ID STAT3_HUMAN Reviewed; 770 AA. AC P40763; O14916; Q9BW54; DT 01-FEB-1995, integrated into UniProtKB/Swiss-Prot. DT 07-JUN-2004, sequence version 2. DT 16-DEC-2008, entry version 93. DE RecName: Full=Signal transducer and activator of transcription 3; DE AltName: Full=Acute-phase response factor; GN Name=STAT3; Synonyms=APRF; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT TYR-561. RC TISSUE=Placenta; RX MEDLINE=94208062; PubMed=7512451; DOI=10.1016/0092-8674(94)90235-6; RA Akira S., Nishio Y., Inoue M., Wang X.-J., Wei S., Matsusaka T., RA Yoshida K., Sudo T., Naruto M., Kishimoto T.; RT "Molecular cloning of APRF, a novel IFN-stimulated gene factor 3 p91- RT related transcription factor involved in the gp130-mediated signaling RT pathway."; RL Cell 77:63-71(1994). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RX MEDLINE=98296260; PubMed=9630560; DOI=10.1016/S0378-1119(98)00185-1; RA Della Pietra L., Bressan A., Pezzotti A., Serlupi-Crescenzi O.; RT "Highly conserved amino-acid sequence between murine STAT3 and a RT revised human STAT3 sequence."; RL Gene 213:119-124(1998). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT ILE-143. RG SeattleSNPs program for genomic applications; RL Submitted (MAR-2004) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND DEL-701). RC TISSUE=Kidney, and Pancreas; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [5] RP NUCLEOTIDE SEQUENCE [MRNA] OF 564-704. RC TISSUE=Liver; RA Della Pietra L., Bressan A., Pezzotti A.R., Serlupi-Crescenzi O.; RL Submitted (OCT-1997) to the EMBL/GenBank/DDBJ databases. RN [6] RP PHOSPHORYLATION AT SERINE RESIDUES. RX MEDLINE=95215843; PubMed=7701321; RA Zhang X., Blenis J., Li H.-C., Schindler C., Chen-Kiang S.; RT "Requirement of serine phosphorylation for formation of STAT-promoter RT complexes."; RL Science 267:1990-1994(1995). RN [7] RP INTERACTION WITH NCOA1. RX PubMed=11773079; DOI=10.1074/jbc.M111486200; RA Giraud S., Bienvenu F., Avril S., Gascan H., Heery D.M., Coqueret O.; RT "Functional interaction of STAT3 transcription factor with the RT coactivator NcoA/SRC1a."; RL J. Biol. Chem. 277:8004-8011(2002). RN [8] RP INTERACTION WITH HCV CORE PROTEIN. RX MEDLINE=22198898; PubMed=12208879; DOI=10.1084/jem.20012127; RA Yoshida T., Hanada T., Tokuhisa T., Kosai K., Sata M., Kohara M., RA Yoshimura A.; RT "Activation of STAT3 by the hepatitis C virus core protein leads to RT cellular transformation."; RL J. Exp. Med. 196:641-653(2002). RN [9] RP INTERACTION WITH IL23R. RX MEDLINE=22018152; PubMed=12023369; RA Parham C., Chirica M., Timans J., Vaisberg E., Travis M., Cheung J., RA Pflanz S., Zhang R., Singh K.P., Vega F., To W., Wagner J., RA O'Farrell A.-M., McClanahan T.K., Zurawski S., Hannum C., Gorman D., RA Rennick D.M., Kastelein R.A., de Waal Malefyt R., Moore K.W.; RT "A receptor for the heterodimeric cytokine IL-23 is composed of IL- RT 12Rbeta1 and a novel cytokine receptor subunit, IL-23R."; RL J. Immunol. 