Property Summary

NCBI Gene PubMed Count 107
PubMed Score 103.86
PubTator Score 220.61

Knowledge Summary

Patent (123,209)


  Differential Expression (10)

Disease log2 FC p
ulcerative colitis 1.800 7.9e-07
gastric cancer -1.100 1.1e-03
hepatocellular carcinoma -1.200 6.8e-06
malignant mesothelioma -1.500 3.0e-07
astrocytic glioma 1.200 2.3e-02
glioblastoma 1.300 1.2e-03
posterior fossa group A ependymoma 1.100 1.5e-07
lung carcinoma -1.800 7.1e-21
invasive ductal carcinoma 1.100 1.7e-03
acute myeloid leukemia 1.200 3.4e-02

 GWAS Trait (1)

MLP Assay (1)

AID Type Active / Inconclusive / Inactive Description
1982 other 0 / 0 / 0 Kinase inhibition selectivity assay for compound SID-48409448

Gene RIF (66)

26646181 RIP2 and RhoGDI bind to p75(NTR) death domain at partially overlapping epitopes with over 100-fold difference in affinity, revealing the mechanism by which RIP2 recruitment displaces RhoGDI upon ligand binding.
26466644 Barettin has inhibitory activity against two protein kinases related to inflammation, namely the receptor-interacting serine/threonine kinase 2 (RIPK2) and calcium/calmodulin-dependent protein kinase 1alpha (CAMK1alpha).
26463597 up-regulated in failing hearts
26297639 RIPK1 and RIPK2 are targets of HIV-1 Protease activity during infection, and their inactivation may contribute to modulation of cell death and host defense pathways by HIV-1
26297639 HIV-1 PR (WT, not D25N) cleaves over-expressed RIPK2 with high specificity and this cleavage is prevent by addition of Saquinavir (protease inhibitor)
26130752 that Rip2 modifies VEGF-induced signalling and vascular permeability in myocardial ischaemia
26040030 Changes in the expression levels of IRS1, IRS2, RIPK2, RSPO1, and DNA JC15 genes might contribute to the development of insulin resistance and glucose intolerance in the obese boys.
25374171 RIP2 protein, human is involved in human colon tumorigenesis and could be a predictive marker for colon carcinoma progression
24958724 the NOD1-RIP2 signaling axis is more complex than previously assumed, that simple engagement of RIP2 is insufficient to mediate signaling
24746552 NOD1 and RIP2 interact with bacterial peptidoglycan on endosomes to promote autophagy and inflammatory signaling.
24670424 NOD2 downregulates colonic inflammation by IRF4-mediated inhibition of K63-linked polyubiquitination of RICK and TRAF6.
24658576 Receptor interacting protein-2 plays a critical role in human lung epithelial cells survival in response to Fas-induced cell-death.
24642040 Data indicate that receptor-interacting protein kinase 2 (RIP2) is an activator of the NF-kappa B and c-Jun N-terminal kinase pathways.
24366254 The Nod1/2-Rip2 axis was critical to induce optimal cytokine and chemokine responses to A. baumannii infection.
24015287 LRRK2 and RIPK2 variants in the NOD 2-mediated signaling pathway are associated with susceptibility to Mycobacterium leprae in Indian populations.
23892723 Our findings identify RIP2 as a substrate for Pellino3 and Pellino3 as an important mediator in the Nod2 pathway and regulator of intestinal inflammation.
23333941 In an attempt to explore TRAF3 binding partners that may be involved in TRAF3-regulated signaling, a yeast two-hybrid screen of a human spleen cDNA library was undertaken. RIP2 was identified as a TRAF3 binding partner.
