NOD1_HUMAN
ID NOD1_HUMAN Reviewed; 953 AA.
AC Q9Y239; B4DTU3; Q549U4; Q8IWF5;
DT 31-JAN-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1999, sequence version 1.
DT 03-AUG-2022, entry version 209.
DE RecName: Full=Nucleotide-binding oligomerization domain-containing protein 1;
DE AltName: Full=Caspase recruitment domain-containing protein 4;
GN Name=NOD1; Synonyms=CARD4;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Endothelial cell;
RX PubMed=10224040; DOI=10.1074/jbc.274.19.12955;
RA Bertin J., Nir W.-J., Fischer C.M., Tayber O.V., Errada P.R., Grant J.R.,
RA Keilty J.J., Gosselin M.L., Robison K.E., Wong G.H.W., Glucksmann M.A.,
RA DiStefano P.S.;
RT "Human CARD4 protein is a novel CED-4/Apaf-1 cell death family member that
RT activates NF-kappaB.";
RL J. Biol. Chem. 274:12955-12958(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1), AND MUTAGENESIS OF
RP VAL-41 AND LYS-208.
RC TISSUE=Mammary gland;
RX PubMed=10329646; DOI=10.1074/jbc.274.21.14560;
RA Inohara N., Koseki T., del Peso L., Hu Y., Yee C., Chen S., Carrio R.,
RA Merino J., Liu D., Ni J., Nunez G.;
RT "Nod1, an Apaf-1-like activator of caspase-9 and nuclear factor-kappaB.";
RL J. Biol. Chem. 274:14560-14567(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Placenta;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12853948; DOI=10.1038/nature01782;
RA Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H.,
RA Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K.,
RA Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A.,
RA Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., Sun H.,
RA Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A.,
RA Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P.,
RA Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M.,
RA Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S.,
RA Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R.,
RA Strowmatt C., Latreille P., Miller N., Johnson D., Murray J.,
RA Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W.,
RA Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A.,
RA Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E.,
RA Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E.,
RA Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A.,
RA Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A.,
RA Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R.,
RA McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H.,
RA Wilson R.K.;
RT "The DNA sequence of human chromosome 7.";
RL Nature 424:157-164(2003).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT HIS-447.
RC TISSUE=Lymph;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP FUNCTION, SUBUNIT, AND INTERACTION WITH RIPK2.
RX PubMed=10880512; DOI=10.1074/jbc.m003415200;
RA Inohara N., Koseki T., Lin J., del Peso L., Lucas P.C., Chen F.F.,
RA Ogura Y., Nunez G.;
RT "An induced proximity model for NF-kappa B activation in the Nod1/RICK and
RT RIP signaling pathways.";
RL J. Biol. Chem. 275:27823-27831(2000).
RN [7]
RP FUNCTION.
RX PubMed=11058605; DOI=10.1074/jbc.m009728200;
RA Inohara N., Ogura Y., Chen F.F., Muto A., Nunez G.;
RT "Human Nod1 confers responsiveness to bacterial lipopolysaccharides.";
RL J. Biol. Chem. 276:2551-2554(2001).
RN [8]
RP SUBCELLULAR LOCATION, AND MUTAGENESIS OF LYS-208; ASP-711; HIS-788; GLY-792
RP AND GLN-877.
RX PubMed=17970764; DOI=10.1111/j.1462-5822.2007.01062.x;
RA Kufer T.A., Kremmer E., Adam A.C., Philpott D.J., Sansonetti P.J.;
RT "The pattern-recognition molecule Nod1 is localized at the plasma membrane
RT at sites of bacterial interaction.";
RL Cell. Microbiol. 10:477-486(2008).
RN [9]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH ARHGEF2.
RX PubMed=19043560; DOI=10.1371/journal.ppat.1000228;
RA Fukazawa A., Alonso C., Kurachi K., Gupta S., Lesser C.F., McCormick B.A.,
RA Reinecker H.C.;
RT "GEF-H1 mediated control of NOD1 dependent NF-kappaB activation by Shigella
RT effectors.";
RL PLoS Pathog. 4:E1000228-E1000228(2008).
