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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
  • Transcription Factor NF-E2 45 KDa Subunit 3 4
  • Leucine Zipper Protein NF-E2 3 4
  • P45 NF-E2 3 4
  • 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 Hematopoietic Stem Cell Differentiation and Factors involved in megakaryocyte development and platelet production. 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
GH12J054291 Promoter/Enhancer 2.5 EPDnew FANTOM5 Ensembl ENCODE dbSUPER 602.8 +3.9 3925 11.8 ZFX CC2D1A SP1 CTCF ELF3 ZKSCAN8 CBFA2T2 ZNF148 MLLT1 RERE NFE2 HNRNPA1 RNU6-950P AAAS MIR148B GPR84 ZNF385A LOC100652999 FLJ12825 GTSF1
GH12J054303 Promoter/Enhancer 2 FANTOM5 Ensembl ENCODE dbSUPER 40.2 -3.6 -3586 2.6 ZNF652 ELF3 CC2D1A ZKSCAN8 CBFA2T2 ZNF148 MLLT1 CEBPG RERE GTF2F1 NFE2 MAP3K12 AAAS LOC100652999 GTSF1 FLJ12825 COPZ1 GC12M054318 RNU6-950P ENSG00000258344
GH12J054306 Promoter/Enhancer 1.8 FANTOM5 Ensembl ENCODE 21.8 -6.2 -6168 2.1 MLLT1 ZNF121 CEBPG NFIB TRIM24 SP7 SP5 KLF14 SMARCA4 MTA1 NFE2 MIR148B GPR84 SMUG1 NCKAP1L ZNF385A COPZ1 GC12M054318 RNU6-950P ENSG00000258344
GH12J053480 Enhancer 1 Ensembl ENCODE dbSUPER 4.3 +819.5 819514 1.8 POLR2A MZF1 ZBTB33 SMAD5 REST BCLAF1 PKNOX1 RAD21 SUPT5H CTCF AAAS NPFF AMHR2 NFE2 ENSG00000273658 MAP3K12 PCBP2
GH12J054277 Promoter/Enhancer 2.3 EPDnew Ensembl ENCODE dbSUPER 0.4 +16.7 16707 13.6 HDGF MTA3 ZFX CC2D1A SP1 ZKSCAN8 MNT CBFA2T2 ZNF148 NKRF HNRNPA1 CBX5 MAP3K12 SP1 PCBP2 ATF7 ENSG00000258344 AAAS NPFF HOXC4
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around NFE2 on UCSC Golden Path with GeneCards custom track

Top Transcription factor binding sites by QIAGEN in the NFE2 gene promoter:
  • AML1a

Genomic Locations for NFE2 Gene

Genomic Locations for NFE2 Gene
chr12:54,292,107-54,301,037
(GRCh38/hg38)
Size:
8,931 bases
Orientation:
Minus strand
chr12:54,685,895-54,694,905
(GRCh37/hg19)
Size:
9,011 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

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

Protein Domains for NFE2 Gene

Suggested Antigen Peptide Sequences for NFE2 Gene

GenScript: Design optimal peptide antigens:
  • cDNA, FLJ93708, Homo sapiens nuclear factor (erythroid-derived 2), 45kDa (NFE2),mRNA (A8K3E0_HUMAN)
  • p45 NF-E2 (NFE2_HUMAN)

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

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.
GENATLAS Biochemistry:
nuclear factor,erythroid derived NF-E2 Cap'n'collar (CNC) family of transcription factor,dimerizing with TFCP2 to form the stage selector protein complex,binding to LCR of globin loci

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 21873635
GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific NAS 19274049
GO:0000987 proximal promoter sequence-specific DNA binding IDA 16263792
GO:0003677 DNA binding IEA,IDA 12609092
GO:0003700 DNA-binding transcription factor activity IBA,IEA 21873635
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

CRISPR 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

Clone Products

  • Applied Biological Materials (abm): Clones for NFE2 - Now 50% OFF >
  • * NFE2 as ready-to-use vector or virus: ORF | Lenti- | Retro- | Adeno- | AAV- | Protein Vector - Browse All
  • * NFE2 tags and reporters available: His, HA, Myc, Flag, GFP, RFP, Luciferase - Browse All

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
mitochondrion 1
endoplasmic reticulum 1
cytosol 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 IEA,IBA 21873635
GO:0005654 nucleoplasm TAS --
GO:0005737 cytoplasm IBA 21873635
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

SIGNOR curated interactions for NFE2 Gene

Activates:

Gene Ontology (GO) - Biological Process for NFE2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006337 nucleosome disassembly 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
GO:0007596 blood coagulation TAS --
genes like me logo Genes that share ontologies with NFE2: view

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
Iron Approved, Experimental Pharma 1426
heme Pharma Agonist 0

(7) Additional Compounds for NFE2 Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
genes like me logo Genes that share compounds with NFE2: view

Transcripts for NFE2 Gene

mRNA/cDNA for NFE2 Gene

Unigene Clusters for NFE2 Gene

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

CRISPR Products

Clone Products

  • Applied Biological Materials (abm): Clones for NFE2 - Now 50% OFF >
  • * NFE2 as ready-to-use vector or virus: ORF | Lenti- | Retro- | Adeno- | AAV- | Protein Vector - Browse All
  • * NFE2 tags and reporters available: His, HA, Myc, Flag, GFP, RFP, Luciferase - Browse All

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, 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 35 34
  • 99.46 (n)
OneToOne
cow
(Bos Taurus)
Mammalia NFE2 35 34
  • 89.28 (n)
OneToOne
dog
(Canis familiaris)
Mammalia NFE2 35 34
  • 88.38 (n)
OneToOne
rat
(Rattus norvegicus)
Mammalia Nfe2 34
  • 85.7 (n)
mouse
(Mus musculus)
Mammalia Nfe2 17 35 34
  • 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 35 36
  • 8 (a)
OneToMany
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)
Aminode:
Evolutionary constrained regions (ECRs) for NFE2: view image

Paralogs for NFE2 Gene

Paralogs for NFE2 Gene

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

  • NFE2_HUMAN
  • A8K3E0_HUMAN
  • F8W1N9_HUMAN
  • L8E770_HUMAN
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

SNP Genotyping and Copy Number Assay Products

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

Disorders for NFE2 Gene

MalaCards: The human disease database

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

Disorder Aliases PubMed IDs
essential thrombocythemia
  • essential thrombocythaemia
spherocytosis, type 4
  • sph4
hereditary spherocytosis
  • spherocytosis, type 1
- 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 23 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 23 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 23 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 23 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 23 58

Products for NFE2 Gene

Sources for NFE2 Gene

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