23300079 Data suggest that ubiquitin (Ub) binding provides a negative feedback loop upon NOD1 and NOD2 (nucleotide-binding oligomerization domain-containing proteins)-dependent activation of receptor-interacting protein kinase 2 (RIP2).
22993319 RIPK2 might play an important role in hepatic cell migration. These findings could shed new light on carcinogenesis and on liver regeneration.
22828789 regulates reduced prostaglandin E2 production in chronic periodontitis
22815893 inositol phosphatase SHIP-1 inhibits NOD2-induced NF-kappaB activation by disturbing the interaction of XIAP with RIP2
22685397 we demonstrate that Porphyromonas gingivalis infection of human aortic endothelial cells resulted in the rapid cleavage of RIPK1 and RIPK2
22665475 RIP2 tyrosine kinase activity is not only required for NOD2-dependent autophagy but plays a dual role in this process.
22615316 These findings mechanisms whereby HBeAg modulates intracellular signaling pathways by targeting RIPK2, supporting the concept that HBeAg could impair both innate and adaptive immune responses to promote chronic HBV infection.
22504414 Association has been found between RIPK2 (rs42490) and cancer risk.
22484241 IL-4 failed to up-regulate expression of RP105 at the cell surface. In conclusion, the anti-inflammatory actions of IL-4 occur independently of IL-10, RP105, and the kinase activity of RIPK2
22075569 RIP2 gene polymorphisms may be associated with susceptibility to systemic lupus erythematosus in the Chinese population.
21887730 GEF-H1 mediated the activation of Rip2 during signaling by NOD2, but not in the presence of the 3020insC variant of NOD2 associated with Crohn's disease. GEF-H1 functioned downstream of NOD2 as part of Rip2-containing signaling complexes.
21862576 the CARD of procaspase-1 is differently involved in the formation of procaspase-1 activating platforms and procaspase-1-mediated, RIP2-dependent NF-kappaB activation.
21757725 Tri-DAP interacts directly with the LRR domain of NOD1 and consequently increases RICK/NOD1 association and RICK phosphorylation activity
21123652 RIP2 undergoes autophosphorylation on Tyr 474 and this event is necessary for effective NOD2 signaling
21048031 Observational study of gene-disease association and gene-environment interaction. (HuGE Navigator)
20800603 Observational study of gene-disease association. (HuGE Navigator)
20645315 RIP2 polymorphisms are not associated with inflammatory bowel diseases.
20025869 Data suggest that inhibition of rip2 upregulation after wounding might contribute to the reduced and delayed wound re-epithelialization phenotype seen in glucocorticoid-treated patients.
20018961 Observational study and genome-wide association study of gene-disease association. (HuGE Navigator)
19911254 MS80 inhibits CD40-NF-kappaB pathway via targeting RIP2.
19773279 Observational study of gene-disease association. (HuGE Navigator)
19721713 the NOD2/RIP2 pathway has a role in recognition of Yersinia, but caspase-12 does not modulate innate host defense against Y. pestis
19693652 Elevated RIP-2 protein levels promote NF-kappaB function via interaction with IKK gamma
19667203 Data suggest a role for XIAP in regulating innate immune responses by interacting with NOD1 and NOD2 through interaction with RIP2.
