title: The nucleotide-binding oligomerization domain-containing protein 1 (NOD1) polymorphism S7N does not affect receptor function.
abstract: BACKGROUND
  Activation and signal transduction in the Nucleotide binding, leucine-rich repeat containing receptor (NLR) family needs to be tightly regulated in order to control the inflammatory response to exogenous and endogenous danger signals. Phosphorylation is a common cellular mechanism of regulation that has recently been shown to be important in signalling in another family of cytoplasmic pattern recognition receptors, the RIG-I like receptors. In addition, single nucleotide polymorphisms can alter receptor activity, potentially leading to dysfunction and/or a predisposition to inflammatory barrier diseases.
  
  
  RESULTS
  We have computationally analysed the N-terminus of NOD1 and found seven theoretical phosphorylation sites in, or immediately before, the NOD1 Caspase Activation Domain (CARD). Two of these, serine 7 and tyrosine 49 are also found as rare polymorphisms in the African-American population and European-American populations respectively. Mutating serine 7 to either an aspartic acid or an asparagine to mimic the potential impact of phosphorylation or the polymorphism respectively did not affect the response of NOD1 to ligand-mediated NFκB signalling.
  
  
  CONCLUSIONS
  The NOD1 polymorphism S7N does not interfere with receptor function in response to ligand stimulation.
authors.forename: Sophie
authors.initials: S
authors.lastname: Mayle
authors.affiliation: Department of Biochemistry, University of Cambridge, 80 Tennis Court Road, CB2 1GA, Cambridge, UK. tpm22@cam.ac.uk.
authors.forename: Tom P
authors.initials: TP
authors.lastname: Monie
mesh_terms: D001741:Black or African American / Q000235:genetics; D000595:Amino Acid Sequence; D001665:Binding Sites / Q000235:genetics; D057809:HEK293 Cells; D006801:Humans; D015151:Immunoblotting; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D053474:Nod1 Signaling Adaptor Protein / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D010766:Phosphorylation; D011110:Polymorphism, Genetic; D017434:Protein Structure, Tertiary; D012694:Serine / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics*; D013912:Threonine / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D014443:Tyrosine / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D044465:White People / Q000235:genetics
chemical_list: D016328:NF-kappa B; C119067:NOD1 protein, human; D053474:Nod1 Signaling Adaptor Protein; D013912:Threonine; D014443:Tyrosine; D012694:Serine; D008156:Luciferases