168:5699-5708(2002). RN [10] RP FUNCTION, AND INTERACTION WITH IL31RA. RX PubMed=15194700; DOI=10.1074/jbc.M401122200; RA Dreuw A., Radtke S., Pflanz S., Lippok B.E., Heinrich P.C., RA Hermanns H.M.; RT "Characterization of the signaling capacities of the novel gp130-like RT cytokine receptor."; RL J. Biol. Chem. 279:36112-36120(2004). RN [11] RP INTERACTION WITH PELP1. RX PubMed=15994929; DOI=10.1158/0008-5472.CAN-04-4664; RA Manavathi B., Nair S.S., Wang R.-A., Kumar R., Vadlamudi R.K.; RT "Proline-, glutamic acid-, and leucine-rich protein-1 is essential in RT growth factor regulation of signal transducers and activators of RT transcription 3 activation."; RL Cancer Res. 65:5571-5577(2005). RN [12] RP INTERACTION WITH SOCS7. RX PubMed=15677474; DOI=10.1074/jbc.M411596200; RA Martens N., Uzan G., Wery M., Hooghe R., Hooghe-Peters E.L., RA Gertler A.; RT "Suppressor of cytokine signaling 7 inhibits prolactin, growth RT hormone, and leptin signaling by interacting with STAT5 or STAT3 and RT attenuating their nuclear translocation."; RL J. Biol. Chem. 280:13817-13823(2005). RN [13] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-705, AND MASS RP SPECTROMETRY. RC TISSUE=Epithelium; RX PubMed=15951569; DOI=10.1074/mcp.M500089-MCP200; RA Zhang Y., Wolf-Yadlin A., Ross P.L., Pappin D.J., Rush J., RA Lauffenburger D.A., White F.M.; RT "Time-resolved mass spectrometry of tyrosine phosphorylation sites in RT the epidermal growth factor receptor signaling network reveals dynamic RT modules."; RL Mol. Cell. Proteomics 4:1240-1250(2005). RN [14] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-705, AND MASS RP SPECTROMETRY. RX PubMed=15592455; DOI=10.1038/nbt1046; RA Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H., RA Zha X.-M., Polakiewicz R.D., Comb M.J.; RT "Immunoaffinity profiling of tyrosine phosphorylation in cancer RT cells."; RL Nat. Biotechnol. 23:94-101(2005). RN [15] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-705, AND MASS RP SPECTROMETRY. RX PubMed=18083107; DOI=10.1016/j.cell.2007.11.025; RA Rikova K., Guo A., Zeng Q., Possemato A., Yu J., Haack H., Nardone J., RA Lee K., Reeves C., Li Y., Hu Y., Tan Z., Stokes M., Sullivan L., RA Mitchell J., Wetzel R., Macneill J., Ren J.M., Yuan J., RA Bakalarski C.E., Villen J., Kornhauser J.M., Smith B., Li D., Zhou X., RA Gygi S.P., Gu T.-L., Polakiewicz R.D., Rush J., Comb M.J.; RT "Global survey of phosphotyrosine signaling identifies oncogenic RT kinases in lung cancer."; RL Cell 131:1190-1203(2007). RN [16] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-691, AND MASS RP SPECTROMETRY. RX PubMed=17525332; DOI=10.1126/science.1140321; RA Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, RA Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N., RA Lerenthal Y., Shiloh Y., Gygi S.P., Elledge S.J.; RT "ATM and ATR substrate analysis reveals extensive protein networks RT responsive to DNA damage."; RL Science 316:1160-1166(2007). RN [17] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-714 AND SER-727, AND RP MASS SPECTROMETRY. RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007; RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., RA Greff Z., Keri G., Stemmann O., Mann M.; RT "Kinase-selective enrichment enables quantitative phosphoproteomics of RT the