RN [10]
RP FUNCTION, INTERACTION WITH NLRP10, AND MUTAGENESIS OF LYS-208 AND ASP-287.
RX PubMed=22672233; DOI=10.1111/j.1462-5822.2012.01822.x;
RA Lautz K., Damm A., Menning M., Wenger J., Adam A.C., Zigrino P.,
RA Kremmer E., Kufer T.A.;
RT "NLRP10 enhances Shigella-induced pro-inflammatory responses.";
RL Cell. Microbiol. 14:1568-1583(2012).
RN [11]
RP INTERACTION WITH RNF34, AND UBIQUITINATION BY RNF34.
RX PubMed=25012219; DOI=10.1159/000362972;
RA Zhang R., Zhao J., Song Y., Wang X., Wang L., Xu J., Song C., Liu F.;
RT "The E3 ligase RNF34 is a novel negative regulator of the NOD1 pathway.";
RL Cell. Physiol. Biochem. 33:1954-1962(2014).
RN [12]
RP FUNCTION.
RX PubMed=27099311; DOI=10.1128/jvi.03230-15;
RA Vegna S., Gregoire D., Moreau M., Lassus P., Durantel D., Assenat E.,
RA Hibner U., Simonin Y.;
RT "NOD1 Participates in the Innate Immune Response Triggered by Hepatitis C
RT Virus Polymerase.";
RL J. Virol. 90:6022-6035(2016).
RN [13]
RP PALMITOYLATION, AND SUBCELLULAR LOCATION.
RX PubMed=31649195; DOI=10.1126/science.aau6391;
RA Lu Y., Zheng Y., Coyaud E., Zhang C., Selvabaskaran A., Yu Y., Xu Z.,
RA Weng X., Chen J.S., Meng Y., Warner N., Cheng X., Liu Y., Yao B., Hu H.,
RA Xia Z., Muise A.M., Klip A., Brumell J.H., Girardin S.E., Ying S.,
RA Fairn G.D., Raught B., Sun Q., Neculai D.;
RT "Palmitoylation of NOD1 and NOD2 is required for bacterial sensing.";
RL Science 366:460-467(2019).
RN [14]
RP FUNCTION, INTERACTION WITH IFIH1, AND SUBCELLULAR LOCATION.
RX PubMed=32169843; DOI=10.4049/jimmunol.1900667;
RA Wu X.M., Zhang J., Li P.W., Hu Y.W., Cao L., Ouyang S., Bi Y.H., Nie P.,
RA Chang M.X.;
RT "NOD1 Promotes Antiviral Signaling by Binding Viral RNA and Regulating the
RT Interaction of MDA5 and MAVS.";
RL J. Immunol. 204:2216-2231(2020).
RN [15]
RP FUNCTION, AND MUTAGENESIS OF HIS-517.
RX PubMed=33942347; DOI=10.15252/embj.2020106272;
RA Pei G., Zyla J., He L., Moura-Alves P., Steinle H., Saikali P., Lozza L.,
RA Nieuwenhuizen N., Weiner J., Mollenkopf H.J., Ellwanger K., Arnold C.,
RA Duan M., Dagil Y., Pashenkov M., Boneca I.G., Kufer T.A., Dorhoi A.,
RA Kaufmann S.H.;
RT "Cellular stress promotes NOD1/2-dependent inflammation via the endogenous
RT metabolite sphingosine-1-phosphate.";
RL EMBO J. 40:e106272-e106272(2021).
RN [16]
RP STRUCTURE BY NMR OF 14-110.
RG RIKEN structural genomics initiative (RSGI);
RT "Solution structure of the CARD domain in human caspase recruitment domain
RT protein 4 (NOD1 protein).";
RL Submitted (DEC-2006) to the PDB data bank.
RN [17]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 16-108, AND SUBUNIT.
RX PubMed=17173864; DOI=10.1016/j.bbrc.2006.11.122;
RA Coussens N.P., Mowers J.C., McDonald C., Nunez G., Ramaswamy S.;
RT "Crystal structure of the Nod1 caspase activation and recruitment domain.";
RL Biochem. Biophys. Res. Commun. 353:1-5(2007).
