ID NFE2_RAT Reviewed; 373 AA.
AC Q6AYT2;
DT 26-FEB-2008, integrated into UniProtKB/Swiss-Prot.
DT 13-SEP-2004, sequence version 1.
DT 24-JAN-2024, entry version 135.
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 Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Kidney;
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 project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
CC -!- FUNCTION: Component of the NF-E2 complex essential for regulating
CC erythroid and megakaryocytic maturation and differentiation. Binds to
CC the hypersensitive site 2 (HS2) of the beta-globin control region
CC (LCR). This subunit (NFE2) recognizes the TCAT/C sequence of the AP-1-
CC like core palindrome present in a number of erythroid and
CC megakaryocytic gene promoters. Requires MAFK or other small MAF
CC proteins for binding to the NF-E2 motif. May play a role in all aspects
CC of hemoglobin production from globin and heme synthesis to procurement
CC of iron (By similarity). {ECO:0000250}.
CC -!- SUBUNIT: Homodimer; can bind DNA as a homodimer (By similarity).
CC Erythroid transcription activator nuclear factor erythroid-derived 2
CC (NF-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); the
CC 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. Interacts with MAPK8
CC (phosphorylated form); the interaction leads to phosphorylation of NFE2
CC in undifferentiated cells (By similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Nucleus, PML body {ECO:0000250}. Cytoplasm
CC {ECO:0000250}. Note=The sumoylated form locates to the nuclear bodies
CC PML oncogenic domains (PODs). Translocated to the cytoplasm through
CC interaction with ITCH. {ECO:0000250}.
CC -!- DOMAIN: The PXY motifs are required for binding WW domains. PXY1 is
CC required to promote transactivation of beta-globin and for
CC hyperacetylation of histone H3, but not for binding to the HS2 promoter
CC site. {ECO:0000250}.
CC -!- PTM: Phosphorylated on serine residues. In undifferentiated
CC erythrocytes, phosphorylated by MAPK8 which then leads to
CC ubiquitination and protein degradation. {ECO:0000250}.
CC -!- PTM: Sumoylated. Sumoylation is required for translocation to nuclear
CC bodies PODs, anchoring to the gene loci, and transactivation of the
CC beta-globin gene. {ECO:0000250}.
CC -!- PTM: Ubiquitinated mainly by 'Lys63'-linked ubiquitin.
CC Polyubiquitination with 'Lys63'-linked ubiquitin by ITCH retains NFE2
CC in the cytoplasm preventing its transactivation activity. In
CC undifferentiated erythrocyte, ubiquitinated after MAPK8-mediatd
CC phosphorylation leading to protein degradation. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the bZIP family. CNC subfamily. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; BC078925; AAH78925.1; -; mRNA.
DR RefSeq; NP_001012224.1; NM_001012224.1.
DR RefSeq; XP_006242494.1; XM_006242432.3.
DR RefSeq; XP_006242495.1; XM_006242433.3.
DR RefSeq; XP_017450513.1; XM_017595024.1.
DR AlphaFoldDB; Q6AYT2; -.
DR SMR; Q6AYT2; -.
DR STRING; 10116.ENSRNOP00000052156; -.
DR PhosphoSitePlus; Q6AYT2; -.
DR PaxDb; 10116-ENSRNOP00000052156; -.
DR Ensembl; ENSRNOT00000055281.4; ENSRNOP00000052156.3; ENSRNOG00000036837.4.
DR Ensembl; ENSRNOT00055050849; ENSRNOP00055041893; ENSRNOG00055029327.
DR Ensembl; ENSRNOT00060028033; ENSRNOP00060022555; ENSRNOG00060016347.
DR Ensembl; ENSRNOT00065040190; ENSRNOP00065032694; ENSRNOG00065023495.
DR GeneID; 366998; -.
DR KEGG; rno:366998; -.
DR UCSC; RGD:1306888; rat.
DR AGR; RGD:1306888; -.
DR CTD; 4778; -.
DR RGD; 1306888; Nfe2.
DR eggNOG; KOG3863; Eukaryota.
DR GeneTree; ENSGT00950000182892; -.
DR HOGENOM; CLU_058451_0_0_1; -.
DR InParanoid; Q6AYT2; -.
DR OrthoDB; 382726at2759; -.
DR PhylomeDB; Q6AYT2; -.
DR Reactome; R-RNO-983231; Factors involved in megakaryocyte development and platelet production.
DR PRO; PR:Q6AYT2; -.
DR Proteomes; UP000002494; Chromosome 7.
DR Bgee; ENSRNOG00000036837; Expressed in spleen and 14 other cell types or tissues.
DR Genevisible; Q6AYT2; RN.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; ISO:RGD.
DR GO; GO:0016605; C:PML body; IEA:UniProtKB-SubCell.
DR GO; GO:0032993; C:protein-DNA complex; ISO:RGD.
