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Q16621

- NFE2_HUMAN

UniProt

Q16621 - NFE2_HUMAN

Protein

Transcription factor NF-E2 45 kDa subunit

Gene

NFE2

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 141 (01 Oct 2014)
      Sequence version 1 (01 Nov 1996)
      Previous versions | rss
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    Functioni

    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.2 Publications

    GO - Molecular functioni

    1. protein N-terminus binding Source: UniProtKB
    2. sequence-specific DNA binding Source: BHF-UCL
    3. sequence-specific DNA binding transcription factor activity Source: ProtInc
    4. transcription coactivator activity Source: ProtInc
    5. WW domain binding Source: BHF-UCL

    GO - Biological processi

    1. blood circulation Source: ProtInc
    2. blood coagulation Source: Reactome
    3. cell-cell signaling Source: Ensembl
    4. hemostasis Source: ProtInc
    5. labyrinthine layer blood vessel development Source: Ensembl
    6. multicellular organismal development Source: ProtInc
    7. negative regulation of bone mineralization Source: Ensembl
    8. negative regulation of syncytium formation by plasma membrane fusion Source: Ensembl
    9. nucleosome disassembly Source: BHF-UCL
    10. positive regulation of peptidyl-lysine acetylation Source: Ensembl
    11. positive regulation of transcription, DNA-templated Source: BHF-UCL
    12. regulation of transcription from RNA polymerase II promoter Source: ProtInc
    13. transcription, DNA-templated Source: BHF-UCL

    Keywords - Molecular functioni

    Activator

    Keywords - Biological processi

    Transcription, Transcription regulation

    Keywords - Ligandi

    DNA-binding

    Enzyme and pathway databases

    ReactomeiREACT_24970. Factors involved in megakaryocyte development and platelet production.
    SignaLinkiQ16621.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Transcription factor NF-E2 45 kDa subunit
    Alternative name(s):
    Leucine zipper protein NF-E2
    Nuclear factor, erythroid-derived 2 45 kDa subunit
    p45 NF-E2
    Gene namesi
    Name:NFE2
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 12

    Organism-specific databases

    HGNCiHGNC:7780. NFE2.

    Subcellular locationi

    NucleusPML body. Cytoplasm
    Note: The sumoylated form locates to the nuclear bodies PML oncogenic domains (PODs). Translocated to the cytoplasm through interaction with ITCH.

    GO - Cellular componenti

    1. actin cytoskeleton Source: HPA
    2. cytoplasm Source: UniProtKB-SubCell
    3. nucleoplasm Source: Reactome
    4. nucleus Source: HPA
    5. PML body Source: UniProtKB-SubCell

    Keywords - Cellular componenti

    Cytoplasm, Nucleus

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi368 – 3681K → R: 60% loss of DNA-binding and 5-fold loss of transactivation activity. Almost no colocalization with nuclear bodies. 1 Publication

    Organism-specific databases

    PharmGKBiPA31586.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 373373Transcription factor NF-E2 45 kDa subunitPRO_0000076446Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei157 – 1571Phosphoserine; by MAPK8By similarity
    Modified residuei170 – 1701Phosphoserine; by PKABy similarity
    Cross-linki368 – 368Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO-1)

    Post-translational modificationi

    Phosphorylated on serine residues. In undifferentiated erythrocytes, phosphorylated by MAPK8 which then leads to ubiquitination and protein degradation.By similarity
    Sumoylated. Sumoylation is required for translocation to nuclear bodies PODs, anchoring to the gene loci, and transactivation of the beta-globin gene.1 Publication
    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.By similarity

    Keywords - PTMi

    Isopeptide bond, Phosphoprotein, Ubl conjugation

    Proteomic databases

    MaxQBiQ16621.
    PaxDbiQ16621.
    PRIDEiQ16621.

    PTM databases

    PhosphoSiteiQ16621.

    Expressioni

    Tissue specificityi

    Expressed in hematopoietic cells and also in colon and testis.

