NOD2
entrez
64127
canonical
uniprot
Q9HC29
canonical
ensembl
ENSG00000167207
resolver
ensp
ENSP00000300589
resolver
ensp
ENSP00000493088
resolver
ensp
ENSP00000495993
resolver
ensp
ENSP00000496533
resolver
ensp
ENSP00000621307
resolver
ensp
ENSP00000692891
resolver
enst
ENST00000641284
resolver
enst
ENST00000646677
resolver
genesymbol
NOD2
resolver
genesymbol_syn
CARD15
resolver
hgnc
HGNC:5331
resolver
uniprot
A0A286YF65
resolver
uniprot
E2JEQ6
resolver
uniprot
Q96RH5
resolver
uniprot
Q96RH6
resolver
uniprot
Q96RH8
resolver
uniprot_entry
A0A286YF65_HUMAN
resolver
uniprot_entry
NOD2_HUMAN
resolver
uniprot_sec
E2JEQ6
resolver
uniprot_sec
Q96RH5
resolver
uniprot_sec
Q96RH6
resolver
uniprot_sec
Q96RH8
resolver
activity_regulation
ACTIVITY REGULATION: ADP-binding promotes an inactive closed conformation. {ECO:0000250|UniProtKB:G1T469}.
uniprot
proteins
amino_acid_sequence
MGEEGGSASHDEEERASVLLGHSPGCEMCSQEAFQAQRSQLVELLVSGSLEGFESVLDWLLSWEVLSWEDYEGFHLLGQPLSHLARRLLDTVWNKGTWACQKLIAAAQEAQADSQSPKLHGCWDPHSLHPARDLQSHRPAIVRRLHSHVENMLDLAWERGFVSQYECDEIRLPIFTPSQRARRLLDLATVKANGLAAFLLQHVQELPVPLALPLEAATCKKYMAKLRTTVSAQSRFLSTYDGAETLCLEDIYTENVLEVWADVGMAGPPQKSPATLGLEELFSTPGHLNDDADTVLVVGEAGSGKSTLLQRLHLLWAAGQDFQEFLFVFPFSCRQLQCMAKPLSVRTLLFEHCCWPDVGQEDIFQLLLDHPDRVLLTFDGFDEFKFRFTDRERHCSPTDPTSVQTLLFNLLQGNLLKNARKVVTSRPAAVSAFLRKYIRTEFNLKGFSEQGIELYLRKRHHEPGVADRLIRLLQETSALHGLCHLPVFSWMVSKCHQELLLQEGGSPKTTTDMYLLILQHFLLHATPPDSASQGLGPSLLRGRLPTLLHLGRLALWGLGMCCYVFSAQQLQAAQVSPDDISLGFLVRAKGVVPGSTAPLEFLHITFQCFFAAFYLALSADVPPALLRHLFNCGRPGNSPMARLLPTMCIQASEGKDSSVAALLQKAEPHNLQITAAFLAGLLSREHWGLLAECQTSEKALLRRQACARWCLARSLRKHFHSIPPAAPGEAKSVHAMPGFIWLIRSLYEMQEERLARKAARGLNVGHLKLTFCSVGPTECAALAFVLQHLRRPVALQLDYNSVGDIGVEQLLPCLGVCKALYLRDNNISDRGICKLIECALHCEQLQKLALFNNKLTDGCAHSMAKLLACRQNFLALRLGNNYITAAGAQVLAEGLRGNTSLQFLGFWGNRVGDEGAQALAEALGDHQSLRWLSLVGNNIGSVGAQALALMLAKNVMLEELCLEENHLQDEGVCSLAEGLKKNSSLKILKLSNNCITYLGAEALLQALERNDTILEVWLRGNTFSLEEVDKLGCRDTRLLL
uniprot
proteins
disease_involvement
DISEASE: Blau syndrome (BLAUS) [MIM:186580]: An autosomal dominant inflammatory disorder characterized by the formation of immune granulomas invading the skin, joints and eye. Other organs may be involved. Clinical manifestations are variable and include early-onset granulomatous arthritis, uveitis and skin rash. Blindness, joint destruction and visceral involvement have been reported in severe cases. {ECO:0000269|PubMed:11528384, ECO:0000269|PubMed:12626759, ECO:0000269|PubMed:15459013, ECO:0000269|PubMed:15812565, ECO:0000269|PubMed:19116920, ECO:0000269|PubMed:19169908, ECO:0000269|PubMed:19359344, ECO:0000269|PubMed:19479837, ECO:0000269|PubMed:20199415, ECO:0000269|PubMed:24960071, ECO:0000269|PubMed:25093298, ECO:0000269|PubMed:25692065, ECO:0000269|PubMed:25724124, ECO:0000269|PubMed:27812135, ECO:0000269|PubMed:34251956}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Inflammatory bowel disease 1 (IBD1) [MIM:266600]: A chronic, relapsing inflammation of the gastrointestinal tract with a complex etiology. It is subdivided into Crohn disease and ulcerative colitis phenotypes. Crohn