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NFE4 Gene

protein-coding   GIFtS: 28
GCID: GC07P102614

Nuclear Factor, Erythroid 4

  Search for NFE4
at  

(According to 1HGNC, 2Entrez Gene,
3UniProtKB/Swiss-Prot, 4UniProtKB/TrEMBL, 5OMIM, 6GeneLoc, 7Ensembl, 8DME, 9miRBase, 10fRNAdb, 12H-InvDB, 13NCBI, 14NONCODE, and/or 15RNAdb)
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This gene clusters with an RNA gene
Subcategory (RNA class): antisense

Quality score for the ORGUL clustered with this gene is 3

Aliases
Nuclear Factor, Erythroid 41 2
NF-E42
Fetal Globin Activator NF-E42
Gamma-Globin Gene Activator2
Transcription Factor NF-E42

External Ids:    HGNC: 299021   Entrez Gene: 581602   Ensembl: ENSG000002302577   OMIM: 6121335   UniProtKB: Q86UQ83   
ORGUL members:         

Export aliases for NFE4 gene to outside databases


(According to Entrez Gene, GeneCards, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
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Entrez Gene summary for NFE4 Gene:
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)

GeneCards Summary for NFE4 Gene:
NFE4 (nuclear factor, erythroid 4) is a protein-coding gene.

UniProtKB/Swiss-Prot: NFE4_HUMAN, Q86UQ8
Function: Functions as part of the SSP (stage selector protein) complex, a complex that contributes to the
preferential expression of the gamma-gene in fetal erythroid cells by facilitating the interaction of the
gamma-globin genes with enhancer elements contained in the locus control region (LCR). The complex binds to the
stage selector element (SSE) in the proximal gamma-globin promoter. In contrast, isoform 2 acts as a repressor of
gamma-globin gene expression by preventing NFE2 and RNA polymerase II recruitment to the promoter




(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 75), Regulatory elements and Epigenetics data according to QIAGEN, and/or SwitchGear Genomics)
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RefSeq DNA sequence at NCBI GenBank:
NC_000007.13  NC_018918.2  NT_007933.16  
Regulatory elements:
   Search for regulatory transcription factor binding sites for NFE4
         Other transcription factors

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Epigenetics:
DNA Methylation CpG Assay Predesigned for Pyrosequencing in human, mouse, rat NFE4


Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 7q22.1   Ensembl cytogenetic band:  7q22.1   HGNC cytogenetic band: 7q22.1

NFE4 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
NFE4 gene location

GeneLoc information about chromosome 7         GeneLoc Exon Structure

GeneLoc location for GC07P102614:  view genomic region     (about GC identifiers)

Start:
102,613,884 bp from pter      End:
102,629,303 bp from pter
Size:
15,420 bases      Orientation:
plus strand

1 alternative location:
Chr7+,CRA_TCAG 101,974,250-101,979,480     

(According to 1UniProtKB, HORDE, 2neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, Cloud-Clone Corp., and/or eBioscience,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, Cloud-Clone Corp., and/or eBioscience, Antibodies by EMD Millipore, R&D Systems, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, LSBio, Abcam, Cloud-Clone Corp, and/or others.)
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UniProtKB/Swiss-Prot: NFE4_HUMAN, Q86UQ8 (See protein sequence)
Recommended Name: Transcription factor NF-E4  
Size: 179 amino acids; 19019 Da
Subunit: Component of the SSP (stage selector protein) complex, which appears to be a heteromer of TFCP2 and 2
copies of NFE4. Interacts with HDAC1 and PCAF. Isoform 2 interacts with TFCP2
Sequence caution: Sequence=AAP13531.1; Type=Miscellaneous discrepancy; Note=Unusual initiator. The initiator
methionine is coded by a non-canonical CTG leucine codon;
Alternative initiation: 2 isoforms:  Q86UQ8-1   Q86UQ8-2   

Explore the universe of human proteins at neXtProt for NFE4: NX_Q86UQ8

Post-translational modifications: 

