ID RIPK2_MOUSE Reviewed; 539 AA.
AC P58801;
DT 02-MAY-2002, integrated into UniProtKB/Swiss-Prot.
DT 02-MAY-2002, sequence version 1.
DT 27-MAR-2024, entry version 196.
DE RecName: Full=Receptor-interacting serine/threonine-protein kinase 2;
DE EC=2.7.11.1 {ECO:0000269|PubMed:19473975};
DE AltName: Full=Receptor-interacting protein 2 {ECO:0000303|PubMed:19473975};
DE AltName: Full=Tyrosine-protein kinase RIPK2;
DE EC=2.7.10.2 {ECO:0000255|PROSITE-ProRule:PRU10027};
GN Name=Ripk2; Synonyms=Rip2 {ECO:0000303|PubMed:19473975};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=C57BL/6J;
RX PubMed=11894097; DOI=10.1038/416190a;
RA Chin A.I., Dempsey P.W., Bruhn K., Miller J.F., Xu Y., Cheng G.;
RT "Involvement of receptor-interacting protein 2 in innate and adaptive
RT immune responses.";
RL Nature 416:190-194(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=129; TISSUE=Mammary gland;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP FUNCTION, CATALYTIC ACTIVITY, PHOSPHORYLATION AT SER-176, AND MUTAGENESIS
RP OF LYS-47 AND SER-176.
RX PubMed=19473975; DOI=10.1074/jbc.m109.006353;
RA Nembrini C., Kisielow J., Shamshiev A.T., Tortola L., Coyle A.J., Kopf M.,
RA Marsland B.J.;
RT "The kinase activity of Rip2 determines its stability and consequently
RT Nod1- and Nod2-mediated immune responses.";
RL J. Biol. Chem. 284:19183-19188(2009).
RN [4]
RP UBIQUITINATION.
RX PubMed=17947236; DOI=10.1074/jbc.m703079200;
RA Yang Y., Yin C., Pandey A., Abbott D., Sassetti C., Kelliher M.A.;
RT "NOD2 pathway activation by MDP or Mycobacterium tuberculosis infection
RT involves the stable polyubiquitination of Rip2.";
RL J. Biol. Chem. 282:36223-36229(2007).
RN [5]
RP DISRUPTION PHENOTYPE, AND FUNCTION.
RX PubMed=17277144; DOI=10.4049/jimmunol.178.4.2380;
RA Park J.H., Kim Y.G., McDonald C., Kanneganti T.D., Hasegawa M.,
RA Body-Malapel M., Inohara N., Nunez G.;
RT "RICK/RIP2 mediates innate immune responses induced through Nod1 and Nod2
RT but not TLRs.";
RL J. Immunol. 178:2380-2386(2007).
RN [6]
RP INTERACTION WITH CARD9.
RX PubMed=17187069; DOI=10.1038/ni1426;
RA Hsu Y.M., Zhang Y., You Y., Wang D., Li H., Duramad O., Qin X.F., Dong C.,
RA Lin X.;
RT "The adaptor protein CARD9 is required for innate immune responses to
RT intracellular pathogens.";
RL Nat. Immunol. 8:198-205(2007).
RN [7]
RP FUNCTION.
RX PubMed=17965022; DOI=10.1074/jbc.m704746200;
RA Kim J.Y., Omori E., Matsumoto K., Nunez G., Ninomiya-Tsuji J.;
RT "TAK1 is a central mediator of NOD2 signaling in epidermal cells.";
RL J. Biol. Chem. 283:137-144(2008).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-411, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Kidney, Liver, Lung, Pancreas, Spleen,
RC and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [9]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=21469090; DOI=10.1002/eji.201040827;
RA Magalhaes J.G., Lee J., Geddes K., Rubino S., Philpott D.J., Girardin S.E.;
RT "Essential role of Rip2 in the modulation of innate and adaptive immunity
RT triggered by Nod1 and Nod2 ligands.";
RL Eur. J. Immunol. 41:1445-1455(2011).
RN [10]
RP UBIQUITINATION BY PELI3, AND MUTAGENESIS OF LYS-47 AND LYS-209.
