General Information of Target

Target ID LDTP13795
Target Name Nucleotide-binding oligomerization domain-containing protein 1 (NOD1)
Gene Name NOD1
Gene ID 10392
Synonyms
CARD4; Nucleotide-binding oligomerization domain-containing protein 1; hNod1; Caspase recruitment domain-containing protein 4
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Sequence
METRSSKTRRSLASRTNECQGTMWAPTSPPAGSSSPSQPTWKSSLYSSLAYSEAFHYSFA
ARPRRLTQLALAQRPEPQLLRLRPSSLRTQDISHLLTGVFRNLYSAEVIGDEVSASLIKA
RGSENERHEEFVDQLQQIRELYKQRLDEFEMLERHITQAQARAIAENERVMSQAGVQDLE
SLVRLPPVKSVSRWCIDSELLRKHHLISPEDYYTDTVPFHSAPKGISLPGCSKLTFSCEK
RSVQKKELNKKLEDSCRKKLAEFEDELDHTVDSLTWNLTPKAKERTREPLKKASQPRNKN
WMNHLRVPQRELDRLLLARMESRNHFLKNPRFFPPNTRYGGKSLVFPPKKPAPIGEFQST
EPEQSCADTPVFLAKPPIGFFTDYEIGPVYEMVIALQNTTTTSRYLRVLPPSTPYFALGL
GMFPGKGGMVAPGMTCQYIVQFFPDCLGDFDDFILVETQSAHTLLIPLQARRPPPVLTLS
PVLDCGYCLIGGVKMTRFICKNVGFSVGRFCIMPKTSWPPLSFKAIATVGFVEQPPFGIL
PSVFELAPGHAILVEVLFSPKSLGKAEQTFIIMCDNCQIKELVTIGIGQLIALDLIYISG
EKSQPDPGELTDLTAQHFIRFEPENLRSTARKQLIIRNATHVELAFYWQIMKPNLQPLMP
GETFSMDSIKCYPDKETAFSIMPRKGVLSPHTDHEFILSFSPHELRDFHSVLQMVLEEVP
EPVSSEAESLGHSSYSVDDVIVLEIEVKGSVEPFQVLLEPYALIIPGENYIGINVKKAFK
MWNNSKSPIRYLWGKISDCHIIEVEPGTGVIEPSEVGDFELNFTGGVPGPTSQDLLCEIE
DSPSPVVLHIEAVFKGPALIINVSALQFGLLRLGQKATNSIQIRNVSQLPATWRMKESPV
SLQERPEDVSPFDIEPSSGQLHSLGECRVDITLEALHCQHLETVLELEVENGAWSYLPVY
AEVQKPHVYLQSSQVEVRNLYLGVPTKTTITLINGTLLPTQFHWGKLLGHQAEFCMVTVS
PKHGLLGPSEECQLKLELTAHTQEELTHLALPCHVSGMKKPLVLGISGKPQGLQVAITIS
KESSDCSTEQWPGHPKELRLDFGSAVPLRTRVTRQLILTNRSPIRTRFSLKFEYFGSPQN
SLSKKTSLPNMPPALLKTVRMQEHLAKREQLDFMESMLSHGKGAAFFPHFSQGMLGPYQQ
LCIDITGCANMWGEYWDNLICTVGDLLPEVIPVHMAAVGCPISSLRTTSYTIDQAQKEPA
MRFGTQVSGGDTVTRTLRLNNSSPCDIRLDWETYVPEDKEDRLVELLVFYGPPFPLRDQA
GNELVCPDTPEGGCLLWSPGPSSSSEFSHETDSSVEGSSSASNRVAQKLISVILQAHEGV
PSGHLYCISPKQVVVPAGGSSTIYISFTPMVLSPEILHKVECTGYALGFMSLDSKVEREI
PGKRHRLQDFAVGPLKLDLHSYVRPAQLSVELDYGGSMEFQCQASDLIPEQPCSGVLSEL
VTTHHLKLTNTTEIPHYFRLMVSRPFSVSQDGASQDHRAPGPGQKQECEEETASADKQLV
LQAQENMLVNVSFSLSLELLSYQKLPADQTLPGVDIQQSASGEREMVFTQNLLLEYTNQT
TQVVPLRAVVAVPELQLSTSWVDFGTCFVSQQRVREVYLMNLSGCRSYWTMLMGQQEPAK
AAVAFRVSPNSGLLEARSANAPPTSIALQVFFTARSSELYESTMVVEGVLGEKSCTLRLR
GQGSYDERYMLPHQP
Target Type
Literature-reported
Target Bioclass
Other
Subcellular location
Cytoplasm
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.; [Isoform 3]: In contrast to isoform 1, does not efficiently recognize and bind gamma-D-glutamyl-meso-diaminopimelic acid (iE-DAP) ligand.
TTD ID
T21038
Uniprot ID
Q9Y239
DrugMap ID
TTYSRXM
Ensemble ID
ENST00000222823.9
HGNC ID
HGNC:16390
ChEMBL ID
CHEMBL1293222

Target Site Mutations in Different Cell Lines

Cell line Mutation details Probe for labeling this protein in this cell
CAL62 SNV: p.L343Q .
HCT116 SNV: p.F342Y .
HT SNV: p.F86S .
IM95 SNV: p.T555A .
KYSE150 SNV: p.C394R .
L428 SNV: p.A220V .

