Covered on Genetics Home Reference: rheumatoid arthritis

     From NCBI Gene: The protein encoded by this gene is a member of the TNF receptor associated factor (TRAF) protein family. TRAF proteins are associated with, and mediate signal transduction from, members of the TNF receptor superfamily. This protein mediates signaling from members of the TNF receptor superfamily as well as the Toll/IL-1 family. Signals from receptors such as CD40, TNFSF11/RANCE and IL-1 have been shown to be mediated by this protein. This protein also interacts with various protein kinases including IRAK1/IRAK, SRC and PKCzeta, which provides a link between distinct signaling pathways. This protein functions as a signal transducer in the NF-kappaB pathway that activates IkappaB kinase (IKK) in response to proinflammatory cytokines. The interaction of this protein with UBE2N/UBC13, and UBE2V1/UEV1A, which are ubiquitin conjugating enzymes catalyzing the formation of polyubiquitin chains, has been found to be required for IKK activation by this protein. This protein also interacts with the transforming growth factor (TGF) beta receptor complex and is required for Smad-independent activation of the JNK and p38 kinases. This protein has an amino terminal RING domain which is followed by four zinc-finger motifs, a central coiled-coil region and a highly conserved carboxyl terminal domain, known as the TRAF-C domain. Two alternatively spliced transcript variants, encoding an identical protein, have been reported. [provided by RefSeq, Feb 2012] From UniProt: E3 ubiquitin ligase that, together with UBE2N and UBE2V1, mediates the synthesis of 'Lys-63'-linked-polyubiquitin chains conjugated to proteins, such as IKBKG, IRAK1, AKT1 and AKT2. Also mediates ubiquitination of free/unanchored polyubiquitin chain that leads to MAP3K7 activation. Leads to the activation of NF-kappa-B and JUN. May be essential for the formation of functional osteoclasts. Seems to also play a role in dendritic cells (DCs) maturation and/or activation. Represses c-Myb-mediated transactivation, in B-lymphocytes. Adapter protein that seems to play a role in signal transduction initiated via TNF receptor, IL-1 receptor and IL-17 receptor. Regulates osteoclast differentiation by mediating the activation of adapter protein complex 1 (AP-1) and NF-kappa-B, in response to RANK-L stimulation. Together with MAP3K8, mediates CD40 signals that activate ERK in B-cells and macrophages, and thus may play a role in the regulation of immunoglobulin production.

The following transcription factors affect gene expression:

• NF-kappaB
• STAT3
• NF-kappaB1
• RelA

Tissue specificity:

Expressed in heart, brain, placenta, lung, liver, skeletal muscle, kidney and pancreas.

Molecular Function:

• Histone Deacetylase Binding
• Identical Protein Binding
• Ligase Activity
• Mitogen-Activated Protein Kinase Kinase Kinase Binding
• Protein Kinase B Binding
• Protein Kinase Binding
• Protein N-Terminus Binding
• Thioesterase Binding
• Tumor Necrosis Factor Receptor Binding
• Ubiquitin Conjugating Enzyme Binding
• Ubiquitin Protein Ligase Activity
• Ubiquitin Protein Ligase Binding
• Ubiquitin-Protein Transferase Activity
• Zinc Ion Binding

Biological Processes:

• Activation Of Mapk Activity
• Activation Of Nf-Kappab-Inducing Kinase Activity
• Activation Of Protein Kinase Activity
• Antigen Processing And Presentation Of Exogenous Peptide Antigen Via Mhc Class Ii
• Bone Resorption
• Cell Development
• Cellular Response To Dna Damage Stimulus
• Cellular Response To Lipopolysaccharide
• Fc-Epsilon Receptor Signaling Pathway
• I-Kappab Kinase/Nf-Kappab Signaling
• Interleukin-1-Mediated Signaling Pathway
• Jnk Cascade
• Membrane Protein Intracellular Domain Proteolysis
• Myd88-Dependent Toll-Like Receptor Signaling Pathway
• Myd88-Independent Toll-Like Receptor Signaling Pathway
• Myeloid Dendritic Cell Differentiation
• Negative Regulation Of Apoptotic Process
• Negative Regulation Of Transcription, Dna-Templated
• Negative Regulation Of Transcription From Rna Polymerase Ii Promoter
• Neural Tube Closure
• Nucleotide-Binding Oligomerization Domain Containing Signaling Pathway
• Odontogenesis Of Dentin-Containing Tooth
• Ossification
• Osteoclast Differentiation
• Positive Regulation Of Apoptotic Process
• Positive Regulation Of I-Kappab Kinase/Nf-Kappab Signaling
• Positive Regulation Of Interleukin-12 Biosynthetic Process
• Positive Regulation Of Interleukin-2 Production
• Positive Regulation Of Interleukin-6 Biosynthetic Process
• Positive Regulation Of Jun Kinase Activity
• Positive Regulation Of Lipopolysaccharide-Mediated Signaling Pathway
• Positive Regulation Of Nf-Kappab Transcription Factor Activity
• Positive Regulation Of Osteoclast Differentiation
• Positive Regulation Of Protein Ubiquitination
• Positive Regulation Of Sequence-Specific Dna Binding Transcription Factor Activity
• Positive Regulation Of Smooth Muscle Cell Proliferation
• Positive Regulation Of T Cell Activation
• Positive Regulation Of T Cell Cytokine Production
• Positive Regulation Of T Cell Proliferation
• Positive Regulation Of Transcription From Rna Polymerase Ii Promoter
• Positive Regulation Of Transcription Regulatory Region Dna Binding
• Protein Autoubiquitination
• Protein Complex Assembly
• Protein K63-Linked Ubiquitination
• Protein Polyubiquitination
• Regulation Of Immunoglobulin Secretion
• Response To Interleukin-1
• Stimulatory C-Type Lectin Receptor Signaling Pathway
• T Cell Receptor Signaling Pathway
• T-Helper 1 Type Immune Response
• Toll-Like Receptor 9 Signaling Pathway
• Toll-Like Receptor Signaling Pathway