RIPK2
Gene Information
- Official Symbol: RIPK2
- Official Name: receptor interacting serine/threonine kinase 2
- Aliases and Previous Symbols: N/A
- Entrez ID: 8767
- UniProt: O43353
- Interactions: BioGRID
- PubMed articles: Open PubMed
- OMIM: Open OMIM
Function Summary
- Entrez Summary: This gene encodes a member of the receptor-interacting protein (RIP) family of serine/threonine protein kinases. The encoded protein contains a C-terminal caspase activation and recruitment domain (CARD), and is a component of signaling complexes in both the innate and adaptive immune pathways. It is a potent activator of NF-kappaB and inducer of apoptosis in response to various stimuli. [provided by RefSeq, Jul 2008].
- UniProt Summary: Serine/threonine/tyrosine kinase that plays an essential role in modulation of innate and adaptive immune responses. Upon stimulation by bacterial peptidoglycans, NOD1 and NOD2 are activated, oligomerize and recruit RIPK2 through CARD-CARD domains. Contributes to the tyrosine phosphorylation of the guanine exchange factor ARHGEF2 through Src tyrosine kinase leading to NF-kappaB activation by NOD2. Once recruited, RIPK2 autophosphorylates and undergoes 'Lys-63'-linked polyubiquitination by E3 ubiquitin ligases XIAP, BIRC2 and BIRC3. The polyubiquitinated protein mediates the recruitment of MAP3K7/TAK1 to IKBKG/NEMO and induces 'Lys-63'-linked polyubiquitination of IKBKG/NEMO and subsequent activation of IKBKB/IKKB. In turn, NF-kappa-B is released from NF-kappa-B inhibitors and translocates into the nucleus where it activates the transcription of hundreds of genes involved in immune response, growth control, or protection against apoptosis. Plays also a role during engagement of the T-cell receptor (TCR) in promoting BCL10 phosphorylation and subsequent NF-kappa-B activation. {ECO:0000269|PubMed:14638696, ECO:0000269|PubMed:17054981, ECO:0000269|PubMed:18079694, ECO:0000269|PubMed:21123652, ECO:0000269|PubMed:21887730}.
Pfam Domains GO Terms
Pfam Domains
| Pkinase |
| CARD |
| Pkinase Tyr |
GO Terms
| nucleotide-binding oligomerization domain containing 1 signaling pathway |
| positive regulation of immature T cell proliferation |
| cellular response to peptidoglycan |
| positive regulation of xenophagy |
| positive regulation of T-helper 1 cell differentiation |
| regulation of xenophagy |
| toll-like receptor 2 signaling pathway |
| LIM domain binding |
| nucleotide-binding oligomerization domain containing 2 signaling pathway |
| JUN kinase kinase kinase activity |
| regulation of immature T cell proliferation |
| cellular response to muramyl dipeptide |
| cellular response to lipoteichoic acid |
| response to interleukin-18 |
| response to lipoteichoic acid |
| regulation of T-helper 1 cell differentiation |
| response to peptidoglycan |
| activation of JNKK activity |
| caspase binding |
| activation of cysteine-type endopeptidase activity |
| CARD domain binding |
| toll-like receptor 4 signaling pathway |
| positive regulation of alpha-beta T cell proliferation |
| response to muramyl dipeptide |
| positive regulation of T-helper 1 type immune response |
| positive regulation of T-helper cell differentiation |
| positive regulation of interferon-alpha production |
| nucleotide-binding oligomerization domain containing signaling pathway |
| regulation of T-helper 1 type immune response |
| nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway |
| positive regulation of peptidyl-threonine phosphorylation |
| positive regulation of CD4-positive, alpha-beta T cell differentiation |
| regulation of interferon-alpha production |
| positive regulation of interferon-beta production |
| regulation of alpha-beta T cell proliferation |
| positive regulation of interleukin-2 production |
| positive regulation of interleukin-1 beta secretion |
| positive regulation of CD4-positive, alpha-beta T cell activation |
| regulation of T-helper cell differentiation |
| lipopolysaccharide-mediated signaling pathway |
| cytoplasmic pattern recognition receptor signaling pathway |
| positive regulation of interleukin-12 production |
| positive regulation of interleukin-1 secretion |
| T cell proliferation |
| activation of JUN kinase activity |
| zymogen activation |
| regulation of peptidyl-threonine phosphorylation |
| response to exogenous dsRNA |