    Gene expression databases

    ArrayExpressiQ16621.
    BgeeiQ16621.
    CleanExiHS_NFE2.
    GenevestigatoriQ16621.

    Organism-specific databases

    HPAiHPA001914.

    Interactioni

    Subunit structurei

    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.By similarity

    Protein-protein interaction databases

    BioGridi110850. 20 interactions.
    DIPiDIP-57844N.
    IntActiQ16621. 5 interactions.
    MINTiMINT-3032845.
    STRINGi9606.ENSP00000312436.

    Structurei

    Secondary structure

    1
    373
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Helixi225 – 2339
    Helixi239 – 2446
    Helixi247 – 25610
    Helixi261 – 27919

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1LVXmodel-A221-294[»]
    2KZ5NMR-A214-293[»]
    ProteinModelPortaliQ16621.
    SMRiQ16621. Positions 214-326.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiQ16621.

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini266 – 32964bZIPPROSITE-ProRule annotationAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni1 – 206206Transactivation domainAdd
    BLAST
    Regioni1 – 8383Required for interaction with MAPK8By similarityAdd
    BLAST
    Regioni268 – 28720Basic motifPROSITE-ProRule annotationAdd
    BLAST
    Regioni291 – 2988Leucine-zipperPROSITE-ProRule annotation

    Motif

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Motifi61 – 655PXY motif 1
    Motifi79 – 835PXY motif 2

    Compositional bias

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Compositional biasi59 – 624Poly-Pro
    Compositional biasi77 – 826Poly-Pro

    Domaini

    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.By similarity

    Sequence similaritiesi

    Belongs to the bZIP family. CNC subfamily.Curated
    Contains 1 bZIP (basic-leucine zipper) domain.PROSITE-ProRule annotation

    Phylogenomic databases

    eggNOGiNOG326795.
    HOGENOMiHOG000234410.
    HOVERGENiHBG002901.
    InParanoidiQ16621.
    KOiK09039.
    OMAiPTDKIVN.
    OrthoDBiEOG715Q3N.
    PhylomeDBiQ16621.
    TreeFamiTF326681.

    Family and domain databases

    Gene3Di1.10.880.10. 1 hit.
    InterProiIPR004827. bZIP.
    IPR004826. bZIP_Maf.
    IPR008917. TF_DNA-bd.
    [Graphical view]
    PfamiPF03131. bZIP_Maf. 1 hit.
    [Graphical view]
    SMARTiSM00338. BRLZ. 1 hit.
    [Graphical view]
    SUPFAMiSSF47454. SSF47454. 1 hit.
    PROSITEiPS50217. BZIP. 1 hit.
    PS00036. BZIP_BASIC. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    Q16621-1 [UniParc]FASTAAdd to Basket

    « Hide

    MSPCPPQQSR NRVIQLSTSE LGEMELTWQE IMSITELQGL NAPSEPSFEP    50
    QAPAPYLGPP PPTTYCPCSI HPDSGFPLPP PPYELPASTS HVPDPPYSYG 100
    NMAIPVSKPL SLSGLLSEPL QDPLALLDIG LPAGPPKPQE DPESDSGLSL 150
    NYSDAESLEL EGTEAGRRRS EYVEMYPVEY PYSLMPNSLA HSNYTLPAAE 200
    TPLALEPSSG PVRAKPTARG EAGSRDERRA LAMKIPFPTD KIVNLPVDDF 250
    NELLARYPLT ESQLALVRDI RRRGKNKVAA QNCRKRKLET IVQLERELER 300
    LTNERERLLR ARGEADRTLE VMRQQLTELY RDIFQHLRDE SGNSYSPEEY 350
    ALQQAADGTI FLVPRGTKME ATD 373
    Length:373
    Mass (Da):41,473
    Last modified:November 1, 1996 - v1
    Checksum:iA9821170FB2ED67C
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti334 – 3352FQ → LE in AAA35612. (PubMed:8355703)Curated

