IKBE_HUMAN
ID IKBE_HUMAN Reviewed; 500 AA.
AC O00221; Q5T9V9;
DT 20-JUN-2001, integrated into UniProtKB/Swiss-Prot.
DT 23-SEP-2008, sequence version 3.
DT 03-AUG-2022, entry version 190.
DE RecName: Full=NF-kappa-B inhibitor epsilon;
DE Short=NF-kappa-BIE;
DE AltName: Full=I-kappa-B-epsilon;
DE Short=IkB-E;
DE Short=IkB-epsilon;
DE Short=IkappaBepsilon;
GN Name=NFKBIE; Synonyms=IKBE;
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], AND MUTAGENESIS OF LYS-145; SER-157 AND
RP SER-161.
RC TISSUE=Fetal brain;
RX PubMed=9135156; DOI=10.1093/emboj/16.6.1413;
RA Whiteside S.T., Epinat J.-C., Rice N.R., Israel A.;
RT "IkappaB epsilon, a novel member of the IkappaB family, controls RelA and
RT cRel NF-kappaB activity.";
RL EMBO J. 16:1413-1426(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=14574404; DOI=10.1038/nature02055;
RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R.,
RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D.,
RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H.,
RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E.,
RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J.,
RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J.,
RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C.,
RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A.,
RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R.,
RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M.,
RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K.,
RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R.,
RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A.,
RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L.,
RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I.,
RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y.,
RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E.,
RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A.,
RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W.,
RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M.,
RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J.,
RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M.,
RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I.,
RA Rogers J., Beck S.;
RT "The DNA sequence and analysis of human chromosome 6.";
RL Nature 425:805-811(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 140-500, FUNCTION, AND INTERACTION WITH RELA;
RP REL; NFKB1 AND NFKB2.
RC TISSUE=B-cell;
RX PubMed=9315679; DOI=10.1128/mcb.17.10.6184;
RA Li Z., Nabel G.J.;
RT "A new member of the IkappaB protein family, IkappaB epsilon, inhibits RelA
RT (p65)-mediated NF-kappaB transcription.";
RL Mol. Cell. Biol. 17:6184-6190(1997).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-157 AND SER-183, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
CC -!- FUNCTION: Inhibits NF-kappa-B by complexing with and trapping it in the
CC cytoplasm. Inhibits DNA-binding of NF-kappa-B p50-p65 and p50-c-Rel
CC complexes. {ECO:0000269|PubMed:9315679}.
CC -!- SUBUNIT: Interacts with RELA, REL, NFKB1 nuclear factor NF-kappa-B p50
CC subunit and NFKB2 nuclear factor NF-kappa-B p52 subunit.
CC {ECO:0000269|PubMed:9315679}.
CC -!- INTERACTION:
CC O00221; Q8IWZ3: ANKHD1; NbExp=2; IntAct=EBI-355098, EBI-359558;
CC O00221; Q9UPN7: PPP6R1; NbExp=2; IntAct=EBI-355098, EBI-359745;
CC O00221; O75170: PPP6R2; NbExp=2; IntAct=EBI-355098, EBI-359739;
CC O00221; Q04864: REL; NbExp=2; IntAct=EBI-355098, EBI-307352;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Highly expressed in spleen, testis and lung,
CC followed by kidney, pancreas, heart, placenta and brain. Also expressed
CC in granulocytes and macrophages.
CC -!- PTM: Serine phosphorylated; followed by proteasome-dependent
CC degradation.
CC -!- SIMILARITY: Belongs to the NF-kappa-B inhibitor family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAC51216.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; U91616; AAC51216.1; ALT_FRAME; mRNA.
DR EMBL; AL139392; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471081; EAX04262.1; -; Genomic_DNA.
DR RefSeq; NP_004547.2; NM_004556.2.
DR AlphaFoldDB; O00221; -.
DR SMR; O00221; -.
DR BioGRID; 110861; 28.
DR CORUM; O00221; -.
DR DIP; DIP-27533N; -.
DR ELM; O00221; -.
DR IntAct; O00221; 28.
DR MINT; O00221; -.
DR STRING; 9606.ENSP00000275015; -.
DR iPTMnet; O00221; -.
DR PhosphoSitePlus; O00221; -.
DR BioMuta; NFKBIE; -.
DR EPD; O00221; -.
DR jPOST; O00221; -.
DR MassIVE; O00221; -.
DR MaxQB; O00221; -.
DR PaxDb; O00221; -.
DR PeptideAtlas; O00221; -.
DR PRIDE; O00221; -.
DR ProteomicsDB; 47791; -.
DR Antibodypedia; 800; 500 antibodies from 37 providers.
DR DNASU; 4794; -.
DR Ensembl; ENST00000275015.9; ENSP00000275015.3; ENSG00000146232.17.
DR GeneID; 4794; -.
DR KEGG; hsa:4794; -.
DR UCSC; uc003oxe.1; human.
DR CTD; 4794; -.
DR DisGeNET; 4794; -.
DR GeneCards; NFKBIE; -.
DR HGNC; HGNC:7799; NFKBIE.
DR HPA; ENSG00000146232; Tissue enhanced (lymphoid).
DR MIM; 604548; gene.
