STAT1_PIG
ID STAT1_PIG Reviewed; 757 AA.
AC Q764M5;
DT 12-APR-2005, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 25-MAY-2022, entry version 118.
DE RecName: Full=Signal transducer and activator of transcription 1;
GN Name=STAT1;
OS Sus scrofa (Pig).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Suina; Suidae; Sus.
OX NCBI_TaxID=9823;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=14681463; DOI=10.1093/nar/gkh037;
RA Uenishi H., Eguchi T., Suzuki K., Sawazaki T., Toki D., Shinkai H.,
RA Okumura N., Hamasima N., Awata T.;
RT "PEDE (Pig EST Data Explorer): construction of a database for ESTs derived
RT from porcine full-length cDNA libraries.";
RL Nucleic Acids Res. 32:D484-D488(2004).
RN [2]
RP INTERACTION WITH AFRICAN SWINE FEVER VIRUS PROTEIN MGF360-9L (MICROBIAL
RP INFECTION), AND SUBCELLULAR LOCATION.
RX PubMed=35076286; DOI=10.1128/mbio.02330-21;
RA Zhang K., Yang B., Shen C., Zhang T., Hao Y., Zhang D., Liu H., Shi X.,
RA Li G., Yang J., Li D., Zhu Z., Tian H., Yang F., Ru Y., Cao W.J., Guo J.,
RA He J., Zheng H., Liu X.;
RT "MGF360-9L Is a Major Virulence Factor Associated with the African Swine
RT Fever Virus by Antagonizing the JAK/STAT Signaling Pathway.";
RL MBio 0:0-0(2022).
CC -!- FUNCTION: Signal transducer and transcription activator that mediates
CC cellular responses to interferons (IFNs), cytokine KITLG/SCF and other
CC cytokines and other growth factors. Following type I IFN (IFN-alpha and
CC IFN-beta) binding to cell surface receptors, signaling via protein
CC kinases leads to activation of Jak kinases (TYK2 and JAK1) and to
CC tyrosine phosphorylation of STAT1 and STAT2. The phosphorylated STATs
CC dimerize and associate with ISGF3G/IRF-9 to form a complex termed ISGF3
CC transcription factor, that enters the nucleus. ISGF3 binds to the IFN
CC stimulated response element (ISRE) to activate the transcription of
CC IFN-stimulated genes (ISG), which drive the cell in an antiviral state.
CC In response to type II IFN (IFN-gamma), STAT1 is tyrosine- and serine-
CC phosphorylated. It then forms a homodimer termed IFN-gamma-activated
CC factor (GAF), migrates into the nucleus and binds to the IFN gamma
CC activated sequence (GAS) to drive the expression of the target genes,
CC inducing a cellular antiviral state. Becomes activated in response to
CC KITLG/SCF and KIT signaling. May mediate cellular responses to
CC activated FGFR1, FGFR2, FGFR3 and FGFR4.
CC {ECO:0000250|UniProtKB:P42224}.
CC -!- SUBUNIT: Homodimerizes upon IFN-gamma induced phosphorylation.
CC Heterodimer with STAT2 upon IFN-alpha/beta induced phosphorylation. The
CC heterodimer STAT1:STAT2 forms the interferon-stimulated gene factor 3
CC complex (ISGF3) with IRF9. Interacts (phosphorylated at Ser-727) with
CC PIAS1; the interaction results in release of STAT1 from its target
CC gene. Interacts with IFNAR1. Interacts with IFNAR2. Found in a complex
CC with NMI and CREBBP/CBP. Interacts with NMI which is required for
CC CREBBP/CBP recruitment to the complex. Interacts with PTK2/FAK1.
CC Interacts with SRC. Interacts with ERBB4 (phosphorylated). Interacts
CC with PARP9 and DTX3L independently of IFN-beta or IFN-gamma-mediated
CC STAT1 'Tyr-701' phosphorylation. Interacts with histone
CC acetyltransferase EP300/p300 in response to INF-gamma stimulation.
CC Interacts with OTOP1. {ECO:0000250|UniProtKB:P42224,
CC ECO:0000250|UniProtKB:P42225}.