RN [18]
RP STRUCTURE BY NMR OF 15-138, FUNCTION, INTERACTION WITH RIPK2, AND
RP MUTAGENESIS OF VAL-41; LEU-44; ASP-48; GLU-53; ASP-54; GLU-56 AND ARG-69.
RX PubMed=17054981; DOI=10.1016/j.jmb.2006.09.067;
RA Manon F., Favier A., Nunez G., Simorre J.P., Cusack S.;
RT "Solution structure of NOD1 CARD and mutational analysis of its interaction
RT with the CARD of downstream kinase RICK.";
RL J. Mol. Biol. 365:160-174(2007).
RN [19]
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 9-106, AND SUBUNIT.
RX PubMed=18186648; DOI=10.1021/bi7016602;
RA Srimathi T., Robbins S.L., Dubas R.L., Hasegawa M., Inohara N., Park Y.C.;
RT "Monomer/dimer transition of the caspase-recruitment domain of human
RT Nod1.";
RL Biochemistry 47:1319-1325(2008).
CC -!- FUNCTION: Pattern recognition receptor (PRR) that detects bacterial
CC peptidoglycan fragments and other danger signals and thus participates
CC in both innate and adaptive immune responses (PubMed:19043560,
CC PubMed:22672233, PubMed:27099311). Ligand binding triggers
CC oligomerization that facilitates the binding and subsequent activation
CC of the receptor interacting protein-2/RIPK2. RIPK2 subsequently
CC recruits the kinase TAK1 to activate NF-kappa-B and MAPK signaling
CC pathways (PubMed:10880512). Regulates also antiviral response elicited
CC by dsRNA and the expression of RLR pathway members by targeting IFIH1
CC and TRAF3 to modulate the formation of IFIH1-MAVS and TRAF3-MAVS
CC complexes leading to increased transcription of type I IFNs
CC (PubMed:32169843). 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 (PubMed:33942347). In addition, plays a role in
CC insulin trafficking in beta cells in a cell-autonomous manner.
CC Mechanistically, upon recognizing cognate ligands, NOD1 and RIPK2
CC localize to insulin vesicles where they recruit RAB1A to direct insulin
CC trafficking through the cytoplasm (By similarity).
CC {ECO:0000250|UniProtKB:Q8BHB0, ECO:0000269|PubMed:10880512,
CC ECO:0000269|PubMed:11058605, ECO:0000269|PubMed:17054981,
CC ECO:0000269|PubMed:19043560, ECO:0000269|PubMed:22672233,
CC ECO:0000269|PubMed:27099311, ECO:0000269|PubMed:32169843}.
CC -!- SUBUNIT: Forms homooligomers(PubMed:10880512). Interacts with RIPK2
CC (PubMed:10880512, PubMed:17054981). Interacts with ARHGEF2
CC (PubMed:19043560). Interacts with NLRP10 and recruits it to the cell
CC membrane following invasive bacterial infection (PubMed:22672233).
CC Interacts with RNF34 (PubMed:25012219). Interacts with IFIH1; this
CC interaction promotes transcription of antiviral genes and inhibition of
CC viral replication (PubMed:32169843). {ECO:0000269|PubMed:10880512,
CC ECO:0000269|PubMed:17054981, ECO:0000269|PubMed:17173864,
CC ECO:0000269|PubMed:18186648, ECO:0000269|PubMed:19043560,
CC ECO:0000269|PubMed:22672233, ECO:0000269|PubMed:32169843}.