19573080 Observational study of gene-disease association. (HuGE Navigator)
19406482 detected on all female reproductive tract tissues
19336552 Observational study of gene-disease association. (HuGE Navigator)
19121870 alternative mRNA splicing may be involved in the regulation of RIP2 actions, underlying the complexity of RIP2-dependent pathways regulating stress signaling and apoptosis.
18566542 upregulation of RIP2 expression is required for rapid resolution of peritonitis
18426885 We conclude that the endogenous IL-8 response induced by C. trachomatis infection is dependent upon NOD1 signaling through RIP2 as part of a signal system requiring multiple inputs for optimal IL-8 induction.
18359207 The encapsulation efficiency of RIPK2 is reported.
18079694 Data show that RICK polyubiquitination links TAK1 to IKK complexes, a critical step in Nod1/Nod2-mediated NF-kappaB activation.
17851464 RIPK2 is a marker for resolution of peritoneal dialysis-associated peritonitis.
17355968 NOD2 is responsible for the membrane recruitment of RICK to induce a regulated NF-kappaB signaling and production of proinflammatory cytokines.
17075290 Although polymorphisms in RIP2 are not likely to be associated with the development of asthma, the genetic variants might contribute to asthma severity in the Japanese population
17054981 mutational analysis shows that interaction of NOD1 with RICK is critically dependent on 3 acidic residues on NOD1 CARD & 3 basic residues on RICK CARD & is likely to have a strong electrostatic component
16920334 Cop inhibition of cell death, at least to a certain extent, results from its interference with the activation of caspase-1 and caspase-4.
16824733 Results indicate that S176 is a regulatory autophosphorylation site for RIP2 and that S176 phosphorylation can be used to monitor the activation state of RIP2.
16582588 review of the regulation of interactions of CARD6 with RICK and microtubules [review]
16492792 NOD2-S interacts with both, NOD2 and receptor-interacting protein kinase 2 and inhibits the "nodosome" assembly by interfering with the oligomerization of NOD2
16418290 CARD6 is a regulator of NF-kappaB activation that modulates the functions of RICK protein
16354923 Caspase-1-mediated cell death is regulated, at least in part, by the balance of Rip2 and Cop; alterations of this balance may contribute to aberrant caspase-1-mediated pathogenesis in Huntington's disease.
15620648 NOD2-dependent ubiquitinylation of NEMO (a key component of the NF-kB signaling complex) is dependent on the scaffolding protein kinase RIP2.
14638696 Rip2 has an important role in TCR-induced NF-kappaB activation and T-cell function
12775719 role in CARD6 modulation of NF-kappa B activation
12755636 equilibrium and kinetic folding of a unique protein domain, caspase recruitment domain (CARD), of the RIP-like interacting CLARP kinase (RICK) (RICK-CARD), which adopts a alpha-helical Greek key fold
12138198 These results implicate RIP2 in a previously unrecognized role: a checkpoint for myogenic proliferation and differentiation.
11894098 Rip2 transduces signals from both innate and adaptive immune responses. Functions downstream of the TLR2/3/4, IL-1 and IL-18 receptors.
11894097 Involvement of receptor-interacting protein 2 in innate and adaptive immune responses

