STAT2_MOUSE
ID STAT2_MOUSE Reviewed; 923 AA.
AC Q9WVL2; Q64188; Q64189; Q64250;
DT 27-APR-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1999, sequence version 1.
DT 03-AUG-2022, entry version 159.
DE RecName: Full=Signal transducer and activator of transcription 2;
GN Name=Stat2;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=CD-1;
RA Paulson M.S., Mui A., Levy D.E.;
RT "Molecular cloning and characterization of murine Stat2.";
RL Submitted (AUG-1998) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 595-658.
RX PubMed=8601453; DOI=10.1016/0014-5793(96)00121-4;
RA Sugiyama T., Nishio Y., Kishimoto T., Akira S.;
RT "Identification of alternative splicing form of Stat2.";
RL FEBS Lett. 381:191-194(1996).
RN [3]
RP IDENTIFICATION IN THE ISGF3 COMPLEX.
RX PubMed=17332413; DOI=10.1126/science.1136567;
RA Tenoever B.R., Ng S.L., Chua M.A., McWhirter S.M., Garcia-Sastre A.,
RA Maniatis T.;
RT "Multiple functions of the IKK-related kinase IKKepsilon in interferon-
RT mediated antiviral immunity.";
RL Science 315:1274-1278(2007).
RN [4]
RP INTERACTION WITH ARL2BP.
RX PubMed=18234692; DOI=10.1093/intimm/dxm154;
RA Muromoto R., Sekine Y., Imoto S., Ikeda O., Okayama T., Sato N.,
RA Matsuda T.;
RT "BART is essential for nuclear retention of STAT3.";
RL Int. Immunol. 20:395-403(2008).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Liver, Lung, Pancreas, and Spleen;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
CC -!- FUNCTION: Signal transducer and activator of transcription that
CC mediates signaling by type I interferons (IFN-alpha and IFN-beta).
CC Following type I IFN binding to cell surface receptors, Jak kinases
CC (TYK2 and JAK1) are activated, leading to tyrosine phosphorylation of
CC STAT1 and STAT2. The phosphorylated STATs dimerize, associate with
CC IRF9/ISGF3G to form a complex termed ISGF3 transcription factor, that
CC enters the nucleus. ISGF3 binds to the IFN stimulated response element
CC (ISRE) to activate the transcription of interferon stimulated genes,
CC which drive the cell in an antiviral state. In addition, has also a
CC negative feedback regulatory role in the type I interferon signaling by
CC recruiting USP18 to the type I IFN receptor subunit IFNAR2 thereby
CC mitigating the response to type I IFNs. Acts as a regulator of
CC mitochondrial fission by modulating the phosphorylation of DNM1L at
CC 'Ser-616' and 'Ser-637' which activate and inactivate the GTPase
CC activity of DNM1L respectively. {ECO:0000250|UniProtKB:P52630}.
CC -!- SUBUNIT: Heterodimer with STAT1 upon IFN-alpha/beta induced
CC phosphorylation. The heterodimer STAT1:STAT2 forms the interferon-
CC stimulated gene factor 3 complex (ISGF3) with IRF9; interacts with IRF9
CC in the cytoplasm (PubMed:17332413). Interacts with CRSP2 and CRSP6 (By
CC similarity). Can form a homodimer upon IFN-alpha induced
CC phosphorylation. Interacts with IFNAR1 and IFNAR2; the interaction is
CC direct. Interacts with ARL2BP (PubMed:18234692). Interacts with E3
CC ubiquitin ligase DCST1; the interaction results in STAT2 ubiquitin-
CC mediated proteasomal degradation (By similarity). Interacts with USP18;
CC the interaction is direct and allows the recruitment of USP18 to IFNAR2
CC (By similarity). {ECO:0000250|UniProtKB:P52630,
CC ECO:0000269|PubMed:17332413, ECO:0000269|PubMed:18234692}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:P52630}. Nucleus
CC {ECO:0000250|UniProtKB:P52630}. Note=Translocated into the nucleus upon
CC activation by IFN-alpha/beta. {ECO:0000250|UniProtKB:P52630}.
