Target General Infomation
Target ID
T92463
Former ID
TTDR01346
Target Name
mRNA of human RIP2
Gene Name
RIPK2
Synonyms
CARD-containing IL-1 beta ICE-kinase (mRNA); CARD-containing interleukin-1 beta-converting enzyme-associated kinase (mRNA); RIP-like-interacting CLARP kinase (mRNA); Receptor-interacting protein 2 (mRNA); Receptor-interacting serine/threonine-protein kinase 2 (mRNA); Tyrosine-protein kinase RIPK2 (mRNA); RIPK2
Target Type
Research
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'-linkedpolyubiquitination 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.
BioChemical Class
Kinase
Target Validation
T92463
UniProt ID
EC Number
EC 2.7.10.2
Sequence
MNGEAICSALPTIPYHKLADLRYLSRGASGTVSSARHADWRVQVAVKHLHIHTPLLDSER
KDVLREAEILHKARFSYILPILGICNEPEFLGIVTEYMPNGSLNELLHRKTEYPDVAWPL
RFRILHEIALGVNYLHNMTPPLLHHDLKTQNILLDNEFHVKIADFGLSKWRMMSLSQSRS
SKSAPEGGTIIYMPPENYEPGQKSRASIKHDIYSYAVITWEVLSRKQPFEDVTNPLQIMY
SVSQGHRPVINEESLPYDIPHRARMISLIESGWAQNPDERPSFLKCLIELEPVLRTFEEI
TFLEAVIQLKKTKLQSVSSAIHLCDKKKMELSLNIPVNHGPQEESCGSSQLHENSGSPET
SRSLPAPQDNDFLSRKAQDCYFMKLHHCPGNHSWDSTISGSQRAAFCDHKTTPCSSAIIN
PLSTAGNSERLQPGIAQQWIQSKREDIVNQMTEACLNQSLDALLSRDLIMKEDYELVSTK
PTRTSKVRQLLDTTDIQGEEFAKVIVQKLKDNKQMGLQPYPEILVVSRSPSLNLLQNKSM
Inhibitor AG-1879 Drug Info [529039]
NM-PP1 Drug Info [529039]
Src kinase inhibitor I Drug Info [529039]
Pathways
KEGG Pathway NOD-like receptor signaling pathway
Neurotrophin signaling pathway
Shigellosis
Tuberculosis
NetPath Pathway IL4 Signaling Pathway
TNFalpha Signaling Pathway
Pathway Interaction Database Canonical NF-kappaB pathway
IL12-mediated signaling events
p75(NTR)-mediated signaling
Reactome NOD1/2 Signaling Pathway
p75NTR recruits signalling complexes
TAK1 activates NFkB by phosphorylation and activation of IKKs complex
Interleukin-1 signaling
activated TAK1 mediates p38 MAPK activation
JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1
WikiPathways TCR Signaling Pathway
FAS pathway and Stress induction of HSP regulation
Apoptosis-related network due to altered Notch3 in ovarian cancer
MAP kinase activation in TLR cascade
Nucleotide-binding domain, leucine rich repeat containing receptor (NLR) signaling pathways
TAK1 activates NFkB by phosphorylation and activation of IKKs complex
Signalling by NGF
TCR signaling
Interleukin-1 signaling
NOD pathway
References
Ref 529039Biochem J. 2007 Dec 15;408(3):297-315.The selectivity of protein kinase inhibitors: a further update.
Ref 549652US patent application no. 6,426,221, Antisense modulation of RIP2 expression.

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