Transcriptional regulator which can act as an activator or a repressor. Inhibits the enhancer element of the AFP gene by binding to its AT-rich core sequence. In concert with SMAD-dependent TGF-beta signaling can repress the transcription of AFP via its interaction with SMAD2/3 (By similarity). Regulates the circadian locomotor rhythms via transcriptional activation of neuropeptidergic genes which are essential for intercellular synchrony and rhythm amplitude in the suprachiasmatic nucleus (SCN) of the brain (PubMed:26232227). Regulator of myoblasts differentiation through the binding to the AT-rich sequence of MYF6 promoter and promoter repression. Down-regulates the MUC5AC promoter in gastric cancer. In association with RUNX3, up-regulates CDKN1A promoter activity following TGF-beta stimulation (By similarity). Interacts with ALKBH4 and PIAS3 (By similarity). Interacts with FNBP3. Interacts with ESR1, RUNX3, TRIM25, SMAD2 and SMAD3 (By similarity). Translocates from the cytoplasm to the nucleus following TGF-beta stimulation. Expressed in nuclear body (NB)-like dots in the nucleus some of which overlap or closely associate with PML body. Expressed in suprachiasmatic nucleus (SCN) of the brain (at protein level). Expressed in skeletal muscle. Levels of expression are high in myoblasts but low in differentiated muscle. Phosphorylated at Ser-2634 in embryonic and adult brain. Phosphorylated at Ser-1600, Ser-2795, Ser-2804, Ser-2900, Ser-3434, Ser-3443, Ser-3616 and Ser-3700 in the embryonic brain only. Hpyerphosphorylated in embryonic brain and phosphorylation decreases its sensitivity to calpain-mediated proteolysis. Adult brain-derived ZFHX3 is sensitive, but embryonic brain-derived ZFHX3 is resistant to calpain 1-mediated proteolysis. Ubiquitinated, leading to its proteasomal degradation. Nuclear localization is essential for its sumoylation.