NOD2_HYLLA
ID NOD2_HYLLA Reviewed; 1040 AA.
AC Q53B88;
DT 05-JUL-2005, integrated into UniProtKB/Swiss-Prot.
DT 24-MAY-2005, sequence version 1.
DT 03-AUG-2022, entry version 77.
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 Hylobates lar (Common gibbon) (White-handed gibbon).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hylobatidae;
OC Hylobates.
OX NCBI_TaxID=9580;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA King K., Sheikh M., Cuthbert A.P., Fisher S.A., Mirza M.M., Sanderson J.,
RA Forbes A., Mansfield J., Roberts R.G., Mathew C.G.;
RT "Mutation, selection and evolution of the Crohn's disease susceptibility
RT gene, CARD15.";
RL Submitted (APR-2004) to the EMBL/GenBank/DDBJ databases.
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 {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}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AY594161; AAS89990.1; -; Genomic_DNA.
DR EMBL; AY594150; AAS89990.1; JOINED; Genomic_DNA.
DR EMBL; AY594151; AAS89990.1; JOINED; Genomic_DNA.
DR EMBL; AY594152; AAS89990.1; JOINED; Genomic_DNA.
DR EMBL; AY594153; AAS89990.1; JOINED; Genomic_DNA.
DR EMBL; AY594154; AAS89990.1; JOINED; Genomic_DNA.
DR EMBL; AY594155; AAS89990.1; JOINED; Genomic_DNA.
DR EMBL; AY594156; AAS89990.1; JOINED; Genomic_DNA.
DR EMBL; AY594157; AAS89990.1; JOINED; Genomic_DNA.
DR EMBL; AY594158; AAS89990.1; JOINED; Genomic_DNA.
DR EMBL; AY594159; AAS89990.1; JOINED; Genomic_DNA.
DR EMBL; AY594160; AAS89990.1; JOINED; Genomic_DNA.
DR AlphaFoldDB; Q53B88; -.
DR SMR; Q53B88; -.
DR GO; GO:0016323; C:basolateral plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0009986; C:cell surface; ISS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005856; C:cytoskeleton; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0032991; C:protein-containing complex; ISS:UniProtKB.
DR GO; GO:0031982; C:vesicle; ISS:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0050700; F:CARD domain binding; ISS:UniProtKB.
DR GO; GO:0019899; F:enzyme binding; ISS:UniProtKB.
DR GO; GO:0032500; F:muramyl dipeptide binding; ISS:UniProtKB.
DR GO; GO:0042834; F:peptidoglycan binding; ISS:UniProtKB.
DR GO; GO:0019901; F:protein kinase binding; ISS:UniProtKB.
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:0042742; P:defense response to bacterium; ISS:UniProtKB.
DR GO; GO:0016045; P:detection of bacterium; ISS:UniProtKB.
DR GO; GO:0032498; P:detection of muramyl dipeptide; ISS:UniProtKB.
DR GO; GO:0045087; P:innate immune response; ISS:UniProtKB.
DR GO; GO:0035556; P:intracellular signal transduction; ISS:UniProtKB.
DR GO; GO:0070431; P:nucleotide-binding oligomerization domain containing 2 signaling pathway; ISS:UniProtKB.
DR GO; GO:0002720; P:positive regulation of cytokine production involved in immune response; ISS:UniProtKB.
DR GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; ISS:UniProtKB.
DR GO; GO:0032731; P:positive regulation of interleukin-1 beta production; ISS:UniProtKB.
DR GO; GO:0032740; P:positive regulation of interleukin-17 production; ISS:UniProtKB.
DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; ISS:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISS:UniProtKB.
DR GO; GO:0042981; P:regulation of apoptotic process; IEA:InterPro.
DR GO; GO:0032495; P:response to muramyl dipeptide; ISS:UniProtKB.
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; 3.
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; 4.
DR PROSITE; PS50837; NACHT; 1.
