Homo sapiens Gene: RIPK2
Summary
InnateDB Gene IDBG-27941.6
Last Modified 2014-10-13 [Report errors or provide feedback]
Gene Symbol RIPK2
Gene Name receptor-interacting serine-threonine kinase 2
Synonyms CARD3; CARDIAK; CCK; GIG30; RICK; RIP2;
Species Homo sapiens
Ensembl Gene ENSG00000104312
Encoded Proteins
receptor-interacting serine-threonine kinase 2
receptor-interacting serine-threonine kinase 2
receptor-interacting serine-threonine kinase 2
Protein Structure
Useful resources Stemformatics EHFPI ImmGen
InnateDB Annotation
Summary
RIPK2 functions in innate immunity by mediating NOD1 and NOD2 signalling but not TLR-mediated immune responses.
RIPK2 polyubiquitination mediates the recruitment of MAP3K7 (TAK1) and the subsequent activation of NF-kappaB signalling via IKK complex in NOD signalling.
RIPK2 deubiquitination by TNFAIP3 (A20) restricts NF-kappaB activation via NOD2 signalling.
RIPK2 is sequestered by MAP3K4 to inhibit the NOD2:RIPK2 complex from activating NF-kappaB signalling pathways.
RIPK2 is a downstream adaptor molecule in the NOD1/2 signaling pathway and is important for the progression and pathogenesis of experimental autoimmune encephalomyelitis (animal model of multiple sclerosis). RIPK2 was found to be critical for the activation of CNS-infiltrating dendritic cells.
RIPK2 is essential for NOD1 and NOD2-signalling upon recognition of bacterial peptidoglycan. RIPK2 is crucial for inflammatory cytokine secretion, activation and recruitment of macrophage and neutrophils as well as the capacity to activate the adaptive immune response. (Demonstrated in murine model)
Following NOD2 activation, IRF4 interacts with MYD88, TRAF6, and RIPK2 and downregulates K63-linked polyubiquitinylation of RICK and TRAF6 leading to disruption of NFkB activation pathways.
InnateDB Annotation from Orthologs
Summary
[Mus musculus] Ripk2 is a downstream adaptor molecule in the Nod1/2 signalling pathway and is important for the progression and pathogenesis of experimental autoimmune encephalomyelitis (animal model of multiple sclerosis). Ripk2 was found to be critical for the activation of CNS-infiltrating dendritic cells.
[Mus musculus] Ripk2 is essential for Nod1 and Nod2-signalling upon recognition of bacterial peptidoglycan. Ripk2 is crucial for inflammatory cytokine secretion, activation and recruitment of macrophage and neutrophils as well as the capacity to activate the adaptive immune response.
Entrez Gene
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]
Gene Information
Type Protein coding
Genomic Location Chromosome 8:89757747-89791063
Strand Forward strand
Band q21.3
Transcripts
ENST00000220751 ENSP00000220751
ENST00000522965 ENSP00000429271
ENST00000517696 ENSP00000427736
ENST00000518673
Interactions
Number of Interactions This gene and/or its encoded proteins are associated with 86 experimentally validated interaction(s) in this database.
They are also associated with 10 interaction(s) predicted by orthology.
Experimentally validated
Total 86 [view]
Protein-Protein 84 [view]
Protein-DNA 2 [view]
Protein-RNA 0
DNA-DNA 0
RNA-RNA 0
DNA-RNA 0
Predicted by orthology
Total 10 [view]
Gene Ontology

Molecular Function
Accession GO Term
GO:0004672 protein kinase activity
GO:0004674 protein serine/threonine kinase activity
GO:0004713 protein tyrosine kinase activity
GO:0004715 non-membrane spanning protein tyrosine kinase activity
GO:0004871 signal transducer activity
GO:0005515 protein binding
GO:0005524 ATP binding
GO:0016772 transferase activity, transferring phosphorus-containing groups
GO:0030274 LIM domain binding
GO:0042803 protein homodimerization activity
GO:0050700 CARD domain binding
Biological Process
GO:0000187 activation of MAPK activity
GO:0001961 positive regulation of cytokine-mediated signaling pathway
GO:0002224 toll-like receptor signaling pathway
GO:0002250 adaptive immune response
GO:0002755 MyD88-dependent toll-like receptor signaling pathway
GO:0002756 MyD88-independent toll-like receptor signaling pathway
GO:0002827 positive regulation of T-helper 1 type immune response
GO:0006468 protein phosphorylation
GO:0006915 apoptotic process
GO:0006954 inflammatory response
GO:0007165 signal transduction
GO:0007249 I-kappaB kinase/NF-kappaB signaling
GO:0007254 JNK cascade
GO:0008152 metabolic process
GO:0010800 positive regulation of peptidyl-threonine phosphorylation
GO:0018108 peptidyl-tyrosine phosphorylation
GO:0031398 positive regulation of protein ubiquitination
GO:0031663 lipopolysaccharide-mediated signaling pathway
GO:0032722 positive regulation of chemokine production
GO:0032727 positive regulation of interferon-alpha production
GO:0032728 positive regulation of interferon-beta production
GO:0032729 positive regulation of interferon-gamma production
GO:0032735 positive regulation of interleukin-12 production
GO:0032743 positive regulation of interleukin-2 production
GO:0032755 positive regulation of interleukin-6 production
