| Literature References | 1. SEN, R. AND BALTIMORE, D.
Multiple nuclear factors interact with the immunoglobulin enhancer sequences.
CELL 46(5) 705-716(1986).
2. BAEUERLE, P.A.
The inducible transcription activator NF-kappa-B - regulation by
distinct protein subunits.
BIOCHIM.BIOPHYS.ACTA 1072(1) 63-80 (1991).
3. GHOSH, G., VAN DUYNE, G., GHOSH, S. AND SIGLER, P.B.
Structure of NF-kB p50 homodimer bound to a kB site.
NATURE 373 303-317 (1995).
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| Documentation | The transcription factor NF-kB was first identified as a DNA-binding
protein specific for the 10-base pair kB site in the immunoglobulin k
light-chain enhancer of B lymphocytes [1]. It is now known to be a member
of a highly similar family of transcription factors, which share a 300
amino acid `rel homology region' (RHR) [2]: members include p50, p52,
p65, c-Rel, v-Rrel, RelB, and the Drosophila proteins, Dorsal and Dif.
These proteins exist as homo- and heterodimers that bind to kB sites in
the enhancer regions of several target genes, most of which are involved
in cellular defence mechanisms and differentiation.
The RHR, which is located N-terminally, is responsible for protein
dimerisation, DNA binding and nuclear localisation. The more variable
C-terminal domains (not found in p50 or p52) may be responsible for
transactivation. DNA binding requires the entire RHR, by contrast with
other eukaryotic and prokaryotic transcription factors, where much
smaller DNA-binding domains confer full specificity and binding
affinity for the target [3].
The structure of the transcription factor NF-kB p50 homodimer bound to
a palindromic kB site shows the RHR to fold into 2 distinct domains,
similar to the beta-sandwich structure of the immunoglobulins [3]. The
p50 dimer envelops an undistorted B-DNA helix, making specific contacts
along the 10bp kB recognition site, mainly through loops connecting
secondary structure elements in both domains. The C-terminal domains
form a dimerisation interface between beta-sheets using residues that
are strongly conserved in the Rel family.
NFKBTNSCPFCT is a 5-element fingerprint that provides a signature for
NF-kB transcription factors and releated RHR sequences. The fingerprint
was derived from an initial alignment of 7 sequences: the motifs were
drawn from conserved regions spanning the full RHR. Two iterations on
OWL25.1 were required to reach convergence, at which point a true set
comprising 27 sequences was identified.
An update on SPTR37_9f identified a true set of 23 sequences, and 3
partial matches.
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