Version 5.4
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
IDBP-27943
receptor-interacting serine-threonine kinase 2
IDBP-480142
receptor-interacting serine-threonine kinase 2
IDBP-477202
receptor-interacting serine-threonine kinase 2
Protein Structure
Useful resources Stemformatics EHFPI ImmGen
InnateDB Annotation
Summary
PMID 17277144
RIPK2 functions in innate immunity by mediating NOD1 and NOD2 signalling but not TLR-mediated immune responses.
PMID 18079694
RIPK2 polyubiquitination mediates the recruitment of MAP3K7 (TAK1) and the subsequent activation of NF-kappaB signalling via IKK complex in NOD signalling.
PMID 18342009
RIPK2 deubiquitination by TNFAIP3 (A20) restricts NF-kappaB activation via NOD2 signalling.
PMID 18775659
RIPK2 is sequestered by MAP3K4 to inhibit the NOD2:RIPK2 complex from activating NF-kappaB signalling pathways.
PMID 21236705
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.
PMID 21469090
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)
PMID 24670424
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
PMID 21236705
[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.
PMID 21469090
[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
ENSMUSG00000041135
View Gene Order
ENSBTAG00000015271
Not yet available
Pathways
NETPATH
NetPath_11
TCR pathway
REACTOME
REACT_21368
JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1 pathway
REACT_21399
activated TAK1 mediates p38 MAPK activation pathway
REACT_21281
TAK1 activates NFkB by phosphorylation and activation of IKKs complex pathway
REACT_6809
MyD88-independent cascade pathway
REACT_6783
Toll Like Receptor 3 (TLR3) Cascade pathway
REACT_6788
MyD88:Mal cascade initiated on plasma membrane pathway
REACT_8005
Toll Like Receptor TLR1:TLR2 Cascade pathway
REACT_8006
Toll Like Receptor TLR6:TLR2 Cascade pathway
REACT_25024
TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation pathway
REACT_25222
MyD88 dependent cascade initiated on endosome pathway
REACT_9047
Toll Like Receptor 9 (TLR9) Cascade pathway
REACT_27215
MyD88 cascade initiated on plasma membrane pathway
REACT_9027
Toll Like Receptor 10 (TLR10) Cascade pathway
REACT_6894
Toll Like Receptor 4 (TLR4) Cascade pathway
REACT_9061
Toll Like Receptor 5 (TLR5) Cascade pathway
REACT_75776
NOD1/2 Signaling Pathway pathway
REACT_12555
Downstream TCR signaling pathway
REACT_22442
Interleukin-1 signaling pathway
REACT_13415
p75NTR recruits signalling complexes pathway
REACT_11061
Signalling by NGF pathway
REACT_9020
Toll Like Receptor 7/8 (TLR7/8) Cascade pathway
REACT_12526
TCR signaling pathway
REACT_75790
Cytokine Signaling in Immune system pathway
REACT_6802
Innate Immune System pathway
REACT_7980
Toll Like Receptor 2 (TLR2) Cascade pathway
REACT_6966
Toll-Like Receptors Cascades pathway
REACT_13776
p75 NTR receptor-mediated signalling pathway
REACT_13537
p75NTR signals via NF-kB pathway
REACT_111102
Signal Transduction pathway
REACT_21308
MAP kinase activation in TLR cascade pathway
REACT_75913
Nucleotide-binding domain, leucine rich repeat containing receptor (NLR) signaling pathways pathway
REACT_75774
Adaptive Immune System pathway
REACT_6900
Immune System pathway
REACT_22232
Signaling by Interleukins pathway
REACT_6890
Activated TLR4 signalling pathway
REACT_25281
TRIF-mediated TLR3/TLR4 signaling pathway
KEGG
hsa04722
Neurotrophin signaling pathway pathway
hsa04621
NOD-like receptor signaling pathway pathway
hsa05131
Shigellosis pathway
INOH
INOH website
IL-7 signaling pathway
INOH website
JAK STAT pathway and regulation pathway
INOH website
EPO signaling pathway pathway
INOH website
VEGF signaling pathway pathway
INOH website
TNFR1 signaling pathway pathway
PID NCI
il12_2pathway
IL12-mediated signaling events
p75ntrpathway
p75(NTR)-mediated signaling
nfkappabcanonicalpathway
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

If you use InnateDB for your research, please cite the following publication:

Breuer et al., InnateDB: systems biology of innate immunity and beyond - recent updates and continuing curation. Nucl. Acids Res. (2013) 41 (D1) 

InnateDB is being developed jointly by the Brinkman Laboratory (Simon Fraser University, British Columbia, Canada), the Hancock Laboratory (University of British Columbia, Vancouver, British Columbia) and the Lynn EMBL Australia Group (South Australian Health & Medical Research Institute and Flinders University, Adelaide, Australia).

Funding is currently provided by Allergen and EMBL Australia. Previous funding has been provided by Genome Canada, the Foundation for the National Institutes of Health through the Grand Challenges in Global Health initiative and by Teagasc. InnateDB curated interactions are licensed under the Design Science License. All other data is licensed under the terms of the originating database. Contact: innatedb-mail@sfu.ca