Nod2 nucleotide-binding oligomerization domain containing 2 [ Rattus norvegicus (Norway rat) ]

Gene ID: 291912, updated on 4-Jan-2025

Summary

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Official Symbol: Nod2provided by RGD
Official Full Name: nucleotide-binding oligomerization domain containing 2provided by RGD
Primary source: RGD:1306368
See related: EnsemblRapid:ENSRNOG00000014124 AllianceGenome:RGD:1306368
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Rattus norvegicus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Rattus
Also known as: Card15
Summary: Enables muramyl dipeptide binding activity. Involved in several processes, including cellular response to peptidoglycan; positive regulation of dendritic cell cytokine production; and response to muramyl dipeptide. Predicted to be located in several cellular components, including Golgi apparatus; basolateral plasma membrane; and phagocytic vesicle. Predicted to be part of protein-containing complex. Predicted to be active in cytosol and plasma membrane. Predicted to be extrinsic component of plasma membrane. Biomarker of colitis; middle cerebral artery infarction; and pancreatitis. Human ortholog(s) of this gene implicated in several diseases, including Blau syndrome; autoimmune disease (multiple); familial Mediterranean fever; intestinal disease (multiple); and lung disease (multiple). Orthologous to human NOD2 (nucleotide binding oligomerization domain containing 2). [provided by Alliance of Genome Resources, Jan 2025]
Expression: Biased expression in Spleen (RPKM 40.7), Adrenal (RPKM 40.1) and 7 other tissues See more
Orthologs: human mouse all
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Genomic context

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See Nod2 in Genome Data Viewer

Location:: 19p11

Exon count:: 13

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCr8 (GCF_036323735.1)	19	NC_086037.1 (34555832..34596281, complement)
RS_2023_06	previous assembly	mRatBN7.2 (GCF_015227675.2)	19	NC_051354.1 (18382369..18422817, complement)
106	previous assembly	Rnor_6.0 (GCF_000001895.5)	19	NC_005118.4 (19342061..19389366, complement)

Chromosome 19 - NC_086037.1 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

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Expression

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See details

Project title: A rat RNA-Seq transcriptomic BodyMap across 11 organs and 4 developmental stages
Description: 320 RNA samples isolated from 11 organs (adrenal gland, brain, heart, kidney, liver, lung, muscle, spleen, thymus, and testes or uterus) from both sexes of Fischer 344 rats across four developmental stages (2-, 6-, 21-, and 104-weeks-old)
BioProject: PRJNA238328
Publication: PMID 24510058
Analysis date: Mon Jun 6 17:44:12 2016

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Role of NOD2 and hepcidin in inflammatory periapical periodontitis.
Title: Role of NOD2 and hepcidin in inflammatory periapical periodontitis.
Mutational analyses of novel rat models with targeted modifications in inflammatory bowel disease susceptibility genes.
Title: Mutational analyses of novel rat models with targeted modifications in inflammatory bowel disease susceptibility genes.
Data show that mRNA expression and protein levels of nucleotide-binding oligomerization domain-containing proteins (NOD1, NOD2) and NLR family, pyrin domain containing 3 protein (NLRP3) were significantly increased in the severe acute pancreatitis (SAP) models.
Title: Involvement of Nucleotide-Binding and Oligomerization Domain-Like Receptors in the Intestinal Injury of Severe Acute Pancreatitis in Rats.
NOD2 could play a role in intestinal pathophysiology not only through its inherent innate immune role but also due to its interaction with other receptors as TLR2 and the modulation of the intestinal serotonergic system decreasing SERT activity and expression.
Title: NOD2 Modulates Serotonin Transporter and Interacts with TLR2 and TLR4 in Intestinal Epithelial Cells.
in rat peritoneal mast cells the ingested cargo can, through interruptions of the phagosome membrane, interact directly with NOD1 and NOD2 proteins, which act as switches in the process of cytokine production.
Title: NOD1 and NOD2 Interact with the Phagosome Cargo in Mast Cells: A Detailed Morphological Evidence.
Nod2-Rip2-NFkappaB signaling involved in the small intestinal inflammatory injury caused by muramyl dipeptide which is transported through PepT1.
Title: Nod2-Rip2 Signaling Contributes to Intestinal Injury Induced by Muramyl Dipeptide Via Oligopeptide Transporter in Rats.
Mammary innate immune responses were activated after Staphylococcus aureus inoculation. TLR2, NOD2, and inflammatory cytokines (TNF-alpha, IL-1beta, IL-6, CXCL1, IL-10, TGF-beta1, and IFN-gamma) are involved in the response to mastitis induced by S. aureus.
Title: Characterization of TLR2, NOD2, and related cytokines in mammary glands infected by Staphylococcus aureus in a rat model.
studies demonstrate that HuR acts as a key posttranscriptional regulator of NOD2 expression, suggesting that targeting of HuR-NOD2 signaling might be crucial for the treatment of DN
Title: Identification of NOD2 as a novel target of RNA-binding protein HuR: evidence from NADPH oxidase-mediated HuR signaling in diabetic nephropathy.
NOD2 triggering induces CD4 antigen-negative dendritic cells to mature and produce high levels of interleukin (IL)-12p40, low levels of IL-10, and tumor necrosis factor-alpha.
Title: Differential pattern recognition receptor expression but stereotyped responsiveness in rat spleen dendritic cell subsets.
The NOD2 may play an important role in the up-regulation and activation of NF-kappaB during inflammation reactions in acute pancreatitis.
Title: Expression of NOD2 in a rat model of acute pancreatitis.

