Seroatlas · Human Serome Atlas

NOD2

Nucleotide-binding oligomerization domain-containing protein 2

Also known as: BLAU, CARD15, CD, CLR16.3, IBD1, NLRC2, NOD2_HUMAN, PSORAS1

Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene

Protein identityUniProt · HPA

UniProt accession: Q9HC29
Gene: NOD2
Ensembl: ENSG00000167207
Chromosome: 16
Canonical length: 1040 aa
Protein class: Disease related genes, FDA approved drug targets, Human disease related genes, Predicted intracellular proteins
Subcellular location: Golgi apparatus,Cytosol
Quaternary structure: Homooligomer

OverviewNCBI Gene

This gene is a member of the Nod1/Apaf-1 family and encodes a protein with two caspase recruitment (CARD) domains and six leucine-rich repeats (LRRs). The protein is primarily expressed in the peripheral blood leukocytes. It plays a role in the immune response to intracellular bacterial lipopolysaccharides (LPS) by recognizing the muramyl dipeptide (MDP) derived from them and activating the NFKB protein. Mutations in this gene have been associated with Crohn disease and Blau syndrome. Alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, Jun 2014]

Canonical amino-acid sequenceUniProt

1040 residues, UniProt reviewed canonical sequence.

>Q9HC29|NOD2
     1  MGEEGGSASH DEEERASVLL GHSPGCEMCS QEAFQAQRSQ LVELLVSGSL EGFESVLDWL
    61  LSWEVLSWED YEGFHLLGQP LSHLARRLLD TVWNKGTWAC QKLIAAAQEA QADSQSPKLH
   121  GCWDPHSLHP ARDLQSHRPA IVRRLHSHVE NMLDLAWERG FVSQYECDEI RLPIFTPSQR
   181  ARRLLDLATV KANGLAAFLL QHVQELPVPL ALPLEAATCK KYMAKLRTTV SAQSRFLSTY
   241  DGAETLCLED IYTENVLEVW ADVGMAGPPQ KSPATLGLEE LFSTPGHLND DADTVLVVGE
   301  AGSGKSTLLQ RLHLLWAAGQ DFQEFLFVFP FSCRQLQCMA KPLSVRTLLF EHCCWPDVGQ
   361  EDIFQLLLDH PDRVLLTFDG FDEFKFRFTD RERHCSPTDP TSVQTLLFNL LQGNLLKNAR
   421  KVVTSRPAAV SAFLRKYIRT EFNLKGFSEQ GIELYLRKRH HEPGVADRLI RLLQETSALH
   481  GLCHLPVFSW MVSKCHQELL LQEGGSPKTT TDMYLLILQH FLLHATPPDS ASQGLGPSLL
   541  RGRLPTLLHL GRLALWGLGM CCYVFSAQQL QAAQVSPDDI SLGFLVRAKG VVPGSTAPLE
   601  FLHITFQCFF AAFYLALSAD VPPALLRHLF NCGRPGNSPM ARLLPTMCIQ ASEGKDSSVA
   661  ALLQKAEPHN LQITAAFLAG LLSREHWGLL AECQTSEKAL LRRQACARWC LARSLRKHFH
   721  SIPPAAPGEA KSVHAMPGFI WLIRSLYEMQ EERLARKAAR GLNVGHLKLT FCSVGPTECA
   781  ALAFVLQHLR RPVALQLDYN SVGDIGVEQL LPCLGVCKAL YLRDNNISDR GICKLIECAL
   841  HCEQLQKLAL FNNKLTDGCA HSMAKLLACR QNFLALRLGN NYITAAGAQV LAEGLRGNTS
   901  LQFLGFWGNR VGDEGAQALA EALGDHQSLR WLSLVGNNIG SVGAQALALM LAKNVMLEEL
   961  CLEENHLQDE GVCSLAEGLK KNSSLKILKL SNNCITYLGA EALLQALERN DTILEVWLRG
  1021  NTFSLEEVDK LGCRDTRLLL

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against NOD2 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability: Cell surface
Secreted: No
Transmembrane segments: 0
Mean surface accessibility (rSASA): 0.25
Highest tissue expression: 13 nTPM

Expression across tissuesHPA

Tissue

skin: 13 nTPM
vagina: 10 nTPM
bone marrow: 10 nTPM
esophagus: 9.5 nTPM
cervix: 8.4 nTPM
appendix: 4.7 nTPM

Single-cell type

monocytes: 61 nCPM
neutrophils: 58 nCPM
esophageal apical cells: 57 nCPM
esophageal suprabasal cells: 42 nCPM
cdc: 36 nCPM
suprabasal keratinocytes: 30 nCPM

Immune cell

classical monocyte: 22 nTPM
myeloid DC: 20 nTPM
intermediate monocyte: 12 nTPM
neutrophil: 10 nTPM
total PBMC: 10 nTPM
non-classical monocyte: 8.4 nTPM

Brain region

thalamus: 3.2 nTPM
medulla oblongata: 2.8 nTPM
midbrain: 2.6 nTPM
pons: 1.8 nTPM
white matter: 1.8 nTPM
spinal cord: 1.6 nTPM

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about NOD2.

Disease | AllUniProt

Conditions NOD2 is implicated in, by any mechanism.

Blau syndrome (BLAUS) MIM:186580
Inflammatory bowel disease 1 (IBD1) MIM:266600
Yao syndrome (YAOS) MIM:617321

Disease | GeneticClinVar

21 pathogenic / likely-pathogenic of 1,256 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

Blau syndrome
Regional enteritis
Behcet disease
Inborn genetic diseases
Inflammatory bowel disease 1

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance): 1.36
gnomAD pLI: 0
gnomAD missense Z: -0.45
DepMap mean gene effect: 0.09
DepMap dependency class: none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

Molecular functions

Cellular components

Protein domainsUniProt · Pfam · InterPro

KeywordsUniProt

InteractionsUniProt · HPA

Protein binding partners of NOD2 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

Antibody and autoantibody relevanceSeroatlas analysis

Seroatlas reads NOD2 as an antibody target. Whether an autoantibody or antibody against NOD2 could matter depends on whether native NOD2 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

NOD2 is annotated at the cell surface, where native NOD2 is exposed to circulating antibodies and is a prime autoantibody target that could block, deplete, or overstimulate it.

Annotation status

The present source text does not explicitly label NOD2 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

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