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Protein

Transcription factor NF-E2 45 kDa subunit

Gene

NFE2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: 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

  • protein N-terminus binding Source: UniProtKB
  • sequence-specific DNA binding Source: BHF-UCL
  • transcription coactivator activity Source: ProtInc
  • transcription factor activity, sequence-specific DNA binding Source: ProtInc
  • transcription regulatory region sequence-specific DNA binding Source: GO_Central
  • WW domain binding Source: BHF-UCL

GO - Biological processi

  • blood circulation Source: ProtInc
  • blood coagulation Source: Reactome
  • hemostasis Source: ProtInc
  • multicellular organism development Source: ProtInc
  • nucleosome disassembly Source: BHF-UCL
  • positive regulation of transcription, DNA-templated Source: BHF-UCL
  • regulation of transcription from RNA polymerase II promoter Source: ProtInc
  • 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

BioCyciZFISH:ENSG00000123405-MONOMER.
ReactomeiR-HSA-983231. 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
Proteomesi
  • UP000005640 Componenti: 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

  • actin cytoskeleton Source: HPA
  • cytoplasm Source: GO_Central
  • nucleoplasm Source: HPA
  • nucleus Source: ProtInc
  • PML body Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi368K → R: 60% loss of DNA-binding and 5-fold loss of transactivation activity. Almost no colocalization with nuclear bodies. 1 Publication1

Organism-specific databases

DisGeNETi4778.
OpenTargetsiENSG00000123405.
PharmGKBiPA31586.

Polymorphism and mutation databases

BioMutaiNFE2.
DMDMi6831585.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000764461 – 373Transcription factor NF-E2 45 kDa subunitAdd BLAST373

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei157Phosphoserine; by MAPK8By similarity1
Modified residuei170Phosphoserine; by PKABy similarity1
Cross-linki368Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1)1 Publication

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

iPTMnetiQ16621.
PhosphoSitePlusiQ16621.

Expressioni

Tissue specificityi

Expressed in hematopoietic cells and also in colon and testis.

Gene expression databases

BgeeiENSG00000123405.
CleanExiHS_NFE2.
ExpressionAtlasiQ16621. baseline and differential.
GenevisibleiQ16621. HS.

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

Binary interactionsi

WithEntry#Exp.IntActNotes
BTRCQ9Y2973EBI-726369,EBI-307461
MDV005Q9DGW52EBI-726369,EBI-10889526From a different organism.
NFE2L3Q9Y4A82EBI-726369,EBI-10890629

GO - Molecular functioni

  • protein N-terminus binding Source: UniProtKB
  • WW domain binding Source: BHF-UCL

Protein-protein interaction databases

BioGridi110850. 20 interactors.
DIPiDIP-57844N.
IntActiQ16621. 12 interactors.
MINTiMINT-3032845.
STRINGi9606.ENSP00000312436.

Structurei

Secondary structure

1373
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi225 – 233Combined sources9
Helixi239 – 244Combined sources6
Helixi247 – 256Combined sources10
Helixi261 – 279Combined sources19

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1LVXmodel-A221-294[»]
2KZ5NMR-A214-293[»]
ProteinModelPortaliQ16621.
SMRiQ16621.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ16621.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini266 – 329bZIPPROSITE-ProRule annotationAdd BLAST64

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 206Transactivation domainAdd BLAST206
Regioni1 – 83Required for interaction with MAPK8By similarityAdd BLAST83
Regioni268 – 287Basic motifPROSITE-ProRule annotationAdd BLAST20
Regioni291 – 298Leucine-zipperPROSITE-ProRule annotation8

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi61 – 65PXY motif 15
Motifi79 – 83PXY motif 25

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi59 – 62Poly-Pro4
Compositional biasi77 – 82Poly-Pro6

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

eggNOGiENOG410ISV1. Eukaryota.
ENOG410YEZR. LUCA.
GeneTreeiENSGT00830000128250.
HOGENOMiHOG000234410.
HOVERGENiHBG002901.
InParanoidiQ16621.
KOiK09039.
OMAiPTDKIVN.
OrthoDBiEOG091G02EB.
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