disease may affect any part of the gastrointestinal tract from the mouth to the anus, but most frequently it involves the terminal ileum and colon. Bowel inflammation is transmural and discontinuous; it may contain granulomas or be associated with intestinal or perianal fistulas. In contrast, in ulcerative colitis, the inflammation is continuous and limited to rectal and colonic mucosal layers; fistulas and granulomas are not observed. Both diseases include extraintestinal inflammation of the skin, eyes, or joints. {ECO:0000269|PubMed:11385576, ECO:0000269|PubMed:11385577, ECO:0000269|PubMed:12514169, ECO:0000269|PubMed:12626759, ECO:0000269|PubMed:15024686, ECO:0000269|PubMed:15044951, ECO:0000269|PubMed:15198989, ECO:0000269|PubMed:15998797, ECO:0000269|PubMed:16485124, ECO:0000269|PubMed:24790089, ECO:0000269|PubMed:24960071, ECO:0000269|PubMed:27812135}. Note=Disease susceptibility is associated with variants affecting the gene represented in this entry.; DISEASE: Yao syndrome (YAOS) [MIM:617321]: An autoinflammatory disease characterized by periodic fever, dermatitis, polyarthritis, leg swelling, and gastrointestinal and sicca-like symptoms. YAOS is a complex disease with multifactorial inheritance. {ECO:0000269|PubMed:21914217, ECO:0000269|PubMed:26070941}. Note=Disease susceptibility is associated with variants affecting the gene represented in this entry.
uniprot
proteins
function
FUNCTION: Pattern recognition receptor (PRR) that detects bacterial peptidoglycan fragments and other danger signals and plays an important role in gastrointestinal immunity (PubMed:12514169, PubMed:12527755, PubMed:12626759, PubMed:15044951, PubMed:15998797, PubMed:27283905, PubMed:27748583, PubMed:31649195). Specifically activated by muramyl dipeptide (MDP), a fragment of bacterial peptidoglycan found in every bacterial peptidoglycan type (PubMed:12514169, PubMed:12527755, PubMed:12626759, PubMed:12871942, PubMed:15044951, PubMed:15198989, PubMed:15998797, PubMed:22857257, PubMed:23322906, PubMed:27748583, PubMed:36002575). NOD2 specifically recognizes and binds 6-O-phospho-MDP, the phosphorylated form of MDP, which is generated by NAGK (PubMed:36002575). 6-O-phospho-MDP-binding triggers oligomerization that facilitates the binding and subsequent activation of the proximal adapter receptor-interacting RIPK2 (PubMed:11087742, PubMed:17355968, PubMed:21887730, PubMed:23806334, PubMed:28436939). Following recruitment, RIPK2 undergoes 'Met-1'- (linear) and 'Lys-63'-linked polyubiquitination by E3 ubiquitin-protein ligases XIAP, BIRC2, BIRC3 and the LUBAC complex, becoming a scaffolding protein for downstream effectors, triggering activation of the NF-kappa-B and MAP kinases signaling (PubMed:11087742, PubMed:12514169, PubMed:12626759, PubMed:15198989, PubMed:21887730, PubMed:23322906, PubMed:23806334, PubMed:28436939). This in turn leads to the transcriptional activation of hundreds of genes involved in immune response (PubMed:15198989). Its ability to detect bacterial MDP plays a central role in maintaining the equilibrium