NOD1

This gene encodes a member of the nucleotide-binding oligomerization domain (NOD)-like receptor (NLR) family of proteins. The encoded protein plays a role in innate immunity by acting as a pattern-recognition receptor (PRR) that binds bacterial peptidoglycans and initiates inflammation. This protein has also been implicated in the immune response to viral and parasitic infection. Major structural features of this protein include an N-terminal caspase recruitment domain (CARD), a centrally located nucleotide-binding domain (NBD), and 10 tandem leucine-rich repeats (LRRs) in its C terminus. The CARD is involved in apoptotic signaling, LRRs participate in protein-protein interactions, and mutations in the NBD may affect the process of oligomerization and subsequent function of the LRR domain. Mutations in this gene are associated with asthma, inflammatory bowel disease, Behcet disease and sarcoidosis in human patients. [provided by RefSeq, Aug 2017]

Full Name

Nucleotide Binding Oligomerization Domain Containing 1

Function

Pattern recognition receptor (PRR) that detects bacterial peptidoglycan fragments and other danger signals and thus participates in both innate and adaptive immune responses (PubMed:19043560, PubMed:22672233, PubMed:27099311).
Ligand binding triggers oligomerization that facilitates the binding and subsequent activation of the receptor interacting protein-2/RIPK2. RIPK2 subsequently recruits the kinase TAK1 to activate NF-kappa-B and MAPK signaling pathways (PubMed:10880512).
Regulates also antiviral response elicited by dsRNA and the expression of RLR pathway members by targeting IFIH1 and TRAF3 to modulate the formation of IFIH1-MAVS and TRAF3-MAVS complexes leading to increased transcription of type I IFNs (PubMed:32169843).
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 (PubMed:33942347).
In addition, plays a role in insulin trafficking in beta cells in a cell-autonomous manner. Mechanistically, upon recognizing cognate ligands, NOD1 and RIPK2 localize to insulin vesicles where they recruit RAB1A to direct insulin trafficking through the cytoplasm (By similarity).

Biological Process

Activation of cysteine-type endopeptidase activity involved in apoptotic processManual Assertion Based On ExperimentIDA:MGI
Apoptotic processManual Assertion Based On ExperimentTAS:ProtInc
Cellular response to muramyl dipeptideManual Assertion Based On ExperimentIMP:UniProtKB
Defense responseManual Assertion Based On ExperimentTAS:HGNC-UCL
Defense response to bacteriumManual Assertion Based On ExperimentIDA:HGNC-UCL
Defense response to Gram-positive bacteriumIEA:Ensembl
Detection of bacteriumManual Assertion Based On ExperimentIDA:HGNC-UCL
Detection of biotic stimulusManual Assertion Based On ExperimentTAS:HGNC-UCL
Inflammatory responseManual Assertion Based On ExperimentTAS:HGNC-UCL
Innate immune responseIEA:UniProtKB-KW
Intracellular signal transductionManual Assertion Based On ExperimentIDA:HGNC-UCL
Pattern recognition receptor signaling pathwayManual Assertion Based On ExperimentIDA:UniProtKB
Positive regulation of cell deathIEA:Ensembl
Positive regulation of cysteine-type endopeptidase activity involved in apoptotic processManual Assertion Based On ExperimentIDA:MGI
Positive regulation of dendritic cell antigen processing and presentationISS:BHF-UCL
Positive regulation of ERK1 and ERK2 cascadeIEA:Ensembl
Positive regulation of I-kappaB kinase/NF-kappaB signalingManual Assertion Based On ExperimentIDA:MGI
Positive regulation of interleukin-1 beta productionIEA:Ensembl
Positive regulation of interleukin-6 productionIEA:Ensembl
Positive regulation of interleukin-8 productionManual Assertion Based On ExperimentIDA:HGNC-UCL
Positive regulation of JNK cascadeIEA:Ensembl
Positive regulation of NF-kappaB transcription factor activityManual Assertion Based On ExperimentIDA:UniProtKB
Positive regulation of NIK/NF-kappaB signalingManual Assertion Based On ExperimentIMP:UniProtKB
Positive regulation of nitric-oxide synthase activityIEA:Ensembl
Positive regulation of tumor necrosis factor productionIEA:Ensembl
Positive regulation of xenophagyIEA:Ensembl
Regulation of apoptotic processIEA:InterPro
Signal transductionManual Assertion Based On ExperimentTAS:HGNC-UCL

Cellular Location

Cytoplasm
Cell membrane
Apical cell membrane
Basolateral cell membrane
Detected in the cytoplasm and at the cell membrane. Following bacterial infection, localizes to bacterial entry sites in the cell membrane. Recruited to the basolateral and apical membranes in polarized epithelial cells.

PTM

Palmitoylated. Palmitoylation is required for proper recruitment to the bacterial entry site and hence for proper signaling upon cognate peptidoglycan detection
Ubiquitinated. 'Lys-48'-linked polyubiquitination by RNF34 promotes proteasomal degradation and thereby negatively regulates NOD1 for instance in NF-kappa-B activation.