P42225 (STAT1_MOUSE) Reviewed, UniProtKB/Swiss-Prot
Last modified April 3, 2013. Version 113. History...
Names and origin
|Protein names||Recommended name:|
Signal transducer and activator of transcription 1
|Organism||Mus musculus (Mouse) [Reference proteome]|
|Taxonomic identifier||10090 [NCBI]|
|Taxonomic lineage||Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus|
|Sequence length||749 AA.|
|Protein existence||Evidence at protein level|
General annotation (Comments)
Signal transducer and transcription activator that mediates cellular responses to interferons (IFNs), cytokine KITLG/SCF and other cytokines and other growth factors. Following type I IFN (IFN-alpha and IFN-beta) binding to cell surface receptors, signaling via protein kinases leads to activation of Jak kinases (TYK2 and JAK1) and to tyrosine phosphorylation of STAT1 and STAT2. The phosphorylated STATs dimerize, associate with ISGF3G/IRF-9 to form a complex termed ISGF3 transcription factor, that enters the nucleus. ISGF3 binds to the IFN stimulated response element (ISRE) to activate the transcription of interferon stimulated genes, which drive the cell in an antiviral state. In response to type II IFN (IFN-gamma), STAT1 is tyrosine- and serine-phosphorylated. It then forms a homodimer termed IFN-gamma-activated factor (GAF), migrates into the nucleus and binds to the IFN gamma activated sequence (GAS) to drive the expression of the target genes, inducing a cellular antiviral state. Becomes activated in response to KITLG/SCF and KIT signaling. May mediate cellular responses to activated FGFR1, FGFR2, FGFR3 and FGFR4. Ref.2 Ref.3 Ref.5
In response to IFN alpha/beta, three subunits (STAT1-alpha, STAT1-beta, STAT2) of ISGF3, become phosphorylated on tyrosine, migrate into the nucleus, and assemble into a complex together with ISGF3 gamma (p48), a DNA-binding protein that specifically binds to the IFN-stimulated response element. In response to IFN gamma, STAT1 forms homodimers, that also translocate into the nucleus to activate IFN gamma-responsive genes. Interacts with PIAS1 (dimethylated on arginine); the interaction results in release of STAT1 from its target gene. Interacts with ERBB4 (phosphorylated). Interacts with PTK2/FAK1 By similarity. Interacts with NMI. Interacts with PIAS1; the interaction requires phosphorylation on Ser-727 and inhibits STAT1 activation. Interacts with IFNAR1, IFNAR2 and SRC. Ref.2
Cytoplasm. Nucleus. Note: Translocated into the nucleus upon tyrosine phosphorylation and dimerization, in response to IFN-gamma and signaling by activated FGFR1; FGFR2; FGFR3 or FGFR4 By similarity. Ref.3
By IFN and EGF.
Phosphorylated on tyrosine and serine residues in response to a variety of cytokines/growth hormones including IFN-alpha, IFN-gamma, PDGF and EGF. Activated KIT promotes phosphorylation on tyrosine residues and subsequent translocation to the nucleus. Upon EGF stimulation, phosphorylation on Tyr-701 (lacking in beta form) by JAK1, JAK2 or TYK2 promotes dimerization and subsequent translocation to the nucleus. Growth hormone (GH) activates STAT1 signaling only via JAK2. Tyrosine phosphorylated in response to constitutively activated FGFR1, FGFR2, FGFR3 and FGFR4. Phosphorylation on Ser-727 by several kinases including MAPK14, ERK1/2 and CAMKII on IFN-gamma stimulation, regulates STAT1 transcriptional activity. Phosphorylation on Ser-727 promotes sumoylation though increasing interaction with PIAS. Phosphorylation on Ser-727 by PKCdelta induces apoptosis in response to DNA-damaging agents. Phosphorylated on tyrosine residues when PTK2/FAK1 is activated; most likely this is catalyzed by a SRC family kinase By similarity. Ref.2 Ref.3 Ref.5 Ref.6
Sumoylated with SUMO1, SUMO2 and SUMO3. Sumoylation is enhanced by IFN-gamma-induced phosphorylation on Ser-727, and by interaction with PIAS proteins. Enhances the transactivation activity By similarity.
