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NFE4 nuclear factor, erythroid 4 [ Homo sapiens (human) ]

Gene ID: 58160, updated on 5-Mar-2024

Summary

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Official Symbol
NFE4provided by HGNC
Official Full Name
nuclear factor, erythroid 4provided by HGNC
Primary source
HGNC:HGNC:29902
See related
Ensembl:ENSG00000230257 MIM:612133; AllianceGenome:HGNC:29902
Gene type
ncRNA
RefSeq status
VALIDATED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
NF-E4
Summary
The erythroid-specific protein encoded by this gene, and the ubiquitous transcription factor CP2, form the stage selector protein (SSP) complex, which is involved in preferential expression of the gamma-globin genes in fetal erythroid cells. Alternate use of an in-frame upstream non-AUG (CUG) translation initiation codon, and a downstream AUG codon, results in two isoforms. While the long isoform (22 kDa) acts as an activator, the short isoform (14 kDa) has been shown to repress gamma-globin gene expression. This gene is located in an intron of the FBXL13 gene on the opposite strand. [provided by RefSeq, Jul 2008]
Expression
Biased expression in adrenal (RPKM 1.2), appendix (RPKM 0.3) and 3 other tissues See more
Orthologs
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Genomic context

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See NFE4 in Genome Data Viewer
Location:
7q22.1
Exon count:
6
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 7 NC_000007.14 (102973430..102988853)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 7 NC_060931.1 (104288525..104303972)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 7 NC_000007.13 (102613877..102629300)

Chromosome 7 - NC_000007.14Genomic Context describing neighboring genes Neighboring gene F-box and leucine rich repeat protein 13 Neighboring gene RN7SK pseudogene 198 Neighboring gene P300/CBP strongly-dependent group 1 enhancer GRCh37_chr7:102516003-102517202 Neighboring gene NANOG hESC enhancer GRCh37_chr7:102541113-102541614 Neighboring gene H3K27ac hESC enhancer GRCh37_chr7:102580673-102581173 Neighboring gene leucine rich repeat containing 17 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr7:102584236-102584801 Neighboring gene MED14-independent group 3 enhancer GRCh37_chr7:102613398-102614597 Neighboring gene ReSE screen-validated silencer GRCh37_chr7:102616989-102617150 Neighboring gene P300/CBP strongly-dependent group 1 enhancer GRCh37_chr7:102631963-102633162 Neighboring gene Sharpr-MPRA regulatory region 7515 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 18509 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 26438 Neighboring gene armadillo repeat containing 10 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr7:102746161-102747030 Neighboring gene crystallin zeta pseudogene 1 Neighboring gene N-acyl phosphatidylethanolamine phospholipase D Neighboring gene uncharacterized LOC105375434 Neighboring gene ribosomal protein L19 pseudogene 12

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. Induction of human fetal globin gene expression by a novel erythroid factor, NF-E4. Zhou W, et al. Mol Cell Biol, 2000 Oct. PMID 11003662, Free PMC Article
  2. PRMT5-mediated methylation of histone H4R3 recruits DNMT3A, coupling histone and DNA methylation in gene silencing. Zhao Q, et al. Nat Struct Mol Biol, 2009 Mar. PMID 19234465, Free PMC Article
  3. The role of p22 NF-E4 in human globin gene switching. Zhou W, et al. J Biol Chem, 2004 Jun 18. PMID 15084587
  4. Repression of human gamma-globin gene expression by a short isoform of the NF-E4 protein is associated with loss of NF-E2 and RNA polymerase II recruitment to the promoter. Zhao Q, et al. Blood, 2006 Mar 1. PMID 16263792, Free PMC Article
  5. Site-specific acetylation of the fetal globin activator NF-E4 prevents its ubiquitination and regulates its interaction with the histone deacetylase, HDAC1. Zhao Q, et al. J Biol Chem, 2004 Oct 1. PMID 15273251

See all (6) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. findings indicate that p22 NF-E4 is capable of influencing human globin gene expression in vivo but is incapable of overriding the intrinsic mechanisms governing gamma-gene silencing in this context
    Title: The role of p22 NF-E4 in human globin gene switching.
  2. stabilization of NF-E4 by acetylation is PCAF-dependent; acetylation of Lys(43) also reduces the interaction between NF-E4 and HDAC1, potentially maximizing the activating ability of the factor
    Title: Site-specific acetylation of the fetal globin activator NF-E4 prevents its ubiquitination and regulates its interaction with the histone deacetylase, HDAC1.
  3. Cloning and characterization of NF-E4 as a component of the stage selector protein complex, and demonstration of non-AUG translation initiation codon usage.
    Title: Induction of human fetal globin gene expression by a novel erythroid factor, NF-E4.
Submit: New GeneRIF Correction

Phenotypes

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Review eQTL and phenotype association data in this region using PheGenI

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Homology

Other Names

  • fetal globin activator NF-E4
  • gamma-globin gene activator
  • transcription factor NF-E4

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables DNA-binding transcription factor binding IPI
Inferred from Physical Interaction
more info
 PubMed 
contributes_to cis-regulatory region sequence-specific DNA binding IMP
Inferred from Mutant Phenotype
more info
 PubMed 
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables protein homodimerization activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables transcription coregulator activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables transcription coregulator activity IMP
Inferred from Mutant Phenotype
more info
 PubMed 
Process Evidence Code Pubs
involved_in positive regulation of transcription by RNA polymerase II IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in positive regulation of transcription by RNA polymerase II IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in protein-containing complex assembly IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in regulation of DNA-templated transcription IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in regulation of transcription by RNA polymerase II IMP
Inferred from Mutant Phenotype
more info
 PubMed 
Component Evidence Code Pubs
located_in nucleus IDA
Inferred from Direct Assay
more info
 PubMed 
part_of protein-containing complex IDA
Inferred from Direct Assay
more info
 PubMed 
part_of protein-containing complex IMP
Inferred from Mutant Phenotype
more info
 PubMed 

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

RNA

  1. NR_166510.1 RNA Sequence

    Status: VALIDATED

    Source sequence(s)
    AC073127
    Related
    ENST00000420058.2

  2. NR_166511.1 RNA Sequence

    Status: VALIDATED

    Source sequence(s)
    AC073127
    Related
    ENST00000703021.1

  3. NR_166512.1 RNA Sequence

    Status: VALIDATED

    Source sequence(s)
    AC073127
    Related
    ENST00000686902.1

  4. NR_166513.1 RNA Sequence

    Status: VALIDATED

    Source sequence(s)
    AC073127

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000007.14 Reference GRCh38.p14 Primary Assembly

    Range
    102973430..102988853
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060931.1 Alternate T2T-CHM13v2.0

    Range
    104288525..104303972
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

  1. NM_001085386.2: Suppressed sequence

    Description
    NM_001085386.2: This RefSeq was removed because currently there is support for the transcript but not for the protein.
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q86UQ8.1 GenPept UniProtKB/Swiss-Prot:Q86UQ8

Gene LinkOut

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Chemical Information
Molecular Biology Databases
Research Materials
Miscellaneous