NOD2_BOVIN
ID NOD2_BOVIN Reviewed; 1013 AA.
AC Q6E804;
DT 26-MAY-2009, integrated into UniProtKB/Swiss-Prot.
DT 16-AUG-2004, sequence version 1.
DT 03-AUG-2022, entry version 140.
DE RecName: Full=Nucleotide-binding oligomerization domain-containing protein 2;
DE AltName: Full=Caspase recruitment domain-containing protein 15;
GN Name=NOD2; Synonyms=CARD15;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], AND VARIANTS ALA-70; MET-196;
RP ASN-505; GLN-681; HIS-689; ARG-733 AND LEU-1007.
RX PubMed=16897345; DOI=10.1007/s00335-005-0148-2;
RA Taylor K.H., Taylor J.F., White S.N., Womack J.E.;
RT "Identification of genetic variation and putative regulatory regions in
RT bovine CARD15.";
RL Mamm. Genome 17:892-901(2006).
CC -!- FUNCTION: Pattern recognition receptor (PRR) that detects bacterial
CC peptidoglycan fragments and other danger signals and plays an important
CC role in gastrointestinal immunity. Upon stimulation by muramyl
CC dipeptide (MDP), a fragment of bacterial peptidoglycan, binds the
CC proximal adapter receptor-interacting RIPK2, which recruits ubiquitin
CC ligases as XIAP, BIRC2, BIRC3, INAVA and the LUBAC complex, triggering
CC activation of MAP kinases and activation of NF-kappa-B signaling. This
CC in turn leads to the transcriptional activation of hundreds of genes
CC involved in immune response. Required for MDP-induced NLRP1-dependent
CC CASP1 activation and IL1B release in macrophages. Component of an
CC autophagy-mediated antibacterial pathway together with ATG16L1. Plays
CC also a role in sensing single-stranded RNA (ssRNA) from viruses.
CC Interacts with mitochondrial antiviral signaling/MAVS, leading to
CC activation of interferon regulatory factor-3/IRF3 and expression of
CC type I interferon. Besides recognizing pathogens, participates in
CC surveillance of cellular homeostasis through sensing and binding to the
CC cytosolic metabolite sphingosine-1-phosphate and then initating
CC inflammation process. {ECO:0000250|UniProtKB:Q9HC29}.
CC -!- SUBUNIT: Component of a signaling complex consisting of ARHGEF2, NOD2
CC and RIPK2. Interacts (via CARD domain) with RIPK2 (via CARD domain).
CC Interacts with ATG16L1. Interacts (via NACHT domain) with CARD9.
CC Interacts with ANKRD17 (via N-terminus). Interacts with HSPA1A; the
CC interaction enhances NOD2 stability. Interacts (via both CARD domains)
CC with HSP90; the interaction enhances NOD2 stability. Interacts (via
CC CARD domain) with SOCS3; the interaction promotes NOD2 degradation.
CC Interacts (via CARD domain) with ERBBI2P; the interaction inhibits
CC activation of NOD2. Interacts (via CARD domain) with CASP1; this
CC interaction leads to IL1B processing. Also interacts with CASP4.
CC Interacts with NLRP1; this interaction is enhanced in the presence of
CC muramyl dipeptide (MDP) and leads to increased IL1B release. Interacts
CC with MAPKBP1; the interaction is enhanced in the presence of muramyl
CC dipeptide (MDP). Interacts with INAVA; the interaction takes place upon
CC PRR stimulation. Interacts with ANKHD1, C10ORF67, CHMP5, DOCK7, ENTR1,
CC KRT15, LDOC1, PPP1R12C, PPP2R3B, TRIM41 and VIM (By similarity).
CC Interacts with NLRP12; this interaction promotes degradation of NOD2
CC through the ubiquitin-proteasome pathway (By similarity).
CC {ECO:0000250|UniProtKB:Q9HC29}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q9HC29}.
CC Membrane {ECO:0000250|UniProtKB:Q9HC29}. Basolateral cell membrane
CC {ECO:0000250|UniProtKB:Q9HC29}.
CC -!- DOMAIN: The ATG16L1-binding motif mediates interaction with ATG16L1.
CC {ECO:0000250}.
CC -!- DOMAIN: Intramolecular interactions between the N-terminal moiety and
CC the leucine-rich repeats (LRR) may be important for autoinhibition in
CC the absence of activating signal. In the absence of LRRs, the protein
CC becomes a constitutive activator of CASP1 cleavage and proIL1B
CC processing. {ECO:0000250|UniProtKB:Q9HC29}.
