NOD1

Summary

NOD1 (nucleotide binding oligomerization domain containing 1, HGNC:16390) is a protein-coding gene on chromosome 7p14.3, encoding Nucleotide-binding oligomerization domain-containing protein 1 (Q9Y239). Pattern recognition receptor (PRR) that detects bacterial peptidoglycan fragments and other danger signals and thus participates in both innate and adaptive immune responses.

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.

Source: NCBI Gene 10392 — RefSeq curated summary.

At a glance

• GWAS associations: 11
• Clinical variants (ClinVar): 205 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_006092

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16390
Approved symbol	NOD1
Name	nucleotide binding oligomerization domain containing 1
Location	7p14.3
Locus type	gene with protein product
Status	Approved
Aliases	NLRC1, CLR7.1
Ensembl gene	ENSG00000106100
Ensembl biotype	protein_coding
OMIM	605980
Entrez	10392

Gene structure

Transcript identifiers

Ensembl transcripts: 33 — 30 protein_coding, 2 retained_intron, 1 nonsense_mediated_decay

ENST00000222823, ENST00000411552, ENST00000413433, ENST00000419601, ENST00000419799, ENST00000434755, ENST00000467706, ENST00000489614, ENST00000855549, ENST00000855550, ENST00000855551, ENST00000855552, ENST00000855553, ENST00000855554, ENST00000855555, ENST00000855556, ENST00000855557, ENST00000855558, ENST00000855559, ENST00000931850, ENST00000931851, ENST00000931852, ENST00000955987, ENST00000955988, ENST00000955989, ENST00000955990, ENST00000955991, ENST00000955992, ENST00000955993, ENST00000955994, ENST00000955995, ENST00000955996, ENST00000955997

RefSeq mRNA: 2 — MANE Select: NM_006092 NM_001354849, NM_006092

CCDS: CCDS5427

Canonical transcript exons

ENST00000222823 — 14 exons

Exon	Start	End
ENSE00000674725	30446967	30447050
ENSE00000674737	30448298	30448381
ENSE00000674781	30455137	30455311
ENSE00001017072	30459152	30459240
ENSE00001017079	30456721	30457042
ENSE00001124263	30459901	30460041
ENSE00001329693	30451216	30453040
ENSE00001660956	30478606	30478784
ENSE00001929249	30424527	30425710
ENSE00003513414	30435998	30436081
ENSE00003543167	30433096	30433179
ENSE00003562874	30429374	30429457
ENSE00003600983	30446141	30446224
ENSE00003615586	30437573	30437656

Expression profiles

Bgee: expression breadth ubiquitous, 220 present calls, max score 91.60.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 5.0017 / max 100.3328, expressed in 1651 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
83437	3.7973	1544
83438	0.9121	574
83439	0.1935	72
83436	0.0987	23

Top tissues by expression

269 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
sural nerve	UBERON:0015488	91.60	gold quality
left ovary	UBERON:0002119	87.80	gold quality
right lobe of thyroid gland	UBERON:0001119	87.50	gold quality
omental fat pad	UBERON:0010414	87.39	gold quality
peritoneum	UBERON:0002358	87.34	gold quality
right ovary	UBERON:0002118	86.74	gold quality
adipose tissue of abdominal region	UBERON:0007808	86.74	gold quality
gingival epithelium	UBERON:0001949	86.62	silver quality
upper lobe of left lung	UBERON:0008952	86.24	gold quality
nerve	UBERON:0001021	86.13	gold quality
tibial nerve	UBERON:0001323	86.13	gold quality
left lobe of thyroid gland	UBERON:0001120	86.12	gold quality
apex of heart	UBERON:0002098	86.01	gold quality
subcutaneous adipose tissue	UBERON:0002190	85.99	gold quality
spleen	UBERON:0002106	85.90	gold quality
granulocyte	CL:0000094	85.63	gold quality
thyroid gland	UBERON:0002046	85.50	gold quality
upper lobe of lung	UBERON:0008948	85.40	gold quality
right lung	UBERON:0002167	84.78	gold quality
ovary	UBERON:0000992	83.55	gold quality
right atrium auricular region	UBERON:0006631	83.45	gold quality
left uterine tube	UBERON:0001303	83.39	gold quality
adipose tissue	UBERON:0001013	83.38	gold quality
skin of leg	UBERON:0001511	83.28	gold quality
secondary oocyte	CL:0000655	83.11	gold quality
connective tissue	UBERON:0002384	82.87	gold quality
heart left ventricle	UBERON:0002084	82.82	gold quality
visceral pleura	UBERON:0002401	82.79	gold quality
lung	UBERON:0002048	82.76	gold quality
lower esophagus muscularis layer	UBERON:0035833	82.68	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.87

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): HAND1, IRF1, MYC, NR1I2

Literature-anchored findings (GeneRIF, showing 40)

• role in CARD6 modulation of NF-kappa B activation (PMID:12775719)
• results show that Nod1 specifically detects a unique diaminopimelate-containing N-acetylglucosamine-N-acetylmuramic acid (GlcNAc-MurNAc) tripeptide motif found in Gram-negative bacterial peptidoglycan, resulting in activation of the NF-kappaB pathway (PMID:12791997)
• NOD1/CARD4 is activated by interferon gamma in intestinal mucosal inflammation (PMID:12813035)
• Using a wide array of natural or modified muramyl peptides, it is shown that Nod1 and Nod2 have evolved divergent strategies to achieve peptidoglycan sensing (PMID:12871942)
• signaling through Nod1 is required for activating NF-kappaB in human intestinal epithelial cells infected with gram-negative enteric bacteria that can bypass TLR activation (PMID:14977954)
• NOD1 variation has a role in inflammatory bowel disease and childhood asthma (PMID:15718249)
• inflammatory bowel disease susceptibility (PMID:15790594)
• genetic variants within NOD1 are important determinants of atopy susceptibility. (PMID:15990792)
• Nod1 is demonstrated to be a client protein of the Hsp90 chaperone complex containing the Chp-1. (PMID:16083881)
• there is cross-talk between the Nod1 and Nod2 pathways; down-regulation of the Nod1/M-Tri(DAP) pathway may be associated with Crohn disease (PMID:16115863)
• analysis of the molecular mechanisms responsible for the detection of bacterial peptidoglycan by Nod1 (PMID:16172124)
• IL-32 synergizes with nucleotide oligomerization domain (NOD) 1 and NOD2 ligands for IL-1beta and IL-6 production through a caspase 1-dependent mechanism. (PMID:16260731)
• absence of Nod1 correlates with tumor growth, an increased sensitivity to estrogen-induced cell proliferation, and a failure to undergo Nod1-dependent apoptosis (PMID:16446438)
• Finds somatic mutation in P-loop domains of proapoptotic NOD1 genes uncommon in colon cancers. (PMID:16464805)
• Review focuses on the molecular interactions by which NOD1 and NOD2 contribute to the maintenance of mucosal homeostasis and the induction of mucosal inflammation. (PMID:16493424)
• Polymorphism observed in the NOD1/CARD4 gene is not genetic susceptibility factors for Crohn’s disease or ulcerative colitis in Turkey. (PMID:16741608)
• The results suggest that the analysed CARD4 mutations do not play a major role in the aetiology of coronary heart disease. (PMID:16893397)
• Polymorphisms significantly modify the protective effect of exposure to a farming environment on allergies. (PMID:16918516)
• The results indicate that impaired recognition of intracellular P. acnes through NOD1 affects the susceptibility to sarcoidosis in the Japanese population. (PMID:16935475)
• CENTB1 selectively down-regulates NF-kappaB activation via NODs pathways, creating a “feedback” loop and suggesting a novel role of CENTB1 in innate immune responses to bacteria and inflammatory responses (PMID:17005562)
• high resolution NMR structure of NOD1 CARD; mutational analysis shows that interaction of NOD1 with RICK is critically dependent on 3 acidic residues on NOD1 CARD & 3 basic residues on RICK CARD & is likely to have a strong electrostatic component (PMID:17054981)
• Both NOD1 and NOD2 were expressed by first trimester placental villi and localized to trophoblast cells (PMID:17156193)
• This variant allele of NOD1/CARD4+32656 is not associated with a strong effect on susceptibility to IBD in children and adults in Northern Europe. (PMID:17285593)
• NOD1 gene polymorphism increases the risk of peptic ulceration in H. pylori-positive patients. (PMID:17309748)
• lipophilic peptidoglycan-related molecules have roles in induction of Nod1-mediated immune responses (PMID:17322292)
• epithelial cells, did not secrete IL-6, IL-8 or monocyte chemoattractant protein-1 in response to NOD1 and NOD2 agonists; stimulation with NODs ligands induced beta-defensin 2 generation in all epithelial cells examined (PMID:17403538)
• These results suggest that anti-PR3 Abs prime human monocytic cells to produce cytokines upon stimulation with various bacterial components by up-regulating the TLR and NOD signaling pathway. (PMID:17452051)
• NOD1, but not NOD2 is a major PRR for C. jejuni in IEC. (PMID:17521327)
• NOD2/CARD15 variant carriage had no influence on NOD1/CARD4 effect on inflammatory bowel disease susceptibility. (PMID:17613538)
• Suggest population differences in the inheritance of NOD1 polymorphism and NOD2 mutations. Relationship between disease location and Nod-like receptor molecules was established. (PMID:17907287)
• Carriage of the NOD1 G796A mutation increases susceptibility for Crohn’s disease in the Hungarian population. (PMID:17964870)
• Nod1 localization at the plasma membrane in human cells is dependent on the integrity of the protein, on its signalling capacity and on an intact actin cytoskeleton. (PMID:17970764)
• homodimerization of Nod1_CARD is achieved by swapping the H6 helices at the carboxy termini and stabilized by forming an interchain disulfide bond between the Cys39 residues of the two monomers in solution and in the crystal. (PMID:18186648)
• We conclude that the endogenous IL-8 response induced by C. trachomatis infection is dependent upon NOD1 signaling through RIP2 as part of a signal system requiring multiple inputs for optimal IL-8 induction. (PMID:18426885)
• The NOD1 receptors may have a role in preventing disruption of the epithelial barrier in lung, during inflammatory states. (PMID:18536738)
• in innate immune responses to invading microbes, a combination of signaling through TLRs and NOD1/2 leads to the synergistic activation of antibacterial responses in the oral epithelium. (PMID:18573991)
• These data indicate that the NLR family members Nod1 and Nod2 have different functions in controlling inflammation, and that intracellular Nod1-Nod2 interactions may determine the severity of arthritis in this experimental model. (PMID:18574154)
• GEF-H1 is a critical component of cellular defenses forming an intracellular sensing system with NOD1 for the detection of microbial effectors during cell invasion by pathogens. (PMID:19043560)
• polymorphisms are associated with increased risk of developing atopic eczema and asthma (PMID:19120480)
• There is functional expression of the intracellular pattern recognition receptor NOD1 in human keratinocytes. (PMID:19122645)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	nod1	ENSDARG00000036308
mus_musculus	Nod1	ENSMUSG00000038058
rattus_norvegicus	Nod1	ENSRNOG00000010629

