Target Information
Target General Information | Top | |||||
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Target ID |
T75643
(Former ID: TTDI01990)
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Target Name |
Pattern recognition receptor NOD2 (NOD2)
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Synonyms |
Nucleotidebinding oligomerization domaincontaining protein 2; Nucleotide-binding oligomerization domain-containing protein 2; Inflammatory bowel disease protein 1; IBD1; Caspase recruitment domaincontaining protein 15; Caspase recruitment domain-containing protein 15; CARD15
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Gene Name |
NOD2
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Target Type |
Clinical trial target
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[1] | ||||
Disease | [+] 2 Target-related Diseases | + | ||||
1 | Diabetes mellitus [ICD-11: 5A10] | |||||
2 | Hepatitis virus infection [ICD-11: 1E50-1E51] | |||||
Function |
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. Plays also 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. Involved in gastrointestinal immunity.
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UniProt ID | ||||||
Sequence |
MGEEGGSASHDEEERASVLLGHSPGCEMCSQEAFQAQRSQLVELLVSGSLEGFESVLDWL
LSWEVLSWEDYEGFHLLGQPLSHLARRLLDTVWNKGTWACQKLIAAAQEAQADSQSPKLH GCWDPHSLHPARDLQSHRPAIVRRLHSHVENMLDLAWERGFVSQYECDEIRLPIFTPSQR ARRLLDLATVKANGLAAFLLQHVQELPVPLALPLEAATCKKYMAKLRTTVSAQSRFLSTY DGAETLCLEDIYTENVLEVWADVGMAGPPQKSPATLGLEELFSTPGHLNDDADTVLVVGE AGSGKSTLLQRLHLLWAAGQDFQEFLFVFPFSCRQLQCMAKPLSVRTLLFEHCCWPDVGQ EDIFQLLLDHPDRVLLTFDGFDEFKFRFTDRERHCSPTDPTSVQTLLFNLLQGNLLKNAR KVVTSRPAAVSAFLRKYIRTEFNLKGFSEQGIELYLRKRHHEPGVADRLIRLLQETSALH GLCHLPVFSWMVSKCHQELLLQEGGSPKTTTDMYLLILQHFLLHATPPDSASQGLGPSLL RGRLPTLLHLGRLALWGLGMCCYVFSAQQLQAAQVSPDDISLGFLVRAKGVVPGSTAPLE FLHITFQCFFAAFYLALSADVPPALLRHLFNCGRPGNSPMARLLPTMCIQASEGKDSSVA ALLQKAEPHNLQITAAFLAGLLSREHWGLLAECQTSEKALLRRQACARWCLARSLRKHFH SIPPAAPGEAKSVHAMPGFIWLIRSLYEMQEERLARKAARGLNVGHLKLTFCSVGPTECA ALAFVLQHLRRPVALQLDYNSVGDIGVEQLLPCLGVCKALYLRDNNISDRGICKLIECAL HCEQLQKLALFNNKLTDGCAHSMAKLLACRQNFLALRLGNNYITAAGAQVLAEGLRGNTS LQFLGFWGNRVGDEGAQALAEALGDHQSLRWLSLVGNNIGSVGAQALALMLAKNVMLEEL CLEENHLQDEGVCSLAEGLKKNSSLKILKLSNNCITYLGAEALLQALERNDTILEVWLRG NTFSLEEVDKLGCRDTRLLL Click to Show/Hide
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3D Structure | Click to Show 3D Structure of This Target | AlphaFold | ||||
HIT2.0 ID | T65JUB |
Drugs and Modes of Action | Top | |||||
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Clinical Trial Drug(s) | [+] 2 Clinical Trial Drugs | + | ||||
1 | MIS-416 | Drug Info | Phase 2 | Autoimmune diabetes | [2] | |
2 | SB-9200 | Drug Info | Phase 2 | Hepatitis B virus infection | [3] | |
Mode of Action | [+] 2 Modes of Action | + | ||||
Modulator | [+] 2 Modulator drugs | + | ||||
1 | MIS-416 | Drug Info | [1] | |||
2 | SB-9200 | Drug Info | [4] | |||
Agonist | [+] 1 Agonist drugs | + | ||||
1 | muramyl dipeptide | Drug Info | [5] |
Cell-based Target Expression Variations | Top | |||||
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Cell-based Target Expression Variations |
Different Human System Profiles of Target | Top |
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Human Similarity Proteins
of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target.
A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs
(Brief Bioinform, 21: 649-662, 2020).
