NFKBIE

{{Short description|Protein-coding gene in the species Homo sapiens}} {{Confusing|date=May 2009}} {{Infobox_gene}} '''Nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, epsilon''', also known as '''NFKBIE''', is a protein which in humans is encoded by the ''NFKBIE'' gene.<ref name="entrez">{{cite web | title = Entrez Gene: NFKBIE nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, epsilon| url = https://www.ncbi.nlm.nih.gov/gene?Db=gene&Cmd=ShowDetailView&TermToSearch=4794}}</ref><ref name="pmid9135156">{{cite journal |vauthors=Whiteside ST, Epinat JC, Rice NR, Israël A | title = I kappa B epsilon, a novel member of the I kappa B family, controls RelA and cRel NF-kappa B activity | journal = EMBO J. | volume = 16 | issue = 6 | pages = 1413–26 |date=March 1997 | pmid = 9135156 | pmc = 1169738 | doi = 10.1093/emboj/16.6.1413 }}</ref>

== Function ==

NFKBIE protein expression is up-regulated following NF-κB activation and during myelopoiesis. NFKBIE is able to inhibit NF-κB-directed transactivation via cytoplasmic retention of REL proteins.<ref name="pmid9135156"/>

NFKB1 or NFKB2 is bound to REL, RELA, or RELB to form the NF-κB transcription factor complex. The NF-κB complex is inhibited by I-kappa-B proteins (NFKBIA or NFKBIB), which inactivate NF-kappa-B by trapping it in the cytoplasm. Phosphorylation of serine residues on the I-kappa-B proteins by kinases (IKBKA, or IKBKB) marks them for destruction via the ubiquitination pathway, thereby allowing activation of the NF-kappa-B complex. Activated NF-κB complex translocates into the nucleus and binds DNA at kappa-B-binding motifs such as 5-prime GGGRNNYYCC 3-prime or 5-prime HGGARNYYCC 3-prime (where H is A, C, or T; R is an A or G purine; and Y is a C or T pyrimidine). For some genes, activation requires NF-κB interaction with other transcription factors, such as STAT (see STAT6), AP-1 (JUN), and NFAT (see NFATC1).<ref name="entrez"/>

==Interactions== NFKBIE has been shown to interact with NFKB2,<ref name=pmid9315679>{{cite journal |last=Li |first=Z |author2=Nabel G J |date=October 1997 |title=A new member of the I kappaB protein family, I kappaB epsilon, inhibits RelA (p65)-mediated NF-kappaB transcription |journal=Mol. Cell. Biol. |volume=17 |issue=10 |pages=6184–90 |location = United States| issn = 0270-7306| pmid = 9315679 |pmc=232469 | doi=10.1128/mcb.17.10.6184}}</ref> RELA,<ref name=pmid9315679/> NFKB1<ref name=pmid9315679/> and REL.<ref name=pmid9315679/><ref name=pmid8415639>{{cite journal |last=Kumar |first=S |author2=Gélinas C |date=October 1993 |title=I kappa B alpha-mediated inhibition of v-Rel DNA binding requires direct interaction with the RXXRXRXXC Rel/kappa B DNA-binding motif |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=90 |issue=19 |pages=8962–6 |location = United States| issn = 0027-8424| pmid = 8415639 | bibcode =1993PNAS...90.8962K |doi=10.1073/pnas.90.19.8962 |pmc=47481 |doi-access=free }}</ref><ref name=pmid10706725>{{cite journal |last=Spiecker |first=M |author2=Darius H |author3=Liao J K |date=March 2000 |title=A functional role of I kappa B-epsilon in endothelial cell activation |journal=J. Immunol. |volume=164 |issue=6 |pages=3316–22 |location = United States|doi=10.4049/jimmunol.164.6.3316 | issn = 0022-1767| pmid = 10706725 |doi-access=free }}</ref>