  • Acetylation at Lys-43 prolongs the protein half-life by preventing ubiquitin-mediated degradation and reduces the
    interaction between NF-E4 and HDAC1, potentially maximizing the activating ability of the factor at the
    gamma-promoter1
  • Ubiquitinated; leading to its degradation by the proteasome. Acetylation at Lys-43 prevents ubiquitination1
  • Modification sites at neXtProt
  • Modification sites at PhosphoSitePlus
  • REFSEQ proteins: NP_001078855.1  

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    (According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
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    ProtoNet protein and cluster: Q86UQ8


    (According to 1UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or 2DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, inGenious Targeting Laboratory, genOway,
    transcription factor targeting from QIAGEN and/or HOMER, miRNA Gene Targets from miRTarBase, shRNA from OriGene, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, SwitchGear Genomics, Gene Editing from DNA2.0, Clones from OriGene, GenScript, Sino Biological, DNA2.0, Vector BioLabs and/or Addgene, Cell Lines from GenScript, ESI BIO, In Situ Hybridization Assays from Advanced Cell Diagnostics, Flow cytometry from eBioscience, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Molecular Function:

         UniProtKB/Swiss-Prot Summary: NFE4_HUMAN, Q86UQ8
    Function: Functions as part of the SSP (stage selector protein) complex, a complex that contributes to the
    preferential expression of the gamma-gene in fetal erythroid cells by facilitating the interaction of the
    gamma-globin genes with enhancer elements contained in the locus control region (LCR). The complex binds to the
    stage selector element (SSE) in the proximal gamma-globin promoter. In contrast, isoform 2 acts as a repressor of
    gamma-globin gene expression by preventing NFE2 and RNA polymerase II recruitment to the promoter

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    (According to UniProtKB, COMPARTMENTS Subcellular localization database, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Subcellular locations from UniProtKB/Swiss-Prot
    NFE4_HUMAN, Q86UQ8: Nucleus (Probable)

    Gene Ontology (GO): 1 cellular component term:    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005634nucleus IEA--

    Find genes that share ontologies with NFE4           About GenesLikeMe


    (SuperPaths according to PathCards, Pathways according to R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Sino Biological, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to QIAGEN, and/or STRING, Interactions according to 1UniProtKB, 2MINT, 3I2D, and/or 4STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene).
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        Custom Pathway & Disease-focused RT2 Profiler PCR Arrays for NFE4
    Interactions:

        Search GeneGlobe Interaction Network for NFE4

    5 Interacting proteins for NFE4 (Q86UQ83) via UniProtKB, MINT, STRING, and/or I2D
    InteractantInteraction Details
    GeneCardExternal ID(s)
    HDAC1Q135473I2D: score=2 
    KAT2BQ928313I2D: score=2 
    TFCP2Q128003I2D: score=2 
    PRMT5O147443I2D: score=1 
    UBCP0CG483I2D: score=1 
    About this table

    Gene Ontology (GO): 2 biological process terms:    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0006351transcription, DNA-templated IEA--
    GO:0006355regulation of transcription, DNA-templated IEA--

    Find genes that share ontologies with NFE4           About GenesLikeMe



    (Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience, ApexBio, HMDB, BitterDB, and/or Novoseek, Ligands according to IUPHAR, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB)
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    Browse Small Molecules at EMD Millipore
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    Browse Tocris compounds for NFE4



    (Secondary structures according to fRNAdb,
    GenBank/EMBL/DDBJ Accessions according to
    Unigene (Build 236 Homo sapiens; Apr 25 2013) or GenBank,
    RefSeq according to Entrez Gene,
    DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
    exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
    siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN, SwitchGear Genomics,
    Tagged/untagged cDNA clones from OriGene, GenScript, DNA2.0, Vector BioLabs, and/or Addgene, Primers from OriGene, and/or QIAGEN, Flow cytometry from eBioscience )
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    REFSEQ mRNAs for NFE4 gene: 
    NM_001085386.1  

    Unigene Cluster for NFE4:

    Transcription factor NF-E4
    Hs.621233
    Unigene Representative Sequence: BC036938
    1 Ensembl transcript including schematic representation, and UCSC links where relevant:
    ENST00000420058(antisense)
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    Additional mRNA sequence: BC036938.1 

    1 DOTS entry:

    DT.99929296 

    GeneLoc Exon Structure


    (RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, Protein expression images according to data from SPIRE 1MOPED, 2PaxDb, and 3MaxQB, plus additional links to SOURCE, and/or BioGPS, and/or UniProtKB,
    PCR Arrays from QIAGEN, Primers from OriGene, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
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    NFE4 expression in normal human tissues (normalized intensities)
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS <intensity>2/3
    CGAP TAG: --
    NFE4 Expression
    About this image


    NFE4 expression in embryonic tissues and stem cells    About this table
    Data from LifeMap, the Embryonic Development and Stem Cells Database
     selected tissues (see all 2) fully expand
     
     Endothelium (Cardiovascular System)
             Endothelial-like cells
     
     NULL (Uncategorized)
             CD31, CD144 positive cells
    NFE4 Protein expression data from MOPED1, PaxDb2 and MaxQB3 --

    SOURCE GeneReport for Unigene cluster: Hs.621233

    UniProtKB/Swiss-Prot: NFE4_HUMAN, Q86UQ8
    Tissue specificity: Specifically expressed in fetal liver, cord blood and bone marrow. Also expressed in the K562
    and HEL cell lines, which constitutively express the fetal globin genes

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    (Orthologs according to 1,2HomoloGene (2older version, for species not in 1newer version), 3euGenes, 4SGD , 5MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or 6Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
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      --

    ENSEMBL Gene Tree for NFE4 (if available)
    TreeFam Gene Tree for NFE4 (if available)

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
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      --

    (SNPs/Variants according to the 1NCBI SNP Database, 2Ensembl, 3PupaSUITE, 4UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD), the Human Cytochrome P450 Allele Nomenclature Database, and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers, Cancer Mutation PCR Arrays and Assays, and Copy Number PCR Arrays from QIAGEN)
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    2 SNPs for NFE4    About this table                                 

    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance
    Chr 7 posSequence#AA
    Chg
    TypeMore#Allele
    freq
    PopTotal
    sample
    More
    ----------
    rs22286871,2,4
    ----see VAR_0466232 mis40--------
    rs64658861,2,4
    ----see VAR_0466222 mis40--------

    HapMap Linkage Disequilibrium report for NFE4 (102613884 - 102629303 bp)

    Structural Variations
          Database of Genomic Variants (DGV) variations for NFE4: --
    Site Specific Mutation Identification with PCR Assays
    Search QIAGEN SeqTarget long-range PCR primers for resequencing NFE4
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    (in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
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    OMIM gene information: 612133    OMIM disorders: --


    Find genes that share disorders with NFE4           About GenesLikeMe


    Export disorders for NFE4 gene to outside databases

    (in PubMed. Associations of this gene to articles via 1Entrez Gene, 2UniProtKB/Swiss-Prot, 3HGNC, 4GAD, 5PharmGKB, 6HMDB, 7DrugBank, 8UniProtKB/TrEMBL, 9 Novoseek, and/or 10fRNAdb)
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    PubMed articles for NFE4 gene integrated from 10 sources:
    (articles sorted by number of sources associating them with NFE4)
        Utopia: connect your pdf to the dynamic
    world of online information

