RIPK2
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. Plays a role in the inactivation of RHOA in response to NGFR signaling. Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family. Detected in heart, brain, placenta, lung, peripheral blood leukocytes, spleen, kidney, testis, prostate, pancreas and lymph node. 2 alternatively spliced human isoforms have been reported. Note: This description may include information from UniProtKB.
Protein type: EC 2.7.10.2; EC 2.7.11.1; Kinase, protein; Protein kinase, Ser/Thr (non-receptor); Protein kinase, TKL; Protein kinase, tyrosine (non-receptor); RIPK family; TKL group
Molecular Function: ATP binding; CARD domain binding; caspase binding; identical protein binding; JUN kinase kinase kinase activity; LIM domain binding; non-membrane spanning protein tyrosine kinase activity; protein binding; protein homodimerization activity; protein serine kinase activity; protein serine/threonine kinase activity; signaling adaptor activity; signaling receptor binding
Biological Process: activation of cysteine-type endopeptidase activity; adaptive immune response; apoptotic process; CD4-positive, alpha-beta T cell proliferation; cellular response to lipoteichoic acid; cellular response to muramyl dipeptide; cellular response to peptidoglycan; cytokine-mediated signaling pathway; defense response to bacterium; defense response to Gram-positive bacterium; ERK1 and ERK2 cascade; I-kappaB kinase/NF-kappaB signaling; immature T cell proliferation in thymus; inflammatory response; innate immune response; JNK cascade; lipopolysaccharide-mediated signaling pathway; nucleotide-binding oligomerization domain containing 1 signaling pathway; nucleotide-binding oligomerization domain containing 2 signaling pathway; positive regulation of apoptotic process; positive regulation of CD4-positive, alpha-beta T cell proliferation; positive regulation of chemokine production; positive regulation of cytokine-mediated signaling pathway; positive regulation of ERK1 and ERK2 cascade; positive regulation of I-kappaB kinase/NF-kappaB signaling; positive regulation of immature T cell proliferation in thymus; positive regulation of interferon-alpha production; positive regulation of interferon-beta production; positive regulation of interleukin-1 beta production; positive regulation of interleukin-12 production; positive regulation of interleukin-2 production; positive regulation of interleukin-6 production; positive regulation of JNK cascade; positive regulation of macrophage cytokine production; positive regulation of NF-kappaB transcription factor activity; positive regulation of peptidyl-serine phosphorylation; positive regulation of peptidyl-threonine phosphorylation; positive regulation of peptidyl-tyrosine phosphorylation; positive regulation of protein binding; positive regulation of protein K63-linked ubiquitination; positive regulation of protein ubiquitination; positive regulation of T-helper 1 cell differentiation; positive regulation of T-helper 1 type immune response; positive regulation of transcription by RNA polymerase II; positive regulation of tumor necrosis factor production; positive regulation of type II interferon production; positive regulation of xenophagy; protein homooligomerization; protein phosphorylation; response to exogenous dsRNA; response to interleukin-1; response to interleukin-12; response to interleukin-18; signal transduction; T cell receptor signaling pathway; toll-like receptor 2 signaling pathway; toll-like receptor 4 signaling pathway; xenophagy
