Q16621 · NFE2_HUMAN
- ProteinTranscription factor NF-E2 45 kDa subunit
- GeneNFE2
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids373 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
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.
GO annotations
all annotations | all molecular function | virus receptor activity | dna binding | rna binding | cytoskeletal motor activity | catalytic activity | gtpase activity | structural molecule activity | transporter activity | cytoskeletal protein binding | lipid binding | cyclase activity | antioxidant activity | oxidoreductase activity | transferase activity | hydrolase activity | lyase activity | isomerase activity | ligase activity | protein tag activity | cargo receptor activity | histone binding | protein folding chaperone | translation regulator activity | nutrient reservoir activity | receptor ligand activity | molecular transducer activity | molecular adaptor activity | toxin activity | cell adhesion mediator activity | molecular function regulator activity | virus coreceptor activity | catalytic activity, acting on a protein | catalytic activity, acting on dna | catalytic activity, acting on rna | molecular carrier activity | transcription regulator activity | general transcription initiation factor activity | molecular sensor activity | molecular sequestering activity | atp-dependent activity | other molecular function | all biological process | mitotic cell cycle | cytokinesis | cytoplasmic translation | immune system process | muscle system process | circulatory system process | renal system process | respiratory system process | carbohydrate metabolic process | generation of precursor metabolites and energy | dna replication | dna repair | dna recombination | chromatin organization | dna-templated transcription | regulation of dna-templated transcription | trna metabolic process | protein folding | protein glycosylation | amino acid metabolic process | modified amino acid metabolic process | lipid metabolic process | vitamin metabolic process | sulfur compound metabolic process | intracellular protein transport | nucleocytoplasmic transport | autophagy | inflammatory response | mitochondrion organization | cytoskeleton organization | microtubule-based movement | peroxisome organization | lysosome organization | chromosome segregation | cell adhesion | establishment or maintenance of cell polarity | programmed cell death | photosynthesis | mrna metabolic process | snrna metabolic process | vesicle-mediated transport | reproductive process | digestive system process | signaling | cell differentiation | protein catabolic process | extracellular matrix organization | regulatory ncrna-mediated gene silencing | telomere organization | cell junction organization | wound healing | ribosome biogenesis | cilium organization | anatomical structure development | cell motility | nervous system process | endocrine process | protein maturation | transmembrane transport | nucleobase-containing small molecule metabolic process | hepaticobiliary system process | membrane organization | protein-containing complex assembly | cell wall organization or biogenesis | nitrogen cycle metabolic process | protein localization to plasma membrane | defense response to other organism | detoxification | meiotic nuclear division | mitotic nuclear division | mitochondrial gene expression | carbohydrate derivative metabolic process | other biological process | all cellular component | nuclear chromosome | extracellular region | extracellular space | cell wall | nucleus | nuclear envelope | nucleoplasm | chromosome | nucleolus | mitochondrion | lysosome | endosome | vacuole | peroxisome | endoplasmic reticulum | golgi apparatus | lipid droplet | microtubule organizing center | cytosol | ribosome | cytoskeleton | plasma membrane | cilium | plastid | thylakoid | external encapsulating structure | extracellular matrix | cytoplasmic vesicle | organelle | other cellular component | |||
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Aspect | Term | |
---|---|---|
Cellular Component | chromatin | |
Cellular Component | cytoplasm | |
Cellular Component | nucleoplasm | |
Cellular Component | nucleus | |
Cellular Component | PML body | |
Cellular Component | protein-DNA complex | |
Cellular Component | RNA polymerase II transcription regulator complex | |
Molecular Function | DNA binding | |
Molecular Function | DNA-binding transcription factor activity | |
Molecular Function | DNA-binding transcription factor activity, RNA polymerase II-specific | |
Molecular Function | identical protein binding | |
Molecular Function | RNA polymerase II cis-regulatory region sequence-specific DNA binding | |
Molecular Function | sequence-specific DNA binding | |
Molecular Function | sequence-specific double-stranded DNA binding | |
Molecular Function | WW domain binding | |
Biological Process | hemostasis | |
Biological Process | integrated stress response signaling | |
Biological Process | nucleosome disassembly | |
Biological Process | positive regulation of DNA-templated transcription | |
Biological Process | regulation of transcription by RNA polymerase II |
Keywords
- Molecular function
- Biological process
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameTranscription factor NF-E2 45 kDa subunit
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionQ16621
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Note: The sumoylated form locates to the nuclear bodies PML oncogenic domains (PODs). Translocated to the cytoplasm through interaction with ITCH.
Keywords
- Cellular component
Disease & Variants
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 368 | 60% loss of DNA-binding and 5-fold loss of transactivation activity. Almost no colocalization with nuclear bodies. | ||||
Sequence: K → R |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 468 variants from UniProt as well as other sources including ClinVar and dbSNP.