between intestinal microbiota and host immune responses to control inflammation (By similarity). An imbalance in this relationship results in dysbiosis, whereby pathogenic bacteria prevail on commensals, causing damage in the intestinal epithelial barrier as well as allowing bacterial invasion and inflammation (By similarity). Acts as a regulator of appetite by sensing MDP in a subset of brain neurons: microbiota-derived MDP reach the brain, where they bind and activate NOD2 in inhibitory hypothalamic neurons, decreasing neuronal activity, thereby regulating satiety and body temperature (By similarity). NOD2-dependent MDP-sensing of bacterial cell walls in the intestinal epithelial compartment contributes to sustained postnatal growth upon undernutrition (By similarity). Also plays a role in antiviral response by acting as a sensor of single-stranded RNA (ssRNA) from viruses: upon ssRNA-binding, interacts with MAVS, leading to activation of interferon regulatory factor-3/IRF3 and expression of type I interferon (PubMed:19701189). Also acts as a regulator of autophagy in dendritic cells via its interaction with ATG16L1, possibly by recruiting ATG16L1 at the site of bacterial entry (PubMed:20637199). NOD2 activation in the small intestine crypt also contributes to intestinal stem cells survival and function: acts by promoting mitophagy via its association with ATG16L1 (By similarity). In addition to its main role in innate immunity, also regulates the adaptive immune system by acting as regulator of helper T-cell and regulatory T-cells (Tregs) (By similarity). Besides recognizing pathogens, also involved in the endoplasmic reticulum stress response: acts by sensing and binding to the cytosolic metabolite sphingosine-1-phosphate generated in response to endoplasmic reticulum stress, initiating an inflammation process that leads to activation of the NF-kappa-B and MAP kinases signaling (PubMed:27007849, PubMed:33942347). May also be involved in NLRP1 activation following activation by MDP, leading to CASP1 activation and IL1B release in macrophages (PubMed:18511561). {ECO:0000250|UniProtKB:Q8K3Z0, ECO:0000269|PubMed:11087742, ECO:0000269|PubMed:12514169, ECO:0000269|PubMed:12527755, ECO:0000269|PubMed:12626759, ECO:0000269|PubMed:12871942, ECO:0000269|PubMed:15044951, ECO:0000269|PubMed:15198989, ECO:0000269|PubMed:15998797, ECO:0000269|PubMed:17355968, ECO:0000269|PubMed:18511561, ECO:0000269|PubMed:19701189, ECO:0000269|PubMed:20637199, ECO:0000269|PubMed:21887730, ECO:0000269|PubMed:22857257, ECO:0000269|PubMed:23322906, ECO:0000269|PubMed:23806334, ECO:0000269|PubMed:27007849, ECO:0000269|PubMed:27283905, ECO:0000269|PubMed:27748583, ECO:0000269|PubMed:28436939, ECO:0000269|PubMed:31649195, ECO:0000269|PubMed:33942347, ECO:0000269|PubMed:36002575}.; FUNCTION: [Isoform 2]: Acts as a pattern recognition receptor (PRR); able to activate NF-kappa-B. {ECO:0000269|PubMed:11087742}.; FUNCTION: [Isoform 3]: Can activate NF-kappa-B in a muramyl dipeptide (MDP)-independent manner. {ECO:0000269|PubMed:20698950}.