Submit: New GeneRIF Correction See all GeneRIFs (14)

General gene information

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Gene Ontology Provided by RGD

Function	Evidence Code	Pubs
enables ATP binding	IEA Inferred from Electronic Annotation more info
enables CARD domain binding	ISO Inferred from Sequence Orthology more info
enables Hsp70 protein binding	ISO Inferred from Sequence Orthology more info
enables Hsp90 protein binding	ISO Inferred from Sequence Orthology more info
enables actin binding	ISO Inferred from Sequence Orthology more info
enables enzyme binding	ISO Inferred from Sequence Orthology more info
enables hydrolase activity	IEA Inferred from Electronic Annotation more info
enables muramyl dipeptide binding	IDA Inferred from Direct Assay more info	PubMed
enables muramyl dipeptide binding	ISO Inferred from Sequence Orthology more info
enables pattern recognition receptor activity	ISO Inferred from Sequence Orthology more info
enables peptidoglycan binding	ISO Inferred from Sequence Orthology more info
enables protein kinase binding	ISO Inferred from Sequence Orthology more info
enables protein-containing complex binding	ISO Inferred from Sequence Orthology more info
enables scaffold protein binding	IEA Inferred from Electronic Annotation more info
enables ubiquitin binding	ISO Inferred from Sequence Orthology more info

