UniProt Accession

 STAT1_HUMAN; P42224; A8K989; B2RCA0; D2KFR8; D3DPI7; Q53S88; Q53XW4; Q68D00; Q9UDL5 

Genbank Protein ID

 M97935; M97936; GU211347; AY865620; AK292604; AK315002; CR749636; BT007241; AC067945; CH471058; CH471058; CH471058; CH471058; BC002704; U18662; U18663; U18664; U18665; U18666; U18667; U18668; U18669; U18670 

Genbank Nucleotide ID

 AAB64012.1; ADA59516.1; AAW56072.1; BAF85293.1; BAG37497.1; CAH18430.1; AAP35905.1; AAY24183.1; EAX10850.1; EAX10851.1; EAX10852.1; EAX10855.1; AAH02704.1 

Protein Name

 Signal transducer and activator of transcription 1-alpha/beta 

Protein Synonyms/Alias

 Transcription factor ISGF-3 components p91/p84 

Gene Name

 STAT1 

Gene Synonyms/Alias

  

Created Date

 July 27, 2013 

Organism

 Homo sapiens (Human) 

NCBI Taxa ID

 9606 

Lysine Modification

Position	Peptide	Type	References
114	SCLKEERKILENAQR	ubiquitination	[1]
138	QSTVMLDKQKELDSK	ubiquitination	[1, 2]
152	KVRNVKDKVMCIEHE	ubiquitination	[1]
173	LQDEYDFKCKTLQNR	ubiquitination	[1]
193	GVAKSDQKQEQLLLK	ubiquitination	[1]
201	QEQLLLKKMYLMLDN	ubiquitination	[1]
240	NDELVEWKRRQQSAC	ubiquitination	[2]
296	YEHDPITKNKQVLWD	ubiquitination	[2]
379	NTVKGFRKFNILGTH	ubiquitination	[1]
410	EFRHLQLKEQKNAGT	acetylation	[3]
410	EFRHLQLKEQKNAGT	ubiquitination	[2]
413	HLQLKEQKNAGTRTN	acetylation	[3]
511	WQFSSVTKRGLNVDQ	ubiquitination	[2]
525	QLNMLGEKLLGPNAS	ubiquitination	[2]
592	ERERALLKDQQPGTF	ubiquitination	[1, 2, 4]
636	HAVEPYTKKELSAVT	ubiquitination	[2]
637	AVEPYTKKELSAVTF	ubiquitination	[1, 5, 6]
652	PDIIRNYKVMAAENI	ubiquitination	[1, 2, 5, 7]
665	NIPENPLKYLYPNID	ubiquitination	[1, 2]
673	YLYPNIDKDHAFGKY	ubiquitination	[1]
685	GKYYSRPKEAPEPME	ubiquitination	[1]
697	PMELDGPKGTGYIKT	ubiquitination	[1]
703	PKGTGYIKTELISVS	sumoylation	[8, 9, 10, 11, 12, 13]

Reference

 [1] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
 Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
 Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
 [2] Systematic and quantitative assessment of the ubiquitin-modified proteome.
 Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
 Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983]
 [3] Acetylation of Stat1 modulates NF-kappaB activity.
 Krämer OH, Baus D, Knauer SK, Stein S, Jäger E, Stauber RH, Grez M, Pfitzner E, Heinzel T.
 Genes Dev. 2006 Feb 15;20(4):473-85. [PMID: 16481475]
 [4] A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles.
 Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C.
 Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. [PMID: 21890473]
 [5] Proteomic analyses reveal divergent ubiquitylation site patterns in murine tissues.
 Wagner SA, Beli P, Weinert BT, Schölz C, Kelstrup CD, Young C, Nielsen ML, Olsen JV, Brakebusch C, Choudhary C.
 Mol Cell Proteomics. 2012 Dec;11(12):1578-85. [PMID: 22790023]
 [6] Systems-wide analysis of ubiquitylation dynamics reveals a key role for PAF15 ubiquitylation in DNA-damage bypass.
 Povlsen LK, Beli P, Wagner SA, Poulsen SL, Sylvestersen KB, Poulsen JW, Nielsen ML, Bekker-Jensen S, Mailand N, Choudhary C.
 Nat Cell Biol. 2012 Oct;14(10):1089-98. [PMID: 23000965]
 [7] Methods for quantification of in vivo changes in protein ubiquitination following proteasome and deubiquitinase inhibition.
 Udeshi ND, Mani DR, Eisenhaure T, Mertins P, Jaffe JD, Clauser KR, Hacohen N, Carr SA.
 Mol Cell Proteomics. 2012 May;11(5):148-59. [PMID: 22505724]
 [8] SUMO modification of STAT1 and its role in PIAS-mediated inhibition of gene activation.
 Rogers RS, Horvath CM, Matunis MJ.
 J Biol Chem. 2003 Aug 8;278(32):30091-7. [PMID: 12764129]
 [9] PIAS proteins promote SUMO-1 conjugation to STAT1.
 Ungureanu D, Vanhatupa S, Kotaja N, Yang J, Aittomaki S, Jänne OA, Palvimo JJ, Silvennoinen O.
 Blood. 2003 Nov 1;102(9):3311-3. [PMID: 12855578]
 [10] The 'PINIT' motif, of a newly identified conserved domain of the PIAS protein family, is essential for nuclear retention of PIAS3L.
 Duval D, Duval G, Kedinger C, Poch O, Boeuf H.
 FEBS Lett. 2003 Nov 6;554(1-2):111-8. [PMID: 14596924]
 [11] SUMO-1 conjugation selectively modulates STAT1-mediated gene responses.
 Ungureanu D, Vanhatupa S, Grönholm J, Palvimo JJ, Silvennoinen O.
 Blood. 2005 Jul 1;106(1):224-6. [PMID: 15761017]
 [12] Site-specific identification of SUMO-2 targets in cells reveals an inverted SUMOylation motif and a hydrophobic cluster SUMOylation motif.
 Matic I, Schimmel J, Hendriks IA, van Santen MA, van de Rijke F, van Dam H, Gnad F, Mann M, Vertegaal AC.
 Mol Cell. 2010 Aug 27;39(4):641-52. [PMID: 20797634]
 [13] Cytokine-induced paracrystals prolong the activity of signal transducers and activators of transcription (STAT) and provide a model for the regulation of protein solubility by small ubiquitin-like modifier (SUMO).
 Droescher M, Begitt A, Marg A, Zacharias M, Vinkemeier U.
 J Biol Chem. 2011 May 27;286(21):18731-46. [PMID: 21460228] 