    1. Induction of human fetal globin gene expression by a novel erythroid factor, NF-E4. (PubMed id 11003662)1, 2, 3, 9 Zhou W....Jane S.M. (Mol. Cell. Biol. 2000)
    2. 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. (PubMed id 16263792)1, 2, 9 Zhao Q.... Jane S.M. (Blood 2006)
    3. Site-specific acetylation of the fetal globin activator NF-E4 prevents its ubiquitination and regulates its interaction with the histone deacetylase, HDAC1. (PubMed id 15273251)1, 2, 9 Zhao Q.... Jane S.M. (J. Biol. Chem. 2004)
    4. The role of p22 NF-E4 in human globin gene switching. (PubMed id 15084587)1, 2 Zhou W.... Jane S.M. (J. Biol. Chem. 2004)
    5. PRMT5-mediated methylation of histone H4R3 recruits DNMT3A, coupling histone and DNA methylation in gene silencing. (PubMed id 19234465)1 Zhao Q....Jane S.M. (amp 2009)
    6. The DNA sequence of human chromosome 7. (PubMed id 12853948)2 Hillier L.W.... Wilson R.K. (Nature 2003)
    7. Biochemical characterization of the developmental stage- and tissue-specific erythroid transcription factor, NF-E4. (PubMed id 8144507)9 Yang Z. and Engel J.D. (J. Biol. Chem. 1994)
    8. Developmental regulation of the human beta-globin cluster. (PubMed id 8770365)9 Jane S.M....Cunningham J.M. (Aust N Z J Med 1995)

    (in PubMed, OMIM, and NCBI Bookshelf)
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     ANDOR
    Aliases
    Free Text  

      Query String
    PubMed
    OMIM
    NCBI Bookshelf
      (Note: In FireFox, select the above section and copy using Ctrl-C)

    (According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
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    Entrez Gene: 58160 HGNC: 29902 Ensembl:ENSG00000230257 euGenes: HUgn58160 ECgene: NFE4
    H-InvDB: NFE4

    (According to HUGE)
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      --

    (According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, UniProtKB/TrEMBL, and/or others, e.g. Wikipedia and GeneReviews, via UniProtKB/Swiss-Prot)
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      --

    (Patent information from GeneIP,
    Licensable technologies from WIS Yeda, Salk, Tufts,
    IP news from LifeMap Sciences, Inc.)
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    Patent Information for NFE4 gene:
    Search GeneIP for patents involving NFE4

    GeneCards and IP:
    Japan Patent Office Licenses GeneCards     European Patent Office Licenses GeneCards     Improving the IP Search



    (Antibodies, recombinant proteins, and assays from EMD Millipore, R&D Systems, OriGene, QIAGEN, GenScript, Cell Signaling Technology, Novus Biologicals, Sino Biological, Enzo Life Sciences, Abcam, ProSpec, Cloud-Clone Corp., Thermo Fisher Scientific, LSBio, eBioscience, and/or others, Gene Editing from DNA2.0. Clones from OriGene, GenScript, Sino Biological, DNA2.0, SwitchGear Genomics, Vector BioLabs, Addgene, Cell lines from GenScript, and ESI BIO, Flow cytometery from eBioscience, PCR Arrays from QIAGEN, Drugs and/or compounds from EMD Millipore, Tocris Bioscience, Enzo Life Sciences, and/or ApexBio, In Situ Hybridization Assays from
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     Browse Proteins at Cloud-Clone Corp.
     Browse Antibodies at Cloud-Clone Corp.
     Browse ELISAs at Cloud-Clone Corp.
     Browse CLIAs at Cloud-Clone Corp.



     Browse ESI BIO Cell Lines and PureStem Progenitors for NFE4
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     Browse SwitchGear 3'UTR luciferase reporter plasmids for NFE4
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     Search ThermoFisher Antibodies for NFE4
     Search Vector BioLabs for ready-to-use adenovirus/AAV for human, mouse, rat NFE4
     inGenious Targeting Laboratory: Let us create your new Knockout/Knockin mouse model for NFE4
     inGenious Targeting Laboratory: Contact us about creating complex and humanized mouse models for NFE4
     Search LSBio for Antibodies for NFE4
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     Browse compounds at ApexBio
     Search Addgene for plasmids for NFE4
      Search eBioscience for proteins for NFE4
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      eBioscience FlowRNA Probe Sets
           
    GeneCards Homepage - Last full update: 7 May 2014 - Incrementals: 9 May 2014 , 2 Jun 2014 , 26 Jun 2014 , 30 Jun 2014 , 21 Aug 2014 , 8 Sep 2014

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