Full text data of NFE2
NFE2
[Confidence: low (only semi-automatic identification from reviews)]
Transcription factor NF-E2 45 kDa subunit (Leucine zipper protein NF-E2; Nuclear factor, erythroid-derived 2 45 kDa subunit; p45 NF-E2)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Transcription factor NF-E2 45 kDa subunit (Leucine zipper protein NF-E2; Nuclear factor, erythroid-derived 2 45 kDa subunit; p45 NF-E2)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
Q16621
ID NFE2_HUMAN Reviewed; 373 AA.
AC Q16621; Q07720; Q6ICV9;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-NOV-1996, sequence version 1.
DT 22-JAN-2014, entry version 133.
DE RecName: Full=Transcription factor NF-E2 45 kDa subunit;
DE AltName: Full=Leucine zipper protein NF-E2;
DE AltName: Full=Nuclear factor, erythroid-derived 2 45 kDa subunit;
DE AltName: Full=p45 NF-E2;
GN Name=NFE2;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=8248255; DOI=10.1073/pnas.90.23.11366;
RA Chan J.Y., Han X.L., Kan Y.W.;
RT "Isolation of cDNA encoding the human NF-E2 protein.";
RL Proc. Natl. Acad. Sci. U.S.A. 90:11366-11370(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=8355703;
RA Ney P.A., Andrews N.C., Jane S.M., Safer B., Purucker M.E.,
RA Weremowicz S., Goff S.C., Orkin S.H., Neinhuis A.W.;
RT "Purification of the human NF-E2 complex: cDNA cloning of the
RT hematopoietic cell-specific subunit and evidence for an associated
RT partner.";
RL Mol. Cell. Biol. 13:5604-5612(1993).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Fetal liver;
RX PubMed=7724591; DOI=10.1073/pnas.92.8.3511;
RA Pischedda C., Cocco S., Melis A., Marini M.G., Kan Y.W., Cao A.,
RA Moi P.;
RT "Isolation of a differentially regulated splicing isoform of human NF-
RT E2.";
RL Proc. Natl. Acad. Sci. U.S.A. 92:3511-3515(1995).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (MAY-2004) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor
RT vector.";
RL Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RG SeattleSNPs variation discovery resource;
RL Submitted (JAN-2006) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lung;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
RP INTERACTION WITH MAFG, AND FUNCTION.
RX PubMed=11154691; DOI=10.1074/jbc.M007846200;
RA Hung H.-L., Kim A.Y., Hong W., Rakowski C., Blobel G.A.;
RT "Stimulation of NF-E2 DNA binding by CREB-binding protein (CBP)-
RT mediated acetylation.";
RL J. Biol. Chem. 276:10715-10721(2001).
RN [9]
RP SUMOYLATION AT LYS-368, SUBCELLULAR LOCATION, FUNCTION, MASS
RP SPECTROMETRY, AND MUTAGENESIS OF LYS-368.
RX PubMed=16287851; DOI=10.1128/MCB.25.23.10365-10378.2005;
RA Shyu Y.-C., Lee T.-L., Ting C.-Y., Wen S.-C., Hsieh L.-J., Li Y.-C.,
RA Hwang J.-L., Lin C.-C., Shen C.-K.J.;
RT "Sumoylation of p45/NF-E2: nuclear positioning and transcriptional
RT activation of the mammalian beta-like globin gene locus.";
RL Mol. Cell. Biol. 25:10365-10378(2005).
RN [10]
RP INTERACTION WITH ITCH, SUBCELLULAR LOCATION, AND UBIQUITINATION.
RX PubMed=18718448; DOI=10.1016/j.bbrc.2008.07.164;
RA Lee T.-L., Shyu Y.-C., Hsu T.-Y., Shen C.-K.J.;
RT "Itch regulates p45/NF-E2 in vivo by Lys63-linked ubiquitination.";
RL Biochem. Biophys. Res. Commun. 375:326-330(2008).
RN [11]
RP STRUCTURE BY NMR OF 214-293.
RG Northeast structural genomics consortium (NESG);
RT "Northeast structural genomics consortium target HR4653B.";
RL Submitted (NOV-2010) to the PDB data bank.
CC -!- FUNCTION: Component of the NF-E2 complex essential for regulating
CC erythroid and megakaryocytic maturation and differentiation. Binds
CC to the hypersensitive site 2 (HS2) of the beta-globin control
CC region (LCR). This subunit (NFE2) recognizes the TCAT/C sequence
CC of the AP-1-like core palindrome present in a number of erythroid
CC and megakaryocytic gene promoters. Requires MAFK or other small
CC MAF proteins for binding to the NF-E2 motif. May play a role in
CC all aspects of hemoglobin production from globin and heme
CC synthesis to procurement of iron.
CC -!- SUBUNIT: Homodimer; can bind DNA as a homodimer. Erythroid
CC transcription activator nuclear factor erythroid-derived 2 (NF-
CC E2), composed of a heterodimer of NFE2 and MAFK, possesses
CC transactivation activity on beta-globin. Also forms high affinity
CC heterodimer with MAFG; the interaction promotes erythropoiesis.
CC Interacts (via the PXY motif 1) with ITCH (via the WW 1 domain);
CC the interaction promotes 'Lys63'-linked ubiquitination of NFE2,
CC translocates it to the cytoplasm and inhibits its transactivation
CC activity. Interacts with KMT2D/MLL2; the interaction promotes
CC transactivation of the beta-globin locus (By similarity).
CC Interacts with MAPK8 (phosphorylated form); the interaction leads
CC to phosphorylation of NFE2 in undifferentiated cells (By
CC similarity).
CC -!- SUBCELLULAR LOCATION: Nucleus, PML body. Cytoplasm. Note=The
CC sumoylated form locates to the nuclear bodies PML oncogenic
CC domains (PODs). Translocated to the cytoplasm through interaction
CC with ITCH.
CC -!- TISSUE SPECIFICITY: Expressed in hematopoietic cells and also in
CC colon and testis.
CC -!- DOMAIN: The PXY motifs are required for binding WW domains. PXY1
CC is required to promote transactivation of beta-globin and for
CC hyperacetylation of histone H3, but not for binding to the HS2
CC promoter site (By similarity).
CC -!- PTM: Phosphorylated on serine residues (By similarity). In
CC undifferentiated erythrocytes, phosphorylated by MAPK8 which then
CC leads to ubiquitination and protein degradation (By similarity).
