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RIPK2 gene, also known as RIP2, RICK or CARDAK gene, is mainly distributed in the cytoplasm and is widely expressed in various tissues of human body. Its mRNA is highly expressed in peripheral blood leukocytes, heart, placenta, spleen and testis, which is a signal transduction pathway. A key serine-threonine kinase involved in the induction of innate and acquired immune responses mediated by Toll-like receptors and NOD (nucleotide-binding oligomerization domain)-like receptors. It produces inflammatory cytokines. The RIPK2 protein is a 61 kD kinase with a serine/threonine kinase domain at the N-terminus and a caspase activation and recruitment domain (CARD) at the C-terminus. As a protein kinase, RIPK2 plays an important role in maintaining the homeostasis of the immune system. It interacts with NOD1 and NOD2-dependent signaling pathways, which can affect the secretion of inflammatory factors and the activation and recruitment of macrophages. After the infected site, the spleen inner marrow-like cells and T and B lymphocytes can be systemically activated. In innate immunity, RIPK2 has the effect of scavenging extracellular bacteria and plays an important role in host protection against the intracellular pathogen Legionella pneumophila. At the same time, RIPK2 interacts with a variety of proteins, participates in the signal transduction of multiple receptors, and exerts physiological functions.
Protein class

Enzymes, Metabolic proteins

Predicted location


Single cell type specificity

Cell type enhanced (Glandular and luminal cells, Langerhans cells, Macrophages)

Immune cell specificity

Low immune cell specificity

Cell line specificity

Cell line enhanced (hTERT-HME1)


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). Interacts (via CARD domain) with NGFR (via death domain) (PubMed:26646181).

Molecular function

Kinase, Serine/threonine-protein kinase, Transferase

More Types Infomation

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