Reviewed,
UniProtKB/Swiss-Prot P40763 (STAT3_HUMAN)
Last modified
June 16, 2009.
Version 101.
History...
Clusters with 100%,
90%,
50% identity |
Documents (5) |
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Names and origin
| Protein names | Recommended name: Signal transducer and activator of transcription 3 Alternative name(s): Acute-phase response factor | ||||
| Gene names |
| ||||
| Organism | Homo sapiens (Human) | ||||
| Taxonomic identifier | 9606 [NCBI] | ||||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Protein attributes
| Sequence length | 770 AA. |
| Sequence status | Complete. |
| Sequence processing | The displayed sequence is not processed. |
| Protein existence | Evidence at protein level. |
General annotation (Comments)
| Function | Transcription factor that 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.10 |
| Subunit structure | Forms a homodimer or a heterodimer with a related family member (at least STAT1). Interacts with NCOA1, PELP1, SOCS7 and STATIP1. Interacts with HCV core protein. Interacts with IL23R in presence of IL23. Interacts with IL31RA. Interacts with SIPAR. Interacts (via SH2 domain) with NLK By similarity. Interacts with KPNA4 and KPNA5; KPNA4 may be the primary mediator of nuclear import By similarity. Interacts with TMF1. |
| Subcellular location | Cytoplasm. Nucleus. Note: Shuttles between the nucleus and the cytoplasm. Constitutive nuclear presence is independent of tyrosine phosphorylation. |
| Tissue specificity | Heart, brain, placenta, lung, liver, skeletal muscle, kidney and pancreas. |
| Post-translational modification | Tyrosine phosphorylated in response to IL-6, IL-11, CNTF, LIF, CSF-1, EGF, PDGF, IFN-alpha and OSM. 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. Ref.6 Ref.14 Ref.15 Ref.17 Ref.18 Ref.19 Ref.20 |
| 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.22 Ref.23 |
| Miscellaneous | Involved in the gp130-mediated signaling pathway. |
| Sequence similarities | Belongs to the transcription factor STAT family. Contains 1 SH2 domain. |
Ontologies
Binary interactions
With | Entry | #Exp. | IntAct | Notes |
|---|---|---|---|---|
| DAXX | Q9UER7 | 2 | EBI-518675,EBI-77321 | |
| KHDRBS1 | Q07666 | 1 | EBI-518675,EBI-1364 | |
| MAP3K7 | O43318 | 1 | EBI-518675,EBI-358684 | |
| NMI | Q13287 | 1 | EBI-518675,EBI-372942 | |
| RBM8A | Q9Y5S9 | 2 | EBI-518675,EBI-447231 | |
| STAT2 | P52630 | 1 | EBI-518675,EBI-1546963 |
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. |
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 By similarity | ||||||
Amino acid modifications | |||||||||
| Modified residue | 691 | 1 | Phosphoserine Ref.6 Ref.18 | ||||||
| Modified residue | 705 | 1 | Phosphotyrosine Ref.6 Ref.14 Ref.15 Ref.17 | ||||||
| Modified residue | 714 | 1 | Phosphothreonine Ref.6 Ref.19 Ref.20 | ||||||
| Modified residue | 727 | 1 | Phosphoserine; by NLK Ref.6 Ref.19 Ref.20 | ||||||
Natural variations | |||||||||
| Alternative sequence | 701 | 1 | Missing in isoform Del-701. | VSP_010474 | |||||
| Natural variant | 32 | 1 | Q → K: dbSNP rs1803125. | VAR_018683 | |||||
| Natural variant | 143 | 1 | M → I: dbSNP rs17878478. Ref.3 | VAR_018679 | |||||
| Natural variant | 382 | 1 | R → L in AD-HIES. Ref.22 Ref.23 | VAR_037365 | |||||
| Natural variant | 382 | 1 | R → Q in AD-HIES; loss of function. Ref.22 Ref.23 | VAR_037366 | |||||
| Natural variant | 382 | 1 | R → W in AD-HIES; loss of function. Ref.22 Ref.23 | VAR_037367 | |||||
| Natural variant | 384 | 1 | F → L in AD-HIES. Ref.22 | VAR_037368 | |||||
| Natural variant | 384 | 1 | F → S in AD-HIES. Ref.22 | VAR_037369 | |||||
| Natural variant | 389 | 1 | T → I in AD-HIES; loss of function. Ref.23 | VAR_037370 | |||||
| Natural variant | 423 | 1 | R → Q in AD-HIES. Ref.22 | VAR_037371 | |||||
| Natural variant | 437 | 1 | H → Y in AD-HIES; loss of function. Ref.23 | VAR_037372 | |||||
| Natural variant | 463 | 1 | Missing in AD-HIES; loss of function. Ref.22 Ref.23 | VAR_037373 | |||||
| Natural variant | 561 | 1 | F → Y: dbSNP rs1064116. Ref.1 | VAR_037374 | |||||
| Natural variant | 611 | 1 | S → N in AD-HIES. Ref.22 | VAR_037375 | |||||
| Natural variant | 621 | 1 | F → V in AD-HIES. Ref.22 | VAR_037376 | |||||
| Natural variant | 622 | 1 | T → I in AD-HIES. Ref.22 | VAR_037377 | |||||
| Natural variant | 637 | 1 | V → L in AD-HIES. Ref.22 | VAR_037378 | |||||
| Natural variant | 637 | 1 | V → M in AD-HIES. Ref.22 | VAR_037379 | |||||
