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Aliases for NFE2 Gene

Aliases for NFE2 Gene

  • Nuclear Factor, Erythroid 2 2 3 5
  • Nuclear Factor, Erythroid-Derived 2 45 KDa Subunit 3 4
  • Nuclear Factor (Erythroid-Derived 2), 45kDa 2 3
  • Nuclear Factor (Erythroid-Derived 2), 45kD 2 3
  • Leucine Zipper Protein NF-E2 3 4
  • P45 NF-E2 3 4
  • Transcription Factor NF-E2 45 KDa Subunit 3
  • NF-E2 3
  • P45 3

External Ids for NFE2 Gene

Previous GeneCards Identifiers for NFE2 Gene

  • GC12M054813
  • GC12M054402
  • GC12M052972
  • GC12M054685
  • GC12M051725

Summaries for NFE2 Gene

GeneCards Summary for NFE2 Gene

NFE2 (Nuclear Factor, Erythroid 2) is a Protein Coding gene. Diseases associated with NFE2 include Polycythemia and Hereditary Spherocytosis Type 2. Among its related pathways are Hematopoietic Stem Cell Differentiation and Factors involved in megakaryocyte development and platelet production. GO annotations related to this gene include transcription factor activity, sequence-specific DNA binding and transcription coactivator activity. An important paralog of this gene is NFE2L1.

UniProtKB/Swiss-Prot for NFE2 Gene

  • 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.

Gene Wiki entry for NFE2 Gene

No data available for Entrez Gene Summary , CIViC summary , Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for NFE2 Gene

Genomics for NFE2 Gene

Regulatory Elements for NFE2 Gene

Enhancers for NFE2 Gene
GeneHancer Identifier Enhancer Score Enhancer Sources Gene-Enhancer Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor Binding Sites within enhancer Gene Targets for Enhancer
GH12G054303 2 FANTOM5 Ensembl ENCODE dbSUPER 40.3 -3.5 -3502 2.6 HDGF PKNOX1 ARNT ARID4B SIN3A DMAP1 ZNF766 KLF13 DEK SP5 NFE2 MAP3K12 GTSF1 FLJ12825 COPZ1 GC12M054318 RNU6-950P
GH12G054306 1.6 FANTOM5 Ensembl ENCODE 21.8 -6.1 -6085 2.1 HDGF PKNOX1 ATF1 CREB3L1 ZNF121 ZNF766 DEK SP3 SP5 YY2 NFE2 MIR148B GPR84 SMUG1 NCKAP1L ZNF385A COPZ1 GC12M054318 RNU6-950P
GH12G054291 1.9 FANTOM5 Ensembl ENCODE dbSUPER 2.9 +4.0 4010 11.8 HDGF PKNOX1 CREB3L1 ARNT ARID4B SIN3A YBX1 DMAP1 ZNF2 YY1 HNRNPA1 MAP3K12 ITGA5 RNU6-950P MIR148B GPR84 ZNF385A FLJ12825 GTSF1 AAAS
GH12G053480 1.1 ENCODE dbSUPER 4.3 +819.6 819589 1.8 CTCF PKNOX1 ZNF146 ZFP64 ZNF140 ZNF266 RAD21 ZNF101 ZNF697 POLR2A AAAS MAP3K12 NPFF CBX5 AMHR2 NFE2 ENSG00000273658
GH12G054285 1.6 Ensembl ENCODE dbSUPER 0.4 +13.0 12951 6.0 HNRNPUL1 PKNOX1 FOXA2 AGO1 SIN3A FEZF1 ZNF2 YY1 ZNF766 KLF13 RNU6-950P GPR84 ENSG00000270175 MIR148B GTSF1 FLJ12825 HNRNPA1 NFE2
- Elite enhancer and/or Elite enhancer-gene association Download GeneHancer data dump

Enhancers around NFE2 on UCSC Golden Path with GeneCards custom track

Promoters for NFE2 Gene
Ensembl Regulatory Elements (ENSRs) TSS Distance (bp) Size (bp) Binding Sites for Transcription Factors within promoters
ENSR00000052338 321 401 SIN3A DMAP1 ZNF48 GLIS2 KLF7 KLF13 NCOA1 MBD2 MAFF SMARCA4

Transcription factor binding sites by QIAGEN in the NFE2 gene promoter:

Genomic Location for NFE2 Gene

Chromosome:
12
Start:
54,292,107 bp from pter
End:
54,301,121 bp from pter
Size:
9,015 bases
Orientation:
Minus strand

Genomic View for NFE2 Gene

Genes around NFE2 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
NFE2 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for NFE2 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for NFE2 Gene

Proteins for NFE2 Gene

  • Protein details for NFE2 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q16621-NFE2_HUMAN
    Recommended name:
    Transcription factor NF-E2 45 kDa subunit
    Protein Accession:
    Q16621
    Secondary Accessions:
    • Q07720
    • Q6ICV9

    Protein attributes for NFE2 Gene

    Size:
    373 amino acids
    Molecular mass:
    41473 Da
    Quaternary structure:
    • 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 KMT2D/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).

