RIPK1
Gene Information
- Official Symbol: RIPK1
- Official Name: receptor interacting serine/threonine kinase 1
- Aliases and Previous Symbols: N/A
- Entrez ID: 8737
- UniProt: Q13546
- Interactions: BioGRID
- PubMed articles: Open PubMed
- OMIM: Open OMIM
Function Summary
- Entrez Summary: N/A
- UniProt Summary: 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. {ECO:0000269|PubMed:11101870, ECO:0000269|PubMed:17389591, ECO:0000269|PubMed:19524512, ECO:0000269|PubMed:19524513}.
Pfam Domains GO Terms
Pfam Domains
| Pkinase |
| RHIM |
| Pkinase Tyr |
| Death |
GO Terms
| regulation of ATP:ADP antiporter activity |
| ripoptosome assembly involved in necroptotic process |
| ripoptosome assembly |
| positive regulation of necroptotic process |
| positive regulation of programmed necrotic cell death |
| death domain binding |
| positive regulation of hydrogen peroxide-induced cell death |
| ripoptosome |
| necroptotic signaling pathway |
| death-inducing signaling complex |
| positive regulation of response to reactive oxygen species |
| peptidyl-serine autophosphorylation |
| death-inducing signaling complex assembly |
| positive regulation of necrotic cell death |
| JUN kinase kinase kinase activity |
| amyloid fibril formation |
| positive regulation of tumor necrosis factor-mediated signaling pathway |
| positive regulation of production of miRNAs involved in gene silencing by miRNA |
| positive regulation of cellular response to drug |
| toll-like receptor 3 signaling pathway |
| activation of JNKK activity |
| negative regulation of cardiac muscle cell proliferation |
| T cell apoptotic process |
| positive regulation of macrophage differentiation |
| positive regulation of oxidative stress-induced cell death |
| death receptor binding |
| regulation of nucleobase-containing compound transport |
| regulation of necroptotic process |
| positive regulation of cellular response to oxidative stress |
| lymphocyte apoptotic process |
| regulation of production of miRNAs involved in gene silencing by miRNA |
| positive regulation of response to oxidative stress |
| regulation of production of small RNA involved in gene silencing by RNA |
| regulation of programmed necrotic cell death |
| regulation of macrophage differentiation |
| regulation of hydrogen peroxide-induced cell death |
| necroptotic process |
| positive regulation of gene silencing by miRNA |
| negative regulation of heart growth |
| negative regulation of cardiac muscle tissue growth |
| leukocyte apoptotic process |
| positive regulation of posttranscriptional gene silencing |
| regulation of anion transmembrane transport |
| programmed necrotic cell death |
| TRIF-dependent toll-like receptor signaling pathway |
| regulation of necrotic cell death |
| necrotic cell death |
| positive regulation of response to drug |
| negative regulation of organ growth |
| negative regulation of cardiac muscle tissue development |
| MyD88-independent toll-like receptor signaling pathway |
| regulation of response to reactive oxygen species |
| negative regulation of extrinsic apoptotic signaling pathway in absence of ligand |
| regulation of cellular response to drug |
| negative regulation of signal transduction in absence of ligand |
| negative regulation of extrinsic apoptotic signaling pathway via death domain receptors |
| activation of JUN kinase activity |
| regulation of cardiac muscle cell proliferation |
| negative regulation of I-kappaB kinase/NF-kappaB signaling |
| regulation of extrinsic apoptotic signaling pathway in absence of ligand |
| negative regulation of striated muscle tissue development |
| positive regulation of interleukin-8 production |
| positive regulation of extrinsic apoptotic signaling pathway |
| negative regulation of muscle organ development |
| positive regulation of cytokine-mediated signaling pathway |
| negative regulation of muscle tissue development |
| activation of MAPKK activity |
| positive regulation of myeloid leukocyte differentiation |
| regulation of extrinsic apoptotic signaling pathway via death domain receptors |
| positive regulation of response to cytokine stimulus |
| regulation of cardiac muscle tissue growth |