DR neXtProt; NX_O00221; -.
DR OpenTargets; ENSG00000146232; -.
DR PharmGKB; PA31603; -.
DR VEuPathDB; HostDB:ENSG00000146232; -.
DR eggNOG; KOG0504; Eukaryota.
DR GeneTree; ENSGT00940000159120; -.
DR InParanoid; O00221; -.
DR OrthoDB; 1341288at2759; -.
DR PhylomeDB; O00221; -.
DR TreeFam; TF320166; -.
DR PathwayCommons; O00221; -.
DR Reactome; R-HSA-1169091; Activation of NF-kappaB in B cells.
DR SignaLink; O00221; -.
DR SIGNOR; O00221; -.
DR BioGRID-ORCS; 4794; 160 hits in 1080 CRISPR screens.
DR ChiTaRS; NFKBIE; human.
DR GeneWiki; NFKBIE; -.
DR GenomeRNAi; 4794; -.
DR Pharos; O00221; Tbio.
DR PRO; PR:O00221; -.
DR Proteomes; UP000005640; Chromosome 6.
DR RNAct; O00221; protein.
DR Bgee; ENSG00000146232; Expressed in granulocyte and 107 other tissues.
DR ExpressionAtlas; O00221; baseline and differential.
DR Genevisible; O00221; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0001650; C:fibrillar center; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0042994; P:cytoplasmic sequestering of transcription factor; TAS:ProtInc.
DR Gene3D; 1.25.40.20; -; 1.
DR InterPro; IPR002110; Ankyrin_rpt.
DR InterPro; IPR036770; Ankyrin_rpt-contain_sf.
DR Pfam; PF12796; Ank_2; 2.
DR PRINTS; PR01415; ANKYRIN.
DR SMART; SM00248; ANK; 6.
DR SUPFAM; SSF48403; SSF48403; 1.
DR PROSITE; PS50297; ANK_REP_REGION; 1.
DR PROSITE; PS50088; ANK_REPEAT; 3.
PE 1: Evidence at protein level;
KW ANK repeat; Cytoplasm; Phosphoprotein; Reference proteome; Repeat.
FT CHAIN 1..500
FT /note="NF-kappa-B inhibitor epsilon"
FT /id="PRO_0000067007"
FT REPEAT 258..291
FT /note="ANK 1"
FT REPEAT 293..322
FT /note="ANK 2"
FT REPEAT 326..355
FT /note="ANK 3"
FT REPEAT 369..398
FT /note="ANK 4"
FT REPEAT 403..432
FT /note="ANK 5"
FT REPEAT 436..465
FT /note="ANK 6"
FT REGION 1..66
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 84..215
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 222..241
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 157..183
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 194..208
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 157
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 161
FT /note="Phosphoserine"
FT /evidence="ECO:0000305"
FT MOD_RES 183
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT VARIANT 95
FT /note="H -> Q (in dbSNP:rs28362857)"
FT /id="VAR_046631"
FT VARIANT 194
FT /note="V -> A (in dbSNP:rs2233434)"
FT /id="VAR_046632"
FT MUTAGEN 145
FT /note="K->R: No effect."
FT /evidence="ECO:0000269|PubMed:9135156"
FT MUTAGEN 157
FT /note="S->A: No degradation."
FT /evidence="ECO:0000269|PubMed:9135156"
FT MUTAGEN 161
FT /note="S->A: No degradation."
FT /evidence="ECO:0000269|PubMed:9135156"
FT CONFLICT 63..64
FT /note="PA -> RP (in Ref. 1; AAC51216)"
FT /evidence="ECO:0000305"
FT CONFLICT 101
FT /note="P -> R (in Ref. 1; AAC51216)"
FT /evidence="ECO:0000305"
FT CONFLICT 233
FT /note="A -> P (in Ref. 1; AAC51216)"
FT /evidence="ECO:0000305"
FT CONFLICT 402
FT /note="T -> S (in Ref. 1; AAC51216)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 500 AA; 52864 MW; 45E726E7A0E8D478 CRC64;
MNQRRSESRP GNHRLQAYAE PGKGDSGGAG PLSGSARRGR GGGGAIRVRR PCWSGGAGRG
GGPAWAVRLP TVTAGWTWPA LRTLSSLRAG PSEPHSPGRR PPRAGRPLCQ ADPQPGKAAR
RSLEPDPAQT GPRPARAAGM SEARKGPDEA EESQYDSGIE SLRSLRSLPE STSAPASGPS
DGSPQPCTHP PGPVKEPQEK EDADGERADS TYGSSSLTYT LSLLGGPEAE DPAPRLPLPH
VGALSPQQLE ALTYISEDGD TLVHLAVIHE APAVLLCCLA LLPQEVLDIQ NNLYQTALHL
AVHLDQPGAV RALVLKGASR ALQDRHGDTA LHVACQRQHL ACARCLLEGR PEPGRGTSHS
LDLQLQNWQG LACLHIATLQ KNQPLMELLL RNGADIDVQE GTSGKTALHL AVETQERGLV
QFLLQAGAQV DARMLNGCTP LHLAAGRGLM GISSTLCKAG ADSLLRNVED ETPQDLTEES
LVLLPFDDLK ISGKLLLCTD
