Molecular Target Synopsis
Overview
Domains and Structures
Drugs and Clinical Candidates
Druggability
Chemistry
Ligand Efficiency Plot
Pathways
Family Cladogram
Interaction Network
Gene Expression
Gene Copy Number Variation
RNAi
Mutations
Germline Genetics

RIPK2 (O43353) - Overview - Molecular Target Synopsis

Protein


RIPK2, Receptor-interacting serine/threonine-protein kinase 2
Enzyme Classification 2.7.11.1
UniProt O43353

Also Known as RIPK2_HUMAN, RIPK2, CARDIAK, RICK, RIP2

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. Found in a signaling complex consisting of at least ARHGEF2, NOD2 and RIPK2. Interacts with ARHGEF2; the interaction mediates tyrosine phosphorylation of RIPK2 by Src kinase CSK. Binds to CFLAR/CLARP and CASP1 via their CARD domains. Binds to BIRC3/c-IAP1 and BIRC2/c-IAP2, TRAF1, TRAF2, TRAF5 and TRAF6. May be a component of both the TNFRSF1A and TNRFSF5/CD40 receptor complex. Interacts with NOD1. Interacts (via CARD domain) with NOD2 (via CARD domain) (PubMed:19592251, PubMed:21887730, PubMed:27812135). Interacts with MAP3K4; this interaction sequesters RIPK2 from the NOD2 signaling pathway. Interacts with IKBKG/NEMO. The polyubiquitinated protein interacts with MAP3K7/TAK1. Interacts with XIAP/BIRC4. Interacts with NLRP10. Interacts with CARD9. Interacts with INAVA; the interaction takes place upon PRR stimulation (PubMed:28436939).

6GFJ
STRUCTURE OF RIP2 CARD DOMAIN FUSED TO CRYSTALLISABLE MBP TAG
RCSB/PDB
Inspect Structure
See all 3D Structures for RIPK2

Isoforms / Transcripts (Protein Coding)


Sub-cellular localization


UniProt: RIPK2 is active in the following subcellular-locations: cytoplasm.
GO terms: RIPK2 is active in the following subcellular-locations: cytoplasm, cytoskeleton, cytosol, protein-containing complex, vesicle.



UniProt
GO terms

Gene Copy Number Variation


In COSMIC - Cell Lines Project RIPK2 has gain in 12 cell-lines, loss in 3 cell-lines and no signal in 990 cell-lines. (see details)

Gene Expression


In NCI60, the highest expressing cell lines are: CAKI_1, IGROV1, RXF_393

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: Hs 746T, CAL51, HCC1954

In Array Express (RNA-seq of long poly adenylated RNA and long non poly adenylated RNA from ENCODE cell lines), the highest expressing cell lines are: SK-N-SH, NHLF, A549

(see details)

RNA Interference


RIPK2 was reported in the following RNAI studies:

Cell - Large Scale Profiling of Kinase Dependencies in Cancer Cell Lines, the highest RNAi cell lines are: OVAS, BT549. (see details)

3D Structures


For RIPK2 there are:
22 structures (78 chains) solved
16 are solved in complex with at least one small molecule ligand
1 are solved with an approved drug

RIPK2 is solved in complex with the approved drug(s):

0LI/PONATINIB (4C8B_A, 4C8B_B).

(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


RIPK2 has been screened with 398 compounds (696 bioactivities), 37 compounds have bioactivities that show binding affinity of <= 500nM (57 bioactivities). (see details)