P40763 (STAT3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

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) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	770 AA.
Sequence status	Complete.
Protein existence	Evidence 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. 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. Interacts with the 'Lys-129' acetylated form of BIRC5/survivin. Interacts with FER. Ref.8 Ref.9 Ref.10 Ref.11 Ref.12 Ref.13 Ref.16 Ref.18 Ref.19 Ref.20 Ref.21 Ref.24 Ref.26 Ref.28 Ref.29 Ref.32 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.25 Ref.29
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. Ref.7 Ref.9 Ref.14 Ref.17 Ref.20 Ref.23 Ref.24 Ref.27 Ref.29 Ref.32 Ref.36
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.37 Ref.38
Miscellaneous	Involved in the gp130-mediated signaling pathway.
Sequence similarities	Belongs to the transcription factor STAT family. Contains 1 SH2 domain.

Ontologies

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)
Biological_process	JAK-STAT cascade involved in growth hormone signaling pathway Inferred from sequence or structural similarity. Source: UniProtKB acute-phase response Inferred from electronic annotation. Source: Compara astrocyte differentiation Inferred from sequence or structural similarity. Source: UniProtKB cell proliferation Inferred from electronic annotation. Source: Compara 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 PubMed 12552091PubMed 17324931. Source: BHF-UCL negative regulation of transcription from RNA polymerase II promoter Traceable author statement PubMed 8675499. 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 PubMed 17324931. Source: BHF-UCL protein import into nucleus Inferred from direct assay Ref.29. Source: UniProtKB radial glial cell differentiation Inferred from sequence or structural similarity. Source: UniProtKB regulation of multicellular organism growth Inferred from electronic annotation. Source: Compara response to drug Inferred from electronic annotation. Source: Compara response to estradiol stimulus Inferred from direct assay PubMed 12552091. Source: BHF-UCL response to ethanol Inferred from electronic annotation. Source: Compara sexual reproduction Inferred from sequence or structural similarity. Source: UniProtKB stem cell maintenance Inferred from electronic annotation. Source: Compara temperature homeostasis Inferred from sequence or structural similarity. Source: UniProtKB virus-host interaction Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	cytosol Traceable author statement. Source: Reactome nucleoplasm Traceable author statement. Source: Reactome plasma membrane Inferred from sequence or structural similarity. Source: UniProtKB
Molecular_function	calcium 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: Compara transcription regulatory region DNA binding Inferred from direct assay PubMed 17324931. Source: BHF-UCL
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
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
DIRAS3	O95661	3	EBI-518675,EBI-6139214
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
PGR	P06401	3	EBI-518675,EBI-78539
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

