dbPAF Protein Information

Tag Content
dbPAF ID dbPAF-0001521
Uniprot Accession O43353; RIPK2_HUMAN; B7Z748; Q6UWF0;
Genbank Protein ID NP_003812.1; XP_005251149.1;
Genbank Nucleotide ID NM_003821.5; XM_005251092.2;
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;
Organism Homo sapiens(Human)
NCBI Taxa ID 9606
Functional Description
(View all)		 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.
Phosphorylation Sites
 dbPAF PTMs: 26 (View all)
PositionPeptidesSourceReferences ( PMIDs )
23HKLADLRYLSRGASGPhosphoSitePlus22135298
168KIADFGLSKWRMMSLdbPTM 3.0;HPRD 9;PHOSIDA;PhosphoPep 2.0;PhosphoSitePlus;SysPTM 2.0;UniProt;curated18691976; 19369195; 16381945; 23193290; 18988627; 21081558;
174LSKWRMMSLSQSRSSdbPTM 3.0;PHOSIDA;PhosphoPep 2.0;PhosphoSitePlus;curated19369195; 16381945; 23193290; 21081558; 19060867; 22135298;
176KWRMMSLSQSRSSKSdbPTM 3.0;Phospho.ELM 9.0;HPRD 9;PHOSIDA;PhosphoPep 2.0;PhosphoSitePlus;SysPTM 2.0;curated16824733; 17525332; 18691976; 19369195; 16381945; 23193290;
178RMMSLSQSRSSKSAPdbPTM 3.0;HPRD 9;PHOSIDA;PhosphoPep 2.0;PhosphoSitePlus;SysPTM 2.0;curated18691976; 19369195; 16381945; 23193290; 22115753; 18988627;
181SLSQSRSSKSAPEGGdbPTM 3.0;PhosphoSitePlus22322096; 16381945; 23193290; 22135298
332DKKKMELSLNIPVNHdbPTM 3.0;curated19369195; 16381945; 23193290
345NHGPQEESCGSSQLHdbPTM 3.0;HPRD 9;PHOSIDA;PhosphoSitePlus;curated19369195; 16381945; 23193290; 18691976; 18988627; 21081558;
348PQEESCGSSQLHENSdbPTM 3.0;HPRD 9;curated18691976; 16381945; 23193290; 18988627; 25627689; 22817900
349QEESCGSSQLHENSGdbPTM 3.0;curated19369195; 16381945; 23193290; 25627689
355SSQLHENSGSPETSRdbPTM 3.0;curated19369195; 16381945; 23193290; 25627689; 23898821
357QLHENSGSPETSRSLdbPTM 3.0;PhosphoSitePlus;curated19276368; 16381945; 23193290; 22135298; 25627689; 23898821;
360ENSGSPETSRSLPAPdbPTM 3.0;curated19369195; 16381945; 23193290
363GSPETSRSLPAPQDNdbPTM 3.0;HPRD 9;PHOSIDA;PhosphoPep 2.0;PhosphoSitePlus;SysPTM 2.0;UniProt;curated18691976; 19369195; 16381945; 23193290; 18988627; 21081558;
381SRKAQDCYFMKLHHCdbPTM 3.0;HPRD 9;PHOSIDA;PhosphoPep 2.0;PhosphoSitePlus;curated19369195; 16381945; 23193290; 18083107; 18180459; 19901323;
393HHCPGNHSWDSTISGdbPTM 3.0;PHOSIDA;PhosphoPep 2.0;PhosphoSitePlus;UniProt;curated19369195; 16381945; 23193290; 21081558; 19060867; 22135298;
411AAFCDHKTTPCSSAIPhosphoSitePlus;curated22135298; 25627689
412AFCDHKTTPCSSAIIcurated25627689
474DLIMKEDYELVSTKPdbPTM 3.0;HPRD 9;PhosphoPep 2.0;PhosphoSitePlus;curated16381945; 23193290; 21123652; 18691976; 18988627; 19060867;
482ELVSTKPTRTSKVRQdbPTM 3.0;HPRD 9;curated18691976; 16381945; 23193290; 18988627; 22817900
Sequence
(Fasta)		MNGEAICSAL PTIPYHKLAD LRYLSRGASG TVSSARHADW RVQVAVKHLH IHTPLLDSER 60
KDVLREAEIL HKARFSYILP ILGICNEPEF LGIVTEYMPN GSLNELLHRK TEYPDVAWPL 120
RFRILHEIAL GVNYLHNMTP PLLHHDLKTQ NILLDNEFHV KIADFGLSKW RMMSLSQSRS 180
SKSAPEGGTI IYMPPENYEP GQKSRASIKH DIYSYAVITW EVLSRKQPFE DVTNPLQIMY 240
SVSQGHRPVI NEESLPYDIP HRARMISLIE SGWAQNPDER PSFLKCLIEL EPVLRTFEEI 300
TFLEAVIQLK KTKLQSVSSA IHLCDKKKME LSLNIPVNHG PQEESCGSSQ LHENSGSPET 360
SRSLPAPQDN DFLSRKAQDC YFMKLHHCPG NHSWDSTISG SQRAAFCDHK TTPCSSAIIN 420
PLSTAGNSER LQPGIAQQWI QSKREDIVNQ MTEACLNQSL DALLSRDLIM KEDYELVSTK 480
PTRTSKVRQL LDTTDIQGEE FAKVIVQKLK DNKQMGLQPY PEILVVSRSP SLNLLQNKSM 540
541
Keyword