Probe(s) Labeling This Target

ABPP Probe
Click To Hide/Show 5 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
ONAyne
 Probe Info 
K598(7.14)  LDD0275  [1]
BTD
 Probe Info 
C39(1.33)  LDD2135  [2]
AHL-Pu-1
 Probe Info 
C726(20.00)  LDD0170  [3]
DBIA
 Probe Info 
C676(15.99)  LDD0204  [4]
CY4
 Probe Info 
T897(0.00); T909(0.00)  LDD0247  [5]

Competitor(s) Related to This Target

Competitor ID Name Cell line Binding Site(Ratio) Interaction ID Ref
 LDCM0025  4SU-RNA DM93 C726(20.00)  LDD0170  [3]
 LDCM0026  4SU-RNA+native RNA DM93 C726(16.26)  LDD0171  [3]
 LDCM0237  AC12 HEK-293T C303(1.05)  LDD1510  [6]
 LDCM0280  AC20 HEK-293T C303(1.18)  LDD1519  [6]
 LDCM0288  AC28 HEK-293T C303(1.13)  LDD1527  [6]
 LDCM0297  AC36 HEK-293T C303(1.18)  LDD1536  [6]
 LDCM0301  AC4 HEK-293T C303(1.08)  LDD1540  [6]
 LDCM0306  AC44 HEK-293T C303(1.53)  LDD1545  [6]
 LDCM0315  AC52 HEK-293T C303(1.21)  LDD1554  [6]
 LDCM0324  AC60 HEK-293T C303(1.45)  LDD1563  [6]
 LDCM0102  BDHI 8 Jurkat C676(15.99)  LDD0204  [4]
 LDCM0408  CL20 HEK-293T C303(1.23)  LDD1612  [6]
 LDCM0421  CL32 HEK-293T C303(1.32)  LDD1625  [6]
 LDCM0434  CL44 HEK-293T C303(1.28)  LDD1638  [6]
 LDCM0447  CL56 HEK-293T C303(1.31)  LDD1650  [6]
 LDCM0460  CL68 HEK-293T C303(1.33)  LDD1663  [6]
 LDCM0473  CL8 HEK-293T C303(1.31)  LDD1676  [6]
 LDCM0474  CL80 HEK-293T C303(0.97)  LDD1677  [6]
 LDCM0487  CL92 HEK-293T C303(1.04)  LDD1690  [6]
 LDCM0542  Nucleophilic fragment 37 MDA-MB-231 C39(1.33)  LDD2135  [2]

The Interaction Atlas With This Target

The Protein(s) Related To This Target

Enzyme
Click To Hide/Show 2 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Kallikrein-6 (KLK6) Peptidase S1 family Q92876
Serine/threonine-protein kinase PAK 1 (PAK1) STE Ser/Thr protein kinase family Q13153
Transporter and channel
Click To Hide/Show 3 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
mRNA export factor GLE1 (GLE1) GLE1 family Q53GS7
Huntingtin (HTT) Huntingtin family P42858
Alpha-crystallin A chain (CRYAA) Small heat shock protein (HSP20) family P02489
Other
Click To Hide/Show 6 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Glial fibrillary acidic protein (GFAP) Intermediate filament family P14136
Prelamin-A/C (LMNA) Intermediate filament family P02545
Protein SGT1 homolog (SUGT1) SGT1 family Q9Y2Z0
Nucleotide-binding oligomerization domain-containing protein 1 (NOD1) . Q9Y239
Olfactomedin-4 (OLFM4) . Q6UX06
Sprouty-related, EVH1 domain-containing protein 1 (SPRED1) . Q7Z699

The Drug(s) Related To This Target

Investigative
Click To Hide/Show 1 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
Meso-dap Small molecular drug D0A1GQ

References

1 A Paal-Knorr agent for chemoproteomic profiling of targets of isoketals in cells. Chem Sci. 2021 Oct 15;12(43):14557-14563. doi: 10.1039/d1sc02230j. eCollection 2021 Nov 10.
Mass spectrometry data entry: PXD028270
2 Nucleophilic covalent ligand discovery for the cysteine redoxome. Nat Chem Biol. 2023 Nov;19(11):1309-1319. doi: 10.1038/s41589-023-01330-5. Epub 2023 May 29.
Mass spectrometry data entry: PXD039908 , PXD029761
3 Chemoproteomic capture of RNA binding activity in living cells. Nat Commun. 2023 Oct 7;14(1):6282. doi: 10.1038/s41467-023-41844-z.
Mass spectrometry data entry: PXD044625
4 Covalent Inhibition by a Natural Product-Inspired Latent Electrophile. J Am Chem Soc. 2023 May 24;145(20):11097-11109. doi: 10.1021/jacs.3c00598. Epub 2023 May 15.
5 Cyclopropenone, Cyclopropeniminium Ion, and Cyclopropenethione as Novel Electrophilic Warheads for Potential Target Discovery of Triple-Negative Breast Cancer. J Med Chem. 2023 Feb 23;66(4):2851-2864. doi: 10.1021/acs.jmedchem.2c01889. Epub 2023 Feb 10.
6 Accelerating multiplexed profiling of protein-ligand interactions: High-throughput plate-based reactive cysteine profiling with minimal input. Cell Chem Biol. 2024 Mar 21;31(3):565-576.e4. doi: 10.1016/j.chembiol.2023.11.015. Epub 2023 Dec 19.
Mass spectrometry data entry: PXD044402