RX PubMed=23892723; DOI=10.1038/ni.2669;
RA Yang S., Wang B., Humphries F., Jackson R., Healy M.E., Bergin R.,
RA Aviello G., Hall B., McNamara D., Darby T., Quinlan A., Shanahan F.,
RA Melgar S., Fallon P.G., Moynagh P.N.;
RT "Pellino3 ubiquitinates RIP2 and mediates Nod2-induced signaling and
RT protective effects in colitis.";
RL Nat. Immunol. 14:927-936(2013).
RN [11]
RP FUNCTION.
RX PubMed=26646181; DOI=10.7554/elife.11692;
RA Lin Z., Tann J.Y., Goh E.T., Kelly C., Lim K.B., Gao J.F., Ibanez C.F.;
RT "Structural basis of death domain signaling in the p75 neurotrophin
RT receptor.";
RL Elife 4:e11692-e11692(2015).
RN [12]
RP FUNCTION, AND DEUBIQUITINATION BY MYSM1.
RX PubMed=30405132; DOI=10.1038/s41467-018-07016-0;
RA Panda S., Gekara N.O.;
RT "The deubiquitinase MYSM1 dampens NOD2-mediated inflammation and tissue
RT damage by inactivating the RIP2 complex.";
RL Nat. Commun. 9:4654-4654(2018).
CC -!- FUNCTION: Serine/threonine/tyrosine-protein kinase that plays an
CC essential role in modulation of innate and adaptive immune responses
CC (By similarity). Acts as a key effector of NOD1 and NOD2 signaling
CC pathways: upon activation by bacterial peptidoglycans, NOD1 and NOD2
CC oligomerize and recruit RIPK2 via CARD-CARD domains, leading to the
CC formation of RIPK2 filaments (PubMed:17277144, PubMed:21469090,
CC PubMed:30405132). Once recruited, RIPK2 autophosphorylates and
CC undergoes 'Lys-63'-linked polyubiquitination by E3 ubiquitin ligases
CC XIAP, BIRC2 and BIRC3, as well as 'Met-1'-linked (linear)
CC polyubiquitination by the LUBAC complex, becoming a scaffolding protein
CC for downstream effectors (PubMed:30405132). 'Met-1'-linked
CC polyubiquitin chains attached to RIPK2 recruit IKBKG/NEMO, which
CC undergoes 'Lys-63'-linked polyubiquitination in a RIPK2-dependent
CC process (By similarity). 'Lys-63'-linked polyubiquitin chains attached
CC to RIPK2 serve as docking sites for TAB2 and TAB3 and mediate the
CC recruitment of MAP3K7/TAK1 to IKBKG/NEMO, inducing subsequent
CC activation of IKBKB/IKKB (PubMed:17965022). In turn, NF-kappa-B is
CC released from NF-kappa-B inhibitors and translocates into the nucleus
CC where it activates the transcription of hundreds of genes involved in
CC immune response, growth control, or protection against apoptosis (By
CC similarity). The protein kinase activity is dispensable for the NOD1
CC and NOD2 signaling pathways (By similarity). Contributes to the
CC tyrosine phosphorylation of the guanine exchange factor ARHGEF2 through
CC Src tyrosine kinase leading to NF-kappa-B activation by NOD2 (By
CC similarity). Also involved in adaptive immunity: plays a role during
CC engagement of the T-cell receptor (TCR) in promoting BCL10
CC phosphorylation and subsequent NF-kappa-B activation (By similarity).
CC Plays a role in the inactivation of RHOA in response to NGFR signaling
CC (PubMed:26646181). {ECO:0000250|UniProtKB:O43353,
CC ECO:0000269|PubMed:17277144, ECO:0000269|PubMed:17965022,
CC ECO:0000269|PubMed:21469090, ECO:0000269|PubMed:26646181,
CC ECO:0000269|PubMed:30405132}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1;
CC Evidence={ECO:0000269|PubMed:19473975};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC EC=2.7.11.1; Evidence={ECO:0000250|UniProtKB:O43353};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-tyrosyl-[protein] = ADP + H(+) + O-phospho-L-tyrosyl-
CC [protein]; Xref=Rhea:RHEA:10596, Rhea:RHEA-COMP:10136, Rhea:RHEA-
CC COMP:10137, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:46858,
CC ChEBI:CHEBI:82620, ChEBI:CHEBI:456216; EC=2.7.10.2;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU10027};
CC -!- ACTIVITY REGULATION: In the inactive state, the helix alphaC is packed
CC against the helical, non-phosphorylated activation segment (AS). Upon
CC activation, helix alphaC is displaced and the phosphorylated AS becomes
CC disordered. {ECO:0000250|UniProtKB:O43353}.
