RIPK1 Serine-threonine kinase which transduces inflammatory and cell-death signals (programmed necrosis) 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. Phosphorylates DAB2IP at 'Ser-728' in a TNF-alpha-dependent manner, and thereby activates the MAP3K5-JNK apoptotic cascade. 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 necrosis-inducing complex. Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family. 2 alternatively spliced human isoforms have been reported. 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; death-inducing signaling complex; endosome membrane; membrane raft; mitochondrion; plasma membrane; protein-containing complex; receptor complex; ripoptosome
Molecular Function:  ATP binding; death domain binding; death receptor binding; identical protein binding; JUN kinase kinase kinase activity; protein binding; protein homodimerization activity; protein kinase activity; protein serine kinase activity; protein serine/threonine kinase activity; protein-containing complex binding; ubiquitin protein ligase binding
Biological Process:  amyloid fibril formation; apoptotic process; cell death; cellular response to growth factor stimulus; cellular response to hydrogen peroxide; cellular response to tumor necrosis factor; extrinsic apoptotic signaling pathway; inflammatory response; MAPK cascade; necroptotic process; necroptotic signaling pathway; negative regulation of apoptotic process; negative regulation of extrinsic apoptotic signaling pathway; negative regulation of extrinsic apoptotic signaling pathway in absence of ligand; negative regulation of I-kappaB kinase/NF-kappaB signaling; negative regulation of necroptotic process; peptidyl-serine autophosphorylation; positive regulation of apoptotic process; positive regulation of extrinsic apoptotic signaling pathway; positive regulation of gene expression; positive regulation of hydrogen peroxide-induced cell death; positive regulation of I-kappaB kinase/NF-kappaB signaling; positive regulation of inflammatory response; positive regulation of interleukin-6-mediated signaling pathway; positive regulation of interleukin-8 production; positive regulation of JNK cascade; positive regulation of macrophage differentiation; positive regulation of necroptotic process; positive regulation of necrotic cell death; positive regulation of NF-kappaB transcription factor activity; positive regulation of programmed cell death; positive regulation of protein phosphorylation; positive regulation of reactive oxygen species metabolic process; positive regulation of transcription by RNA polymerase II; positive regulation of tumor necrosis factor production; positive regulation of tumor necrosis factor-mediated signaling pathway; programmed necrotic cell death; protein autophosphorylation; protein catabolic process; regulation of ATP:ADP antiporter activity; response to tumor necrosis factor; ripoptosome assembly; ripoptosome assembly involved in necroptotic process; T cell apoptotic process; tumor necrosis factor-mediated signaling pathway
Disease: Autoinflammation With Episodic Fever And Lymphadenopathy; Immunodeficiency 57
Reference #:  Q13546 (UniProtKB)
Alt. Names/Synonyms: AIEFL; Cell death protein RIP; FLJ39204; IMD57; receptor (TNFRSF)-interacting serine-threonine kinase 1; receptor interacting protein; receptor interacting serine/threonine kinase 1; Receptor-interacting protein 1; receptor-interacting protein kinase 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, siRNAs or Recombinant Proteins from Cell Signaling Technology® Total Proteins
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Protein Structure Not Found.

Cross-references to other databases:  AlphaFold  |  STRING  |  cBioPortal  |  Wikipedia  |  Reactome  |  neXtProt  |  Protein Atlas  |  BioGPS  |  KinBase  |  Pfam  |  RCSB PDB  |  ENZYME  |  Phospho.ELM  |  NetworKIN  |  GeneCards  |  UniProtKB  |  Entrez-Gene  |  GenPept  |  Ensembl Gene