CC -!- PTM: Polyubiquitinated following MDP stimulation, leading to
CC proteasome-mediated degradation. {ECO:0000250|UniProtKB:Q9HC29}.
CC -!- PTM: Palmitoylated. Palmitoylation is required for proper recruitment
CC to the bacterial entry site and hence for proper signaling upon cognate
CC peptidoglycan detection. {ECO:0000250|UniProtKB:Q9Y239}.
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DR EMBL; AY518737; AAS09824.1; -; mRNA.
DR EMBL; AY518748; AAS09826.1; -; Genomic_DNA.
DR EMBL; AY518739; AAS09826.1; JOINED; Genomic_DNA.
DR EMBL; AY518740; AAS09826.1; JOINED; Genomic_DNA.
DR EMBL; AY518741; AAS09826.1; JOINED; Genomic_DNA.
DR EMBL; AY518742; AAS09826.1; JOINED; Genomic_DNA.
DR EMBL; AY518743; AAS09826.1; JOINED; Genomic_DNA.
DR EMBL; AY518744; AAS09826.1; JOINED; Genomic_DNA.
DR EMBL; AY518745; AAS09826.1; JOINED; Genomic_DNA.
DR EMBL; AY518746; AAS09826.1; JOINED; Genomic_DNA.
DR EMBL; AY518747; AAS09826.1; JOINED; Genomic_DNA.
DR RefSeq; NP_001002889.1; NM_001002889.1.
DR RefSeq; XP_005218524.1; XM_005218467.3.
DR RefSeq; XP_010812724.1; XM_010814422.2.
DR RefSeq; XP_015331193.1; XM_015475707.1.
DR AlphaFoldDB; Q6E804; -.
DR SMR; Q6E804; -.
DR STRING; 9913.ENSBTAP00000027887; -.
DR CarbonylDB; Q6E804; -.
DR PaxDb; Q6E804; -.
DR PRIDE; Q6E804; -.
DR Ensembl; ENSBTAT00000027887; ENSBTAP00000027887; ENSBTAG00000020936.
DR GeneID; 444867; -.
DR KEGG; bta:444867; -.
DR CTD; 64127; -.
DR VEuPathDB; HostDB:ENSBTAG00000020936; -.
DR VGNC; VGNC:32151; NOD2.
DR eggNOG; KOG4308; Eukaryota.
DR GeneTree; ENSGT00940000160934; -.
DR HOGENOM; CLU_011291_0_0_1; -.
DR InParanoid; Q6E804; -.
DR OMA; FWGNKVG; -.
DR OrthoDB; 88836at2759; -.
DR TreeFam; TF352118; -.
DR Proteomes; UP000009136; Chromosome 18.
DR Bgee; ENSBTAG00000020936; Expressed in neutrophil and 97 other tissues.
DR ExpressionAtlas; Q6E804; baseline.
DR GO; GO:0046658; C:anchored component of plasma membrane; IEA:Ensembl.
DR GO; GO:0016323; C:basolateral plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0009986; C:cell surface; IEA:Ensembl.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005856; C:cytoskeleton; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0005794; C:Golgi apparatus; IEA:Ensembl.
DR GO; GO:0045335; C:phagocytic vesicle; IEA:Ensembl.
DR GO; GO:0032991; C:protein-containing complex; ISS:UniProtKB.
DR GO; GO:0031982; C:vesicle; ISS:UniProtKB.
DR GO; GO:0003779; F:actin binding; IEA:Ensembl.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0050700; F:CARD domain binding; IEA:Ensembl.
DR GO; GO:0030544; F:Hsp70 protein binding; IEA:Ensembl.
DR GO; GO:0051879; F:Hsp90 protein binding; IEA:Ensembl.
DR GO; GO:0032500; F:muramyl dipeptide binding; IEA:Ensembl.
DR GO; GO:0038187; F:pattern recognition receptor activity; IEA:Ensembl.
DR GO; GO:0042834; F:peptidoglycan binding; IEA:Ensembl.
DR GO; GO:0019901; F:protein kinase binding; IEA:Ensembl.
DR GO; GO:0044877; F:protein-containing complex binding; IEA:Ensembl.
