ID NOD2_MOUSE Reviewed; 1020 AA. AC Q8K3Z0; DT 28-MAR-2003, integrated into UniProtKB/Swiss-Prot. DT 01-OCT-2002, sequence version 1. DT 27-MAR-2024, entry version 182. DE RecName: Full=Nucleotide-binding oligomerization domain-containing protein 2 {ECO:0000303|PubMed:12835899}; DE AltName: Full=Caspase recruitment domain-containing protein 15 {ECO:0000303|PubMed:12835899}; GN Name=Nod2 {ECO:0000303|PubMed:12835899, ECO:0000312|MGI:MGI:2429397}; GN Synonyms=Card15 {ECO:0000303|PubMed:12835899}; OS Mus musculus (Mouse). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Mus; Mus. OX NCBI_TaxID=10090; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC STRAIN=BALB/cJ; TISSUE=Monocyte; RX PubMed=12835899; DOI=10.1007/s00011-003-1170-z; RA Iwanaga Y., Davey M.P., Martin T.M., Planck S.R., DePriest M.L., RA Baugh M.M., Suing C.M., Rosenbaum J.T.; RT "Cloning, sequencing and expression analysis of the mouse Nod2/Card15 RT gene."; RL Inflamm. Res. 52:272-276(2003). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND VARIANTS ALA-212; RP ARG-240; CYS-422; VAL-485; ALA-603; ILE-675 AND GLN-925. RC STRAIN=NMRI; TISSUE=Mammary cancer; 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 [3] RP INTERACTION WITH ERBIN. RX PubMed=16203728; DOI=10.1074/jbc.m508538200; RA McDonald C., Chen F.F., Ollendorff V., Ogura Y., Marchetto S., Lecine P., RA Borg J.P., Nunez G.; RT "A role for Erbin in the regulation of Nod2-dependent NF-kappaB RT signaling."; RL J. Biol. Chem. 280:40301-40309(2005). RN [4] RP FUNCTION, TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE. RX PubMed=15692051; DOI=10.1126/science.1104911; RA Kobayashi K.S., Chamaillard M., Ogura Y., Henegariu O., Inohara N., RA Nunez G., Flavell R.A.; RT "Nod2-dependent regulation of innate and adaptive immunity in the RT intestinal tract."; RL Science 307:731-734(2005). RN [5] RP FUNCTION, AND MUTAGENESIS OF 987-LEU--LEU-1020. RX PubMed=15692052; DOI=10.1126/science.1103685; RA Maeda S., Hsu L.C., Liu H., Bankston L.A., Iimura M., Kagnoff M.F., RA Eckmann L., Karin M.; RT "Nod2 mutation in Crohn's disease potentiates NF-kappaB activity and IL- RT 1beta processing."; RL Science 307:734-738(2005). RN [6] RP INTERACTION WITH CARD9. RX PubMed=17187069; DOI=10.1038/ni1426; RA Hsu Y.M., Zhang Y., You Y., Wang D., Li H., Duramad O., Qin X.F., Dong C., RA Lin X.; RT "The adaptor protein CARD9 is required for innate immune responses to RT intracellular pathogens."; RL Nat. Immunol. 8:198-205(2007). RN [7] RP FUNCTION, AND INTERACTION WITH CASP1. RX PubMed=18511561; DOI=10.1073/pnas.0802726105; RA Hsu L.C., Ali S.R., McGillivray S., Tseng P.H., Mariathasan S., Humke E.W., RA Eckmann L., Powell J.J., Nizet V., Dixit V.M., Karin M.; RT "A NOD2-NALP1 complex mediates caspase-1-dependent IL-1beta secretion in RT response to Bacillus anthracis infection and muramyl dipeptide."; RL Proc. Natl. Acad. Sci. U.S.A. 105:7803-7808(2008). RN [8] RP DISRUPTION PHENOTYPE, AND FUNCTION. RX PubMed=19805227; DOI=10.1073/pnas.0907722106; RA Petnicki-Ocwieja T., Hrncir T., Liu Y.J., Biswas A., Hudcovic T., RA Tlaskalova-Hogenova H., Kobayashi K.S.; RT "Nod2 is required for the regulation of commensal microbiota in the RT intestine."; RL Proc. Natl. Acad. Sci. U.S.A. 106:15813-15818(2009). RN [9] RP FUNCTION, AND INTERACTION WITH ATG16L1. RX PubMed=19898471; DOI=10.1038/ni.1823; RA Travassos L.H., Carneiro L.A., Ramjeet M., Hussey S., Kim Y.G., RA Magalhaes J.G., Yuan L., Soares F., Chea E., Le Bourhis L., Boneca I.G., RA Allaoui A., Jones N.L., Nunez G., Girardin S.E., Philpott D.J.; RT "Nod1 and Nod2 direct autophagy by recruiting ATG16L1 to the plasma RT membrane at the site of bacterial entry."; RL Nat. Immunol. 