Process	Evidence Code	Pubs
acts_upstream_of ERK1 and ERK2 cascade	ISO Inferred from Sequence Orthology more info
acts_upstream_of JNK cascade	ISO Inferred from Sequence Orthology more info
acts_upstream_of MAPK cascade	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within activation of immune response	ISO Inferred from Sequence Orthology more info
involved_in adaptive immune response	IEA Inferred from Electronic Annotation more info
involved_in antibacterial innate immune response	ISO Inferred from Sequence Orthology more info
acts_upstream_of biosynthetic process of antibacterial peptides active against Gram-positive bacteria	ISO Inferred from Sequence Orthology more info
involved_in cellular response to lipopolysaccharide	ISO Inferred from Sequence Orthology more info
involved_in cellular response to muramyl dipeptide	ISO Inferred from Sequence Orthology more info
involved_in cellular response to organic cyclic compound	IEP Inferred from Expression Pattern more info	PubMed
involved_in cellular response to peptidoglycan	IEP Inferred from Expression Pattern more info	PubMed
acts_upstream_of_or_within cellular response to peptidoglycan	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within defense response to Gram-positive bacterium	ISO Inferred from Sequence Orthology more info
involved_in defense response to bacterium	IBA Inferred from Biological aspect of Ancestor more info
involved_in defense response to bacterium	ISO Inferred from Sequence Orthology more info
involved_in detection of bacterium	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within detection of muramyl dipeptide	ISO Inferred from Sequence Orthology more info
involved_in detection of muramyl dipeptide	ISO Inferred from Sequence Orthology more info
acts_upstream_of establishment of localization in cell	ISO Inferred from Sequence Orthology more info
involved_in host-mediated regulation of intestinal microbiota composition	ISO Inferred from Sequence Orthology more info
involved_in inflammatory response	IEA Inferred from Electronic Annotation more info
involved_in innate immune response	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within innate immune response in mucosa	ISO Inferred from Sequence Orthology more info
involved_in intestinal stem cell homeostasis	ISO Inferred from Sequence Orthology more info
involved_in intracellular signal transduction	IBA Inferred from Biological aspect of Ancestor more info
involved_in intracellular signal transduction	ISO Inferred from Sequence Orthology more info
involved_in maintenance of gastrointestinal epithelium	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within negative regulation of NF-kappaB transcription factor activity	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within negative regulation of T cell mediated immunity	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of cellular defense response	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within negative regulation of inflammatory response to antigenic stimulus	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within negative regulation of interleukin-12 production	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within negative regulation of interleukin-18 production	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within negative regulation of interleukin-2 production	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of macrophage apoptotic process	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within negative regulation of macrophage cytokine production	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within negative regulation of toll-like receptor 2 signaling pathway	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within negative regulation of tumor necrosis factor production	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within negative regulation of type II interferon production	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within nucleotide-binding oligomerization domain containing 2 signaling pathway	ISO Inferred from Sequence Orthology more info
involved_in nucleotide-binding oligomerization domain containing 2 signaling pathway	ISO Inferred from Sequence Orthology more info
involved_in pattern recognition receptor signaling pathway	ISO Inferred from Sequence Orthology more info
acts_upstream_of peptidyl-tyrosine phosphorylation	ISO Inferred from Sequence Orthology more info
acts_upstream_of phagocytosis	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of B cell activation	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within positive regulation of ERK1 and ERK2 cascade	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of ERK1 and ERK2 cascade	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within positive regulation of JNK cascade	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within positive regulation of MAPK cascade	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of MAPK cascade	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within positive regulation of NF-kappaB transcription factor activity	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of NF-kappaB transcription factor activity	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of Notch signaling pathway	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within positive regulation of antibacterial peptide biosynthetic process	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of autophagy	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within positive regulation of biosynthetic process of antibacterial peptides active against Gram-positive bacteria	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of canonical NF-kappaB signal transduction	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within positive regulation of canonical NF-kappaB signal transduction	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of canonical NF-kappaB signal transduction	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of cell population proliferation	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of cytokine production involved in immune response	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of cytokine production involved in inflammatory response	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of dendritic cell antigen processing and presentation	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of dendritic cell cytokine production	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of epithelial cell proliferation	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within positive regulation of humoral immune response mediated by circulating immunoglobulin	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within positive regulation of innate immune response	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of innate immune response	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of interleukin-1 beta production	ISO Inferred from Sequence Orthology more info
acts_upstream_of positive regulation of interleukin-10 production	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within positive regulation of interleukin-12 production	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of interleukin-17 production	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within positive regulation of interleukin-6 production	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of interleukin-6 production	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of interleukin-8 production	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within positive regulation of macrophage cytokine production	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of mitophagy	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of monocyte chemotactic protein-1 production	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of non-canonical NF-kappaB signal transduction	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within positive regulation of peptidyl-tyrosine phosphorylation	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within positive regulation of phagocytosis	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of protein K63-linked ubiquitination	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of protein ubiquitination	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of pyroptotic inflammatory response	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within positive regulation of stress-activated MAPK cascade	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of transcription by RNA polymerase II	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within positive regulation of tumor necrosis factor production	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of tumor necrosis factor production	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of type 2 immune response	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within positive regulation of xenophagy	ISO Inferred from Sequence Orthology more info
involved_in regulation of appetite	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within regulation of inflammatory response	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within regulation of neutrophil chemotaxis	ISO Inferred from Sequence Orthology more info
involved_in response to endoplasmic reticulum stress	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within response to exogenous dsRNA	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within response to lipopolysaccharide	ISO Inferred from Sequence Orthology more info
involved_in response to muramyl dipeptide	IBA Inferred from Biological aspect of Ancestor more info
involved_in response to muramyl dipeptide	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within response to muramyl dipeptide	ISO Inferred from Sequence Orthology more info
involved_in response to muramyl dipeptide	ISO Inferred from Sequence Orthology more info
involved_in response to nutrient	IEP Inferred from Expression Pattern more info	PubMed
acts_upstream_of_or_within response to peptidoglycan	ISO Inferred from Sequence Orthology more info
acts_upstream_of stress-activated MAPK cascade	ISO Inferred from Sequence Orthology more info
involved_in temperature homeostasis	ISO Inferred from Sequence Orthology more info
acts_upstream_of toll-like receptor 2 signaling pathway	ISO Inferred from Sequence Orthology more info
acts_upstream_of xenophagy	ISO Inferred from Sequence Orthology more info

