Nucleotide-binding oligomerization domain-containing protein 1

UniProt Q9Y239 Organism Homo sapiens Gene CARD4, NOD1

Also known as: CARD4, NOD1

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 (By similarity). 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 (By similarity). 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).

Classification

Family (Pfam): PF00619 CARD, PF13516 LRR_6, PF05729 NACHT, PF17776 NLRC4_HD2, PF17779 WHD_NOD2
InterPro: CARD, DEATH-like_dom_sf, Leu-rich_rpt, LRR_dom_sf, NACHT_NTPase, NLR, NLRP_HD2, NOD1/2_WH, P-loop_NTPase
Functional cluster: Eukaryotic Transcription Factors & related

Experimental structures · PDB · 6

2B1W NMR
2DBD NMR
2NSN X-ray 2.00A
2NZ7 X-ray 1.90A
4E9M X-ray 2.15A
4JQW X-ray 2.90A

A predicted model is available from AlphaFold.

Gene Ontology · 37

Neighborhood · nearest proteins

Nearest neighbours of Nucleotide-binding oligomerization domain-containing protein 1: 3 by sequence/function similarity (left); 3 co-cited in the literature (right).

Related proteins · sequence + function similarity

Co-cited proteins · studied together in the literature

Nucleotide-binding oligomerization domain-containing protein 1 3 shared papers
Nucleotide-binding oligomerization domain-containing protein 2 8 shared papers
Receptor-interacting serine/threonine-protein kinase 2 5 shared papers
E3 ubiquitin-protein ligase RNF34 1 shared papers
Rho guanine nucleotide exchange factor 2 1 shared papers
Interferon-induced helicase C domain-containing protein 1 1 shared papers
Palmitoyltransferase ZDHHC5 1 shared papers
Immunity-related GTPase family M protein 1 shared papers
NACHT, LRR and PYD domains-containing protein 10 1 shared papers
Nucleotide-binding oligomerization domain-containing protein 2 1 shared papers
Nuclear receptor subfamily 2 group C member 2 1 shared papers
NF-kappa-B essential modulator 1 shared papers

Literature · 29 cited papers

Selective autophagy of RIPosomes maintains innate immune homeostasis during bacterial infection. EMBO J. · 2022
Cellular stress promotes NOD1/2-dependent inflammation via the endogenous metabolite sphingosine-1-phosphate. EMBO J. · 2021
NOD1 Promotes Antiviral Signaling by Binding Viral RNA and Regulating the Interaction of MDA5 and MAVS. J. Immunol. · 2020
Palmitoylation of NOD1 and NOD2 is required for bacterial sensing. Science · 2019
Structural basis of RIP2 activation and signaling. Nat. Commun. · 2018
NOD1 Participates in the Innate Immune Response Triggered by Hepatitis C Virus Polymerase. J. Virol. · 2016
NOD1 and NOD2 signalling links ER stress with inflammation. Nature · 2016
Crystal structure of a complex of NOD1 CARD and ubiquitin. PLoS ONE · 2014
The E3 ligase RNF34 is a novel negative regulator of the NOD1 pathway. Cell. Physiol. Biochem. · 2014
Ubiquitin regulates caspase recruitment domain-mediated signaling by nucleotide-binding oligomerization domain-containing proteins NOD1 and NOD2. J. Biol. Chem. · 2013
NLRP10 enhances Shigella-induced pro-inflammatory responses. Cell. Microbiol. · 2012
GEF-H1 mediated control of NOD1 dependent NF-kappaB activation by Shigella effectors. PLoS Pathog. · 2008
… and 17 more in the literature graph

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