Organism-specific databases
Miscellaneous
Chemistry
Genetic variation databases
PTM/Processing
Features
Showing features for chain, modified residue, cross-link.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000076446 | 1-373 | Transcription factor NF-E2 45 kDa subunit | |||
Sequence: MSPCPPQQSRNRVIQLSTSELGEMELTWQEIMSITELQGLNAPSEPSFEPQAPAPYLGPPPPTTYCPCSIHPDSGFPLPPPPYELPASTSHVPDPPYSYGNMAIPVSKPLSLSGLLSEPLQDPLALLDIGLPAGPPKPQEDPESDSGLSLNYSDAESLELEGTEAGRRRSEYVEMYPVEYPYSLMPNSLAHSNYTLPAAETPLALEPSSGPVRAKPTARGEAGSRDERRALAMKIPFPTDKIVNLPVDDFNELLARYPLTESQLALVRDIRRRGKNKVAAQNCRKRKLETIVQLERELERLTNERERLLRARGEADRTLEVMRQQLTELYRDIFQHLRDESGNSYSPEEYALQQAADGTIFLVPRGTKMEATD | ||||||
Modified residue | 157 | Phosphoserine; by MAPK8 | ||||
Sequence: S | ||||||
Modified residue | 170 | Phosphoserine; by PKA | ||||
Sequence: S | ||||||
Cross-link | 368 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1) | ||||
Sequence: K |
Post-translational modification
Phosphorylated on serine residues. In undifferentiated erythrocytes, phosphorylated by MAPK8 which then leads to ubiquitination and protein degradation.
Sumoylated. Sumoylation is required for translocation to nuclear bodies PODs, anchoring to the gene loci, and transactivation of the beta-globin gene.
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).
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Expressed in hematopoietic cells and also in colon and testis.
Gene expression databases
Organism-specific databases
Interaction
Subunit
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).
Interacts with MAPK8 (phosphorylated form); the interaction leads to phosphorylation of NFE2 in undifferentiated cells (By similarity).
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | Q16621 | BTRC Q9Y297 | 3 | EBI-726369, EBI-307461 | |
BINARY | Q16621 | FGFR3 P22607 | 3 | EBI-726369, EBI-348399 | |
BINARY | Q16621 | GLE1 Q53GS7 | 3 | EBI-726369, EBI-1955541 | |
BINARY | Q16621 | GSN P06396 | 3 | EBI-726369, EBI-351506 | |
XENO | Q16621 | MDV005 Q9DGW5 | 2 | EBI-726369, EBI-10889526 | |
BINARY | Q16621 | NFE2 Q16621 | 2 | EBI-726369, EBI-726369 | |
BINARY | Q16621 | NFE2L3 Q9Y4A8 | 4 | EBI-726369, EBI-10890629 | |
BINARY | Q16621 | Q9Y649 | 3 | EBI-726369, EBI-25900580 | |
BINARY | Q16621 | SPRED1 Q7Z699 | 3 | EBI-726369, EBI-5235340 |
Protein-protein interaction databases
Chemistry
Miscellaneous
Structure
Family & Domains
Features
Showing features for region, motif, domain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 1-83 | Required for interaction with MAPK8 | ||||
Sequence: MSPCPPQQSRNRVIQLSTSELGEMELTWQEIMSITELQGLNAPSEPSFEPQAPAPYLGPPPPTTYCPCSIHPDSGFPLPPPPY | ||||||
Region | 1-206 | Transactivation domain | ||||
Sequence: MSPCPPQQSRNRVIQLSTSELGEMELTWQEIMSITELQGLNAPSEPSFEPQAPAPYLGPPPPTTYCPCSIHPDSGFPLPPPPYELPASTSHVPDPPYSYGNMAIPVSKPLSLSGLLSEPLQDPLALLDIGLPAGPPKPQEDPESDSGLSLNYSDAESLELEGTEAGRRRSEYVEMYPVEYPYSLMPNSLAHSNYTLPAAETPLALE | ||||||
Motif | 61-65 | PXY motif 1 | ||||
Sequence: PPTTY | ||||||
Motif | 79-83 | PXY motif 2 | ||||
Sequence: PPPPY | ||||||
Region | 127-150 | Disordered | ||||
Sequence: LDIGLPAGPPKPQEDPESDSGLSL | ||||||
Region | 205-226 | Disordered | ||||
Sequence: LEPSSGPVRAKPTARGEAGSRD | ||||||
Domain | 266-329 | bZIP | ||||
Sequence: LVRDIRRRGKNKVAAQNCRKRKLETIVQLERELERLTNERERLLRARGEADRTLEVMRQQLTEL | ||||||
Region | 268-287 | Basic motif | ||||
Sequence: RDIRRRGKNKVAAQNCRKRK | ||||||
Region | 291-298 | Leucine-zipper | ||||
Sequence: IVQLEREL |
Domain
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 similarities
Belongs to the bZIP family. CNC subfamily.
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length373
- Mass (Da)41,473
- Last updated1996-11-01 v1
- ChecksumA9821170FB2ED67C
Computationally mapped potential isoform sequences
There is 1 potential isoform mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
F8W1N9 | F8W1N9_HUMAN | NFE2 | 343 |
Features
Showing features for sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 334-335 | in Ref. 2; AAA35612 | ||||
Sequence: FQ → LE |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
L24122 EMBL· GenBank· DDBJ | AAA16118.1 EMBL· GenBank· DDBJ | mRNA | ||
L13974 EMBL· GenBank· DDBJ | AAA35612.1 EMBL· GenBank· DDBJ | mRNA | ||
S77763 EMBL· GenBank· DDBJ | AAB34115.1 EMBL· GenBank· DDBJ | mRNA | ||
CR450284 EMBL· GenBank· DDBJ | CAG29280.1 EMBL· GenBank· DDBJ | mRNA | ||
BT007288 EMBL· GenBank· DDBJ | AAP35952.1 EMBL· GenBank· DDBJ | mRNA | ||
DQ367844 EMBL· GenBank· DDBJ | ABC79302.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BC005044 EMBL· GenBank· DDBJ | AAH05044.1 EMBL· GenBank· DDBJ | mRNA |