ID:RIPK2_HUMAN DESCRIPTION: RecName: Full=Receptor-interacting serine/threonine-protein kinase 2; EC=2.7.11.1; AltName: Full=CARD-containing interleukin-1 beta-converting enzyme-associated kinase; Short=CARD-containing IL-1 beta ICE-kinase; AltName: Full=RIP-like-interacting CLARP kinase; AltName: Full=Receptor-interacting protein 2; Short=RIP-2; AltName: Full=Tyrosine-protein kinase RIPK2; EC=2.7.10.2; FUNCTION: 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. Once recruited, RIPK2 autophosphorylates and undergoes 'Lys-63'-linked polyubiquitination by E3 ubiquitin ligases 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. CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein. CATALYTIC ACTIVITY: ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate. SUBUNIT: 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 and NOD2. 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. INTERACTION: Q13490:BIRC2; NbExp=3; IntAct=EBI-358522, EBI-514538; Q13489:BIRC3; NbExp=3; IntAct=EBI-358522, EBI-517709; Q7Z434:MAVS; NbExp=3; IntAct=EBI-358522, EBI-995373; SUBCELLULAR LOCATION: Cytoplasm (Probable). TISSUE SPECIFICITY: Detected in heart, brain, placenta, lung, peripheral blood leukocytes, spleen, kidney, testis, prostate, pancreas and lymph node. DOMAIN: Contains an N-terminal kinase domain and a C-terminal caspase activation and recruitment domain (CARD) that mediates the recruitment of CARD-containing proteins. PTM: Autophosphorylated. Autophosphorylation at Tyr-474 is necessary for effective NOD2 signaling. Phosphorylated upon DNA damage, probably by ATM or ATR. PTM: 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. SIMILARITY: Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family. SIMILARITY: Contains 1 CARD domain. SIMILARITY: Contains 1 protein kinase domain.
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
Pfam Domains: PF00069 - Protein kinase domain PF00619 - Caspase recruitment domain PF07714 - Protein tyrosine and serine/threonine kinase
SCOP Domains: 47819 - HRDC-like 47986 - DEATH domain 56112 - Protein kinase-like (PK-like)
ModBase Predicted Comparative 3D Structure on O43353
Front
Top
Side
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.
Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
US Server
Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
