ID:NFE2_HUMAN DESCRIPTION: RecName: Full=Transcription factor NF-E2 45 kDa subunit; AltName: Full=Leucine zipper protein NF-E2; AltName: Full=Nuclear factor, erythroid-derived 2 45 kDa subunit; AltName: Full=p45 NF-E2; FUNCTION: Component 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. SUBUNIT: Homodimer; can bind DNA as a homodimer. Erythroid transcription activator nuclear factor erythroid-derived 2 (NF- E2), composed of a heterodimer of NFE2 and MAFK, possesses transactivation activity on beta-globin. Also forms high affinity heterodimer with MAFG; the interaction promotes erythropoiesis. Interacts (via the PXY motif 1) with ITCH (via the WW 1 domain); the interaction promotes 'Lys63'-linked ubiquitination of NFE2, translocates it to the cytoplasm and inhibits its transactivation activity. Interacts with MLL2; the interaction promotes transactivation of the beta-globin locus (By similarity). Interacts with MAPK8 (phosphorylated form); the interaction leads to phosphorylation of NFE2 in undifferentiated cells (By similarity). SUBCELLULAR LOCATION: Nucleus, PML body. Cytoplasm. Note=The sumoylated form locates to the nuclear bodies PML oncogenic domains (PODs). Translocated to the cytoplasm through interaction with ITCH. TISSUE SPECIFICITY: Expressed in hematopoietic cells and also in colon and testis. DOMAIN: The 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 (By similarity). PTM: Phosphorylated on serine residues (By similarity). In undifferentiated erythrocytes, phosphorylated by MAPK8 which then leads to ubiquitination and protein degradation (By similarity). PTM: Sumoylated. Sumoylation is required for translocation to nuclear bodies PODs, anchoring to the gene loci, and transactivation of the beta-globin gene. PTM: 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 (By similarity). SIMILARITY: Belongs to the bZIP family. CNC subfamily. SIMILARITY: Contains 1 bZIP (basic-leucine zipper) domain. WEB RESOURCE: Name=SeattleSNPs; URL="http://pga.gs.washington.edu/data/nfe2/";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on Q16621
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
LF210487 - JP 2014500723-A/17990: Polycomb-Associated Non-Coding RNAs. S77763 - nuclear factor erythroid 2 isoform f=basic leucine zipper protein {alternatively spliced, exon 1f} [human, fetal liver, mRNA, 1678 nt]. BC005044 - Homo sapiens nuclear factor (erythroid-derived 2), 45kDa, mRNA (cDNA clone MGC:12809 IMAGE:4040433), complete cds. L24122 - Homo sapiens NF-E2 protein (NF-E2) mRNA, complete cds. JD374115 - Sequence 355139 from Patent EP1572962. AK290555 - Homo sapiens cDNA FLJ78153 complete cds, highly similar to nuclear factor erythroid 2 isoform f=basic leucine zipper protein. JD431256 - Sequence 412280 from Patent EP1572962. AK290564 - Homo sapiens cDNA FLJ78141 complete cds, highly similar to nuclear factor erythroid 2 isoform f=basic leucine zipper protein. JD507157 - Sequence 488181 from Patent EP1572962. JD258637 - Sequence 239661 from Patent EP1572962. L13974 - Human leucine zipper mRNA, complete cds. JD096508 - Sequence 77532 from Patent EP1572962. AK313207 - Homo sapiens cDNA, FLJ93708, Homo sapiens nuclear factor (erythroid-derived 2), 45kDa (NFE2),mRNA. KJ891695 - Synthetic construct Homo sapiens clone ccsbBroadEn_01089 NFE2 gene, encodes complete protein. BT007288 - Homo sapiens nuclear factor (erythroid-derived 2), 45kDa mRNA, complete cds. DQ893437 - Synthetic construct clone IMAGE:100006067; FLH199527.01X; RZPDo839G1282D nuclear factor (erythroid-derived 2), 45kDa (NFE2) gene, encodes complete protein. DQ896796 - Synthetic construct Homo sapiens clone IMAGE:100011256; FLH199434.01L; RZPDo839G1281D nuclear factor (erythroid-derived 2), 45kDa (NFE2) gene, encodes complete protein. EU176417 - Synthetic construct Homo sapiens clone IMAGE:100006563; FLH263571.01X; RZPDo839G05252D nuclear factor (erythroid-derived 2), 45kDa (NFE2) gene, encodes complete protein. AB463935 - Synthetic construct DNA, clone: pF1KB8977, Homo sapiens NFE2 gene for nuclear factor (erythroid-derived 2), 45kDa, without stop codon, in Flexi system. CR450284 - Homo sapiens full open reading frame cDNA clone RZPDo834A071D for gene NFE2, nuclear factor (erythroid-derived 2), 45kDa; complete cds; without stopcodon. CU674969 - Synthetic construct Homo sapiens gateway clone IMAGE:100019132 5' read NFE2 mRNA. GU068583 - Homo sapiens NFE2 protein (R3HDM2/NFE2 fusion) mRNA, partial cds. JD297774 - Sequence 278798 from Patent EP1572962. MA446064 - JP 2018138019-A/17990: Polycomb-Associated Non-Coding RNAs.
Biochemical and Signaling Pathways
Reactome (by CSHL, EBI, and GO)
Protein Q16621 (Reactome details) participates in the following event(s):
R-HSA-1008240 NFE2 is a heterodimer R-HSA-1008200 NFE2 binds the beta globin locus control region R-HSA-983231 Factors involved in megakaryocyte development and platelet production R-HSA-8936459 RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function R-HSA-109582 Hemostasis R-HSA-8878171 Transcriptional regulation by RUNX1 R-HSA-212436 Generic Transcription Pathway R-HSA-73857 RNA Polymerase II Transcription R-HSA-74160 Gene expression (Transcription)
US Server
Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