CC -!- PTM: Sumoylated. Sumoylation is required for translocation to
CC nuclear bodies PODs, anchoring to the gene loci, and
CC transactivation of the beta-globin gene.
CC -!- PTM: Ubiquitinated mainly by 'Lys63'-linked ubiquitin.
CC Polyubiquitination with 'Lys63'-linked ubiquitin by ITCH retains
CC NFE2 in the cytoplasm preventing its transactivation activity. In
CC undifferentiated erythrocyte, ubiquitinated after MAPK8-mediatd
CC phosphorylation leading to protein degradation (By similarity).
CC -!- SIMILARITY: Belongs to the bZIP family. CNC subfamily.
CC -!- SIMILARITY: Contains 1 bZIP (basic-leucine zipper) domain.
CC -!- WEB RESOURCE: Name=SeattleSNPs;
CC URL="http://pga.gs.washington.edu/data/nfe2/";
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
DR EMBL; L24122; AAA16118.1; -; mRNA.
DR EMBL; L13974; AAA35612.1; -; mRNA.
DR EMBL; S77763; AAB34115.1; -; mRNA.
DR EMBL; CR450284; CAG29280.1; -; mRNA.
DR EMBL; BT007288; AAP35952.1; -; mRNA.
DR EMBL; DQ367844; ABC79302.1; -; Genomic_DNA.
DR EMBL; BC005044; AAH05044.1; -; mRNA.
DR PIR; A49671; A49671.
DR PIR; A54692; A54692.
DR RefSeq; NP_001129495.1; NM_001136023.2.
DR RefSeq; NP_001248390.1; NM_001261461.1.
DR RefSeq; NP_006154.1; NM_006163.2.
DR RefSeq; XP_005268963.1; XM_005268906.1.
DR RefSeq; XP_005268964.1; XM_005268907.1.
DR UniGene; Hs.75643; -.
DR PDB; 1LVX; Model; -; A=221-294.
DR PDB; 2KZ5; NMR; -; A=214-293.
DR PDBsum; 1LVX; -.
DR PDBsum; 2KZ5; -.
DR ProteinModelPortal; Q16621; -.
DR SMR; Q16621; 214-293.
DR DIP; DIP-57844N; -.
DR IntAct; Q16621; 4.
DR MINT; MINT-3032845; -.
DR STRING; 9606.ENSP00000312436; -.
DR PhosphoSite; Q16621; -.
DR DMDM; 6831585; -.
DR PaxDb; Q16621; -.
DR PRIDE; Q16621; -.
DR DNASU; 4778; -.
DR Ensembl; ENST00000312156; ENSP00000312436; ENSG00000123405.
DR Ensembl; ENST00000435572; ENSP00000397185; ENSG00000123405.
DR Ensembl; ENST00000540264; ENSP00000439120; ENSG00000123405.
DR Ensembl; ENST00000553070; ENSP00000447558; ENSG00000123405.
DR GeneID; 4778; -.
DR KEGG; hsa:4778; -.
DR UCSC; uc001sfq.4; human.
DR CTD; 4778; -.
DR GeneCards; GC12M054685; -.
DR HGNC; HGNC:7780; NFE2.
DR HPA; HPA001914; -.
DR MIM; 601490; gene.
DR neXtProt; NX_Q16621; -.
DR PharmGKB; PA31586; -.
DR eggNOG; NOG326795; -.
DR HOGENOM; HOG000234410; -.
DR HOVERGEN; HBG002901; -.
DR InParanoid; Q16621; -.
DR KO; K09039; -.
DR OMA; PTDKIVN; -.
DR OrthoDB; EOG715Q3N; -.
DR PhylomeDB; Q16621; -.
DR Reactome; REACT_604; Hemostasis.
DR SignaLink; Q16621; -.
DR EvolutionaryTrace; Q16621; -.
DR GeneWiki; NFE2; -.
DR GenomeRNAi; 4778; -.
DR NextBio; 18424; -.
DR PRO; PR:Q16621; -.
DR ArrayExpress; Q16621; -.
DR Bgee; Q16621; -.
DR CleanEx; HS_NFE2; -.
DR Genevestigator; Q16621; -.
DR GO; GO:0015629; C:actin cytoskeleton; IDA:HPA.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0016605; C:PML body; IEA:UniProtKB-SubCell.
DR GO; GO:0043565; F:sequence-specific DNA binding; TAS:BHF-UCL.
DR GO; GO:0003700; F:sequence-specific DNA binding transcription factor activity; TAS:ProtInc.
DR GO; GO:0003713; F:transcription coactivator activity; TAS:ProtInc.
DR GO; GO:0050699; F:WW domain binding; IDA:MGI.
DR GO; GO:0008015; P:blood circulation; TAS:ProtInc.
DR GO; GO:0007596; P:blood coagulation; TAS:Reactome.
DR GO; GO:0007267; P:cell-cell signaling; IEA:Ensembl.
DR GO; GO:0007275; P:multicellular organismal development; TAS:ProtInc.
DR GO; GO:0030502; P:negative regulation of bone mineralization; IEA:Ensembl.
DR GO; GO:0006337; P:nucleosome disassembly; TAS:BHF-UCL.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-dependent; TAS:BHF-UCL.
DR GO; GO:0006357; P:regulation of transcription from RNA polymerase II promoter; TAS:ProtInc.
DR GO; GO:0006351; P:transcription, DNA-dependent; TAS:BHF-UCL.
DR Gene3D; 1.10.880.10; -; 1.
DR InterPro; IPR004827; bZIP.
DR InterPro; IPR004826; bZIP_Maf.
DR InterPro; IPR008917; TF_DNA-bd.
DR Pfam; PF03131; bZIP_Maf; 1.
DR SMART; SM00338; BRLZ; 1.
DR SUPFAM; SSF47454; SSF47454; 1.
DR PROSITE; PS50217; BZIP; 1.
DR PROSITE; PS00036; BZIP_BASIC; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Activator; Complete proteome; Cytoplasm; DNA-binding;
KW Isopeptide bond; Nucleus; Phosphoprotein; Reference proteome;
KW Transcription; Transcription regulation; Ubl conjugation.
FT CHAIN 1 373 Transcription factor NF-E2 45 kDa
FT subunit.
FT /FTId=PRO_0000076446.