Paralogs (20): NLRP2 (ENSG00000022556), NLRP1 (ENSG00000091592), NLRC5 (ENSG00000140853), NLRP12 (ENSG00000142405), NLRP14 (ENSG00000158077), NLRP4 (ENSG00000160505), NLRX1 (ENSG00000160703), NLRP3 (ENSG00000162711), NOD2 (ENSG00000167207), NLRP7 (ENSG00000167634), NLRC3 (ENSG00000167984), NLRP5 (ENSG00000171487), NLRP13 (ENSG00000173572), NLRP6 (ENSG00000174885), CIITA (ENSG00000179583), NLRP8 (ENSG00000179709), NLRP11 (ENSG00000179873), NLRP10 (ENSG00000182261), NLRP9 (ENSG00000185792), PYDC2 (ENSG00000253548)

Protein

Protein identifiers

Nucleotide-binding oligomerization domain-containing protein 1 — Q9Y239 (reviewed: Q9Y239)

Alternative names: Caspase recruitment domain-containing protein 4

All UniProt accessions (5): Q9Y239, A0A024RA73, A0A1B0GX71, C9J8X8, G3XAL1

UniProt curated annotations — full annotation on UniProt →

Function. Pattern recognition receptor (PRR) that detects bacterial peptidoglycan fragments and other danger signals and thus participates in both innate and adaptive immune responses. Specifically recognizes and binds gamma-D-glutamyl-meso-diaminopimelic acid (iE-DAP), a dipeptide present in peptidoglycan of Gram-negative bacteria. Preferentially binds iE-DAP in tripeptide-containing muropeptides (MurNAc-TriDAP or TriDAP). Ligand binding triggers oligomerization that facilitates the binding and subsequent activation of the proximal adapter receptor-interacting RIPK2. 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. This in turn leads to the transcriptional activation of hundreds of genes involved in immune response. Also acts as a regulator of 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. Also acts as a regulator of autophagy via its interaction with ATG16L1, possibly by recruiting ATG16L1 at the site of bacterial entry. 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. 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. In contrast to isoform 1, does not efficiently recognize and bind gamma-D-glutamyl-meso-diaminopimelic acid (iE-DAP) ligand.

Subunit / interactions. Homooligomer: homooligomerizes following ligand-binding, promoting RIPK2 recruitment. Interacts (via CARD domain) with RIPK2 (via CARD domain). Following RIPK2 recruitment, RIPK2 homooligomerizes via its CARD domain and forms long filaments named RIPosomes. Interacts with ARHGEF2. Interacts (via CARD domain) with ubiquitin; inhibiting interaction with RIPK2. Interacts with NLRP10 and recruits it to the cell membrane following invasive bacterial infection. Interacts with IFIH1; this interaction promotes transcription of antiviral genes and inhibition of viral replication. Interacts with IRGM; promoting NOD1 degradation. Interacts with ATG16L1.

Subcellular location. Cell membrane. Apical cell membrane. Basolateral cell membrane. Cytoplasm.

Tissue specificity. Highly expressed in adult heart, skeletal muscle, pancreas, spleen and ovary. Also detected in placenta, lung, liver, kidney, thymus, testis, small intestine and colon.

Post-translational modifications. 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. Degraded via selective autophagy following interaction with IRGM. IRGM promotes NOD1-RIPK2 RIPosome recruitment to autophagosome membranes, promoting their SQSTM1/p62-dependent autophagic degradation.

Domain organisation. The LRR repeats recognize and bind gamma-D-glutamyl-meso-diaminopimelic acid (iE-DAP).

Similarity. Belongs to the NOD1-NOD2 family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9Y239-1	1, Alpha	yes
Q9Y239-2	2
Q9Y239-3	3, Beta, delta10

RefSeq proteins (2): NP_001341778, NP_006083* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001315	CARD	Domain
IPR001611	Leu-rich_rpt	Repeat
IPR007111	NACHT_NTPase	Domain
IPR011029	DEATH-like_dom_sf	Homologous_superfamily
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR032675	LRR_dom_sf	Homologous_superfamily
IPR041075	NOD1/2_WH	Domain
IPR041267	NLRP_HD2	Domain
IPR051261	NLR	Family

Pfam: PF00619, PF05729, PF13516, PF17776, PF17779

UniProt features (59 total): mutagenesis site 26, repeat 9, helix 8, sequence variant 5, lipid moiety-binding region 3, splice variant 3, domain 2, chain 1, binding site 1, strand 1

Structure

Experimental structures (PDB)

6 structures.

