ID STAT3_BOVIN Reviewed; 770 AA. AC P61635; DT 07-JUN-2004, integrated into UniProtKB/Swiss-Prot. DT 07-JUN-2004, sequence version 1. DT 27-MAR-2024, entry version 150. DE RecName: Full=Signal transducer and activator of transcription 3; GN Name=STAT3; OS Bos taurus (Bovine). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae; OC Bovinae; Bos. OX NCBI_TaxID=9913; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Mammary gland; RA Seyfert H.M., Wheeler T.T., Moolenaar A., Pitra C.; RT "The STAT5B-encoding gene was flipped across the STAT3/STAT5A-locus during RT ruminant evolution."; RL Submitted (JAN-2004) to the EMBL/GenBank/DDBJ databases. 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): acetylation promotes its transcription activity and cell CC differentiation while deacetylation and oxidation of lysine residues by CC LOXL3 inhibits differentiation (By similarity). Involved in cell cycle CC regulation by inducing the expression of key genes for the progression CC from G1 to S phase, such as CCND1 (By similarity). Mediates the effects CC of LEP on melanocortin production, body energy homeostasis and CC lactation. May play an apoptotic role by transctivating BIRC5 CC expression under LEP activation (By similarity). Cytoplasmic STAT3 CC represses macroautophagy by inhibiting EIF2AK2/PKR activity (By CC similarity). Plays a crucial role in basal beta cell functions, such as CC regulation of insulin secretion. Following JAK/STAT signaling CC activation and as part of a complex with NFATC3 and NFATC4, binds to CC the alpha-beta E4 promoter region of CRYAB and activates transcription CC in cardiomyocytes (By similarity). Plays an important role in host CC defense in methicillin-resistant S.aureus lung infection by regulating CC the expression of the 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). Component of a promoter-binding complex CC composed of STAT3, NFATC3 and NFATC4; complex formation is enhanced by CC calcineurin (By similarity). Interacts with IL31RA, NCOA1, PELP1, CC SIPAR, SOCS7, STATIP1 and TMF1. Interacts with IL23R in presence of CC IL23. Interacts (via SH2 domain) with NLK. Interacts with ARL2BP; the CC interaction is enhanced by LIF and JAK1 expression (By similarity). CC Interacts with KPNA4 and KPNA5; KPNA4 may be the primary mediator of CC nuclear import (By similarity). Interacts with CAV2; the interaction is CC increased on insulin-induced tyrosine phosphorylation of CAV2 and leads CC to STAT3 activation (By similarity). Interacts with ARL2BP; interaction CC is enhanced with ARL2. Interacts with NEK6 (By similarity). Binds to CC CDK9 when activated and nuclear. Interacts with BMX. Interacts with CC ZIPK/DAPK3. Interacts with PIAS3; the interaction occurs on stimulation CC by IL6, CNTF or OSM and inhibits the DNA binding activity of STAT3. In CC prostate cancer cells, interacts with PRKCE and promotes DNA binding CC activity of STAT3 (By similarity). Interacts with STMN3, antagonizing CC its microtubule-destabilizing activity (By similarity). Interacts with CC the 'Lys-129' acetylated form of BIRC5/survivin. Interacts with FER. CC Interacts (via SH2 domain) with EIF2AK2/PKR (via the kinase catalytic CC domain) (By similarity). Interacts with FGFR4 (By similarity). CC Interacts with INPP5F; the interaction is independent of STAT3 Tyr-705 CC phosphorylation status (By similarity). Interacts with OCAD1 (By CC similarity). Interacts (unphosphorylated or phosphorylated at Ser-727) CC with PHB1 (By similarity). Interacts and may form heterodimers with CC NHLH1 (By similarity). Found in a complex with SLC39A6, SLC39A10 and CC with the 'Ser-727' phosphorylated form of STAT3 throughout mitosis (By CC similarity). Interacts (when acetylated) with EP300 (via bromo domain); CC interaction takes place following STAT3 acetylation by EP300 and CC promotes enhanceosome assembly (By similarity). Interacts (when CC acetylated) with BRD2 (via bromo domain); interaction promotes STAT3 CC recruitment to chromatin and T-helper Th17 cell differentiation (By CC similarity). {ECO:0000250|UniProtKB:P40763, CC ECO:0000250|UniProtKB:P42227, ECO:0000250|UniProtKB:P52631}. CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Nucleus {ECO:0000250}. CC Note=Shuttles between the nucleus and the cytoplasm. Translocated into CC the nucleus upon tyrosine phosphorylation and dimerization, in response CC to signaling by activated FGFR1, FGFR2, FGFR3 or FGFR4. Constitutive CC nuclear presence is independent of tyrosine phosphorylation. CC Predominantly present in the cytoplasm without stimuli. Upon leukemia CC inhibitory factor (LIF) stimulation, accumulates in the nucleus (By CC similarity). The complex composed of BART and ARL2 plays an important CC role in the nuclear translocation and retention of STAT3. Translocates CC to the nucleus in the presence of EDN1 (By similarity). {ECO:0000250, CC ECO:0000250|UniProtKB:P52631}. CC -!