Covered on Genetics Home Reference: rheumatoid arthritis

     From NCBI Gene: This gene encodes a protein that belongs to the Rel homology domain/immunoglobulin-like fold, plexin, transcription factor (RHD/IPT) family. Members of this family regulate genes involved in apoptosis, inflammation, the immune response, and oncogenic processes. This proto-oncogene plays a role in the survival and proliferation of B lymphocytes. Mutation or amplification of this gene is associated with B-cell lymphomas, including Hodgkin's lymphoma. Single nucleotide polymorphisms in this gene are associated with susceptibility to ulcerative colitis and rheumatoid arthritis. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Apr 2014] From UniProt: Proto-oncogene that may play a role in differentiation and lymphopoiesis. 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. 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 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. 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 NF-kappa-B heterodimer RELA/p65-c-Rel is a transcriptional activator.

The following transcription factors affect gene expression:

• c-Rel
• NF-kappaB
• NF-kappaB1
• C/EBPbeta
• NF-kappaB2
• AP-1
• c-Jun
• IRF-1

Molecular Function:

• Rna Polymerase Ii Distal Enhancer Sequence-Specific Dna Binding
• Transcriptional Activator Activity, Rna Polymerase Ii Distal Enhancer Sequence-Specific Binding
• Chromatin Binding
• Transcription Factor Activity, Sequence-Specific Dna Binding

Biological Processes:

• Negative Regulation Of Transcription From Rna Polymerase Ii Promoter
• Inflammatory Response
• I-Kappab Kinase/Nf-Kappab Signaling
• Negative Regulation Of Gene Expression
• Negative Regulation Of Interferon-Beta Production
• Response To Cytokine
• Nik/Nf-Kappab Signaling
• Positive Regulation Of I-Kappab Kinase/Nf-Kappab Signaling
• Innate Immune Response
• Positive Regulation Of Transcription From Rna Polymerase Ii Promoter
• Negative Regulation Of Neuron Death