UniProt Accession

 RIPK2_HUMAN; O43353; Q6UWF0 

Genbank Protein ID

 AF027706; AF078530; AF064824; AY358813; AY358814; AC004003; AF117829; BC004553 

Genbank Nucleotide ID

 AAC34970.1; AAC27722.1; AAC25668.1; AAQ89172.1; AAQ89173.1; AAC24561.1; AAH04553.1 

Protein Name

 Receptor-interacting serine/threonine-protein kinase 2 

Protein Synonyms/Alias

 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 

Gene Name

 RIPK2 

Gene Synonyms/Alias

 CARDIAK; RICK; RIP2; UNQ277/PRO314/PRO34092 

Created Date

 July 27, 2013 

Organism

 Homo sapiens (Human) 

NCBI Taxa ID

 9606 

Lysine Modification

Position	Peptide	Type	References
182	LSQSRSSKSAPEGGT	ubiquitination	[1, 2]
203	ENYEPGQKSRASIKH	ubiquitination	[1, 2]

Reference

 [1] Systematic and quantitative assessment of the ubiquitin-modified proteome.
 Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
 Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983]
 [2] Landscape of the PARKIN-dependent ubiquitylome in response to mitochondrial depolarization.
 Sarraf SA, Raman M, Guarani-Pereira V, Sowa ME, Huttlin EL, Gygi SP, Harper JW.
 Nature. 2013 Apr 18;496(7445):372-6. [PMID: 23503661] 

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, 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. 

Sequence Annotation

 DOMAIN 18 294 Protein kinase.
 DOMAIN 432 524 CARD.
 NP_BIND 24 32 ATP (By similarity).
 ACT_SITE 146 146 Proton acceptor.
 BINDING 47 47 ATP.
 MOD_RES 168 168 Phosphoserine.
 MOD_RES 176 176 Phosphoserine; by autocatalysis.
 MOD_RES 363 363 Phosphoserine.
 MOD_RES 393 393 Phosphoserine.
 MOD_RES 474 474 Phosphotyrosine; by autocatalysis.
 MOD_RES 527 527 Phosphoserine.
 MOD_RES 529 529 Phosphoserine.
 MOD_RES 531 531 Phosphoserine.
 MOD_RES 539 539 Phosphoserine.  

Keyword

 Adaptive immunity; Alternative splicing; Apoptosis; ATP-binding; Complete proteome; Cytoplasm; Immunity; Innate immunity; Kinase; Nucleotide-binding; Phosphoprotein; Polymorphism; Reference proteome; Serine/threonine-protein kinase; Transferase; Ubl conjugation. 

Sequence Source

 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 

Protein Length

 540 AA 

Protein Sequence

Gene Ontology

 GO:0005829; C:cytosol; TAS:Reactome.
 GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
 GO:0050700; F:CARD domain binding; IDA:MGI.
 GO:0004715; F:non-membrane spanning protein tyrosine kinase activity; IEA:EC.
 GO:0042803; F:protein homodimerization activity; IDA:BHF-UCL.
 GO:0004674; F:protein serine/threonine kinase activity; TAS:ProtInc.
 GO:0004871; F:signal transducer activity; TAS:ProtInc.
 GO:0000187; P:activation of MAPK activity; TAS:Reactome.
 GO:0002250; P:adaptive immune response; ISS:UniProtKB.
 GO:0006915; P:apoptotic process; TAS:ProtInc.
 GO:0071223; P:cellular response to lipoteichoic acid; IEA:Compara.
 GO:0071224; P:cellular response to peptidoglycan; IEA:Compara.
 GO:0050830; P:defense response to Gram-positive bacterium; IEA:Compara.
 GO:0007249; P:I-kappaB kinase/NF-kappaB cascade; ISS:UniProtKB.
 GO:0006954; P:inflammatory response; TAS:ProtInc.
 GO:0045087; P:innate immune response; ISS:UniProtKB.
 GO:0007254; P:JNK cascade; TAS:Reactome.
 GO:0031663; P:lipopolysaccharide-mediated signaling pathway; IEA:Compara.
 GO:0002755; P:MyD88-dependent toll-like receptor signaling pathway; TAS:Reactome.
 GO:0043066; P:negative regulation of apoptotic process; TAS:Reactome.
 GO:0048011; P:neurotrophin TRK receptor signaling pathway; TAS:Reactome.
 GO:0070427; P:nucleotide-binding oligomerization domain containing 1 signaling pathway; IEA:Compara.
 GO:0070431; P:nucleotide-binding oligomerization domain containing 2 signaling pathway; IEA:Compara.
 GO:0070423; P:nucleotide-binding oligomerization domain containing signaling pathway; TAS:Reactome.
 GO:0046641; P:positive regulation of alpha-beta T cell proliferation; IEA:Compara.
 GO:0043065; P:positive regulation of apoptotic process; IEA:Compara.
 GO:0032722; P:positive regulation of chemokine production; IEA:Compara.
 GO:0001961; P:positive regulation of cytokine-mediated signaling pathway; IEA:Compara.
 GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IEA:Compara.
 GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB cascade; IDA:MGI.
 GO:0033091; P:positive regulation of immature T cell proliferation; IEA:Compara.
 GO:0032727; P:positive regulation of interferon-alpha production; NAS:BHF-UCL.
 GO:0032728; P:positive regulation of interferon-beta production; NAS:BHF-UCL.
 GO:0032729; P:positive regulation of interferon-gamma production; IEA:Compara.
 GO:0032735; P:positive regulation of interleukin-12 production; NAS:BHF-UCL.
 GO:0032743; P:positive regulation of interleukin-2 production; IEA:Compara.
 GO:0032755; P:positive regulation of interleukin-6 production; IEA:Compara.
 GO:0046330; P:positive regulation of JNK cascade; IEA:Compara.
 GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; TAS:Reactome.
 GO:0031398; P:positive regulation of protein ubiquitination; IMP:UniProtKB.
 GO:0045627; P:positive regulation of T-helper 1 cell differentiation; IEA:Compara.
 GO:0002827; P:positive regulation of T-helper 1 type immune response; IEA:Compara.
 GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; NAS:BHF-UCL.
 GO:0032760; P:positive regulation of tumor necrosis factor production; IEA:Compara.
 GO:0043330; P:response to exogenous dsRNA; IEA:Compara.
 GO:0070555; P:response to interleukin-1; IEA:Compara.
 GO:0070671; P:response to interleukin-12; IEA:Compara.
 GO:0070673; P:response to interleukin-18; IEA:Compara.
 GO:0042098; P:T cell proliferation; IEA:Compara.
 GO:0050852; P:T cell receptor signaling pathway; ISS:UniProtKB.
 GO:0034166; P:toll-like receptor 10 signaling pathway; TAS:Reactome.
 GO:0034134; P:toll-like receptor 2 signaling pathway; IDA:MGI.
 GO:0034138; P:toll-like receptor 3 signaling pathway; TAS:Reactome.
 GO:0034142; P:toll-like receptor 4 signaling pathway; TAS:Reactome.
 GO:0034146; P:toll-like receptor 5 signaling pathway; TAS:Reactome.
 GO:0034162; P:toll-like receptor 9 signaling pathway; TAS:Reactome.
 GO:0038123; P:toll-like receptor TLR1:TLR2 signaling pathway; TAS:Reactome.
 GO:0038124; P:toll-like receptor TLR6:TLR2 signaling pathway; TAS:Reactome.
 GO:0035666; P:TRIF-dependent toll-like receptor signaling pathway; TAS:Reactome. 

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