receptor-interacting serine/threonine protein kinase 2; CARD-containing interleukin-1 beta-converting enzyme-associated kinase; CARD-containing IL-1 beta ICE-kinase; RIP-like-interacting CLARP kinase; receptor-interacting protein 2; RIP-2; tyrosine-protein kinase RIPK2 (RIPK2, CARDIAK, RICK, RIP2, UNQ277/PRO314/PRO34092)
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Function
- serine/threonine/tyrosine kinase
- role in modulation of innate immune response & adaptive immune response
- upon stimulation by bacterial peptidoglycans, NOD1 & NOD2 are activated, oligomerize & recruit RIPK2 through CARD- CARD domains
- once recruited, RIPK2 autophosphorylates & undergoes Lys-63-linked polyubiquitination by E3 ubiquitin ligases BIRC2 & BIRC3
- the polyubiquitinated protein mediates the recruitment of MAP3K7/TAK1 to IKBKG/NEMO & induces Lys-63-linked polyubiquitination of IKBKG/NEMO & subsequent activation of IKBKB/IKKB.
- in turn, NF-kappa-B is released from NF-kappa-B inhibitors & translocates into the nucleus where it activates transcription of many genes involved in immune response, growth control, or protection against apoptosis
- role during engagement of the T-cell receptor (TCR) in promoting BCL10 phosphorylation & subsequent NF-kappa-B activation
- autophosphorylated
- autophosphorylation at Tyr-474 is necessary for effective NOD2 signaling
- phosphorylated upon DNA damage, probably by ATM or ATR
- ubiquitinated on Lys-209
- undergoes Lys-63-linked polyubiquitination catalyzed by ITCH, BIRC2 or BIRC3
- binds to CFLAR/CLARP & CASP1 via their CARD domains
- binds to BIRC3/c-IAP1 & BIRC2/c-IAP2, TRAF1, TRAF2, TRAF5 & TRAF6
- may be a component of both the TNFRSF1A & TNRFSF5/CD40 receptor complex
- interacts with NOD1 & NOD2
- interacts with MAP3K4
- interaction sequesters RIPK2 from the NOD2 signaling pathway
- interacts with IKBKG/NEMO
- polyubiquitinated RIPK2 interacts with MAP3K7/TAK1
Structure
- contains an N-terminal kinase domain & a C-terminal caspase activation & recruitment domain (CARD) that mediates the recruitment of CARD-containing proteins
- belongs to the protein kinase superfamily, TKL Ser/Thr protein kinase family
- contains 1 CARD domain
- contains 1 protein kinase domain
Compartment
cytoplasm (probable)
Alternative splicing
named isoforms=2
Expression
- detected in heart, brain, placenta, lung, peripheral blood leukocytes, spleen, kidney, testis, prostate, pancreas & lymph node