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    L24122 mRNA. Translation: AAA16118.1.
    L13974 mRNA. Translation: AAA35612.1.
    S77763 mRNA. Translation: AAB34115.1.
    CR450284 mRNA. Translation: CAG29280.1.
    BT007288 mRNA. Translation: AAP35952.1.
    DQ367844 Genomic DNA. Translation: ABC79302.1.
    BC005044 mRNA. Translation: AAH05044.1.
    CCDSiCCDS8876.1.
    PIRiA49671.
    A54692.
    RefSeqiNP_001129495.1. NM_001136023.2.
    NP_001248390.1. NM_001261461.1.
    NP_006154.1. NM_006163.2.
    XP_005268963.1. XM_005268906.2.
    XP_005268964.1. XM_005268907.1.
    UniGeneiHs.75643.

    Genome annotation databases

    EnsembliENST00000312156; ENSP00000312436; ENSG00000123405.
    ENST00000435572; ENSP00000397185; ENSG00000123405.
    ENST00000540264; ENSP00000439120; ENSG00000123405.
    ENST00000553070; ENSP00000447558; ENSG00000123405.
    GeneIDi4778.
    KEGGihsa:4778.
    UCSCiuc001sfq.4. human.

    Polymorphism databases

    DMDMi6831585.

    Cross-referencesi

    Web resourcesi

    SeattleSNPs

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    L24122 mRNA. Translation: AAA16118.1 .
    L13974 mRNA. Translation: AAA35612.1 .
    S77763 mRNA. Translation: AAB34115.1 .
    CR450284 mRNA. Translation: CAG29280.1 .
    BT007288 mRNA. Translation: AAP35952.1 .
    DQ367844 Genomic DNA. Translation: ABC79302.1 .
    BC005044 mRNA. Translation: AAH05044.1 .
    CCDSi CCDS8876.1.
    PIRi A49671.
    A54692.
    RefSeqi NP_001129495.1. NM_001136023.2.
    NP_001248390.1. NM_001261461.1.
    NP_006154.1. NM_006163.2.
    XP_005268963.1. XM_005268906.2.
    XP_005268964.1. XM_005268907.1.
    UniGenei Hs.75643.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    1LVX model - A 221-294 [» ]
    2KZ5 NMR - A 214-293 [» ]
    ProteinModelPortali Q16621.
    SMRi Q16621. Positions 214-326.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 110850. 20 interactions.
    DIPi DIP-57844N.
    IntActi Q16621. 5 interactions.
    MINTi MINT-3032845.
    STRINGi 9606.ENSP00000312436.

    PTM databases

    PhosphoSitei Q16621.

    Polymorphism databases

    DMDMi 6831585.

    Proteomic databases

    MaxQBi Q16621.
    PaxDbi Q16621.
    PRIDEi Q16621.

    Protocols and materials databases

    DNASUi 4778.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000312156 ; ENSP00000312436 ; ENSG00000123405 .
    ENST00000435572 ; ENSP00000397185 ; ENSG00000123405 .
    ENST00000540264 ; ENSP00000439120 ; ENSG00000123405 .
    ENST00000553070 ; ENSP00000447558 ; ENSG00000123405 .
    GeneIDi 4778.
    KEGGi hsa:4778.
    UCSCi uc001sfq.4. human.

    Organism-specific databases

    CTDi 4778.
    GeneCardsi GC12M054685.
    HGNCi HGNC:7780. NFE2.
    HPAi HPA001914.
    MIMi 601490. gene.
    neXtProti NX_Q16621.
    PharmGKBi PA31586.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG326795.
    HOGENOMi HOG000234410.
    HOVERGENi HBG002901.
    InParanoidi Q16621.
    KOi K09039.
    OMAi PTDKIVN.
    OrthoDBi EOG715Q3N.
    PhylomeDBi Q16621.
    TreeFami TF326681.

    Enzyme and pathway databases

    Reactomei REACT_24970. Factors involved in megakaryocyte development and platelet production.
    SignaLinki Q16621.

