Protein: Signal transducer and activator of transcription 3 (Acute-phase response factor) (P40763)
Organism: Homo sapiens (Human)
Function: Signal transducer and transcription activator that mediates cellular responses to interleukins, KITLG/SCF, LEP and other growth factors. Once activated, recruits coactivators, such as NCOA1 or MED1, to the promoter region of the target gene. May mediate cellular responses to activated FGFR1, FGFR2, FGFR3 and FGFR4. Upon activation of IL6ST/gp130 signaling by interleukin-6 (IL6), binds to the IL6-responsive elements identified in the promoters of various acute-phase protein genes. Activated by IL31 through IL31RA. Acts as a regulator of inflammatory response by regulating differentiation of naive CD4(+) T-cells into T-helper Th17 or regulatory T-cells (Treg): deacetylation and oxidation of lysine residues by LOXL3, leads to disrupt STAT3 dimerization and inhibit its transcription activity. Involved in cell cycle regulation by inducing the expression of key genes for the progression from G1 to S phase, such as CCND1. Mediates the effects of LEP on melanocortin production, body energy homeostasis and lactation (By similarity). May play an apoptotic role by transctivating BIRC5 expression under LEP activation. Cytoplasmic STAT3 represses macroautophagy by inhibiting EIF2AK2/PKR activity. Plays a crucial role in basal beta cell functions, such as regulation of insulin secretion (By similarity).
Subcellular location: Cytoplasm {ECO:0000269|PubMed:15653507, ECO:0000269|PubMed:16285960, ECO:0000269|PubMed:28065600, ECO:0000269|PubMed:31899195}. Nucleus {ECO:0000269|PubMed:15653507, ECO:0000269|PubMed:16285960, ECO:0000269|PubMed:28065600, ECO:0000269|PubMed:29162862, ECO:0000269|PubMed:31899195}. Note=Shuttles between the nucleus and the cytoplasm (PubMed:29162862). Translocated into the nucleus upon tyrosine phosphorylation and dimerization, in response to signaling by activated FGFR1, FGFR2, FGFR3 or FGFR4 (PubMed:15653507, PubMed:16285960). Constitutive nuclear presence is independent of tyrosine phosphorylation. Predominantly present in the cytoplasm without stimuli. Upon leukemia inhibitory factor (LIF) stimulation, accumulates in the nucleus. The complex composed of BART and ARL2 plays an important role in the nuclear translocation and retention of STAT3. Identified in a complex with LYN and PAG1. Translocates to the nucleus in the presence of EDN1 (By similarity). {ECO:0000250|UniProtKB:P52631, ECO:0000269|PubMed:15653507, ECO:0000269|PubMed:16285960, ECO:0000269|PubMed:29162862}.
Interaction partners:
- Tyrosine-protein kinase JAK1
- Tyrosine-protein kinase JAK2
- Signal transducer and activator of transcription 1-alpha/beta
- E3 SUMO-protein ligase PIAS3
- Proto-oncogene tyrosine-protein kinase Src
- Histone acetyltransferase p300
- Epidermal growth factor receptor
- Signal transducer and activator of transcription 5B
- Tyrosine-protein kinase JAK3
- Non-receptor tyrosine-protein kinase TYK2
Sequence:
MAQWNQLQQLDTRYLEQLHQLYSDSFPMELRQFLAPWIESQDWAYAASKESHATLVFHNLLGEIDQQYSRFLQESNVLYQHNLRRIKQFLQSRYLEKPMEIARIVARCLWEESRLLQTAATAAQQGGQANHPTAAVVTEKQQMLEQHLQDVRKRVQDLEQKMKVVENLQDDFDFNYKTLKSQGDMQDLNGNNQSVTRQKMQQLEQMLTALDQMRRSIVSELAGLLSAMEYVQKTLTDEELADWKRRQQIACIGGPPNICLDRLENWITSLAESQLQTRQQIKKLEELQQKVSYKGDPIVQHRPMLEERIVELFRNLMKSAFVVERQPCMPMHPDRPLVIKTGVQFTTKVRLLVKFPELNYQLKIKVCIDKDSGDVAALRGSRKFNILGTNTKVMNMEESNNGSLSAEFKHLTLREQRCGNGGRANCDASLIVTEELHLITFETEVYHQGLKIDLETHSLPVVVISNICQMPNAWASILWYNMLTNNPKNVNFFTKPPIGTWDQVAEVLSWQFSSTTKRGLSIEQLTTLAEKLLGPGVNYSGCQITWAKFCKENMAGKGFSFWVWLDNIIDLVKKYILALWNEGYIMGFISKERERAILSTKPPGTFLLRFSESSKEGGVTFTWVEKDISGKTQIQSVEPYTKQQLNNMSFAEIIMGYKIMDATNILVSPLVYLYPDIPKEEAFGKYCRPESQEHPEADPGSAAPYLKTKFICVTPTTCSNTIDLPMSPRTLDSLMQFGNNGEGAEPSAGGQFESLTFDMELTSECATSPM