CC -!- INTERACTION:
CC Q9Y239; P02489: CRYAA; NbExp=3; IntAct=EBI-1051262, EBI-6875961;
CC Q9Y239; P14136: GFAP; NbExp=3; IntAct=EBI-1051262, EBI-744302;
CC Q9Y239; Q53GS7: GLE1; NbExp=3; IntAct=EBI-1051262, EBI-1955541;
CC Q9Y239; P42858: HTT; NbExp=9; IntAct=EBI-1051262, EBI-466029;
CC Q9Y239; Q92876: KLK6; NbExp=3; IntAct=EBI-1051262, EBI-2432309;
CC Q9Y239; P02545: LMNA; NbExp=3; IntAct=EBI-1051262, EBI-351935;
CC Q9Y239; Q9Y239: NOD1; NbExp=2; IntAct=EBI-1051262, EBI-1051262;
CC Q9Y239; Q6UX06: OLFM4; NbExp=2; IntAct=EBI-1051262, EBI-2804156;
CC Q9Y239; Q13153: PAK1; NbExp=3; IntAct=EBI-1051262, EBI-1307;
CC Q9Y239; Q7Z699: SPRED1; NbExp=3; IntAct=EBI-1051262, EBI-5235340;
CC Q9Y239; Q9Y2Z0: SUGT1; NbExp=5; IntAct=EBI-1051262, EBI-307008;
CC Q9Y239; A0A0H3NF38: sspH2; Xeno; NbExp=4; IntAct=EBI-1051262, EBI-10689860;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Cell membrane
CC {ECO:0000269|PubMed:31649195}. Apical cell membrane. Basolateral cell
CC membrane. Note=Detected in the cytoplasm and at the cell membrane.
CC Following bacterial infection, localizes to bacterial entry sites in
CC the cell membrane. Recruited to the basolateral and apical membranes in
CC polarized epithelial cells.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9Y239-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9Y239-2; Sequence=VSP_055825, VSP_055826;
CC -!- TISSUE SPECIFICITY: Highly expressed in adult heart, skeletal muscle,
CC pancreas, spleen and ovary. Also detected in placenta, lung, liver,
CC kidney, thymus, testis, small intestine and colon.
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:0000269|PubMed:31649195}.
CC -!- PTM: Ubiquitinated. 'Lys-48'-linked polyubiquitination by RNF34
CC promotes proteasomal degradation and thereby negatively regulates NOD1
CC for instance in NF-kappa-B activation. {ECO:0000269|PubMed:25012219}.
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DR EMBL; AF126484; AAD29125.1; -; mRNA.
DR EMBL; AF149774; AAD43922.1; -; Genomic_DNA.
DR EMBL; AF113925; AAD28350.1; -; mRNA.
DR EMBL; AK300367; BAG62105.1; -; mRNA.
DR EMBL; AC005154; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC006027; AAS46897.1; -; Genomic_DNA.
DR EMBL; BC040339; AAH40339.1; -; mRNA.
DR CCDS; CCDS5427.1; -. [Q9Y239-1]
DR RefSeq; NP_006083.1; NM_006092.2. [Q9Y239-1]
DR RefSeq; XP_005249625.1; XM_005249568.1. [Q9Y239-1]
DR RefSeq; XP_005249629.1; XM_005249572.1. [Q9Y239-1]
DR RefSeq; XP_006715696.1; XM_006715633.2. [Q9Y239-1]
DR RefSeq; XP_011513381.1; XM_011515079.1. [Q9Y239-1]
DR RefSeq; XP_011513382.1; XM_011515080.2. [Q9Y239-1]
DR RefSeq; XP_011513383.1; XM_011515081.2. [Q9Y239-1]
DR PDB; 2B1W; NMR; -; A=15-138.
DR PDB; 2DBD; NMR; -; A=17-110.
DR PDB; 2NSN; X-ray; 2.00 A; A=16-108.
DR PDB; 2NZ7; X-ray; 1.90 A; A/B=9-106.
DR PDB; 4E9M; X-ray; 2.15 A; A/B/C/D/E/F=2-138.
DR PDB; 4JQW; X-ray; 2.90 A; A=16-108.
DR PDBsum; 2B1W; -.
DR PDBsum; 2DBD; -.
DR PDBsum; 2NSN; -.
DR PDBsum; 2NZ7; -.
DR PDBsum; 4E9M; -.
DR PDBsum; 4JQW; -.
DR AlphaFoldDB; Q9Y239; -.
DR BMRB; Q9Y239; -.
DR SMR; Q9Y239; -.
DR BioGRID; 115664; 30.
