NFE2_MOUSE
ID NFE2_MOUSE Reviewed; 373 AA.
AC Q07279; Q6P6K5;
DT 26-FEB-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 167.
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 Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=DBA;
RX PubMed=8469283; DOI=10.1038/362722a0;
RA Andrews N.C., Erdjument-Bromage H., Davidson M.B., Tempst P., Orkin S.H.;
RT "Erythroid transcription factor NF-E2 is a haematopoietic-specific basic-
RT leucine zipper protein.";
RL Nature 362:722-728(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=NOD; TISSUE=Spleen;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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).
RN [4]
RP TRANSACTIVATION DOMAIN.
RX PubMed=9171106; DOI=10.1093/nar/25.12.2509;
RA Bean T.L., Ney P.A.;
RT "Multiple regions of p45 NF-E2 are required for beta-globin gene expression
RT in erythroid cells.";
RL Nucleic Acids Res. 25:2509-2515(1997).
RN [5]
RP PHOSPHORYLATION AT SER-170, FUNCTION, AND MUTAGENESIS OF SER-170.
RX PubMed=9558374;
RA Casteel D., Suhasini M., Gudi T., Naima R., Pilz R.B.;
RT "Regulation of the erythroid transcription factor NF-E2 by cyclic adenosine
RT monophosphate-dependent protein kinase.";
RL Blood 91:3193-3201(1998).
RN [6]
RP PXY MOTIF DOMAIN, AND MUTAGENESIS OF 63-PRO--TYR-65.
RX PubMed=14597626; DOI=10.1074/jbc.m309750200;
RA Kiekhaefer C.M., Boyer M.E., Johnson K.D., Bresnick E.H.;
RT "A WW domain-binding motif within the activation domain of the
RT hematopoietic transcription factor NF-E2 is essential for establishment of
RT a tissue-specific histone modification pattern.";
RL J. Biol. Chem. 279:7456-7461(2004).
RN [7]
RP SUMOYLATION.
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 [8]
RP INTERACTION WITH KMT2D.
RX PubMed=17707229; DOI=10.1016/j.molcel.2007.06.022;
RA Demers C., Chaturvedi C.-P., Ranish J.A., Juban G., Lai P., Morle F.,
RA Aebersold R., Dilworth F.J., Groudine M., Brand M.;
RT "Activator-mediated recruitment of the MLL2 methyltransferase complex to
RT the beta-globin locus.";
RL Mol. Cell 27:573-584(2007).
RN [9]
RP PHOSPHORYLATION AT SER-157, INTERACTION WITH MAPK8, UBIQUITINATION,
RP IDENTIFICATION BY MASS SPECTROMETRY, AND MUTAGENESIS OF SER-157.
RX PubMed=19966288; DOI=10.1073/pnas.0909153107;
RA Lee T.L., Shyu Y.C., Hsu P.H., Chang C.W., Wen S.C., Hsiao W.Y., Tsai M.D.,
RA Shen C.K.;
RT "JNK-mediated turnover and stabilization of the transcription factor
RT p45/NF-E2 during differentiation of murine erythroleukemia cells.";
RL Proc. Natl. Acad. Sci. U.S.A. 107:52-57(2010).
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. {ECO:0000269|PubMed:9558374}.
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. {ECO:0000250, ECO:0000269|PubMed:17707229,
CC ECO:0000269|PubMed:19966288}.
CC -!- INTERACTION:
CC Q07279; P79621: Ciita; NbExp=2; IntAct=EBI-6554737, EBI-26668013;
CC Q07279; Q9Z148-1: Ehmt2; NbExp=4; IntAct=EBI-6554737, EBI-444981;
CC Q07279; P62991: Ubc; NbExp=2; IntAct=EBI-6554737, EBI-413074;
CC -!- SUBCELLULAR LOCATION: Nucleus, PML body. Cytoplasm {ECO:0000250}.
CC Note=The sumoylated form locates to the nuclear bodies PML oncogenic
CC domains (PODs). Translocated to the cytoplasm through interaction with
CC ITCH (By similarity). {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.
CC -!- PTM: Phosphorylated on serine residues. In undifferentiated
CC erythrocytes, phosphorylated by MAPK8 which then leads to
CC ubiquitination and protein degradation (By similarity). {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 (By similarity). {ECO:0000250}.
CC -!- PTM: Ubiquitinated mainly by 'Lys63'-linked ubiquitin (By similarity).
CC Polyubiquitination with 'Lys63'-linked ubiquitin by ITCH retains NFE2
CC in the cytoplasm preventing its transactivation activity (By
CC similarity). In undifferentiated erythrocyte, ubiquitinated after
CC MAPK8-mediatd phosphorylation leading to protein degradation.
CC {ECO:0000250, ECO:0000269|PubMed:19966288, ECO:0000269|PubMed:9558374}.
CC -!- SIMILARITY: Belongs to the bZIP family. CNC subfamily. {ECO:0000305}.
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DR EMBL; L09600; AAA40417.1; -; mRNA.
DR EMBL; AK156702; BAE33812.1; -; mRNA.
DR EMBL; BC062171; AAH62171.1; -; mRNA.
DR CCDS; CCDS27900.1; -.
DR PIR; S32537; S32537.
DR RefSeq; NP_001289267.1; NM_001302338.1.
DR RefSeq; NP_001289268.1; NM_001302339.1.
DR RefSeq; NP_001289269.1; NM_001302340.1.
DR RefSeq; NP_001289270.1; NM_001302341.1.