CC -!- SUBUNIT: (Microbial infection) Interacts with African swine fever virus
CC (ASFV) MGF360-9L; this interaction mediates degradation of STAT1
CC through apoptosis. {ECO:0000269|PubMed:35076286}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:35076286}. Nucleus
CC {ECO:0000269|PubMed:35076286}. Note=Translocated into the nucleus upon
CC tyrosine phosphorylation and dimerization, in response to IFN-gamma and
CC signaling by activated FGFR1, FGFR2, FGFR3 or FGFR4. Monomethylation at
CC Lys-525 is required for phosphorylation at Tyr-701 and translocation
CC into the nucleus. Translocates into the nucleus in response to
CC interferon-beta stimulation. {ECO:0000250|UniProtKB:P42224}.
CC -!- PTM: Phosphorylated on tyrosine and serine residues in response to a
CC variety of cytokines/growth hormones including IFN-alpha, IFN-gamma,
CC PDGF and EGF. Activated KIT promotes phosphorylation on tyrosine
CC residues and subsequent translocation to the nucleus. Upon EGF
CC stimulation, phosphorylation on Tyr-701 (lacking in beta form) by JAK1,
CC JAK2 or TYK2 promotes dimerization and subsequent translocation to the
CC nucleus. Growth hormone (GH) activates STAT1 signaling only via JAK2.
CC Tyrosine phosphorylated in response to constitutively activated FGFR1,
CC FGFR2, FGFR3 and FGFR4. Phosphorylation on Ser-727 by several kinases
CC including MAPK14, ERK1/2 and CAMKII on IFN-gamma stimulation, regulates
CC STAT1 transcriptional activity. Phosphorylation on Ser-727 promotes
CC sumoylation though increasing interaction with PIAS. Phosphorylation on
CC Ser-727 by PRKCD induces apoptosis in response to DNA-damaging agents.
CC Phosphorylated on tyrosine residues when PTK2/FAK1 is activated; most
CC likely this is catalyzed by a SRC family kinase. Dephosphorylation on
CC tyrosine residues by PTPN2 negatively regulates interferon-mediated
CC signaling. Upon viral infection or IFN induction, phosphorylation on
CC Ser-708 occurs much later than phosphorylation on Tyr-701 and is
CC required for the binding of ISGF3 on the ISREs of a subset of IFN-
CC stimulated genes IKBKE-dependent. Phosphorylation at Tyr-701 and Ser-
CC 708 are mutually exclusive, phosphorylation at Ser-708 requires
CC previous dephosphorylation of Tyr-701. {ECO:0000250|UniProtKB:P42224}.
CC -!- PTM: Sumoylated with SUMO1, SUMO2 and SUMO3. Sumoylation is enhanced by
CC IFN-gamma-induced phosphorylation on Ser-727, and by interaction with
CC PIAS proteins. Enhances the transactivation activity.
CC {ECO:0000250|UniProtKB:P42224}.
CC -!- PTM: ISGylated. {ECO:0000250|UniProtKB:P42224}.
CC -!- PTM: Mono-ADP-ribosylated at Glu-657 and Glu-705 by PARP14; ADP-
CC riboslyation prevents phosphorylation at Tyr-701. However, the role of
CC ADP-ribosylation in the prevention of phosphorylation has been called
CC into question and the lack of phosphorylation may be due to sumoylation
CC of Lys-703. {ECO:0000250|UniProtKB:P42224}.
CC -!- PTM: Monomethylated at Lys-525 by SETD2; monomethylation is necessary
CC for phosphorylation at Tyr-701, translocation into the nucleus and
CC activation of the antiviral defense. {ECO:0000250|UniProtKB:P42224}.
CC -!- SIMILARITY: Belongs to the transcription factor STAT family.
CC {ECO:0000305}.
CC -!- CAUTION: Has been shown to be mono-ADP-ribosylated at Glu-657 and Glu-
CC 705 by PARP14 which prevents phosphorylation at Tyr-701 (By
CC similarity). However, the role of ADP-ribosylation in the prevention of
CC phosphorylation has been called into question (By similarity). It has
CC been suggested that the lack of phosphorylation may be due to
CC sumoylation of Lys-703 (By similarity). {ECO:0000250|UniProtKB:P42224}.
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DR EMBL; AB116564; BAD06318.1; -; mRNA.
DR RefSeq; NP_998934.1; NM_213769.1.
DR AlphaFoldDB; Q764M5; -.
