Candidate Genes Diabetic Retinopathy

Nuclear factor of kappa light polypeptide gene enhancer in B-cells 1

Official Symbol
NFKB1
Alternative Names
Nuclear factor NF-kappa-B p105 subunit
NF-kappabeta
OTTHUMP00000161765
DNA binding factor KBF1
nuclear factor NF-kappa-B p50 subunit
DKFZp686C01211, EBP-1, KBF1, MGC54151, NF-kappa-B, NF-kappaB, NFKB-p105, NFKB-p50, NFkappaB, p50
Description
NF-kappaB (nuclear factor-kappa B) is a rapidly acting primary transcription factor found in all cell types. It is involved in cellular responses to stimuli such as cytokines and stress and plays a key role in regulating the immune response to infection. In unstimulated cells NF-kappaB dimers are sequestered inactively in the cytoplasm by a protein complex called inhibitor of kappa B (IkappaB). IkappaB inactivates NF-kappaB by masking the nuclear localization signals (NLS). Activation of NF-kappaB occurs via degradation of IkappaB, a process that is initiated by its phosphorylation by IkappaB kinase (IKK). NF-kappaB can now enter the nucleus and regulate gene expression. NF-kappaB turns on expression of IkappaB forming a negative feedback loop.
Location
4q24
Map
Chr 17
Start: 103,422,486 bp from pter
End: 103,538,459 bp from pter
Size: 115,974 bases
Orientation: plus strand
Exons and Introns
24 exons 34 distinct introns (33 gt-ag, 1 gc-ag).
Nucleotide Sequence
Aminoacid Sequence
Variation
rs1287 C/T
Motif
Pfam:RHD Ank_2 Ank Death HTH_11
PROSITE: REL_1 GLY_RICH ANK_REPEAT ANK_REP_REGION REL_2
Induction
By phorbol ester and TNF.
Pathway
NOD-like receptor signaling pathway
Pathway
RIG-I-like receptor signaling pathway
Pathway
Cytosolic DNA-sensing pathway
Pathway
Adipocytokine signaling pathway
Pathway
Neurotrophin signaling pathway
Interactors
Protein interactors
Glucocorticoid receptor
C-Rel proto-oncogene protein
Beta TrCP2
Karyopherin alpha3
STAT3
Ubiquitin conjugating enzyme E2D 3
STAT6
Myotrophin
HBXAP
Catenin beta

Non protein interactors
Dna
Post Translational Modification
While translation occurs, the particular unfolded structure after the GRR repeat promotes the generation of p50 making it an acceptable substrate for the proteasome. This process is known as cotranslational processing. The processed form is active and the unprocessed form acts as an inhibitor (I kappa B-like), being able to form cytosolic complexes with NF-kappa B, trapping it in the cytoplasm. Complete folding of the region downstream of the GRR repeat precludes processing. Phosphorylation at 'Ser-903' and 'Ser-907' primes p105 for proteolytic processing in response to TNF-alpha stimulation. Phosphorylation at 'Ser-927' and 'Ser-932' are required for BTRC/BTRCP-mediated proteolysis. Polyubiquitination seems to allow p105 processing.

S-nitrosylation of Cys-61 affects DNA binding.

The covalent modification of cysteine by 15-deoxy-Delta12,14-prostaglandin-J2 is autocatalytic and reversible. It may occur as an alternative to other cysteine modifications, such as S-nitrosylation and S-palmitoylation.

Ubl conjugation
Molecular Weight
105427 da
Molecular Class
Transcription factor
Molecular Function
NF-kappa-B is a pleiotropic transcription factor which is present in almost all cell types and is involved in many biological processed such as inflammation, immunity, differentiation, cell growth, tumorigenesis and apoptosis.
3D Structure