| regulation of tumor necrosis factor-mediated signaling pathway |
| regulation of oxidative stress-induced cell death |
| regulation of heart growth |
| regulation of interleukin-8 production |
| I-kappaB kinase/NF-kappaB signaling |
| cellular response to hydrogen peroxide |
| positive regulation of JUN kinase activity |
| regulation of cellular response to oxidative stress |
| regulation of cardiac muscle tissue development |
| JNK cascade |
| regulation of response to oxidative stress |
| positive regulation of tumor necrosis factor production |
| regulation of gene silencing by miRNA |
| regulation of JUN kinase activity |
| activation of cysteine-type endopeptidase activity involved in apoptotic process |
| positive regulation of tumor necrosis factor superfamily cytokine production |
| regulation of gene silencing by RNA |
| regulation of posttranscriptional gene silencing |
| positive regulation of myeloid cell differentiation |
| regulation of organ growth |
| positive regulation of reactive oxygen species metabolic process |
| regulation of anion transport |
| extrinsic apoptotic signaling pathway |
| toll-like receptor signaling pathway |
| regulation of response to drug |
| negative regulation of extrinsic apoptotic signaling pathway |
| negative regulation of G1/S transition of mitotic cell cycle |
| negative regulation of developmental growth |
| stress-activated MAPK cascade |
| negative regulation of cell cycle G1/S phase transition |
| protein heterooligomerization |
| regulation of myeloid leukocyte differentiation |
| cellular response to antibiotic |
| tumor necrosis factor-mediated signaling pathway |
| response to hydrogen peroxide |
| pattern recognition receptor signaling pathway |
| regulation of gene silencing |
| cellular response to reactive oxygen species |
| regulation of striated muscle tissue development |
| positive regulation of cysteine-type endopeptidase activity involved in apoptotic process |
| regulation of muscle tissue development |
| regulation of muscle organ development |
| positive regulation of JNK cascade |
| stress-activated protein kinase signaling cascade |
| positive regulation of leukocyte differentiation |
| regulation of tumor necrosis factor production |
| regulation of G1/S transition of mitotic cell cycle |
| positive regulation of cysteine-type endopeptidase activity |
| regulation of tumor necrosis factor superfamily cytokine production |
| positive regulation of NF-kappaB transcription factor activity |
| regulation of extrinsic apoptotic signaling pathway |
| activation of MAPK activity |
| regulation of cytokine-mediated signaling pathway |
| regulation of cell cycle G1/S phase transition |
| positive regulation of stress-activated MAPK cascade |
| positive regulation of stress-activated protein kinase signaling cascade |
| positive regulation of endopeptidase activity |
| peptidyl-serine phosphorylation |
| positive regulation of apoptotic signaling pathway |
| regulation of response to cytokine stimulus |
| regulation of reactive oxygen species metabolic process |
| positive regulation of I-kappaB kinase/NF-kappaB signaling |
| regulation of JNK cascade |
| positive regulation of hemopoiesis |
| positive regulation of peptidase activity |
| protein autophosphorylation |
| response to reactive oxygen species |
| peptidyl-serine modification |
| receptor complex |
| negative regulation of mitotic cell cycle phase transition |
| endosome membrane |
| cellular response to toxic substance |
| regulation of cysteine-type endopeptidase activity involved in apoptotic process |
| membrane raft |
| negative regulation of apoptotic signaling pathway |
| regulation of myeloid cell differentiation |
| negative regulation of cell cycle phase transition |
| innate immune response-activating signal transduction |
| regulation of stress-activated MAPK cascade |
| regulation of I-kappaB kinase/NF-kappaB signaling |
| regulation of stress-activated protein kinase signaling cascade |
| protein kinase activity |
| cellular response to oxidative stress |
| cellular response to tumor necrosis factor |
| regulation of cysteine-type endopeptidase activity |