Belongs to the transcription factor STAT family.
Contains 1 SH2 domain.
Sequence annotation (Features)
|Feature key||Position(s)||Length||Description||Graphical view||Feature identifier|
|Chain||1 – 749||749||Signal transducer and activator of transcription 1||PRO_0000182411|
|Domain||573 – 670||98||SH2|
Amino acid modifications
|Modified residue||701||1||Phosphotyrosine; by JAK1, JAK2 or TYK2 Ref.5|
|Modified residue||727||1||Phosphoserine; by MAPK14 By similarity|
|Cross-link||703||Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) By similarity|
|||"Stat3 and Stat4: members of the family of signal transducers and activators of transcription."|
Zhong Z., Wen Z., Darnell J.E. Jr.
Proc. Natl. Acad. Sci. U.S.A. 91:4806-4810(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
|||"c-Src activates both STAT1 and STAT3 in PDGF-stimulated NIH3T3 cells."|
Cirri P., Chiarugi P., Marra F., Raugei G., Camici G., Manao G., Ramponi G.
Biochem. Biophys. Res. Commun. 239:493-497(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION, FUNCTION, INTERACTION WITH SRC.
|||"Identification of tyrosine residues in constitutively activated fibroblast growth factor receptor 3 involved in mitogenesis, Stat activation, and phosphatidylinositol 3-kinase activation."|
Hart K.C., Robertson S.C., Donoghue D.J.
Mol. Biol. Cell 12:931-942(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, PHOSPHORYLATION.
|||"Proteomic identification of proteins conjugated to ISG15 in mouse and human cells."|
Giannakopoulos N.V., Luo J.K., Papov V., Zou W., Lenschow D.J., Jacobs B.S., Borden E.C., Li J., Virgin H.W., Zhang D.E.
Biochem. Biophys. Res. Commun. 336:496-506(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: ISGYLATION.
|||"Analysis of STAT1 activation by six FGFR3 mutants associated with skeletal dysplasia undermines dominant role of STAT1 in FGFR3 signaling in cartilage."|
Krejci P., Salazar L., Kashiwada T.A., Chlebova K., Salasova A., Thompson L.M., Bryja V., Kozubik A., Wilcox W.R.
PLoS ONE 3:E3961-E3961(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, PHOSPHORYLATION AT TYR-701 IN RESPONSE TO CONSTITUTIVELY ACTIVATED FGFR3.
|||"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 IN RESPONSE TO KIT SIGNALING.
|+||Additional computationally mapped references.|
|U06924 mRNA. Translation: AAA19454.1.|
3D structure databases
|SMR||P42225. Positions 2-749. |
Protein-protein interaction databases
|IntAct||P42225. 7 interactions.|
Protocols and materials databases
|MGI||MGI:103063. Stat1. |
Enzyme and pathway databases
|Reactome||REACT_107772. Immune System. |
Gene expression databases
|GermOnline||ENSMUSG00000026104. Mus musculus. |
Family and domain databases
|Gene3D||188.8.131.52. 1 hit. |
1.10.532.10. 1 hit.
1.20.1050.20. 1 hit.
184.108.40.2060. 1 hit.
3.30.505.10. 1 hit.
|InterPro||IPR011992. EF-hand-like_dom. |
|PANTHER||PTHR11801. PTHR11801. 1 hit. |
|Pfam||PF00017. SH2. 1 hit. |
PF12162. STAT1_TAZ2bind. 1 hit.
PF01017. STAT_alpha. 1 hit.
PF02864. STAT_bind. 1 hit.
PF02865. STAT_int. 1 hit.
|SMART||SM00252. SH2. 1 hit. |
SM00964. STAT_int. 1 hit.
|SUPFAM||SSF49417. P53_like_DNA_bnd. 1 hit. |
SSF47655. STAT. 1 hit.
SSF48092. STAT. 1 hit.
|PROSITE||PS50001. SH2. 1 hit. |
|ChiTaRS||STAT1. mouse. |
|Accession||Primary (citable) accession number: P42225|
|Entry status||Reviewed (UniProtKB/Swiss-Prot)|
|Annotation program||Chordata Protein Annotation Program|