DR CORUM; Q9Y239; -.
DR DIP; DIP-41064N; -.
DR IntAct; Q9Y239; 34.
DR MINT; Q9Y239; -.
DR STRING; 9606.ENSP00000222823; -.
DR BindingDB; Q9Y239; -.
DR ChEMBL; CHEMBL1293222; -.
DR GuidetoPHARMACOLOGY; 1762; -.
DR GlyGen; Q9Y239; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q9Y239; -.
DR PhosphoSitePlus; Q9Y239; -.
DR SwissPalm; Q9Y239; -.
DR BioMuta; NOD1; -.
DR DMDM; 20137579; -.
DR EPD; Q9Y239; -.
DR MassIVE; Q9Y239; -.
DR MaxQB; Q9Y239; -.
DR PaxDb; Q9Y239; -.
DR PeptideAtlas; Q9Y239; -.
DR PRIDE; Q9Y239; -.
DR ProteomicsDB; 5129; -.
DR ProteomicsDB; 85636; -. [Q9Y239-1]
DR Antibodypedia; 26181; 414 antibodies from 37 providers.
DR DNASU; 10392; -.
DR Ensembl; ENST00000222823.9; ENSP00000222823.4; ENSG00000106100.11. [Q9Y239-1]
DR GeneID; 10392; -.
DR KEGG; hsa:10392; -.
DR MANE-Select; ENST00000222823.9; ENSP00000222823.4; NM_006092.4; NP_006083.1.
DR UCSC; uc003tav.4; human. [Q9Y239-1]
DR CTD; 10392; -.
DR DisGeNET; 10392; -.
DR GeneCards; NOD1; -.
DR HGNC; HGNC:16390; NOD1.
DR HPA; ENSG00000106100; Low tissue specificity.
DR MIM; 605980; gene.
DR neXtProt; NX_Q9Y239; -.
DR OpenTargets; ENSG00000106100; -.
DR PharmGKB; PA162398098; -.
DR VEuPathDB; HostDB:ENSG00000106100; -.
DR eggNOG; KOG4308; Eukaryota.
DR GeneTree; ENSGT00940000157845; -.
DR HOGENOM; CLU_011291_1_0_1; -.
DR InParanoid; Q9Y239; -.
DR OMA; SYEFFHI; -.
DR PhylomeDB; Q9Y239; -.
DR TreeFam; TF352118; -.
DR PathwayCommons; Q9Y239; -.
DR Reactome; R-HSA-168638; NOD1/2 Signaling Pathway.
DR Reactome; R-HSA-445989; TAK1-dependent IKK and NF-kappa-B activation.
DR Reactome; R-HSA-450302; activated TAK1 mediates p38 MAPK activation.
DR Reactome; R-HSA-450321; JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1.
DR Reactome; R-HSA-5689896; Ovarian tumor domain proteases.
DR Reactome; R-HSA-9020702; Interleukin-1 signaling.
DR Reactome; R-HSA-9705671; SARS-CoV-2 activates/modulates innate and adaptive immune responses.
DR SignaLink; Q9Y239; -.
DR SIGNOR; Q9Y239; -.
DR BioGRID-ORCS; 10392; 10 hits in 1077 CRISPR screens.
DR ChiTaRS; NOD1; human.
DR EvolutionaryTrace; Q9Y239; -.
DR GeneWiki; NOD1; -.
DR GenomeRNAi; 10392; -.
DR Pharos; Q9Y239; Tchem.
DR PRO; PR:Q9Y239; -.
DR Proteomes; UP000005640; Chromosome 7.
DR RNAct; Q9Y239; protein.
DR Bgee; ENSG00000106100; Expressed in sural nerve and 148 other tissues.
DR ExpressionAtlas; Q9Y239; baseline and differential.
DR Genevisible; Q9Y239; HS.
DR GO; GO:0046658; C:anchored component of plasma membrane; IMP:UniProtKB.
DR GO; GO:0016324; C:apical plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016323; C:basolateral plasma membrane; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0045335; C:phagocytic vesicle; IEA:Ensembl.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0050700; F:CARD domain binding; IDA:MGI.