| non-membrane spanning protein tyrosine kinase activity |
| positive regulation of alpha-beta T cell differentiation |
| regulation of CD4-positive, alpha-beta T cell differentiation |
| regulation of interleukin-1 beta secretion |
| regulation of interferon-beta production |
| response to interleukin-12 |
| positive regulation of cytokine-mediated signaling pathway |
| positive regulation of interleukin-1 beta production |
| response to dsRNA |
| activation of MAPKK activity |
| regulation of interleukin-2 production |
| regulation of interleukin-1 secretion |
| regulation of interleukin-12 production |
| positive regulation of chemokine production |
| positive regulation of response to cytokine stimulus |
| positive regulation of interleukin-1 production |
| positive regulation of alpha-beta T cell activation |
| regulation of CD4-positive, alpha-beta T cell activation |
| regulation of alpha-beta T cell differentiation |
| positive regulation of interferon-gamma production |
| positive regulation of macroautophagy |
| I-kappaB kinase/NF-kappaB signaling |
| positive regulation of JUN kinase activity |
| regulation of chemokine production |
| positive regulation of type I interferon production |
| regulation of interleukin-1 beta production |
| JNK cascade |
| positive regulation of T cell differentiation |
| lymphocyte proliferation |
| positive regulation of tumor necrosis factor production |
| mononuclear cell proliferation |
| regulation of JUN kinase activity |
| positive regulation of tumor necrosis factor superfamily cytokine production |
| regulation of alpha-beta T cell activation |
| positive regulation of lymphocyte differentiation |
| positive regulation of protein binding |
| defense response to Gram-positive bacterium |
| positive regulation of interleukin-6 production |
| positive regulation of T cell proliferation |
| regulation of interleukin-1 production |
| interleukin-1-mediated signaling pathway |
| leukocyte proliferation |
| regulation of interferon-gamma production |
| toll-like receptor signaling pathway |
| positive regulation of adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains |
| positive regulation of peptidyl-serine phosphorylation |
| stress-activated MAPK cascade |
| positive regulation of adaptive immune response |
| positive regulation of protein ubiquitination |
| positive regulation of autophagy |
| regulation of type I interferon production |
| pattern recognition receptor signaling pathway |
| positive regulation of lymphocyte proliferation |
| positive regulation of mononuclear cell proliferation |
| positive regulation of protein modification by small protein conjugation or removal |
| regulation of peptidyl-serine phosphorylation |
| positive regulation of leukocyte proliferation |
| regulation of T cell differentiation |
| positive regulation of cytokine secretion |
| positive regulation of JNK cascade |
| regulation of interleukin-6 production |
| stress-activated protein kinase signaling cascade |
| vesicle |
| peptidyl-tyrosine phosphorylation |
| regulation of adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains |
| positive regulation of leukocyte differentiation |
| peptidyl-tyrosine modification |
| regulation of tumor necrosis factor production |
| positive regulation of cysteine-type endopeptidase activity |
| positive regulation of NF-kappaB transcription factor activity |
| regulation of tumor necrosis factor superfamily cytokine production |
| activation of MAPK activity |
| regulation of T cell proliferation |
| protein processing |
| regulation of adaptive immune response |
| regulation of cytokine-mediated signaling pathway |
| intracellular receptor signaling pathway |
| positive regulation of stress-activated MAPK cascade |
| positive regulation of stress-activated protein kinase signaling cascade |
| regulation of lymphocyte differentiation |
| regulation of macroautophagy |
| positive regulation of endopeptidase activity |
| cellular response to interleukin-1 |
| T cell receptor signaling pathway |
| regulation of response to cytokine stimulus |
| positive regulation of binding |
| positive regulation of I-kappaB kinase/NF-kappaB signaling |
| cellular response to lipopolysaccharide |
| regulation of JNK cascade |
| positive regulation of hemopoiesis |
