Homo sapiens Protein: RIPK2
InnateDB Protein IDBP-27943.6
Last Modified 2014-10-13 [Report errors or provide feedback]
Gene Symbol RIPK2
Protein Name receptor-interacting serine-threonine kinase 2
Species Homo sapiens
Ensembl Protein ENSP00000220751
InnateDB Gene IDBG-27941 (RIPK2)
Protein Structure
UniProt Annotation
Function 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:0000269PubMed:14638696, ECO:0000269PubMed:17054981, ECO:0000269PubMed:18079694, ECO:0000269PubMed:21123652, ECO:0000269PubMed:21887730}.
Subcellular Localization Cytoplasm {ECO:0000305}.
Disease Associations
Tissue Specificity Detected in heart, brain, placenta, lung, peripheral blood leukocytes, spleen, kidney, testis, prostate, pancreas and lymph node.
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
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: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
Protein Structure and Domains
InterPro IPR000719 Protein kinase domain
IPR001245 Serine-threonine/tyrosine-protein kinase catalytic domain
IPR001315 CARD domain
IPR002290 Serine/threonine/dual specificity protein kinase, catalytic domain
IPR011009 Protein kinase-like domain
IPR011029 Death-like domain
IPR017322 Receptor-interacting serine/threonine-protein kinase 2
IPR020635 Tyrosine-protein kinase, catalytic domain
PFAM PF00069
Post-translational Modifications
SwissProt O43353
PhosphoSite PhosphoSite-O43353
UniProt Splice Variant
Entrez Gene 8767
UniGene Hs.103755
RefSeq NP_003812
OMIM 603455
HPRD 04585
EMBL AC004003 AF027706 AF064824 AF078530 AF117829 AK301448 AY358813 AY358814 BC004553
GenPept AAC24561 AAC25668 AAC27722 AAC34970 AAH04553 AAQ89172 AAQ89173 BAH13484