PDB	Method	Resolution (Å)
2NZ7	X-RAY DIFFRACTION	1.9
2NSN	X-RAY DIFFRACTION	2
4E9M	X-RAY DIFFRACTION	2.15
4JQW	X-RAY DIFFRACTION	2.9
2B1W	SOLUTION NMR
2DBD	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y239-F1	85.87	0.53

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (1): 202–209

Post-translational modifications (3): 558, 567, 952

Mutagenesis-validated functional residues (26):

Position	Phenotype
41	abolishes interaction with ripk2/rick.
41	abolishes caspase-9 activation.
44	abolishes activation of nf-kappa-b. no effect on interaction with ripk2.
48	abolishes activation of nf-kappa-b. no effect on interaction with ripk2.
53	no effect on activation of nf-kappa-b. abolishes interaction with ripk2.
54	abolishes activation of nf-kappa-b. abolishes interaction with ripk2.
56	abolishes activation of nf-kappa-b. abolishes interaction with ripk2.
69	abolishes activation of nf-kappa-b. abolished interaction with ubiquitin and ripk2.
84–88	abolished interaction with ubiquitin without affecting interaction with ripk2.
208	reduces caspase-9 activation. reduced binding affinity for nlrp10. does not associate with cell membrane. reduced nf-kap
284	reduced nf-kappa-b activation in response to ligand binding.
287	reduced binding affinity for nlrp10.
517	loss of activation by sphingosine-1-phosphate.
558	strongly reduced palmitoylation and localization to the cell membrane; when associated with s-567 and s-952.
567	strongly reduced palmitoylation and localization to the cell membrane; when associated with s-558 and s-952.
711	does not associate with cell membrane.
788	no effect on association with cell membrane. reduced binding to gamma-d-glutamyl-meso-diaminopimelic acid (ie-dap).
790	reduced binding to gamma-d-glutamyl-meso-diaminopimelic acid (ie-dap).
792	does not associate with cell membrane. reduced binding to gamma-d-glutamyl-meso-diaminopimelic acid (ie-dap).
816	increased binding to gamma-d-glutamyl-meso-diaminopimelic acid (ie-dap) in tetrapeptide-containing muropeptides (murnac-
816	reduced binding to gamma-d-glutamyl-meso-diaminopimelic acid (ie-dap).
818	reduced binding to gamma-d-glutamyl-meso-diaminopimelic acid (ie-dap).
820	reduced binding to gamma-d-glutamyl-meso-diaminopimelic acid (ie-dap).
874	reduced binding to gamma-d-glutamyl-meso-diaminopimelic acid (ie-dap).
877	does not associate with cell membrane.

Function

Pathways and Gene Ontology

Reactome pathways

7 pathways

ID	Pathway
R-HSA-168638	NOD1/2 Signaling Pathway
R-HSA-445989	TAK1-dependent IKK and NF-kappa-B activation
R-HSA-450302	activated TAK1 mediates p38 MAPK activation
R-HSA-450321	JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1
R-HSA-5689896	Ovarian tumor domain proteases
R-HSA-9020702	Interleukin-1 signaling
R-HSA-9705671	SARS-CoV-2 activates/modulates innate and adaptive immune responses

MSigDB gene sets: 315 (showing top): GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_REGULATION_OF_AUTOPHAGY, REACTOME_INNATE_IMMUNE_SYSTEM, REACTOME_NOD1_2_SIGNALING_PATHWAY, GOBP_REGULATION_OF_STRESS_ACTIVATED_PROTEIN_KINASE_SIGNALING_CASCADE, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_INFLAMMATORY_RESPONSE, GOBP_POSITIVE_REGULATION_OF_INTERLEUKIN_8_PRODUCTION, REACTOME_NUCLEOTIDE_BINDING_DOMAIN_LEUCINE_RICH_REPEAT_CONTAINING_RECEPTOR_NLR_SIGNALING_PATHWAYS, GOBP_RESPONSE_TO_ENDOPLASMIC_RETICULUM_STRESS, GOBP_NUCLEOTIDE_BINDING_DOMAIN_LEUCINE_RICH_REPEAT_CONTAINING_RECEPTOR_SIGNALING_PATHWAY, GOBP_CANONICAL_NF_KAPPAB_SIGNAL_TRANSDUCTION, GOBP_POSITIVE_REGULATION_OF_MAPK_CASCADE, GOBP_POSITIVE_REGULATION_OF_CYTOKINE_PRODUCTION, GOBP_DETECTION_OF_OTHER_ORGANISM

GO Biological Process (37): pattern recognition receptor signaling pathway (GO:0002221), positive regulation of dendritic cell antigen processing and presentation (GO:0002606), apoptotic process (GO:0006915), defense response (GO:0006952), inflammatory response (GO:0006954), signal transduction (GO:0007165), JNK cascade (GO:0007254), detection of biotic stimulus (GO:0009595), detection of bacterium (GO:0016045), positive regulation of interleukin-1 beta production (GO:0032731), positive regulation of interleukin-6 production (GO:0032755), positive regulation of interleukin-8 production (GO:0032757), positive regulation of tumor necrosis factor production (GO:0032760), positive regulation of stress-activated MAPK cascade (GO:0032874), response to endoplasmic reticulum stress (GO:0034976), intracellular signal transduction (GO:0035556), defense response to bacterium (GO:0042742), positive regulation of apoptotic process (GO:0043065), positive regulation of canonical NF-kappaB signal transduction (GO:0043123), innate immune response (GO:0045087), positive regulation of JNK cascade (GO:0046330), defense response to Gram-negative bacterium (GO:0050829), defense response to Gram-positive bacterium (GO:0050830), obsolete positive regulation of NF-kappaB transcription factor activity (GO:0051092), stress-activated MAPK cascade (GO:0051403), positive regulation of macrophage cytokine production (GO:0060907), ERK1 and ERK2 cascade (GO:0070371), positive regulation of ERK1 and ERK2 cascade (GO:0070374), nucleotide-binding oligomerization domain containing 1 signaling pathway (GO:0070427), cellular response to muramyl dipeptide (GO:0071225), xenophagy (GO:0098792), positive regulation of non-canonical NF-kappaB signal transduction (GO:1901224), positive regulation of xenophagy (GO:1904417), positive regulation of cytokine production (GO:0001819), immune system process (GO:0002376), positive regulation of autophagy (GO:0010508), regulation of apoptotic process (GO:0042981)

GO Molecular Function (12): ATP binding (GO:0005524), cysteine-type endopeptidase activator activity involved in apoptotic process (GO:0008656), pattern recognition receptor activity (GO:0038187), identical protein binding (GO:0042802), protein homodimerization activity (GO:0042803), peptidoglycan binding (GO:0042834), ubiquitin binding (GO:0043130), protein-containing complex binding (GO:0044877), CARD domain binding (GO:0050700), nucleotide binding (GO:0000166), protein binding (GO:0005515), carbohydrate derivative binding (GO:0097367)

GO Cellular Component (7): cytoplasm (GO:0005737), cytosol (GO:0005829), plasma membrane (GO:0005886), basolateral plasma membrane (GO:0016323), apical plasma membrane (GO:0016324), phagocytic vesicle (GO:0045335), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-11 pathways:

Category	Pathways
MAP kinase activation	2
Nucleotide-binding domain, leucine rich repeat containing receptor (NLR) signaling pathways	1
MyD88:MAL(TIRAP) cascade initiated on plasma membrane	1
Toll Like Receptor 3 (TLR3) Cascade	1
Interleukin-1 signaling	1
TRIF (TICAM1)-mediated TLR4 signaling	1
TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation	1
MyD88 cascade initiated on plasma membrane	1
Deubiquitination	1
Interleukin-1 family signaling	1
SARS-CoV-2-host interactions	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	3
cellular anatomical structure	3
defense response	2
response to bacterium	2
positive regulation of cytokine production	2
intracellular anatomical structure	2
plasma membrane region	2
innate immune response-activating signaling pathway	1
dendritic cell antigen processing and presentation	1
positive regulation of antigen processing and presentation	1
regulation of dendritic cell antigen processing and presentation	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
response to stress	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
MAPK cascade	1
response to biotic stimulus	1
detection of stimulus	1
detection of other organism	1
interleukin-1 beta production	1
regulation of interleukin-1 beta production	1
positive regulation of interleukin-1 production	1
interleukin-6 production	1
regulation of interleukin-6 production	1
interleukin-8 production	1
regulation of interleukin-8 production	1
tumor necrosis factor production	1
regulation of tumor necrosis factor production	1
positive regulation of tumor necrosis factor superfamily cytokine production	1
regulation of stress-activated MAPK cascade	1
positive regulation of MAPK cascade	1
stress-activated MAPK cascade	1
positive regulation of stress-activated protein kinase signaling cascade	1
cellular response to stress	1
signal transduction	1