kinome across the cell cycle."; RL Mol. Cell 31:438-448(2008). RN [18] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-714 AND SER-727, AND RP MASS SPECTROMETRY. RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [19] RP VARIANTS AD-HIES GLN-382; LEU-382; TRP-382; LEU-384; SER-384; GLN-423; RP VAL-463 DEL; ASN-611; VAL-621; ILE-622; LEU-637; MET-637; GLN-644 DEL RP AND CYS-657. RX PubMed=17881745; DOI=10.1056/NEJMoa073687; RA Holland S.M., DeLeo F.R., Elloumi H.Z., Hsu A.P., Uzel G., Brodsky N., RA Freeman A.F., Demidowich A., Davis J., Turner M.L., Anderson V.L., RA Darnell D.N., Welch P.A., Kuhns D.B., Frucht D.M., Malech H.L., RA Gallin J.I., Kobayashi S.D., Whitney A.R., Voyich J.M., Musser J.M., RA Woellner C., Schaffer A.A., Puck J.M., Grimbacher B.; RT "STAT3 mutations in the hyper-IgE syndrome."; RL N. Engl. J. Med. 357:1608-1619(2007). RN [20] RP VARIANTS AD-HIES GLN-382; TRP-382; ILE-389; TYR-437 AND VAL-463 DEL, RP AND CHARACTERIZATION OF VARIANTS AD-HIES GLN-382; TRP-382; ILE-389; RP TYR-437 AND VAL-463 DEL. RX PubMed=17676033; DOI=10.1038/nature06096; RA Minegishi Y., Saito M., Tsuchiya S., Tsuge I., Takada H., Hara T., RA Kawamura N., Ariga T., Pasic S., Stojkovic O., Metin A., RA Karasuyama H.; RT "Dominant-negative mutations in the DNA-binding domain of STAT3 cause RT hyper-IgE syndrome."; RL Nature 448:1058-1062(2007). CC -!- FUNCTION: Transcription factor that binds to the interleukin-6 CC (IL-6)-responsive elements identified in the promoters of various CC acute-phase protein genes. Activated by IL31 through IL31RA. CC -!- SUBUNIT: Forms a homodimer or a heterodimer with a related family CC member (at least STAT1). Interacts with NCOA1, PELP1, SOCS7 and CC STATIP1. Interacts with HCV core protein. Interacts with IL23R in CC presence of IL23. Interacts with IL31RA. Interacts with SIPAR (By CC similarity). CC -!- INTERACTION: CC Q9UER7:DAXX; NbExp=2; IntAct=EBI-518675, EBI-77321; CC Q07666:KHDRBS1; NbExp=1; IntAct=EBI-518675, EBI-1364; CC O43318:MAP3K7; NbExp=1; IntAct=EBI-518675, EBI-358684; CC Q13287:NMI; NbExp=1; IntAct=EBI-518675, EBI-372942; CC P52630:STAT2; NbExp=1; IntAct=EBI-518675, EBI-1546963; CC -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Note=Translocated into CC the nucleus in response to phosphorylation. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=P40763-1; Sequence=Displayed; CC Name=Del-701; CC IsoId=P40763-2; Sequence=VSP_010474; CC -!- TISSUE SPECIFICITY: Heart, brain, placenta, lung, liver, skeletal CC muscle, kidney and pancreas. CC -!- PTM: Tyrosine phosphorylated in response to IL-6, IL-11, CNTF, CC LIF, CSF-1, EGF, PDGF, IFN-alpha and OSM. Phosphorylated on serine CC upon DNA damage, probably by ATM or ATR. Serine phosphorylation is CC important for the formation of stable DNA-binding STAT3 homodimers CC and maximal transcriptional activity. CC -!- DISEASE: Defects in STAT3 are the cause of hyperimmunoglobulin E CC recurrent infection syndrome autosomal dominant (AD-HIES) CC [MIM:147060]; also known as hyper-IgE syndrome or Job syndrome. CC AD-HIES is a rare disorder of immunity and connective tissue CC characterized by immunodeficiency, chronic eczema, recurrent CC Staphylococcal infections, increased serum IgE, eosinophilia, CC distinctive coarse facial appearance, abnormal dentition, CC hyperextensibility of the joints, and bone fractures. CC -!