NFE4_HUMAN
ID NFE4_HUMAN Reviewed; 179 AA.
AC Q86UQ8;
DT 23-SEP-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2003, sequence version 1.
DT 25-MAY-2022, entry version 87.
DE RecName: Full=Transcription factor NF-E4;
GN Name=NFE4;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], IDENTIFICATION OF NON-CANONICAL INITIATOR
RP CODON, FUNCTION, TISSUE SPECIFICITY, AND INTERACTION WITH TFCP2.
RX PubMed=11003662; DOI=10.1128/mcb.20.20.7662-7672.2000;
RA Zhou W., Clouston D.R., Wang X., Cerruti L., Cunningham J.M., Jane S.M.;
RT "Induction of human fetal globin gene expression by a novel erythroid
RT factor, NF-E4.";
RL Mol. Cell. Biol. 20:7662-7672(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12853948; DOI=10.1038/nature01782;
RA Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H.,
RA Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K.,
RA Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A.,
RA Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., Sun H.,
RA Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A.,
RA Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P.,
RA Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M.,
RA Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S.,
RA Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R.,
RA Strowmatt C., Latreille P., Miller N., Johnson D., Murray J.,
RA Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W.,
RA Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A.,
RA Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E.,
RA Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E.,
RA Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A.,
RA Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A.,
RA Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R.,
RA McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H.,
RA Wilson R.K.;
RT "The DNA sequence of human chromosome 7.";
RL Nature 424:157-164(2003).
RN [3]
RP PROTEIN SEQUENCE OF 101-110 (ISOFORM 2), ALTERNATIVE SPLICING (ISOFORM 2),
RP AND FUNCTION.
RX PubMed=16263792; DOI=10.1182/blood-2005-06-2497;
RA Zhao Q., Zhou W., Rank G., Sutton R., Wang X., Cumming H., Cerruti L.,
RA Cunningham J.M., Jane S.M.;
RT "Repression of human gamma-globin gene expression by a short isoform of the
RT NF-E4 protein is associated with loss of NF-E2 and RNA polymerase II
RT recruitment to the promoter.";
RL Blood 107:2138-2145(2006).
RN [4]
RP FUNCTION.
RX PubMed=15084587; DOI=10.1074/jbc.m402191200;
RA Zhou W., Zhao Q., Sutton R., Cumming H., Wang X., Cerruti L., Hall M.,
RA Wu R., Cunningham J.M., Jane S.M.;
RT "The role of p22 NF-E4 in human globin gene switching.";
RL J. Biol. Chem. 279:26227-26232(2004).
RN [5]
RP INTERACTION WITH HDAC1 AND PCAF, UBIQUITINATION, ACETYLATION AT LYS-43, AND
RP MUTAGENESIS OF LYS-43.
RX PubMed=15273251; DOI=10.1074/jbc.m405129200;
RA Zhao Q., Cumming H., Cerruti L., Cunningham J.M., Jane S.M.;
RT "Site-specific acetylation of the fetal globin activator NF-E4 prevents its
RT ubiquitination and regulates its interaction with the histone deacetylase,
RT HDAC1.";
RL J. Biol. Chem. 279:41477-41486(2004).
CC -!- FUNCTION: Functions as part of the SSP (stage selector protein)
CC complex, a complex that contributes to the preferential expression of
CC the gamma-gene in fetal erythroid cells by facilitating the interaction
CC of the gamma-globin genes with enhancer elements contained in the locus
CC control region (LCR). The complex binds to the stage selector element
CC (SSE) in the proximal gamma-globin promoter. In contrast, isoform 2
CC acts as a repressor of gamma-globin gene expression by preventing NFE2
CC and RNA polymerase II recruitment to the promoter.
CC {ECO:0000269|PubMed:11003662, ECO:0000269|PubMed:15084587,
CC ECO:0000269|PubMed:16263792}.
CC -!- SUBUNIT: Component of the SSP (stage selector protein) complex, which
CC appears to be a heteromer of TFCP2 and 2 copies of NFE4. Interacts with
CC HDAC1 and PCAF. Isoform 2 interacts with TFCP2.
CC {ECO:0000269|PubMed:11003662, ECO:0000269|PubMed:15273251}.