uniprot
proteins
mass_dalton
115283
uniprot
proteins
mutagenesis
MUTAGEN 31; /note="Q->H: Abolished NF-kappa-B activation in response to muramyl dipeptide stimulation. Decreased interaction with RIPK2."; /evidence="ECO:0000269|PubMed:15044951"; MUTAGEN 69; /note="E->K: Abolished NF-kappa-B activation in response to muramyl dipeptide stimulation."; /evidence="ECO:0000269|PubMed:15044951"; MUTAGEN 91; /note="T->I: Abolished NF-kappa-B activation in response to muramyl dipeptide stimulation."; /evidence="ECO:0000269|PubMed:15044951"; MUTAGEN 104; /note="I->R: Abolished binding to ubiquitin; when associated with R-200."; /evidence="ECO:0000269|PubMed:23300079"; MUTAGEN 106; /note="A->V: Abolished NF-kappa-B activation in response to muramyl dipeptide stimulation. Decreased interaction with RIPK2."; /evidence="ECO:0000269|PubMed:15044951"; MUTAGEN 145; /note="L->P: Dominant-negative mutant. Abolished NF-kappa-B activation in response to muramyl dipeptide stimulation. Decreased interaction with RIPK2."; /evidence="ECO:0000269|PubMed:15044951"; MUTAGEN 152; /note="M->L: Does not affect NF-kappa-B activation in response to muramyl dipeptide stimulation."; /evidence="ECO:0000269|PubMed:15044951"; MUTAGEN 177; /note="P->S: Abolished NF-kappa-B activation in response to muramyl dipeptide stimulation."; /evidence="ECO:0000269|PubMed:15044951"; MUTAGEN 180; /note="R->K: Abolished NF-kappa-B activation in response to muramyl dipeptide stimulation."; /evidence="ECO:0000269|PubMed:15044951"; MUTAGEN 200; /note="L->R: Abolished binding to ubiquitin; when associated with R-104."; /evidence="ECO:0000269|PubMed:23300079"; MUTAGEN 232; /note="A->P: Abolished NF-kappa-B activation in response to muramyl dipeptide stimulation."; /evidence="ECO:0000269|PubMed:15044951"; MUTAGEN 295; /note="V->E: Abolished NF-kappa-B activation in response to muramyl dipeptide stimulation."; /evidence="ECO:0000269|PubMed:15044951"; MUTAGEN 305; /note="K->R: No activation."; /evidence="ECO:0000269|PubMed:11087742"; MUTAGEN 327; /note="F->Y: Abolished NF-kappa-B activation in response to muramyl dipeptide stimulation."; /evidence="ECO:0000269|PubMed:15044951"; MUTAGEN 333; /note="C->Y: Abolished NF-kappa-B activation in response to muramyl dipeptide stimulation."; /evidence="ECO:0000269|PubMed:15044951"; MUTAGEN 334; /note="R->A: Increased NF-kappa-B activation in response to muramyl dipeptide stimulation."; /evidence="ECO:0000269|PubMed:27283905"; MUTAGEN 344; /note="S->T: Abolished NF-kappa-B activation in response to muramyl dipeptide stimulation."; /evidence="ECO:0000269|PubMed:15044951"; MUTAGEN 379; /note="D->A: No disruption in NOD2-CARD9 interaction. Decreased NF-kappa-B activation in response to muramyl dipeptide stimulation."; /evidence="ECO:0000269|PubMed:15044951, ECO:0000269|PubMed:24960071"; MUTAGEN 395; /note="C->S: Abolished palmitoylation and localization to the cell membrane; when associated with S-1033."; /evidence="ECO:0000269|PubMed:31649195, ECO:0000269|PubMed:34293401, ECO:0000269|PubMed:35066577"; MUTAGEN 396; /note="S->Y: Abolished NF-kappa-B activation in response to muramyl dipeptide stimulation."; /evidence="ECO:0000269|PubMed:15044951"; MUTAGEN 401; /note="T->I,S: Abolished NF-kappa-B activation in response to muramyl dipeptide stimulation."; /evidence="ECO:0000269|PubMed:15044951"; MUTAGEN 