STAT3 (pY705) Antibody – Rabbit

The protein encoded by this gene is a member of the STAT protein family. In response to cytokines and growth factors, STAT family members are phosphorylated by the receptor associated kinases, and then form homo- or heterodimers that translocate to the cell nucleus where they act as transcription activators. This protein is activated through phosphorylation in response to various cytokines and growth factors including IFNs, EGF, IL5, IL6, HGF, LIF and BMP2. This protein mediates the expression of a variety of genes in response to cell stimuli, and thus plays a key role in many cellular processes such as cell growth and apoptosis. The small GTPase Rac1 has been shown to bind and regulate the activity of this protein. PIAS3 protein is a specific inhibitor of this protein. Three alternatively spliced transcript variants encoding distinct isoforms have been described. [provided by RefSeq]

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. Ref.10

Subunit structure: Forms a homodimer or a heterodimer with a related family member (at least STAT1). Interacts with IL31RA, NCOA1, PELP1, SIPAR, SOCS7, STATIP1 and TMF1. Interacts with HCV core protein. Interacts with IL23R in presence of IL23. Interacts (via SH2 domain) with NLK. Interacts with ARL2BP; the interaction is enhanced by LIF and JAK1 expression

By similarity. Interacts with KPNA4 and KPNA5; KPNA4 may be the primary mediator of nuclear import

By similarity. Interacts with CAV2; the interaction is increased on insulin-induced tyrosine phosphorylation of CAV2 and leads to STAT3 activation

By similarity. Interacts with ARL2BP; interaction is enhanced with ARL2. Ref.7 Ref.8 Ref.9 Ref.10 Ref.11 Ref.12 Ref.13 Ref.20

Subcellular location: Cytoplasm. Nucleus. Note: Shuttles between the nucleus and the cytoplasm. 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. Ref.16 Ref.20

Tissue specificity: Heart, brain, placenta, lung, liver, skeletal muscle, kidney and pancreas.

Post-translational modification: Tyrosine phosphorylated upon stimulation with EGF

By similarity. 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. ARL2BP may participate in keeping the phosphorylated state of STAT3 within the nucleus. Ref.6 Ref.14 Ref.15 Ref.17 Ref.18 Ref.19 Ref.20 Ref.21 Ref.22 Ref.23 Ref.24

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. Ref.26 Ref.27

Miscellaneous: Involved in the gp130-mediated signaling pathway.

Sequence similarities: Belongs to the transcription factor STAT family.Contains 1 SH2 domain.