Protein interactions and networks

STRING

1941 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NOD1	RIPK2	O43353	999
NOD1	ATG16L1	Q676U5	991
NOD1	CASP1	P29466	925
NOD1	NOD2	Q9HC29	883
NOD1	CARD6	Q9BX69	849
NOD1	TLR2	O60603	845
NOD1	TNF	P01375	817
NOD1	PYCARD	Q9ULZ3	790
NOD1	TLR4	O00206	781
NOD1	BIRC2	Q13490	779
NOD1	NLRP1	Q9C000	773
NOD1	IL1B	P01584	770
NOD1	IL18	Q14116	765
NOD1	TLR1	Q15399	763
NOD1	RIGI	O95786	761

IntAct

75 interactions, top by confidence:

A	B	Type	Score
XIAP	RIPK2	psi-mi:“MI:0914”(association)	0.950
RIPK2	NOD1	psi-mi:“MI:2364”(proximity)	0.760
NOD1	RIPK2	psi-mi:“MI:0915”(physical association)	0.760
RIPK2	NOD1	psi-mi:“MI:0915”(physical association)	0.760
HSP90AA1	NOD1	psi-mi:“MI:0915”(physical association)	0.590
SUGT1	NOD1	psi-mi:“MI:0915”(physical association)	0.560
NOD1	SUGT1	psi-mi:“MI:0915”(physical association)	0.560
CRYAA	NOD1	psi-mi:“MI:0915”(physical association)	0.560
NOD1	GFAP	psi-mi:“MI:0915”(physical association)	0.560
NOD1	GLE1	psi-mi:“MI:0915”(physical association)	0.560
LMNA	NOD1	psi-mi:“MI:0915”(physical association)	0.560
NOD1	PAK1	psi-mi:“MI:0915”(physical association)	0.560
NOD1	KLK6	psi-mi:“MI:0915”(physical association)	0.560
NOD1	SPRED1	psi-mi:“MI:0915”(physical association)	0.560
HTT	NOD1	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (51): NOD1 (Affinity Capture-RNA), NOD1 (Affinity Capture-RNA), NOD1 (Affinity Capture-Western), ATG16L1 (Affinity Capture-Western), NOD2 (Affinity Capture-Western), NOD1 (Affinity Capture-Western), RIPK2 (Reconstituted Complex), ATG16L1 (Reconstituted Complex), UBC (Co-crystal Structure), NOD1 (Reconstituted Complex), NOD1 (Affinity Capture-Western), NOD1 (Affinity Capture-Western), NOD1 (Affinity Capture-Western), NOD1 (FRET), NOD1 (Negative Genetic)

ESM2 similar proteins: A1Z198, A4D126, A6QLE5, A6QP75, B0FPE9, C3VPR6, D3ZI76, D4A523, D9I2F9, D9I2G1, D9I2G3, D9I2G4, D9I2H0, E9Q5R7, G1T469, P59046, P59047, Q0GKD5, Q14DK4, Q288C4, Q2LKU9, Q2LKV2, Q2LKV5, Q2LKW6, Q3TL44, Q53B87, Q53B88, Q5FVQ8, Q60953, Q60I26, Q60I27, Q647I9, Q6E804, Q6NUI2, Q86UT6, Q86W28, Q8BH06, Q8BHB0, Q8IV45, Q8K3Z0

Diamond homologs: G1T469, P10775, Q53B87, Q53B88, Q6E804, Q8BHB0, Q8K3Z0, Q9HC29, Q9Y239, A1Z198, A6QLE5, B0FPE9, D4A523, D9I2F9, D9I2G1, D9I2G3, D9I2G4, D9I2H0, E9Q5R7, O15553, P13489, P29315, P33076, P59044, P59046, P59047, P79621, Q0GKD5, Q288C4, Q2LKU9, Q2LKV2, Q2LKV5, Q2LKW6, Q63035, Q647I9, Q6B966, Q6NZL6, Q7RTR0, Q86W24, Q86W25

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
NOD1	up-regulates	Autophagy
NOD1	“up-regulates activity”	ATG16L1	binding
NOD1	up-regulates	NfKb-p65/p50

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 35 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand	5	38.7×	2e-05
ESR-mediated signaling	5	25.7×	5e-05

GO biological processes:

GO term	Partners	Fold	FDR
protein folding	6	20.7×	5e-05
protein stabilization	6	13.4×	4e-04
negative regulation of apoptotic process	6	7.0×	6e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

205 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	140
Likely benign	17
Benign	6

Top pathogenic / likely-pathogenic (0)

SpliceAI

2959 predictions. Top by Δscore:

Variant	Effect	Δscore
7:30425709:GG:G	acceptor_gain	1.0000
7:30425711:C:CC	acceptor_gain	1.0000
7:30446140:CCCAA:C	donor_gain	1.0000
7:30446220:CCAGT:C	acceptor_gain	1.0000
7:30446221:CAGT:C	acceptor_gain	1.0000
7:30446221:CAGTC:C	acceptor_gain	1.0000
7:30446222:AGT:A	acceptor_gain	1.0000
7:30446222:AGTC:A	acceptor_loss	1.0000
7:30446223:GT:G	acceptor_gain	1.0000
7:30446223:GTC:G	acceptor_loss	1.0000
7:30446224:TCT:T	acceptor_loss	1.0000
7:30446225:C:CC	acceptor_gain	1.0000
7:30446225:CTG:C	acceptor_loss	1.0000
7:30446226:T:C	acceptor_loss	1.0000
7:30446965:A:AC	donor_gain	1.0000
7:30446966:C:CC	donor_gain	1.0000
7:30447051:C:CC	acceptor_gain	1.0000
7:30451214:A:T	donor_loss	1.0000
7:30451215:CC:C	donor_loss	1.0000
7:30453039:CA:C	acceptor_gain	1.0000
7:30453041:C:CC	acceptor_gain	1.0000
7:30455134:TA:T	donor_loss	1.0000
7:30455136:C:G	donor_loss	1.0000
7:30478604:A:AC	donor_gain	1.0000
7:30478605:C:CC	donor_gain	1.0000
7:30478606:TTGGC:T	donor_gain	1.0000
7:30478607:TGGCC:T	donor_gain	1.0000
7:30425706:TTAGG:T	acceptor_gain	0.9900
7:30425707:TAGG:T	acceptor_gain	0.9900
7:30425708:AGG:A	acceptor_gain	0.9900

AlphaMissense

6266 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:30451278:G:C	N713K	0.997
7:30451278:G:T	N713K	0.997
7:30437644:A:C	N822K	0.996
7:30437644:A:T	N822K	0.996
7:30448369:G:C	N738K	0.996
7:30448369:G:T	N738K	0.996
7:30451288:A:G	L710P	0.996
7:30446212:G:C	N794K	0.995
7:30446212:G:T	N794K	0.995
7:30447038:G:C	N766K	0.995
7:30447038:G:T	N766K	0.995
7:30451249:A:G	L723P	0.995
7:30451285:T:A	D711V	0.995
7:30433177:A:G	L875P	0.994
7:30447048:A:G	L763S	0.994
7:30448370:T:A	N738I	0.994
7:30429445:A:C	N906K	0.993
7:30429445:A:T	N906K	0.993
7:30429455:A:G	L903P	0.993
7:30433167:A:C	N878K	0.993
7:30433167:A:T	N878K	0.993
7:30437652:A:G	W820R	0.993
7:30437652:A:T	W820R	0.993
7:30436079:A:G	L847P	0.991
7:30448328:A:G	L752P	0.991
7:30448375:G:C	S736R	0.991
7:30448375:G:T	S736R	0.991
7:30448377:T:G	S736R	0.991
7:30448379:A:G	L735P	0.991
7:30451216:C:G	R734T	0.991

dbSNP variants (sampled 300 via entrez): RS1000038395 (7:30424568 G>T), RS1000139661 (7:30474503 A>C,G), RS1000140525 (7:30458099 CT>C), RS1000142194 (7:30450910 C>T), RS1000152551 (7:30424825 C>A,G), RS1000229277 (7:30453386 G>A,C), RS1000230664 (7:30450073 A>G), RS1000369919 (7:30461072 C>A,T), RS1000382557 (7:30430942 G>A), RS1000423793 (7:30461335 G>A), RS1000498660 (7:30465106 G>C,T), RS1000554153 (7:30428802 G>A,C), RS1000562630 (7:30470673 G>A), RS1000593316 (7:30465469 G>A), RS1000705207 (7:30459196 A>G)

