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Category   Symbol Source: HGNC EntrezGene Ensembl GeneCards RNA genes CroW21
GIFtS

NFE4 Gene

RNA gene   GIFtS: 26
GCID: GC07P102614

NFE4


  Search for NFE4
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(According to 1HGNC, 2Entrez Gene,
3UniProtKB/Swiss-Prot, 4UniProtKB/TrEMBL, 5OMIM, 6GeneLoc, 7Ensembl, 8DME, 9miRBase, and/or 10fRNAdb)
About This Section

Subcategory (RNA class): lncRNA

Quality score for this RNA gene is 2

Aliases
NF-E42
Fetal Globin Activator NF-E42
Gamma-Globin Gene Activator2
Transcription Factor NF-E42

External Ids:    Entrez Gene: 581602   Ensembl: ENSG000002302577   OMIM: 6121335   UniProtKB: Q86UQ83   
ORGUL members:         
NONCODE:n341286    

Export aliases for NFE4 gene to outside databases


(According to Entrez Gene, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
About This Section

Entrez Gene summary for NFE4:
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)

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 69), Regulatory elements and Epigenetics data according to QIAGEN, SABiosciences, and/or SwitchGear Genomics)
About This Section
RefSeq DNA sequence:
NC_000007.13  NC_018918.1  NT_007933.15  NT_079596.2  
Regulatory elements:
   Search SABiosciences Regulatory transcription factor binding sites for NFE4
         Other transcription factors

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Epigenetics:
QIAGEN PyroMark CpG Assay predesigned Pyrosequencing DNA Methylation assays 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   

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, neXtProt, Ensembl, and/or Reactome, Modification sites according to 2PhosphoSitePlus, Specific Peptides from DME, Protein expression images according to data from SPIRE MOPED and PaxDb, 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, and/or Uscn,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Uscn, Ontologies according to Gene Ontology Consortium 01 Mar 2013 and Entrez Gene, Antibodies by EMD Millipore, R&D Systems, GenScript, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, Abcam, and/or Uscn)
About This Section

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
Subcellular location: Nucleus (Probable)
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
  • View modification sites using PhosphoSitePlus2
  • View neXtProt modification sites for NX_Q86UQ8

  • NFE4 Protein expression data from MOPED and PaxDb: --
    REFSEQ proteins: NP_001078855.1  
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    Gene Ontology (GO): 1 cellular component term (GO ID links to tree view):    About this table

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


    NFE4 for ontologies           About GeneDecksing



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    (According to InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
    About This Section

    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,
    bound targets from SABiosciences, miRNA Gene Targets from miRTarBase shRNA from OriGene, RNAi from EMD Millipore, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, Gene Editing from DNA2.0, Clones from EMD Millipore, OriGene, SwitchGear Genomics, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, LifeMap BioReagents, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Mar 2013 via Entrez Gene.)
    About This Section

    Function Summary:

         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

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    (Pathways according to EMD Millipore, R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to SABiosciences, 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 Mar 2013 via Entrez Gene).
    About This Section



    Interactions:

        Search SABiosciences Gene Network CentralTM Interacting Genes and Proteins Networks 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 (GO ID links to tree view):    About this table

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


    NFE4 for ontologies           About GeneDecksing



    (Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience HMDB, BitterDB, and/or Novoseek, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB, with drugs/clinical trials/news search links to CenterWatch)
    About This Section
    Browse Small Molecules at EMD Millipore
    Browse drugs & compounds from Enzo Life Sciences

    Browse Tocris compounds for NFE4
    Search CenterWatch for drugs/clinical trials and news about NFE4 

    (Secondary structures according to fRNAdb,
    GenBank/EMBL/DDBJ Accessions according to
    Unigene (Build 235 Homo sapiens; Mar 10 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,
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    About This Section

    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(lincRNA)

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    Additional cDNA 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™, plus additional links to Genevestigator, and/or SOURCE, and/or BioGPS, and/or UniProtKB,
    PCR Arrays from SABiosciences, Primers from OriGene, SABiosciences, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
    About This Section

    Expression evidence for NFE4:none

    NFE4 expression in normal human tissues (normalized intensities)
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS
    CGAP TAG: --

    Microarray
    RNAseq (Illumina Body Map)
    (100×FPKM)½
    SAGE (Serial Analysis of Gene Expression)

    About this image
    Genevestigator expression for NFE4

    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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    In Situ
    Assay Products:
     