CC -!- SUBUNIT: Interacts (via CARD domain) with NOD2 (via CARD domain) (By
CC similarity). Interacts (via CARD domain) with NOD1 (via CARD domain)
CC (By similarity). Homooligomer; following interaction with NOD1 or NOD2,
CC homooligomerizes via its CARD domain and forms long filaments named
CC RIPosomes (By similarity). Found in a signaling complex consisting of
CC at least ARHGEF2, NOD2 and RIPK2 (By similarity). Interacts with
CC ARHGEF2; the interaction mediates tyrosine phosphorylation of RIPK2 by
CC Src kinase CSK (By similarity). Interacts with MAP3K4; this interaction
CC sequesters RIPK2 from the NOD2 signaling pathway (By similarity).
CC Interacts with IKBKG/NEMO (By similarity). The polyubiquitinated
CC protein interacts with MAP3K7/TAK1; interaction is indirect and is
CC mediated by TAB2 and TAB3 that bind to polyubiquitin chains attached to
CC RIPK2 (By similarity). Binds to CFLAR/CLARP and CASP1 via their CARD
CC domains (By similarity). Binds to BIRC3/c-IAP1 and BIRC2/c-IAP2, TRAF1,
CC TRAF2, TRAF5 and TRAF6 (By similarity). Interacts with NLRP10 (By
CC similarity). Interacts with CARD9 (PubMed:17187069). Interacts with
CC INAVA; the interaction takes place upon PRR stimulation (By
CC similarity). Interacts (via CARD domain) with NGFR (via death domain)
CC (By similarity). Interacts with Irgm1; promoting RIPK2 degradation (By
CC similarity). {ECO:0000250|UniProtKB:O43353,
CC ECO:0000269|PubMed:17187069}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:O43353}. Cell
CC membrane {ECO:0000250|UniProtKB:O43353}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:O43353}. Endoplasmic reticulum
CC {ECO:0000250|UniProtKB:O43353}. Note=Recruited to the cell membrane by
CC NOD2 following stimulation by bacterial peptidoglycans.
CC {ECO:0000250|UniProtKB:O43353}.
CC -!- DOMAIN: Contains an N-terminal kinase domain and a C-terminal caspase
CC activation and recruitment domain (CARD) that mediates the recruitment
CC of CARD-containing proteins. {ECO:0000250|UniProtKB:P51617}.
CC -!- PTM: Polyubiquitinated via both 'Lys-63'- and 'Met-1'-linked
CC polyubiquitin following recruitment by NOD1 or NOD2, creating docking
CC sites for downstream effectors, triggering activation of the NF-kappa-B
CC and MAP kinases signaling (PubMed:17947236). 'Lys-63'-linked
CC polyubiquitination by XIAP is essential for NOD2 signaling and promotes
CC recruitment of the LUBAC complex (By similarity). Also
CC polyubiquitinated with 'Lys-63'-linked chains by PELI3, BIRC2/c-IAP1
CC and BIRC3/c-IAP2 (PubMed:23892723). Ubiquitinated on Lys-209 via 'Lys-
CC 63'-linked by ITCH (By similarity). Undergoes 'Lys-63'-linked
CC deubiquitination by MYSM1 to attenuate NOD2-mediated inflammation and
CC tissue damage (PubMed:30405132). Polyubiquitinated with 'Lys-63'-linked
CC chains in response to Shigella infection, promoting its SQSTM1/p62-
CC dependent autophagic degradation (By similarity). Undergoes 'Met-1'-
CC linked polyubiquitination; the head-to-tail linear polyubiquitination
CC is mediated by the LUBAC complex in response to NOD2 stimulation 'Met-
CC 1'-linked polyubiquitination (By similarity). 'Lys-63'-linked
CC polyubiquitination by XIAP is required for recruimtent of the LUBAC
CC complex and subsequent (By similarity). Linear polyubiquitination is
CC restricted by FAM105B/otulin, probably to limit NOD2-dependent pro-
CC inflammatory signaling activation of NF-kappa-B (By similarity).