FT DOMAIN 266 329 bZIP.
FT REGION 1 206 Transactivation domain.
FT REGION 1 83 Required for interaction with MAPK8 (By
FT similarity).
FT REGION 268 287 Basic motif (By similarity).
FT REGION 291 298 Leucine-zipper (By similarity).
FT MOTIF 61 65 PXY motif 1.
FT MOTIF 79 83 PXY motif 2.
FT COMPBIAS 59 62 Poly-Pro.
FT COMPBIAS 77 82 Poly-Pro.
FT MOD_RES 157 157 Phosphoserine; by MAPK8 (By similarity).
FT MOD_RES 170 170 Phosphoserine; by PKA (By similarity).
FT CROSSLNK 368 368 Glycyl lysine isopeptide (Lys-Gly)
FT (interchain with G-Cter in SUMO-1).
FT MUTAGEN 368 368 K->R: 60% loss of DNA-binding and 5-fold
FT loss of transactivation activity. Almost
FT no colocalization with nuclear bodies.
FT CONFLICT 334 335 FQ -> LE (in Ref. 2; AAA35612).
FT HELIX 225 233
FT HELIX 239 244
FT HELIX 247 256
FT HELIX 261 279
SQ SEQUENCE 373 AA; 41473 MW; A9821170FB2ED67C CRC64;
MSPCPPQQSR NRVIQLSTSE LGEMELTWQE IMSITELQGL NAPSEPSFEP QAPAPYLGPP
PPTTYCPCSI HPDSGFPLPP PPYELPASTS HVPDPPYSYG NMAIPVSKPL SLSGLLSEPL
QDPLALLDIG LPAGPPKPQE DPESDSGLSL NYSDAESLEL EGTEAGRRRS EYVEMYPVEY
PYSLMPNSLA HSNYTLPAAE TPLALEPSSG PVRAKPTARG EAGSRDERRA LAMKIPFPTD
KIVNLPVDDF NELLARYPLT ESQLALVRDI RRRGKNKVAA QNCRKRKLET IVQLERELER
LTNERERLLR ARGEADRTLE VMRQQLTELY RDIFQHLRDE SGNSYSPEEY ALQQAADGTI
FLVPRGTKME ATD
//
ID NFE2_HUMAN Reviewed; 373 AA.
AC Q16621; Q07720; Q6ICV9;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-NOV-1996, sequence version 1.
DT 22-JAN-2014, entry version 133.
DE RecName: Full=Transcription factor NF-E2 45 kDa subunit;
DE AltName: Full=Leucine zipper protein NF-E2;
DE AltName: Full=Nuclear factor, erythroid-derived 2 45 kDa subunit;
DE AltName: Full=p45 NF-E2;
GN Name=NFE2;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=8248255; DOI=10.1073/pnas.90.23.11366;
RA Chan J.Y., Han X.L., Kan Y.W.;
RT "Isolation of cDNA encoding the human NF-E2 protein.";
RL Proc. Natl. Acad. Sci. U.S.A. 90:11366-11370(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=8355703;
RA Ney P.A., Andrews N.C., Jane S.M., Safer B., Purucker M.E.,
RA Weremowicz S., Goff S.C., Orkin S.H., Neinhuis A.W.;
RT "Purification of the human NF-E2 complex: cDNA cloning of the
RT hematopoietic cell-specific subunit and evidence for an associated
RT partner.";
RL Mol. Cell. Biol. 13:5604-5612(1993).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Fetal liver;
RX PubMed=7724591; DOI=10.1073/pnas.92.8.3511;
RA Pischedda C., Cocco S., Melis A., Marini M.G., Kan Y.W., Cao A.,
RA Moi P.;
RT "Isolation of a differentially regulated splicing isoform of human NF-
RT E2.";
RL Proc. Natl. Acad. Sci. U.S.A. 92:3511-3515(1995).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (MAY-2004) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor
RT vector.";
RL Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RG SeattleSNPs variation discovery resource;
RL Submitted (JAN-2006) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lung;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
RP INTERACTION WITH MAFG, AND FUNCTION.
RX PubMed=11154691; DOI=10.1074/jbc.M007846200;
RA Hung H.-L., Kim A.Y., Hong W., Rakowski C., Blobel G.A.;
RT "Stimulation of NF-E2 DNA binding by CREB-binding protein (CBP)-
RT mediated acetylation.";
RL J. Biol. Chem. 276:10715-10721(2001).
RN [9]
RP SUMOYLATION AT LYS-368, SUBCELLULAR LOCATION, FUNCTION, MASS
RP SPECTROMETRY, AND MUTAGENESIS OF LYS-368.
RX PubMed=16287851; DOI=10.1128/MCB.25.23.10365-10378.2005;
RA Shyu Y.-C., Lee T.-L., Ting C.-Y., Wen S.-C., Hsieh L.-J., Li Y.-C.,
RA Hwang J.-L., Lin C.-C., Shen C.-K.J.;
RT "Sumoylation of p45/NF-E2: nuclear positioning and transcriptional
RT activation of the mammalian beta-like globin gene locus.";
RL Mol. Cell. Biol. 25:10365-10378(2005).
RN [10]
RP INTERACTION WITH ITCH, SUBCELLULAR LOCATION, AND UBIQUITINATION.
RX PubMed=18718448; DOI=10.1016/j.bbrc.2008.07.164;
RA Lee T.-L., Shyu Y.-C., Hsu T.-Y., Shen C.-K.J.;
RT "Itch regulates p45/NF-E2 in vivo by Lys63-linked ubiquitination.";
RL Biochem. Biophys. Res. Commun. 375:326-330(2008).
RN [11]
RP STRUCTURE BY NMR OF 214-293.
RG Northeast structural genomics consortium (NESG);
RT "Northeast structural genomics consortium target HR4653B.";
RL Submitted (NOV-2010) to the PDB data bank.
CC -!- FUNCTION: Component of the NF-E2 complex essential for regulating
CC erythroid and megakaryocytic maturation and differentiation. Binds
CC to the hypersensitive site 2 (HS2) of the beta-globin control
CC region (LCR). This subunit (NFE2) recognizes the TCAT/C sequence
CC of the AP-1-like core palindrome present in a number of erythroid
CC and megakaryocytic gene promoters. Requires MAFK or other small
CC MAF proteins for binding to the NF-E2 motif. May play a role in
CC all aspects of hemoglobin production from globin and heme
CC synthesis to procurement of iron.