GO:0032760 positive regulation of tumor necrosis factor production
GO:0032874 positive regulation of stress-activated MAPK cascade
GO:0033091 positive regulation of immature T cell proliferation
GO:0033138 positive regulation of peptidyl-serine phosphorylation
GO:0034134 toll-like receptor 2 signaling pathway
GO:0034138 toll-like receptor 3 signaling pathway
GO:0034142 toll-like receptor 4 signaling pathway
GO:0034146 toll-like receptor 5 signaling pathway
GO:0034162 toll-like receptor 9 signaling pathway
GO:0034166 toll-like receptor 10 signaling pathway
GO:0035666 TRIF-dependent toll-like receptor signaling pathway
GO:0035872 nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway
GO:0038123 toll-like receptor TLR1:TLR2 signaling pathway
GO:0038124 toll-like receptor TLR6:TLR2 signaling pathway
GO:0042098 T cell proliferation
GO:0042981 regulation of apoptotic process
GO:0043065 positive regulation of apoptotic process
GO:0043066 negative regulation of apoptotic process
GO:0043123 positive regulation of I-kappaB kinase/NF-kappaB signaling
GO:0043330 response to exogenous dsRNA
GO:0045087 innate immune response (InnateDB)
GO:0045627 positive regulation of T-helper 1 cell differentiation
GO:0045944 positive regulation of transcription from RNA polymerase II promoter
GO:0046330 positive regulation of JNK cascade
GO:0046641 positive regulation of alpha-beta T cell proliferation
GO:0048011 neurotrophin TRK receptor signaling pathway
GO:0050731 positive regulation of peptidyl-tyrosine phosphorylation
GO:0050830 defense response to Gram-positive bacterium
GO:0050852 T cell receptor signaling pathway
GO:0051092 positive regulation of NF-kappaB transcription factor activity
GO:0051403 stress-activated MAPK cascade
GO:0070374 positive regulation of ERK1 and ERK2 cascade
GO:0070423 nucleotide-binding oligomerization domain containing signaling pathway
GO:0070427 nucleotide-binding oligomerization domain containing 1 signaling pathway
GO:0070431 nucleotide-binding oligomerization domain containing 2 signaling pathway
GO:0070555 response to interleukin-1
GO:0070671 response to interleukin-12
GO:0070673 response to interleukin-18
GO:0071222 cellular response to lipopolysaccharide
GO:0071223 cellular response to lipoteichoic acid
GO:0071224 cellular response to peptidoglycan
GO:0071225 cellular response to muramyl dipeptide
Cellular Component
GO:0005737 cytoplasm
GO:0005829 cytosol
GO:0005856 cytoskeleton
GO:0031982 vesicle
GO:0043234 protein complex
Orthologs
Species
Mus musculus
Bos taurus
Gene ID
Gene Order
Method
Confidence
Comments
SSD Ortholog
Ortholog supports species divergence
Not yet available
SSD Ortholog
Ortholog supports species divergence
Pathways
NETPATH
TCR pathway
REACTOME
MyD88 dependent cascade initiated on endosome pathway
Signalling by NGF pathway
Toll Like Receptor 7/8 (TLR7/8) Cascade pathway
p75NTR recruits signalling complexes pathway
Toll Like Receptor TLR1:TLR2 Cascade pathway
Toll Like Receptor 9 (TLR9) Cascade pathway
Toll Like Receptor TLR6:TLR2 Cascade pathway
TCR signaling pathway
MyD88 cascade initiated on plasma membrane pathway
Cytokine Signaling in Immune system pathway
Innate Immune System pathway
Toll Like Receptor 3 (TLR3) Cascade pathway
Toll Like Receptor 2 (TLR2) Cascade pathway
Toll-Like Receptors Cascades pathway
p75 NTR receptor-mediated signalling pathway
p75NTR signals via NF-kB pathway
Signal Transduction pathway
MAP kinase activation in TLR cascade pathway
Nucleotide-binding domain, leucine rich repeat containing receptor (NLR) signaling pathways pathway
Adaptive Immune System pathway
NOD1/2 Signaling Pathway pathway
TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation pathway
Immune System pathway
MyD88-independent cascade pathway
MyD88:Mal cascade initiated on plasma membrane pathway
JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1 pathway
Signaling by Interleukins pathway
Downstream TCR signaling pathway
Interleukin-1 signaling pathway
Toll Like Receptor 4 (TLR4) Cascade pathway
Activated TLR4 signalling pathway
activated TAK1 mediates p38 MAPK activation pathway
TRIF-mediated TLR3/TLR4 signaling pathway
Toll Like Receptor 5 (TLR5) Cascade pathway
TAK1 activates NFkB by phosphorylation and activation of IKKs complex pathway
Toll Like Receptor 10 (TLR10) Cascade pathway
KEGG
NOD-like receptor signaling pathway pathway
Neurotrophin signaling pathway pathway
Shigellosis pathway
INOH
TNFR1 signaling pathway pathway
IL-7 signaling pathway
JAK STAT pathway and regulation pathway
EPO signaling pathway pathway
VEGF signaling pathway pathway
PID BIOCARTA
Fas signaling pathway (cd95) [Biocarta view]
PID NCI
IL12-mediated signaling events
p75(NTR)-mediated signaling
Canonical NF-kappaB pathway
Cross-References
SwissProt
TrEMBL E5RGK6
UniProt Splice Variant
Entrez Gene 8767
UniGene Hs.103755
RefSeq NM_003821
HUGO HGNC:10020
OMIM 603455
CCDS CCDS6247
HPRD 04585
IMGT
EMBL AF117829
GenPept
RNA Seq Atlas 8767