Ripk2
entrez
192656
canonical
uniprot
P58801
canonical
ensembl
ENSMUSG00000041135
resolver
ensp
ENSMUSP00000038833
resolver
ensp
ENSMUSP00000166964
resolver
enst
ENSMUST00000037035
resolver
genesymbol
Ripk2
resolver
genesymbol_syn
Rip2
resolver
uniprot
Q547H1
resolver
uniprot_entry
Q547H1_MOUSE
resolver
uniprot_entry
RIPK2_MOUSE
resolver
activity_regulation
ACTIVITY REGULATION: In the inactive state, the helix alphaC is packed against the helical, non-phosphorylated activation segment (AS). Upon activation, helix alphaC is displaced and the phosphorylated AS becomes disordered. {ECO:0000250|UniProtKB:O43353}.
uniprot
proteins
amino_acid_sequence
MNGDAICSALPPIPYHKLADLHYLSRGASGTVSSARHADWRVRVAVKHLHIHTPLLDSERNDILREAEILHKARFSYILPILGICNEPEFLGIVTEYMPNGSLNELLHRKTEYPDIAWPLRFRILHEIALGVNYLHNMNPPLLHHDLKTQNILLDNEFHVKIADFGLSKWRMMSLSQSRSYKSAPEGGTIIYMPPENYEPGQKSRASVKHDIYSYAVIMWEVLSRKQPFEEVTNPLQIMYSVSQGHRPDTSEENLPFDIPHRGLMISLIQSGWAQNPDERPSFLKCLIELEPVLRTFEDITFLEAVIQLKKAKIQSSSSTIHLCDKKMDLSLNIPANHPPQEESCGSSLLSRNTGSPGPSRSLSAPQDKGFLSGAPQDCSSLKAHHCPGNHSWDGIVSVPPGAAFCDRRASSCSLAVISPFLVEKGSERPPIGIAQQWIQSKREAIVSQMTEACLNQSLDALLSRDLIMKEDYELISTKPTRTSKVRQLLDTSDIQGEEFAKVVVQKLKDNKQLGLQPYPEVPVLSKAPPSNFPQNKSL
uniprot
proteins
ec_number
2.7.10.2
uniprot
proteins
ec_number
2.7.11.1
uniprot
proteins
function
FUNCTION: Serine/threonine/tyrosine-protein kinase that plays an essential role in modulation of innate and adaptive immune responses (By similarity). Acts as a key effector of NOD1 and NOD2 signaling pathways: upon activation by bacterial peptidoglycans, NOD1 and NOD2 oligomerize and recruit RIPK2 via CARD-CARD domains, leading to the formation of RIPK2 filaments (PubMed:17277144, PubMed:21469090, PubMed:30405132). Once recruited, RIPK2 autophosphorylates and undergoes 'Lys-63'-linked polyubiquitination by E3 ubiquitin ligases XIAP, BIRC2 and BIRC3, as well as 'Met-1'-linked (linear) polyubiquitination by the LUBAC complex, becoming a scaffolding protein for downstream effectors (PubMed:30405132). 'Met-1'-linked polyubiquitin chains attached to RIPK2 recruit IKBKG/NEMO, which undergoes 'Lys-63'-linked polyubiquitination in a RIPK2-dependent process (By similarity). 'Lys-63'-linked polyubiquitin chains attached to RIPK2 serve as docking sites for TAB2 and TAB3 and mediate the recruitment of MAP3K7/TAK1 to IKBKG/NEMO, inducing subsequent activation of IKBKB/IKKB (PubMed:17965022). 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 (By similarity). The protein kinase activity is dispensable for the NOD1 and NOD2 signaling pathways (By similarity). Contributes to the tyrosine phosphorylation of the guanine exchange factor ARHGEF2 through Src tyrosine kinase leading to NF-kappa-B activation by NOD2 (By similarity). Also involved in adaptive immunity: plays a role during engagement of the T-cell receptor (TCR) in promoting BCL10 phosphorylation and subsequent NF-kappa-B activation (By similarity). Plays a role in the inactivation of RHOA in response to NGFR signaling (PubMed:26646181). {ECO:0000250|UniProtKB:O43353, ECO:0000269|PubMed:17277144, ECO:0000269|PubMed:17965022, ECO:0000269|PubMed:21469090, ECO:0000269|PubMed:26646181, ECO:0000269|PubMed:30405132}.