CC Ubiquitination at Lys-502 by ZNRF4 via 'Lys-48'-linked
CC polyubiquitination promotes RIPK2 degradation by the proteasome;
CC ubiquitination by ZNRF4 takes place during both acute and NOD2
CC tolerance conditions (By similarity). {ECO:0000250|UniProtKB:O43353,
CC ECO:0000269|PubMed:17947236, ECO:0000269|PubMed:23892723,
CC ECO:0000269|PubMed:30405132}.
CC -!- PTM: Autophosphorylated (PubMed:19473975). Phosphorylated at Ser-176,
CC either via autophosphorylation or by LRRK2, enhancing activity
CC (PubMed:19473975). Autophosphorylation at Tyr-473 is required for
CC effective NOD2 signaling (By similarity). Autophosphorylation is
CC however not essential for NOD2 signaling (By similarity).
CC {ECO:0000250|UniProtKB:O43353, ECO:0000269|PubMed:19473975}.
CC -!- PTM: Degraded via selective autophagy following interaction with Irgm1.
CC Irgm1 promotes NOD1/NOD2-RIPK2 RIPosome recruitment to autophagosome
CC membranes. RIPK2 biquitinated via 'Lys-63'-linked chains is then
CC recognized by SQSTM1/p62, leading to the SQSTM1/p62-dependent
CC autophagic degradation of the NOD1/NOD2-RIPK2 RIPosome.
CC {ECO:0000250|UniProtKB:O43353}.
CC -!- DISRUPTION PHENOTYPE: Mice show a lack of chemokine production induced
CC by bacterial peptidoglycans. RIPK2 deficiency affects cellular
CC signaling and cytokine responses triggered by NOD1 and NOD2 ligands,
CC but not TLR ligands. {ECO:0000269|PubMed:17277144,
CC ECO:0000269|PubMed:21469090}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. TKL Ser/Thr
CC protein kinase family. {ECO:0000305}.
CC -!- CAUTION: The role of autophosphorylation in RIPK2 activation is
CC unclear: an initial studies suggested that autophosphorylation is
CC essential to activate NOD2 signaling pathway (PubMed:19473975).
CC However, it was later shown that autophosphorylation is however not
CC essential for NOD2 signaling (By similarity).
CC {ECO:0000250|UniProtKB:O43353, ECO:0000269|PubMed:19473975}.
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DR EMBL; AF461040; AAL96436.1; -; mRNA.
DR EMBL; BC069878; AAH69878.1; -; mRNA.
DR CCDS; CCDS17988.1; -.
DR RefSeq; NP_620402.1; NM_138952.4.
DR AlphaFoldDB; P58801; -.
DR SMR; P58801; -.
DR BioGRID; 228697; 8.
DR CORUM; P58801; -.
DR IntAct; P58801; 2.
DR STRING; 10090.ENSMUSP00000038833; -.
DR BindingDB; P58801; -.
DR ChEMBL; CHEMBL4296021; -.
DR GlyGen; P58801; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P58801; -.
DR PhosphoSitePlus; P58801; -.
DR EPD; P58801; -.
DR jPOST; P58801; -.
DR PaxDb; 10090-ENSMUSP00000038833; -.
DR PeptideAtlas; P58801; -.
DR ProteomicsDB; 254886; -.
DR Pumba; P58801; -.
DR Antibodypedia; 12695; 750 antibodies from 45 providers.
DR DNASU; 192656; -.
DR Ensembl; ENSMUST00000037035.12; ENSMUSP00000038833.6; ENSMUSG00000041135.16.
DR GeneID; 192656; -.
DR KEGG; mmu:192656; -.
DR UCSC; uc008sbr.1; mouse.