    Miscellaneous databases

    EvolutionaryTracei Q16621.
    GeneWikii NFE2.
    GenomeRNAii 4778.
    NextBioi 18424.
    PROi Q16621.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q16621.
    Bgeei Q16621.
    CleanExi HS_NFE2.
    Genevestigatori Q16621.

    Family and domain databases

    Gene3Di 1.10.880.10. 1 hit.
    InterProi IPR004827. bZIP.
    IPR004826. bZIP_Maf.
    IPR008917. TF_DNA-bd.
    [Graphical view ]
    Pfami PF03131. bZIP_Maf. 1 hit.
    [Graphical view ]
    SMARTi SM00338. BRLZ. 1 hit.
    [Graphical view ]
    SUPFAMi SSF47454. SSF47454. 1 hit.
    PROSITEi PS50217. BZIP. 1 hit.
    PS00036. BZIP_BASIC. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Isolation of cDNA encoding the human NF-E2 protein."
      Chan J.Y., Han X.L., Kan Y.W.
      Proc. Natl. Acad. Sci. U.S.A. 90:11366-11370(1993) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    2. "Purification of the human NF-E2 complex: cDNA cloning of the hematopoietic cell-specific subunit and evidence for an associated partner."
      Ney P.A., Andrews N.C., Jane S.M., Safer B., Purucker M.E., Weremowicz S., Goff S.C., Orkin S.H., Neinhuis A.W.
      Mol. Cell. Biol. 13:5604-5612(1993) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    3. "Isolation of a differentially regulated splicing isoform of human NF-E2."
      Pischedda C., Cocco S., Melis A., Marini M.G., Kan Y.W., Cao A., Moi P.
      Proc. Natl. Acad. Sci. U.S.A. 92:3511-3515(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Tissue: Fetal liver.
    4. "Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)."
      Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.
      Submitted (MAY-2004) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    5. "Cloning of human full-length CDSs in BD Creator(TM) system donor vector."
      Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A.
      Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    6. SeattleSNPs variation discovery resource
      Submitted (JAN-2006) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    7. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
      Tissue: Lung.
    8. "Stimulation of NF-E2 DNA binding by CREB-binding protein (CBP)-mediated acetylation."
      Hung H.-L., Kim A.Y., Hong W., Rakowski C., Blobel G.A.
      J. Biol. Chem. 276:10715-10721(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH MAFG, FUNCTION.
    9. "Sumoylation of p45/NF-E2: nuclear positioning and transcriptional activation of the mammalian beta-like globin gene locus."
      Shyu Y.-C., Lee T.-L., Ting C.-Y., Wen S.-C., Hsieh L.-J., Li Y.-C., Hwang J.-L., Lin C.-C., Shen C.-K.J.
      Mol. Cell. Biol. 25:10365-10378(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: SUMOYLATION AT LYS-368, SUBCELLULAR LOCATION, FUNCTION, MUTAGENESIS OF LYS-368, IDENTIFICATION BY MASS SPECTROMETRY.
    10. "Itch regulates p45/NF-E2 in vivo by Lys63-linked ubiquitination."
      Lee T.-L., Shyu Y.-C., Hsu T.-Y., Shen C.-K.J.
      Biochem. Biophys. Res. Commun. 375:326-330(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH ITCH, SUBCELLULAR LOCATION, UBIQUITINATION.
    11. "Northeast structural genomics consortium target HR4653B."
      Northeast structural genomics consortium (NESG)
      Submitted (NOV-2010) to the PDB data bank
      Cited for: STRUCTURE BY NMR OF 214-293.

    Entry informationi

    Entry nameiNFE2_HUMAN
    AccessioniPrimary (citable) accession number: Q16621
    Secondary accession number(s): Q07720, Q6ICV9
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: May 30, 2000
    Last sequence update: November 1, 1996
    Last modified: October 1, 2014
    This is version 141 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. Human chromosome 12
      Human chromosome 12: entries, gene names and cross-references to MIM
    2. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    3. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    4. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3