| positive regulation of peptidyl-tyrosine phosphorylation |
| positive regulation of peptidase activity |
| cellular response to molecule of bacterial origin |
| response to interleukin-1 |
| regulation of protein ubiquitination |
| positive regulation of T cell activation |
| regulation of cytokine secretion |
| regulation of lymphocyte proliferation |
| regulation of mononuclear cell proliferation |
| positive regulation of ERK1 and ERK2 cascade |
| cellular response to biotic stimulus |
| positive regulation of leukocyte cell-cell adhesion |
| positive regulation of immune effector process |
| regulation of protein binding |
| regulation of leukocyte proliferation |
| protein maturation |
| regulation of protein modification by small protein conjugation or removal |
| regulation of stress-activated MAPK cascade |
| innate immune response-activating signal transduction |
| T cell activation |
| regulation of I-kappaB kinase/NF-kappaB signaling |
| regulation of stress-activated protein kinase signaling cascade |
| regulation of cysteine-type endopeptidase activity |
| regulation of peptidyl-tyrosine phosphorylation |
| positive regulation of cell-cell adhesion |
| activation of innate immune response |
| positive regulation of MAP kinase activity |
| positive regulation of DNA-binding transcription factor activity |
| positive regulation of protein secretion |
| regulation of leukocyte differentiation |
| positive regulation of peptide secretion |
| regulation of ERK1 and ERK2 cascade |
| antigen receptor-mediated signaling pathway |
| regulation of leukocyte cell-cell adhesion |
| response to lipopolysaccharide |
| regulation of T cell activation |
| response to molecule of bacterial origin |
| cellular response to peptide |
| activation of protein kinase activity |
| defense response to bacterium |
| regulation of autophagy |
| signaling receptor binding |
| positive regulation of protein serine/threonine kinase activity |
| positive regulation of innate immune response |
| regulation of MAP kinase activity |
| positive regulation of proteolysis |
| positive regulation of lymphocyte activation |
| positive regulation of response to biotic stimulus |
| protein serine/threonine kinase activity |
| positive regulation of cellular catabolic process |
| cytoskeleton |
| MAPK cascade |
| regulation of binding |
| lymphocyte activation |
| signal transduction by protein phosphorylation |
| regulation of cell-cell adhesion |
| positive regulation of secretion by cell |
| positive regulation of cell adhesion |
| positive regulation of leukocyte activation |
| cellular response to drug |
| regulation of endopeptidase activity |
| positive regulation of cell activation |
| positive regulation of protein transport |
| regulation of DNA-binding transcription factor activity |
| positive regulation of catabolic process |
| positive regulation of secretion |
| regulation of peptidase activity |
| immune response-activating cell surface receptor signaling pathway |
| positive regulation of cytokine production |
| regulation of hemopoiesis |
| regulation of innate immune response |
| positive regulation of establishment of protein localization |
| regulation of protein secretion |
| regulation of immune effector process |
| response to peptide |
| positive regulation of defense response |
| immune response-regulating cell surface receptor signaling pathway |
| regulation of peptide secretion |
| inflammatory response |
| positive regulation of multi-organism process |
| regulation of lymphocyte activation |
| regulation of protein serine/threonine kinase activity |
| cellular response to lipid |
| regulation of response to biotic stimulus |
| positive regulation of protein kinase activity |
| positive regulation of MAPK cascade |
| cell population proliferation |
| immune response-activating signal transduction |
| positive regulation of kinase activity |
| protein-containing complex |
| immune response-regulating signaling pathway |
| cellular response to organonitrogen compound |
| positive regulation of response to external stimulus |
| regulation of leukocyte activation |
| adaptive immune response |
| activation of immune response |
| regulation of cell activation |
| positive regulation of apoptotic process |
| positive regulation of programmed cell death |