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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 770	770	Signal transducer and activator of transcription 3		PRO_0000182417
Regions
	Domain	580 – 670	91	SH2
	Motif	150 – 162	13	Essential for nuclear import
Amino acid modifications
	Modified residue	705	1	Phosphotyrosine; by FER and PTK6 Ref.7 Ref.14 Ref.22 Ref.23 Ref.29 Ref.36
	Modified residue	727	1	Phosphoserine; by DYRK2, NLK, NEK6, IRAK1, RPS6KA5, ZIPK/DAPK3 and PKC/PRKCE Ref.7 Ref.14 Ref.17 Ref.20 Ref.24 Ref.27 Ref.29 Ref.30 Ref.31 Ref.34 Ref.36
Natural variations
	Alternative sequence	701	1	Missing in isoform Del-701.		VSP_010474
	Natural variant	32	1	Q → K. Corresponds to variant rs1803125 [ dbSNP | Ensembl ].		VAR_018683
	Natural variant	143	1	M → I. Ref.3 Corresponds to variant rs17878478 [ dbSNP | Ensembl ].		VAR_018679
	Natural variant	382	1	R → L in AD-HIES. Ref.37		VAR_037365
	Natural variant	382	1	R → Q in AD-HIES; loss of function. Ref.37 Ref.38		VAR_037366
	Natural variant	382	1	R → W in AD-HIES; loss of function. Ref.37 Ref.38		VAR_037367
	Natural variant	384	1	F → L in AD-HIES. Ref.37		VAR_037368
	Natural variant	384	1	F → S in AD-HIES. Ref.37		VAR_037369
	Natural variant	389	1	T → I in AD-HIES; loss of function. Ref.38		VAR_037370
	Natural variant	423	1	R → Q in AD-HIES. Ref.37		VAR_037371
	Natural variant	437	1	H → Y in AD-HIES; loss of function. Ref.38		VAR_037372
	Natural variant	463	1	Missing in AD-HIES; loss of function. Ref.37 Ref.38		VAR_037373
	Natural variant	561	1	F → Y. Ref.1 Corresponds to variant rs1064116 [ dbSNP | Ensembl ].		VAR_037374
	Natural variant	611	1	S → N in AD-HIES. Ref.37		VAR_037375
	Natural variant	621	1	F → V in AD-HIES. Ref.37		VAR_037376
	Natural variant	622	1	T → I in AD-HIES. Ref.37		VAR_037377
	Natural variant	637	1	V → L in AD-HIES. Ref.37		VAR_037378
	Natural variant	637	1	V → M in AD-HIES. Ref.37		VAR_037379
	Natural variant	644	1	Missing in AD-HIES. Ref.37		VAR_037380
	Natural variant	657	1	Y → C in AD-HIES. Ref.37		VAR_037381
Experimental info
	Sequence conflict	133	1	T → A in BAF84622. Ref.4
	Sequence conflict	288	1	Q → H in AAA58374. Ref.1
	Sequence conflict	460	1	P → S in AAA58374. Ref.1
	Sequence conflict	548	1	K → N in AAA58374. Ref.1
	Sequence conflict	652	1	E → V in BAF84622. Ref.4
	Sequence conflict	667	1	V → L in AAA58374. Ref.1
	Sequence conflict	730	1	T → A in AAA58374. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified June 7, 2004. Version 2. Checksum: 6C00632211C8012D	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
	Isoform Del-701 [UniParc]. Checksum: A374A32AB9D28077	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

References

	« 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] [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. , 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]	"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.
[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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [Abstract] Cited for: INTERACTION WITH SOCS7.
[22]	"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), MASS SPECTROMETRY.
[23]	"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.
[24]	"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.
[25]	"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.
[26]	"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.
[27]	"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.
[28]	"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.
[29]	"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.
[30]	"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, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[31]	"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, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[32]	"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.
[33]	"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.
[34]	"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, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[35]	"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].
[36]	"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.
[37]	"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. , 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.
[38]	"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.

Web resources

Wikipedia

STAT3 entry

Atlas of Genetics and Cytogenetics in Oncology and Haematology

STAT3base

STAT3 mutation db

SeattleSNPs

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.
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.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-33584N.
IntAct	P40763. 68 interactions.
MINT	MINT-146801.
STRING	9606.ENSP00000264657.
PTM databases
PhosphoSite	P40763.
Polymorphism databases
DMDM	48429227.
Proteomic databases
PaxDb	P40763.
PeptideAtlas	P40763.
PRIDE	P40763.
Protocols and materials databases
DNASU	6774.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000264657; ENSP00000264657; ENSG00000168610. ENST00000404395; ENSP00000384943; ENSG00000168610. ENST00000588969; ENSP00000467985; ENSG00000168610.
GeneID	6774.
KEGG	hsa:6774.
UCSC	uc002hzk.1. human. uc002hzm.1. human.
Organism-specific databases
CTD	6774.
GeneCards	GC17M040465.
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	NOG303257.
HOGENOM	HOG000220792.
HOVERGEN	HBG055669.
InParanoid	P40763.
KO	K04692.
OMA	NKESHAT.
OrthoDB	EOG4G4GPS.
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_116125. Disease. REACT_6900. Immune System.
Gene expression databases
ArrayExpress	P40763.
Bgee	P40763.
CleanEx	HS_STAT3.
Genevestigator	P40763.
GermOnline	ENSG00000168610. Homo sapiens.
Family and domain databases
Gene3D	1.10.238.10. 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.
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]
PANTHER	PTHR11801. PTHR11801. 1 hit.
Pfam	PF00017. SH2. 1 hit. PF01017. STAT_alpha. 1 hit. PF02864. STAT_bind. 1 hit. PF02865. STAT_int. 1 hit. [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
BindingDB	P40763.
ChEMBL	CHEMBL4026.
ChiTaRS	STAT3. human.
GenomeRNAi	6774.
NextBio	26438.
PMAP-CutDB	P40763.
SOURCE	Search...

Entry information

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:	May 1, 2013
This is version 146 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.