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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 Essential Thrombocythemia and Spherocytosis, Type 4. Among its related pathways are Response to elevated platelet cytosolic Ca2+ and Hematopoietic Stem Cell Differentiation. Gene Ontology (GO) annotations related to this gene include DNA binding transcription factor activity 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

Additional gene information 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

GeneHancer (GH) Regulatory Elements for NFE2 Gene

Promoters and enhancers for NFE2 Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH12I054291 Promoter/Enhancer 2.7 EPDnew FANTOM5 Ensembl ENCODE dbSUPER 552.9 +4.0 4009 11.8 HDGF PKNOX1 SMAD1 ARNT ARID4B YBX1 DMAP1 ZNF2 POLR2B ZNF766 NFE2 HNRNPA1 RNU6-950P MIR148B GPR84 ZNF385A FLJ12825 GTSF1 AAAS COPZ1
GH12I054303 Enhancer 1.7 FANTOM5 Ensembl ENCODE dbSUPER 40.3 -3.5 -3502 2.6 HDGF PKNOX1 SMAD1 FOXA2 ARNT ARID4B DMAP1 ZNF766 E2F8 DEK NFE2 MAP3K12 GTSF1 FLJ12825 COPZ1 RNU6-950P GC12M054318 ENSG00000258344
GH12I054306 Enhancer 1.5 FANTOM5 Ensembl ENCODE 21.8 -6.1 -6084 2.1 HDGF PKNOX1 SMAD1 ATF1 ZNF121 POLR2B ZNF766 ATF7 DEK SP3 NFE2 MIR148B GPR84 SMUG1 NCKAP1L ZNF385A COPZ1 RNU6-950P GC12M054318 ENSG00000258344
GH12I053480 Enhancer 0.9 ENCODE dbSUPER 4.3 +819.6 819589 1.8 CTCF PKNOX1 MZF1 SIN3A RAD21 POLR2B POLR2A NFATC1 BCLAF1 SMAD5 AAAS NPFF AMHR2 NFE2 ENSG00000273658 MAP3K12 PCBP2
GH12I054277 Promoter/Enhancer 2.3 EPDnew Ensembl ENCODE dbSUPER 0.3 +20.1 20056 7.1 CLOCK MLX DMAP1 YY1 SLC30A9 ZNF213 E2F8 ZNF143 SP3 NFYC CBX5 HNRNPA1 SP1 PCBP2 MAP3K12 AAAS ENSG00000258344 COPZ1 ATF7 TARBP2
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data dump

GeneHancers around NFE2 on UCSC Golden Path with GeneCards custom track

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

Genomic Locations for NFE2 Gene

Genomic Locations for NFE2 Gene
chr12:54,292,107-54,301,121
(GRCh38/hg38)
Size:
9,015 bases
Orientation:
Minus strand
chr12:54,685,895-54,694,905
(GRCh37/hg19)

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).

No data available for DME Specific Peptides for NFE2 Gene

Domains & Families for NFE2 Gene

Gene Families for NFE2 Gene

HGNC:
Human Protein Atlas (HPA):
  • Predicted intracellular proteins
  • Transcription factors

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.

Phenotypes From GWAS Catalog for NFE2 Gene

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:0000987 proximal promoter sequence-specific DNA binding IDA 16263792
GO:0003677 DNA binding IDA,IEA 12609092
GO:0003700 DNA binding transcription factor activity IBA,IEA --
GO:0003713 transcription coactivator activity TAS 8355703
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:

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

Clone Products

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
endoplasmic reticulum 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Actin filaments (2)
  • Nucleoplasm (2)
See all subcellular structures

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 --
GO:0016605 PML body IEA --
GO:0032993 protein-DNA complex IDA 12609092
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 by RNA polymerase II IEA --
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:

Clone Products

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(4.3)
  • Blood(3)
  • Bone marrow(2.6)
genes like me logo Genes that share expression patterns with NFE2: view

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 33 34
  • 99.46 (n)
cow
(Bos Taurus)
Mammalia NFE2 33 34
  • 89.28 (n)
dog
(Canis familiaris)
Mammalia NFE2 33 34
  • 88.38 (n)
rat
(Rattus norvegicus)
Mammalia Nfe2 33
  • 85.7 (n)
mouse
(Mus musculus)
Mammalia Nfe2 33 16 34
  • 84.99 (n)
platypus
(Ornithorhynchus anatinus)
Mammalia -- 34
  • 37 (a)
ManyToMany
lizard
(Anolis carolinensis)
Reptilia NFE2 34
  • 54 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia nfe2 33
  • 50.71 (n)
zebrafish
(Danio rerio)
Actinopterygii nfe2 34
  • 32 (a)
OneToOne
fruit fly
(Drosophila melanogaster)
Insecta cnc 35 34
  • 49 (a)
sea squirt
(Ciona savignyi)
Ascidiacea -- 34
  • 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 Variation AA Info Type
rs1000117846 -- 54,296,011(-) C/T genic_upstream_transcript_variant, intron_variant, upstream_transcript_variant
rs1000665005 -- 54,301,273(-) A/G upstream_transcript_variant
rs1001104553 -- 54,300,958(-) A/T 5_prime_UTR_variant, genic_upstream_transcript_variant
rs1001312384 -- 54,293,943(-) T/C intron_variant
rs1001570173 -- 54,302,957(-) T/C upstream_transcript_variant

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)

Additional Variant Information 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

(4) MalaCards diseases for NFE2 Gene - From: DISEASES and GeneCards

Disorder Aliases PubMed IDs
essential thrombocythemia
  • essential thrombocythaemia
spherocytosis, type 4
  • sph4
myelofibrosis
  • myelofibrosis with myeloid metaplasia, somatic
hereditary spherocytosis
  • congenital spherocytic hemolytic anemia
- elite association - COSMIC cancer census association via MalaCards
Search NFE2 in MalaCards View complete list of genes associated with diseases

Additional Disease Information for 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 PA … Nienhuis AW (Molecular and cellular biology 1993) 2 3 4 22 58
  2. Sumoylation of p45/NF-E2: nuclear positioning and transcriptional activation of the mammalian beta-like globin gene locus. (PMID: 16287851) Shyu YC … Shen CK (Molecular and cellular biology 2005) 3 4 22 58
  3. Stimulation of NF-E2 DNA binding by CREB-binding protein (CBP)-mediated acetylation. (PMID: 11154691) Hung HL … Blobel GA (The Journal of biological chemistry 2001) 3 4 22 58
  4. Isolation of a differentially regulated splicing isoform of human NF-E2. (PMID: 7724591) Pischedda C … Moi P (Proceedings of the National Academy of Sciences of the United States of America 1995) 3 4 22 58
  5. Isolation of cDNA encoding the human NF-E2 protein. (PMID: 8248255) Chan JY … Kan YW (Proceedings of the National Academy of Sciences of the United States of America 1993) 3 4 22 58

Products for NFE2 Gene

Sources for NFE2 Gene

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