| positive regulation of transferase activity |
| cellular response to nitrogen compound |
| cytokine-mediated signaling pathway |
| regulation of cell adhesion |
| response to bacterium |
| regulation of cytokine production |
| positive regulation of cell death |
| regulation of protein transport |
| regulation of proteolysis |
| regulation of cellular response to stress |
| regulation of peptide transport |
| regulation of establishment of protein localization |
| regulation of secretion by cell |
| regulation of MAPK cascade |
| regulation of defense response |
| innate immune response |
| positive regulation of hydrolase activity |
| regulation of multi-organism process |
| regulation of protein kinase activity |
| regulation of secretion |
| regulation of cellular catabolic process |
| response to lipid |
| positive regulation of immune response |
| regulation of kinase activity |
| protein homodimerization activity |
| peptidyl-amino acid modification |
| negative regulation of apoptotic process |
| negative regulation of programmed cell death |
| positive regulation of cell population proliferation |
| response to organic cyclic compound |
| apoptotic process |
| leukocyte activation |
| defense response to other organism |
| positive regulation of cell differentiation |
| protein phosphorylation |
| regulation of transferase activity |
| positive regulation of transport |
| regulation of catabolic process |
| negative regulation of cell death |
| response to organonitrogen compound |
| cellular response to cytokine stimulus |
| positive regulation of protein phosphorylation |
| positive regulation of intracellular signal transduction |
| response to drug |
| regulation of protein localization |
| programmed cell death |
| cellular response to oxygen-containing compound |
| positive regulation of phosphorylation |
| identical protein binding |
| cell activation |
| response to nitrogen compound |
| cell death |
| regulation of response to external stimulus |
| response to cytokine |
| positive regulation of phosphorus metabolic process |
| positive regulation of phosphate metabolic process |
| positive regulation of immune system process |
| regulation of immune response |
| positive regulation of transcription by RNA polymerase II |
| cellular response to endogenous stimulus |
| positive regulation of protein modification process |
| proteolysis |
| regulation of hydrolase activity |
| phosphorylation |
| response to other organism |
| response to external biotic stimulus |
| response to biotic stimulus |
| defense response |
| positive regulation of developmental process |
| positive regulation of catalytic activity |
| regulation of protein phosphorylation |
| response to endogenous stimulus |
| regulation of response to stress |
| ATP binding |
| positive regulation of transcription, DNA-templated |
| regulation of apoptotic process |
| response to oxygen-containing compound |
| regulation of programmed cell death |
| regulation of phosphorylation |
| positive regulation of cellular protein metabolic process |
| regulation of cell population proliferation |
| positive regulation of nucleic acid-templated transcription |
| positive regulation of RNA biosynthetic process |
| regulation of immune system process |
| positive regulation of signal transduction |
| 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 |
| positive regulation of molecular function |
| regulation of phosphate metabolic process |
| regulation of phosphorus metabolic process |
| regulation of cell differentiation |
| positive regulation of cell communication |
| positive regulation of signaling |
| regulation of intracellular signal transduction |
| regulation of protein modification process |
| regulation of transport |
| immune response |
| 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 |
| 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 |
|---|---|
| Calcium Ionophore 0.4μM R07 exp342 | 1.71 |
| Cyclosporin-A 0.8μM R07 exp347 | 1.87 |
| Golgicide-A 2μM R03 exp121 | 2.03 |
Most Correlated Genes in Chemogenomics
| Gene | Correlation |
|---|---|
| HGC6.3 | 0.404 |
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: 11942
- Expression level (log2 read counts): 4.31
Expression Distribution
RIPK2 Expression in NALM6 Cells: 4.31