CC -!- SUBUNIT: Homodimer; can bind DNA as a homodimer. Erythroid
CC transcription activator nuclear factor erythroid-derived 2 (NF-
CC E2), composed of a heterodimer of NFE2 and MAFK, possesses
CC transactivation activity on beta-globin. Also forms high affinity
CC heterodimer with MAFG; the interaction promotes erythropoiesis.
CC Interacts (via the PXY motif 1) with ITCH (via the WW 1 domain);
CC the interaction promotes 'Lys63'-linked ubiquitination of NFE2,
CC translocates it to the cytoplasm and inhibits its transactivation
CC activity. Interacts with KMT2D/MLL2; the interaction promotes
CC transactivation of the beta-globin locus (By similarity).
CC Interacts with MAPK8 (phosphorylated form); the interaction leads
CC to phosphorylation of NFE2 in undifferentiated cells (By
CC similarity).
CC -!- SUBCELLULAR LOCATION: Nucleus, PML body. Cytoplasm. Note=The
CC sumoylated form locates to the nuclear bodies PML oncogenic
CC domains (PODs). Translocated to the cytoplasm through interaction
CC with ITCH.
CC -!- TISSUE SPECIFICITY: Expressed in hematopoietic cells and also in
CC colon and testis.
CC -!- DOMAIN: The PXY motifs are required for binding WW domains. PXY1
CC is required to promote transactivation of beta-globin and for
CC hyperacetylation of histone H3, but not for binding to the HS2
CC promoter site (By similarity).
CC -!- PTM: Phosphorylated on serine residues (By similarity). In
CC undifferentiated erythrocytes, phosphorylated by MAPK8 which then
CC leads to ubiquitination and protein degradation (By similarity).
CC -!- PTM: Sumoylated. Sumoylation is required for translocation to
CC nuclear bodies PODs, anchoring to the gene loci, and
CC transactivation of the beta-globin gene.
CC -!- PTM: Ubiquitinated mainly by 'Lys63'-linked ubiquitin.
CC Polyubiquitination with 'Lys63'-linked ubiquitin by ITCH retains
CC NFE2 in the cytoplasm preventing its transactivation activity. In
CC undifferentiated erythrocyte, ubiquitinated after MAPK8-mediatd
CC phosphorylation leading to protein degradation (By similarity).
CC -!- SIMILARITY: Belongs to the bZIP family. CNC subfamily.
CC -!- SIMILARITY: Contains 1 bZIP (basic-leucine zipper) domain.
CC -!- WEB RESOURCE: Name=SeattleSNPs;
CC URL="http://pga.gs.washington.edu/data/nfe2/";
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
DR EMBL; L24122; AAA16118.1; -; mRNA.
DR EMBL; L13974; AAA35612.1; -; mRNA.
DR EMBL; S77763; AAB34115.1; -; mRNA.
DR EMBL; CR450284; CAG29280.1; -; mRNA.
DR EMBL; BT007288; AAP35952.1; -; mRNA.
DR EMBL; DQ367844; ABC79302.1; -; Genomic_DNA.
DR EMBL; BC005044; AAH05044.1; -; mRNA.
DR PIR; A49671; A49671.
DR PIR; A54692; A54692.
DR RefSeq; NP_001129495.1; NM_001136023.2.
DR RefSeq; NP_001248390.1; NM_001261461.1.
DR RefSeq; NP_006154.1; NM_006163.2.
DR RefSeq; XP_005268963.1; XM_005268906.1.
DR RefSeq; XP_005268964.1; XM_005268907.1.
DR UniGene; Hs.75643; -.
DR PDB; 1LVX; Model; -; A=221-294.
DR PDB; 2KZ5; NMR; -; A=214-293.
DR PDBsum; 1LVX; -.
DR PDBsum; 2KZ5; -.
DR ProteinModelPortal; Q16621; -.
DR SMR; Q16621; 214-293.
DR DIP; DIP-57844N; -.
DR IntAct; Q16621; 4.
DR MINT; MINT-3032845; -.
DR STRING; 9606.ENSP00000312436; -.
DR PhosphoSite; Q16621; -.
DR DMDM; 6831585; -.
DR PaxDb; Q16621; -.
DR PRIDE; Q16621; -.
DR DNASU; 4778; -.
DR Ensembl; ENST00000312156; ENSP00000312436; ENSG00000123405.
DR Ensembl; ENST00000435572; ENSP00000397185; ENSG00000123405.
DR Ensembl; ENST00000540264; ENSP00000439120; ENSG00000123405.
DR Ensembl; ENST00000553070; ENSP00000447558; ENSG00000123405.
DR GeneID; 4778; -.
DR KEGG; hsa:4778; -.
DR UCSC; uc001sfq.4; human.
DR CTD; 4778; -.
DR GeneCards; GC12M054685; -.
DR HGNC; HGNC:7780; NFE2.
DR HPA; HPA001914; -.
DR MIM; 601490; gene.
DR neXtProt; NX_Q16621; -.
DR PharmGKB; PA31586; -.
DR eggNOG; NOG326795; -.
DR HOGENOM; HOG000234410; -.
DR HOVERGEN; HBG002901; -.
DR InParanoid; Q16621; -.
DR KO; K09039; -.
DR OMA; PTDKIVN; -.
DR OrthoDB; EOG715Q3N; -.
DR PhylomeDB; Q16621; -.
DR Reactome; REACT_604; Hemostasis.
DR SignaLink; Q16621; -.
DR EvolutionaryTrace; Q16621; -.
DR GeneWiki; NFE2; -.
DR GenomeRNAi; 4778; -.
DR NextBio; 18424; -.
DR PRO; PR:Q16621; -.
DR ArrayExpress; Q16621; -.
DR Bgee; Q16621; -.
DR CleanEx; HS_NFE2; -.
DR Genevestigator; Q16621; -.
DR GO; GO:0015629; C:actin cytoskeleton; IDA:HPA.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0016605; C:PML body; IEA:UniProtKB-SubCell.
DR GO; GO:0043565; F:sequence-specific DNA binding; TAS:BHF-UCL.
DR GO; GO:0003700; F:sequence-specific DNA binding transcription factor activity; TAS:ProtInc.
DR GO; GO:0003713; F:transcription coactivator activity; TAS:ProtInc.