Human Pathway Affiliation
of target is determined by the life-essential pathways provided on KEGG database. The target-affiliated pathways were defined based on the following two criteria (a) the pathways of the studied target should be life-essential for both healthy individuals and patients, and (b) the studied target should occupy an upstream position in the pathways and therefore had the ability to regulate biological function.
Targets involved in a fewer pathways have greater likelihood to be successfully developed, while those associated with more human pathways increase the chance of undesirable interferences with other human processes
(Pharmacol Rev, 58: 259-279, 2006).
Biological Network Descriptors
of target is determined based on a human protein-protein interactions (PPI) network consisting of 9,309 proteins and 52,713 PPIs, which were with a high confidence score of ≥ 0.95 collected from STRING database.
The network properties of targets based on protein-protein interactions (PPIs) have been widely adopted for the assessment of target’s druggability. Proteins with high node degree tend to have a high impact on network function through multiple interactions, while proteins with high betweenness centrality are regarded to be central for communication in interaction networks and regulate the flow of signaling information
(Front Pharmacol, 9, 1245, 2018;
Curr Opin Struct Biol. 44:134-142, 2017).
Human Similarity Proteins
Human Pathway Affiliation
Biological Network Descriptors
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Protein Name | Pfam ID | Percentage of Identity (%) | E value |
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Tropomodulin-1 (TMOD1) | 34.314 (35/102) | 3.69E-06 | |
Tropomodulin-4 (TMOD4) | 31.081 (23/74) | 3.00E-03 |
KEGG Pathway | Pathway ID | Affiliated Target | Pathway Map |
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NOD-like receptor signaling pathway | hsa04621 | Affiliated Target |
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Class: Organismal Systems => Immune system | Pathway Hierarchy | ||
TNF signaling pathway | hsa04668 | Affiliated Target |
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Class: Environmental Information Processing => Signal transduction | Pathway Hierarchy |
Degree | 15 | Degree centrality | 1.61E-03 | Betweenness centrality | 2.51E-04 |
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Closeness centrality | 2.21E-01 | Radiality | 1.39E+01 | Clustering coefficient | 7.62E-02 |
Neighborhood connectivity | 2.30E+01 | Topological coefficient | 1.08E-01 | Eccentricity | 12 |
Download | Click to Download the Full PPI Network of This Target | ||||
Chemical Structure based Activity Landscape of Target | Top |
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Target Regulators | Top | |||||
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Target-regulating microRNAs | ||||||
Target-interacting Proteins |
Target Affiliated Biological Pathways | Top | |||||
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KEGG Pathway | [+] 5 KEGG Pathways | + | ||||
1 | NOD-like receptor signaling pathway | |||||
2 | TNF signaling pathway | |||||
3 | Shigellosis | |||||
4 | Tuberculosis | |||||
5 | Inflammatory bowel disease (IBD) | |||||
PID Pathway | [+] 1 PID Pathways | + | ||||
1 | Canonical NF-kappaB pathway | |||||
Reactome | [+] 5 Reactome Pathways | + | ||||
1 | NOD1/2 Signaling Pathway | |||||
2 | TAK1 activates NFkB by phosphorylation and activation of IKKs complex | |||||
3 | Interleukin-1 signaling | |||||
4 | activated TAK1 mediates p38 MAPK activation | |||||
5 | JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1 | |||||
WikiPathways | [+] 5 WikiPathways | + | ||||
1 | MAP kinase activation in TLR cascade | |||||
2 | Nucleotide-binding domain, leucine rich repeat containing receptor (NLR) signaling pathways | |||||
3 | TAK1 activates NFkB by phosphorylation and activation of IKKs complex | |||||
4 | Interleukin-1 signaling | |||||
5 | NOD pathway |
References | Top | |||||
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REF 1 | DOI: 10.1371/journal.pone.0087712 | |||||
REF 2 | Targeting Innate Receptors with MIS416 Reshapes Th Responses and Suppresses CNS Disease in a Mouse Model of Multiple Sclerosis. PLoS ONE 9(1): e87712. January 31, 2014. | |||||
REF 3 | ClinicalTrials.gov (NCT02751996) A Study Evaluating the Safety, Pharmacokinetics, and Antiviral Efficacy of SB 9200 in Subjects Infected With Chronic HBV (ACHIEVE). U.S. National Institutes of Health. | |||||
REF 4 | Company reprot (Spring Bank Pharmaceuticals) (drug: SB 9200) | |||||
REF 5 | URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 1763). |
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