AA Sequence


Text Mined References (120)

PMID Year Title
26871637 2016 Widespread Expansion of Protein Interaction Capabilities by Alternative Splicing.
26646181 2015 Structural basis of death domain signaling in the p75 neurotrophin receptor.
26466644 2015 The immunomodulatory effects of barettin and involvement of the kinases CAMK1? and RIPK2.
26463597 2015 Regulatory role of CARD3 in left ventricular remodelling and dysfunction after myocardial infarction.
26297639 2015 HIV-1 protease cleaves the serine-threonine kinases RIPK1 and RIPK2.
26130752 2015 Rip2 modifies VEGF-induced signalling and vascular permeability in myocardial ischaemia.
26040030 2015 The expression of CCN2, IQSEC, RSPO1, DNAJC15, RIPK2, IL13RA2, IRS1, and IRS2 genes in blood of obese boys with insulin resistance.
25642632 2015 Discovery of six new susceptibility loci and analysis of pleiotropic effects in leprosy.
25416956 2014 A proteome-scale map of the human interactome network.
25374171 2014 hARIP2 is a putative growth-promoting factor involved in human colon tumorigenesis.
24958724 2014 Engagement of nucleotide-binding oligomerization domain-containing protein 1 (NOD1) by receptor-interacting protein 2 (RIP2) is insufficient for signal transduction.
24790089 2014 The molecular chaperone HSP70 binds to and stabilizes NOD2, an important protein involved in Crohn disease.
24746552 2014 The immune receptor NOD1 and kinase RIP2 interact with bacterial peptidoglycan on early endosomes to promote autophagy and inflammatory signaling.
24670424 2014 NOD2 downregulates colonic inflammation by IRF4-mediated inhibition of K63-linked polyubiquitination of RICK and TRAF6.
24658576 2014 Receptor interacting protein-2 plays a critical role in human lung epithelial cells survival in response to Fas-induced cell-death.
24642040 2014 Receptor-interacting protein kinase 2 promotes triple-negative breast cancer cell migration and invasion via activation of nuclear factor-kappaB and c-Jun N-terminal kinase pathways.
24366254 2014 The Nod1, Nod2, and Rip2 axis contributes to host immune defense against intracellular Acinetobacter baumannii infection.
24275569 2014 An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.
24015287 2013 LRRK2 and RIPK2 variants in the NOD 2-mediated signaling pathway are associated with susceptibility to Mycobacterium leprae in Indian populations.
23892723 2013 Pellino3 ubiquitinates RIP2 and mediates Nod2-induced signaling and protective effects in colitis.
23806334 2013 OTULIN restricts Met1-linked ubiquitination to control innate immune signaling.
23333941 2013 Identification and characterization of receptor-interacting protein 2 as a TNFR-associated factor 3 binding partner.
23300079 2013 Ubiquitin regulates caspase recruitment domain-mediated signaling by nucleotide-binding oligomerization domain-containing proteins NOD1 and NOD2.
23186163 2013 Toward a comprehensive characterization of a human cancer cell phosphoproteome.
23128233 2012 Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease.
22993319 2012 Knockdown of receptor-interacting serine/threonine protein kinase-2 (RIPK2) affects EMT-associated gene expression in human hepatoma cells.
22829933 2012 TRIM27 negatively regulates NOD2 by ubiquitination and proteasomal degradation.
22828789 2012 ASC-dependent RIP2 kinase regulates reduced PGE2 production in chronic periodontitis.
22815893 2012 The inositol phosphatase SHIP-1 inhibits NOD2-induced NF-?B activation by disturbing the interaction of XIAP with RIP2.
22685397 2012 Pathogen-mediated proteolysis of the cell death regulator RIPK1 and the host defense modulator RIPK2 in human aortic endothelial cells.
22672233 2012 NLRP10 enhances Shigella-induced pro-inflammatory responses.
22665475 2012 A dual role for receptor-interacting protein kinase 2 (RIP2) kinase activity in nucleotide-binding oligomerization domain 2 (NOD2)-dependent autophagy.
22615316 2012 Hepatitis B virus e antigen physically associates with receptor-interacting serine/threonine protein kinase 2 and regulates IL-6 gene expression.
22504414 2012 Association between C13ORF31, NOD2, RIPK2 and TLR10 polymorphisms and urothelial bladder cancer.
22484241 2012 The anti-inflammatory actions of IL-4 in human monocytes are not mediated by IL-10, RP105 or the kinase activity of RIPK2.
22412986 2012 Activation of interferon regulatory factor 5 by site specific phosphorylation.
22075569 2012 Association of RIP2 gene polymorphisms and systemic lupus erythematosus in a Chinese population.