DR GO; GO:0008656; F:cysteine-type endopeptidase activator activity involved in apoptotic process; TAS:ProtInc.
DR GO; GO:0042802; F:identical protein binding; IDA:MGI.
DR GO; GO:0038187; F:pattern recognition receptor activity; IDA:UniProtKB.
DR GO; GO:0042834; F:peptidoglycan binding; TAS:HGNC-UCL.
DR GO; GO:0042803; F:protein homodimerization activity; IPI:UniProtKB.
DR GO; GO:0044877; F:protein-containing complex binding; IPI:UniProtKB.
DR GO; GO:0006919; P:activation of cysteine-type endopeptidase activity involved in apoptotic process; IDA:MGI.
DR GO; GO:0006915; P:apoptotic process; TAS:ProtInc.
DR GO; GO:0071225; P:cellular response to muramyl dipeptide; IMP:UniProtKB.
DR GO; GO:0006952; P:defense response; TAS:HGNC-UCL.
DR GO; GO:0042742; P:defense response to bacterium; IDA:HGNC-UCL.
DR GO; GO:0050830; P:defense response to Gram-positive bacterium; IEA:Ensembl.
DR GO; GO:0016045; P:detection of bacterium; IDA:HGNC-UCL.
DR GO; GO:0009595; P:detection of biotic stimulus; TAS:HGNC-UCL.
DR GO; GO:0070371; P:ERK1 and ERK2 cascade; IEA:Ensembl.
DR GO; GO:0007249; P:I-kappaB kinase/NF-kappaB signaling; IEA:Ensembl.
DR GO; GO:0006954; P:inflammatory response; TAS:HGNC-UCL.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:0035556; P:intracellular signal transduction; IDA:HGNC-UCL.
DR GO; GO:0007254; P:JNK cascade; IEA:Ensembl.
DR GO; GO:0002221; P:pattern recognition receptor signaling pathway; IDA:UniProtKB.
DR GO; GO:0010942; P:positive regulation of cell death; IEA:Ensembl.
DR GO; GO:0043280; P:positive regulation of cysteine-type endopeptidase activity involved in apoptotic process; IDA:MGI.
DR GO; GO:0002606; P:positive regulation of dendritic cell antigen processing and presentation; ISS:BHF-UCL.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IEA:Ensembl.
DR GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; IDA:MGI.
DR GO; GO:0032731; P:positive regulation of interleukin-1 beta 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; IDA:HGNC-UCL.
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:0051092; P:positive regulation of NF-kappaB transcription factor activity; IDA:UniProtKB.
DR GO; GO:1901224; P:positive regulation of NIK/NF-kappaB signaling; IMP:UniProtKB.
DR GO; GO:0051000; P:positive regulation of nitric-oxide synthase activity; IEA:Ensembl.
DR GO; GO:0032760; P:positive regulation of tumor necrosis factor production; IEA:Ensembl.
DR GO; GO:1904417; P:positive regulation of xenophagy; IEA:Ensembl.
DR GO; GO:0042981; P:regulation of apoptotic process; IEA:InterPro.
DR GO; GO:0007165; P:signal transduction; TAS:HGNC-UCL.
DR GO; GO:0098792; P:xenophagy; IEA:Ensembl.
DR DisProt; DP01446; -.
DR Gene3D; 1.10.533.10; -; 1.
DR Gene3D; 3.40.50.300; -; 1.
DR Gene3D; 3.80.10.10; -; 2.
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; 4.
DR Pfam; PF05729; NACHT; 1.
DR Pfam; PF17776; NLRC4_HD2; 1.
DR Pfam; PF17779; NOD2_WH; 1.
DR SUPFAM; SSF47986; SSF47986; 1.
DR PROSITE; PS50209; CARD; 1.
DR PROSITE; PS50837; NACHT; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Apoptosis; ATP-binding; Cell membrane;
KW Cytoplasm; Immunity; Innate immunity; Leucine-rich repeat; Lipoprotein;
KW Membrane; Nucleotide-binding; Palmitate; Reference proteome; Repeat;
KW Ubl conjugation.