PE 3: Inferred from homology;
KW ATP-binding; Cell membrane; Cytoplasm; Immunity; Innate immunity;
KW Leucine-rich repeat; Lipoprotein; Membrane; Nucleotide-binding; Palmitate;
KW Repeat; Ubl conjugation.
FT CHAIN 1..1040
FT /note="Nucleotide-binding oligomerization domain-containing
FT protein 2"
FT /id="PRO_0000144090"
FT DOMAIN 26..122
FT /note="CARD 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00046"
FT DOMAIN 126..218
FT /note="CARD 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00046"
FT DOMAIN 293..618
FT /note="NACHT"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00136"
FT REPEAT 791..812
FT /note="LRR 1"
FT REPEAT 816..839
FT /note="LRR 2"
FT REPEAT 844..865
FT /note="LRR 3"
FT REPEAT 872..884
FT /note="LRR 4"
FT REPEAT 900..920
FT /note="LRR 5"
FT REPEAT 928..949
FT /note="LRR 6"
FT REPEAT 956..976
FT /note="LRR 7"
FT REPEAT 984..1005
FT /note="LRR 8"
FT REPEAT 1012..1032
FT /note="LRR 9"
FT REGION 241..274
FT /note="Required for CARD9 binding"
FT /evidence="ECO:0000250|UniProtKB:Q9HC29"
FT MOTIF 63..77
FT /note="ATG16L1-binding motif"
FT BINDING 299..306
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00136"
SQ SEQUENCE 1040 AA; 115262 MW; 2BE59A6C96AAC0D1 CRC64;
MGEEGGSVSH DEEERASVLL GQYLGCEMCS QEAFQAQRSQ LVELLVSGSL EGFESVLDWL
LSWEVLSWED YEGFHLLGQP LSHLARRLLD TVWNKGTWAC QKLIAAAQEA QADSQSPKLH
GCWDPHSLHP ARDLQSHRPA IVRRLHSHVE GVLDLAWERG FVSQYECDEI RLPIFTPSQR
ARRLLDLATV KANGLAAFLL QHVQELPVPL ALPLEAATCR KYMAKLRTTV SAQSRFLSTY
DGAETLCLED IYTENVLEVW ADVGTAGPPP KSPATLGLEE LFSTPGHLND DADTVLVVGE
AGSGKSTLLQ RLHLLWAAGR DFQEFLFVFP FSCRQLQCMA KPLSVRTLLF EHCCWPDVGQ
EDIFQLLLDH PDRVLLTFDG FDEFKFRFTD RERHCSPTDP TSVQTLLFNL LQGNLLKNAR
KVVTSRPAAV SAFLRKYIRT EFNLKGFSEQ GIELYLRKRH REPGVADRLI RLLQATSALH
GLCHLPVFSW MVSKCHQELL LQEGGSPKTT TDMYLLILQH FLLHAIPPDS ASQGLGPSLL
RGRLPTLLHL GRLALWGLGM CCYVFSAQQL QAAQVSPDDI SLGFLVRAKG VVPGSTAPLE
FLHITFQCFF AAFYLALSAD VPPALLRHLF NCGRPGNSPV ARLLPTLCIQ GSEGKDSSVA
ALLQKAEPHN LQITAAFLAG LLSREHWGLL AECQTSEKAL LRRQACARWC LARSLRKHFH
SIPPAAPGEA KSMHAMPGFI WLIRSLYEMQ EERLARKAAR GLNVGHLKLT FCSVGPAECA
ALAFVLQHLR RPVALQLDYN SVGDIGVEQL LPCLGVCKAL YLRDNNISDR GICKLIECAL
HCEQLQKLVL FNNKLTDGCA HSMAKLLACR QNFLALRLGN NHITPAGAQV LAEGLRGNTS
LQFLGFWGNR VGDEGAQALA EALGDHQSLR WLSLVGNNIG SVGAQALALM LAKNVMLEEL
CLEENHIQDE GVCSLAEGLK KNSSLKILKL SNNCITYLGA KALLQALERN DTILEVWLRG
NIFSLEEVDK LGCRDIRLLL