408; /note="F->L: Abolished NF-kappa-B activation in response to muramyl dipeptide stimulation."; /evidence="ECO:0000269|PubMed:15044951"; MUTAGEN 426; /note="R->A: Does not affect NF-kappa-B activation in response to muramyl dipeptide stimulation."; /evidence="ECO:0000269|PubMed:27283905"; MUTAGEN 429; /note="A->T: Abolished NF-kappa-B activation in response to muramyl dipeptide stimulation."; /evidence="ECO:0000269|PubMed:15044951"; MUTAGEN 481; /note="G->A: Increased NF-kappa-B activation in response to muramyl dipeptide stimulation."; /evidence="ECO:0000269|PubMed:27283905"; MUTAGEN 492; /note="V->E: Abolished NF-kappa-B activation in response to muramyl dipeptide stimulation."; /evidence="ECO:0000269|PubMed:15044951"; MUTAGEN 600; /note="E->A: Increased NF-kappa-B activation in response to muramyl dipeptide stimulation."; /evidence="ECO:0000269|PubMed:27283905"; MUTAGEN 603; /note="H->A: Does not affect NF-kappa-B activation in response to muramyl dipeptide stimulation."; /evidence="ECO:0000269|PubMed:27283905"; MUTAGEN 626; /note="L->F: Abolished NF-kappa-B activation in response to muramyl dipeptide stimulation."; /evidence="ECO:0000269|PubMed:15044951"; MUTAGEN 637; /note="N->I: Constitutive NF-kappa-B activation; when associated with V-725."; /evidence="ECO:0000269|PubMed:15044951"; MUTAGEN 639; /note="P->S: Abolished NF-kappa-B activation in response to muramyl dipeptide stimulation."; /evidence="ECO:0000269|PubMed:15044951"; MUTAGEN 655; /note="K->E: Abolished NF-kappa-B activation in response to muramyl dipeptide stimulation."; /evidence="ECO:0000269|PubMed:15044951"; MUTAGEN 668; /note="P->H: Constitutive NF-kappa-B activation."; /evidence="ECO:0000269|PubMed:15044951"; MUTAGEN 670; /note="N->A: Increased NF-kappa-B activation in response to muramyl dipeptide stimulation."; /evidence="ECO:0000269|PubMed:27283905"; MUTAGEN 673; /note="I->F: Constitutive NF-kappa-B activation."; /evidence="ECO:0000269|PubMed:15044951"; MUTAGEN 680; /note="G->R: Abolished NF-kappa-B activation in response to muramyl dipeptide stimulation."; /evidence="ECO:0000269|PubMed:15044951"; MUTAGEN 680; /note="Missing: Constitutive NF-kappa-B activation; when associated with Y-710."; /evidence="ECO:0000269|PubMed:15044951"; MUTAGEN 690; /note="L->P: Abolished NF-kappa-B activation in response to muramyl dipeptide stimulation."; /evidence="ECO:0000269|PubMed:15044951"; MUTAGEN 691; /note="A->T: Abolished NF-kappa-B activation in response to muramyl dipeptide stimulation."; /evidence="ECO:0000269|PubMed:15044951"; MUTAGEN 710; /note="C->Y: Constitutive NF-kappa-B activation; when associated with R-680."; /evidence="ECO:0000269|PubMed:15044951"; MUTAGEN 714; /note="S->N: Abolished NF-kappa-B activation in response to muramyl dipeptide stimulation."; /evidence="ECO:0000269|PubMed:15044951"; MUTAGEN 719; /note="F->I: Constitutive NF-kappa-B activation; when associated with R-731."; /evidence="ECO:0000269|PubMed:15044951"; MUTAGEN 725; /note="A->V: Constitutive NF-kappa-B activation; when associated with I-637."; /evidence="ECO:0000269|PubMed:15044951"; MUTAGEN 731; /note="K->R: Constitutive NF-kappa-B activation; when associated with I-719."; /evidence="ECO:0000269|PubMed:15044951"; MUTAGEN 734; /note="H->L: Abolished NF-kappa-B activation in response to muramyl dipeptide