FT CHAIN 1..953
FT /note="Nucleotide-binding oligomerization domain-containing
FT protein 1"
FT /id="PRO_0000144077"
FT DOMAIN 15..105
FT /note="CARD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00046"
FT DOMAIN 196..531
FT /note="NACHT"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00136"
FT REPEAT 632..656
FT /note="LRR 1"
FT REPEAT 702..725
FT /note="LRR 2"
FT REPEAT 727..750
FT /note="LRR 3"
FT REPEAT 755..778
FT /note="LRR 4"
FT REPEAT 783..806
FT /note="LRR 5"
FT REPEAT 839..862
FT /note="LRR 6"
FT REPEAT 867..891
FT /note="LRR 7"
FT REPEAT 895..918
FT /note="LRR 8"
FT REPEAT 923..946
FT /note="LRR 9"
FT BINDING 202..209
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00136"
FT VAR_SEQ 195..249
FT /note="GETIFILGDAGVGKSMLLQRLQSLWATGRLDAGVKFFFHFRCRMFSCFKESD
FT RLC -> AASRKVTGCVCRTCSSSTTATQSGTPRRCLPSCCASPTWPSSPSMAWTSCTR
FT TWT (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_055825"
FT VAR_SEQ 250..953
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_055826"
FT VARIANT 266
FT /note="E -> K (in dbSNP:rs2075820)"
FT /id="VAR_020371"
FT VARIANT 372
FT /note="D -> N (in dbSNP:rs5743342)"
FT /id="VAR_053624"
FT VARIANT 447
FT /note="R -> H (in dbSNP:rs2975634)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_053625"
FT VARIANT 605
FT /note="R -> W (in dbSNP:rs5743345)"
FT /id="VAR_053626"
FT VARIANT 610
FT /note="A -> T (in dbSNP:rs5743346)"
FT /id="VAR_053627"
FT MUTAGEN 41
FT /note="V->A: Abolishes interaction with RIPK2/RICK."
FT /evidence="ECO:0000269|PubMed:10329646,
FT ECO:0000269|PubMed:17054981"
FT MUTAGEN 41
FT /note="V->Q: Abolishes caspase-9 activation."
FT /evidence="ECO:0000269|PubMed:10329646,
FT ECO:0000269|PubMed:17054981"
FT MUTAGEN 44
FT /note="L->A: Abolishes activation of NF-kappa-B. No effect
FT on interaction with RIPK2."
FT /evidence="ECO:0000269|PubMed:17054981"
FT MUTAGEN 48
FT /note="D->K: Abolishes activation of NF-kappa-B. No effect
FT on interaction with RIPK2."
FT /evidence="ECO:0000269|PubMed:17054981"
FT MUTAGEN 53
FT /note="E->K: No effect on activation of NF-kappa-B.
FT Abolishes interaction with RIPK2."
FT /evidence="ECO:0000269|PubMed:17054981"
FT MUTAGEN 54
FT /note="D->K: Abolishes activation of NF-kappa-B. Abolishes
FT interaction with RIPK2."
FT /evidence="ECO:0000269|PubMed:17054981"
FT MUTAGEN 56
FT /note="E->K: Abolishes activation of NF-kappa-B. Abolishes
FT interaction with RIPK2."
FT /evidence="ECO:0000269|PubMed:17054981"
FT MUTAGEN 69
FT /note="R->E: Abolishes activation of NF-kappa-B. Abolishes
FT interaction with RIPK2."
FT /evidence="ECO:0000269|PubMed:17054981"
FT MUTAGEN 208
FT /note="K->R: Reduces caspase-9 activation. Reduced binding
FT affinity for NLRP10. Does not associate with cell
FT membrane."
FT /evidence="ECO:0000269|PubMed:10329646,
FT ECO:0000269|PubMed:17970764, ECO:0000269|PubMed:22672233"
FT MUTAGEN 287
FT /note="D->A: Reduced binding affinity for NLRP10."