11:55-62(2010). RN [10] RP FUNCTION, AND INTERACTION WITH ATG16L1. RX PubMed=19966812; DOI=10.1038/nm.2069; RA Cooney R., Baker J., Brain O., Danis B., Pichulik T., Allan P., RA Ferguson D.J., Campbell B.J., Jewell D., Simmons A.; RT "NOD2 stimulation induces autophagy in dendritic cells influencing RT bacterial handling and antigen presentation."; RL Nat. Med. 16:90-97(2010). RN [11] RP DISRUPTION PHENOTYPE, AND FUNCTION. RX PubMed=21715553; DOI=10.2337/db11-0004; RA Schertzer J.D., Tamrakar A.K., Magalhaes J.G., Pereira S., Bilan P.J., RA Fullerton M.D., Liu Z., Steinberg G.R., Giacca A., Philpott D.J., Klip A.; RT "NOD1 activators link innate immunity to insulin resistance."; RL Diabetes 60:2206-2215(2011). RN [12] RP FUNCTION, AND DISRUPTION PHENOTYPE. RX PubMed=21421666; DOI=10.1136/gut.2010.216259; RA Rehman A., Sina C., Gavrilova O., Haesler R., Ott S., Baines J.F., RA Schreiber S., Rosenstiel P.; RT "Nod2 is essential for temporal development of intestinal microbial RT communities."; RL Gut 60:1354-1362(2011). RN [13] RP FUNCTION. RX PubMed=21856952; DOI=10.1073/pnas.1015063108; RA Magalhaes J.G., Rubino S.J., Travassos L.H., Le Bourhis L., Duan W., RA Sellge G., Geddes K., Reardon C., Lechmann M., Carneiro L.A., RA Selvanantham T., Fritz J.H., Taylor B.C., Artis D., Mak T.W., Comeau M.R., RA Croft M., Girardin S.E., Philpott D.J.; RT "Nucleotide oligomerization domain-containing proteins instruct T cell RT helper type 2 immunity through stromal activation."; RL Proc. Natl. Acad. Sci. U.S.A. 108:14896-14901(2011). RN [14] RP INTERACTION WITH HSP90 AND SOCS3. RX PubMed=23019338; DOI=10.1074/jbc.m112.410027; RA Lee K.H., Biswas A., Liu Y.J., Kobayashi K.S.; RT "Proteasomal degradation of Nod2 protein mediates tolerance to bacterial RT cell wall components."; RL J. Biol. Chem. 287:39800-39811(2012). RN [15] RP FUNCTION. RX PubMed=22607974; DOI=10.1016/j.molcel.2012.04.014; RA Damgaard R.B., Nachbur U., Yabal M., Wong W.W., Fiil B.K., Kastirr M., RA Rieser E., Rickard J.A., Bankovacki A., Peschel C., Ruland J., RA Bekker-Jensen S., Mailand N., Kaufmann T., Strasser A., Walczak H., RA Silke J., Jost P.J., Gyrd-Hansen M.; RT "The ubiquitin ligase XIAP recruits LUBAC for NOD2 signaling in RT inflammation and innate immunity."; RL Mol. Cell 46:746-758(2012). RN [16] RP FUNCTION, AND DISRUPTION PHENOTYPE. RX PubMed=25088769; DOI=10.1016/j.immuni.2014.06.015; RA Ramanan D., Tang M.S., Bowcutt R., Loke P., Cadwell K.; RT "Bacterial sensor Nod2 prevents inflammation of the small intestine by RT restricting the expansion of the commensal Bacteroides vulgatus."; RL Immunity 41:311-324(2014). RN [17] RP FUNCTION, AND DISRUPTION PHENOTYPE. RX PubMed=23281400; DOI=10.1172/jci62236; RA Couturier-Maillard A., Secher T., Rehman A., Normand S., De Arcangelis A., RA Haesler R., Huot L., Grandjean T., Bressenot A., Delanoye-Crespin A., RA Gaillot O., Schreiber S., Lemoine Y., Ryffel B., Hot D., Nunez G., Chen G., RA Rosenstiel P., Chamaillard M.; RT "NOD2-mediated dysbiosis predisposes mice to transmissible colitis and RT colorectal cancer."; RL J. Clin. Invest. 123:700-711(2013). RN [18] RP FUNCTION, AND DISRUPTION PHENOTYPE. RX PubMed=24062413; DOI=10.1084/jem.20122490; RA Jiang W., Wang X., Zeng B., Liu L., Tardivel A., Wei H., Han J., RA MacDonald H.R., Tschopp J., Tian Z., Zhou R.; RT "Recognition of gut microbiota by NOD2 is essential for the homeostasis of RT intestinal intraepithelial lymphocytes."; RL J. Exp. Med. 210:2465-2476(2013). RN [19] RP FUNCTION, AND TISSUE SPECIFICITY. RX PubMed=24882705; DOI=10.1016/j.chom.2014.05.003; RA Nigro G., Rossi R., Commere P.H., Jay P., Sansonetti P.J.; RT "The cytosolic bacterial peptidoglycan sensor Nod2 affords stem cell RT protection and links microbes to gut epithelial regeneration."; RL Cell Host Microbe 15:792-798(2014). RN [20] RP FUNCTION, DISRUPTION PHENOTYPE, AND TISSUE SPECIFICITY. RX PubMed=25666722; DOI=10.15252/emmm.201404169; RA Denou E., Lolmede K., Garidou L., Pomie C., Chabo C., Lau T.C., RA Fullerton M.D., Nigro G., Zakaroff-Girard A., Luche E., Garret C., RA Serino M., Amar J., Courtney M., Cavallari J.F., Henriksbo B.D., RA Barra N.G., Foley K.P., McPhee J.B., Duggan B.M., O'Neill H.M., Lee A.J., RA Sansonetti P., Ashkar A.A., Khan W.I., Surette M.G., Bouloumie A., RA Steinberg G.R., Burcelin R., Schertzer J.D.; RT "Defective NOD2 peptidoglycan sensing promotes diet-induced inflammation, RT dysbiosis, and insulin resistance."; RL EMBO Mol. Med. 7:259-274(2015). RN [21] RP MUTAGENESIS OF ARG-314. RX PubMed=25429073; DOI=10.4049/jimmunol.1402330; RA Dugan J., Griffiths E., Snow P., Rosenzweig H., Lee E., Brown B., RA Carr D.W., Rose C., Rosenbaum J., Davey M.P.; RT "Blau syndrome-associated Nod2 mutation alters expression of full-length RT NOD2 and limits responses to muramyl dipeptide in knock-in mice."; RL J. Immunol. 