21931591 2011 cIAP1/2 are direct E3 ligases conjugating diverse types of ubiquitin chains to receptor interacting proteins kinases 1 to 4 (RIP1-4).
21903422 2011 Mapping a dynamic innate immunity protein interaction network regulating type I interferon production.
21887730 2012 Control of NOD2 and Rip2-dependent innate immune activation by GEF-H1.
21862576 2011 Interaction patches of procaspase-1 caspase recruitment domains (CARDs) are differently involved in procaspase-1 activation and receptor-interacting protein 2 (RIP2)-dependent nuclear factor ?B signaling.
21757725 2011 L-Ala-?-D-Glu-meso-diaminopimelic acid (DAP) interacts directly with leucine-rich region domain of nucleotide-binding oligomerization domain 1, increasing phosphorylation activity of receptor-interacting serine/threonine-protein kinase 2 and its interaction with nucleotide-binding oligomerization domain 1.
21269460 2011 Initial characterization of the human central proteome.
21123652 2010 Inhibition of RIP2's tyrosine kinase activity limits NOD2-driven cytokine responses.
21048031 2011 Single nucleotide polymorphisms of matrix metalloproteinase 9 (MMP9) and tumor protein 73 (TP73) interact with Epstein-Barr virus in chronic lymphocytic leukemia: results from the European case-control study EpiLymph.
20800603 2010 Investigation of genetic susceptibility factors for human longevity - a targeted nonsynonymous SNP study.
20645315 2011 RIP2 polymorphisms in inflammatory bowel diseases.
20125193 2010 Common genetic variation and performance on standardized cognitive tests.
20068231 2010 Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis.
20025869 2010 RIP2: a novel player in the regulation of keratinocyte proliferation and cutaneous wound repair?
20018961 2009 Genomewide association study of leprosy.
19911254 2010 MS80, a novel sulfated polysaccharide, inhibits CD40-NF-kappaB pathway via targeting RIP2.
19773279 2009 Association between genetic variants in VEGF, ERCC3 and occupational benzene haematotoxicity.
19721713 2009 Caspase-12 and the inflammatory response to Yersinia pestis.
19693652 2010 Induction of RIP-2 kinase by proinflammatory cytokines is mediated via NF-kappaB signaling pathways and involves a novel feed-forward regulatory mechanism.
19667203 2009 XIAP mediates NOD signaling via interaction with RIP2.
19592251 2009 ITCH K63-ubiquitinates the NOD2 binding protein, RIP2, to influence inflammatory signaling pathways.
19573080 2009 Common genetic variants in candidate genes and risk of familial lymphoid malignancies.
19464198 2009 Cellular inhibitors of apoptosis cIAP1 and cIAP2 are required for innate immunity signaling by the pattern recognition receptors NOD1 and NOD2.
19406482 2009 Functional expression of pattern recognition receptors in tissues of the human female reproductive tract.
19369195 2009 Large-scale proteomics analysis of the human kinome.
19337385 2009 Evaluation of Nod-like receptor (NLR) effector domain interactions.
19336552 2009 Risk of non-Hodgkin lymphoma associated with germline variation in genes that regulate the cell cycle, apoptosis, and lymphocyte development.
19121870 2009 RIP2-beta: a novel alternative mRNA splice variant of the receptor interacting protein kinase RIP2.
18775659 2008 MEKK4 sequesters RIP2 to dictate NOD2 signal specificity.
18691976 2008 Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle.
18669648 2008 A quantitative atlas of mitotic phosphorylation.
18566542 2008 Receptor-interacting protein-2 deficiency delays macrophage migration and increases intracellular infection during peritoneal dialysis-associated peritonitis.
18426885 2008 The cytosolic pattern recognition receptor NOD1 induces inflammatory interleukin-8 during Chlamydia trachomatis infection.
18359207 2008 Membrane interactions of ternary phospholipid/cholesterol bilayers and encapsulation efficiencies of a RIP II protein.
18079694 2008 A critical role of RICK/RIP2 polyubiquitination in Nod-induced NF-kappaB activation.
18029348 2008 Toward a confocal subcellular atlas of the human proteome.
17851464 2007 Receptor-interacting protein 2 is a marker for resolution of peritoneal dialysis-associated peritonitis.
17468049 2007 Post-translational modifications regulate distinct functions of CARMA1 and BCL10.
17355968 2007 The NOD2-RICK complex signals from the plasma membrane.
17353931 2007 Large-scale mapping of human protein-protein interactions by mass spectrometry.