CC -!- TISSUE SPECIFICITY: Found in the brain, lung, heart, spleen, liver,
CC kidney, muscle and the testis.
CC -!- PTM: Tyrosine phosphorylated in response to IFN-alpha. {ECO:0000250}.
CC -!- PTM: 'Lys-48'-linked ubiquitination by DCST1 leads to STAT2 proteasomal
CC degradation. {ECO:0000250|UniProtKB:P52630}.
CC -!- SIMILARITY: Belongs to the transcription factor STAT family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAB36230.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
CC Sequence=AAB36231.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
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DR EMBL; AF088862; AAD38329.1; -; mRNA.
DR EMBL; S81342; AAB36228.2; -; Genomic_DNA.
DR EMBL; S81342; AAB36230.1; ALT_SEQ; Genomic_DNA.
DR EMBL; S81342; AAB36231.1; ALT_SEQ; Genomic_DNA.
DR PIR; S63681; S63681.
DR PIR; S63682; S63682.
DR AlphaFoldDB; Q9WVL2; -.
DR SMR; Q9WVL2; -.
DR STRING; 10090.ENSMUSP00000100872; -.
DR iPTMnet; Q9WVL2; -.
DR PhosphoSitePlus; Q9WVL2; -.
DR EPD; Q9WVL2; -.
DR MaxQB; Q9WVL2; -.
DR PaxDb; Q9WVL2; -.
DR PeptideAtlas; Q9WVL2; -.
DR PRIDE; Q9WVL2; -.
DR ProteomicsDB; 258658; -.
DR MGI; MGI:103039; Stat2.
DR eggNOG; KOG3667; Eukaryota.
DR InParanoid; Q9WVL2; -.
DR PhylomeDB; Q9WVL2; -.
DR Reactome; R-MMU-8854691; Interleukin-20 family signaling.
DR Reactome; R-MMU-909733; Interferon alpha/beta signaling.
DR Reactome; R-MMU-912694; Regulation of IFNA/IFNB signaling.
DR ChiTaRS; Stat2; mouse.
DR PRO; PR:Q9WVL2; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; Q9WVL2; protein.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0070721; C:ISGF3 complex; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IBA:GO_Central.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR GO; GO:0044389; F:ubiquitin-like protein ligase binding; ISO:MGI.
DR GO; GO:0019221; P:cytokine-mediated signaling pathway; IBA:GO_Central.
DR GO; GO:0006952; P:defense response; IBA:GO_Central.
DR GO; GO:0051607; P:defense response to virus; ISS:UniProtKB.
DR GO; GO:0060339; P:negative regulation of type I interferon-mediated signaling pathway; IMP:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISO:MGI.
DR GO; GO:0007259; P:receptor signaling pathway via JAK-STAT; IBA:GO_Central.
DR GO; GO:0042127; P:regulation of cell population proliferation; IBA:GO_Central.
DR GO; GO:0090140; P:regulation of mitochondrial fission; ISS:UniProtKB.
DR GO; GO:0001932; P:regulation of protein phosphorylation; ISS:UniProtKB.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0043434; P:response to peptide hormone; IBA:GO_Central.
DR GO; GO:0060337; P:type I interferon signaling pathway; IMP:UniProtKB.
DR CDD; cd10373; SH2_STAT2; 1.
DR Gene3D; 1.10.532.10; -; 1.
DR Gene3D; 2.60.40.630; -; 1.
DR Gene3D; 3.30.505.10; -; 1.
DR InterPro; IPR008967; p53-like_TF_DNA-bd.
DR InterPro; IPR000980; SH2.
DR InterPro; IPR036860; SH2_dom_sf.
DR InterPro; IPR001217; STAT.
DR InterPro; IPR022756; STAT2_C.
DR InterPro; IPR035854; STAT2_SH2.
DR InterPro; IPR036535; STAT_N_sf.
DR InterPro; IPR013800; STAT_TF_alpha.
DR InterPro; IPR015988; STAT_TF_coiled-coil.
DR InterPro; IPR013801; STAT_TF_DNA-bd.
