ZFHX3

ZFHX3 is a transcription factor with multiple homeodomains and zinc finger motifs, and regulates myogenic and neuronal differentiation. The encoded protein suppresses expression of the alpha-fetoprotein gene by binding to an AT-rich enhancer motif. The pr

Full Name

Zinc Finger Homeobox 3

Function

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 (PubMed:25105025).
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 (By similarity).
Regulator of myoblasts differentiation through the binding to the AT-rich sequence of MYF6 promoter and promoter repression (PubMed:11312261).
Down-regulates the MUC5AC promoter in gastric cancer (PubMed:17330845).
In association with RUNX3, up-regulates CDKN1A promoter activity following TGF-beta stimulation (PubMed:20599712).
Inhibits estrogen receptor (ESR1) function by selectively competing with coactivator NCOA3 for binding to ESR1 in ESR1-positive breast cancer cells (PubMed:20720010).

Biological Process

Biological Process brain development Source:GO_Central1 Publication
Biological Process circadian regulation of gene expression Source:UniProtKB
Biological Process muscle organ development Source:UniProtKB-KW
Biological Process negative regulation of myoblast differentiation Source:UniProtKB
Biological Process negative regulation of transcription by RNA polymerase II Source:NTNU_SB1 Publication
Biological Process positive regulation of cell adhesion Source:ARUK-UCL
Biological Process positive regulation of DNA-templated transcription Source:UniProtKB1 Publication
Biological Process positive regulation of myoblast differentiation Source:UniProtKB
Biological Process positive regulation of transcription by RNA polymerase II Source:ARUK-UCL
Biological Process regulation of cell cycle Source:Ensembl
Biological Process regulation of DNA-templated transcription Source:UniProtKB1 Publication
Biological Process regulation of locomotor rhythm Source:UniProtKB
Biological Process regulation of neuron differentiation Source:GO_Central1 Publication
Biological Process regulation of transcription by RNA polymerase II Source:GO_Central1 Publication
Biological Process response to transforming growth factor beta Source:UniProtKB1 Publication

Cellular Location

Nucleus
Cytoplasm
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.

PTM

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.