DR GO; GO:0050699; F:WW domain binding; IDA:MGI.
DR GO; GO:0008015; P:blood circulation; TAS:ProtInc.
DR GO; GO:0007596; P:blood coagulation; TAS:Reactome.
DR GO; GO:0007267; P:cell-cell signaling; IEA:Ensembl.
DR GO; GO:0007275; P:multicellular organismal development; TAS:ProtInc.
DR GO; GO:0030502; P:negative regulation of bone mineralization; IEA:Ensembl.
DR GO; GO:0006337; P:nucleosome disassembly; TAS:BHF-UCL.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-dependent; TAS:BHF-UCL.
DR GO; GO:0006357; P:regulation of transcription from RNA polymerase II promoter; TAS:ProtInc.
DR GO; GO:0006351; P:transcription, DNA-dependent; TAS:BHF-UCL.
DR Gene3D; 1.10.880.10; -; 1.
DR InterPro; IPR004827; bZIP.
DR InterPro; IPR004826; bZIP_Maf.
DR InterPro; IPR008917; TF_DNA-bd.
DR Pfam; PF03131; bZIP_Maf; 1.
DR SMART; SM00338; BRLZ; 1.
DR SUPFAM; SSF47454; SSF47454; 1.
DR PROSITE; PS50217; BZIP; 1.
DR PROSITE; PS00036; BZIP_BASIC; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Activator; Complete proteome; Cytoplasm; DNA-binding;
KW Isopeptide bond; Nucleus; Phosphoprotein; Reference proteome;
KW Transcription; Transcription regulation; Ubl conjugation.
FT CHAIN 1 373 Transcription factor NF-E2 45 kDa
FT subunit.
FT /FTId=PRO_0000076446.
FT DOMAIN 266 329 bZIP.
FT REGION 1 206 Transactivation domain.
FT REGION 1 83 Required for interaction with MAPK8 (By
FT similarity).
FT REGION 268 287 Basic motif (By similarity).
FT REGION 291 298 Leucine-zipper (By similarity).
FT MOTIF 61 65 PXY motif 1.
FT MOTIF 79 83 PXY motif 2.
FT COMPBIAS 59 62 Poly-Pro.
FT COMPBIAS 77 82 Poly-Pro.
FT MOD_RES 157 157 Phosphoserine; by MAPK8 (By similarity).
FT MOD_RES 170 170 Phosphoserine; by PKA (By similarity).
FT CROSSLNK 368 368 Glycyl lysine isopeptide (Lys-Gly)
FT (interchain with G-Cter in SUMO-1).
FT MUTAGEN 368 368 K->R: 60% loss of DNA-binding and 5-fold
FT loss of transactivation activity. Almost
FT no colocalization with nuclear bodies.
FT CONFLICT 334 335 FQ -> LE (in Ref. 2; AAA35612).
FT HELIX 225 233
FT HELIX 239 244
FT HELIX 247 256
FT HELIX 261 279
SQ SEQUENCE 373 AA; 41473 MW; A9821170FB2ED67C CRC64;
MSPCPPQQSR NRVIQLSTSE LGEMELTWQE IMSITELQGL NAPSEPSFEP QAPAPYLGPP
PPTTYCPCSI HPDSGFPLPP PPYELPASTS HVPDPPYSYG NMAIPVSKPL SLSGLLSEPL
QDPLALLDIG LPAGPPKPQE DPESDSGLSL NYSDAESLEL EGTEAGRRRS EYVEMYPVEY
PYSLMPNSLA HSNYTLPAAE TPLALEPSSG PVRAKPTARG EAGSRDERRA LAMKIPFPTD
KIVNLPVDDF NELLARYPLT ESQLALVRDI RRRGKNKVAA QNCRKRKLET IVQLERELER
LTNERERLLR ARGEADRTLE VMRQQLTELY RDIFQHLRDE SGNSYSPEEY ALQQAADGTI
FLVPRGTKME ATD
//
MIM
601490
*RECORD*
*FIELD* NO
601490
*FIELD* TI
*601490 NUCLEAR FACTOR ERYTHROID 2, p45 SUBUNIT; NFE2
;;p45
*FIELD* TX
DESCRIPTION
read more
The NFE2 gene encodes a hematopoietic transcription factor (summary by
Jutzi et al., 2013).
CLONING
Ney et al. (1993) cloned the 45-kD subunit of the human globin locus
control region binding protein, NFE2, by homology to the murine gene.
Immunoprecipitation experiments demonstrated in vivo association of the
p45 subunit with an 18-kD protein (see MAFG, 602020, and MAFK, 600197).
Because bZIP proteins bind DNA as dimers, Ney et al. (1993) considered
it likely that native NFE2 is a heterodimer of 45- and 18-kD subunits.
Chan et al. (1993) likewise cloned the human homolog of mouse NFE2.
Extensive survey of human tissue samples found that NFE2 expression is
not limited to erythropoietic organs. Expression in the colon and testis
suggested that NFE2 may participate in the regulation of genes other
than globin.
Peters et al. (1993) demonstrated Nfe2 expression in the mouse small
intestine and NFE2 binding activity in nuclear extracts of a human colon
carcinoma cell line (Caco-2). Caco-2 cells possess properties of the
small intestine, including the ability to transport iron.
MAPPING
By fluorescence in situ hybridization, the NFE2 gene was assigned to
chromosome 12q13 (Weremowicz et al., 1993; Ney et al., 1993).
By fluorescence in situ hybridization, Chan et al. (1995) confirmed the
localization to 12q13.1-q13.3 and demonstrated that 2 genes of the same
family of transcription factors with many similarities of gene
structure, NFE2L1 (163260) and NFE2L2 (600492), are each located on
other chromosomes. The 3 genes probably were derived from a single
ancestor by chromosomal duplication inasmuch as other genes that also
map to the 3 chromosomal regions are related to one another.