FT /evidence="ECO:0000269|PubMed:22672233"
FT MUTAGEN 517
FT /note="H->A: Loss of activation by sphingosine-1-
FT phosphate."
FT /evidence="ECO:0000269|PubMed:33942347"
FT MUTAGEN 711
FT /note="D->S: Does not associate with cell membrane."
FT /evidence="ECO:0000269|PubMed:17970764"
FT MUTAGEN 788
FT /note="H->S: No effect on association with cell membrane."
FT /evidence="ECO:0000269|PubMed:17970764"
FT MUTAGEN 792
FT /note="G->S: Does not associate with cell membrane."
FT /evidence="ECO:0000269|PubMed:17970764"
FT MUTAGEN 877
FT /note="Q->S: Does not associate with cell membrane."
FT /evidence="ECO:0000269|PubMed:17970764"
FT HELIX 18..25
FT /evidence="ECO:0007829|PDB:2NZ7"
FT HELIX 27..33
FT /evidence="ECO:0007829|PDB:2NZ7"
FT HELIX 38..46
FT /evidence="ECO:0007829|PDB:2NZ7"
FT HELIX 52..59
FT /evidence="ECO:0007829|PDB:2NZ7"
FT STRAND 61..63
FT /evidence="ECO:0007829|PDB:4E9M"
FT HELIX 64..78
FT /evidence="ECO:0007829|PDB:2NZ7"
FT HELIX 80..95
FT /evidence="ECO:0007829|PDB:2NZ7"
FT HELIX 98..100
FT /evidence="ECO:0007829|PDB:2NZ7"
FT HELIX 101..105
FT /evidence="ECO:0007829|PDB:2NZ7"
SQ SEQUENCE 953 AA; 107691 MW; 0A9DF5FC6487E21A CRC64;
MEEQGHSEME IIPSESHPHI QLLKSNRELL VTHIRNTQCL VDNLLKNDYF SAEDAEIVCA
CPTQPDKVRK ILDLVQSKGE EVSEFFLYLL QQLADAYVDL RPWLLEIGFS PSLLTQSKVV
VNTDPVSRYT QQLRHHLGRD SKFVLCYAQK EELLLEEIYM DTIMELVGFS NESLGSLNSL
ACLLDHTTGI LNEQGETIFI LGDAGVGKSM LLQRLQSLWA TGRLDAGVKF FFHFRCRMFS
CFKESDRLCL QDLLFKHYCY PERDPEEVFA FLLRFPHVAL FTFDGLDELH SDLDLSRVPD
SSCPWEPAHP LVLLANLLSG KLLKGASKLL TARTGIEVPR QFLRKKVLLR GFSPSHLRAY
ARRMFPERAL QDRLLSQLEA NPNLCSLCSV PLFCWIIFRC FQHFRAAFEG SPQLPDCTMT
LTDVFLLVTE VHLNRMQPSS LVQRNTRSPV ETLHAGRDTL CSLGQVAHRG MEKSLFVFTQ
EEVQASGLQE RDMQLGFLRA LPELGPGGDQ QSYEFFHLTL QAFFTAFFLV LDDRVGTQEL
LRFFQEWMPP AGAATTSCYP PFLPFQCLQG SGPAREDLFK NKDHFQFTNL FLCGLLSKAK
QKLLRHLVPA AALRRKRKAL WAHLFSSLRG YLKSLPRVQV ESFNQVQAMP TFIWMLRCIY
ETQSQKVGQL AARGICANYL KLTYCNACSA DCSALSFVLH HFPKRLALDL DNNNLNDYGV
RELQPCFSRL TVLRLSVNQI TDGGVKVLSE ELTKYKIVTY LGLYNNQITD VGARYVTKIL
DECKGLTHLK LGKNKITSEG GKYLALAVKN SKSISEVGMW GNQVGDEGAK AFAEALRNHP
SLTTLSLASN GISTEGGKSL ARALQQNTSL EILWLTQNEL NDEVAESLAE MLKVNQTLKH
LWLIQNQITA KGTAQLADAL QSNTGITEIC LNGNLIKPEE AKVYEDEKRI ICF