DR SMR; Q764M5; -.
DR STRING; 9823.ENSSSCP00000017010; -.
DR iPTMnet; Q764M5; -.
DR PaxDb; Q764M5; -.
DR PeptideAtlas; Q764M5; -.
DR PRIDE; Q764M5; -.
DR GeneID; 396655; -.
DR KEGG; ssc:396655; -.
DR CTD; 6772; -.
DR eggNOG; KOG3667; Eukaryota.
DR InParanoid; Q764M5; -.
DR OrthoDB; 327469at2759; -.
DR Proteomes; UP000008227; Unplaced.
DR Proteomes; UP000314985; Unplaced.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005730; C:nucleolus; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISS:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR GO; GO:0000979; F:RNA polymerase II core promoter sequence-specific DNA binding; ISS:UniProtKB.
DR GO; GO:0006919; P:activation of cysteine-type endopeptidase activity involved in apoptotic process; ISS:UniProtKB.
DR GO; GO:0008015; P:blood circulation; ISS:UniProtKB.
DR GO; GO:0032869; P:cellular response to insulin stimulus; ISS:UniProtKB.
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:0060333; P:interferon-gamma-mediated signaling pathway; ISS:UniProtKB.
DR GO; GO:0010742; P:macrophage derived foam cell differentiation; ISS:UniProtKB.
DR GO; GO:0072162; P:metanephric mesenchymal cell differentiation; ISS:UniProtKB.
DR GO; GO:0072136; P:metanephric mesenchymal cell proliferation involved in metanephros development; ISS:UniProtKB.
DR GO; GO:0016525; P:negative regulation of angiogenesis; ISS:UniProtKB.
DR GO; GO:0001937; P:negative regulation of endothelial cell proliferation; ISS:UniProtKB.
DR GO; GO:0043124; P:negative regulation of I-kappaB kinase/NF-kappaB signaling; ISS:UniProtKB.
DR GO; GO:0072308; P:negative regulation of metanephric nephron tubule epithelial cell differentiation; ISS:UniProtKB.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; ISS:UniProtKB.
DR GO; GO:0045648; P:positive regulation of erythrocyte differentiation; ISS:UniProtKB.
DR GO; GO:0032727; P:positive regulation of interferon-alpha production; ISS:UniProtKB.
DR GO; GO:0048661; P:positive regulation of smooth muscle cell proliferation; ISS:UniProtKB.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISS:UniProtKB.
DR GO; GO:0007259; P:receptor signaling pathway via JAK-STAT; ISS:UniProtKB.
DR GO; GO:0042127; P:regulation of cell population proliferation; IBA:GO_Central.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0051591; P:response to cAMP; ISS:UniProtKB.
DR GO; GO:0034097; P:response to cytokine; ISS:UniProtKB.
DR GO; GO:0007584; P:response to nutrient; ISS:UniProtKB.
DR GO; GO:0043434; P:response to peptide hormone; ISS:UniProtKB.
DR GO; GO:0033209; P:tumor necrosis factor-mediated signaling pathway; ISS:UniProtKB.
DR GO; GO:0060337; P:type I interferon signaling pathway; ISS:UniProtKB.
DR CDD; cd10372; SH2_STAT1; 1.
DR Gene3D; 1.10.532.10; -; 1.
DR Gene3D; 2.60.40.630; -; 1.
DR Gene3D; 3.30.505.10; -; 1.
DR Gene3D; 6.10.250.3310; -; 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; IPR038295; STAT1_C_sf.
DR InterPro; IPR035859; STAT1_SH2.
DR InterPro; IPR022752; STAT1_TAZ2-bd_C.
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; PF12162; STAT1_TAZ2bind; 1.
DR Pfam; PF01017; STAT_alpha; 1.
DR Pfam; PF02864; STAT_bind; 1.
