FunctionComponent of the NF-E2 complex essential for regulating erythroid and megakaryocytic maturation and differentiation. Binds to the hypersensitive site 2 (HS2) of the beta-globin control region (LCR). This subunit (NFE2) recognizes the TCAT/C sequence of the AP-1-like core palindrome present in a number of erythroid and megakaryocytic gene promoters. Requires MAFK or other small MAF proteins for binding to the NF-E2 motif. May play a role in all aspects of hemoglobin production from globin and heme synthesis to procurement of iron.
Tissue specificityExpressed in hematopoietic cells and also in colon and testis.
Sequence similaritiesBelongs to the bZIP family. CNC subfamily. Contains 1 bZIP domain.
DomainThe PXY motifs are required for binding WW domains. PXY1 is required to promote transactivation of beta-globin and for hyperacetylation of histone H3, but not for binding to the HS2 promoter site.
Post-translational modificationsPhosphorylated on serine residues (By similarity). In undifferentiated erythrocytes, phosphorylated by MAPK8 which then leads to ubiquitination and protein degradation. Sumoylated. Sumoylation is required for translocation to nuclear bodies PODs, anchoring to the gene loci, and transactivation of the beta-globin gene. Ubiquitinated mainly by 'Lys63'-linked ubiquitin. Polyubiquitination with 'Lys63'-linked ubiquitin by ITCH retains NFE2 in the cytoplasm preventing its transactivation activity. In undifferentiated erythrocyte, ubiquitinated after MAPK8-mediatd phosphorylation leading to protein degradation.
Cellular localizationNucleus > PML body. Cytoplasm. The sumoylated form locates to the nuclear bodies PML oncogenic domains (PODs). Translocated to the cytoplasm through interaction with ITCH.