        10         20         30         40         50
MSPCPPQQSR NRVIQLSTSE LGEMELTWQE IMSITELQGL NAPSEPSFEP
60 70 80 90 100
QAPAPYLGPP PPTTYCPCSI HPDSGFPLPP PPYELPASTS HVPDPPYSYG
110 120 130 140 150
NMAIPVSKPL SLSGLLSEPL QDPLALLDIG LPAGPPKPQE DPESDSGLSL
160 170 180 190 200
NYSDAESLEL EGTEAGRRRS EYVEMYPVEY PYSLMPNSLA HSNYTLPAAE
210 220 230 240 250
TPLALEPSSG PVRAKPTARG EAGSRDERRA LAMKIPFPTD KIVNLPVDDF
260 270 280 290 300
NELLARYPLT ESQLALVRDI RRRGKNKVAA QNCRKRKLET IVQLERELER
310 320 330 340 350
LTNERERLLR ARGEADRTLE VMRQQLTELY RDIFQHLRDE SGNSYSPEEY
360 370
ALQQAADGTI FLVPRGTKME ATD
Length:373
Mass (Da):41,473
Last modified:November 1, 1996 - v1
Checksum:iA9821170FB2ED67C
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti334 – 335FQ → LE in AAA35612 (PubMed:8355703).Curated2

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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_005268906.4.
UniGeneiHs.75643.

Genome annotation databases

EnsembliENST00000312156; ENSP00000312436; ENSG00000123405.
ENST00000435572; ENSP00000397185; ENSG00000123405.
ENST00000540264; ENSP00000439120; ENSG00000123405.
ENST00000553070; ENSP00000447558; ENSG00000123405.
GeneIDi4778.
KEGGihsa:4778.
UCSCiuc001sfq.5. human.

Cross-referencesi

Web resourcesi

SeattleSNPs

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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_005268906.4.
UniGeneiHs.75643.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1LVXmodel-A221-294[»]
2KZ5NMR-A214-293[»]
ProteinModelPortaliQ16621.
SMRiQ16621.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi110850. 20 interactors.
DIPiDIP-57844N.
IntActiQ16621. 12 interactors.
MINTiMINT-3032845.
STRINGi9606.ENSP00000312436.

PTM databases

iPTMnetiQ16621.
PhosphoSitePlusiQ16621.

Polymorphism and mutation databases

BioMutaiNFE2.
DMDMi6831585.

Proteomic databases

MaxQBiQ16621.
PaxDbiQ16621.
PRIDEiQ16621.

Protocols and materials databases

DNASUi4778.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000312156; ENSP00000312436; ENSG00000123405.
ENST00000435572; ENSP00000397185; ENSG00000123405.
ENST00000540264; ENSP00000439120; ENSG00000123405.
ENST00000553070; ENSP00000447558; ENSG00000123405.
GeneIDi4778.
KEGGihsa:4778.
UCSCiuc001sfq.5. human.

Organism-specific databases

CTDi4778.
DisGeNETi4778.
GeneCardsiNFE2.
HGNCiHGNC:7780. NFE2.
HPAiHPA001914.
MIMi601490. gene.
neXtProtiNX_Q16621.
OpenTargetsiENSG00000123405.
PharmGKBiPA31586.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410ISV1. Eukaryota.
ENOG410YEZR. LUCA.
GeneTreeiENSGT00830000128250.
HOGENOMiHOG000234410.
HOVERGENiHBG002901.
InParanoidiQ16621.
KOiK09039.
OMAiPTDKIVN.
OrthoDBiEOG091G02EB.
PhylomeDBiQ16621.
TreeFamiTF326681.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000123405-MONOMER.
ReactomeiR-HSA-983231. Factors involved in megakaryocyte development and platelet production.
SignaLinkiQ16621.

Miscellaneous databases

ChiTaRSiNFE2. human.
EvolutionaryTraceiQ16621.
GeneWikiiNFE2.
GenomeRNAii4778.
PROiQ16621.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000123405.
CleanExiHS_NFE2.
ExpressionAtlasiQ16621. baseline and differential.
GenevisibleiQ16621. HS.

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]
ProtoNetiSearch...

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: November 2, 2016
This is version 161 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.