==References== {{reflist}}

==Further reading== {{refbegin | 2}} *{{cite journal |vauthors=Hansen SK, Baeuerle PA, Blasi F |title=Purification, reconstitution, and I kappa B association of the c-Rel-p65 (RelA) complex, a strong activator of transcription. |journal=Mol. Cell. Biol. |volume=14 |issue= 4 |pages= 2593–603 |year= 1994 |pmid= 8139561 |doi= 10.1128/mcb.14.4.2593| pmc=358627 }} *{{cite journal |vauthors=Kumar S, Gélinas C |title=I kappa B alpha-mediated inhibition of v-Rel DNA binding requires direct interaction with the RXXRXRXXC Rel/kappa B DNA-binding motif. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=90 |issue= 19 |pages= 8962–6 |year= 1993 |pmid= 8415639 |doi=10.1073/pnas.90.19.8962 | pmc=47481 |bibcode=1993PNAS...90.8962K |doi-access=free }} *{{cite journal |vauthors=Whiteside ST, Epinat JC, Rice NR, Israël A |title=I kappa B epsilon, a novel member of the I kappa B family, controls RelA and cRel NF-kappa B activity. |journal=EMBO J. |volume=16 |issue= 6 |pages= 1413–26 |year= 1997 |pmid= 9135156 |doi= 10.1093/emboj/16.6.1413 | pmc=1169738 }} *{{cite journal |vauthors=Curristin SM, Bird KJ, Tubbs RJ, Ruddell A |title=VBP and RelA regulate avian leukosis virus long terminal repeat-enhanced transcription in B cells. |journal=J. Virol. |volume=71 |issue= 8 |pages= 5972–81 |year= 1997 |pmid= 9223487 |doi= 10.1128/JVI.71.8.5972-5981.1997| pmc=191853 }} *{{cite journal |vauthors=Li Z, Nabel GJ |title=A new member of the I kappaB protein family, I kappaB epsilon, inhibits RelA (p65)-mediated NF-kappaB transcription. |journal=Mol. Cell. Biol. |volume=17 |issue= 10 |pages= 6184–90 |year= 1997 |pmid= 9315679 |doi= 10.1128/mcb.17.10.6184| pmc=232469 }} *{{cite journal |vauthors=Spiecker M, Darius H, Liao JK |title=A functional role of I kappa B-epsilon in endothelial cell activation. |journal=J. Immunol. |volume=164 |issue= 6 |pages= 3316–22 |year= 2000 |pmid= 10706725 |doi= 10.4049/jimmunol.164.6.3316|doi-access=free }} *{{cite journal |vauthors=Bourke E, Kennedy EJ, Moynagh PN |title=Loss of Ikappa B-beta is associated with prolonged NF-kappa B activity in human glial cells. |journal=J. Biol. Chem. |volume=275 |issue= 51 |pages= 39996–40002 |year= 2001 |pmid= 10998424 |doi= 10.1074/jbc.M007693200 |s2cid=56360025 |url= http://eprints.maynoothuniversity.ie/7195/1/PM-loss-2000.pdf |doi-access= free }} *{{cite journal |vauthors=Lee SH, Hannink M |title=Characterization of the nuclear import and export functions of Ikappa B(epsilon). |journal=J. Biol. Chem. |volume=277 |issue= 26 |pages= 23358–66 |year= 2002 |pmid= 11970947 |doi= 10.1074/jbc.M111559200 |doi-access= free }} *{{cite journal |vauthors=Bruno ME, Borchers CH, Dial JM, etal |title=Effects of TCDD upon IkappaB and IKK subunits localized in microsomes by proteomics. |journal=Arch. Biochem. Biophys. |volume=406 |issue= 2 |pages= 153–64 |year= 2002 |pmid= 12361703 |doi=10.1016/S0003-9861(02)00452-6 |url=https://zenodo.org/record/1259525 }} *{{cite journal |vauthors=Strausberg RL, Feingold EA, Grouse LH, etal |title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 26 |pages= 16899–903 |year= 2003 |pmid= 12477932 |doi= 10.1073/pnas.242603899 | pmc=139241 |bibcode=2002PNAS...9916899M |doi-access=free }} *{{cite journal |vauthors=Emmerich F, Theurich S, Hummel M, etal |title=Inactivating I kappa B epsilon mutations in Hodgkin/Reed-Sternberg cells. |journal=J. Pathol. |volume=201 |issue= 3 |pages= 413–20 |year= 2004 |pmid= 14595753 |doi= 10.1002/path.1454 |s2cid=33577004 }} *{{cite journal |vauthors=Bouwmeester T, Bauch A, Ruffner H, etal |title=A physical and functional map of the human TNF-alpha/NF-kappa B signal transduction pathway. |journal=Nat. Cell Biol. |volume=6 |issue= 2 |pages= 97–105 |year= 2004 |pmid= 14743216 |doi= 10.1038/ncb1086 |s2cid=11683986 }} *{{cite journal |vauthors=Rual JF, Venkatesan K, Hao T, etal |title=Towards a proteome-scale map of the human protein-protein interaction network. |journal=Nature |volume=437 |issue= 7062 |pages= 1173–8 |year= 2005 |pmid= 16189514 |doi= 10.1038/nature04209 |bibcode=2005Natur.437.1173R |s2cid=4427026 }} *{{cite journal |vauthors=Nasu-Nishimura Y, Hayashi T, Ohishi T, etal |title=Role of the Rho GTPase-activating protein RICS in neurite outgrowth. |journal=Genes Cells |volume=11 |issue= 6 |pages= 607–14 |year= 2006 |pmid= 16716191 |doi= 10.1111/j.1365-2443.2006.00966.x |s2cid=7935936 |doi-access=free }} *{{cite journal |vauthors=Stefansson B, Brautigan DL |title=Protein phosphatase 6 subunit with conserved Sit4-associated protein domain targets IkappaBepsilon. |journal=J. Biol. Chem. |volume=281 |issue= 32 |pages= 22624–34 |year= 2006 |pmid= 16769727 |doi= 10.1074/jbc.M601772200 |doi-access= free }} *{{cite journal |vauthors=Chapman SJ, Khor CC, Vannberg FO, etal |title=IkappaB genetic polymorphisms and invasive pneumococcal disease. |journal=Am. J. Respir. Crit. Care Med. |volume=176 |issue= 2 |pages= 181–7 |year= 2007 |pmid= 17463416 |doi= 10.1164/rccm.200702-169OC }} {{refend}}