stimulation."; /evidence="ECO:0000269|PubMed:15044951"; MUTAGEN 761; /note="G->H: Abolished pattern recognition receptor activity."; /evidence="ECO:0000269|PubMed:15044951"; MUTAGEN 762; /note="L->M: Abolished pattern recognition receptor activity."; /evidence="ECO:0000269|PubMed:15044951"; MUTAGEN 799; /note="Y->A: Does not affect response to muramyl dipeptide (MDP)."; /evidence="ECO:0000269|PubMed:27283905"; MUTAGEN 805; /note="I->N: Abolished pattern recognition receptor activity."; /evidence="ECO:0000269|PubMed:15044951"; MUTAGEN 812; /note="P->T: Abolished pattern recognition receptor activity."; /evidence="ECO:0000269|PubMed:15044951"; MUTAGEN 823; /note="R->A: Slightly decreased response to muramyl dipeptide (MDP)."; /evidence="ECO:0000269|PubMed:27283905"; MUTAGEN 824; /note="D->A: Does not affect response to muramyl dipeptide (MDP)."; /evidence="ECO:0000269|PubMed:27283905"; MUTAGEN 824; /note="D->N: Abolished pattern recognition receptor activity."; /evidence="ECO:0000269|PubMed:15044951"; MUTAGEN 851; /note="F->A: Decreased response to muramyl dipeptide (MDP)."; /evidence="ECO:0000269|PubMed:27283905"; MUTAGEN 852; /note="N->A: Does not affect response to muramyl dipeptide (MDP)."; /evidence="ECO:0000269|PubMed:27283905"; MUTAGEN 860; /note="A->G: Abolished pattern recognition receptor activity."; /evidence="ECO:0000269|PubMed:15044951"; MUTAGEN 876; /note="L->I: Abolished pattern recognition receptor activity."; /evidence="ECO:0000269|PubMed:15044951"; MUTAGEN 877; /note="R->A: Strongly decreased binding to muramyl dipeptide (MDP)."; /evidence="ECO:0000269|PubMed:27283905, ECO:0000269|PubMed:27748583"; MUTAGEN 889; /note="Q->P: Abolished pattern recognition receptor activity."; /evidence="ECO:0000269|PubMed:15044951"; MUTAGEN 891; /note="L->M: Abolished pattern recognition receptor activity."; /evidence="ECO:0000269|PubMed:15044951"; MUTAGEN 892; /note="A->V: Abolished pattern recognition receptor activity."; /evidence="ECO:0000269|PubMed:15044951"; MUTAGEN 904; /note="L->M: Abolished pattern recognition receptor activity."; /evidence="ECO:0000269|PubMed:15044951"; MUTAGEN 905; /note="G->A: Decreased response to muramyl dipeptide (MDP)."; /evidence="ECO:0000269|PubMed:27283905"; MUTAGEN 907; /note="W->A: Decreased response to muramyl dipeptide (MDP)."; /evidence="ECO:0000269|PubMed:27283905"; MUTAGEN 913; /note="D->V: Abolished pattern recognition receptor activity."; /evidence="ECO:0000269|PubMed:15044951"; MUTAGEN 920; /note="A->T: Abolished pattern recognition receptor activity."; /evidence="ECO:0000269|PubMed:15044951"; MUTAGEN 931; /note="W->A: Strongly decreased binding to muramyl dipeptide (MDP)."; /evidence="ECO:0000269|PubMed:27283905, ECO:0000269|PubMed:27748583"; MUTAGEN 933; /note="S->A: Decreased binding to muramyl dipeptide (MDP)."; /evidence="ECO:0000269|PubMed:27283905, ECO:0000269|PubMed:27748583"; MUTAGEN 935; /note="V->A: Slightly decreased response to muramyl dipeptide (MDP)."; /evidence="ECO:0000269|PubMed:27283905"; MUTAGEN 936; /note="G->A: Does not affect response to muramyl dipeptide (MDP)."; /evidence="ECO:0000269|PubMed:27283905"; MUTAGEN 944; /note="A->V: Abolished pattern recognition receptor activity."; /evidence="ECO:0000269|PubMed:15044951"; MUTAGEN 947; /note="L->M: Abolished pattern recognition receptor