STAT3_PIG
ID STAT3_PIG Reviewed; 770 AA.
AC Q19S50;
DT 02-SEP-2008, integrated into UniProtKB/Swiss-Prot.
DT 11-JUL-2006, sequence version 1.
DT 03-AUG-2022, entry version 134.
DE RecName: Full=Signal transducer and activator of transcription 3;
GN Name=STAT3;
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 [MRNA], PHOSPHORYLATION, SUBCELLULAR LOCATION, AND
RP TISSUE SPECIFICITY.
RC TISSUE=Skin;
RX PubMed=16940292; DOI=10.1530/rep.1.01055;
RA Wen L., Craig J., Dyce P.W., Li J.;
RT "Cloning of porcine signal transducer and activator of transcription 3 cDNA
RT and its expression in reproductive tissues.";
RL Reproduction 132:511-518(2006).
CC -!- FUNCTION: Signal transducer and transcription activator that mediates
CC cellular responses to interleukins, KITLG/SCF, LEP and other growth
CC factors. Once activated, recruits coactivators, such as NCOA1 or MED1,
CC to the promoter region of the target gene. May mediate cellular
CC responses to activated FGFR1, FGFR2, FGFR3 and FGFR4. Upon activation
CC of IL6ST/gp130 signaling by interleukin-6 (IL6), binds to the IL6-
CC responsive elements identified in the promoters of various acute-phase
CC protein genes. Activated by IL31 through IL31RA (By similarity). Acts
CC as a regulator of inflammatory response by regulating differentiation
CC of naive CD4(+) T-cells into T-helper Th17 or regulatory T-cells
CC (Treg): deacetylation and oxidation of lysine residues by LOXL3, leads
CC to disrupt STAT3 dimerization and inhibit its transcription activity
CC (By similarity). Involved in cell cycle regulation by inducing the
CC expression of key genes for the progression from G1 to S phase, such as
CC CCND1 (By similarity). Mediates the effects of LEP on melanocortin
CC production, body energy homeostasis and lactation. May play an
CC apoptotic role by transctivating BIRC5 expression under LEP activation
CC (By similarity). Cytoplasmic STAT3 represses macroautophagy by
CC inhibiting EIF2AK2/PKR activity (By similarity). Plays a crucial role
CC in basal beta cell functions, such as regulation of insulin secretion.
CC Plays an important role in host defense in methicillin-resistant
CC S.aureus lung infection by regulating the expression of the
CC antimicrobial lectin REG3G (By similarity).
CC {ECO:0000250|UniProtKB:P40763, ECO:0000250|UniProtKB:P42227}.
CC -!- SUBUNIT: Forms a homodimer or a heterodimer with a related family
CC member (at least STAT1). Interacts with IL31RA, NCOA1, PELP1, SIPAR,
CC SOCS7, STATIP1 and TMF1 (By similarity). Interacts with IL23R in
CC presence of IL23 (By similarity). Interacts (via SH2 domain) with NLK.
CC Interacts with ARL2BP; the interaction is enhanced by LIF and JAK1
CC expression (By similarity). Interacts with KPNA4 and KPNA5; KPNA4 may
CC be the primary mediator of nuclear import (By similarity). Interacts
CC with CAV2; the interaction is increased on insulin-induced tyrosine
CC phosphorylation of CAV2 and leads to STAT3 activation (By similarity).
CC Interacts with ARL2BP; interaction is enhanced with ARL2 (By
CC similarity). Interacts with NEK6 (By similarity). Binds to CDK9 when
CC activated and nuclear. Interacts with BMX. Interacts with ZIPK/DAPK3.
CC Interacts with PIAS3; the interaction occurs on stimulation by IL6,
CC CNTF or OSM and inhibits the DNA binding activity of STAT3. In prostate
CC cancer cells, interacts with PRKCE and promotes DNA binding activity of
CC STAT3 (By similarity). Interacts with STMN3, antagonizing its
CC microtubule-destabilizing activity (By similarity). Interacts with the
CC 'Lys-129' acetylated form of BIRC5/survivin. Interacts with FER.
CC Interacts (via SH2 domain) with EIF2AK2/PKR (via the kinase catalytic
CC domain). Interacts with INPP5F; the interaction is independent of STAT3
CC Tyr-705 phosphorylation status. Interacts with FGFR4 (By similarity).