- MISCELLANEOUS: Involved in the gp130-mediated signaling pathway. CC -!- SIMILARITY: Belongs to the transcription factor STAT family. CC -!- SIMILARITY: Contains 1 SH2 domain. CC -!- WEB RESOURCE: Name=Wikipedia; Note=STAT3 entry; CC URL="http://en.wikipedia.org/wiki/STAT3"; CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology CC and Haematology; CC URL="http://atlasgeneticsoncology.org/Genes/STAT3ID444.html"; CC -!- WEB RESOURCE: Name=SeattleSNPs; CC URL="http://pga.gs.washington.edu/data/stat3/"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; L29277; AAA58374.1; -; mRNA. DR EMBL; AJ012463; CAA10032.1; -; mRNA. DR EMBL; AY572796; AAS66986.1; -; Genomic_DNA. DR EMBL; BC000627; AAH00627.1; -; mRNA. DR EMBL; BC014482; AAH14482.1; -; mRNA. DR EMBL; AF029311; AAB84254.1; -; mRNA. DR PIR; A54444; A54444. DR RefSeq; NP_003141.2; -. DR RefSeq; NP_644805.1; -. DR RefSeq; NP_998827.1; -. DR UniGene; Hs.463059; -. DR HSSP; P42227; 1BG1. DR SMR; P40763; 136-703. DR IntAct; P40763; 12. DR PhosphoSite; P40763; -. DR PeptideAtlas; P40763; -. DR PRIDE; P40763; -. DR Ensembl; ENSG00000168610; Homo sapiens. DR GeneID; 6774; -. DR KEGG; hsa:6774; -. DR GeneCards; GC17M037718; -. DR H-InvDB; HIX0013840; -. DR HGNC; HGNC:11364; STAT3. DR HPA; CAB003859; -. DR HPA; HPA001671; -. DR MIM; 102582; gene. DR MIM; 147060; phenotype. DR Orphanet; 2314; Job syndrome. DR PharmGKB; PA337; -. DR HOVERGEN; P40763; -. DR NextBio; 26438; -. DR ArrayExpress; P40763; -. DR CleanEx; HS_STAT3; -. DR GermOnline; ENSG00000168610; Homo sapiens. DR GO; GO:0005737; C:cytoplasm; TAS:ProtInc. DR GO; GO:0005634; C:nucleus; IDA:HGNC. DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro. DR GO; GO:0005062; F:hematopoietin/interferon-class (D200-domain...; TAS:ProtInc. DR GO; GO:0003700; F:transcription factor activity; TAS:ProtInc. DR GO; GO:0008134; F:transcription factor binding; IPI:UniProtKB. DR GO; GO:0006928; P:cell motion; TAS:ProtInc. DR GO; GO:0019221; P:cytokine-mediated signaling pathway; NAS:UniProtKB. DR GO; GO:0044419; P:interspecies interaction between organisms; IEA:UniProtKB-KW. DR GO; GO:0007259; P:JAK-STAT cascade; TAS:UniProtKB. DR GO; GO:0000122; P:negative regulation of transcription from R...; TAS:ProtInc. DR GO; GO:0007399; P:nervous system development; TAS:ProtInc. DR InterPro; IPR011992; EF-Hand_type. DR InterPro; IPR000980; SH2. DR InterPro; IPR013800; STAT_TF_alpha. DR InterPro; IPR001217; STAT_TF_core. DR InterPro; IPR013801; STAT_TF_DNA-bd. DR InterPro; IPR012345; STAT_TF_DNA-bd_sub. DR InterPro; IPR013799; STAT_TF_prot_interaction. DR Gene3D; G3DSA:1.10.238.10; EF-Hand_type; 1. DR Gene3D; G3DSA:3.30.505.10; SH2; 1. DR Gene3D; G3DSA:1.20.1050.20; STAT_alpha; 1. DR Gene3D; G3DSA:2.60.40.630; STAT_DNA_bd_sub; 1. DR Gene3D; G3DSA:1.10.532.10; STAT_protein_interaction; 1. DR PANTHER; PTHR11801; STAT; 1. DR Pfam; PF00017; SH2; 1. DR