DR GO; GO:0090575; C:RNA polymerase II transcription regulator complex; ISO:RGD.
DR GO; GO:0003677; F:DNA binding; ISO:RGD.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IBA:GO_Central.
DR GO; GO:0042802; F:identical protein binding; ISO:RGD.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; ISO:RGD.
DR GO; GO:0050699; F:WW domain binding; ISO:RGD.
DR GO; GO:0030282; P:bone mineralization; ISO:RGD.
DR GO; GO:0008283; P:cell population proliferation; ISO:RGD.
DR GO; GO:0007267; P:cell-cell signaling; ISO:RGD.
DR GO; GO:0010467; P:gene expression; ISO:RGD.
DR GO; GO:0060716; P:labyrinthine layer blood vessel development; ISO:RGD.
DR GO; GO:0030502; P:negative regulation of bone mineralization; ISO:RGD.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; ISO:RGD.
DR GO; GO:0034242; P:negative regulation of syncytium formation by plasma membrane fusion; ISO:RGD.
DR GO; GO:2000758; P:positive regulation of peptidyl-lysine acetylation; ISO:RGD.
DR GO; GO:0010468; P:regulation of gene expression; ISO:RGD.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0000768; P:syncytium formation by plasma membrane fusion; ISO:RGD.
DR CDD; cd14720; bZIP_NFE2-like; 1.
DR Gene3D; 1.10.880.10; Transcription factor, Skn-1-like, DNA-binding domain; 1.
DR InterPro; IPR004827; bZIP.
DR InterPro; IPR004826; bZIP_Maf.
DR InterPro; IPR046347; bZIP_sf.
DR InterPro; IPR047167; NFE2-like.
DR InterPro; IPR008917; TF_DNA-bd_sf.
DR PANTHER; PTHR24411; NUCLEAR FACTOR ERYTHROID 2-RELATED FACTOR; 1.
DR PANTHER; PTHR24411:SF26; TRANSCRIPTION FACTOR NF-E2 45 KDA SUBUNIT; 1.
DR Pfam; PF03131; bZIP_Maf; 1.
DR SMART; SM00338; BRLZ; 1.
DR SUPFAM; SSF47454; A DNA-binding domain in eukaryotic transcription factors; 1.
DR SUPFAM; SSF57959; Leucine zipper domain; 1.
DR PROSITE; PS50217; BZIP; 1.
DR PROSITE; PS00036; BZIP_BASIC; 1.
PE 2: Evidence at transcript level;
KW Activator; Cytoplasm; DNA-binding; Isopeptide bond; Nucleus;
KW Phosphoprotein; Reference proteome; Transcription;
KW Transcription regulation; Ubl conjugation.
FT CHAIN 1..373
FT /note="Transcription factor NF-E2 45 kDa subunit"
FT /id="PRO_0000320079"
FT DOMAIN 266..329
FT /note="bZIP"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00978"
FT REGION 1..206
FT /note="Transactivation domain"
FT /evidence="ECO:0000250"
FT REGION 1..83
FT /note="Required for interaction with MAPK8"
FT /evidence="ECO:0000250"
FT REGION 1..22
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 40..60
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 131..163
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 206..225
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 268..287
FT /note="Basic motif"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00978"
FT REGION 291..298
FT /note="Leucine-zipper"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00978"
FT MOTIF 61..65
FT /note="PXY motif 1"
FT MOTIF 79..83
FT /note="PXY motif 2"
FT MOD_RES 157
FT /note="Phosphoserine; by MAPK8"
FT /evidence="ECO:0000250|UniProtKB:Q07279"
FT MOD_RES 170
FT /note="Phosphoserine; by PKA"
FT /evidence="ECO:0000250|UniProtKB:Q07279"
FT CROSSLNK 368
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO); alternate"
FT /evidence="ECO:0000250"
FT CROSSLNK 368
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO1); alternate"
FT /evidence="ECO:0000250|UniProtKB:Q16621"
SQ SEQUENCE 373 AA; 41496 MW; D9140F9F23CAC23C CRC64;
MPPCPPQPNR NRLPQLPTGE LGEMELTWQE IMSITELQGL NVPSEPSFEP QAPTPYPGPL
PPPTYCPCSI HPDAGFTLPP PPYELPASTP HAPDLPYSYG NIAIPVSKPL TLSGLLNEPL
PDPLALLDIG LPVGQPKPQE DPESDSGLSL NYSDAESLEL EGTEAGRRRS EYVDMYPVEY
PYSLMPNSLA HPNYTLPPTE TPLVLESSSG PVRAKPAVRG EAGSRDERRA LAMKIPFPTD
KIVNLPVDDF NELLAQYPLT ESQLALVRDI RRRGKNKVAA QNCRKRKLET IVQLERELER
LGSERERLLR ARGEADRTLE VMRQQLTELY HDIFQHLRDE SGNSYSPEEY VLQQAADGAI
FLVPRGTKME ATD
//
