P42225 (STAT1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Signal transducer and activator of transcription 1

Gene names

Name:

Stat1

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	749 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	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
Subunit structure	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
Subcellular location	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
Induction	By IFN and EGF.
Post-translational modification	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. ISGylated. Ref.4
Sequence similarities	Belongs to the transcription factor STAT family. Contains 1 SH2 domain.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Cytoplasm Nucleus
Domain	SH2 domain
Ligand	DNA-binding
Molecular function	Activator
PTM	Isopeptide bond Phosphoprotein Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	activation of cysteine-type endopeptidase activity involved in apoptotic process Inferred from mutant phenotype PubMed 10692450. Source: UniProtKB blood circulation Inferred from sequence or structural similarity. Source: UniProtKB cytokine-mediated signaling pathway Inferred from direct assay PubMed 12872135. Source: MGI induction of apoptosis Inferred from sequence or structural similarity. Source: UniProtKB lipopolysaccharide-mediated signaling pathway Inferred from direct assay PubMed 12872135. Source: MGI metanephric mesenchymal cell differentiation Inferred from sequence or structural similarity. Source: UniProtKB metanephric mesenchymal cell proliferation involved in metanephros development Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of mesenchymal to epithelial transition involved in metanephros morphogenesis Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of metanephric nephron tubule epithelial cell differentiation Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of transcription from RNA polymerase II promoter Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of mesenchymal cell proliferation Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of smooth muscle cell proliferation Inferred from sequence or structural similarity. Source: UniProtKB renal tubule development Inferred from sequence or structural similarity. Source: UniProtKB response to cAMP Inferred from sequence or structural similarity. Source: UniProtKB response to exogenous dsRNA Inferred from direct assay PubMed 12872135. Source: MGI response to peptide hormone stimulus Inferred from sequence or structural similarity. Source: UniProtKB transcription, DNA-dependent Inferred from mutant phenotype PubMed 15485925. Source: MGI
Cellular_component	axon Inferred from sequence or structural similarity. Source: UniProtKB cytosol Traceable author statement. Source: Reactome dendrite Inferred from sequence or structural similarity. Source: UniProtKB nucleus Inferred from direct assay PubMed 12957148. Source: MGI
Molecular_function	DNA binding Inferred from electronic annotation. Source: UniProtKB-KW calcium ion binding Inferred from electronic annotation. Source: InterPro sequence-specific DNA binding transcription factor activity Inferred from mutant phenotype PubMed 15485925. Source: MGI signal transducer activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
Stat4	P42228	2	EBI-647118,EBI-6253572

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 749	749	Signal transducer and activator of transcription 1		PRO_0000182411
Regions
	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

Sequences

	Sequence		Length	Mass (Da)
	P42225 [UniParc]. Last modified November 1, 1995. Version 1. Checksum: 249D919952BE65F1	FASTA	749	87,197
	10 20 30 40 50 60 MSQWFELQQL DSKFLEQVHQ LYDDSFPMEI RQYLAQWLEK QDWEHAAYDV SFATIRFHDL 70 80 90 100 110 120 LSQLDDQYSR FSLENNFLLQ HNIRKSKRNL QDNFQEDPVQ MSMIIYNCLK EERKILENAQ 130 140 150 160 170 180 RFNQAQEGNI QNTVMLDKQK ELDSKVRNVK DQVMCIEQEI KTLEELQDEY DFKCKTSQNR 190 200 210 220 230 240 EGEANGVAKS DQKQEQLLLH KMFLMLDNKR KEIIHKIREL LNSIELTQNT LINDELVEWK 250 260 270 280 290 300 RRQQSACIGG PPNACLDQLQ TWFTIVAETL QQIRQQLKKL EELEQKFTYE PDPITKNKQV 310 320 330 340 350 360 LSDRTFLLFQ QLIQSSFVVE RQPCMPTHPQ RPLVLKTGVQ FTVKSRLLVK LQESNLLTKV 370 380 390 400 410 420 KCHFDKDVNE KNTVKGFRKF NILGTHTKVM NMEESTNGSL AAELRHLQLK EQKNAGNRTN 430 440 450 460 470 480 EGPLIVTEEL HSLSFETQLC QPGLVIDLET TSLPVVVISN VSQLPSGWAS ILWYNMLVTE 490 500 510 520 530 540 PRNLSFFLNP PCAWWSQLSE VLSWQFSSVT KRGLNADQLS MLGEKLLGPN AGPDGLIPWT 550 560 570 580 590 600 RFCKENINDK NFSFWPWIDT ILELIKNDLL CLWNDGCIMG FISKERERAL LKDQQPGTFL 610 620 630 640 650 660 LRFSESSREG AITFTWVERS QNGGEPDFHA VEPYTKKELS AVTFPDIIRN YKVMAAENIP 670 680 690 700 710 720 ENPLKYLYPN IDKDHAFGKY YSRPKEAPEP MELDDPKRTG YIKTELISVS EVHPSRLQTT 730 740 DNLLPMSPEE FDEMSRIVGP EFDSMMSTV

References

[1]	"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]. Tissue: Thymus.
[2]	"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.
[3]	"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.
[4]	"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.
[5]	"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.
[6]	"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.

Cross-references

Sequence databases
EMBL GenBank DDBJ	U06924 mRNA. Translation: AAA19454.1.
IPI	IPI00467004.
UniGene	Mm.277406. Mm.487336.
3D structure databases
ProteinModelPortal	P42225.
SMR	P42225. Positions 2-749.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-38739N.
IntAct	P42225. 7 interactions.
PTM databases
PhosphoSite	P42225.
Proteomic databases
PaxDb	P42225.
PRIDE	P42225.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Organism-specific databases
MGI	MGI:103063. Stat1.
Phylogenomic databases
eggNOG	NOG310130.
HOVERGEN	HBG055669.
InParanoid	P42225.
OrthoDB	EOG4N5VWB.
Enzyme and pathway databases
Reactome	REACT_107772. Immune System.
Gene expression databases
Genevestigator	P42225.
GermOnline	ENSMUSG00000026104. Mus musculus.
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. IPR022752. STAT1_TAZ2-bd_C. 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. PF12162. STAT1_TAZ2bind. 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	P42225.
ChEMBL	CHEMBL1667670.
ChiTaRS	STAT1. mouse.
SOURCE	Search...

Entry information

Entry name

STAT1_MOUSE

Accession

Primary (citable) accession number: P42225

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1995
Last sequence update:	November 1, 1995
Last modified:	April 3, 2013
This is version 113 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program