    Three dimensional structures from OCA and Proteopedia for NFE2 Gene

neXtProt entry for NFE2 Gene

Post-translational modifications for NFE2 Gene

  • Phosphorylated on serine residues. 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 (By similarity).
  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

No data available for DME Specific Peptides for NFE2 Gene

Domains & Families for NFE2 Gene

Gene Families for NFE2 Gene

Protein Domains for NFE2 Gene

Suggested Antigen Peptide Sequences for NFE2 Gene

Graphical View of Domain Structure for InterPro Entry

Q16621

UniProtKB/Swiss-Prot:

NFE2_HUMAN :
  • 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).
  • Belongs to the bZIP family. CNC subfamily.
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).
Family:
  • Belongs to the bZIP family. CNC subfamily.
genes like me logo Genes that share domains with NFE2: view

Function for NFE2 Gene

Molecular function for NFE2 Gene

GENATLAS Biochemistry:
nuclear factor,erythroid derived NF-E2 Capncollar (CNC) family of transcription factor,dimerizing with TFCP2 to form the stage selector protein complex,binding to LCR of globin loci
UniProtKB/Swiss-Prot 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.

Gene Ontology (GO) - Molecular Function for NFE2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000976 transcription regulatory region sequence-specific DNA binding IBA --
GO:0003677 DNA binding IEA --
GO:0003700 transcription factor activity, sequence-specific DNA binding IEA,IBA --
GO:0003713 transcription coactivator activity TAS 8355703
GO:0005515 protein binding IPI 20102225
genes like me logo Genes that share ontologies with NFE2: view
genes like me logo Genes that share phenotypes with NFE2: view

Animal Models for NFE2 Gene

MGI Knock Outs for NFE2:

Animal Model Products

Transcription Factor Targets for NFE2 Gene

Selected GeneGlobe predicted Target genes for NFE2
Targeted motifs for NFE2 Gene
HOMER Transcription Factor Regulatory Elements motif NFE2
  • Consensus sequence: GATGACTCAGCA Submotif: canonical Cell Type: K562 GEO ID: GSE31477

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology and miRNA for NFE2 Gene

Localization for NFE2 Gene

Subcellular locations from UniProtKB/Swiss-Prot for NFE2 Gene

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.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for NFE2 gene
Compartment Confidence
nucleus 5
cytoskeleton 2
cytosol 2
mitochondrion 1

Gene Ontology (GO) - Cellular Components for NFE2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus TAS,IEA 7774011
GO:0005654 nucleoplasm TAS --
GO:0005737 cytoplasm IBA,IEA --
GO:0016605 PML body IEA --
genes like me logo Genes that share ontologies with NFE2: view

Pathways & Interactions for NFE2 Gene

genes like me logo Genes that share pathways with NFE2: view

Pathways by source for NFE2 Gene

Gene Ontology (GO) - Biological Process for NFE2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006337 nucleosome disassembly TAS 9305852
GO:0006351 transcription, DNA-templated TAS 9305852
GO:0006355 regulation of transcription, DNA-templated IEA --
GO:0006357 regulation of transcription from RNA polymerase II promoter TAS 8355703
GO:0007275 multicellular organism development TAS 7774011
genes like me logo Genes that share ontologies with NFE2: view

No data available for SIGNOR curated interactions for NFE2 Gene

Drugs & Compounds for NFE2 Gene

(6) Drugs for NFE2 Gene - From: HMDB and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
heme Pharma Agonist 0

(8) Additional Compounds for NFE2 Gene - From: Novoseek and HMDB

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
Fe2+
  • Armco iron
  • Carbonyl iron
  • FE
  • Ferrovac e
  • Hematite
15438-31-0
genes like me logo Genes that share compounds with NFE2: view

Transcripts for NFE2 Gene

Unigene Clusters for NFE2 Gene

Nuclear factor (erythroid-derived 2), 45kDa:
Representative Sequences:

Alternative Splicing Database (ASD) splice patterns (SP) for NFE2 Gene

ExUns: 1a · 1b ^ 2 ^ 3 ^ 4a · 4b ^ 5a · 5b · 5c
SP1: - -
SP2: - - -
SP3: -
SP4:

Relevant External Links for NFE2 Gene

GeneLoc Exon Structure for
NFE2
ECgene alternative splicing isoforms for
NFE2

Expression for NFE2 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for NFE2 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for NFE2 Gene

This gene is overexpressed in Whole Blood (x48.7).

Protein differential expression in normal tissues from HIPED for NFE2 Gene

This gene is overexpressed in Cervix (65.7).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, MaxQB, and MOPED for NFE2 Gene



Protein tissue co-expression partners for NFE2 Gene

- Elite partner

NURSA nuclear receptor signaling pathways regulating expression of NFE2 Gene:

NFE2

SOURCE GeneReport for Unigene cluster for NFE2 Gene:

Hs.75643

mRNA Expression by UniProt/SwissProt for NFE2 Gene:

Q16621-NFE2_HUMAN
Tissue specificity: Expressed in hematopoietic cells and also in colon and testis.