DR InterPro; IPR012345; STAT_TF_DNA-bd_N.
DR InterPro; IPR013799; STAT_TF_prot_interaction.
DR PANTHER; PTHR11801; PTHR11801; 1.
DR Pfam; PF00017; SH2; 1.
DR Pfam; PF12188; STAT2_C; 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 SMART; SM00964; STAT_int; 1.
DR SUPFAM; SSF47655; SSF47655; 1.
DR SUPFAM; SSF48092; SSF48092; 1.
DR SUPFAM; SSF49417; SSF49417; 1.
DR SUPFAM; SSF55550; SSF55550; 1.
DR PROSITE; PS50001; SH2; 1.
PE 1: Evidence at protein level;
KW Activator; Cytoplasm; DNA-binding; Nucleus; Phosphoprotein;
KW Reference proteome; SH2 domain; Transcription; Transcription regulation;
KW Ubl conjugation.
FT CHAIN 1..923
FT /note="Signal transducer and activator of transcription 2"
FT /id="PRO_0000182414"
FT DOMAIN 571..666
FT /note="SH2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00191"
FT REGION 137..571
FT /note="Mediates interaction with USP18"
FT /evidence="ECO:0000250|UniProtKB:P52630"
FT MOD_RES 284
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P52630"
FT MOD_RES 689
FT /note="Phosphotyrosine; by JAK"
FT /evidence="ECO:0000250|UniProtKB:P52630"
FT CONFLICT 596
FT /note="T -> A (in Ref. 2; AAB36228/AAB36231)"
FT /evidence="ECO:0000305"
FT CONFLICT 620
FT /note="H -> D (in Ref. 2; AAB36228)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 923 AA; 105417 MW; D50BB54C535B0774 CRC64;
MAQWEMLQNL DSPFLDQLHQ VYSQSFLPMD FRQHLASWIE DQNWREAALE SDDAKANMLY
FSILDQLNQW DHYSSDPKSL LLQHNLRKFS RDIQPFPNGP SQLAEMIFNL LLEEQRILIQ
AQRAQEVQPP PAPEAVVESQ QLEIENRIQG LHVDIEFLVR SIRQLKDEQD VFSFRYTVFS
LKKTSSSDPH QSQQAHVVQA TANKVDRMRK EVLDISKGLV GRLTTLVDLL LPKLDEWKVQ
QQKSCIGAPP PVKSAAEQLE QWLTAGAKFL FHLRQLLKQL KEMSCLRYQG DMFAKGVDLR
NAQVMELLQR LLQRSFVVET QPCMPQTLHR PLILKTGNKF TVRTRLLVRL QEGSESLKAE
VSVDRNSDLP GFRKFNILTS NQKTLTPEKG QRQGLIWDFG FLTLVEQRAV GAGKGNNKGP
LAVTEELHVI SFVVEYTYQG LKMKLQTDTL PVVIISNMNQ LSFAWASILW FNMLSPNPKN
QQFFCQAPKA PWSLLGPVLS WQFSSYVARG LDSEQLGMLR TKLFGKSCKM EDALLSWVDF
CKRESPPGKI PFWTWLDKIL ELVHDHLKDL WKDGRIMGFV SRNQERRLLK KMLSGTFLLR
FSETSEGGIT CSWVEHQDDH KVEIYSVQPY TKEVLQSLPL TEIIRHYQVL AEENIPENPL
RFLYPRIPRD EAFGCYYQEK VNLEEQEEYL KHKLIVISNR QVDELQQPLE LKQDSESLEV
NAELLLAHDQ ELPLMMQTGL VLGTELKVDP ILSTAPQVLL EPAPQVLLEP APQVLLEPAP
QVLLEPAPQV LLEPAPQVLL EPAPQVLLEP APQVQLEPAP QVLLELAPQV LLEPAPQVLL
ELAPQVQLEP AHLLQQPSES DLPEDLQQIS VEDLKKLSNP STEYITTNEN PMLAGESSGD
ETSIPYHSHF DADGLLGWTL DTF