CC Interacts with OCAD1 (By similarity). Interacts (unphosphorylated or
CC phosphorylated at Ser-727) with PHB1 (By similarity). Interacts and may
CC form heterodimers with NHLH1 (By similarity).
CC {ECO:0000250|UniProtKB:P40763, ECO:0000250|UniProtKB:P42227,
CC ECO:0000250|UniProtKB:P52631}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:16940292}. Nucleus
CC {ECO:0000269|PubMed:16940292}. Note=Shuttles between the nucleus and
CC the cytoplasm. Translocated into the nucleus upon tyrosine
CC phosphorylation and dimerization, in response to signaling by activated
CC FGFR1, FGFR2, FGFR3 or FGFR4. Constitutive nuclear presence is
CC independent of tyrosine phosphorylation. Predominantly present in the
CC cytoplasm without stimuli. Upon leukemia inhibitory factor (LIF)
CC stimulation, accumulates in the nucleus. The complex composed of BART
CC and ARL2 plays an important role in the nuclear translocation and
CC retention of STAT3 (By similarity). {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Detected in lung, heart, oviduct, ovary, uterus and
CC kidney (at protein level). Detected in ovary, oviduct, and at lower
CC levels in uterus and lung. {ECO:0000269|PubMed:16940292}.
CC -!- PTM: Activated through tyrosine phosphorylation by BMX. Tyrosine
CC phosphorylated in response to IL6, IL11, CNTF, LIF, KITLG/SCF, CSF1,
CC EGF, PDGF, IFN-alpha and OSM. Activated KIT promotes phosphorylation on
CC tyrosine residues and subsequent translocation to the nucleus. Tyrosine
CC phosphorylated in response to constitutively activated FGFR1, FGFR2,
CC FGFR3 and FGFR4. Phosphorylated on serine upon DNA damage, probably by
CC ATM or ATR. Serine phosphorylation is important for the formation of
CC stable DNA-binding STAT3 homodimers and maximal transcriptional
CC activity. ARL2BP may participate in keeping the phosphorylated state of
CC STAT3 within the nucleus. Tyrosine phosphorylated upon stimulation with
CC EGF. Upon LPS challenge, phosphorylated within the nucleus by IRAK1.
CC Phosphorylated on Ser-727 by RPS6KA5 (By similarity). Phosphorylation
CC at Tyr-705 by FER, isoform M2 of PKM (PKM2) or PTK6 leads to an
CC increase of its transcriptional activity (By similarity).
CC Dephosphorylation on tyrosine residues by PTPN2 negatively regulates
CC IL6/interleukin-6 signaling (By similarity). {ECO:0000250}.
CC -!- PTM: Acetylated on lysine residues by CREBBP. Deacetylation by LOXL3
CC leads to disrupt STAT3 dimerization and inhibit STAT3 transcription
CC activity. Oxidation of lysine residues to allysine on STAT3
CC preferentially takes place on lysine residues that are acetylated.
CC {ECO:0000250|UniProtKB:P40763}.
CC -!- PTM: Some lysine residues are oxidized to allysine by LOXL3, leading to
CC disrupt STAT3 dimerization and inhibit STAT3 transcription activity.
CC Oxidation of lysine residues to allysine on STAT3 preferentially takes
CC place on lysine residues that are acetylated.
CC {ECO:0000250|UniProtKB:P40763}.
CC -!- MISCELLANEOUS: Involved in the gp130-mediated signaling pathway.
CC -!- SIMILARITY: Belongs to the transcription factor STAT family.
CC {ECO:0000305}.
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DR EMBL; DQ470570; ABF21150.1; -; mRNA.
DR RefSeq; NP_001038045.1; NM_001044580.1.
DR AlphaFoldDB; Q19S50; -.
DR SMR; Q19S50; -.
DR STRING; 9823.ENSSSCP00000018439; -.
DR iPTMnet; Q19S50; -.
DR PaxDb; Q19S50; -.
DR PeptideAtlas; Q19S50; -.
DR PRIDE; Q19S50; -.
DR Ensembl; ENSSSCT00015084631; ENSSSCP00015034340; ENSSSCG00015062720.
DR Ensembl; ENSSSCT00030095248; ENSSSCP00030043893; ENSSSCG00030068070.
DR Ensembl; ENSSSCT00040019448; ENSSSCP00040008054; ENSSSCG00040014380.