194:349-357(2015). RN [22] RP FUNCTION. RX PubMed=27007849; DOI=10.1038/nature17631; RA Keestra-Gounder A.M., Byndloss M.X., Seyffert N., Young B.M., RA Chavez-Arroyo A., Tsai A.Y., Cevallos S.A., Winter M.G., Pham O.H., RA Tiffany C.R., de Jong M.F., Kerrinnes T., Ravindran R., Luciw P.A., RA McSorley S.J., Baeumler A.J., Tsolis R.M.; RT "NOD1 and NOD2 signalling links ER stress with inflammation."; RL Nature 532:394-397(2016). RN [23] RP FUNCTION. RX PubMed=27230380; DOI=10.1126/science.aad9948; RA Chu H., Khosravi A., Kusumawardhani I.P., Kwon A.H., Vasconcelos A.C., RA Cunha L.D., Mayer A.E., Shen Y., Wu W.L., Kambal A., Targan S.R., RA Xavier R.J., Ernst P.B., Green D.R., McGovern D.P., Virgin H.W., RA Mazmanian S.K.; RT "Gene-microbiota interactions contribute to the pathogenesis of RT inflammatory bowel disease."; RL Science 352:1116-1120(2016). RN [24] RP FUNCTION. RX PubMed=28127403; DOI=10.1186/s13099-017-0155-3; RA Bereswill S., Grundmann U., Alutis M.E., Fischer A., Heimesaat M.M.; RT "Campylobacter jejuni infection of conventionally colonized mice lacking RT nucleotide-oligomerization-domain-2."; RL Gut Pathog. 9:5-5(2017). RN [25] RP FUNCTION, AND INTERACTION WITH ATG16L1. RX PubMed=31919280; DOI=10.1073/pnas.1902788117; RA Levy A., Stedman A., Deutsch E., Donnadieu F., Virgin H.W., RA Sansonetti P.J., Nigro G.; RT "Innate immune receptor NOD2 mediates LGR5+ intestinal stem cell protection RT against ROS cytotoxicity via mitophagy stimulation."; RL Proc. Natl. Acad. Sci. U.S.A. 117:1994-2003(2020). RN [26] RP FUNCTION. RX PubMed=36002575; DOI=10.1038/s41586-022-05125-x; RA Stafford C.A., Gassauer A.M., de Oliveira Mann C.C., Tanzer M.C., RA Fessler E., Wefers B., Nagl D., Kuut G., Sulek K., Vasilopoulou C., RA Schwojer S.J., Wiest A., Pfautsch M.K., Wurst W., Yabal M., Froehlich T., RA Mann M., Gisch N., Jae L.T., Hornung V.; RT "Phosphorylation of muramyl peptides by NAGK is required for NOD2 RT activation."; RL Nature 609:590-596(2022). RN [27] RP FUNCTION, DISRUPTION PHENOTYPE, AND TISSUE SPECIFICITY. RX PubMed=35420957; DOI=10.1126/science.abj3986; RA Gabanyi I., Lepousez G., Wheeler R., Vieites-Prado A., Nissant A., RA Chevalier G., Wagner S., Moigneu C., Dulauroy S., Hicham S., Polomack B., RA Verny F., Rosenstiel P., Renier N., Boneca I.G., Eberl G., Lledo P.M.; RT "Bacterial sensing via neuronal Nod2 regulates appetite and body RT temperature."; RL Science 376:eabj3986-eabj3986(2022). RN [28] RP FUNCTION. RX PubMed=36821686; DOI=10.1126/science.ade9767; RA Schwarzer M., Gautam U.K., Makki K., Lambert A., Brabec T., Joly A., RA Srutkova D., Poinsot P., Novotna T., Geoffroy S., Courtin P., RA Hermanova P.P., Matos R.C., Landry J.J.M., Gerard C., Bulteau A.L., RA Hudcovic T., Kozakova H., Filipp D., Chapot-Chartier M.P., Sinkora M., RA Peretti N., Boneca I.G., Chamaillard M., Vidal H., De Vadder F., RA Leulier F.; RT "Microbe-mediated intestinal NOD2 stimulation improves linear growth of RT undernourished infant mice."; RL Science 379:826-833(2023). 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 (PubMed:15692051, PubMed:15692052, CC PubMed:19805227, PubMed:21715553). Specifically activated by muramyl CC dipeptide (MDP), a fragment of bacterial peptidoglycan found in every CC bacterial peptidoglycan type (PubMed:15692051, PubMed:15692052, CC PubMed:25429073). NOD2 specifically recognizes and binds 6-O-phospho- CC MDP, the phosphorylated form of MDP, which is generated by NAGK CC (PubMed:36002575). 6-O-phospho-MDP-binding triggers oligomerization CC that facilitates the binding and subsequent activation of the proximal CC adapter receptor-interacting RIPK2 (PubMed:15692051, PubMed:15692052, CC PubMed:22607974). Following recruitment, RIPK2 undergoes 'Met- CC 1'- (linear) and 'Lys-63'-linked polyubiquitination by E3 ubiquitin- CC protein ligases XIAP, BIRC2, BIRC3 and the LUBAC complex, becoming a CC scaffolding protein for downstream effectors, triggering activation of CC the NF-kappa-B and MAP kinases signaling (PubMed:15692051, CC PubMed:15692052, PubMed:22607974). This in turn leads to the CC transcriptional activation of hundreds of genes involved in immune CC response (PubMed:22607974). Its ability to detect bacterial MDP plays a CC central role in maintaining the equilibrium