DR AGR; MGI:1891456; -.
DR CTD; 8767; -.
DR MGI; MGI:1891456; Ripk2.
DR VEuPathDB; HostDB:ENSMUSG00000041135; -.
DR eggNOG; KOG0192; Eukaryota.
DR GeneTree; ENSGT00940000156113; -.
DR InParanoid; P58801; -.
DR OMA; IPQCNIL; -.
DR OrthoDB; 5349889at2759; -.
DR PhylomeDB; P58801; -.
DR TreeFam; TF106506; -.
DR Reactome; R-MMU-168638; NOD1/2 Signaling Pathway.
DR Reactome; R-MMU-202424; Downstream TCR signaling.
DR Reactome; R-MMU-209543; p75NTR recruits signalling complexes.
DR Reactome; R-MMU-450302; activated TAK1 mediates p38 MAPK activation.
DR Reactome; R-MMU-450321; JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1.
DR Reactome; R-MMU-5689896; Ovarian tumor domain proteases.
DR BioGRID-ORCS; 192656; 2 hits in 80 CRISPR screens.
DR ChiTaRS; Ripk2; mouse.
DR PRO; PR:P58801; -.
DR Proteomes; UP000000589; Chromosome 4.
DR RNAct; P58801; Protein.
DR Bgee; ENSMUSG00000041135; Expressed in animal zygote and 156 other cell types or tissues.
DR ExpressionAtlas; P58801; baseline and differential.
DR Genevisible; P58801; MM.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005856; C:cytoskeleton; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005783; C:endoplasmic reticulum; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0032991; C:protein-containing complex; ISS:UniProtKB.
DR GO; GO:0031982; C:vesicle; ISS:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0050700; F:CARD domain binding; ISO:MGI.
DR GO; GO:0089720; F:caspase binding; ISO:MGI.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0004706; F:JUN kinase kinase kinase activity; IBA:GO_Central.
DR GO; GO:0030274; F:LIM domain binding; ISO:MGI.
DR GO; GO:0004715; F:non-membrane spanning protein tyrosine kinase activity; IEA:UniProtKB-EC.
DR GO; GO:0042803; F:protein homodimerization activity; ISO:MGI.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:UniProtKB.
DR GO; GO:0035591; F:signaling adaptor activity; ISS:UniProtKB.
DR GO; GO:0005102; F:signaling receptor binding; ISO:MGI.
DR GO; GO:0002250; P:adaptive immune response; IMP:UniProtKB.
DR GO; GO:0006915; P:apoptotic process; ISO:MGI.
DR GO; GO:0007249; P:canonical NF-kappaB signal transduction; IMP:UniProtKB.
DR GO; GO:0035739; P:CD4-positive, alpha-beta T cell proliferation; IMP:MGI.
DR GO; GO:0071222; P:cellular response to lipopolysaccharide; IMP:MGI.
DR GO; GO:0071223; P:cellular response to lipoteichoic acid; IMP:MGI.
DR GO; GO:0071225; P:cellular response to muramyl dipeptide; IDA:UniProtKB.
DR GO; GO:0071224; P:cellular response to peptidoglycan; IMP:MGI.
DR GO; GO:0019221; P:cytokine-mediated signaling pathway; IMP:MGI.
DR GO; GO:0042742; P:defense response to bacterium; ISO:MGI.
DR GO; GO:0050830; P:defense response to Gram-positive bacterium; IMP:MGI.
DR GO; GO:0070371; P:ERK1 and ERK2 cascade; IDA:MGI.
DR GO; GO:0033080; P:immature T cell proliferation in thymus; IMP:MGI.
DR GO; GO:0045087; P:innate immune response; IMP:UniProtKB.
DR GO; GO:0007254; P:JNK cascade; IMP:MGI.
DR GO; GO:0031663; P:lipopolysaccharide-mediated signaling pathway; IMP:MGI.
DR GO; GO:0070427; P:nucleotide-binding oligomerization domain containing 1 signaling pathway; IMP:MGI.
DR GO; GO:0070431; P:nucleotide-binding oligomerization domain containing 2 signaling pathway; IDA:UniProtKB.