MOLECULAR GENETICS
Jutzi et al. (2013) identified 7 different somatic insertion or deletion
mutations in the NFE2 gene in 8 patients with myeloproliferative
disorders, including 3 with polycythemia vera (PV; 263300) and 5 with
myelofibrosis (254450), either primary or secondary. In vitro studies
showed that the mutant truncated NFE2 proteins were unable to bind DNA
and had lost reporter gene activity. However, coexpression of mutant
NFE2 constructs with wildtype NFE2 resulted in significantly enhanced
transcriptional activity. Analysis of patient cells showed low levels of
the mutant truncated protein, but increased levels of the wildtype NFE2
protein compared to control cells, likely due to both increased mRNA and
increased stability of the wildtype protein. All 7 patients tested also
carried a JAK2 V617F mutation (147796.0001). Hematopoietic cell colonies
grown from 3 patients showed that the NFE2 mutation was acquired
subsequent to the JAK2 mutation, and further cellular studies indicated
that an NFE2 mutation conferred a proliferative advantage of cells
compared to cells carrying only the JAK2 mutation. Cells carrying mutant
NFE2 displayed an increase in the proportion of cells in the S phase,
consistent with enhanced cell division and proliferation, and this was
associated with higher levels of cell cycle regulators. These findings
were replicated in mice carrying NFE2 mutations, who developed
thrombocytosis, erythrocytosis, and neutrophilia.
ANIMAL MODEL
Peters et al. (1993) mapped the Nfe2 gene to mouse chromosome 15 in a
region containing the microcytic anemia (mk) gene. Homozygous mk mice
were shown by Bannerman et al. (1972) to have defective intestinal iron
transport and severe anemia. Peters et al. (1993) identified what they
thought was a mutation in the Nfe2 gene in mk mice (V173A), but later
confirmed the change to be a polymorphism.
The mechanisms regulating the formation of blood platelets within
megakaryocytes are not fully understood. Shivdasani et al. (1995)
generated mice lacking the hematopoietic subunit (p45) of the
heterodimeric erythroid transcription factor Nfe2. Unexpectedly,
homozygous Nfe2-deficient mice lacked circulating platelets and died of
hemorrhage; their megakaryocytes showed no cytoplasmic platelet
formation. Though platelets were absent, serum levels of the growth
factor thrombopoietin/Mgdf (600044) were not elevated above those of
controls. Nevertheless, the homozygous Nfe2 deficient megakaryocytes
proliferated in vivo in response to thrombopoietin administration. Thus,
the authors concluded that, as an essential factor for megakaryocyte
maturation and platelet production, NFE2 must regulate critical target
genes independent of the action of thrombopoietin. In contrast to the
dramatic absence of circulating platelets in homozygous mutant mice, the
effect of loss of Nfe2 on the erythroid lineage was surprisingly mild
(Shivdasani and Orkin, 1995). Although neonates exhibited severe anemia
and dysmorphic red cell changes, probably compounded by concomitant
bleeding, surviving adults exhibited only mild changes consistent with a
small decrease in the hemoglobin content per cell. p45 Nfe2-null mice
responded to anemia with compensatory reticulocytosis and splenomegaly.
Globin chain synthesis was balanced, and switching from fetal to adult
globins progressed normally. Although these findings were consistent
with the substitution of NFE2 function in vivo by one or more
compensating proteins, gel shift assays using nuclear extracts from p45
Nfe2-null mice failed to reveal novel complexes formed on an Nfe2
binding site. Thus, the authors concluded that regulation of globin gene
transcription through NFE2 binding sites in vivo is more complex than
had previously been appreciated.
Kaufmann et al. (2012) found that mice with overexpression of the Nfe2
gene in hematopoietic cells developed features of myeloproliferative
disorders, including thrombocytosis, leukocytosis, Epo-independent
colony formation, characteristic bone marrow histology, expansion of
stem and progenitor compartments, and spontaneous transformation to
acute myeloid leukemia. This phenotype was transplantable to secondary
recipient mice. Cells from Nfe2 transgenic mice showed hypoacetylation
of histone H3 (602810). Treatment of mice with a histone deacetylase
inhibitor (HDAC-I) restored physiologic levels of histone H3
acetylation, decreased Nfe2 expression, and normalized platelet numbers.
Similarly, patients with myeloproliferative disorders treated with an
HDAC-I showed a decrease in NFE2 expression. These data established a
role for aberrant NFE2 expression in the pathophysiology of
myeloproliferative disorders.
*FIELD* RF
1. Bannerman, R. M.; Edwards, J. A.; Kreimer-Birnbaum, M.; McFarland,
E.; Russell, E. S.: Hereditary microcytic anaemia in the mouse; studies
in iron distribution and metabolism. Brit. J. Haemat. 23: 235-245,
1972.
2. Chan, J. Y.; Cheung, M.-C.; Moi, P.; Chan, K.; Kan, Y. W.: Chromosomal
localization of the human NF-E2 family of bZIP transcription factors
by fluorescence in situ hybridization. Hum. Genet. 95: 265-269,
1995.
3. Chan, J. Y.; Han, X.-L.; Kan, Y. W.: Isolation of cDNA encoding
the human NF-E2 protein. Proc. Nat. Acad. Sci. 90: 11366-11370,
1993.
4. Jutzi, J. S.; Bogeska, R.; Nikoloski, G.; Schmid, C. A.; Seeger,
T. S.; Stegelmann, F.; Schwemmers, S.; Grunder, A.; Peeken, J. C.;
Gothwal, M.; Wehrle, J.; Aumann, K.; Hamdi, K.; Dierks, C.; Wang,
W.; Dohner, K.; Jansen, J. H.; Pahl, H. L.: MPN patients harbor recurrent
truncating mutations in transcription factor NF-E2. J. Exp. Med. 210:
1003-1019, 2013.
5. Kaufmann, K. B.; Grunder, A.; Hadlich, T.; Wehrle, J.; Gothwal,
M.; Bogeska, R.; Seeger, T. S.; Kayser, S.; Pham, K.-B.; Jutzi, J.
S.; Ganzenmuller, L.; Steinemann, D.; and 11 others: A novel murine
model of myeloproliferative disorders generated by overexpression
of the transcription factor NF-E2. J. Exp. Med. 209: 35-50, 2012.
6. Ney, P. A.; Andrews, N. C.; Jane, S. M.; Safer, B.; Purucker, M.
E.; Weremowicz, S.; Morton, C. C.; Goff, S. C.; Orkin, S. H.; Nienhuis,
A. W.: Purification of the human NF-E2 complex: cDNA cloning of the
hematopoietic cell-specific subunit and evidence for an associated
partner. Molec. Cell. Biol. 13: 5604-5612, 1993.