between intestinal CC microbiota and host immune responses to control inflammation CC (PubMed:19805227, PubMed:21421666, PubMed:25088769, PubMed:23281400, CC PubMed:24062413, PubMed:24882705, PubMed:25666722, PubMed:28127403). An CC imbalance in this relationship results in dysbiosis, whereby pathogenic CC bacteria prevail on commensals, causing damage in the intestinal CC epithelial barrier as well as allowing bacterial invasion and CC inflammation (PubMed:25088769, PubMed:23281400). Acts as a regulator of CC appetite by sensing MDP in a subset of brain neurons: microbiota- CC derived MDP reach the brain, where they bind and activate NOD2 in CC inhibitory hypothalamic neurons, decreasing neuronal activity, thereby CC regulating satiety and body temperature (PubMed:35420957). NOD2- CC dependent MDP-sensing of bacterial cell walls in the intestinal CC epithelial compartment contributes to sustained postnatal growth upon CC undernutrition (PubMed:36821686). Also plays a role in antiviral CC response by acting as a sensor of single-stranded RNA (ssRNA) from CC viruses: upon ssRNA-binding, interacts with MAVS, leading to activation CC of interferon regulatory factor-3/IRF3 and expression of type I CC interferon (By similarity). Also acts as a regulator of autophagy in CC dendritic cells via its interaction with ATG16L1, possibly by CC recruiting ATG16L1 at the site of bacterial entry (PubMed:19898471, CC PubMed:19966812, PubMed:27230380). NOD2 activation in the small CC intestine crypt also contributes to intestinal stem cells survival and CC function: acts by promoting mitophagy via its association with ATG16L1 CC (PubMed:31919280). In addition to its main role in innate immunity, CC also regulates the adaptive immune system by acting as regulator of CC helper T-cell and regulatory T-cells (Tregs) (PubMed:21856952, CC PubMed:27230380). Besides recognizing pathogens, also involved in the CC endoplasmic reticulum stress response: acts by sensing and binding to CC the cytosolic metabolite sphingosine-1-phosphate generated in response CC to endoplasmic reticulum stress, initiating an inflammation process CC that leads to activation of the NF-kappa-B and MAP kinases signaling CC (PubMed:27007849). May also be involved in NLRP1 activation following CC activation by MDP, leading to CASP1 activation and IL1B release in CC macrophages (PubMed:18511561). {ECO:0000250|UniProtKB:G1T469, CC ECO:0000269|PubMed:15692051, ECO:0000269|PubMed:15692052, CC ECO:0000269|PubMed:18511561, ECO:0000269|PubMed:19805227, CC ECO:0000269|PubMed:19898471, ECO:0000269|PubMed:19966812, CC ECO:0000269|PubMed:21421666, ECO:0000269|PubMed:21715553, CC ECO:0000269|PubMed:21856952, ECO:0000269|PubMed:22607974, CC ECO:0000269|PubMed:23281400, ECO:0000269|PubMed:24062413, CC ECO:0000269|PubMed:24882705, ECO:0000269|PubMed:25088769, CC ECO:0000269|PubMed:25429073, ECO:0000269|PubMed:25666722, CC ECO:0000269|PubMed:27007849, ECO:0000269|PubMed:27230380, CC ECO:0000269|PubMed:28127403, ECO:0000269|PubMed:31919280, CC ECO:0000269|PubMed:35420957, ECO:0000269|PubMed:36002575, CC ECO:0000269|PubMed:36821686}. CC -!- ACTIVITY REGULATION: ADP-binding promotes an inactive closed CC conformation. {ECO:0000250|UniProtKB:G1T469}. CC -!- SUBUNIT: Homooligomer: homooligomerizes following muramyl dipeptide CC (MDP)-binding, promoting RIPK2 recruitment (By similarity). Interacts CC (via CARD domain) with RIPK2 (via CARD domain) (By similarity). CC Following RIPK2 recruitment, RIPK2 homooligomerizes via its CARD domain CC and forms long filaments named RIPosomes (By similarity). Interacts CC (via CARD domain) with ubiquitin; inhibiting interaction with RIPK2 (By CC similarity). Component of a signaling complex consisting of ARHGEF2, CC NOD2 and RIPK2 (By similarity). Interacts with ANKRD17 (via N-terminus) CC (By similarity). Interacts with HSPA1A; the interaction enhances NOD2 CC stability (By similarity). Interacts (via both CARD domains) with CC HSP90; the interaction enhances NOD2 stability (PubMed:23019338). CC Interacts (via CARD domain) with SOCS3; the interaction promotes NOD2 CC degradation (PubMed:23019338). Interacts (via CARD domain) with ERBIN; CC the interaction inhibits activation of NOD2 (PubMed:16203728). CC Interacts with MAPKBP1; the interaction