DR GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW.
DR GO; GO:0043065; P:positive regulation of apoptotic process; IDA:MGI.
DR GO; GO:0043123; P:positive regulation of canonical NF-kappaB signal transduction; IDA:UniProtKB.
DR GO; GO:2000563; P:positive regulation of CD4-positive, alpha-beta T cell proliferation; IMP:MGI.
DR GO; GO:0032722; P:positive regulation of chemokine production; IMP:MGI.
DR GO; GO:0001961; P:positive regulation of cytokine-mediated signaling pathway; IMP:MGI.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IDA:MGI.
DR GO; GO:0033092; P:positive regulation of immature T cell proliferation in thymus; IMP:MGI.
DR GO; GO:0032731; P:positive regulation of interleukin-1 beta production; ISO:MGI.
DR GO; GO:0032743; P:positive regulation of interleukin-2 production; IMP:MGI.
DR GO; GO:0032755; P:positive regulation of interleukin-6 production; IMP:UniProtKB.
DR GO; GO:0046330; P:positive regulation of JNK cascade; IMP:MGI.
DR GO; GO:0060907; P:positive regulation of macrophage cytokine production; IMP:MGI.
DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; IMP:UniProtKB.
DR GO; GO:0033138; P:positive regulation of peptidyl-serine phosphorylation; ISS:UniProtKB.
DR GO; GO:0010800; P:positive regulation of peptidyl-threonine phosphorylation; ISS:UniProtKB.
DR GO; GO:0050731; P:positive regulation of peptidyl-tyrosine phosphorylation; ISS:UniProtKB.
DR GO; GO:1902523; P:positive regulation of protein K63-linked ubiquitination; ISS:UniProtKB.
DR GO; GO:0031398; P:positive regulation of protein ubiquitination; ISO:MGI.
DR GO; GO:0032874; P:positive regulation of stress-activated MAPK cascade; IMP:MGI.
DR GO; GO:0045627; P:positive regulation of T-helper 1 cell differentiation; IMP:MGI.
DR GO; GO:0002827; P:positive regulation of T-helper 1 type immune response; IMP:MGI.
DR GO; GO:0032760; P:positive regulation of tumor necrosis factor production; IMP:UniProtKB.
DR GO; GO:0032729; P:positive regulation of type II interferon production; IMP:MGI.
DR GO; GO:1904417; P:positive regulation of xenophagy; IMP:MGI.
DR GO; GO:0051260; P:protein homooligomerization; ISO:MGI.
DR GO; GO:0043330; P:response to exogenous dsRNA; IMP:MGI.
DR GO; GO:0070555; P:response to interleukin-1; IMP:MGI.
DR GO; GO:0070671; P:response to interleukin-12; IMP:MGI.
DR GO; GO:0070673; P:response to interleukin-18; IMP:MGI.
DR GO; GO:0051403; P:stress-activated MAPK cascade; IMP:MGI.
DR GO; GO:0042098; P:T cell proliferation; IMP:MGI.
DR GO; GO:0050852; P:T cell receptor signaling pathway; IMP:UniProtKB.
DR GO; GO:0034134; P:toll-like receptor 2 signaling pathway; ISO:MGI.
DR GO; GO:0034142; P:toll-like receptor 4 signaling pathway; IMP:MGI.
DR GO; GO:0098792; P:xenophagy; IMP:MGI.
DR CDD; cd08786; CARD_RIP2_CARD3; 1.
DR CDD; cd14026; STKc_RIP2; 1.
DR Gene3D; 1.10.533.10; Death Domain, Fas; 1.
DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1.
DR InterPro; IPR001315; CARD.
DR InterPro; IPR042149; CARD_RIP2.
DR InterPro; IPR011029; DEATH-like_dom_sf.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017322; Rcpt-int_Ser/Thr_kinase-2.
DR InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR PANTHER; PTHR23257:SF985; RECEPTOR-INTERACTING SERINE_THREONINE-PROTEIN KINASE 3; 1.
DR PANTHER; PTHR23257; SERINE-THREONINE PROTEIN KINASE; 1.
DR Pfam; PF00619; CARD; 1.