17344846 2007 Patterns of somatic mutation in human cancer genomes.
17192257 2007 Proteomics analysis of protein kinases by target class-selective prefractionation and tandem mass spectrometry.
17075290 2006 Association of the RIP2 gene with childhood atopic asthma.
17054981 2007 Solution structure of NOD1 CARD and mutational analysis of its interaction with the CARD of downstream kinase RICK.
16997282 2006 NF-kappaB functions in the nervous system: from development to disease.
16920334 2006 Protective role of Cop in Rip2/caspase-1/caspase-4-mediated HeLa cell death.
16824733 2006 Identification of a regulatory autophosphorylation site in the serine-threonine kinase RIP2.
16582588 2006 CARD tricks: controlling the interactions of CARD6 with RICK and microtubules.
16492792 2006 A short isoform of NOD2/CARD15, NOD2-S, is an endogenous inhibitor of NOD2/receptor-interacting protein kinase 2-induced signaling pathways.
16421571 2006 DNA sequence and analysis of human chromosome 8.
16418290 2006 Caspase recruitment domain protein 6 is a microtubule-interacting protein that positively modulates NF-kappaB activation.
16354923 2005 Dysregulation of receptor interacting protein-2 and caspase recruitment domain only protein mediates aberrant caspase-1 activation in Huntington's disease.
16344560 2006 Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes.
16189514 2005 Towards a proteome-scale map of the human protein-protein interaction network.
15761153 2005 High-throughput mapping of a dynamic signaling network in mammalian cells.
15691841 2005 Participation of Rip2 in lipopolysaccharide signaling is independent of its kinase activity.
15657077 2005 TRIP6 is a RIP2-associated common signaling component of multiple NF-kappaB activation pathways.
15620648 2004 The Crohn's disease protein, NOD2, requires RIP2 in order to induce ubiquitinylation of a novel site on NEMO.
15489334 2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
15276183 2004 MD-2: the Toll 'gatekeeper' in endotoxin signalling.
14743216 2004 A physical and functional map of the human TNF-alpha/NF-kappa B signal transduction pathway.
14702039 2004 Complete sequencing and characterization of 21,243 full-length human cDNAs.
14638696 2004 Rip2 participates in Bcl10 signaling and T-cell receptor-mediated NF-kappaB activation.
12975309 2003 The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment.
12775719 2003 CARD6 is a modulator of NF-kappa B activation by Nod1- and Cardiak-mediated pathways.
12761501 2003 Large-scale identification and characterization of human genes that activate NF-kappaB and MAPK signaling pathways.
12755636 2003 Equilibrium and kinetic folding of an alpha-helical Greek key protein domain: caspase recruitment domain (CARD) of RICK.
12477932 2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.
12459189 2002 Nod1, a CARD protein, enhances pro-interleukin-1beta processing through the interaction with pro-caspase-1.
12138198 2002 RIP2, a checkpoint in myogenic differentiation.
11894098 2002 RICK/Rip2/CARDIAK mediates signalling for receptors of the innate and adaptive immune systems.
11894097 2002 Involvement of receptor-interacting protein 2 in innate and adaptive immune responses.
11536016 2001 Regulation of IL-1beta generation by Pseudo-ICE and ICEBERG, two dominant negative caspase recruitment domain proteins.
11487608 2001 A prosurvival function for the p75 receptor death domain mediated via the caspase recruitment domain receptor-interacting protein 2.
11432859 2001 Cop, a caspase recruitment domain-containing protein and inhibitor of caspase-1 activation processing.
11087742 2001 Nod2, a Nod1/Apaf-1 family member that is restricted to monocytes and activates NF-kappaB.
10880512 2000 An induced proximity model for NF-kappa B activation in the Nod1/RICK and RIP signaling pathways.
10719670 2000 Innate immune recognition: mechanisms and pathways.
10559258 1999 RIP2 is a Raf1-activated mitogen-activated protein kinase kinase.
10329646 1999 Nod1, an Apaf-1-like activator of caspase-9 and nuclear factor-kappaB.
10224040 1999 Human CARD4 protein is a novel CED-4/Apaf-1 cell death family member that activates NF-kappaB.
9705938 1998 Identification of CARDIAK, a RIP-like kinase that associates with caspase-1.
9642260 1998 RIP2 is a novel NF-kappaB-activating and cell death-inducing kinase.
9575181 1998 RICK, a novel protein kinase containing a caspase recruitment domain, interacts with CLARP and regulates CD95-mediated apoptosis.