DR Ensembl; ENSSSCT00040019994; ENSSSCP00040008333; ENSSSCG00040014380.
DR Ensembl; ENSSSCT00045066831; ENSSSCP00045047441; ENSSSCG00045038505.
DR Ensembl; ENSSSCT00060070708; ENSSSCP00060030502; ENSSSCG00060051919.
DR Ensembl; ENSSSCT00060070768; ENSSSCP00060030532; ENSSSCG00060051919.
DR Ensembl; ENSSSCT00060070776; ENSSSCP00060030536; ENSSSCG00060051919.
DR Ensembl; ENSSSCT00070027546; ENSSSCP00070022915; ENSSSCG00070014017.
DR Ensembl; ENSSSCT00070027606; ENSSSCP00070022971; ENSSSCG00070014017.
DR GeneID; 733648; -.
DR KEGG; ssc:733648; -.
DR CTD; 6774; -.
DR eggNOG; KOG3667; Eukaryota.
DR HOGENOM; CLU_014189_3_0_1; -.
DR InParanoid; Q19S50; -.
DR OrthoDB; 327469at2759; -.
DR TreeFam; TF318648; -.
DR Reactome; R-SSC-1059683; Interleukin-6 signaling.
DR Reactome; R-SSC-1266695; Interleukin-7 signaling.
DR Reactome; R-SSC-1433557; Signaling by SCF-KIT.
DR Reactome; R-SSC-186763; Downstream signal transduction.
DR Reactome; R-SSC-201556; Signaling by ALK.
DR Reactome; R-SSC-6783783; Interleukin-10 signaling.
DR Reactome; R-SSC-6785807; Interleukin-4 and Interleukin-13 signaling.
DR Reactome; R-SSC-8849474; PTK6 Activates STAT3.
DR Reactome; R-SSC-8854691; Interleukin-20 family signaling.
DR Reactome; R-SSC-8983432; Interleukin-15 signaling.
DR Reactome; R-SSC-8985947; Interleukin-9 signaling.
DR Reactome; R-SSC-9008059; Interleukin-37 signaling.
DR Reactome; R-SSC-9020933; Interleukin-23 signaling.
DR Reactome; R-SSC-9020956; Interleukin-27 signaling.
DR Reactome; R-SSC-9020958; Interleukin-21 signaling.
DR Reactome; R-SSC-9701898; STAT3 nuclear events downstream of ALK signaling.
DR Proteomes; UP000008227; Unplaced.
DR Proteomes; UP000314985; Chromosome 12.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0031490; F:chromatin DNA binding; ISS:UniProtKB.
DR GO; GO:0003677; F:DNA binding; ISS:UniProtKB.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; ISS:UniProtKB.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IBA:GO_Central.
DR GO; GO:0046983; F:protein dimerization activity; ISS:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB.
DR GO; GO:0019901; F:protein kinase binding; ISS:UniProtKB.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR GO; GO:0048708; P:astrocyte differentiation; ISS:UniProtKB.
DR GO; GO:0044320; P:cellular response to leptin 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:0042755; P:eating behavior; ISS:UniProtKB.
DR GO; GO:0097009; P:energy homeostasis; ISS:UniProtKB.
DR GO; GO:0001754; P:eye photoreceptor cell differentiation; ISS:UniProtKB.
DR GO; GO:0042593; P:glucose homeostasis; ISS:UniProtKB.
DR GO; GO:0060397; P:growth hormone receptor signaling pathway via JAK-STAT; ISS:UniProtKB.
DR GO; GO:0006954; P:inflammatory response; ISS:UniProtKB.
DR GO; GO:0070102; P:interleukin-6-mediated signaling pathway; ISS:UniProtKB.
DR GO; GO:0033210; P:leptin-mediated signaling pathway; ISS:UniProtKB.
DR GO; GO:0016310; P:phosphorylation; ISS:UniProtKB.
DR GO; GO:0045648; P:positive regulation of erythrocyte differentiation; ISS:UniProtKB.
DR GO; GO:0045747; P:positive regulation of Notch signaling pathway; ISS:UniProtKB.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISS:UniProtKB.
DR GO; GO:0006606; P:protein import into nucleus; ISS:UniProtKB.
DR GO; GO:0060019; P:radial glial cell differentiation; ISS:UniProtKB.
DR GO; GO:0007259; P:receptor signaling pathway via JAK-STAT; IBA:GO_Central.
