NOD2_PANTR
ID NOD2_PANTR Reviewed; 1040 AA.
AC Q53B87;
DT 05-JUL-2005, integrated into UniProtKB/Swiss-Prot.
DT 24-MAY-2005, sequence version 1.
DT 03-AUG-2022, entry version 94.
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 Pan troglodytes (Chimpanzee).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Pan.
OX NCBI_TaxID=9598;
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: Involved in gastrointestinal immunity. Upon stimulation by
CC muramyl dipeptide (MDP), a fragment of bacterial peptidoglycan, binds
CC the proximal adapter receptor-interacting RIPK2, which recruits
CC ubiquitin ligases as XIAP, BIRC2, BIRC3, INAVA and the LUBAC complex,
CC triggering activation of MAP kinases and activation of NF-kappa-B
CC signaling. This in turn leads to the transcriptional activation of
CC hundreds of genes involved in immune response. Required for MDP-induced
CC NLRP1-dependent CASP1 activation and IL1B release in macrophages.
CC Component of an autophagy-mediated antibacterial pathway together with
CC ATG16L1. Also plays a role in sensing single-stranded RNA (ssRNA) from
CC viruses. Interacts with mitochondrial antiviral signaling/MAVS, leading
CC to activation of interferon regulatory factor-3/IRF3 and expression of
CC type I interferon. {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}.
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DR EMBL; AY594173; AAS89991.1; -; Genomic_DNA.
DR EMBL; AY594162; AAS89991.1; JOINED; Genomic_DNA.
DR EMBL; AY594163; AAS89991.1; JOINED; Genomic_DNA.
DR EMBL; AY594164; AAS89991.1; JOINED; Genomic_DNA.
DR EMBL; AY594165; AAS89991.1; JOINED; Genomic_DNA.
DR EMBL; AY594166; AAS89991.1; JOINED; Genomic_DNA.
DR EMBL; AY594167; AAS89991.1; JOINED; Genomic_DNA.
DR EMBL; AY594168; AAS89991.1; JOINED; Genomic_DNA.
DR EMBL; AY594169; AAS89991.1; JOINED; Genomic_DNA.
DR EMBL; AY594170; AAS89991.1; JOINED; Genomic_DNA.
DR EMBL; AY594171; AAS89991.1; JOINED; Genomic_DNA.
DR EMBL; AY594172; AAS89991.1; JOINED; Genomic_DNA.
DR AlphaFoldDB; Q53B87; -.
DR SMR; Q53B87; -.
DR STRING; 9598.ENSPTRP00000013836; -.
DR PaxDb; Q53B87; -.
DR eggNOG; KOG4308; Eukaryota.
DR InParanoid; Q53B87; -.
DR Proteomes; UP000002277; Unplaced.
DR GO; GO:0016323; C:basolateral plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005856; C:cytoskeleton; 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:0071222; P:cellular response to lipopolysaccharide; ISS:UniProtKB.
DR GO; GO:0071225; P:cellular response to muramyl dipeptide; ISS:UniProtKB.
DR GO; GO:0045087; P:innate immune response; ISS:UniProtKB.
DR GO; GO:0070431; P:nucleotide-binding oligomerization domain containing 2 signaling pathway; 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 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; 1.
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; Membrane; Nucleotide-binding; Reference proteome;
KW Repeat; Ubl conjugation.
FT CHAIN 1..1040
FT /note="Nucleotide-binding oligomerization domain-containing
FT protein 2"
FT /id="PRO_0000144092"
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; 115298 MW; BF0496FFF39D0428 CRC64;
MGEEGGSVSH DEEERASVLL GHSLGCEMCS QEAFQAQRSQ LVELLVSGSL EGFESVLDWL
LSWEVLSWED YEGFHLLGQP LSHLARRLLD TVWNKGTWAC QKLIAAAQEA QADSQSPKLH
GCWDPHSLHP ARDLQSHRPA IVRRLHNHVE NMLDLAWERG FVSQYECDEI RLPIFTPSQR
ARRLLDLATV KANGLAAFLL QHVQELPVPL ALPLEAATCK KYMAKLRTTV SAQSRFLSTY
DGAETLCLED IYTENVLEVW ADVGMAGPPQ 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 FLLHATPPDS ASQGLGPSLL
RGRLPTLLHL GRLALWGLGM CCYVFSAQQL QAAQVSPDDI SLGFLVRAKG VVPGSTAPLE
FLHITFQCFF AAFYLALSAD VPPALLRHLF NCGRPGNSPM ARLLPTMCIQ GSEGKDSSVA
ALLQKAEPHN LQITAAFLAG LLSREHWGLL AECQTSEKAL LRRQACARWC LARSLRKHFH
SIPPAAPGEA KSVHAMPGFI WLIRSLYEMQ EERLARKAAR GLNVGHLKLT FCSVGPAECA
ALAFVLQHLR RPVALQLDYN SVGDIGVEQL LPCLGVCKAL YLRDNNISDR GICKLIECAL
HCEQLQKLAL FNNKLTDGCA HSMAKLLACR QNFLALRLGN NYITAAGAQV LAQGLRGNTS
LQFLGFWGNR VGDEGAQALA EALGDHQSLR WLSLVGNNIG SVGAQALALM LAKNVMLEEL
CLEENHLQDE GVCSLAEGLK KNSSLKILKL SNNCITYLGA EALLQALERN DTILEVWLRG
NTFSLEEVDK LGCRDTRLLL