| negative regulation of growth |
| activation of innate immune response |
| regulation of ion transmembrane transporter activity |
| positive regulation of DNA-binding transcription factor activity |
| positive regulation of MAP kinase activity |
| response to tumor necrosis factor |
| regulation of transmembrane transporter activity |
| protein-containing complex binding |
| regulation of leukocyte differentiation |
| regulation of transporter activity |
| protein deubiquitination |
| apoptotic signaling pathway |
| ubiquitin protein ligase binding |
| protein modification by small protein removal |
| response to antibiotic |
| negative regulation of mitotic cell cycle |
| negative regulation of cell cycle process |
| activation of protein kinase activity |
| regulation of developmental growth |
| positive regulation of protein serine/threonine kinase activity |
| protein homooligomerization |
| positive regulation of innate immune response |
| regulation of MAP kinase activity |
| positive regulation of proteolysis |
| positive regulation of response to biotic stimulus |
| protein serine/threonine kinase activity |
| MAPK cascade |
| response to oxidative stress |
| signal transduction by protein phosphorylation |
| regulation of apoptotic signaling pathway |
| cellular response to drug |
| regulation of mitotic cell cycle phase transition |
| regulation of endopeptidase activity |
| regulation of DNA-binding transcription factor activity |
| regulation of peptidase activity |
| regulation of cell cycle phase transition |
| positive regulation of cytokine production |
| regulation of hemopoiesis |
| regulation of innate immune response |
| supramolecular fiber organization |
| positive regulation of defense response |
| regulation of ion transmembrane transport |
| cellular response to growth factor stimulus |
| response to toxic substance |
| negative regulation of intracellular signal transduction |
| positive regulation of multi-organism process |
| regulation of protein serine/threonine kinase activity |
| protein complex oligomerization |
| regulation of response to biotic stimulus |
| response to growth factor |
| response to inorganic substance |
| positive regulation of protein kinase activity |
| positive regulation of MAPK cascade |
| immune response-activating signal transduction |
| regulation of transmembrane transport |
| negative regulation of cell cycle |
| positive regulation of kinase activity |
| immune response-regulating signaling pathway |
| positive regulation of response to external stimulus |
| cellular protein catabolic process |
| activation of immune response |
| regulation of mitotic cell cycle |
| positive regulation of apoptotic process |
| positive regulation of programmed cell death |
| positive regulation of transferase activity |
| regulation of growth |
| cytokine-mediated signaling pathway |
| negative regulation of cell population proliferation |
| protein catabolic process |
| regulation of cytokine production |
| positive regulation of cell death |
| regulation of ion transport |
| viral process |
| regulation of proteolysis |
| regulation of cellular response to stress |
| regulation of cell cycle process |
| regulation of MAPK cascade |
| regulation of defense response |
| positive regulation of hydrolase activity |
| regulation of multi-organism process |
| symbiotic process |
| regulation of protein kinase activity |
| interspecies interaction between organisms |
| positive regulation of immune response |
| regulation of kinase activity |
| peptidyl-amino acid modification |
| negative regulation of apoptotic process |
| cellular macromolecule catabolic process |
| negative regulation of programmed cell death |
| apoptotic process |
| negative regulation of developmental process |
| positive regulation of cell differentiation |
| protein phosphorylation |
| regulation of transferase activity |
| protein modification by small protein conjugation or removal |
| negative regulation of cell death |
| cellular response to cytokine stimulus |
| positive regulation of protein phosphorylation |
| positive regulation of intracellular signal transduction |