7. Peters, L. L.; Andrews, N. C.; Eicher, E. M.; Davidson, M. B.;
Orkin, S. H.; Lux, S. E.: Mouse microcytic anaemia caused by a defect
in the gene encoding the globin enhancer-binding protein NF-E2. Nature 362:
768-770, 1993. Note: Erratum: Nature 371: 358 only, 1994.
8. Peters, L. L.; Bishop, T. R.; Andrews, N. C.: Globin-enhancer
binding factor NF-E2 is implicated in the regulation of heme biosynthesis
and iron uptake in mk/mk mice. (Abstract) Blood 82 (suppl. 1): 179a,
1993.
9. Shivdasani, R. A.; Orkin, S. H.: Erythropoiesis and globin gene
expression in mice lacking the transcription factor NF-E2. Proc.
Nat. Acad. Sci. 92: 8690-8694, 1995.
10. Shivdasani, R. A.; Rosenblatt, M. F.; Zucker-Franklin, D.; Jackson,
C. W.; Hunt, P.; Saris, C. J. M.; Orkin, S. H.: Transcription factor
NF-E2 is required for platelet formation independent of the actions
of thrombopoietin/MGDF in megakaryocyte development. Cell 81: 695-704,
1995.
11. Weremowicz, S.; Andrews, N. C.; Orkin, S. H.; Morton, C. C.:
Mapping the p45 subunit of human NFE2 to 12q13. (Abstract) Human
Genome Mapping Workshop 93 25, 1993.
*FIELD* CN
Cassandra L. Kniffin - updated: 1/7/2014
Anne M. Stumpf - updated: 9/14/2010
*FIELD* CD
Alan F. Scott: 11/7/1996
*FIELD* ED
carol: 01/08/2014
ckniffin: 1/7/2014
carol: 10/9/2012
alopez: 11/16/2010
alopez: 9/14/2010
carol: 11/6/2008
ckniffin: 1/5/2006
carol: 8/13/2001
mgross: 3/16/1999
mgross: 3/15/1999
carol: 6/23/1998
mark: 11/12/1996
carol: 11/10/1996
joanna: 11/7/1996
*RECORD*
*FIELD* NO
601490
*FIELD* TI
*601490 NUCLEAR FACTOR ERYTHROID 2, p45 SUBUNIT; NFE2
;;p45
*FIELD* TX
DESCRIPTION
read more
The NFE2 gene encodes a hematopoietic transcription factor (summary by
Jutzi et al., 2013).
CLONING
Ney et al. (1993) cloned the 45-kD subunit of the human globin locus
control region binding protein, NFE2, by homology to the murine gene.
Immunoprecipitation experiments demonstrated in vivo association of the
p45 subunit with an 18-kD protein (see MAFG, 602020, and MAFK, 600197).
Because bZIP proteins bind DNA as dimers, Ney et al. (1993) considered
it likely that native NFE2 is a heterodimer of 45- and 18-kD subunits.
Chan et al. (1993) likewise cloned the human homolog of mouse NFE2.
Extensive survey of human tissue samples found that NFE2 expression is
not limited to erythropoietic organs. Expression in the colon and testis
suggested that NFE2 may participate in the regulation of genes other
than globin.
Peters et al. (1993) demonstrated Nfe2 expression in the mouse small
intestine and NFE2 binding activity in nuclear extracts of a human colon
carcinoma cell line (Caco-2). Caco-2 cells possess properties of the
small intestine, including the ability to transport iron.
MAPPING
By fluorescence in situ hybridization, the NFE2 gene was assigned to
chromosome 12q13 (Weremowicz et al., 1993; Ney et al., 1993).
By fluorescence in situ hybridization, Chan et al. (1995) confirmed the
localization to 12q13.1-q13.3 and demonstrated that 2 genes of the same
family of transcription factors with many similarities of gene
structure, NFE2L1 (163260) and NFE2L2 (600492), are each located on
other chromosomes. The 3 genes probably were derived from a single
ancestor by chromosomal duplication inasmuch as other genes that also
map to the 3 chromosomal regions are related to one another.
MOLECULAR GENETICS
Jutzi et al. (2013) identified 7 different somatic insertion or deletion
mutations in the NFE2 gene in 8 patients with myeloproliferative
disorders, including 3 with polycythemia vera (PV; 263300) and 5 with
myelofibrosis (254450), either primary or secondary. In vitro studies
showed that the mutant truncated NFE2 proteins were unable to bind DNA
and had lost reporter gene activity. However, coexpression of mutant
NFE2 constructs with wildtype NFE2 resulted in significantly enhanced
transcriptional activity. Analysis of patient cells showed low levels of
the mutant truncated protein, but increased levels of the wildtype NFE2
protein compared to control cells, likely due to both increased mRNA and
increased stability of the wildtype protein. All 7 patients tested also
carried a JAK2 V617F mutation (147796.0001). Hematopoietic cell colonies
grown from 3 patients showed that the NFE2 mutation was acquired
subsequent to the JAK2 mutation, and further cellular studies indicated
that an NFE2 mutation conferred a proliferative advantage of cells
compared to cells carrying only the JAK2 mutation. Cells carrying mutant
NFE2 displayed an increase in the proportion of cells in the S phase,
consistent with enhanced cell division and proliferation, and this was
associated with higher levels of cell cycle regulators. These findings
were replicated in mice carrying NFE2 mutations, who developed
thrombocytosis, erythrocytosis, and neutrophilia.
ANIMAL MODEL
Peters et al. (1993) mapped the Nfe2 gene to mouse chromosome 15 in a
region containing the microcytic anemia (mk) gene. Homozygous mk mice
were shown by Bannerman et al. (1972) to have defective intestinal iron
transport and severe anemia. Peters et al. (1993) identified what they
thought was a mutation in the Nfe2 gene in mk mice (V173A), but later
confirmed the change to be a polymorphism.
The mechanisms regulating the formation of blood platelets within
megakaryocytes are not fully understood. Shivdasani et al. (1995)
generated mice lacking the hematopoietic subunit (p45) of the
heterodimeric erythroid transcription factor Nfe2. Unexpectedly,
homozygous Nfe2-deficient mice lacked circulating platelets and died of
hemorrhage; their megakaryocytes showed no cytoplasmic platelet
formation. Though platelets were absent, serum levels of the growth
factor thrombopoietin/Mgdf (600044) were not elevated above those of
controls. Nevertheless, the homozygous Nfe2 deficient megakaryocytes
proliferated in vivo in response to thrombopoietin administration. Thus,
the authors concluded that, as an essential factor for megakaryocyte
maturation and platelet production, NFE2 must regulate critical target
genes independent of the action of thrombopoietin. In contrast to the
dramatic absence of circulating platelets in homozygous mutant mice, the
effect of loss of Nfe2 on the erythroid lineage was surprisingly mild
(Shivdasani and Orkin, 1995). Although neonates exhibited severe anemia
and dysmorphic red cell changes, probably compounded by concomitant
bleeding, surviving adults exhibited only mild changes consistent with a
small decrease in the hemoglobin content per cell. p45 Nfe2-null mice
responded to anemia with compensatory reticulocytosis and splenomegaly.
