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RIPK1 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: EC; Kinase, protein; Protein kinase, Ser/Thr (non-receptor); Protein kinase, TKL; RIPK family; TKL group
Chromosomal Location of Human Ortholog: 6p25.2
Cellular Component: cytosol; mitochondrion; receptor complex
Molecular Function: death receptor binding; identical protein binding; protein binding; protein complex binding; protein kinase activity; protein serine/threonine kinase activity; signal transducer 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 deubiquitination; protein heterooligomerization; protein homooligomerization; tumor necrosis factor-mediated signaling pathway
Reference #:  Q13546 (UniProtKB)
Alt. Names/Synonyms: Cell death protein RIP; FLJ39204; receptor (TNFRSF)-interacting serine-threonine kinase 1; receptor interacting protein; Receptor-interacting protein 1; Receptor-interacting serine/threonine-protein kinase 1; RIP; RIP-1; RIP1; RIPK1; Serine/threonine-protein kinase RIP
Gene Symbols: RIPK1
Molecular weight: 75,931 Da
Basal Isoelectric point: 5.92  Predict pI for various phosphorylation states
CST Pathways:  Apoptosis Regulation  |  Death Receptor Signaling  |  Inhibition of Apoptosis  |  NF-kB Signaling  |  Regulation of P38 MAPKs  |  SAPK/JNK Signaling Cascades  |  Toll-Like Receptor Signaling
Protein-Specific Antibodies or siRNAs from Cell Signaling Technology® Total Proteins
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