activity."; /evidence="ECO:0000269|PubMed:15044951"; MUTAGEN 949; /note="L->M: Abolished pattern recognition receptor activity."; /evidence="ECO:0000269|PubMed:15044951"; MUTAGEN 956; /note="M->T: Abolished pattern recognition receptor activity."; /evidence="ECO:0000269|PubMed:15044951"; MUTAGEN 961; /note="C->A: Does not affect response to muramyl dipeptide (MDP)."; /evidence="ECO:0000269|PubMed:27283905"; MUTAGEN 964; /note="E->A: Does not affect response to muramyl dipeptide (MDP)."; /evidence="ECO:0000269|PubMed:27283905"; MUTAGEN 968; /note="Q->H: Abolished pattern recognition receptor activity."; /evidence="ECO:0000269|PubMed:15044951"; MUTAGEN 978; /note="G->E: Abolished pattern recognition receptor activity."; /evidence="ECO:0000269|PubMed:15044951"; MUTAGEN 984; /note="S->T: Abolished pattern recognition receptor activity."; /evidence="ECO:0000269|PubMed:15044951"; MUTAGEN 986; /note="K->I: Abolished pattern recognition receptor activity."; /evidence="ECO:0000269|PubMed:15044951"; MUTAGEN 992; /note="N->A: Does not affect response to muramyl dipeptide (MDP)."; /evidence="ECO:0000269|PubMed:27283905"; MUTAGEN 1002; /note="A->S: Abolished pattern recognition receptor activity."; /evidence="ECO:0000269|PubMed:15044951"; MUTAGEN 1017..1019; /note="WLR->GGG: Abolished localization to the cell membrane."; /evidence="ECO:0000269|PubMed:15998797"; MUTAGEN 1017; /note="W->G: Decreased ability to promote NF-kappa-B activation."; /evidence="ECO:0000269|PubMed:15998797"; MUTAGEN 1018; /note="L->G: Decreased ability to promote NF-kappa-B activation."; /evidence="ECO:0000269|PubMed:15998797"; MUTAGEN 1019; /note="R->G: Does not affect ability to promote NF-kappa-B activation."; /evidence="ECO:0000269|PubMed:15998797"; MUTAGEN 1033; /note="C->S: Abolished palmitoylation and localization to the cell membrane; when associated with S-395."; /evidence="ECO:0000269|PubMed:31649195, ECO:0000269|PubMed:34293401, ECO:0000269|PubMed:35066577"; MUTAGEN 1039..1040; /note="LL->GG: Abolished localization to the cell membrane."; /evidence="ECO:0000269|PubMed:15998797
uniprot
proteins
post_translational_modification
PTM: Palmitoylated by ZDHHC5; palmitoylation is required for proper recruitment to the bacterial entry site and hence for proper signaling upon cognate peptidoglycan detection (PubMed:31649195, PubMed:34293401, PubMed:35066577). Palmitoylation promotes localization to the cell membrane (PubMed:34293401). Palmitoylation protects from SQSTM1/p62-dependent autophagic degradation (PubMed:35066577). {ECO:0000269|PubMed:31649195, ECO:0000269|PubMed:34293401, ECO:0000269|PubMed:35066577}.; PTM: Polyubiquitinated by TRIM27, leading to proteasome-mediated degradation (PubMed:22829933). Polyubiquitinated and degraded following muramyl dipeptide (MDP) stimulation, conferring MDP tolerance and preventing septic shock (PubMed:23019338). {ECO:0000269|PubMed:22829933, ECO:0000269|PubMed:23019338}.; PTM: Degraded via selective autophagy following interaction with IRGM (PubMed:35066577, PubMed:36221902). IRGM promotes NOD2-RIPK2 RIPosome recruitment to autophagosome membranes, promoting their SQSTM1/p62-dependent autophagic degradation (PubMed:36221902). {ECO:0000269|PubMed:35066577, ECO:0000269|PubMed:36221902}.; PTM: O-glycosylated by OGT, O-GlcNAcylation increases protein stability. {ECO:0000269|PubMed:26369908}.