CC -!- INTERACTION:
CC Q86UQ8-1; O14744: PRMT5; NbExp=2; IntAct=EBI-15759783, EBI-351098;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative initiation; Named isoforms=2;
CC Name=1; Synonyms=p22 NF-E4;
CC IsoId=Q86UQ8-1; Sequence=Displayed;
CC Name=2; Synonyms=p14 NF-E4;
CC IsoId=Q86UQ8-2; Sequence=VSP_035468;
CC -!- TISSUE SPECIFICITY: Specifically expressed in fetal liver, cord blood
CC and bone marrow. Also expressed in the K562 and HEL cell lines, which
CC constitutively express the fetal globin genes.
CC {ECO:0000269|PubMed:11003662}.
CC -!- PTM: Acetylation at Lys-43 prolongs the protein half-life by preventing
CC ubiquitin-mediated degradation and reduces the interaction between NF-
CC E4 and HDAC1, potentially maximizing the activating ability of the
CC factor at the gamma-promoter. {ECO:0000269|PubMed:15273251}.
CC -!- PTM: Ubiquitinated; leading to its degradation by the proteasome.
CC Acetylation at Lys-43 prevents ubiquitination.
CC {ECO:0000269|PubMed:15273251}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAP13531.1; Type=Miscellaneous discrepancy; Note=Unusual initiator. The initiator methionine is coded by a non-canonical CTG leucine codon.; Evidence={ECO:0000305};
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DR EMBL; AY258907; AAP13531.1; ALT_SEQ; mRNA.
DR EMBL; AC073127; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR RefSeq; NP_001078855.1; NM_001085386.1.
DR AlphaFoldDB; Q86UQ8; -.
DR BioGRID; 121800; 7.
DR DIP; DIP-48507N; -.
DR IntAct; Q86UQ8; 3.
DR iPTMnet; Q86UQ8; -.
DR PhosphoSitePlus; Q86UQ8; -.
DR BioMuta; NFE4; -.
DR DMDM; 74714021; -.
DR PRIDE; Q86UQ8; -.
DR DNASU; 58160; -.
DR GeneID; 58160; -.
DR CTD; 58160; -.
DR DisGeNET; 58160; -.
DR GeneCards; NFE4; -.
DR HGNC; HGNC:29902; NFE4.
DR MIM; 612133; gene.
DR neXtProt; NX_Q86UQ8; -.
DR OrthoDB; 1775156at2759; -.
DR PathwayCommons; Q86UQ8; -.
DR SignaLink; Q86UQ8; -.
DR BioGRID-ORCS; 58160; 1 hit in 81 CRISPR screens.
DR GenomeRNAi; 58160; -.
DR Pharos; Q86UQ8; Tbio.
DR PRO; PR:Q86UQ8; -.
DR Proteomes; UP000005640; Unplaced.
DR RNAct; Q86UQ8; protein.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0032991; C:protein-containing complex; IDA:UniProtKB.
DR GO; GO:0140297; F:DNA-binding transcription factor binding; IPI:GO_Central.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB.
DR GO; GO:0003712; F:transcription coregulator activity; IDA:GO_Central.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:UniProtKB.
DR GO; GO:0065003; P:protein-containing complex assembly; IDA:UniProtKB.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IMP:UniProtKB.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; IDA:UniProtKB.
PE 1: Evidence at protein level;
KW Acetylation; Activator; Alternative initiation; Direct protein sequencing;
KW Nucleus; Reference proteome; Repressor; Transcription;
KW Transcription regulation; Ubl conjugation.
FT CHAIN 1..179
FT /note="Transcription factor NF-E4"
FT /id="PRO_0000351118"
FT REGION 100..179
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 103..128
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 143..179
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 43
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000269|PubMed:15273251"
FT VAR_SEQ 1..100
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_035468"
FT VARIANT 45
FT /note="A -> D (in dbSNP:rs6465886)"
FT /id="VAR_046622"
FT VARIANT 116
FT /note="Q -> R (in dbSNP:rs2228687)"
FT /id="VAR_046623"
FT MUTAGEN 43
FT /note="K->R: Abolishes acetylation."
FT /evidence="ECO:0000269|PubMed:15273251"
SQ SEQUENCE 179 AA; 19019 MW; 19925152D2ABBEB9 CRC64;
MPRVVCWHTL KSLNGYKNLS SGAETREGLR SSSPVDLPLR PRKQATAAGQ RKLLSLQLLL
CACTSVTDLT YWGPAGHGAT APHRSLLAIH LHLVPASSAA MKATGPHNAQ TQVNPQGHAP
SAEDPTGTWT VSGPCKDHPH PFLSQSNPPT RISSALPLKT DSALEQTPQQ LPSLHLSQG