is enhanced in the presence of CC muramyl dipeptide (MDP) and inhibits NOD2 homooligomerization and CC activation (By similarity). Interacts with INAVA; the interaction takes CC place upon Pattern recognition receptor (PRR) stimulation (By CC similarity). Interacts (via NACHT domain) with CARD9 (PubMed:17187069). CC Interacts (via CARD domain) with CASP1; this interaction leads to IL1B CC processing (PubMed:18511561). Also interacts with CASP4 (By CC similarity). Interacts with NLRP1; this interaction is enhanced in the CC presence of muramyl dipeptide (MDP) and leads to increased IL1B release CC (By similarity). Interacts with NLRP12; this interaction promotes CC degradation of NOD2 through the ubiquitin-proteasome pathway (By CC similarity). Interacts with ANKHD1, C10orf67, CHMP5, DOCK7, ENTR1, CC KRT15, LDOC1, PPP1R12C, PPP2R3B, TRIM41 and VIM (By similarity). CC Interacts with MAVS; interaction takes place following single-stranded CC RNA (ssRNA)-binding (By similarity). Interacts with ATG16L1 CC (PubMed:19898471, PubMed:19966812, PubMed:31919280). Interacts with CC Irgm1; promoting Irgm1 'Lys-63'-linked polyubiquitination, which is CC required for interactions with the core autophagy factors (By CC similarity). {ECO:0000250|UniProtKB:Q9HC29, CC ECO:0000269|PubMed:16203728, ECO:0000269|PubMed:17187069, CC ECO:0000269|PubMed:18511561, ECO:0000269|PubMed:19898471, CC ECO:0000269|PubMed:19966812, ECO:0000269|PubMed:23019338, CC ECO:0000269|PubMed:31919280}. CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q9HC29}; CC Lipid-anchor {ECO:0000250|UniProtKB:Q9HC29}. Basolateral cell membrane CC {ECO:0000250|UniProtKB:Q9HC29}. Cytoplasm CC {ECO:0000250|UniProtKB:Q9HC29}. Mitochondrion CC {ECO:0000250|UniProtKB:Q9HC29}. Note=Palmitoylation promotes CC localization to the cell membrane, where it detects bacterial invasion CC at the point of entry. {ECO:0000250|UniProtKB:Q9HC29}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q8K3Z0-1; Sequence=Displayed; CC Name=2; CC IsoId=Q8K3Z0-2; Sequence=VSP_007069, VSP_007070; CC -!- TISSUE SPECIFICITY: Expressed in monocytes, macrophages, dendritic CC cells, hepatocytes, preadipocytes, epithelial cells of oral cavity, CC lung and intestine (PubMed:25666722). In intestine, highly expressed in CC ileal Paneth cells of the crypt and in intestinal stem cells CC (PubMed:15692051, PubMed:24882705, PubMed:25666722). Also expressed in CC neurons of several brain regions including the hypothalamus CC (PubMed:35420957). {ECO:0000269|PubMed:15692051, CC ECO:0000269|PubMed:24882705, ECO:0000269|PubMed:25666722, CC ECO:0000269|PubMed:35420957}. CC -!- DOMAIN: The ATG16L1-binding motif mediates interaction with ATG16L1. CC {ECO:0000250|UniProtKB:Q9HC29}. 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. {ECO:0000250|UniProtKB:Q9HC29}. CC -!- DOMAIN: The LRR repeats recognize and bind muramyl dipeptide (MDP). CC {ECO:0000250|UniProtKB:Q9HC29}. CC -!- DOMAIN: The NACHT domain recognizes and binds sphingosine-1-phosphate CC in response to endoplasmic reticulum stress. CC {ECO:0000250|UniProtKB:Q9HC29}. CC -!- PTM: Palmitoylated by ZDHHC5; palmitoylation is required for proper CC recruitment to the bacterial entry site and hence for proper signaling CC upon cognate peptidoglycan detection (By similarity). Palmitoylation CC promotes localization to the cell membrane (By similarity). CC Palmitoylation protects from SQSTM1/p62-dependent autophagic CC degradation (By similarity). {ECO:0000250|UniProtKB:Q9HC29, CC ECO:0000250|UniProtKB:Q9Y239}. CC -!- PTM: Polyubiquitinated by TRIM27, leading to proteasome-mediated CC degradation (By similarity). Polyubiquitinated and degraded following CC muramyl dipeptide (MDP) stimulation, conferring MDP tolerance and CC preventing septic shock (By similarity). CC {ECO:0000250|UniProtKB:Q9HC29}. CC -!- PTM: Degraded via selective autophagy following interaction with Irgm1. CC Irgm1 promotes NOD2-RIPK2 RIPosome recruitment to autophagosome CC membranes, promoting their SQSTM1/p62-dependent autophagic degradation. CC {ECO:0000250|UniProtKB:Q9HC29}. CC -!- PTM: O-glycosylated by OGT, O-GlcNAcylation increases protein CC stability. {ECO:0000250|UniProtKB:Q9HC29}. CC -!