uniprot
proteins
protein_family
NOD1-NOD2 family
uniprot
proteins
pubmed
11087742
uniprot
proteins
pubmed
11385576
uniprot
proteins
pubmed
11385577
uniprot
proteins
pubmed
11528384
uniprot
proteins
pubmed
12514169
uniprot
proteins
pubmed
12527755
uniprot
proteins
pubmed
12626759
uniprot
proteins
pubmed
12871942
uniprot
proteins
pubmed
14570728
uniprot
proteins
pubmed
15024686
uniprot
proteins
pubmed
15044951
uniprot
proteins
pubmed
15198989
uniprot
proteins
pubmed
15459013
uniprot
proteins
pubmed
15812565
uniprot
proteins
pubmed
15998797
uniprot
proteins
pubmed
16203728
uniprot
proteins
pubmed
16485124
uniprot
proteins
pubmed
17355968
uniprot
proteins
pubmed
18511561
uniprot
proteins
pubmed
19116920
uniprot
proteins
pubmed
19169908
uniprot
proteins
pubmed
19359344
uniprot
proteins
pubmed
19479837
uniprot
proteins
pubmed
19592251
uniprot
proteins
pubmed
19701189
uniprot
proteins
pubmed
20199415
uniprot
proteins
pubmed
20637199
uniprot
proteins
pubmed
20698950
uniprot
proteins
pubmed
21887730
uniprot
proteins
pubmed
21914217
uniprot
proteins
pubmed
22700971
uniprot
proteins
pubmed
22829933
uniprot
proteins
pubmed
22857257
uniprot
proteins
pubmed
23019338
uniprot
proteins
pubmed
23300079
uniprot
proteins
pubmed
23322906
uniprot
proteins
pubmed
23376921
uniprot
proteins
pubmed
23711367
uniprot
proteins
pubmed
23806334
uniprot
proteins
pubmed
24790089
uniprot
proteins
pubmed
24960071
uniprot
proteins
pubmed
25093298
uniprot
proteins
pubmed
25692065
uniprot
proteins
pubmed
25724124
uniprot
proteins
pubmed
25891078
uniprot
proteins
pubmed
26070941
uniprot
proteins
pubmed
26369908
uniprot
proteins
pubmed
27007849
uniprot
proteins
pubmed
27283905
uniprot
proteins
pubmed
27748583
uniprot
proteins
pubmed
27812135
uniprot
proteins
pubmed
28436939
uniprot
proteins
pubmed
30279485
uniprot
proteins
pubmed
30478312
uniprot
proteins
pubmed
30559449
uniprot
proteins
pubmed
31649195
uniprot
proteins
pubmed
33942347
uniprot
proteins
pubmed
34251956
uniprot
proteins
pubmed
34293401
uniprot
proteins
pubmed
35066577
uniprot
proteins
pubmed
36002575
uniprot
proteins
pubmed
36221902
uniprot
proteins
sequence_length
1040
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:15998797, ECO:0000269|PubMed:25093298, ECO:0000269|PubMed:31649195, ECO:0000269|PubMed:34293401}; Lipid-anchor {ECO:0000269|PubMed:31649195, ECO:0000269|PubMed:34293401}. Basolateral cell membrane {ECO:0000269|PubMed:16203728, ECO:0000269|PubMed:17355968}. Cytoplasm {ECO:0000269|PubMed:14570728, ECO:0000269|PubMed:15998797, ECO:0000269|PubMed:19701189, ECO:0000269|PubMed:24790089, ECO:0000269|PubMed:25093298}. Mitochondrion {ECO:0000269|PubMed:19701189}. Note=Palmitoylation promotes localization to the cell membrane, where it detects bacterial invasion at the point of entry. {ECO:0000269|PubMed:34293401}.; SUBCELLULAR LOCATION: [Isoform 3]: Cytoplasm {ECO:0000269|PubMed:20698950}.
uniprot
proteins