uniprot
proteins
mass_dalton
60400
uniprot
proteins
mutagenesis
MUTAGEN 47; /note="K->A: Abolishes protein-kinase activity. Does not affect ubiquitination by PELI3."; /evidence="ECO:0000269|PubMed:19473975, ECO:0000269|PubMed:23892723"; MUTAGEN 176; /note="S->E: Mimics phosphorylation; does not promote stabilization of RIPK2."; /evidence="ECO:0000269|PubMed:19473975"; MUTAGEN 209; /note="K->R: Does not prevent polyubiquitination by PELI3."; /evidence="ECO:0000269|PubMed:23892723
uniprot
proteins
post_translational_modification
PTM: Polyubiquitinated via both 'Lys-63'- and 'Met-1'-linked polyubiquitin following recruitment by NOD1 or NOD2, creating docking sites for downstream effectors, triggering activation of the NF-kappa-B and MAP kinases signaling (PubMed:17947236). 'Lys-63'-linked polyubiquitination by XIAP is essential for NOD2 signaling and promotes recruitment of the LUBAC complex (By similarity). Also polyubiquitinated with 'Lys-63'-linked chains by PELI3, BIRC2/c-IAP1 and BIRC3/c-IAP2 (PubMed:23892723). Ubiquitinated on Lys-209 via 'Lys-63'-linked by ITCH (By similarity). Undergoes 'Lys-63'-linked deubiquitination by MYSM1 to attenuate NOD2-mediated inflammation and tissue damage (PubMed:30405132). Polyubiquitinated with 'Lys-63'-linked chains in response to Shigella infection, promoting its SQSTM1/p62-dependent autophagic degradation (By similarity). Undergoes 'Met-1'-linked polyubiquitination; the head-to-tail linear polyubiquitination is mediated by the LUBAC complex in response to NOD2 stimulation 'Met-1'-linked polyubiquitination (By similarity). 'Lys-63'-linked polyubiquitination by XIAP is required for recruitment of the LUBAC complex and subsequent (By similarity). Linear polyubiquitination is restricted by FAM105B/otulin, probably to limit NOD2-dependent pro-inflammatory signaling activation of NF-kappa-B (By similarity). Ubiquitination at Lys-502 by ZNRF4 via 'Lys-48'-linked polyubiquitination promotes RIPK2 degradation by the proteasome; ubiquitination by ZNRF4 takes place during both acute and NOD2 tolerance conditions (By similarity). {ECO:0000250|UniProtKB:O43353, ECO:0000269|PubMed:17947236, ECO:0000269|PubMed:23892723, ECO:0000269|PubMed:30405132}.; PTM: Autophosphorylated (PubMed:19473975). Phosphorylated at Ser-176, either via autophosphorylation or by LRRK2, enhancing activity (PubMed:19473975). Autophosphorylation at Tyr-473 is required for effective NOD2 signaling (By similarity). Autophosphorylation is however not essential for NOD2 signaling (By similarity). {ECO:0000250|UniProtKB:O43353, ECO:0000269|PubMed:19473975}.; PTM: Degraded via selective autophagy following interaction with Irgm1. Irgm1 promotes NOD1/NOD2-RIPK2 RIPosome recruitment to autophagosome membranes. RIPK2 biquitinated via 'Lys-63'-linked chains is then recognized by SQSTM1/p62, leading to the SQSTM1/p62-dependent autophagic degradation of the NOD1/NOD2-RIPK2 RIPosome. {ECO:0000250|UniProtKB:O43353}.
uniprot
proteins
protein_family
Protein kinase superfamily
uniprot
proteins
protein_family
TKL Ser/Thr protein kinase family
uniprot
proteins
pubmed
11894097
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
17187069
uniprot
proteins
pubmed
17277144
uniprot
proteins
pubmed
17947236
uniprot
proteins
pubmed
17965022
uniprot
proteins
pubmed
19473975
uniprot
proteins
pubmed
21183079
uniprot
proteins
pubmed
21469090
uniprot
proteins
pubmed
23892723
uniprot
proteins
pubmed
26646181
uniprot
proteins
pubmed
30405132
uniprot
proteins
sequence_length
539
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:O43353}. Cell membrane {ECO:0000250|UniProtKB:O43353}; Peripheral membrane protein {ECO:0000250|UniProtKB:O43353}. Endoplasmic reticulum {ECO:0000250|UniProtKB:O43353}. Note=Recruited to the cell membrane by NOD2 following stimulation by bacterial peptidoglycans. {ECO:0000250|UniProtKB:O43353}.
uniprot
proteins