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)

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

Properties

SIZE: entity length = 540 aa MW = 61 kD COMPARTMENT: cytoplasm STATE: active state MOTIF: kinase domain SITE: 18-294 MOTIF: ATP-binding site NAME: ATP-binding site SITE: 24-32 ATP-binding site NAME: ATP-binding site SITE: 47-47 aspartate residue {D146} Ser phosphorylation site {S168} Ser phosphorylation site {S174} Ser phosphorylation site {S176} Ser phosphorylation site {S178} Ser phosphorylation site {S332} Ser phosphorylation site {S345} Ser phosphorylation site {S349} Ser phosphorylation site {S355} Thr phosphorylation site {T360} Ser phosphorylation site {S363} Tyr phosphorylation site {Y381} Ser phosphorylation site {S393} CARD domain {432-524} MOTIF: Tyr phosphorylation site {Y474} Ser phosphorylation site {S527} Ser phosphorylation site {S529} Ser phosphorylation site {S531} Ser phosphorylation site {S539}

Database Correlations

OMIM 603455 UniProt O43353 PFAM correlations Entrez Gene 8767 Kegg hsa:8767 ENZYME correlations

References

UniProt :accession O43353