RIPK2 - Receptor-interacting serine/threonine-protein kinase 2 - human protein (Function)
 
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RIPK2 »  Receptor-interacting serine/threonine-protein kinase 2   [ EC 2.7.11.1 ]
 
Protein also known as:  CARD-containing interleukin-1 beta-converting enzyme-associated kinase (CARD-containing IL-1 beta ICE-kinase).
Gene name:  RIPK2
Entry whose protein(s) existence is based on evidence at protein level
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GENE REF ISO

Function

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Overview 
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.  
6
  • UniProtKB
GO molecular function 
ATP bindingdefinition[GO:0005524]  
1
  • UniProtKB KW
CARD domain bindingdefinition[GO:0050700]  
2
  • UniProtKB
  • MGI
LIM domain bindingdefinition[GO:0030274]  
1
  • UniProtKB
Non-membrane spanning protein tyrosine kinase activitydefinition[GO:0004715]  
1
  • EC 2 GO
Protein bindingdefinition[GO:0005515]  
6
  • IntAct
  • UniProtKB
  • BHF-UCL
Protein homodimerization activitydefinition[GO:0042803]  
1
  • BHF-UCL
Protein serine/threonine kinase activitydefinition[GO:0004674]  
1
  • UniProtKB KW
Signal transducer activitydefinition[GO:0004871]  
1
  • PINC
GO biological process 
Adaptive immune responsedefinition[GO:0002250]  
1
  • Ortholog Curator
Apoptotic processdefinition[GO:0006915]  
1
  • UniProtKB KW
Cellular response to lipoteichoic aciddefinition[GO:0071223] silver  
1
  • Ortholog Compara
Cellular response to muramyl dipeptidedefinition[GO:0071225]  
1
  • UniProtKB
Cellular response to peptidoglycandefinition[GO:0071224] silver  
1
  • Ortholog Compara
Defense response to Gram-positive bacteriumdefinition[GO:0050830] silver  
1
  • Ortholog Compara
I-kappaB kinase/NF-kappaB signalingdefinition[GO:0007249]  
1
  • Ortholog Curator
Inflammatory responsedefinition[GO:0006954]  
1
  • PINC
Innate immune responsedefinition[GO:0045087]  
2
  • UniProtKB
  • Ortholog Curator
Lipopolysaccharide-mediated signaling pathwaydefinition[GO:0031663] silver  
1
  • Ortholog Compara
Nucleotide-binding oligomerization domain containing 1 signaling pathwaydefinition[GO:0070427] silver  
1
  • Ortholog Compara
Nucleotide-binding oligomerization domain containing 2 signaling pathwaydefinition[GO:0070431]  
1
  • UniProtKB
Peptidyl-tyrosine phosphorylationdefinition[GO:0018108]  
1
  • EC 2 GO
Positive regulation of alpha-beta T cell proliferationdefinition[GO:0046641] silver  
1
  • Ortholog Compara
Positive regulation of apoptotic processdefinition[GO:0043065] silver  
1
  • Ortholog Compara
Positive regulation of chemokine productiondefinition[GO:0032722] silver  
1
  • Ortholog Compara
Positive regulation of cytokine-mediated signaling pathwaydefinition[GO:0001961] silver  
1
  • Ortholog Compara
Positive regulation of ERK1 and ERK2 cascadedefinition[GO:0070374] silver  
1
  • Ortholog Compara
Positive regulation of I-kappaB kinase/NF-kappaB signalingdefinition[GO:0043123]  
1
  • MGI
Positive regulation of immature T cell proliferationdefinition[GO:0033091] silver  
1
  • Ortholog Compara
Positive regulation of interferon-alpha productiondefinition[GO:0032727]  
1
  • BHF-UCL
Positive regulation of interferon-beta productiondefinition[GO:0032728]  
1
  • BHF-UCL
Positive regulation of interferon-gamma productiondefinition[GO:0032729] silver  
1
  • Ortholog Compara
Positive regulation of interleukin-12 productiondefinition[GO:0032735]  
1
  • BHF-UCL
Positive regulation of interleukin-2 productiondefinition[GO:0032743] silver  
1
  • Ortholog Compara
Positive regulation of interleukin-6 productiondefinition[GO:0032755] silver  
1
  • Ortholog Compara
Positive regulation of JNK cascadedefinition[GO:0046330] silver  
1
  • Ortholog Compara
Positive regulation of NF-kappaB transcription factor activitydefinition[GO:0051092]  
2
  • UniProtKB
Positive regulation of peptidyl-serine phosphorylationdefinition[GO:0033138]  
1
  • UniProtKB
Positive regulation of peptidyl-threonine phosphorylationdefinition[GO:0010800]  
1
  • UniProtKB
Positive regulation of peptidyl-tyrosine phosphorylationdefinition[GO:0050731]  
1
  • UniProtKB
Positive regulation of protein ubiquitinationdefinition[GO:0031398]  
2
  • BHF-UCL
  • UniProtKB
Positive regulation of T-helper 1 cell differentiationdefinition[GO:0045627] silver  
1
  • Ortholog Compara
Positive regulation of transcription from RNA polymerase II promoterdefinition[GO:0045944]  
1
  • BHF-UCL
Positive regulation of tumor necrosis factor productiondefinition[GO:0032760] silver  
1
  • Ortholog Compara
Response to exogenous dsRNAdefinition[GO:0043330] silver  
1
  • Ortholog Compara
Response to interleukin-1definition[GO:0070555] silver  
1
  • Ortholog Compara
Response to interleukin-12definition[GO:0070671] silver  
1
  • Ortholog Compara
Response to interleukin-18definition[GO:0070673] silver  
1
  • Ortholog Compara
Signal transductiondefinition[GO:0007165]  
1
  • PINC
T cell proliferationdefinition[GO:0042098] silver  
1
  • Ortholog Compara
T cell receptor signaling pathwaydefinition[GO:0050852]  
1
  • Ortholog Curator
Toll-like receptor 2 signaling pathwaydefinition[GO:0034134]  
1
  • MGI
Enzymatic activity 
This protein acts as an enzyme. It is known to catalyze the following reactions
EC 2.7.11.1: ATP + a protein ADP + a phosphoprotein.  
1
  • UniProtKB
EC 2.7.10.2: ATP + a [protein]-L-tyrosine ADP + a [protein]-L-tyrosine phosphate.  
2
  • PROSITE-ProRule
  • UniProtKB
 