DR Pfam; PF02865; STAT_int; 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 Acetylation; Activator; ADP-ribosylation; Coiled coil; Cytoplasm;
KW DNA-binding; Host-virus interaction; Isopeptide bond; Methylation; Nucleus;
KW Phosphoprotein; Reference proteome; SH2 domain; Transcription;
KW Transcription regulation; Ubl conjugation.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:P42224"
FT CHAIN 2..757
FT /note="Signal transducer and activator of transcription 1"
FT /id="PRO_0000182412"
FT DOMAIN 573..670
FT /note="SH2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00191"
FT COILED 136..317
FT /evidence="ECO:0000250"
FT MOD_RES 2
FT /note="N-acetylserine"
FT /evidence="ECO:0000250|UniProtKB:P42224"
FT MOD_RES 114
FT /note="N6-methyllysine"
FT /evidence="ECO:0000250|UniProtKB:P42224"
FT MOD_RES 175
FT /note="N6-methyllysine"
FT /evidence="ECO:0000250|UniProtKB:P42224"
FT MOD_RES 296
FT /note="N6-methyllysine"
FT /evidence="ECO:0000250|UniProtKB:P42224"
FT MOD_RES 366
FT /note="N6-methyllysine"
FT /evidence="ECO:0000250|UniProtKB:P42224"
FT MOD_RES 525
FT /note="N6-methyllysine"
FT /evidence="ECO:0000250|UniProtKB:P42224"
FT MOD_RES 637
FT /note="N6-methyllysine"
FT /evidence="ECO:0000250|UniProtKB:P42224"
FT MOD_RES 657
FT /note="ADP-ribosyl glutamic acid"
FT /evidence="ECO:0000250|UniProtKB:P42224"
FT MOD_RES 665
FT /note="N6-methyllysine"
FT /evidence="ECO:0000250|UniProtKB:P42224"
FT MOD_RES 701
FT /note="Phosphotyrosine; by JAK1, JAK2 or TYK2"
FT /evidence="ECO:0000250|UniProtKB:P42224"
FT MOD_RES 705
FT /note="ADP-ribosyl glutamic acid"
FT /evidence="ECO:0000250|UniProtKB:P42224"
FT MOD_RES 708
FT /note="Phosphoserine; by IKKE"
FT /evidence="ECO:0000250|UniProtKB:P42224"
FT MOD_RES 727
FT /note="Phosphoserine; by MAPK14"
FT /evidence="ECO:0000250|UniProtKB:P42224"
FT CROSSLNK 703
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO); alternate"
FT /evidence="ECO:0000250"
FT CROSSLNK 703
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO1); alternate"
FT /evidence="ECO:0000250|UniProtKB:P42224"
FT CROSSLNK 703
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2); alternate"
FT /evidence="ECO:0000250|UniProtKB:P42224"
SQ SEQUENCE 757 AA; 88167 MW; B6093218F2F6A029 CRC64;
MSQWYELQQL DSKFLEQVHQ LYDDSFPMEI RQYLAQWLEN QDWEHAANDV SFATIRFHDL
LSQLDDQYSR FSLENNFLLQ HNIRKSKRNL QDNFQEDPIQ MSMIICNCLK EERKILENAQ
RFNQTQSGNI QSTVMLDKHK ELDSKVRNVK DKVMCIEHEI KTLEDLQDEY DFKCKTLQNR
EHDTNGVAKN DQKQEQMLLQ KMYLMLDNKR KEVVHKIIEL LNVTELTQKA LINDELVEWK
RRQQSACIGG PPNACLDQLQ NWFTIVAESL QQVRQQLKKL EELEQKYTYE HDPITKNKQA
LWDRTFSLFQ QLIQSSFVVE RQPCMPTHPQ RPLVLKTGVQ FTVKLRLLVK LQKLNYNLKV
KVLFDKDVSE RNTVKGFRKF NILGTHTKVM NMEESTNGSL AAEFRHLQLK EQKNAGARTN
EGPLIVTEEL HSLSFETQLC QPGLVIDLET TSLPVVVISN VSQLPSGWAS ILWYNMLVAE
PRNLSFFLNP PCARWSQLSE VLSWQFSSVT KRGLNVDQLN MLGEKLLGPT AGPDGLIPWT
RFCKENINDK NFPFWLWIES ILELIKKHLL SLWNDGCIVG FISKERERAL LKDQQPGTFL
LRFSESCREG AITFTWVERS QNGGEPYFHA VEPYTKKELS AVTFPDIIRN YKVMAAENIP
ENPLKYLYPN IDKDHAFGKY YSRPKEAPEP MELDGPKGTG YIKTELISVS EVHPSRLQTT
DNLLPMSPEE FDEVSRMVGP VEFDVTWNKF SGTMNLD
