Serine-threonine kinase which transduces inflammatory and cell-death signals (necroptosis) following death receptors ligation, activation of pathogen recognition receptors (PRRs), and DNA damage. Upon activation of TNFR1 by the TNF-alpha family cytokines, TRADD and TRAF2 are recruited to the receptor. Ubiquitination by TRAF2 via 'Lys-63'-link chains acts as a critical enhancer of communication with downstream signal transducers in the mitogen-activated protein kinase pathway and the NF-kappa-B pathway, which in turn mediate downstream events including the activation of genes encoding inflammatory molecules. Polyubiquitinated protein binds to IKBKG/NEMO, the regulatory subunit of the IKK complex, a critical event for NF-kappa-B activation. Interaction with other cellular RHIM-containing adapters initiates gene activation and cell death. RIPK1 and RIPK3 association, in particular, forms a necroptosis-inducing complex. Interacts (via RIP homotypic interaction motif) with RIPK3 (via RIP homotypic interaction motif); this interaction induces RIPK1 necroptosis-specific phosphorylation, formation of the necroptosis-inducing complex. Interacts (via the death domain) with TNFRSF6 (via the death domain) and TRADD (via the death domain). Is recruited by TRADD to TNFRSF1A in a TNF-dependent process. Binds RNF216, EGFR, IKBKG, TRAF1, TRAF2 and TRAF3. Interacts with BNLF1. Interacts with SQSTM1 upon TNF-alpha stimulation. May interact with MAVS/IPS1. Interacts with ZFAND5. Interacts with RBCK1. Interacts with BIRC2/c-IAP1, BIRC3/c-IAP2 and XIAP/BIRC4. Inhibited by necrostatin-1. Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family. 2 isoforms of the human protein are produced by alternative splicing. Note: This description may include information from UniProtKB.
Protein type: Protein kinase, TKL; Protein kinase, Ser/Thr (non-receptor); Kinase, protein; EC 184.108.40.206; TKL group; RIPK family
Molecular Function: ATP binding; death receptor binding; identical protein binding; protein binding; protein complex binding; protein kinase activity; protein serine/threonine kinase activity; ubiquitin protein ligase binding
Biological Process: activation of JNK activity; activation of NF-kappaB transcription factor; apoptosis; caspase activation; cellular protein catabolic process; I-kappaB kinase/NF-kappaB cascade; negative regulation of I-kappaB kinase/NF-kappaB cascade; positive regulation of apoptosis; positive regulation of I-kappaB kinase/NF-kappaB cascade; positive regulation of interleukin-8 production; positive regulation of JNK cascade; positive regulation of macrophage differentiation; positive regulation of programmed cell death; positive regulation of protein amino acid phosphorylation; positive regulation of transcription from RNA polymerase II promoter; positive regulation of tumor necrosis factor production; protein amino acid autophosphorylation; protein heterooligomerization; protein homooligomerization; tumor necrosis factor-mediated signaling pathway
LTP: 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.