KW-0002--3D-structure
KW-1064--Adaptive immunity
KW-0025--Alternative splicing
KW-0053--Apoptosis
KW-0067--ATP-binding
KW-0181--Complete proteome
KW-0963--Cytoplasm
KW-0391--Immunity
KW-0399--Innate immunity
KW-1017--Isopeptide bond
KW-0418--Kinase
KW-0547--Nucleotide-binding
KW-0597--Phosphoprotein
KW-0621--Polymorphism
KW-1185--Reference proteome
KW-0723--Serine/threonine-protein kinase
KW-0808--Transferase
KW-0832--Ubl conjugation
Interpro

IPR001315--CARD
IPR011029--DEATH-like_dom
IPR011009--Kinase-like_dom
IPR000719--Prot_kinase_dom
IPR017322--Rcpt-int_Ser/Thr_kinase-2
IPR001245--Ser-Thr/Tyr_kinase_cat_dom
IPR008271--Ser/Thr_kinase_AS
PROSITE

PS50209--CARD
PS50011--PROTEIN_KINASE_DOM
PS00108--PROTEIN_KINASE_ST
Pfam

PF00619--CARD
PF07714--Pkinase_Tyr
Gene Ontology

GO:0005737--C:cytoplasm
GO:0005856--C:cytoskeleton
GO:0005829--C:cytosol
GO:0043234--C:protein complex
GO:0031982--C:vesicle
GO:0005524--F:ATP binding
GO:0050700--F:CARD domain binding
GO:0030274--F:LIM domain binding
GO:0004715--F:non-membrane spanning protein tyrosine kinase activity
GO:0042803--F:protein homodimerization activity
GO:0004674--F:protein serine/threonine kinase activity
GO:0005102--F:receptor binding
GO:0004871--F:signal transducer activity
GO:0000187--P:activation of MAPK activity
GO:0002250--P:adaptive immune response
GO:0006915--P:apoptotic process
GO:0071223--P:cellular response to lipoteichoic acid
GO:0071225--P:cellular response to muramyl dipeptide
GO:0071224--P:cellular response to peptidoglycan
GO:0050830--P:defense response to Gram-positive bacterium
GO:0007249--P:I-kappaB kinase/NF-kappaB signaling
GO:0006954--P:inflammatory response
GO:0045087--P:innate immune response
GO:0007254--P:JNK cascade
GO:0031663--P:lipopolysaccharide-mediated signaling pathway
GO:0002755--P:MyD88-dependent toll-like receptor signaling pathway
GO:0002756--P:MyD88-independent toll-like receptor signaling pathway
GO:0043066--P:negative regulation of apoptotic process
GO:0048011--P:neurotrophin TRK receptor signaling pathway
GO:0035872--P:nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway
GO:0070427--P:nucleotide-binding oligomerization domain containing 1 signaling pathway
GO:0070431--P:nucleotide-binding oligomerization domain containing 2 signaling pathway
GO:0070423--P:nucleotide-binding oligomerization domain containing signaling pathway
GO:0046641--P:positive regulation of alpha-beta T cell proliferation
GO:0043065--P:positive regulation of apoptotic process
GO:0032722--P:positive regulation of chemokine production
GO:0001961--P:positive regulation of cytokine-mediated signaling pathway
GO:0070374--P:positive regulation of ERK1 and ERK2 cascade
GO:0043123--P:positive regulation of I-kappaB kinase/NF-kappaB signaling
GO:0033091--P:positive regulation of immature T cell proliferation
GO:0032727--P:positive regulation of interferon-alpha production
GO:0032728--P:positive regulation of interferon-beta production
GO:0032729--P:positive regulation of interferon-gamma production
GO:0032735--P:positive regulation of interleukin-12 production
GO:0032743--P:positive regulation of interleukin-2 production
GO:0032755--P:positive regulation of interleukin-6 production
GO:0046330--P:positive regulation of JNK cascade
GO:0051092--P:positive regulation of NF-kappaB transcription factor activity
GO:0033138--P:positive regulation of peptidyl-serine phosphorylation
GO:0010800--P:positive regulation of peptidyl-threonine phosphorylation
GO:0050731--P:positive regulation of peptidyl-tyrosine phosphorylation
GO:0031398--P:positive regulation of protein ubiquitination
GO:0045627--P:positive regulation of T-helper 1 cell differentiation
GO:0045944--P:positive regulation of transcription from RNA polymerase II promoter
GO:0032760--P:positive regulation of tumor necrosis factor production
GO:0043330--P:response to exogenous dsRNA
GO:0070555--P:response to interleukin-1
GO:0070671--P:response to interleukin-12
GO:0070673--P:response to interleukin-18
GO:0007165--P:signal transduction
GO:0051403--P:stress-activated MAPK cascade
GO:0042098--P:T cell proliferation
GO:0050852--P:T cell receptor signaling pathway
GO:0034166--P:toll-like receptor 10 signaling pathway
GO:0034134--P:toll-like receptor 2 signaling pathway
GO:0034138--P:toll-like receptor 3 signaling pathway
GO:0034142--P:toll-like receptor 4 signaling pathway
GO:0034146--P:toll-like receptor 5 signaling pathway
GO:0034162--P:toll-like receptor 9 signaling pathway
GO:0002224--P:toll-like receptor signaling pathway
GO:0038123--P:toll-like receptor TLR1:TLR2 signaling pathway
GO:0038124--P:toll-like receptor TLR6:TLR2 signaling pathway
GO:0035666--P:TRIF-dependent toll-like receptor signaling pathway