     
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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)
    About This Section
      --

    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)
    About This Section
      --

    (SNPs/Variants according to the 1NCBI SNP Database, 2Ensembl, 3PupaSUITE, UniProtKB, 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) and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers from QIAGEN, Cancer Mutation PCR Arrays and Assays and Copy Number PCR Arrays from SABiosciences)
    About This Section

    10/117 NCBI SNPs in NFE4 are shown (see all 117    About this table
    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance
    Chr 7 posSequence#AA
    Chg
    TypeMore#Allele
    freq
    PopTotal
    sample
    More
    ----------
    rs69459631,2
    C,--102611888(+) AAAAAT/CACAAA 3 -- int1 us2k15Minor allele frequency- C:0.00NA WA CSA 9
    rs69459971,2
    C,A,--102611958(+) AGAATT/CGCTTG 3 -- us2k1 int15Minor allele frequency- C:0.11NA WA CSA 9
    rs1901171191,2
    --102611970(+) ACCCGA/GGCGGA 3 -- us2k1 int10--------
    rs1931318241,2
    --102611973(+) CGGGCA/GGAGGT 3 -- us2k1 int10--------
    rs1846133231,2
    --102611990(+) GAGCCA/GAGATT 3 -- us2k1 int10--------
    rs1883301271,2
    --102612014(+) CCAGCC/TTAGGC 3 -- int1 us2k10--------
    rs672166421,2
    C--102612042(+) AAAAAA/-GACAT 3 -- int1 us2k11Minor allele frequency- -:0.00NA 2
    rs784131851,2
    F,--102612126(+) GATTAC/TCTGAG 3 -- int1 us2k11Minor allele frequency- T:0.07EA 120
    rs1808030901,2
    --102612192(+) TTAAGA/GCCAGG 3 -- us2k1 int10--------
    rs102391621,2
    C,--102612206(+) AGTGGC/TTCATG 3 -- int1 us2k12Minor allele frequency- T:0.13CSA EA 122

    HapMap Linkage Disequilibrium report for NFE4 (102613884 - 102629303 bp)
    Structural Variations (Copy Number Variations, Insertions/Deletions, Inversions)
          Database of Genomic Variants (DGV) variations for NFE4: --

    SABiosciences Cancer Mutation PCR Assays
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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.)
    About This Section

    NFE4 for disorders           About MalaCards

    NFE4 for disorders           About GeneDecksing

    OMIM gene information: 612133    OMIM disorders: --


    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)
    About This Section

    PubMed articles for NFE4 gene integrated from 9 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, 9 Zhou W....Jane S.M. (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. (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. (2004)
    4. The role of p22 NF-E4 in human globin gene switching. (PubMed id 15084587)1, 2 Zhou W.... Jane S.M. (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. (2009)
    6. Biochemical characterization of the developmental sta ge- and tissue-specific erythroid transcription factor, NF-E4. (PubMed id 8144507)9 Yang Z. and Engel J.D. (1994)
    7. Developmental regulation of the human beta-globin cluster. (PubMed id 8770365)9 Jane S.M....Cunningham J.M. (1995)

    (in PubMed, OMIM, and NCBI Bookshelf)
    About This Section
     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)
    About This Section
    Entrez Gene: 58160 Ensembl:ENSG00000230257 euGenes: HUgn58160

    (According to HUGE)
    About This Section
      --

    (According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL,
    Wikipedia and/or GeneReviews via UniProtKB/Swiss-Prot)
    About This Section
      --

    (Patent information from GeneIP,
    Licensable technologies from WIS Yeda, Salk, Tufts,
    IP news from LifeMap Sciences, Inc.)
    About This Section
    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, SABiosciences, Novus Biologicals, Sino Biological, Enzo Life Sciences, Abcam, ProSpec, Uscn, Thermo Fisher Scientific, Gene Editing from DNA2.0, Clones from EMD Millipore, OriGene, GenScript, Sino Biological, DNA2.0, SwitchGear Genomics, Vector BioLabs, Cell lines from GenScript and LifeMap BioReagents, PCR Arrays from SABiosciences, Drugs and/or compounds from EMD Millipore, Tocris Bioscience, and/or Enzo Life Sciences),
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    About This Section

     
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    GeneCards Homepage - Last full update: 19 Mar 2013 - Incrementals: 21 Mar 2013 , 15 Apr 2013 , 26 Apr 2013

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    VWF
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    von Willebrand factor
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