STAT3_BOVIN
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 25-MAY-2022, entry version 142.
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): 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. Interacts with IL23R in presence of IL23.
CC 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). {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.
CC {ECO:0000250}.
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). Phosphorylation at Tyr-705 by
CC FER, isoform M2 of PKM (PKM2) or PTK6 leads to an increase of its
CC transcriptional activity (By similarity). Dephosphorylation on tyrosine
CC residues by PTPN2 negatively regulates IL6/interleukin-6 signaling (By
CC 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; 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; P61635; -.
DR PRIDE; P61635; -.
DR GeneID; 508541; -.
DR KEGG; bta:508541; -.
DR CTD; 6774; -.
DR eggNOG; KOG3667; Eukaryota.
DR InParanoid; P61635; -.
DR OrthoDB; 327469at2759; -.
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: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:0048708; P:astrocyte differentiation; ISS:UniProtKB.
DR GO; GO:0044320; P:cellular response to leptin stimulus; ISS:UniProtKB.
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:0051726; P:regulation of cell cycle; 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:0006355; P:regulation of transcription, DNA-templated; ISS:UniProtKB.
DR GO; GO:0044321; P:response to leptin; ISS:UniProtKB.
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 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 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