Evidence on tissue expression from TISSUES for NFE2 Gene

  • Lung(4.2)
  • Blood(2.9)
  • Bone marrow(2.6)
genes like me logo Genes that share expression patterns with NFE2: view

Primer Products

No data available for Phenotype-based relationships between genes and organs from Gene ORGANizer for NFE2 Gene

Orthologs for NFE2 Gene

This gene was present in the common ancestor of animals.

Orthologs for NFE2 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia NFE2 34 35
  • 99.46 (n)
cow
(Bos Taurus)
Mammalia NFE2 34 35
  • 89.28 (n)
dog
(Canis familiaris)
Mammalia NFE2 34 35
  • 88.38 (n)
rat
(Rattus norvegicus)
Mammalia Nfe2 34
  • 85.7 (n)
mouse
(Mus musculus)
Mammalia Nfe2 34 16 35
  • 84.99 (n)
platypus
(Ornithorhynchus anatinus)
Mammalia -- 35
  • 37 (a)
ManyToMany
lizard
(Anolis carolinensis)
Reptilia NFE2 35
  • 54 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia nfe2 34
  • 50.71 (n)
zebrafish
(Danio rerio)
Actinopterygii nfe2 35
  • 32 (a)
OneToOne
fruit fly
(Drosophila melanogaster)
Insecta cnc 36 35
  • 49 (a)
sea squirt
(Ciona savignyi)
Ascidiacea -- 35
  • 11 (a)
OneToMany
Species where no ortholog for NFE2 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • chicken (Gallus gallus)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • oppossum (Monodelphis domestica)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)

Evolution for NFE2 Gene

ENSEMBL:
Gene Tree for NFE2 (if available)
TreeFam:
Gene Tree for NFE2 (if available)

Paralogs for NFE2 Gene

Paralogs for NFE2 Gene

(1) SIMAP similar genes for NFE2 Gene using alignment to 4 proteins:

genes like me logo Genes that share paralogs with NFE2: view

Variants for NFE2 Gene

Sequence variations from dbSNP and Humsavar for NFE2 Gene

SNP ID Clin Chr 12 pos Sequence Context AA Info Type
rs1000117846 -- 54,296,011(+) TTAAC(C/T)CATAC intron-variant, upstream-variant-2KB
rs1000665005 -- 54,301,273(+) GGTCC(A/G)CTCGA upstream-variant-2KB
rs1001104553 -- 54,300,958(+) CGCTG(A/T)GTGTG utr-variant-5-prime
rs1001312384 -- 54,293,943(+) TGAAC(C/T)CTCCT intron-variant
rs1001570173 -- 54,302,957(+) GAGTG(C/T)CTACT upstream-variant-2KB

Structural Variations from Database of Genomic Variants (DGV) for NFE2 Gene

Variant ID Type Subtype PubMed ID
nsv1049160 CNV gain 25217958
nsv832420 CNV loss 17160897

Variation tolerance for NFE2 Gene

Residual Variation Intolerance Score: 18.5% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 0.57; 12.23% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for NFE2 Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
NFE2

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for NFE2 Gene

Disorders for NFE2 Gene

MalaCards: The human disease database

(6) MalaCards diseases for NFE2 Gene - From: DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
polycythemia
  • polycythemia vera
hereditary spherocytosis type 2
  • hereditary spherocytosis 2
spherocytosis, type 4
  • hereditary spherocytosis type 4
essential thrombocythemia
  • essential thrombocythaemia
spherocytosis, type 1
  • hereditary spherocytosis type 1
- elite association - COSMIC cancer census association via MalaCards
Search NFE2 in MalaCards View complete list of genes associated with diseases

Relevant External Links for NFE2

Genetic Association Database (GAD)
NFE2
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
NFE2
genes like me logo Genes that share disorders with NFE2: view

No data available for UniProtKB/Swiss-Prot and Genatlas for NFE2 Gene

Publications for NFE2 Gene

  1. Purification of the human NF-E2 complex: cDNA cloning of the hematopoietic cell-specific subunit and evidence for an associated partner. (PMID: 8355703) Ney P.A. … Neinhuis A.W. (Mol. Cell. Biol. 1993) 2 3 4 22 64
  2. Sumoylation of p45/NF-E2: nuclear positioning and transcriptional activation of the mammalian beta-like globin gene locus. (PMID: 16287851) Shyu Y.-C. … Shen C.-K.J. (Mol. Cell. Biol. 2005) 3 4 22 64
  3. Stimulation of NF-E2 DNA binding by CREB-binding protein (CBP)- mediated acetylation. (PMID: 11154691) Hung H.-L. … Blobel G.A. (J. Biol. Chem. 2001) 3 4 22 64
  4. Isolation of a differentially regulated splicing isoform of human NF- E2. (PMID: 7724591) Pischedda C. … Moi P. (Proc. Natl. Acad. Sci. U.S.A. 1995) 3 4 22 64
  5. Isolation of cDNA encoding the human NF-E2 protein. (PMID: 8248255) Chan J.Y. … Kan Y.W. (Proc. Natl. Acad. Sci. U.S.A. 1993) 3 4 22 64

Products for NFE2 Gene

Sources for NFE2 Gene

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