DR RefSeq; NP_001289272.1; NM_001302343.1.
DR RefSeq; NP_032711.2; NM_008685.3.
DR RefSeq; XP_006520636.1; XM_006520573.2.
DR AlphaFoldDB; Q07279; -.
DR SMR; Q07279; -.
DR BioGRID; 201742; 69.
DR DIP; DIP-44849N; -.
DR IntAct; Q07279; 63.
DR STRING; 10090.ENSMUSP00000122476; -.
DR iPTMnet; Q07279; -.
DR PhosphoSitePlus; Q07279; -.
DR PaxDb; Q07279; -.
DR PRIDE; Q07279; -.
DR ProteomicsDB; 287489; -.
DR DNASU; 18022; -.
DR GeneID; 18022; -.
DR KEGG; mmu:18022; -.
DR CTD; 4778; -.
DR MGI; MGI:97308; Nfe2.
DR eggNOG; KOG3863; Eukaryota.
DR InParanoid; Q07279; -.
DR PhylomeDB; Q07279; -.
DR TreeFam; TF326681; -.
DR Reactome; R-MMU-983231; Factors involved in megakaryocyte development and platelet production.
DR BioGRID-ORCS; 18022; 3 hits in 75 CRISPR screens.
DR PRO; PR:Q07279; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; Q07279; protein.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0016605; C:PML body; IEA:UniProtKB-SubCell.
DR GO; GO:0032993; C:protein-DNA complex; ISO:MGI.
DR GO; GO:0090575; C:RNA polymerase II transcription regulator complex; ISO:MGI.
DR GO; GO:0000987; F:cis-regulatory region sequence-specific DNA binding; ISO:MGI.
DR GO; GO:0003677; F:DNA binding; ISO:MGI.
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:MGI.
DR GO; GO:0047485; F:protein N-terminus binding; ISO:MGI.
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:MGI.
DR GO; GO:0050699; F:WW domain binding; ISO:MGI.
DR GO; GO:0030282; P:bone mineralization; IMP:MGI.
DR GO; GO:0008283; P:cell population proliferation; IDA:MGI.
DR GO; GO:0007267; P:cell-cell signaling; IMP:MGI.
DR GO; GO:0010467; P:gene expression; IDA:MGI.
DR GO; GO:0060716; P:labyrinthine layer blood vessel development; IMP:MGI.
DR GO; GO:0030502; P:negative regulation of bone mineralization; IMP:MGI.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; IDA:MGI.
DR GO; GO:0034242; P:negative regulation of syncytium formation by plasma membrane fusion; IMP:MGI.
DR GO; GO:2000758; P:positive regulation of peptidyl-lysine acetylation; IMP:MGI.
DR GO; GO:0010468; P:regulation of gene expression; IDA:MGI.
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; IMP:MGI.
DR InterPro; IPR004827; bZIP.
DR InterPro; IPR004826; bZIP_Maf.
DR InterPro; IPR046347; bZIP_sf.
DR InterPro; IPR029853; NF-E2_p45.
DR InterPro; IPR008917; TF_DNA-bd_sf.
DR PANTHER; PTHR24411:SF26; PTHR24411:SF26; 1.
DR Pfam; PF03131; bZIP_Maf; 1.
DR SMART; SM00338; BRLZ; 1.
DR SUPFAM; SSF47454; SSF47454; 1.
DR SUPFAM; SSF57959; SSF57959; 1.
DR PROSITE; PS50217; BZIP; 1.
DR PROSITE; PS00036; BZIP_BASIC; 1.
PE 1: Evidence at protein 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_0000320078"
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 204..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:0000269|PubMed:19966288"
FT MOD_RES 170
FT /note="Phosphoserine; by PKA"
FT /evidence="ECO:0000269|PubMed:9558374"
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"
FT MUTAGEN 63..65
FT /note="PTY->AAA: Loss of transactivation activity. No
FT induction of histone H3 'K-4' acetylation."
FT /evidence="ECO:0000269|PubMed:14597626"
FT MUTAGEN 157
FT /note="S->A: Loss of MAPK8-mediated phosphorylation and no
FT protein degradation."
FT /evidence="ECO:0000269|PubMed:19966288"
FT MUTAGEN 170
FT /note="S->A: Abolishes phosphorylation by PKA. No effect on
FT ability to bind DNA nor on transactivation activity."
FT /evidence="ECO:0000269|PubMed:9558374"
FT CONFLICT 173
FT /note="V -> A (in Ref. 3; AAH62171)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 373 AA; 41565 MW; 47E505F78B6EEB65 CRC64;
MPPCPPQQNR NRLSQLPVGE LGEMELTWQE IMSITELQGL NVPSETSFEP QAPTPYPGPL
PPPTYCPCSI HPDAGFSLPP PSYELPASTP HVPELPYSYG NVAIPVSKPL TLSGLLNEPL
PDHLALLDIG LPVGQPKPQE DPESDSGLSL NYSDAESLEL EGMEAGRRRS EYVDMYPVEY
PYSLMPNSLA HPNYTLPPTE TPLALESSSG PVRAKPAVRG EAGSRDERRA LAMKIPFPTD
KIVNLPVDDF NELLAQYPLT ESQLALVRDI RRRGKNKVAA QNCRKRKLET IVQLERELER
LSSERERLLR ARGEADRTLE VMRQQLAELY HDIFQHLRDE SGNSYSPEEY VLQQAADGAI
FLVPRGTKME ATD
