Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTCQ2E5)

• DTT Name: RIP2 messenger RNA (RIP2 mRNA)
• Synonyms: UNQ277/PRO314/PRO34092 (mRNA); Tyrosine-protein kinase RIPK2 (mRNA); Receptor-interacting serine/threonine-protein kinase 2 (mRNA); Receptor-interacting protein 2 (mRNA); RIP2 (mRNA); RIP-like-interacting CLARP kinase (mRNA); RIP-2 (mRNA); RICK (mRNA); CARDIAK (mRNA); CARD-containing interleukin-1 beta-converting enzyme-associated kinase (mRNA); CARD-containing IL-1 beta ICE-kinase (mRNA)
• Gene Name: RIPK2
• DTT Type: Clinical trial target; [1]
• BioChemical Class: mRNA target
• UniProt ID: RIPK2_HUMAN
• TTD ID: T92463
• EC Number: EC 2.7.11.1
• Sequence:
  MNGEAICSALPTIPYHKLADLRYLSRGASGTVSSARHADWRVQVAVKHLHIHTPLLDSER
  KDVLREAEILHKARFSYILPILGICNEPEFLGIVTEYMPNGSLNELLHRKTEYPDVAWPL
  RFRILHEIALGVNYLHNMTPPLLHHDLKTQNILLDNEFHVKIADFGLSKWRMMSLSQSRS
  SKSAPEGGTIIYMPPENYEPGQKSRASIKHDIYSYAVITWEVLSRKQPFEDVTNPLQIMY
  SVSQGHRPVINEESLPYDIPHRARMISLIESGWAQNPDERPSFLKCLIELEPVLRTFEEI
  TFLEAVIQLKKTKLQSVSSAIHLCDKKKMELSLNIPVNHGPQEESCGSSQLHENSGSPET
  SRSLPAPQDNDFLSRKAQDCYFMKLHHCPGNHSWDSTISGSQRAAFCDHKTTPCSSAIIN
  PLSTAGNSERLQPGIAQQWIQSKREDIVNQMTEACLNQSLDALLSRDLIMKEDYELVSTK
  PTRTSKVRQLLDTTDIQGEEFAKVIVQKLKDNKQMGLQPYPEILVVSRSPSLNLLQNKSM
• Function: 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. Serine/threonine/tyrosine kinase that plays an essential role in modulation of innate and adaptive immune responses.
• KEGG Pathway:
  NOD-like receptor signaling pathway (hsa04621)
  Neurotrophin signaling pathway (hsa04722)
  Shigellosis (hsa05131)
  Tuberculosis (hsa05152)
• Reactome Pathway:
  p75NTR recruits signalling complexes (R-HSA-209543)
  TAK1 activates NFkB by phosphorylation and activation of IKKs complex (R-HSA-445989)
  Interleukin-1 signaling (R-HSA-446652)
  activated TAK1 mediates p38 MAPK activation (R-HSA-450302)
  JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1 (R-HSA-450321)
  NOD1/2 Signaling Pathway (R-HSA-168638)

Molecular Interaction Atlas (MIA) of This DTT

1 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
ISIS-CRP	DMQDUG4	Cardiovascular disease	BA00-BE2Z	Phase 1	[1]

9 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
ISIS 104211	DMPKQ61	Discovery agent	N.A.	Investigative	[2]
ISIS 104253	DMME8JP	Discovery agent	N.A.	Investigative	[2]
ISIS 104254	DMDEI9X	Discovery agent	N.A.	Investigative	[2]
ISIS 104255	DMAI5B8	Discovery agent	N.A.	Investigative	[2]
ISIS 104256	DMHUX9A	Discovery agent	N.A.	Investigative	[2]
ISIS 104257	DMSDCGV	Discovery agent	N.A.	Investigative	[2]
ISIS 104258	DMUC3L0	Discovery agent	N.A.	Investigative	[2]
NM-PP1	DMS8H5Q	Discovery agent	N.A.	Investigative	[1]
Src kinase inhibitor I	DMUZP9V	Discovery agent	N.A.	Investigative	[1]

References

• [1] The selectivity of protein kinase inhibitors: a further update. Biochem J. 2007 Dec 15;408(3):297-315.
• [2] US patent application no. 6,426,221, Antisense modulation of RIP2 expression.