DR GO; GO:0002253; P:activation of immune response; IEA:Ensembl.
DR GO; GO:0002815; P:biosynthetic process of antibacterial peptides active against Gram-positive bacteria; IEA:Ensembl.
DR GO; GO:0071222; P:cellular response to lipopolysaccharide; ISS:UniProtKB.
DR GO; GO:0071225; P:cellular response to muramyl dipeptide; ISS:UniProtKB.
DR GO; GO:0071224; P:cellular response to peptidoglycan; IEA:Ensembl.
DR GO; GO:0042742; P:defense response to bacterium; IBA:GO_Central.
DR GO; GO:0016045; P:detection of bacterium; IEA:Ensembl.
DR GO; GO:0032498; P:detection of muramyl dipeptide; IEA:Ensembl.
DR GO; GO:0070371; P:ERK1 and ERK2 cascade; IEA:Ensembl.
DR GO; GO:0051649; P:establishment of localization in cell; IEA:Ensembl.
DR GO; GO:0007249; P:I-kappaB kinase/NF-kappaB signaling; IEA:Ensembl.
DR GO; GO:0045087; P:innate immune response; ISS:UniProtKB.
DR GO; GO:0002227; P:innate immune response in mucosa; IEA:Ensembl.
DR GO; GO:0035556; P:intracellular signal transduction; IBA:GO_Central.
DR GO; GO:0007254; P:JNK cascade; IEA:Ensembl.
DR GO; GO:0030277; P:maintenance of gastrointestinal epithelium; IEA:Ensembl.
DR GO; GO:0002862; P:negative regulation of inflammatory response to antigenic stimulus; IEA:Ensembl.
DR GO; GO:0032689; P:negative regulation of interferon-gamma production; IEA:Ensembl.
DR GO; GO:0032695; P:negative regulation of interleukin-12 production; IEA:Ensembl.
DR GO; GO:0032701; P:negative regulation of interleukin-18 production; IEA:Ensembl.
DR GO; GO:0032703; P:negative regulation of interleukin-2 production; IEA:Ensembl.
DR GO; GO:2000110; P:negative regulation of macrophage apoptotic process; IEA:Ensembl.
DR GO; GO:0010936; P:negative regulation of macrophage cytokine production; IEA:Ensembl.
DR GO; GO:0032088; P:negative regulation of NF-kappaB transcription factor activity; IEA:Ensembl.
DR GO; GO:0002710; P:negative regulation of T cell mediated immunity; IEA:Ensembl.
DR GO; GO:0034136; P:negative regulation of toll-like receptor 2 signaling pathway; IEA:Ensembl.
DR GO; GO:0032720; P:negative regulation of tumor necrosis factor production; IEA:Ensembl.
DR GO; GO:0038061; P:NIK/NF-kappaB signaling; IEA:Ensembl.
DR GO; GO:0070431; P:nucleotide-binding oligomerization domain containing 2 signaling pathway; ISS:UniProtKB.
DR GO; GO:0018108; P:peptidyl-tyrosine phosphorylation; IEA:Ensembl.
DR GO; GO:0006909; P:phagocytosis; IEA:Ensembl.
DR GO; GO:0050871; P:positive regulation of B cell activation; IEA:Ensembl.
DR GO; GO:0006965; P:positive regulation of biosynthetic process of antibacterial peptides active against Gram-positive bacteria; IEA:Ensembl.
DR GO; GO:1900017; P:positive regulation of cytokine production involved in inflammatory response; IEA:Ensembl.
DR GO; GO:0002606; P:positive regulation of dendritic cell antigen processing and presentation; IEA:Ensembl.
DR GO; GO:0050679; P:positive regulation of epithelial cell proliferation; IEA:Ensembl.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IEA:Ensembl.
DR GO; GO:0046645; P:positive regulation of gamma-delta T cell activation; IMP:BHF-UCL.
DR GO; GO:0002925; P:positive regulation of humoral immune response mediated by circulating immunoglobulin; IEA:Ensembl.
DR GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; IBA:GO_Central.
DR GO; GO:0045089; P:positive regulation of innate immune response; IEA:Ensembl.
DR GO; GO:0032731; P:positive regulation of interleukin-1 beta production; IEA:Ensembl.
DR GO; GO:0032733; P:positive regulation of interleukin-10 production; IEA:Ensembl.
DR GO; GO:0032735; P:positive regulation of interleukin-12 production; IEA:Ensembl.