- DISRUPTION PHENOTYPE: No visible phenotype in absence of infection; CC mice are healthy and display normal lymphoid and myeloid cellular CC composition in the thymus and spleen (PubMed:15692051). Mice are CC however susceptible to bacterial infection due to the inability to CC detect bacterial muramyl dipeptide and trigger an innate immune CC response (PubMed:15692051). Deletion mice have an altered composition CC of the gut microbiota with a net increase in the abundance of CC bacteroidetes and firmicutes phyla in the feces and terminal ileum CC compared to wild-type mice due to the fact that they are unable to kill CC bacteria effectively (PubMed:19805227, PubMed:21421666). Mice show CC inflammation of the small intestine, due to an imbalance of the CC equilibrium between intestinal microbiota and host immune responses CC (PubMed:25088769). Dysbiosis caused by the absence of Nod2 predisposes CC mice to transmissible colitis and colorectal cancer (PubMed:23281400). CC Mice show increased bacterial adherence to the intestinal mucosa and CC bacterial infiltration in metabolic tissues, such as hepatic and CC adipose tissue, exacerbating inflammation and insulin resistance CC (PubMed:25666722). Mice show a reduced number of intestinal CC intraepithelial lymphocytes impairing the epithelium integrity and CC leading to altered immune response to the resident microbiota CC (PubMed:24062413). Conditional deletion in GABAergic neurons leads to CC metabolic alterations, characterized by a delay in achieving satiety CC and delayed temperature drops in response to fasting (PubMed:35420957). CC Mice lacking Nod1 and Nod2 are protected from high-fat diet-induced CC inflammation, lipid accumulation, and peripheral insulin intolerance CC (PubMed:21715553). {ECO:0000269|PubMed:15692051, CC ECO:0000269|PubMed:19805227, ECO:0000269|PubMed:21421666, CC ECO:0000269|PubMed:21715553, ECO:0000269|PubMed:23281400, CC ECO:0000269|PubMed:24062413, ECO:0000269|PubMed:25088769, CC ECO:0000269|PubMed:25666722, ECO:0000269|PubMed:35420957}. CC -!- SIMILARITY: Belongs to the NOD1-NOD2 family. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAH44774.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; 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; AF520774; AAM76073.1; -; mRNA. DR EMBL; BC044774; AAH44774.1; ALT_INIT; mRNA. DR AlphaFoldDB; Q8K3Z0; -. DR SMR; Q8K3Z0; -. DR CORUM; Q8K3Z0; -. DR DIP; DIP-46115N; -. DR IntAct; Q8K3Z0; 3. DR STRING; 10090.ENSMUSP00000113773; -. DR ChEMBL; CHEMBL5169176; -. DR PhosphoSitePlus; Q8K3Z0; -. DR PaxDb; 10090-ENSMUSP00000050538; -. DR Antibodypedia; 28302; 555 antibodies from 37 providers. DR Ensembl; ENSMUST00000054324.15; ENSMUSP00000050538.9; ENSMUSG00000055994.16. [Q8K3Z0-2] DR Ensembl; ENSMUST00000109634.3; ENSMUSP00000105262.3; ENSMUSG00000055994.16. [Q8K3Z0-1] DR UCSC; uc009mrq.1; mouse. [Q8K3Z0-1] DR AGR; MGI:2429397; -. DR MGI; MGI:2429397; Nod2. DR VEuPathDB; HostDB:ENSMUSG00000055994; -. DR eggNOG; KOG4308; Eukaryota. DR GeneTree; ENSGT00940000160934; -. DR InParanoid; Q8K3Z0; -. DR PhylomeDB; Q8K3Z0; -. DR TreeFam; TF352118; -. DR Reactome; R-MMU-168638; NOD1/2 Signaling Pathway. DR Reactome; R-MMU-450302; activated TAK1 mediates p38 MAPK activation. DR Reactome; R-MMU-450321; JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1. DR Reactome; R-MMU-5689896; Ovarian tumor domain proteases. DR PRO; PR:Q8K3Z0; -. DR Proteomes; UP000000589; Chromosome 8. DR RNAct; Q8K3Z0; Protein. DR Bgee; ENSMUSG00000055994; Expressed in granulocyte and 40 other cell types or tissues. DR ExpressionAtlas; Q8K3Z0; baseline and differential. DR GO; GO:0016323; C:basolateral plasma membrane; ISO:MGI. 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:HGNC-UCL. DR GO; GO:0019897; C:extrinsic component of plasma membrane; ISS:UniProtKB. DR GO; GO:0005794; C:Golgi apparatus; ISO:MGI. DR GO; GO:0005739; C:mitochondrion; IEA:UniProtKB-SubCell. DR GO; GO:0045335; C:phagocytic vesicle; ISO:MGI. DR GO; GO:0005886; C:plasma membrane; ISS:HGNC-UCL. DR GO; GO:0032991; C:protein-containing complex; ISS:UniProtKB. DR GO; GO:0031982; C:vesicle; ISS:HGNC-UCL. DR GO; GO:0003779; F:actin binding; ISO:MGI. DR GO; GO:0043531; F:ADP binding; ISS:UniProtKB. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0050700; F:CARD domain binding; ISS:HGNC-UCL. DR GO; GO:0019899; F:enzyme binding; ISS:HGNC-UCL. DR GO; GO:0030544; F:Hsp70 protein binding; ISO:MGI. DR GO; GO:0051879; F:Hsp90 protein binding; ISO:MGI. DR GO; GO:0032500; F:muramyl dipeptide binding; IDA:MGI. DR GO; GO:0038187; F:pattern recognition receptor activity; IDA:UniProtKB. DR GO; GO:0042834; F:peptidoglycan binding; ISS:HGNC-UCL. DR GO; GO:0019901; F:protein kinase binding; ISS:HGNC-UCL. DR GO; GO:0044877; F:protein-containing complex binding; ISO:MGI. DR GO; GO:0043130; F:ubiquitin binding; ISS:UniProtKB. DR GO; GO:0002253; P:activation of immune response; IMP:MGI. DR GO; GO:0002250; P:adaptive immune response; IEA:UniProtKB-KW. DR GO; GO:0140367; P:antibacterial innate immune response; IEA:Ensembl. DR GO; GO:0002815; P:biosynthetic process of antibacterial peptides active against Gram-positive bacteria; IMP:MGI. 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:0071407; P:cellular response to organic cyclic compound; IEA:Ensembl. DR GO; GO:0071224; P:cellular response to peptidoglycan; IMP:MGI. DR GO; GO:0006952; P:defense response; TAS:HGNC-UCL. DR GO; GO:0042742; P:defense response to bacterium; IMP:UniProtKB. DR GO; GO:0050830; P:defense response to Gram-positive bacterium; IMP:MGI. DR GO; GO:0016045; P:detection of bacterium; ISS:HGNC-UCL. DR GO; GO:0009595; P:detection of biotic stimulus; TAS:HGNC-UCL. DR GO; GO:0032498; P:detection of muramyl dipeptide; ISS:HGNC-UCL. DR GO; GO:0070371; P:ERK1 and ERK2 cascade; IDA:MGI. DR GO; GO:0051649; P:establishment of localization in cell; IMP:MGI. DR GO; GO:0048874; P:host-mediated regulation of intestinal microbiota composition; IMP:UniProtKB. DR GO; GO:0006954; P:inflammatory response; TAS:HGNC-UCL. DR GO; GO:0045087; P:innate immune response; ISS:UniProtKB. DR GO; GO:0002227; P:innate immune response in mucosa; IMP:MGI. DR GO; GO:0036335; P:intestinal stem cell homeostasis; IMP:UniProtKB. DR GO; GO:0035556; P:intracellular signal transduction; ISS:UniProtKB. DR GO; GO:0007254; P:JNK cascade; IDA:MGI. DR GO; GO:0030277; P:maintenance of gastrointestinal epithelium; ISO:MGI. DR GO; GO:0000165; P:MAPK cascade; IMP:MGI. DR GO; GO:0002862; P:negative regulation of inflammatory response to antigenic stimulus; IMP:MGI. DR GO; GO:0032695; P:negative regulation of interleukin-12 production; IDA:MGI. DR GO; GO:0032701; P:negative regulation of interleukin-18 production; IMP:MGI. DR GO; GO:0032703; P:negative regulation of interleukin-2 production; IMP:MGI. DR GO; GO:2000110; P:negative regulation of macrophage apoptotic process; IDA:BHF-UCL. DR GO; GO:0010936; P:negative regulation of macrophage cytokine production; IDA:MGI. DR GO; GO:0002710; P:negative regulation of T cell mediated immunity; IMP:MGI. DR GO; GO:0034136; P:negative regulation of toll-like receptor 2 signaling pathway; IMP:MGI. DR GO; GO:0032720; P:negative regulation of tumor necrosis factor production; IMP:MGI. DR GO; GO:0032689; P:negative regulation of type II interferon production; IMP:MGI. DR GO; GO:0070431; P:nucleotide-binding oligomerization domain containing 2 signaling pathway; IDA:UniProtKB. DR GO; GO:0002221; P:pattern recognition receptor signaling pathway; ISO:MGI. DR GO; GO:0006909; P:phagocytosis; IMP:MGI. DR GO; GO:0006963; P:positive regulation of antibacterial peptide biosynthetic process; IDA:MGI. DR GO; GO:0010508; P:positive regulation of autophagy; IDA:UniProtKB. DR GO; GO:0050871; P:positive regulation of B cell activation; ISO:MGI. DR GO; GO:0006965; P:positive regulation of biosynthetic process of antibacterial peptides active against Gram-positive bacteria; IMP:MGI. DR GO; GO:0043123; P:positive regulation of canonical NF-kappaB signal transduction; IDA:UniProtKB. DR GO; GO:0008284; P:positive regulation of cell population proliferation; ISO:MGI. DR GO; GO:0002720; P:positive regulation of cytokine production involved in immune response; ISS:UniProtKB. DR GO; GO:1900017; P:positive regulation of cytokine production involved in inflammatory response; ISO:MGI. DR GO; GO:0002606; P:positive regulation of dendritic cell antigen processing and presentation; IMP:BHF-UCL. DR GO; GO:0002732; P:positive regulation of dendritic cell cytokine production; ISO:MGI. DR GO; GO:0050679; P:positive regulation of epithelial cell proliferation; IMP:BHF-UCL. DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IDA:BHF-UCL. DR