RIPK2 — Receptor interacting serine/threonine kinase 2
RIPK2 belongs to a gene co-expression module in 6 of 28 SCUBA cell types. Each module groups genes that rise and fall together in that cell type; the genes it shares a module with are its closest co-expression partners there.
RIPK2's module in each cell type
| Cell type | Module | Shares the module with | |
|---|---|---|---|
| Endothelial | IFN-gamma Response Inflammation | APOL2, APOL6, BATF2, CARD16, CASP1, CD40, CXCL10, CXCL11 +18 more | View in SCUBA |
| Fibroblasts | Cytokine Chemokine Secretion Inflammatory | CCL2, CSF3, CXCL1, CXCL3, CXCL8, G0S2, GLIS3, IL6 +1 more | View in SCUBA |
| Gamma-delta T cells | mRNA Splicing Regulation RNA processing & translation | ARF6, BTG3, CAPN7, CDV3, CELF2, CNBD2, CUL3, CYTIP +18 more | |
| Innate lymphoid cells | Inflammasome Activation Inflammation | ANKRD28, AP3D1, ARHGEF7, CCNH, CD55, CDC42SE1, CHD7, CHKA +19 more | View in SCUBA |
| Lymphatic endothelial | Genotoxic Innate Inflammation Inflammation | CSF2, CSF3, E2F7, GBP2, NBN, PLA1A, SELENOM, SQOR +1 more | View in SCUBA |
| Macrophages | Alternative Activation Lipid Lipid metabolism | ACSL1, ADCY3, AGFG1, ARHGEF10L, ARID5B, ATP2B4, BCL6, CCL13 +24 more | View in SCUBA |
About the gene
| Synonyms | CARD3, CARDIAK, RICK, RIP2 |
|---|---|
| Chromosome | 8: 89757806-89791064 |
| Predicted location | Intracellular |
| Essential gene | No |
| Protein class | Enzymes, Predicted intracellular proteins |
| Molecular function | Kinase, Serine/threonine-protein kinase, Transferase |
| Biological process | Adaptive immunity, Apoptosis, Immunity, Innate immunity |
Function
Serine/threonine/tyrosine-protein kinase that plays an essential role in modulation of innate and adaptive immune responses. Acts as a key effector of NOD1 and NOD2 signaling pathways: upon activation by bacterial peptidoglycans, NOD1 and NOD2 oligomerize and recruit RIPK2 via CARD-CARD domains, leading to the formation of RIPK2 filaments. Once recruited, RIPK2 autophosphorylates and undergoes 'Lys-63'-linked polyubiquitination by E3 ubiquitin ligases XIAP, BIRC2 and BIRC3, as well as 'Met-1'-linked (linear) polyubiquitination by the LUBAC complex, becoming a scaffolding protein for downstream effectors. 'Met-1'-linked polyubiquitin chains attached to RIPK2 recruit IKBKG/NEMO, which undergoes 'Lys-63'-linked polyubiquitination in a RIPK2-dependent process. 'Lys-63'-linked polyubiquitin chains attached to RIPK2 serve as docking sites for TAB2 and TAB3 and mediate the recruitment of MAP3K7/TAK1 to IKBKG/NEMO, inducing 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. The protein kinase activity is dispensable for the NOD1 and NOD2 signaling pathways. Contributes to the tyrosine phosphorylation of the guanine exchange factor ARHGEF2 through Src tyrosine kinase leading to NF-kappa-B activation by NOD2. Also involved in adaptive immunity: plays a role during engagement of the T-cell receptor (TCR) in promoting BCL10 phosphorylation and subsequent NF-kappa-B activation. Plays a role in the inactivation of RHOA in response to NGFR signaling.
Human Protein Atlas · Open Targets · UniProt
Gene annotation from the Human Protein Atlas and UniProt; see sources & licences.