DR GO; GO:0032740; P:positive regulation of interleukin-17 production; IEA:Ensembl.
DR GO; GO:0032755; P:positive regulation of interleukin-6 production; IEA:Ensembl.
DR GO; GO:0032757; P:positive regulation of interleukin-8 production; IEA:Ensembl.
DR GO; GO:0046330; P:positive regulation of JNK cascade; IEA:Ensembl.
DR GO; GO:0060907; P:positive regulation of macrophage cytokine production; IEA:Ensembl.
DR GO; GO:0043406; P:positive regulation of MAP kinase activity; IEA:Ensembl.
DR GO; GO:0071639; P:positive regulation of monocyte chemotactic protein-1 production; IEA:Ensembl.
DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; ISS:UniProtKB.
DR GO; GO:1901224; P:positive regulation of NIK/NF-kappaB signaling; IEA:Ensembl.
DR GO; GO:0051770; P:positive regulation of nitric-oxide synthase biosynthetic process; IEA:Ensembl.
DR GO; GO:0045747; P:positive regulation of Notch signaling pathway; IEA:Ensembl.
DR GO; GO:0050731; P:positive regulation of peptidyl-tyrosine phosphorylation; IEA:Ensembl.
DR GO; GO:0050766; P:positive regulation of phagocytosis; IEA:Ensembl.
DR GO; GO:0043552; P:positive regulation of phosphatidylinositol 3-kinase activity; IEA:Ensembl.
DR GO; GO:2000363; P:positive regulation of prostaglandin-E synthase activity; IEA:Ensembl.
DR GO; GO:0060585; P:positive regulation of prostaglandin-endoperoxide synthase activity; IEA:Ensembl.
DR GO; GO:1902523; P:positive regulation of protein K63-linked ubiquitination; IEA:Ensembl.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISS:UniProtKB.
DR GO; GO:0032760; P:positive regulation of tumor necrosis factor production; IEA:Ensembl.
DR GO; GO:0002830; P:positive regulation of type 2 immune response; ISS:BHF-UCL.
DR GO; GO:1904417; P:positive regulation of xenophagy; IEA:Ensembl.
DR GO; GO:0090022; P:regulation of neutrophil chemotaxis; IEA:Ensembl.
DR GO; GO:0043330; P:response to exogenous dsRNA; IEA:Ensembl.
DR GO; GO:0032495; P:response to muramyl dipeptide; IDA:BHF-UCL.
DR GO; GO:0034134; P:toll-like receptor 2 signaling pathway; IEA:Ensembl.
DR GO; GO:0098792; P:xenophagy; IEA:Ensembl.
DR Gene3D; 1.10.533.10; -; 2.
DR Gene3D; 3.40.50.300; -; 1.
DR Gene3D; 3.80.10.10; -; 1.
DR InterPro; IPR001315; CARD.
DR InterPro; IPR011029; DEATH-like_dom_sf.
DR InterPro; IPR001611; Leu-rich_rpt.
DR InterPro; IPR032675; LRR_dom_sf.
DR InterPro; IPR007111; NACHT_NTPase.
DR InterPro; IPR041267; NLRP_HD2.
DR InterPro; IPR041075; NOD2_WH.
DR InterPro; IPR027417; P-loop_NTPase.
DR Pfam; PF00619; CARD; 2.
DR Pfam; PF13516; LRR_6; 4.
DR Pfam; PF05729; NACHT; 1.
DR Pfam; PF17776; NLRC4_HD2; 1.
DR Pfam; PF17779; NOD2_WH; 1.
DR SUPFAM; SSF47986; SSF47986; 2.
DR SUPFAM; SSF52540; SSF52540; 1.
DR PROSITE; PS50209; CARD; 2.
DR PROSITE; PS51450; LRR; 5.
DR PROSITE; PS50837; NACHT; 1.
PE 2: Evidence at transcript level;
KW ATP-binding; Cell membrane; Cytoplasm; Immunity; Innate immunity;
KW Leucine-rich repeat; Lipoprotein; Membrane; Nucleotide-binding; Palmitate;
KW Reference proteome; Repeat; Ubl conjugation.
