CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-009146
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 Receptor-interacting serine/threonine-protein kinase 2 
Protein Synonyms/Alias
 Tyrosine-protein kinase RIPK2 
Gene Name
 Ripk2 
Gene Synonyms/Alias
  
Created Date
 July 27, 2013 
Organism
 Mus musculus (Mouse) 
NCBI Taxa ID
 10090 
Lysine Modification
Position
Peptide
Type
References
203ENYEPGQKSRASVKHubiquitination[1]
Reference
 [1] Proteomic analyses reveal divergent ubiquitylation site patterns in murine tissues.
 Wagner SA, Beli P, Weinert BT, Schölz C, Kelstrup CD, Young C, Nielsen ML, Olsen JV, Brakebusch C, Choudhary C.
 Mol Cell Proteomics. 2012 Dec;11(12):1578-85. [PMID: 22790023] 
Functional Description
 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, 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 release 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. 
Sequence Annotation
 DOMAIN 18 294 Protein kinase.
 DOMAIN 431 523 CARD.
 NP_BIND 24 32 ATP (By similarity).
 ACT_SITE 146 146 Proton acceptor (By similarity).
 BINDING 47 47 ATP (By similarity).
 MOD_RES 168 168 Phosphoserine (By similarity).
 MOD_RES 176 176 Phosphoserine; by autocatalysis (By
 MOD_RES 362 362 Phosphoserine (By similarity).
 MOD_RES 392 392 Phosphoserine (By similarity).
 MOD_RES 473 473 Phosphotyrosine; by autocatalysis (By
 MOD_RES 526 526 Phosphoserine (By similarity).
 MOD_RES 538 538 Phosphoserine (By similarity).  
Keyword
 Adaptive immunity; Apoptosis; ATP-binding; Complete proteome; Cytoplasm; Immunity; Innate immunity; Kinase; Nucleotide-binding; Phosphoprotein; Reference proteome; Serine/threonine-protein kinase; Transferase; Ubl conjugation. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 539 AA 
Protein Sequence
MNGDAICSAL PPIPYHKLAD LHYLSRGASG TVSSARHADW RVRVAVKHLH IHTPLLDSER 60
NDILREAEIL HKARFSYILP ILGICNEPEF LGIVTEYMPN GSLNELLHRK TEYPDIAWPL 120
RFRILHEIAL GVNYLHNMNP PLLHHDLKTQ NILLDNEFHV KIADFGLSKW RMMSLSQSRS 180
YKSAPEGGTI IYMPPENYEP GQKSRASVKH DIYSYAVIMW EVLSRKQPFE EVTNPLQIMY 240
SVSQGHRPDT SEENLPFDIP HRGLMISLIQ SGWAQNPDER PSFLKCLIEL EPVLRTFEDI 300
TFLEAVIQLK KAKIQSSSST IHLCDKKMDL SLNIPANHPP QEESCGSSLL SRNTGSPGPS 360
RSLSAPQDKG FLSGAPQDCS SLKAHHCPGN HSWDGIVSVP PGAAFCDRRA SSCSLAVISP 420
FLVEKGSERP PIGIAQQWIQ SKREAIVSQM TEACLNQSLD ALLSRDLIMK EDYELISTKP 480
TRTSKVRQLL DTSDIQGEEF AKVVVQKLKD NKQLGLQPYP EVPVLSKAPP SNFPQNKSL 539 
Gene Ontology
 GO:0005829; C:cytosol; TAS:Reactome.
 GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
 GO:0004715; F:non-membrane spanning protein tyrosine kinase activity; IEA:EC.
 GO:0004674; F:protein serine/threonine kinase activity; IEA:UniProtKB-KW.
 GO:0002250; P:adaptive immune response; IMP:UniProtKB.
 GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
 GO:0071223; P:cellular response to lipoteichoic acid; IMP:MGI.
 GO:0071224; P:cellular response to peptidoglycan; IMP:MGI.
 GO:0050830; P:defense response to Gram-positive bacterium; IMP:MGI.
 GO:0007249; P:I-kappaB kinase/NF-kappaB cascade; IMP:UniProtKB.
 GO:0045087; P:innate immune response; IMP:UniProtKB.
 GO:0031663; P:lipopolysaccharide-mediated signaling pathway; IMP:MGI.
 GO:0070427; P:nucleotide-binding oligomerization domain containing 1 signaling pathway; IMP:MGI.
 GO:0070431; P:nucleotide-binding oligomerization domain containing 2 signaling pathway; IMP:MGI.
 GO:0046641; P:positive regulation of alpha-beta T cell proliferation; IMP:MGI.
 GO:0043065; P:positive regulation of apoptotic process; IDA:MGI.
 GO:0032722; P:positive regulation of chemokine production; IMP:MGI.
 GO:0001961; P:positive regulation of cytokine-mediated signaling pathway; IMP:MGI.
 GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IDA:MGI.
 GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB cascade; IMP:MGI.
 GO:0033091; P:positive regulation of immature T cell proliferation; IMP:MGI.
 GO:0032729; P:positive regulation of interferon-gamma production; IMP:MGI.
 GO:0032743; P:positive regulation of interleukin-2 production; IMP:MGI.
 GO:0032755; P:positive regulation of interleukin-6 production; IMP:MGI.
 GO:0046330; P:positive regulation of JNK cascade; IMP:MGI.
 GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; IMP:MGI.
 GO:0031398; P:positive regulation of protein ubiquitination; IEA:Compara.
 GO:0045627; P:positive regulation of T-helper 1 cell differentiation; IMP:MGI.
 GO:0002827; P:positive regulation of T-helper 1 type immune response; IMP:MGI.
 GO:0032760; P:positive regulation of tumor necrosis factor production; IMP:MGI.
 GO:0043330; P:response to exogenous dsRNA; IMP:MGI.
 GO:0070555; P:response to interleukin-1; IMP:MGI.
 GO:0070671; P:response to interleukin-12; IMP:MGI.
 GO:0070673; P:response to interleukin-18; IMP:MGI.
 GO:0042098; P:T cell proliferation; IMP:MGI.
 GO:0050852; P:T cell receptor signaling pathway; IMP:UniProtKB.
 GO:0034134; P:toll-like receptor 2 signaling pathway; IEA:Compara.
 GO:0034142; P:toll-like receptor 4 signaling pathway; IMP:MGI. 
Interpro
 IPR001315; CARD.
 IPR011029; DEATH-like_dom.
 IPR011009; Kinase-like_dom.
 IPR000719; Prot_kinase_cat_dom.
 IPR017322; Rcpt-int_Ser/Thr_kinase-2.
 IPR008271; Ser/Thr_kinase_AS. 
Pfam
 PF00619; CARD
 PF00069; Pkinase 
SMART
 SM00114; CARD 
PROSITE
 PS50209; CARD
 PS00107; PROTEIN_KINASE_ATP
 PS50011; PROTEIN_KINASE_DOM
 PS00108; PROTEIN_KINASE_ST 
PRINTS