Globin chain synthesis was balanced, and switching from fetal to adult
globins progressed normally. Although these findings were consistent
with the substitution of NFE2 function in vivo by one or more
compensating proteins, gel shift assays using nuclear extracts from p45
Nfe2-null mice failed to reveal novel complexes formed on an Nfe2
binding site. Thus, the authors concluded that regulation of globin gene
transcription through NFE2 binding sites in vivo is more complex than
had previously been appreciated.
Kaufmann et al. (2012) found that mice with overexpression of the Nfe2
gene in hematopoietic cells developed features of myeloproliferative
disorders, including thrombocytosis, leukocytosis, Epo-independent
colony formation, characteristic bone marrow histology, expansion of
stem and progenitor compartments, and spontaneous transformation to
acute myeloid leukemia. This phenotype was transplantable to secondary
recipient mice. Cells from Nfe2 transgenic mice showed hypoacetylation
of histone H3 (602810). Treatment of mice with a histone deacetylase
inhibitor (HDAC-I) restored physiologic levels of histone H3
acetylation, decreased Nfe2 expression, and normalized platelet numbers.
Similarly, patients with myeloproliferative disorders treated with an
HDAC-I showed a decrease in NFE2 expression. These data established a
role for aberrant NFE2 expression in the pathophysiology of
myeloproliferative disorders.
*FIELD* RF
1. Bannerman, R. M.; Edwards, J. A.; Kreimer-Birnbaum, M.; McFarland,
E.; Russell, E. S.: Hereditary microcytic anaemia in the mouse; studies
in iron distribution and metabolism. Brit. J. Haemat. 23: 235-245,
1972.
2. Chan, J. Y.; Cheung, M.-C.; Moi, P.; Chan, K.; Kan, Y. W.: Chromosomal
localization of the human NF-E2 family of bZIP transcription factors
by fluorescence in situ hybridization. Hum. Genet. 95: 265-269,
1995.
3. Chan, J. Y.; Han, X.-L.; Kan, Y. W.: Isolation of cDNA encoding
the human NF-E2 protein. Proc. Nat. Acad. Sci. 90: 11366-11370,
1993.
4. Jutzi, J. S.; Bogeska, R.; Nikoloski, G.; Schmid, C. A.; Seeger,
T. S.; Stegelmann, F.; Schwemmers, S.; Grunder, A.; Peeken, J. C.;
Gothwal, M.; Wehrle, J.; Aumann, K.; Hamdi, K.; Dierks, C.; Wang,
W.; Dohner, K.; Jansen, J. H.; Pahl, H. L.: MPN patients harbor recurrent
truncating mutations in transcription factor NF-E2. J. Exp. Med. 210:
1003-1019, 2013.
5. Kaufmann, K. B.; Grunder, A.; Hadlich, T.; Wehrle, J.; Gothwal,
M.; Bogeska, R.; Seeger, T. S.; Kayser, S.; Pham, K.-B.; Jutzi, J.
S.; Ganzenmuller, L.; Steinemann, D.; and 11 others: A novel murine
model of myeloproliferative disorders generated by overexpression
of the transcription factor NF-E2. J. Exp. Med. 209: 35-50, 2012.
6. Ney, P. A.; Andrews, N. C.; Jane, S. M.; Safer, B.; Purucker, M.
E.; Weremowicz, S.; Morton, C. C.; Goff, S. C.; Orkin, S. H.; Nienhuis,
A. W.: Purification of the human NF-E2 complex: cDNA cloning of the
hematopoietic cell-specific subunit and evidence for an associated
partner. Molec. Cell. Biol. 13: 5604-5612, 1993.
7. Peters, L. L.; Andrews, N. C.; Eicher, E. M.; Davidson, M. B.;
Orkin, S. H.; Lux, S. E.: Mouse microcytic anaemia caused by a defect
in the gene encoding the globin enhancer-binding protein NF-E2. Nature 362:
768-770, 1993. Note: Erratum: Nature 371: 358 only, 1994.
8. Peters, L. L.; Bishop, T. R.; Andrews, N. C.: Globin-enhancer
binding factor NF-E2 is implicated in the regulation of heme biosynthesis
and iron uptake in mk/mk mice. (Abstract) Blood 82 (suppl. 1): 179a,
1993.
9. Shivdasani, R. A.; Orkin, S. H.: Erythropoiesis and globin gene
expression in mice lacking the transcription factor NF-E2. Proc.
Nat. Acad. Sci. 92: 8690-8694, 1995.
10. Shivdasani, R. A.; Rosenblatt, M. F.; Zucker-Franklin, D.; Jackson,
C. W.; Hunt, P.; Saris, C. J. M.; Orkin, S. H.: Transcription factor
NF-E2 is required for platelet formation independent of the actions
of thrombopoietin/MGDF in megakaryocyte development. Cell 81: 695-704,
1995.
11. Weremowicz, S.; Andrews, N. C.; Orkin, S. H.; Morton, C. C.:
Mapping the p45 subunit of human NFE2 to 12q13. (Abstract) Human
Genome Mapping Workshop 93 25, 1993.
*FIELD* CN
Cassandra L. Kniffin - updated: 1/7/2014
Anne M. Stumpf - updated: 9/14/2010
*FIELD* CD
Alan F. Scott: 11/7/1996
*FIELD* ED
carol: 01/08/2014
ckniffin: 1/7/2014
carol: 10/9/2012
alopez: 11/16/2010
alopez: 9/14/2010
carol: 11/6/2008
ckniffin: 1/5/2006
carol: 8/13/2001
mgross: 3/16/1999
mgross: 3/15/1999
carol: 6/23/1998
mark: 11/12/1996
carol: 11/10/1996
joanna: 11/7/1996