NF-kappa-B p65 (Mus musculus)

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Basic Information
Short Name NFKB3, Rela, Transcription factor p65
UNP ID Q04207
Organism Mus musculus
Cys Site Cys38
Family/Domain Rel homology DNA-binding (RHD) domain
Known Ligand Ligand list
Function Type Transcription factor

Summary

Protein Function

NF-kappa-B is a pleiotropic transcription factor present in almost all cell types and is the endpoint of a series of signal transduction events that are initiated by a vast array of stimuli related to many biological processes such as inflammation, immunity, differentiation, cell growth, tumorigenesis and apoptosis. NF-kappa-B is a homo- or heterodimeric complex formed by the Rel-like domain-containing proteins RELA/p65, RELB, NFKB1/p105, NFKB1/p50, REL and NFKB2/p52. The heterodimeric RELA-NFKB1 complex appears to be most abundant one. The dimers bind at kappa-B sites in the DNA of their target genes and the individual dimers have distinct preferences for different kappa-B sites that they can bind with distinguishable affinity and specificity. Different dimer combinations act as transcriptional activators or repressors, respectively. The NF-kappa-B heterodimeric RELA-NFKB1 and RELA-REL complexes, for instance, function as transcriptional activators. NF-kappa-B is controlled by various mechanisms of post-translational modification and subcellular compartmentalization as well as by interactions with other cofactors or corepressors. NF-kappa-B complexes are held in the cytoplasm in an inactive state complexed with members of the NF-kappa-B inhibitor (I-kappa-B) family. In a conventional activation pathway, I-kappa-B is phosphorylated by I-kappa-B kinases (IKKs) in response to different activators, subsequently degraded thus liberating the active NF-kappa-B complex which translocates to the nucleus. The inhibitory effect of I-kappa-B on NF-kappa-B through retention in the cytoplasm is exerted primarily through the interaction with RELA. RELA shows a weak DNA-binding site which could contribute directly to DNA binding in the NF-kappa-B complex. Beside its activity as a direct transcriptional activator, it is also able to modulate promoters accessibility to transcription factors and thereby indirectly regulate gene expression (PMID: 29813070). Associates with chromatin at the NF-kappa-B promoter region via association with DDX1. Essential for cytokine gene expression in T-cells. The NF-kappa-B homodimeric RELA-RELA complex appears to be involved in invasin-mediated activation of IL-8 expression. (From Uniprot)

Cys Function & Property

Cys38 is very close to the DNA binding site in space.

  • Hydrophobic property:
514-hydro.png
  • SASA：
Cys38: 53.269 A^2

Protein Sequence

MDDLFPLIFP SEPAQASGPY VEIIEQPKQR GMRFRYKCEG RSAGSIPGER
STDTTKTHPT IKINGYTGPG TVRISLVTKD PPHRPHPHEL VGKDCRDGYY
EADLCPDRSI HSFQNLGIQC VKKRDLEQAI SQRIQTNNNP FHVPIEEQRG
DYDLNAVRLC FQVTVRDPAG RPLLLTPVLS HPIFDNRAPN TAELKICRVN
RNSGSCLGGD EIFLLCDKVQ KEDIEVYFTG PGWEARGSFS QADVHRQVAI
VFRTPPYADP SLQAPVRVSM QLRRPSDREL SEPMEFQYLP DTDDRHRIEE
KRKRTYETFK SIMKKSPFNG PTEPRPPTRR IAVPTRNSTS VPKPAPQPYT
FPASLSTINF DEFSPMLLPS GQISNQALAL APSSAPVLAQ TMVPSSAMVP
LAQPPAPAPV LTPGPPQSLS APVPKSTQAG EGTLSEALLH LQFDADEDLG
ALLGNSTDPG VFTDLASVDN SEFQQLLNQG VSMSHSTAEP MLMEYPEAIT
RLVTGSQRPP DPAPTPLGTS GLPNGLSGDE DFSSIADMDF SALLSQISS

Structural Information

  • Known structure with covalent ligand:
Unknown
  • Protein structure:
514.png

Related Pathway

Experimental Evidence

Cys-directed Mutation

Reference

  1. Yadav V R, Prasad S, Gupta S C, et al. 3-Formylchromone interacts with cysteine 38 in p65 protein and with cysteine 179 in IκBα kinase, leading to down-regulation of nuclear factor-κB (NF-κB)-regulated gene products and sensitization of tumor cells[J]. Journal of Biological Chemistry, 2012, 287(1): 245-256. 22065587
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