Disease associations

OMIM: gene MIM:605980 | disease phenotypes: MIM:614557

GenCC curated gene-disease

Mondo (1): Ehlers-Danlos syndrome, kyphoscoliotic type, 2 (MONDO:0013800)

Orphanet (1): Kyphoscoliotic Ehlers-Danlos syndrome due to FKBP22 deficiency (Orphanet:300179)

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

11 associations (top):

Study	Trait	p-value
GCST003820_5	Knee osteoarthritis	5.000000e-06
GCST009268_11	Dental caries (decayed, missing and filled tooth surfaces)	7.000000e-07
GCST010002_346	Refractive error	1.000000e-08
GCST011369_12	Iron status biomarkers (ferritin levels)	5.000000e-23
GCST90002385_183	High light scatter reticulocyte count	5.000000e-16
GCST90002386_445	High light scatter reticulocyte percentage of red cells	8.000000e-15
GCST90002392_717	Mean corpuscular volume	3.000000e-09
GCST90002396_381	Mean reticulocyte volume	1.000000e-09
GCST90002397_498	Mean spheric corpuscular volume	2.000000e-18
GCST90002405_224	Reticulocyte count	2.000000e-14
GCST90002406_243	Reticulocyte fraction of red cells	9.000000e-13

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004459	ferritin measurement
EFO:0007986	reticulocyte count
EFO:0010701	mean reticulocyte volume

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1293222 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 117,814 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL939	GEFITINIB	4	117,814

PharmGKB: 1 entry (VIP=true, CPIC=false)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: catalytic receptor — NOD-like receptor family

Most potent curated ligand interactions (1 total), top 1:

Ligand	Action	Affinity	Parameter
ML130	Inhibition	6.25	pIC50

Binding affinities (BindingDB)

673 measured of 747 human assays (801 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
7-[(E)-but-2-enyl]-3-methyl-8-(3-phenylpropylsulfanyl)purine-2,6-dione	EC50	0.00868 nM
MLS000079200	EC50	7.4 nM
cid_709072	IC50	31.8 nM
cid_44229055	IC50	39.1 nM
MLS-0378444.0001	IC50	43.1 nM
2,6-bis(fluoranyl)-N-pyridin-4-yl-benzamide	IC50	80 nM
MLS-0384970.0001	IC50	98.3 nM
MLS000056239	IC50	106 nM
1-[4-(diethylsulfamoyl)phenyl]-3-[3-(trifluoromethyl)phenyl]urea	IC50	123 nM
cid_44251464	IC50	146 nM
N-[1-(2,3-dimethylphenyl)-4,5,6,7-tetrahydroindazol-4-yl]-2,5-dimethyl-3-pyrazolecarboxamide	EC50	170 nM
4-chloro-1-hydroxy-N-(2-methyl-5-nitrophenyl)-2-naphthalenecarboxamide	IC50	170 nM
3-(2-methyl-6-phenylthieno[2,3-d]pyrimidin-4-yl)sulfanylpropanoic acid	IC50	212 nM
N-[1-(4-tert-butylphenyl)-4,5,6,7-tetrahydroindazol-4-yl]-2-methyl-3-pyrazolecarboxamide	IC50	232 nM
MLS-0412148.0001	IC50	243 nM
7-(3-Methoxy-benzyl)-1,3-dimethyl-8-[(pyridin-3-ylmethyl)-amino]-3,7-dihydro-purine-2,6-dione	EC50	250 nM
MLS-0412140.0001	IC50	260 nM
SMR000415593	EC50	310 nM
cid_3390551	EC50	310 nM
cid_3115883	IC50	375 nM
MLS000100813	IC50	409 nM
cid_2211281	IC50	418 nM
4-(3,4-dihydro-1H-isoquinolin-2-ylmethyl)-N-(4-piperidin-1-ylsulfonylphenyl)benzamide	IC50	432 nM
sodium chloride	IC50	462 nM
cid_45253889	IC50	495 nM
cyclopropyl-[5-[[4-(4-methoxyphenyl)-1-piperazinyl]sulfonyl]-2-methyl-2,3-dihydroindol-1-yl]methanone	IC50	506 nM
MLS-0412192.0001	IC50	513 nM
MLS-0435754.0001	IC50	529 nM
MLS001159274	EC50	560 nM
4-[[4-oxo-2-[2-oxo-2-(4-propan-2-ylanilino)ethyl]sulfanylthieno[3,2-d]pyrimidin-3-yl]methyl]benzoic acid	IC50	561 nM
SMR000653893	EC50	620 nM
MLS-0380219.0001	IC50	677 nM
N-(4-chloro-3-nitrophenyl)-1-hydroxynaphthalene-2-carboxamide	IC50	692 nM
2-methyl-1-(4-methylphenyl)sulfonyl-benzimidazole	IC50	700 nM	US-9320722: Regulators of aldehyde dehydrogenase ALDH3A1 and related therapeutic methods
SMR000523991	IC50	720 nM
SMR000652637	EC50	750 nM
MLS-0425591.0001	IC50	770 nM
N-[(4S)-1-(2-fluorophenyl)-4,5,6,7-tetrahydroindazol-4-yl]-2-methylpyrazole-3-carboxamide	IC50	781 nM
cid_353380	EC50	790 nM
ethyl 4-[[4-(3,4-dihydro-1H-isoquinolin-2-ylmethyl)phenyl]carbonylamino]benzoate	EC50	850 nM
MLS-0425631.0001	IC50	891 nM
MLS001151090	IC50	929 nM
3-methyl-7-pentyl-8-(2-phenylethylsulfanyl)purine-2,6-dione	IC50	935 nM
cid_45253888	IC50	955 nM
MLS-0425704.0001	IC50	990 nM
Thioflavin T, 1	KI	1000 nM
1-[5-[[4-(4-chlorophenyl)-1-piperazinyl]sulfonyl]-2-methyl-2,3-dihydroindol-1-yl]-1-propanone	IC50	1010 nM
cid_1106356	IC50	1030 nM
1-(3-methylphenyl)-3-[(Z)-(2-oxidanylidene-1-prop-2-enyl-indol-3-ylidene)amino]thiourea	EC50	1090 nM
cid_22583043	EC50	1100 nM

