| DOT Name |
Nucleotide-binding oligomerization domain-containing protein 1 (NOD1)
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| Synonyms |
hNod1; Caspase recruitment domain-containing protein 4 |
| Gene Name |
NOD1
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| UniProt ID |
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| 3D Structure |
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| PDB ID |
2B1W ; 2DBD ; 2NSN ; 2NZ7 ; 4E9M ; 4JQW |
| Pfam ID |
PF00619
; PF13516
; PF05729
; PF17776
; PF17779
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| Sequence |
MEEQGHSEMEIIPSESHPHIQLLKSNRELLVTHIRNTQCLVDNLLKNDYFSAEDAEIVCA
CPTQPDKVRKILDLVQSKGEEVSEFFLYLLQQLADAYVDLRPWLLEIGFSPSLLTQSKVV
VNTDPVSRYTQQLRHHLGRDSKFVLCYAQKEELLLEEIYMDTIMELVGFSNESLGSLNSL
ACLLDHTTGILNEQGETIFILGDAGVGKSMLLQRLQSLWATGRLDAGVKFFFHFRCRMFS
CFKESDRLCLQDLLFKHYCYPERDPEEVFAFLLRFPHVALFTFDGLDELHSDLDLSRVPD
SSCPWEPAHPLVLLANLLSGKLLKGASKLLTARTGIEVPRQFLRKKVLLRGFSPSHLRAY
ARRMFPERALQDRLLSQLEANPNLCSLCSVPLFCWIIFRCFQHFRAAFEGSPQLPDCTMT
LTDVFLLVTEVHLNRMQPSSLVQRNTRSPVETLHAGRDTLCSLGQVAHRGMEKSLFVFTQ
EEVQASGLQERDMQLGFLRALPELGPGGDQQSYEFFHLTLQAFFTAFFLVLDDRVGTQEL
LRFFQEWMPPAGAATTSCYPPFLPFQCLQGSGPAREDLFKNKDHFQFTNLFLCGLLSKAK
QKLLRHLVPAAALRRKRKALWAHLFSSLRGYLKSLPRVQVESFNQVQAMPTFIWMLRCIY
ETQSQKVGQLAARGICANYLKLTYCNACSADCSALSFVLHHFPKRLALDLDNNNLNDYGV
RELQPCFSRLTVLRLSVNQITDGGVKVLSEELTKYKIVTYLGLYNNQITDVGARYVTKIL
DECKGLTHLKLGKNKITSEGGKYLALAVKNSKSISEVGMWGNQVGDEGAKAFAEALRNHP
SLTTLSLASNGISTEGGKSLARALQQNTSLEILWLTQNELNDEVAESLAEMLKVNQTLKH
LWLIQNQITAKGTAQLADALQSNTGITEICLNGNLIKPEEAKVYEDEKRIICF
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| 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.
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| 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 . |
| KEGG Pathway |
- NOD-like receptor sig.ling pathway (hsa04621 )
- Epithelial cell sig.ling in Helicobacter pylori infection (hsa05120 )
- Shigellosis (hsa05131 )
- Salmonella infection (hsa05132 )
- Pertussis (hsa05133 )
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| Reactome Pathway |
- TAK1-dependent IKK and NF-kappa-B activation (R-HSA-445989 )
- activated TAK1 mediates p38 MAPK activation (R-HSA-450302 )
- JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1 (R-HSA-450321 )
- Ovarian tumor domain proteases (R-HSA-5689896 )
- Interleukin-1 signaling (R-HSA-9020702 )
- SARS-CoV-2 activates/modulates innate and adaptive immune responses (R-HSA-9705671 )
- NOD1/2 Signaling Pathway (R-HSA-168638 )
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