| Natural variant | 644 | 1 | Missing in AD-HIES. Ref.22 | VAR_037380 | |||||
| Natural variant | 657 | 1 | Y → C in AD-HIES. Ref.22 | VAR_037381 | |||||
Experimental info | |||||||||
| 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 | 667 | 1 | V → L in AAA58374. Ref.1 | ||||||
| Sequence conflict | 730 | 1 | T → A in AAA58374. Ref.1 | ||||||
Sequences
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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: 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] | "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. |
| [5] | 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. |
| [6] | "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. |
| [7] | "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. |
| [8] | "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. |
| [9] | "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. Moore K.W.J. Immunol. 168:5699-5708(2002) [PubMed: 12023369] [Abstract] Cited for: INTERACTION WITH IL23R. |
| [10] | "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. |
| [11] | "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. |
| [12] | "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. |
| [13] | "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. |
| [14] | "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: Epithelium. |
| [15] | "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. |
| [16] | "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. |
| [17] | "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. |
| [18] | "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. |
| [19] | "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. |
| [20] | "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. |
| [21] | Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY. |
| [22] | "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. |
| [23] | "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. |
Web resources
| Wikipedia STAT3 entry |
| Atlas of Genetics and Cytogenetics in Oncology and Haematology |
| STAT3base STAT3 mutation db |
| SeattleSNPs |
Cross-references
Sequence databases | |
|---|---|
| L29277 mRNA. Translation: AAA58374.1. AJ012463 mRNA. Translation: CAA10032.1. AY572796 Genomic DNA. Translation: AAS66986.1. BC000627 mRNA. Translation: AAH00627.1. BC014482 mRNA. Translation: AAH14482.1. AF029311 mRNA. Translation: AAB84254.1. | |
| IPI | IPI00306436. IPI00784414. |
| PIR | A54444. |
| RefSeq | NP_003141.2. NP_644805.1. NP_998827.1. |
| UniGene | Hs.463059 |
3D structure databases | |
| HSSP | HSSP built from PDB template 1BG1 based on UniProtKB P42227. |
| SMR | P40763. Positions 136-703. |
| ModBase | Search... |
Protein-protein interaction databases | |
| IntAct | P40763. 12 interactions. |
PTM databases | |
| PhosphoSite | P40763. |
Proteomic databases | |
| PeptideAtlas | P40763. |
| PRIDE | P40763. |
Genome annotation databases | |
| Ensembl | ENSG00000168610. Homo sapiens. [Contig view] |
| GeneID | 6774. |
| KEGG | hsa:6774. |
Organism-specific databases | |
| GeneCards | GC17M037718. |
| H-InvDB | HIX0013840. |
| HGNC | HGNC:11364. STAT3. |
| HPA | CAB003859. HPA001671. |
| MIM | 102582. gene. 147060. phenotype. |
| Orphanet | 2314. Autosomal dominant hyper IgE syndrome. |
| PharmGKB | PA337. |
| GenAtlas | Search... |
Phylogenomic databases | |
| HOVERGEN | P40763. |
| OMA | P40763. KSQGDMQ. |
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_11061. Signalling by NGF. |
Gene expression databases | |
| ArrayExpress | P40763. |
| Bgee | P40763. |
| CleanEx | HS_STAT3. |
| GermOnline | ENSG00000168610. Homo sapiens. |
Family and domain databases | |
| InterPro | IPR011992. EF-Hand_type. IPR000980. SH2. IPR013800. STAT_TF_alpha. 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. |
| 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. [Graphical view] |
| PROSITE | PS50001. SH2. 1 hit. [Graphical view] |
| ProtoNet | Search... |
Other Resources | |
| NextBio | 26438. |
| PMAP-CutDB | P40763. |
| SOURCE | Search... |
Entry information
| Entry name | STAT3_HUMAN | ||||||||
| Accession | Primary (citable) accession number: P40763 Secondary accession number(s): O14916, Q9BW54 | ||||||||
| Entry history |
| ||||||||
| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation project | HPI (Human Proteome Initiative) | ||||||||
Relevant documents
| 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 |

Clusters with


