Protein: Nucleotide-binding oligomerization domain-containing protein 2 (Caspase recruitment domain-containing protein 15) (Inflammatory bowel disease protein 1) (Q9HC29)
Organism: Homo sapiens (Human)
Function: Pattern recognition receptor (PRR) that detects bacterial peptidoglycan fragments and other danger signals and plays an important role in gastrointestinal immunity. Upon stimulation by muramyl dipeptide (MDP), a fragment of bacterial peptidoglycan, binds the proximal adapter receptor-interacting RIPK2, which recruits ubiquitin ligases as XIAP, BIRC2, BIRC3, INAVA and the LUBAC complex, triggering activation of MAP kinases and activation of NF-kappa-B signaling. This in turn leads to the transcriptional activation of hundreds of genes involved in immune response. Required for MDP-induced NLRP1-dependent CASP1 activation and IL1B release in macrophages. Component of an autophagy-mediated antibacterial pathway together with ATG16L1. Also plays a role in sensing single-stranded RNA (ssRNA) from viruses. Interacts with mitochondrial antiviral signaling/MAVS, leading to activation of interferon regulatory factor-3/IRF3 and expression of type I interferon. Besides recognizing pathogens, participates in surveillance of cellular homeostasis through sensing and binding to the cytosolic metabolite sphingosine-1-phosphate and then initating inflammation process.
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}.
Interaction partners:
- Receptor-interacting serine/threonine-protein kinase 2
- Autophagy-related protein 16-1
- NACHT, LRR and PYD domains-containing protein 1
- Mitochondrial antiviral-signaling protein
- Caspase recruitment domain-containing protein 9
- Erbin
- Toll-like receptor 2
- Nucleotide-binding oligomerization domain-containing protein 1
- Autophagy protein 5
- Ubiquitin-like protein ATG12
Sequence:
MGEEGGSASHDEEERASVLLGHSPGCEMCSQEAFQAQRSQLVELLVSGSLEGFESVLDWLLSWEVLSWEDYEGFHLLGQPLSHLARRLLDTVWNKGTWACQKLIAAAQEAQADSQSPKLHGCWDPHSLHPARDLQSHRPAIVRRLHSHVENMLDLAWERGFVSQYECDEIRLPIFTPSQRARRLLDLATVKANGLAAFLLQHVQELPVPLALPLEAATCKKYMAKLRTTVSAQSRFLSTYDGAETLCLEDIYTENVLEVWADVGMAGPPQKSPATLGLEELFSTPGHLNDDADTVLVVGEAGSGKSTLLQRLHLLWAAGQDFQEFLFVFPFSCRQLQCMAKPLSVRTLLFEHCCWPDVGQEDIFQLLLDHPDRVLLTFDGFDEFKFRFTDRERHCSPTDPTSVQTLLFNLLQGNLLKNARKVVTSRPAAVSAFLRKYIRTEFNLKGFSEQGIELYLRKRHHEPGVADRLIRLLQETSALHGLCHLPVFSWMVSKCHQELLLQEGGSPKTTTDMYLLILQHFLLHATPPDSASQGLGPSLLRGRLPTLLHLGRLALWGLGMCCYVFSAQQLQAAQVSPDDISLGFLVRAKGVVPGSTAPLEFLHITFQCFFAAFYLALSADVPPALLRHLFNCGRPGNSPMARLLPTMCIQASEGKDSSVAALLQKAEPHNLQITAAFLAGLLSREHWGLLAECQTSEKALLRRQACARWCLARSLRKHFHSIPPAAPGEAKSVHAMPGFIWLIRSLYEMQEERLARKAARGLNVGHLKLTFCSVGPTECAALAFVLQHLRRPVALQLDYNSVGDIGVEQLLPCLGVCKALYLRDNNISDRGICKLIECALHCEQLQKLALFNNKLTDGCAHSMAKLLACRQNFLALRLGNNYITAAGAQVLAEGLRGNTSLQFLGFWGNRVGDEGAQALAEALGDHQSLRWLSLVGNNIGSVGAQALALMLAKNVMLEELCLEENHLQDEGVCSLAEGLKKNSSLKILKLSNNCITYLGAEALLQALERNDTILEVWLRGNTFSLEEVDKLGCRDTRLLL