- PTM: Activated through tyrosine phosphorylation by BMX. Tyrosine CC phosphorylated in response to IL-6, IL-11, CNTF, LIF, CSF-1, EGF, PDGF, CC IFN-alpha and OSM. Tyrosine phosphorylated in response to CC constitutively activated FGFR1, FGFR2, FGFR3 and FGFR4. Phosphorylated CC on serine upon DNA damage, probably by ATM or ATR. Serine CC phosphorylation is important for the formation of stable DNA-binding CC STAT3 homodimers and maximal transcriptional activity. ARL2BP may CC participate in keeping the phosphorylated state of STAT3 within the CC nucleus. Tyrosine phosphorylated upon stimulation with EGF. Upon LPS CC challenge, phosphorylated within the nucleus by IRAK1. Phosphorylated CC on Ser-727 by RPS6KA5 (By similarity). Dephosphorylation on tyrosine CC residues by PTPN2 negatively regulates IL6/interleukin-6 signaling (By CC similarity). Phosphorylation at Tyr-705 by FER, isoform M2 of PKM CC (PKM2) or PTK6 leads to an increase of its transcriptional activity (By CC similarity). Phosphorylation at Tyr-705 is increased in the presence of CC calcineurin (By similarity). {ECO:0000250, CC ECO:0000250|UniProtKB:P42227}. CC -!- PTM: Acetylated on lysine residues by EP300/p300, promoting its CC activation (By similarity). Acetylation at Lys-49 and Lys-87 by CC EP300/p300 promotes its activation (By similarity). Acetylation at Lys- CC 87 by EP300/p300 promotes its association with BRD2 and recruitment to CC chromatin (By similarity). Deacetylated at Lys-49 and Lys-87 by HDAC1 CC (By similarity). Acetylation at Lys-685 by EP300/p300 promotes its CC homodimerization and activation (By similarity). Deacetylated at Lys- CC 685 by HDAC3 (By similarity). Acetylated on lysine residues by CREBBP CC (By similarity). Deacetylation by LOXL3 leads to disrupt STAT3 CC dimerization and inhibit STAT3 transcription activity (By similarity). CC Oxidation of lysine residues to allysine on STAT3 preferentially takes CC place on lysine residues that are acetylated (By similarity). 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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AJ620655; CAF06182.1; -; mRNA. DR RefSeq; NP_001012689.2; NM_001012671.2. DR AlphaFoldDB; P61635; -. DR SMR; P61635; -. DR CORUM; P61635; -. DR STRING; 9913.ENSBTAP00000028687; -. DR iPTMnet; P61635; -. DR PaxDb; 9913-ENSBTAP00000028687; -. DR GeneID; 508541; -. DR KEGG; bta:508541; -. DR CTD; 6774; -. DR eggNOG; KOG3667; Eukaryota. DR InParanoid; P61635; -. DR Proteomes; UP000009136; Unplaced. 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:0000976; F:transcription cis-regulatory region binding; ISS:UniProtKB. DR GO; GO:0048708; P:astrocyte differentiation; ISS:UniProtKB. DR GO; GO:0044320; P:cellular response to leptin stimulus; ISS:UniProtKB. 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:0045893; P:positive regulation of DNA-templated transcription; 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:0045944; P:positive regulation of transcription by RNA polymerase II; 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:0006355; P:regulation of DNA-templated transcription; ISS:UniProtKB. 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: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 CDD; cd16853; STAT3_CCD; 1. DR CDD; cd16847; STAT3_DBD; 1. DR Gene3D; 1.10.238.10; EF-hand; 1. DR Gene3D; 3.30.505.10; SH2 domain; 1. DR Gene3D; 1.20.1050.20; STAT transcription factor, all-alpha domain; 1. DR Gene3D; 2.60.40.630; STAT transcription factor, DNA-binding domain; 1. DR Gene3D; 1.10.532.10; STAT transcription factor, N-terminal domain; 1. DR InterPro; IPR008967; p53-like_TF_DNA-bd_sf. DR InterPro; IPR000980; SH2. DR InterPro; IPR036860; SH2_dom_sf. DR InterPro; IPR001217; STAT. DR InterPro; IPR035855; STAT3_SH2. DR InterPro; IPR048988; STAT_linker. 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; SIGNAL TRANSDUCER AND ACTIVATOR OF TRANSCRIPTION; 1. DR PANTHER; PTHR11801:SF2; SIGNAL TRANSDUCER AND ACTIVATOR OF TRANSCRIPTION 3; 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 Pfam; PF21354; STAT_linker; 1. DR SMART; SM00964; STAT_int; 1. DR SUPFAM; SSF49417; p53-like transcription factors; 1. DR SUPFAM; SSF55550; SH2 domain; 1. DR SUPFAM; SSF47655; STAT; 1. DR SUPFAM; SSF48092; Transcription factor STAT-4 N-domain; 1. DR PROSITE; PS50001; SH2; 1. PE 2: Evidence at transcript 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_0000182416" 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 49 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:P40763" FT MOD_RES 87 FT /note="N6-acetyllysine" 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; 87975 MW; 9CEB147C73E83274 CRC64; MAQWNQLQQL DTRYLEQLHQ LYSDSFPMEL RQLLAPWIES QDWAYAASKE SHATLVFHNL LGEIDQQYSR FLQESNVLYQ HNLRRIKQFL QSRYLEKPME IARIVARCLW EESRLLQTAA TAAQQGGQAN HPTAAVVTEK QQMLEQHLQD VRKRVQDLEQ KMKVVENLLD 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 SIEQLTTLAE KLLGPGVNYS GCQITWAKFC KENMAGKGFS FWVWLDNIID LVKKYILALW NEGYIMGFIS KERERAILST KPPGTCLLRF SESSKEGGVT FTWVEKDISG KTQIQSVEPY TKQQLNNMSF AEIIMGYKIM DATNILVSPL VYLYPDIPKE DAFGKYCRPE SQEHPEADPG SAAPYLKTKF ICVTPTTCSN TIDLPMSPRT LDSLMQFGNN GEAAEPSAGG QFESLTFDME LTSECATSPM //