FT CHAIN 1..1013
FT /note="Nucleotide-binding oligomerization domain-containing
FT protein 2"
FT /id="PRO_0000375804"
FT DOMAIN 1..95
FT /note="CARD 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00046"
FT DOMAIN 99..191
FT /note="CARD 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00046"
FT DOMAIN 266..591
FT /note="NACHT"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00136"
FT REPEAT 764..785
FT /note="LRR 1"
FT REPEAT 789..809
FT /note="LRR 2"
FT REPEAT 817..838
FT /note="LRR 3"
FT REPEAT 845..866
FT /note="LRR 4"
FT REPEAT 873..893
FT /note="LRR 5"
FT REPEAT 901..922
FT /note="LRR 6"
FT REPEAT 929..949
FT /note="LRR 7"
FT REPEAT 957..978
FT /note="LRR 8"
FT REPEAT 985..1008
FT /note="LRR 9"
FT REGION 82..106
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 214..247
FT /note="Required for CARD9 binding"
FT /evidence="ECO:0000250|UniProtKB:Q9HC29"
FT MOTIF 36..50
FT /note="ATG16L1-binding motif"
FT BINDING 272..279
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00136"
FT VARIANT 70
FT /note="T -> A"
FT /evidence="ECO:0000269|PubMed:16897345"
FT VARIANT 196
FT /note="V -> M"
FT /evidence="ECO:0000269|PubMed:16897345"
FT VARIANT 505
FT /note="T -> N"
FT /evidence="ECO:0000269|PubMed:16897345"
FT VARIANT 681
FT /note="R -> Q"
FT /evidence="ECO:0000269|PubMed:16897345"
FT VARIANT 689
FT /note="R -> H"
FT /evidence="ECO:0000269|PubMed:16897345"
FT VARIANT 733
FT /note="C -> R"
FT /evidence="ECO:0000269|PubMed:16897345"
FT VARIANT 1007
FT /note="Q -> L"
FT /evidence="ECO:0000269|PubMed:16897345"
SQ SEQUENCE 1013 AA; 112800 MW; ACAE5F8C4BEFE11B CRC64;
MCAQDAFQTQ RSQLVELLVS GSLEGFESIL DRLLSREVLS WEDYEGLSLV GQPISHLARR
LLDTIWNKGT WGCEQLTAAV REAQADSQPP ELPSSWDPHS PHPARDLQSH RPAIVRRLYG
HVEGVLDLTQ QRGFISQYET DEIRRPIFTS SQRARRLLDL ATVKANGLAA FLLQCIQELP
VPLALPFEDA ACKKYVSKLR TVISAQSRFL STYDGAENLC LEEVYTENVL EIQMEVGMAG
PSQQSPTTLG LEELFSTRDH FNKEADTVLV VGEAGSGKST LLQQLHLLWA SGRAFQEFLF
VFPFSCRQLQ CLVKPLSMRT LLFEHCCWPD LGPQDVFQVL LDHPERILLT FDGFDEFRFR
FTDQERHCCP TAPTSVQSLL FNLLQGNLLK NARKVLTSRP SAVSASLRKH VRTELSLKGF
SEEGIELYLR KRHREPGVAD RLLCLLRATS ALHGLCHLPV FSWMVSKCHE ELLLQGRGSP
KTTTDMYLLI LRHFLLHASP LPLATHGLGP SLIQGRLPTL LHLGRLALWG LGTCCYVFSA
KQLQAAHVDS EDLSLGFLVL AKRVVPGSTA PLEFLHITFQ CFFAAFYLAL SADTPPSSLR
HLFQDHRPES SPLARVLPKL FLRGSRCREG SVAALLQGAE PHNLQITGAF LAGLLSQEHR
SLLAECQASE TALLRRWDCV RRCLTRSLRE HFRSIPPALP GEAKSMHALP GFLWLIRSLY
EMQEERLARE AVCRLNVGHL KLTFCGVGPA ECAALAFVLR HLRRPVALQL DHNSVGDIGV
EQLLPCLGVC KALYLRDNNI SDRGICKLVE HALRCEQLQK LALFNNKLTD GCAHSMARLL
ACKQNFLALR LGNNHITAAG AEVLAQGLRT NNSLQFLGFW GNQVGDEGAQ ALAAALGDHQ
SLRWLSLVGN NIGSVGAQAL ALMLEKNMAL EELCLEENHV QDEGVCFLAK GLARNSSLKV
LKLSNNHISS LGAEALLRAL EKNDTILEVW LRGNTFSPEE IEKLSHQDTR LLL