ChEMBL bioactivities

429 potent at pChembl≥5 of 491 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.64	EC50	0.023	nM	CHEMBL1689697
10.57	EC50	0.027	nM	CHEMBL1689694
10.18	EC50	0.066	nM	CHEMBL1687963
10.16	EC50	0.069	nM	CHEMBL1689706
9.92	EC50	0.12	nM	CHEMBL1689699
9.87	EC50	0.134	nM	CHEMBL1689704
9.84	EC50	0.145	nM	CHEMBL1689708
9.74	EC50	0.181	nM	CHEMBL1689707
9.70	EC50	0.2	nM	CHEMBL1689698
9.62	EC50	0.238	nM	CHEMBL1689705
9.43	EC50	0.37	nM	CHEMBL1689715
9.41	EC50	0.39	nM	CHEMBL1689710
9.30	EC50	0.504	nM	CHEMBL1689709
9.26	EC50	0.55	nM	CHEMBL1689695
9.24	EC50	0.58	nM	CHEMBL1689696
9.24	EC50	0.57	nM	CHEMBL1689716
9.21	EC50	0.622	nM	CHEMBL1689702
9.10	IC50	0.8	nM	CHEMBL6133612
9.08	EC50	0.826	nM	CHEMBL1689703
9.05	IC50	0.9	nM	CHEMBL6078534
9.02	EC50	0.96	nM	CHEMBL1689717
8.92	IC50	1.2	nM	CHEMBL6083037
8.89	IC50	1.3	nM	CHEMBL6134693
8.89	IC50	1.3	nM	CHEMBL6102124
8.88	EC50	1.31	nM	CHEMBL1689701
8.76	EC50	1.73	nM	CHEMBL1689713
8.74	IC50	1.8	nM	CHEMBL6133609
8.66	IC50	2.2	nM	CHEMBL6146821
8.51	IC50	3.1	nM	CHEMBL6120266
8.39	IC50	4.1	nM	CHEMBL6091850
8.36	IC50	4.4	nM	CHEMBL6132927
8.30	IC50	5	nM	CHEMBL6143103
8.28	IC50	5.2	nM	CHEMBL6120254
8.12	IC50	7.5	nM	CHEMBL6120520
8.08	IC50	8.4	nM	CHEMBL6133963
8.04	IC50	9.1	nM	CHEMBL6108965
8.01	IC50	9.7	nM	CHEMBL6120408
7.96	IC50	11	nM	CHEMBL6103375
7.92	IC50	12	nM	CHEMBL6134503
7.80	IC50	16	nM	CHEMBL6078530
7.75	IC50	18	nM	CHEMBL6078094
7.60	IC50	25	nM	CHEMBL6078018
7.58	IC50	26	nM	CHEMBL6082994
7.57	IC50	27	nM	CHEMBL6078386
7.50	IC50	32	nM	CHEMBL6103088
7.50	IC50	31.8	nM	CHEMBL1699128
7.48	IC50	33	nM	CHEMBL6161949
7.43	IC50	37	nM	CHEMBL6160755
7.41	IC50	39	nM	CHEMBL6133942
7.40	IC50	40	nM	CHEMBL6151314

