Contents

Search

NF-kappa B p65; nuclear factor NF-kappa-B p65 subunit (RELA, NFKB3)

Function: - p65 subunit of NF-kappa B - component of the NF-kappa-B p65-p50 complex - component of the NF-kappa-B p65-c-Rel complex - component of the NF- kappa-B p65-p65 complex - component of the NF-kappa-B p65-p52 complex - NF-kappa-B heterodimeric p65-p50 & p65-c-Rel complexes are transcriptional activators - NF-kappa-B p65-p65 complex appears to be involved in invasin-mediated activation of IL-8 expression - inhibitory effect of I-kappa-B upon NF-kappa-B in the cytoplasm is exerted primarily through interaction with p65 - NF-kappa-B p65 binds to IKB, inhibiting transcriptional activity of NF-kappa B by retaining it in the cytoplasm - activation of NF-kappa B with translocation to the nucleus appears to require phosphorylation-dependent proteolysis of IKB - p65 shows a weak DNA-binding site which may contribute to DNA binding in the NF-kappa-B complex - may interact with ETHE1 - binds AES & TLE1 - interacts with TP53BP2 - binds to & is phosphorylated by the activated form of either RPS6KA4 or RPS6KA5 - interacts with ING4; interaction may be indirect - interacts with CARM1, USP48 & UNC5CL - interacts with IRAK1BP1 (putative) - interacts with IKBNS (putative) - interacts with NFKBIA - interacts with GSK3B - interacts with NFKBIB (putative) - interacts with NFKBIE - interacts with NFKBIZ (putative) - part of a 70-90 kD complex at least consisting of CHUK, IKBKB, NFKBIA, RELA, IKBKAP & MAP3K14 - interacts with HDAC3; HDAC3 mediates the deacetylation of RELA - interacts with HDAC1; interaction requires non-phosphorylated RELA - interacts with CBP; interaction requires phosphorylated RELA - interacts (phosphorylated at Thr-254) with PIN1; interaction inhibits p65 binding to NFKBIA - interacts with SOCS1 - interacts with UXT - ubiquitinated, leading to its proteosomal degradation - degradation is required for termination of NF-kappa-B response - phosphorylation on Ser-536 stimulates acetylation on Lys-310 & interaction with CBP; the phosphorylated & acetylated forms show enhanced transcriptional activity - reversibly acetylated; the acetylation seems to be mediated by CBP, the deacetylation by HDAC3 - acetylation at Lys-122 enhances DNA binding & impairs association with NFKBIA - acetylation at Lys-310 is required for full transcriptional activity in the absence of effects on DNA binding & NFKBIA association - acetylation can also lower DNA-binding & results in nuclear export Structure: - homodimer - heterodimer with other NF-kappa N - contains 1 RHD (Rel-like) domain Compartment: - nucleus, cytoplasm - nuclear, but also found in the cytoplasm in an inactive form complexed to an inhibitor (I-kappa-B) Alternative splicing: named isoforms=4

Related

rel-A proto-oncogene

General

oligomerizing protein rel protein family

Properties

SIZE: entity length = 551 aa MW = 60 kD COMPARTMENT: cytoplasm cell nucleus MOTIF: RHD {19-306} MOTIF: Thr phosphorylation site {T254} Ser phosphorylation site {S276} Ser phosphorylation site {S281} nuclear translocation signal {301-304} Ser phosphorylation site {S311} Activation {415-459} MOTIF: Thr phosphorylation site {T435} Ser phosphorylation site {S468} Thr phosphorylation site {T505} Ser phosphorylation site {S529} Ser phosphorylation site {S536}

Database Correlations

OMIM 164014 UniProt Q04206 Entrez Gene 5970 Kegg hsa/hsa04210

References

  1. Ruben SM, Dillon PJ, Schreck R, Henkel T, Chen CH, Maher M, Baeuerle PA, Rosen CA. Isolation of a rel-related human cDNA that potentially encodes the 65-kD subunit of NF-kappa B. Science. 1991 Oct 4;254(5028):11. PMID: 1925549 - Ruben SM, Dillon PJ, Schreck R, Henkel T, Chen CH, Maher M, Baeuerle PA, Rosen CA. Isolation of a rel-related human cDNA that potentially encodes the 65-kD subunit of NF-kappa B. Science. 1991 Mar 22;251(5000):1490-3. Erratum in: Science. 1991 Oct 4;254(5028):11. PMID: 2006423
  2. Brown K, Gerstberger S, Carlson L, Franzoso G, Siebenlist U. Control of I kappa B-alpha proteolysis by site-specific, signal-induced phosphorylation. Science. 1995 Mar 10;267(5203):1485-8. PMID: 7878466
  3. Entrez Gene :accession 5970
  4. UniProt :accession Q04206
  5. Atlas of genetics & cytogenetics in oncology & haematology http://atlasgeneticsoncology.org/genes/RELAID325.html
  6. SeattleSNPs http://pga.gs.washington.edu/data/rela/

Component-of

nuclear factor kappa-B (NF-kappa B)