DR Pfam; PF07714; PK_Tyr_Ser-Thr; 1.
DR PIRSF; PIRSF037921; STPK_RIP2; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF47986; DEATH domain; 1.
DR SUPFAM; SSF56112; Protein kinase-like (PK-like); 1.
DR PROSITE; PS50209; CARD; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
PE 1: Evidence at protein level;
KW Adaptive immunity; Apoptosis; ATP-binding; Cell membrane; Cytoplasm;
KW Endoplasmic reticulum; Immunity; Innate immunity; Isopeptide bond; Kinase;
KW Membrane; Nucleotide-binding; Phosphoprotein; Reference proteome;
KW Serine/threonine-protein kinase; Transferase; Ubl conjugation.
FT CHAIN 1..539
FT /note="Receptor-interacting serine/threonine-protein kinase
FT 2"
FT /id="PRO_0000086609"
FT DOMAIN 18..294
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT DOMAIN 431..523
FT /note="CARD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00046"
FT REGION 65..73
FT /note="Helix alphaC"
FT /evidence="ECO:0000250|UniProtKB:O43353"
FT REGION 167..193
FT /note="Activation segment (AS)"
FT /evidence="ECO:0000250|UniProtKB:O43353"
FT REGION 335..368
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 519..539
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 337..367
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 146
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 24..32
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 47
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 168
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O43353"
FT MOD_RES 174
FT /note="Phosphoserine; alternate"
FT /evidence="ECO:0000250|UniProtKB:O43353"
FT MOD_RES 176
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:19473975"
FT MOD_RES 178
FT /note="Phosphoserine; alternate"
FT /evidence="ECO:0000250|UniProtKB:O43353"
FT MOD_RES 180
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O43353"
FT MOD_RES 362
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O43353"
FT MOD_RES 392
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O43353"
FT MOD_RES 411
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 473
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:O43353"
FT MOD_RES 526
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O43353"
FT MOD_RES 538
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O43353"
FT CROSSLNK 209
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:O43353"
FT CROSSLNK 502
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:O43353"
FT CROSSLNK 537
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:O43353"
FT MUTAGEN 47
FT /note="K->A: Abolishes protein-kinase activity. Does not
FT affect ubiquitination by PELI3."
FT /evidence="ECO:0000269|PubMed:19473975,
FT ECO:0000269|PubMed:23892723"
FT MUTAGEN 176
FT /note="S->E: Mimics phosphorylation; does not promote
FT stabilization of RIPK2."
FT /evidence="ECO:0000269|PubMed:19473975"
FT MUTAGEN 209
FT /note="K->R: Does not prevent polyubiquitination by PELI3."
FT /evidence="ECO:0000269|PubMed:23892723"
SQ SEQUENCE 539 AA; 60400 MW; 42951BF97CA15DFA CRC64;
MNGDAICSAL PPIPYHKLAD LHYLSRGASG TVSSARHADW RVRVAVKHLH IHTPLLDSER
NDILREAEIL HKARFSYILP ILGICNEPEF LGIVTEYMPN GSLNELLHRK TEYPDIAWPL
RFRILHEIAL GVNYLHNMNP PLLHHDLKTQ NILLDNEFHV KIADFGLSKW RMMSLSQSRS
YKSAPEGGTI IYMPPENYEP GQKSRASVKH DIYSYAVIMW EVLSRKQPFE EVTNPLQIMY
SVSQGHRPDT SEENLPFDIP HRGLMISLIQ SGWAQNPDER PSFLKCLIEL EPVLRTFEDI
TFLEAVIQLK KAKIQSSSST IHLCDKKMDL SLNIPANHPP QEESCGSSLL SRNTGSPGPS
RSLSAPQDKG FLSGAPQDCS SLKAHHCPGN HSWDGIVSVP PGAAFCDRRA SSCSLAVISP
FLVEKGSERP PIGIAQQWIQ SKREAIVSQM TEACLNQSLD ALLSRDLIMK EDYELISTKP
TRTSKVRQLL DTSDIQGEEF AKVVVQKLKD NKQLGLQPYP EVPVLSKAPP SNFPQNKSL
//