PubChem BioAssay actives

166 with measured affinity, of 927 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
2-amino-6-[[(4R)-4-carboxy-4-(didodecylamino)butanoyl]amino]heptanedioic acid	587775: Agonist activity at human NOD-1 expressed in human HEK293 cells assessed as NF-kappaB induction by spectrophotometric analysis	ec50	<0.0001	uM
2-amino-6-[[(4R)-4-carboxy-4-(dodecanoylamino)butanoyl]amino]heptanedioic acid	587775: Agonist activity at human NOD-1 expressed in human HEK293 cells assessed as NF-kappaB induction by spectrophotometric analysis	ec50	<0.0001	uM
2-amino-6-[[(4R)-4-carboxy-4-(dodecylamino)butanoyl]amino]heptanedioic acid	587775: Agonist activity at human NOD-1 expressed in human HEK293 cells assessed as NF-kappaB induction by spectrophotometric analysis	ec50	<0.0001	uM
2-amino-6-[[(4R)-4-carboxy-4-(dihexadecylamino)butanoyl]amino]heptanedioic acid	587775: Agonist activity at human NOD-1 expressed in human HEK293 cells assessed as NF-kappaB induction by spectrophotometric analysis	ec50	0.0001	uM
2-amino-6-[[(4R)-4-amino-5-oxo-5-undecoxypentanoyl]amino]heptanedioic acid	587775: Agonist activity at human NOD-1 expressed in human HEK293 cells assessed as NF-kappaB induction by spectrophotometric analysis	ec50	0.0001	uM
2-amino-6-[[(4R)-4-(dodecanoylamino)-5-oxo-5-undecoxypentanoyl]amino]heptanedioic acid	587775: Agonist activity at human NOD-1 expressed in human HEK293 cells assessed as NF-kappaB induction by spectrophotometric analysis	ec50	0.0001	uM
2-amino-6-[[(4R)-4-(dodecanoylamino)-5-ethoxy-5-oxopentanoyl]amino]heptanedioic acid	587775: Agonist activity at human NOD-1 expressed in human HEK293 cells assessed as NF-kappaB induction by spectrophotometric analysis	ec50	0.0001	uM
(2R)-5-[(6-amino-1,7-diethoxy-1,7-dioxoheptan-2-yl)amino]-2-(dodecanoylamino)-5-oxopentanoic acid	587775: Agonist activity at human NOD-1 expressed in human HEK293 cells assessed as NF-kappaB induction by spectrophotometric analysis	ec50	0.0001	uM
2-amino-6-[[(4R)-4-carboxy-4-(dioctylamino)butanoyl]amino]heptanedioic acid	587775: Agonist activity at human NOD-1 expressed in human HEK293 cells assessed as NF-kappaB induction by spectrophotometric analysis	ec50	0.0002	uM
2-amino-6-[[(4R)-4-(diaminomethylideneamino)-5-oxo-5-undecoxypentanoyl]amino]heptanedioic acid	587775: Agonist activity at human NOD-1 expressed in human HEK293 cells assessed as NF-kappaB induction by spectrophotometric analysis	ec50	0.0002	uM
diethyl 2-amino-6-[[(4R)-4-amino-5-oxo-5-undecylsulfanylpentanoyl]amino]heptanedioate	587775: Agonist activity at human NOD-1 expressed in human HEK293 cells assessed as NF-kappaB induction by spectrophotometric analysis	ec50	0.0002	uM
(2R)-2-amino-6-[[(4R)-4-carboxy-4-(dodecanoylamino)butanoyl]amino]hexanoic acid	587775: Agonist activity at human NOD-1 expressed in human HEK293 cells assessed as NF-kappaB induction by spectrophotometric analysis	ec50	0.0004	uM
2-amino-6-[(5-oxo-5-undecoxypentanoyl)amino]heptanedioic acid	587775: Agonist activity at human NOD-1 expressed in human HEK293 cells assessed as NF-kappaB induction by spectrophotometric analysis	ec50	0.0004	uM
2-amino-6-[4-(dodecanoylamino)butanoylamino]heptanedioic acid	587775: Agonist activity at human NOD-1 expressed in human HEK293 cells assessed as NF-kappaB induction by spectrophotometric analysis	ec50	0.0005	uM
(2S)-6-amino-2-[[(4R)-4-carboxy-4-(dodecanoylamino)butanoyl]amino]hexanoic acid	587775: Agonist activity at human NOD-1 expressed in human HEK293 cells assessed as NF-kappaB induction by spectrophotometric analysis	ec50	0.0006	uM
2-[[(4R)-4-carboxy-4-(dodecanoylamino)butanoyl]amino]-6-(diaminomethylideneamino)heptanedioic acid	587775: Agonist activity at human NOD-1 expressed in human HEK293 cells assessed as NF-kappaB induction by spectrophotometric analysis	ec50	0.0006	uM
2-[[(4R)-4-amino-4-carboxybutanoyl]amino]-6-(dodecanoylamino)heptanedioic acid	587775: Agonist activity at human NOD-1 expressed in human HEK293 cells assessed as NF-kappaB induction by spectrophotometric analysis	ec50	0.0006	uM
2-[[(4R)-4-carboxy-4-(dodecanoylamino)butanoyl]amino]-6-(dodecanoylamino)heptanedioic acid	587775: Agonist activity at human NOD-1 expressed in human HEK293 cells assessed as NF-kappaB induction by spectrophotometric analysis	ec50	0.0006	uM
2-amino-6-[[(4R)-4-amino-5-oxo-5-(undecylamino)pentanoyl]amino]heptanedioic acid	587775: Agonist activity at human NOD-1 expressed in human HEK293 cells assessed as NF-kappaB induction by spectrophotometric analysis	ec50	0.0008	uM
(2S)-2-amino-6-[[(4R)-4-carboxy-4-(dodecanoylamino)butanoyl]amino]hexanoic acid	587775: Agonist activity at human NOD-1 expressed in human HEK293 cells assessed as NF-kappaB induction by spectrophotometric analysis	ec50	0.0010	uM
(2R)-5-[[4-(2-amino-5-oxo-1,4-dihydroimidazol-4-yl)-1-carboxybutyl]amino]-2-(dodecanoylamino)-5-oxopentanoic acid	587775: Agonist activity at human NOD-1 expressed in human HEK293 cells assessed as NF-kappaB induction by spectrophotometric analysis	ec50	0.0013	uM
(2R)-2-(dodecanoylamino)-5-oxo-5-[(2-oxoazepan-3-yl)amino]pentanoic acid	587775: Agonist activity at human NOD-1 expressed in human HEK293 cells assessed as NF-kappaB induction by spectrophotometric analysis	ec50	0.0017	uM
4-(3,4-dihydro-1H-isoquinolin-2-ylmethyl)-N-[4-(trifluoromethoxy)phenyl]benzamide	1178166: Inhibition of NOD1 (unknown origin) expressed in HEK293T cells coexpressing NF-kappaB driven luciferase reporter gene by HTS primary assay	ic50	0.0800	uM
1-(4-chlorophenyl)sulfonylbenzimidazol-2-amine	1178166: Inhibition of NOD1 (unknown origin) expressed in HEK293T cells coexpressing NF-kappaB driven luciferase reporter gene by HTS primary assay	ic50	0.0900	uM
N-[3-[2-(3,3-difluoropiperidin-1-yl)-2-oxoethyl]-6-[3-(dimethylamino)phenoxy]-4-oxoquinazolin-7-yl]-2-[[4-(trifluoromethyl)phenyl]methoxy]acetamide	1705592: Antagonist activity at NOD1 in HEK-Blue hNOD1 cells assessed as inhibition of C12-iE-DAP-induced NFkappaB activation-mediated SEAP release preincubated for 3 hrs followed by C12-iE-DAP addition and measured after 20 hrs by spectrophotometric method	ic50	0.1400	uM
ethyl 4-[[4-(3,4-dihydro-1H-isoquinolin-2-ylmethyl)benzoyl]amino]benzoate	1178166: Inhibition of NOD1 (unknown origin) expressed in HEK293T cells coexpressing NF-kappaB driven luciferase reporter gene by HTS primary assay	ic50	0.1500	uM
N-[2-[1-[2-(2,3-dihydro-1H-inden-5-ylamino)-2-oxoethyl]benzimidazol-2-yl]ethyl]-N-methylnaphthalene-2-carboxamide	1178166: Inhibition of NOD1 (unknown origin) expressed in HEK293T cells coexpressing NF-kappaB driven luciferase reporter gene by HTS primary assay	ic50	0.2000	uM
N-[6-[3-(dimethylamino)phenoxy]-3-[2-(4-fluoropiperidin-1-yl)-2-oxoethyl]-4-oxoquinazolin-7-yl]-2-[[4-(trifluoromethyl)phenyl]methoxy]acetamide	1705592: Antagonist activity at NOD1 in HEK-Blue hNOD1 cells assessed as inhibition of C12-iE-DAP-induced NFkappaB activation-mediated SEAP release preincubated for 3 hrs followed by C12-iE-DAP addition and measured after 20 hrs by spectrophotometric method	ic50	0.2100	uM
[3-[(3-butyl-1,2,4-oxadiazol-5-yl)methyl]-7-methyl-1,1-dioxo-3H-1,2-benzothiazol-2-yl]-[3-(trifluoromethyl)phenyl]methanone	1741681: Antagonist activity at human NOD1 in HEK-Blue hNOD1 cells assessed as secreted alkaline phosphatase reporter activity preincubated for 3 hrs followed by stimulated with lauroyl-gamma-D-Glu-mDAP for 20 hrs by spectrophotometer method	ic50	0.2300	uM
4-(3,4-dihydro-1H-isoquinolin-2-ylmethyl)-N-(4-methylsulfanylphenyl)benzamide	1178166: Inhibition of NOD1 (unknown origin) expressed in HEK293T cells coexpressing NF-kappaB driven luciferase reporter gene by HTS primary assay	ic50	0.2400	uM
N-[6-[3-(dimethylamino)phenoxy]-4-oxo-3-(2-oxo-2-piperidin-1-ylethyl)quinazolin-7-yl]-2-[[4-(trifluoromethyl)phenyl]methoxy]acetamide	1705592: Antagonist activity at NOD1 in HEK-Blue hNOD1 cells assessed as inhibition of C12-iE-DAP-induced NFkappaB activation-mediated SEAP release preincubated for 3 hrs followed by C12-iE-DAP addition and measured after 20 hrs by spectrophotometric method	ic50	0.2600	uM
cyclopropyl-[2-methyl-5-[4-(4-nitrophenyl)piperazin-1-yl]sulfonyl-2,3-dihydroindol-1-yl]methanone	1178166: Inhibition of NOD1 (unknown origin) expressed in HEK293T cells coexpressing NF-kappaB driven luciferase reporter gene by HTS primary assay	ic50	0.2600	uM
N-[3-[2-(4,4-difluoropiperidin-1-yl)-2-oxoethyl]-6-[3-(dimethylamino)phenoxy]-4-oxoquinazolin-7-yl]-2-[[4-(trifluoromethyl)phenyl]methoxy]acetamide	1705592: Antagonist activity at NOD1 in HEK-Blue hNOD1 cells assessed as inhibition of C12-iE-DAP-induced NFkappaB activation-mediated SEAP release preincubated for 3 hrs followed by C12-iE-DAP addition and measured after 20 hrs by spectrophotometric method	ic50	0.2700	uM
N-[2-[1-[2-(2,3-dihydro-1H-inden-5-ylamino)-2-oxoethyl]benzimidazol-2-yl]ethyl]-N-methylbenzamide	1178166: Inhibition of NOD1 (unknown origin) expressed in HEK293T cells coexpressing NF-kappaB driven luciferase reporter gene by HTS primary assay	ic50	0.4000	uM
N-[(3R)-3-[3-(4,4-difluoropiperidin-1-yl)-3-oxopropyl]-7-[3-(dimethylamino)phenoxy]-2,5-dioxo-3,4-dihydro-1H-1,4-benzodiazepin-8-yl]-2-[[4-(trifluoromethyl)phenyl]methoxy]acetamide	1448680: Antagonist activity at human NOD1 expressed in HEK-blue cells assessed as inhibition of C12-iE-DAP-stimulated cell activation preincubated for 3 hrs followed by C12-iE-DAP addition measured after 20 hrs by by SEAP reporter gene assay	ic50	0.4300	uM
4-(3,4-dihydro-1H-isoquinolin-2-ylmethyl)-N-(4-methoxyphenyl)benzamide	655843: Inhibition of NOD-1 mediated NFkappaB activation in HEK293T cells assessed as inhibition of gamma-tri-DAP-induced luciferase activity after 14 hrs by reporter gene assay	ic50	0.5100	uM
cyclopropyl-[5-[4-(4-methoxyphenyl)piperazin-1-yl]sulfonyl-2-methyl-2,3-dihydroindol-1-yl]methanone	1178166: Inhibition of NOD1 (unknown origin) expressed in HEK293T cells coexpressing NF-kappaB driven luciferase reporter gene by HTS primary assay	ic50	0.5100	uM
N-[3-[2-(3,3-difluoropiperidin-1-yl)-2-oxoethyl]-6-(3-morpholin-4-ylphenoxy)-4-oxoquinazolin-7-yl]-2-[[4-(trifluoromethyl)phenyl]methoxy]acetamide	1705592: Antagonist activity at NOD1 in HEK-Blue hNOD1 cells assessed as inhibition of C12-iE-DAP-induced NFkappaB activation-mediated SEAP release preincubated for 3 hrs followed by C12-iE-DAP addition and measured after 20 hrs by spectrophotometric method	ic50	0.5400	uM
1-(4-methylphenyl)sulfonylbenzimidazol-2-amine	1178166: Inhibition of NOD1 (unknown origin) expressed in HEK293T cells coexpressing NF-kappaB driven luciferase reporter gene by HTS primary assay	ic50	0.5600	uM
methyl 3-[(3S)-7-[3-(dimethylamino)phenoxy]-2,5-dioxo-8-[[2-[[4-(trifluoromethyl)phenyl]methoxy]acetyl]amino]-3,4-dihydro-1H-1,4-benzodiazepin-3-yl]propanoate	1448680: Antagonist activity at human NOD1 expressed in HEK-blue cells assessed as inhibition of C12-iE-DAP-stimulated cell activation preincubated for 3 hrs followed by C12-iE-DAP addition measured after 20 hrs by by SEAP reporter gene assay	ic50	0.5800	uM
methyl 3-[(3R)-8-[[2-[(4-bromophenyl)methoxy]acetyl]amino]-7-[3-(dimethylamino)phenoxy]-2,5-dioxo-3,4-dihydro-1H-1,4-benzodiazepin-3-yl]propanoate	1448680: Antagonist activity at human NOD1 expressed in HEK-blue cells assessed as inhibition of C12-iE-DAP-stimulated cell activation preincubated for 3 hrs followed by C12-iE-DAP addition measured after 20 hrs by by SEAP reporter gene assay	ic50	0.5800	uM
N-[(3R)-7-[3-(dimethylamino)phenoxy]-3-[3-(4-fluoropiperidin-1-yl)-3-oxopropyl]-2,5-dioxo-3,4-dihydro-1H-1,4-benzodiazepin-8-yl]-2-[[4-(trifluoromethyl)phenyl]methoxy]acetamide	1448680: Antagonist activity at human NOD1 expressed in HEK-blue cells assessed as inhibition of C12-iE-DAP-stimulated cell activation preincubated for 3 hrs followed by C12-iE-DAP addition measured after 20 hrs by by SEAP reporter gene assay	ic50	0.5800	uM
methyl 3-[(3R)-8-[[2-[(4-chlorophenyl)methoxy]acetyl]amino]-7-[3-(dimethylamino)phenoxy]-2,5-dioxo-3,4-dihydro-1H-1,4-benzodiazepin-3-yl]propanoate	1448680: Antagonist activity at human NOD1 expressed in HEK-blue cells assessed as inhibition of C12-iE-DAP-stimulated cell activation preincubated for 3 hrs followed by C12-iE-DAP addition measured after 20 hrs by by SEAP reporter gene assay	ic50	0.6100	uM
methyl 2-[6-(3-morpholin-4-ylphenoxy)-4-oxo-7-[[2-[[4-(trifluoromethyl)phenyl]methoxy]acetyl]amino]quinazolin-3-yl]acetate	1705592: Antagonist activity at NOD1 in HEK-Blue hNOD1 cells assessed as inhibition of C12-iE-DAP-induced NFkappaB activation-mediated SEAP release preincubated for 3 hrs followed by C12-iE-DAP addition and measured after 20 hrs by spectrophotometric method	ic50	0.6500	uM
7-benzyl-3-methyl-8-nitropurine-2,6-dione	1178166: Inhibition of NOD1 (unknown origin) expressed in HEK293T cells coexpressing NF-kappaB driven luciferase reporter gene by HTS primary assay	ic50	0.7900	uM
N-[2-[1-[2-oxo-2-(3-propan-2-ylanilino)ethyl]benzimidazol-2-yl]ethyl]benzamide	1178166: Inhibition of NOD1 (unknown origin) expressed in HEK293T cells coexpressing NF-kappaB driven luciferase reporter gene by HTS primary assay	ic50	0.8000	uM
6-(3-chlorophenyl)-4-oxo-3-(2-oxo-2-piperidin-1-ylethyl)-N-[3-[4-(trifluoromethyl)phenoxy]propyl]quinazoline-7-carboxamide	1705592: Antagonist activity at NOD1 in HEK-Blue hNOD1 cells assessed as inhibition of C12-iE-DAP-induced NFkappaB activation-mediated SEAP release preincubated for 3 hrs followed by C12-iE-DAP addition and measured after 20 hrs by spectrophotometric method	ic50	0.8000	uM
N-(4-chlorophenyl)-4-(3,4-dihydro-1H-isoquinolin-2-ylmethyl)benzamide	655843: Inhibition of NOD-1 mediated NFkappaB activation in HEK293T cells assessed as inhibition of gamma-tri-DAP-induced luciferase activity after 14 hrs by reporter gene assay	ic50	0.8300	uM
6-(3-chlorophenyl)-4-oxo-N-[3-[4-(trifluoromethyl)phenoxy]propyl]-3H-quinazoline-7-carboxamide	1705592: Antagonist activity at NOD1 in HEK-Blue hNOD1 cells assessed as inhibition of C12-iE-DAP-induced NFkappaB activation-mediated SEAP release preincubated for 3 hrs followed by C12-iE-DAP addition and measured after 20 hrs by spectrophotometric method	ic50	0.8400	uM
methyl 2-[6-(3-chlorophenyl)-4-oxo-7-[3-[4-(trifluoromethyl)phenoxy]propylcarbamoyl]quinazolin-3-yl]acetate	1705592: Antagonist activity at NOD1 in HEK-Blue hNOD1 cells assessed as inhibition of C12-iE-DAP-induced NFkappaB activation-mediated SEAP release preincubated for 3 hrs followed by C12-iE-DAP addition and measured after 20 hrs by spectrophotometric method	ic50	0.8900	uM

