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Q16621

- NFE2_HUMAN

UniProt

Q16621 - NFE2_HUMAN

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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

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
Complete GO annotation...

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.2 Publications

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
Complete GO annotation...

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 MAPK8 By similarity
Modified residuei170 – 1701Phosphoserine; by PKA By similarity
Cross-linki368 – 368Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO-1)1 Publication

Post-translational modificationi

Phosphorylated on serine residues By similarity. 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.1 Publication

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.2 Publications

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.

Miscellaneous databases

EvolutionaryTraceiQ16621.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini266 – 32964bZIPAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni1 – 206206Transactivation domainAdd
BLAST
Regioni1 – 8383Required for interaction with MAPK8 By similarityAdd
BLAST
Regioni268 – 28720Basic motif By similarityAdd
BLAST
Regioni291 – 2988Leucine-zipper By similarity

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.

Sequence similaritiesi

Belongs to the bZIP family. CNC subfamily.

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

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti334 – 3352FQ → LE in AAA35612. 1 Publication

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

« Hide 'large scale' publications
  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: September 3, 2014
This is version 140 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

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