FUNCTION: Transcription factor that binds to the interleukin-6 (IL-6)-responsive elements identified in the promoters of various acute-phase protein genes. Activated by IL31 through IL31RA.
SUBUNIT STRUCTURE: Forms a homodimer or a heterodimer with a related family member (at least STAT1). Interacts with NCOA1, PELP1, SOCS7 and STATIP1. Interacts with HCV core protein. Interacts with IL23R in presence of IL23. Interacts with IL31RA. Interacts with SIPAR. Interacts (via SH2 domain) with NLK By similarity. Interacts with KPNA4 and KPNA5; KPNA4 may be the primary mediator of nuclear import By similarity. Interacts with TMF1.
SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Note: Shuttles between the nucleus and the cytoplasm. Constitutive nuclear presence is independent of tyrosine phosphorylation.
TISSUE SPECIFICITY: Heart, brain, placenta, lung, liver, skeletal muscle, kidney and pancreas.
PTM: Tyrosine phosphorylated in response to IL-6, IL-11, CNTF, LIF, CSF-1, EGF, PDGF, IFN-alpha and OSM. Phosphorylated on serine upon DNA damage, probably by ATM or ATR. Serine phosphorylation is important for the formation of stable DNA-binding STAT3 homodimers and maximal transcriptional activity.
INVOLVEMENT IN DISEASE: Defects in STAT3 are the cause of hyperimmunoglobulin E recurrent infection syndrome autosomal dominant (AD-HIES) [MIM:147060]; also known as hyper-IgE syndrome or Job syndrome. AD-HIES is a rare disorder of immunity and connective tissue characterized by immunodeficiency, chronic eczema, recurrent Staphylococcal infections, increased serum IgE, eosinophilia, distinctive coarse facial appearance, abnormal dentition, hyperextensibility of the joints, and bone fractures.
MISCELLANEOUS: Involved in the gp130-mediated signaling pathway.
SEQUENCE SIMILARITIES: Belongs to the transcription factor STAT family.
Contains 1 SH2 domain.