| response to drug |
| macromolecule catabolic process |
| programmed cell death |
| cellular response to oxygen-containing compound |
| positive regulation of phosphorylation |
| organonitrogen compound catabolic process |
| identical protein binding |
| cell death |
| regulation of response to external stimulus |
| response to cytokine |
| positive regulation of phosphate metabolic process |
| positive regulation of phosphorus metabolic process |
| regulation of immune response |
| positive regulation of immune system process |
| regulation of cell cycle |
| negative regulation of multicellular organismal process |
| positive regulation of transcription by RNA polymerase II |
| positive regulation of protein modification process |
| mitochondrion |
| negative regulation of signal transduction |
| proteolysis |
| regulation of hydrolase activity |
| phosphorylation |
| negative regulation of cell communication |
| negative regulation of signaling |
| positive regulation of developmental process |
| positive regulation of catalytic activity |
| regulation of protein phosphorylation |
| regulation of response to stress |
| ATP binding |
| positive regulation of transcription, DNA-templated |
| regulation of apoptotic process |
| response to oxygen-containing compound |
| protein-containing complex assembly |
| regulation of programmed cell death |
| regulation of phosphorylation |
| positive regulation of cellular protein metabolic process |
| regulation of cell population proliferation |
| negative regulation of response to stimulus |
| positive regulation of nucleic acid-templated transcription |
| positive regulation of RNA biosynthetic process |
| positive regulation of signal transduction |
| regulation of immune system process |
| regulation of cell death |
| intracellular signal transduction |
| cellular response to stress |
| positive regulation of protein metabolic process |
| positive regulation of RNA metabolic process |
| positive regulation of multicellular organismal process |
| organic substance catabolic process |
| positive regulation of molecular function |
| regulation of phosphate metabolic process |
| regulation of phosphorus metabolic process |
| cellular catabolic process |
| regulation of cell differentiation |
| positive regulation of cell communication |
| positive regulation of signaling |
| regulation of intracellular signal transduction |
| regulation of protein modification process |
| protein-containing complex subunit organization |
| regulation of transport |
| positive regulation of nucleobase-containing compound metabolic process |
| positive regulation of macromolecule biosynthetic process |
| positive regulation of cellular biosynthetic process |
| positive regulation of gene expression |
| positive regulation of biosynthetic process |
CRISPR Data
Compound Hit Most Correlated Genes in Chemogenomics Tissues where Essential in the Avana Dataset (DepMap 20Q1)
Compound Hit
| Screen | Score |
|---|---|
| TNF-alpha 44ng/ml R08 exp533 | -2.43 |
| TRAIL 50ng/ml R00 exp36 | -2.15 |
| TRAIL 5ng/ml R00 exp35 | -2.05 |
| Suberoylanilide-Hydroxamic-Acid 0.02μM R01 exp53 | -1.75 |
| Isonicotinamide 500μM R03 exp129 | 2.41 |
Most Correlated Genes in Chemogenomics
No correlation found to any other genes in chemogenomics.
Tissues where Essential in the Avana Dataset (DepMap 20Q1)
Global Fraction of Cell Lines Where Essential: 0/739
| Tissue | Fraction Of Cell Lines Where Essential |
|---|---|
| 1290807.0 | 0/1 |
| 909776.0 | 0/1 |
| bile duct | 0/28 |
| blood | 0/28 |
| bone | 0/26 |
| breast | 0/33 |
| central nervous system | 0/56 |
| cervix | 0/4 |
| colorectal | 0/17 |
| esophagus | 0/13 |
| fibroblast | 0/1 |
| gastric | 0/16 |
| kidney | 0/21 |
| liver | 0/20 |
| lung | 0/75 |
| lymphocyte | 0/16 |
| ovary | 0/26 |
| pancreas | 0/24 |
| peripheral nervous system | 0/16 |
| plasma cell | 0/15 |
| prostate | 0/1 |
| skin | 0/24 |
| soft tissue | 0/9 |
| thyroid | 0/2 |
| upper aerodigestive | 0/22 |
| urinary tract | 0/29 |
| uterus | 0/5 |
Essentiality in NALM6
- Essentiality Rank: 5387
- Expression level (log2 read counts): 4.96
Expression Distribution
RIPK1 Expression in NALM6 Cells: 4.96