CTD chemical–gene interactions

39 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	increases expression, increases methylation	2
Cisplatin	affects expression, increases expression	2
Nickel	increases expression	2
beauvericin	increases expression	1
triphenyl phosphate	affects expression	1
arsenite	decreases reaction, affects binding	1
nickel chloride	decreases reaction, decreases expression	1
cordycepin	increases expression	1
usnic acid	increases expression	1
4-(4-fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)imidazole	decreases reaction, increases secretion	1
lipopolysaccharide, E. coli O26-B6	decreases expression, decreases reaction	1
abrine	decreases expression, increases expression	1
3,5-bis(2-fluorobenzylidene)piperidin-4-one	decreases reaction, increases expression	1
Resveratrol	decreases reaction, increases expression	1
Decitabine	affects expression	1
Sunitinib	decreases expression	1
Acetaminophen	increases expression	1
Aerosols	affects localization, increases expression	1
Air Pollutants	increases expression	1
Curcumin	decreases reaction, increases expression	1
Doxorubicin	decreases expression	1
Hydralazine	affects cotreatment, increases expression	1
Ivermectin	decreases expression	1
Menthol	decreases expression	1
Mercury	decreases expression	1
Metformin	affects cotreatment, decreases expression	1
Methotrexate	decreases expression	1
Oxygen	decreases reaction, increases expression	1
Phthalic Acids	increases methylation	1
Plant Extracts	decreases reaction, increases expression	1

ChEMBL screening assays

111 unique, capped per target: 100 binding, 11 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1613826	Functional	PUBCHEM_BIOASSAY: SAR analysis of NF-kappaB dependent luciferase using DAP as an inducer - Set 2. (Class of assay: confirmatory) [Related pubchem assays (depositor defined):AID1566, AID1575, AID1578, AID1579, AID1849, AID1852, AID2264]	PubChem BioAssay data set
CHEMBL1769280	Binding	Induction of human NOD1 activity expressed in HEK293T cells assessed as NFKB activation at 1 to 100 ng/ml by luciferase reporter assay	Structures, synthesis, and human Nod1 stimulation of immunostimulatory bacterial peptidoglycan fragments in the environment. — J Nat Prod

Cellosaurus cell lines

7 cell lines: 5 cancer cell line, 2 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_A7YQ	HEK-Blue hNOD1	Transformed cell line	Female
CVCL_A7YV	293/hNOD1	Transformed cell line	Female
CVCL_C7DC	Abcam A-549 NOD1 KO	Cancer cell line	Male
CVCL_C7E2	Abcam HCT 116 NOD1 KO	Cancer cell line	Male
CVCL_E0J7	Ubigene HeLa NOD1 KO	Cancer cell line	Female
CVCL_VP28	AGS NOD1 KO clone 41A8	Cancer cell line	Female
CVCL_VP29	AGS NOD1 KO clone 41H8	Cancer cell line	Female

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.