DR GO; GO:0051726; P:regulation of cell cycle; ISS:UniProtKB.
DR GO; GO:0042127; P:regulation of cell population proliferation; IBA:GO_Central.
DR GO; GO:0060259; P:regulation of feeding behavior; ISS:UniProtKB.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; ISS:UniProtKB.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; ISS:UniProtKB.
DR GO; GO:0044321; P:response to leptin; ISS:UniProtKB.
DR GO; GO:0043434; P:response to peptide hormone; IBA:GO_Central.
DR GO; GO:0019953; P:sexual reproduction; ISS:UniProtKB.
DR GO; GO:0072540; P:T-helper 17 cell lineage commitment; ISS:UniProtKB.
DR GO; GO:0072538; P:T-helper 17 type immune response; ISS:UniProtKB.
DR GO; GO:0001659; P:temperature homeostasis; ISS:UniProtKB.
DR CDD; cd10374; SH2_STAT3; 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; IPR035855; STAT3_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; 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; Cytoplasm; DNA-binding; Nucleus; Phosphoprotein;
KW Reference proteome; SH2 domain; Transcription; Transcription regulation.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:P40763"
FT CHAIN 2..770
FT /note="Signal transducer and activator of transcription 3"
FT /id="PRO_0000347216"
FT DOMAIN 580..670
FT /note="SH2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00191"
FT MOTIF 150..162
FT /note="Essential for nuclear import"
FT /evidence="ECO:0000250"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000250|UniProtKB:P40763"
FT MOD_RES 601
FT /note="Allysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P40763"
FT MOD_RES 601
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P40763"
FT MOD_RES 615
FT /note="Allysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P40763"
FT MOD_RES 615
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P40763"
FT MOD_RES 631
FT /note="Allysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P40763"
FT MOD_RES 631
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P40763"
FT MOD_RES 685
FT /note="Allysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P40763"
FT MOD_RES 685
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P40763"
FT MOD_RES 705
FT /note="Phosphotyrosine; by FER and PTK6"
FT /evidence="ECO:0000250|UniProtKB:P40763"
FT MOD_RES 707
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P40763"
FT MOD_RES 714
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P40763"
FT MOD_RES 727
FT /note="Phosphoserine; by DYRK2, NLK, NEK6, IRAK1, RPS6KA5,
FT ZIPK/DAPK3 and PKC/PRKCE"
FT /evidence="ECO:0000250|UniProtKB:P40763"
SQ SEQUENCE 770 AA; 88067 MW; 03E26322108D5478 CRC64;
MAQWNQLQQL DTRYLEQLHQ LYSDSFPMEL RQFLAPWIES QDWAYAASKE SHATLVFHNL
LGEIDQQYSR FLQESNVLYQ HNLRRIKQFL QSRYLEKPME IARIVARCLW EESRLLQTAA
TAAQQGGQAN HPTAAVVTEK QQMLEQHLQD VRKRVQDLEQ KMKVVENLQD DFDFNYKTLK
SQGDMQDLNG NNQSVTRQKM QQLEQMLTAL DQMRRSIVSE LAGLLSAMEY VQKTLTDEEL
ADWKRRQQIA CIGGPPNICL DRLENWITSL AESQLQTRQQ IKKLEELQQK VSYKGDPIVQ
HRPMLEERIV ELFRNLMKSA FVVERQPCMP MHPDRPLVIK TGVQFTTKVR LLVKFPELNY
QLKIKVCIDK DSGDVAALRG SRKFNILGTN TKVMNMEESN NGSLSAEFKH LTLREQRCGN
GGRANCDASL IVTEELHLIT FETEVYHQGL KIDLETHSLP VVVISNICQM PNAWASILWY
NMLTNNPKNV NFFTKPPIGT WDQVAEVLSW QFSSTTKRGL SIEQLSTLAE KLLGPGVNYS
GCQITWAKFC KENMAGKGFS FWVWLDNIID LVKKYILALW NEGYIMGFIS KERERAILST
KPPGTFLLRF SESSKEGGVT FTWVEKDISG KTQIQSVEPY TKQQLNNMSF AEIIMGYKIM
DATNILVSPL VYLYPDIPKE EAFGKYCRPE SQEHPEADPG SAAPYLKTKF ICVTPTTCSN
TIDLPMSPRT LDSLMQFGNN GEGAEPSAGG QFESLTFDME LNSECATSPM
