RIPK2

This gene encodes a member of the receptor-interacting protein (RIP) family of serine/threonine protein kinases. The encoded protein contains a C-terminal caspase activation and recruitment domain (CARD), and is a component of signaling complexes in both the innate and adaptive immune pathways. It is a potent activator of NF-kappaB and inducer of apoptosis in response to various stimuli. [provided by RefSeq, Jul 2008]

Receptor Interacting Serine/Threonine Kinase 2

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 (PubMed:26646181).

Activation of cysteine-type endopeptidase activityManual Assertion Based On ExperimentIDA:UniProtKB
Adaptive immune responseISS:UniProtKB
Apoptotic processManual Assertion Based On ExperimentTAS:ProtInc
Cellular response to lipoteichoic acidIEA:Ensembl
Cellular response to muramyl dipeptideManual Assertion Based On ExperimentIDA:UniProtKB
Cellular response to peptidoglycanIEA:Ensembl
Defense response to Gram-positive bacteriumIEA:Ensembl
I-kappaB kinase/NF-kappaB signalingISS:UniProtKB
Inflammatory responseManual Assertion Based On ExperimentTAS:ProtInc
Innate immune responseManual Assertion Based On ExperimentIDA:UniProtKB
Lipopolysaccharide-mediated signaling pathwayIEA:Ensembl
Nucleotide-binding oligomerization domain containing 1 signaling pathwayIEA:Ensembl
Nucleotide-binding oligomerization domain containing 2 signaling pathwayManual Assertion Based On ExperimentIDA:UniProtKB
Positive regulation of alpha-beta T cell proliferationIEA:Ensembl
Positive regulation of apoptotic processIEA:Ensembl
Positive regulation of cell deathManual Assertion Based On ExperimentIDA:UniProtKB
Positive regulation of chemokine productionIEA:Ensembl
Positive regulation of cytokine-mediated signaling pathwayIEA:Ensembl
Positive regulation of ERK1 and ERK2 cascadeIEA:Ensembl
Positive regulation of I-kappaB kinase/NF-kappaB signalingManual Assertion Based On ExperimentIDA:MGI
Positive regulation of immature T cell proliferationIEA:Ensembl
Positive regulation of interferon-alpha production1 PublicationNAS:BHF-UCL
Positive regulation of interferon-beta production1 PublicationNAS:BHF-UCL
Positive regulation of interferon-gamma productionIEA:Ensembl
Positive regulation of interleukin-1 beta productionManual Assertion Based On ExperimentIDA:UniProtKB
Positive regulation of interleukin-12 production1 PublicationNAS:BHF-UCL
Positive regulation of interleukin-2 productionIEA:Ensembl
Positive regulation of interleukin-6 productionIEA:Ensembl
Positive regulation of JNK cascadeIEA:Ensembl
Positive regulation of NF-kappaB transcription factor activityManual Assertion Based On ExperimentIDA:UniProtKB
Positive regulation of peptidyl-serine phosphorylationManual Assertion Based On ExperimentIDA:UniProtKB
Positive regulation of peptidyl-threonine phosphorylationManual Assertion Based On ExperimentIDA:UniProtKB
Positive regulation of peptidyl-tyrosine phosphorylationManual Assertion Based On ExperimentIDA:UniProtKB
Positive regulation of protein bindingManual Assertion Based On ExperimentIMP:UniProtKB
Positive regulation of protein ubiquitinationManual Assertion Based On ExperimentIMP:UniProtKB
Positive regulation of T-helper 1 cell differentiationIEA:Ensembl
Positive regulation of T-helper 1 type immune responseIEA:Ensembl
Positive regulation of transcription by RNA polymerase II1 PublicationNAS:BHF-UCL
Positive regulation of tumor necrosis factor productionIEA:Ensembl
Positive regulation of xenophagyIEA:Ensembl
Response to exogenous dsRNAIEA:Ensembl
Response to interleukin-1IEA:Ensembl
Response to interleukin-12IEA:Ensembl
Response to interleukin-18IEA:Ensembl
Signal transductionManual Assertion Based On ExperimentTAS:ProtInc
T cell proliferationIEA:Ensembl
T cell receptor signaling pathwayISS:UniProtKB
Toll-like receptor 2 signaling pathwayManual Assertion Based On ExperimentIDA:MGI
Toll-like receptor 4 signaling pathwayIEA:Ensembl

Cytoplasm

Immunodeficiency 57 with autoinflammation (IMD57):
An autosomal recessive primary immunodeficiency characterized by lymphopenia and recurrent viral, bacterial, and fungal infections. Patients exhibit early-onset inflammatory bowel disease involving the upper and lower gastrointestinal tract, and develop progressive polyarthritis.
Autoinflammation with episodic fever and lymphadenopathy (AIEFL):
An autosomal dominant immunologic disorder characterized by early onset of recurrent episodes of unexplained fever, lymphadenopathy, hepatosplenomegaly, and increased levels of inflammatory cytokines and chemokines in patient serum.

Autophosphorylated. Autophosphorylation at Tyr-474 is necessary for effective NOD2 signaling. Phosphorylated. Phosphorylation at Tyr-381 by Src kinase CSK occurs in a ARHGEF2-dependent manner and is required for NOD2-dependent innate immune activation.3 Publications
Ubiquitinated on Lys-209; undergoes 'Lys-63'-linked polyubiquitination catalyzed by ITCH. Polyubiquitinated with 'Lys-48' and 'Lys-63'-linked chains by BIRC2/c-IAP1 and BIRC3/c-IAP2, leading to activation of NF-kappa-B. Also undergoes 'Met-1'-linked polyubiquitination; the head-to-tail linear polyubiquitination is mediated by the LUBAC complex in response to NOD2 stimulation. Linear polyubiquitination is restricted by FAM105B/otulin, probably to limit NOD2-dependent pro-inflammatory signaling activation of NF-kappa-B. Undergoes 'Lys-63'-linked deubiquitination by MYSM1 to attenuate NOD2-mediated inflammation and tissue damage (By similarity).
(Microbial infection) Acetylation of Ser-174, Ser-176 and Ser-178 by Yersinia YopJ prevents phosphorylation and activation, thereby promoting cell death.