Component	Evidence Code	Pubs
located_in Golgi apparatus	IEA Inferred from Electronic Annotation more info
located_in Golgi apparatus	ISO Inferred from Sequence Orthology more info
located_in basolateral plasma membrane	ISO Inferred from Sequence Orthology more info
part_of canonical inflammasome complex	IEA Inferred from Electronic Annotation more info
located_in cell surface	ISO Inferred from Sequence Orthology more info
located_in cytoplasm	ISO Inferred from Sequence Orthology more info
located_in cytoskeleton	ISO Inferred from Sequence Orthology more info
is_active_in cytosol	IBA Inferred from Biological aspect of Ancestor more info
is_active_in cytosol	ISO Inferred from Sequence Orthology more info
located_in cytosol	ISO Inferred from Sequence Orthology more info
is_active_in extrinsic component of plasma membrane	ISO Inferred from Sequence Orthology more info
located_in mitochondrion	IEA Inferred from Electronic Annotation more info
located_in neuronal cell body	IEA Inferred from Electronic Annotation more info
located_in phagocytic vesicle	ISO Inferred from Sequence Orthology more info
is_active_in plasma membrane	ISO Inferred from Sequence Orthology more info
located_in plasma membrane	ISO Inferred from Sequence Orthology more info
part_of protein-containing complex	ISO Inferred from Sequence Orthology more info
located_in vesicle	ISO Inferred from Sequence Orthology more info

General protein information

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Preferred Names: nucleotide-binding oligomerization domain-containing protein 2

Names: caspase recruitment domain family, member 15

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_001414911.2 → NP_001401840.1 nucleotide-binding oligomerization domain-containing protein 2

Status: VALIDATED

Source sequence(s)

JAXUCZ010000019

UniProtKB/TrEMBL

A6KD97, D4A5W3

Related

ENSRNOP00000073236.2, ENSRNOT00000080964.3

RefSeqs of Annotated Genomes: GCF_036323735.1-RS_2024_02

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCr8

Genomic

NC_086037.1 Reference GRCr8

Range

34555832..34596281 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_063277867.1 → XP_063133937.1 nucleotide-binding oligomerization domain-containing protein 2 isoform X3

UniProtKB/TrEMBL

A6KD97, D4A5W3
XM_063277866.1 → XP_063133936.1 nucleotide-binding oligomerization domain-containing protein 2 isoform X2

UniProtKB/TrEMBL

A6KD97, D4A5W3
XM_008772373.4 → XP_008770595.3 nucleotide-binding oligomerization domain-containing protein 2 isoform X1

UniProtKB/TrEMBL

A6KD97, D4A5W3
XM_063277868.1 → XP_063133938.1 nucleotide-binding oligomerization domain-containing protein 2 isoform X4
XM_039097571.1 → XP_038953499.1 nucleotide-binding oligomerization domain-containing protein 2 isoform X5

UniProtKB/TrEMBL

A6KD97, D4A5W3

Conserved Domains (4) summary

pfam05729
Location:266 → 436

NACHT; NACHT domain

pfam17776
Location:576 → 729

NLRC4_HD2; NLRC4 helical domain HD2

pfam17779
Location:518 → 574

NOD2_WH; NOD2 winged helix domain

cl14633
Location:7 → 87

DD; Death Domain Superfamily of protein-protein interaction domains

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

NM_001106172.2: Suppressed sequence

Description

NM_001106172.2: This RefSeq was removed because currently there is insufficient support for the transcript and the protein.