	P40763.
OMA	NKESHAT.
OrthoDB	EOG4G4GPS.
PhylomeDB	P40763.
Enzyme and pathway databases
Pathway_Interaction_DB	ifngpathway. IFN-gamma pathway. il12_stat4pathway. IL12 signaling mediated by STAT4. il12_2pathway. IL12-mediated signaling events. il2_1pathway. IL2-mediated signaling events. il23pathway. IL23-mediated signaling events. il27pathway. IL27-mediated signaling events. il6_7pathway. IL6-mediated signaling events. trkrpathway. Neurotrophic factor-mediated Trk receptor signaling. pdgfrbpathway. PDGFR-beta signaling pathway. met_pathway. Signaling events activated by Hepatocyte Growth Factor Receptor (c-Met). hdac_classi_pathway. Signaling events mediated by HDAC Class I. ptp1bpathway. Signaling events mediated by PTP1B. kitpathway. Signaling events mediated by Stem cell factor receptor (c-Kit).
Reactome	REACT_111102. Signal Transduction. REACT_6900. Immune System.
Gene expression databases
ArrayExpress	P40763.
Bgee	P40763.
CleanEx	HS_STAT3.
Genevestigator	P40763.
GermOnline	ENSG00000168610. Homo sapiens.
Family and domain databases
InterPro	IPR011992. EF-hand-like_dom. IPR008967. p53-like_TF_DNA-bd. IPR000980. SH2. IPR013800. STAT_TF_alpha. IPR015988. STAT_TF_coiled-coil. IPR001217. STAT_TF_core. IPR013801. STAT_TF_DNA-bd. IPR012345. STAT_TF_DNA-bd_sub. IPR013799. STAT_TF_prot_interaction. [Graphical view]
Gene3D	G3DSA:1.10.238.10. EF-Hand_type. 1 hit. G3DSA:3.30.505.10. SH2. 1 hit. G3DSA:1.20.1050.20. STAT_alpha. 1 hit. G3DSA:2.60.40.630. STAT_DNA_bd_sub. 1 hit. G3DSA:1.10.532.10. STAT_protein_interaction. 1 hit.
KO	K04692.
PANTHER	PTHR11801. STAT. 1 hit.
Pfam	PF00017. SH2. 1 hit. PF01017. STAT_alpha. 1 hit. PF02864. STAT_bind. 1 hit. PF02865. STAT_int. 1 hit. [Graphical view]
SMART	SM00252. SH2. 1 hit. SM00964. STAT_int. 1 hit. [Graphical view]
SUPFAM	SSF49417. P53_like_DNA_bnd. 1 hit. SSF47655. STAT. 1 hit. SSF48092. STAT. 1 hit.
PROSITE	PS50001. SH2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	26438.
PMAP-CutDB	P40763.
SOURCE	Search...

Entry name

STAT3_HUMAN

Accession

Primary (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:	January 25, 2012
This is version 132 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.

Human chromosome 17

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

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

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

SIMILARITY comments

Index of protein domains and families

Names·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·Documents

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.