Pfam; PF01017; STAT_alpha; 1. DR Pfam; PF02864; STAT_bind; 1. DR Pfam; PF02865; STAT_int; 1. DR SMART; SM00252; SH2; 1. DR PROSITE; PS50001; SH2; 1. PE 1: Evidence at protein level; KW Activator; Alternative splicing; Cytoplasm; Disease mutation; KW DNA-binding; Host-virus interaction; Nucleus; Phosphoprotein; KW Polymorphism; SH2 domain; Transcription; Transcription regulation. FT CHAIN 1 770 Signal transducer and activator of FT transcription 3. FT /FTId=PRO_0000182417. FT DOMAIN 580 670 SH2. FT MOD_RES 691 691 Phosphoserine. FT MOD_RES 705 705 Phosphotyrosine. FT MOD_RES 714 714 Phosphothreonine. FT MOD_RES 727 727 Phosphoserine. FT VAR_SEQ 701 701 Missing (in isoform Del-701). FT /FTId=VSP_010474. FT VARIANT 32 32 Q -> K (in dbSNP:rs1803125). FT /FTId=VAR_018683. FT VARIANT 143 143 M -> I (in dbSNP:rs17878478). FT /FTId=VAR_018679. FT VARIANT 382 382 R -> L (in AD-HIES). FT /FTId=VAR_037365. FT VARIANT 382 382 R -> Q (in AD-HIES; loss of function). FT /FTId=VAR_037366. FT VARIANT 382 382 R -> W (in AD-HIES; loss of function). FT /FTId=VAR_037367. FT VARIANT 384 384 F -> L (in AD-HIES). FT /FTId=VAR_037368. FT VARIANT 384 384 F -> S (in AD-HIES). FT /FTId=VAR_037369. FT VARIANT 389 389 T -> I (in AD-HIES; loss of function). FT /FTId=VAR_037370. FT VARIANT 423 423 R -> Q (in AD-HIES). FT /FTId=VAR_037371. FT VARIANT 437 437 H -> Y (in AD-HIES; loss of function). FT /FTId=VAR_037372. FT VARIANT 463 463 Missing (in AD-HIES; loss of function). FT /FTId=VAR_037373. FT VARIANT 561 561 F -> Y (in dbSNP:rs1064116). FT /FTId=VAR_037374. FT VARIANT 611 611 S -> N (in AD-HIES). FT /FTId=VAR_037375. FT VARIANT 621 621 F -> V (in AD-HIES). FT /FTId=VAR_037376. FT VARIANT 622 622 T -> I (in AD-HIES). FT /FTId=VAR_037377. FT VARIANT 637 637 V -> L (in AD-HIES). FT /FTId=VAR_037378. FT VARIANT 637 637 V -> M (in AD-HIES). FT /FTId=VAR_037379. FT VARIANT 644 644 Missing (in AD-HIES). FT /FTId=VAR_037380. FT VARIANT 657 657 Y -> C (in AD-HIES). FT /FTId=VAR_037381. FT CONFLICT 288 288 Q -> H (in Ref. 1; AAA58374). FT CONFLICT 460 460 P -> S (in Ref. 1; AAA58374). FT CONFLICT 548 548 K -> N (in Ref. 1; AAA58374). FT CONFLICT 667 667 V -> L (in Ref. 1; AAA58374). FT CONFLICT 730 730 T -> A (in Ref. 1; AAA58374). SQ SEQUENCE 770 AA; 88068 MW; 6C00632211C8012D CRC64; MAQWNQLQQL DTRYLEQLHQ LYSDSFPMEL RQFLAPWIES QDWAYAASKE SHATLVFHNL LGEIDQQYSR FLQESNVLYQ HNLRRIKQFL QSRYLEKPME IARIVARCLW EESRLLQTAA TAAQQGGQAN HPTAAVVTEK QQMLEQHLQD VRKRVQDLEQ KMKVVENLQD DFDFNYKTLK SQGDMQDLNG NNQSVTRQKM QQLEQMLTAL DQMRRSIVSE LAGLLSAMEY VQKTLTDEEL ADWKRRQQIA CIGGPPNICL DRLENWITSL AESQLQTRQQ IKKLEELQQK VSYKGDPIVQ HRPMLEERIV ELFRNLMKSA FVVERQPCMP MHPDRPLVIK TGVQFTTKVR LLVKFPELNY QLKIKVCIDK DSGDVAALRG SRKFNILGTN TKVMNMEESN NGSLSAEFKH LTLREQRCGN GGRANCDASL IVTEELHLIT FETEVYHQGL KIDLETHSLP VVVISNICQM PNAWASILWY NMLTNNPKNV NFFTKPPIGT WDQVAEVLSW QFSSTTKRGL SIEQLTTLAE KLLGPGVNYS GCQITWAKFC KENMAGKGFS FWVWLDNIID LVKKYILALW NEGYIMGFIS KERERAILST KPPGTFLLRF SESSKEGGVT FTWVEKDISG KTQIQSVEPY TKQQLNNMSF AEIIMGYKIM DATNILVSPL VYLYPDIPKE EAFGKYCRPE SQEHPEADPG SAAPYLKTKF ICVTPTTCSN TIDLPMSPRT LDSLMQFGNN GEGAEPSAGG QFESLTFDME LTSECATSPM //