Functional Description

 Signal transducer and transcription activator that mediates cellular responses to interferons (IFNs), cytokine KITLG/SCF and other cytokines and 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. 

Sequence Annotation

 DOMAIN 573 670 SH2.
 MOD_RES 701 701 Phosphotyrosine; by JAK1, JAK2 or TYK2.
 MOD_RES 727 727 Phosphoserine; by MAPK14.
 CROSSLNK 703 703 Glycyl lysine isopeptide (Lys-Gly)  

Keyword

 3D-structure; Activator; Alternative splicing; Antiviral defense; Complete proteome; Cytoplasm; Direct protein sequencing; Disease mutation; DNA-binding; Host-virus interaction; Isopeptide bond; Nucleus; Phosphoprotein; Polymorphism; Reference proteome; SH2 domain; Transcription; Transcription regulation; Ubl conjugation. 

Sequence Source

 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 

Protein Length

 750 AA 

Protein Sequence

Gene Ontology

 GO:0030424; C:axon; ISS:UniProtKB.
 GO:0005829; C:cytosol; TAS:Reactome.
 GO:0030425; C:dendrite; ISS:UniProtKB.
 GO:0000790; C:nuclear chromatin; IDA:BHF-UCL.
 GO:0005730; C:nucleolus; IDA:HPA.
 GO:0005654; C:nucleoplasm; TAS:Reactome.
 GO:0005509; F:calcium ion binding; IEA:InterPro.
 GO:0003690; F:double-stranded DNA binding; IDA:UniProtKB.
 GO:0042803; F:protein homodimerization activity; IDA:UniProtKB.
 GO:0000978; F:RNA polymerase II core promoter proximal region sequence-specific DNA binding; IDA:BHF-UCL.
 GO:0000979; F:RNA polymerase II core promoter sequence-specific DNA binding; IDA:BHF-UCL.
 GO:0000983; F:RNA polymerase II core promoter sequence-specific DNA binding transcription factor activity; IDA:BHF-UCL.
 GO:0003700; F:sequence-specific DNA binding transcription factor activity; IDA:UniProtKB.
 GO:0004871; F:signal transducer activity; IEA:InterPro.
 GO:0008015; P:blood circulation; ISS:UniProtKB.
 GO:0035458; P:cellular response to interferon-beta; IMP:BHF-UCL.
 GO:0051607; P:defense response to virus; IEA:UniProtKB-KW.
 GO:0006917; P:induction of apoptosis; ISS:UniProtKB.
 GO:0060333; P:interferon-gamma-mediated signaling pathway; IDA:BHF-UCL.
 GO:0060397; P:JAK-STAT cascade involved in growth hormone signaling pathway; TAS:Reactome.
 GO:0031663; P:lipopolysaccharide-mediated signaling pathway; IEA:Compara.
 GO:0072162; P:metanephric mesenchymal cell differentiation; ISS:UniProtKB.
 GO:0072136; P:metanephric mesenchymal cell proliferation involved in metanephros development; ISS:UniProtKB.
 GO:0016525; P:negative regulation of angiogenesis; IMP:UniProtKB.
 GO:0001937; P:negative regulation of endothelial cell proliferation; IMP:UniProtKB.
 GO:0043124; P:negative regulation of I-kappaB kinase/NF-kappaB cascade; IMP:UniProtKB.
 GO:0003340; P:negative regulation of mesenchymal to epithelial transition involved in metanephros morphogenesis; ISS:UniProtKB.
 GO:0072308; P:negative regulation of metanephric nephron tubule epithelial cell differentiation; ISS:UniProtKB.
 GO:0000122; P:negative regulation of transcription from RNA polymerase II promoter; ISS:UniProtKB.
 GO:0002053; P:positive regulation of mesenchymal cell proliferation; ISS:UniProtKB.
 GO:0048661; P:positive regulation of smooth muscle cell proliferation; ISS:UniProtKB.
 GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; IDA:UniProtKB.
 GO:0060334; P:regulation of interferon-gamma-mediated signaling pathway; TAS:Reactome.
 GO:0060338; P:regulation of type I interferon-mediated signaling pathway; TAS:Reactome.
 GO:0061326; P:renal tubule development; IMP:UniProtKB.
 GO:0051591; P:response to cAMP; ISS:UniProtKB.
 GO:0043330; P:response to exogenous dsRNA; IEA:Compara.
 GO:0033209; P:tumor necrosis factor-mediated signaling pathway; IDA:UniProtKB.
 GO:0060337; P:type I interferon-mediated signaling pathway; TAS:Reactome.
 GO:0019048; P:virus-host interaction; IEA:UniProtKB-KW. 

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. 

Pfam

 PF00017; SH2
 PF12162; STAT1_TAZ2bind
 PF01017; STAT_alpha
 PF02864; STAT_bind
 PF02865; STAT_int 

SMART

 SM00252; SH2
 SM00964; STAT_int 

PROSITE

 PS50001; SH2 

PRINTS