More information is available from:
Pathways 
According to KEGG, this protein belongs to the following pathways:
Neurotrophin signaling pathway  hsa04722+8767  
NOD-like receptor signaling pathway  hsa04621+8767  
Shigellosis  hsa05131+8767  
Tuberculosis  hsa05152+8767  
According to Reactome, this protein belongs to the following pathways:
activated TAK1 mediates p38 MAPK activation  REACT_21399  
Downstream TCR signaling  REACT_12555  
Interleukin-1 signaling  REACT_22442  
JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1  REACT_21368  
NOD1/2 Signaling Pathway  REACT_75776  
p75NTR recruits signalling complexes  REACT_13415  
TAK1 activates NFkB by phosphorylation and activation of IKKs complex  REACT_21281  
 

Keywords

Biological process 
Adaptive immunity  definition   [KW-1064]
Apoptosis  definition   [KW-0053]
Immunity  definition   [KW-0391]
Innate immunity  definition   [KW-0399]
Molecular function 
Kinase  definition   [KW-0418]
Serine/threonine-protein kinase  definition   [KW-0723]
Transferase  definition   [KW-0808]
Technical term 
Reference proteome  definition   [KW-1185]
 

Further external links

Other
GeneWiki: RIPK2
GenomeRNAi: 8767
PRO: PR:O43353
Chemistry
GuidetoPHARMACOLOGY: 2190