E3 ubiquitin ligase that, together with UBE2N and UBE2V1, mediates the synthesis of 'Lys-63'-linked-polyubiquitin chains conjugated to proteins, such as IKBKG, 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. Homotrimer. Homooligomer. N-terminal region is dimeric while C-terminal region is trimeric; maybe providing a mode of oligomerization. Binds to TNFRSF5/CD40 and TNFRSF11A/RANK. Associates with NGFR, TNFRSF17, IRAK1, IRAK2, IRAK3, IRAK4, RIPK2, MAP3K1, MAP3K5, MAP3K14, CSK, TRAF, TRAF-interacting protein TRIP and TNF receptor associated protein TDP2. Interacts with IL17R. Interacts with SQSTM1 bridging NTRK1 and NGFR. Forms a ternary complex with SQSTM1 and PRKCZ. Interacts with PELI1, PELI2 and PELI3. Binds UBE2V1. Interacts with MAVS/IPS1. Interacts with TAX1BP1. Interacts with IL1RL1. Interacts with TRAFD1. Interacts with ZNF675. Interacts with AJUBA. Interacts with TICAM1 and TICAM2. Interacts with ZFAND5. Interacts with ARRB1 and ARRB2. Interacts with MAP3K7 and TAB1/MAP3K7IP1; during IL-1 signaling. Interacts with UBE2N. Interacts with TGFBR1, HDAC1 and RANGAP1. Interacts with AKT1, AKT2 and AKT3. Interacts (via TRAF domains) with NUMBL (via C-terminal). Interacts (via TRAF domains) with WDR34 (via WD domains). Interacts with RBCK1. Interacts with TRAF3IP2. Interacts with LIMD1 (via LIM domains). Expressed in heart, brain, placenta, lung, liver, skeletal muscle, kidney and pancreas. Belongs to the TNF receptor-associated factor family. A subfamily. Note: This description may include information from UniProtKB.
Protein type: EC 6.3.2.-; Ubiquitin conjugating system; Ligase; Ubiquitin ligase
Cellular Component: internal side of plasma membrane; protein complex; mitochondrion; perinuclear region of cytoplasm; cytoplasm; nucleolus; plasma membrane; endosome membrane; lipid particle; cell cortex; nucleus; cytosol
Molecular Function: protein kinase B binding; protein binding; signal transducer activity; ubiquitin conjugating enzyme binding; zinc ion binding; histone deacetylase binding; ubiquitin protein ligase binding; thioesterase binding; ubiquitin-protein ligase activity; protein N-terminus binding; mitogen-activated protein kinase kinase kinase binding; protein kinase binding; tumor necrosis factor receptor binding; ligase activity
Biological Process: I-kappaB kinase/NF-kappaB cascade; positive regulation of JNK activity; protein polyubiquitination; nerve growth factor receptor signaling pathway; positive regulation of apoptosis; positive regulation of osteoclast differentiation; activation of MAPK activity; stress-activated MAPK cascade; antigen processing and presentation of exogenous peptide antigen via MHC class II; osteoclast differentiation; toll-like receptor 3 signaling pathway; T cell receptor signaling pathway; activation of NF-kappaB transcription factor; toll-like receptor 5 signaling pathway; JNK cascade; positive regulation of T cell proliferation; protein complex assembly; regulation of immunoglobulin secretion; toll-like receptor 4 signaling pathway; bone resorption; T-helper 1 type immune response; membrane protein intracellular domain proteolysis; positive regulation of I-kappaB kinase/NF-kappaB cascade; toll-like receptor 2 signaling pathway; positive regulation of interleukin-2 production; activation of protein kinase activity; positive regulation of transcription factor activity; positive regulation of transcription from RNA polymerase II promoter; toll-like receptor 9 signaling pathway; negative regulation of transcription, DNA-dependent; negative regulation of apoptosis; positive regulation of smooth muscle cell proliferation; positive regulation of interleukin-6 biosynthetic process; positive regulation of lipopolysaccharide-mediated signaling pathway; positive regulation of T cell cytokine production; myeloid dendritic cell differentiation; negative regulation of transcription from RNA polymerase II promoter; toll-like receptor 10 signaling pathway; ossification; protein autoubiquitination; MyD88-independent toll-like receptor signaling pathway; activation of NF-kappaB-inducing kinase; odontogenesis of dentine-containing teeth; MyD88-dependent toll-like receptor signaling pathway; positive regulation of interleukin-12 biosynthetic process; positive regulation of protein ubiquitination; neural tube closure; toll-like receptor signaling pathway; innate immune response; positive regulation of T cell activation; cell development
SS: The number of records in which this modification site was determined using site-specific methods. SS methods include amino acid sequencing, site-directed mutagenesis, modification site-specific antibodies, specific MS strategies, etc.