GO; GO:0002925; P:positive regulation of humoral immune response mediated by circulating immunoglobulin; IMP:MGI. DR GO; GO:0045089; P:positive regulation of innate immune response; IDA:BHF-UCL. DR GO; GO:0032731; P:positive regulation of interleukin-1 beta production; ISS:UniProtKB. DR GO; GO:0032733; P:positive regulation of interleukin-10 production; IMP:BHF-UCL. DR GO; GO:0032735; P:positive regulation of interleukin-12 production; IDA:MGI. DR GO; GO:0032740; P:positive regulation of interleukin-17 production; ISS:UniProtKB. DR GO; GO:0032755; P:positive regulation of interleukin-6 production; IDA:MGI. DR GO; GO:0032757; P:positive regulation of interleukin-8 production; ISO:MGI. DR GO; GO:0046330; P:positive regulation of JNK cascade; IDA:MGI. DR GO; GO:0060907; P:positive regulation of macrophage cytokine production; IDA:MGI. DR GO; GO:0043410; P:positive regulation of MAPK cascade; IDA:BHF-UCL. DR GO; GO:1901526; P:positive regulation of mitophagy; IMP:UniProtKB. DR GO; GO:0071639; P:positive regulation of monocyte chemotactic protein-1 production; IMP:UniProtKB. DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; ISS:HGNC-UCL. DR GO; GO:0051770; P:positive regulation of nitric-oxide synthase biosynthetic process; IMP:BHF-UCL. DR GO; GO:1901224; P:positive regulation of non-canonical NF-kappaB signal transduction; IMP:MGI. DR GO; GO:0045747; P:positive regulation of Notch signaling pathway; IDA:BHF-UCL. DR GO; GO:0050731; P:positive regulation of peptidyl-tyrosine phosphorylation; IMP:MGI. DR GO; GO:0050766; P:positive regulation of phagocytosis; IMP:MGI. DR GO; GO:1902523; P:positive regulation of protein K63-linked ubiquitination; ISO:MGI. DR GO; GO:0031398; P:positive regulation of protein ubiquitination; IDA:UniProtKB. DR GO; GO:0032874; P:positive regulation of stress-activated MAPK cascade; IDA:MGI. 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; IDA:MGI. DR GO; GO:0002830; P:positive regulation of type 2 immune response; ISS:BHF-UCL. DR GO; GO:1904417; P:positive regulation of xenophagy; IMP:MGI. DR GO; GO:0032098; P:regulation of appetite; IMP:UniProtKB. DR GO; GO:0050727; P:regulation of inflammatory response; IMP:MGI. DR GO; GO:0090022; P:regulation of neutrophil chemotaxis; IMP:MGI. DR GO; GO:0034976; P:response to endoplasmic reticulum stress; IDA:UniProtKB. DR GO; GO:0043330; P:response to exogenous dsRNA; IMP:MGI. DR GO; GO:0032496; P:response to lipopolysaccharide; IMP:MGI. DR GO; GO:0032495; P:response to muramyl dipeptide; IDA:UniProtKB. DR GO; GO:0007584; P:response to nutrient; IEA:Ensembl. DR GO; GO:0032494; P:response to peptidoglycan; IDA:MGI. DR GO; GO:0007165; P:signal transduction; TAS:HGNC-UCL. DR GO; GO:0051403; P:stress-activated MAPK cascade; IDA:MGI. DR GO; GO:0001659; P:temperature homeostasis; IMP:UniProtKB. DR GO; GO:0034134; P:toll-like receptor 2 signaling pathway; IMP:MGI. DR GO; GO:0098792; P:xenophagy; IMP:MGI. DR Gene3D; 1.10.533.10; Death Domain, Fas; 2. DR Gene3D; 3.40.50.300; P-loop containing nucleotide triphosphate hydrolases; 1. DR Gene3D; 3.80.10.10; Ribonuclease Inhibitor; 1. DR InterPro; IPR001315; CARD. DR InterPro; IPR011029; DEATH-like_dom_sf. DR InterPro; IPR018228; DNase_TatD-rel_CS. 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 PANTHER; PTHR24106; NACHT, LRR AND CARD DOMAINS-CONTAINING; 1. DR PANTHER; PTHR24106:SF64; NUCLEOTIDE-BINDING OLIGOMERIZATION DOMAIN-CONTAINING PROTEIN 2; 1. DR Pfam; PF00619; CARD; 1. DR Pfam; PF13516; LRR_6; 5. DR Pfam; PF05729; NACHT; 1. DR Pfam; PF17776; NLRC4_HD2; 1. DR Pfam; PF17779; NOD2_WH; 1. DR SMART; SM00368; LRR_RI; 8. DR SUPFAM; SSF47986; DEATH domain; 2. DR SUPFAM; SSF52540; P-loop containing nucleoside triphosphate hydrolases; 1. DR SUPFAM; SSF52047; RNI-like; 1. DR PROSITE; PS50209; CARD; 2. DR PROSITE; PS50837; NACHT; 1. PE 1: Evidence at protein level; KW Adaptive immunity; Alternative splicing; ATP-binding; Autophagy; KW Cell membrane; Cytoplasm; Glycoprotein; Immunity; Innate immunity; KW Leucine-rich repeat; Lipoprotein; Membrane; Mitochondrion; KW Nucleotide-binding; Palmitate; Reference proteome; Repeat; Ubl conjugation. FT CHAIN 1..1020 FT /note="Nucleotide-binding oligomerization domain-containing FT protein 2" FT /id="PRO_0000144091" FT DOMAIN 6..104 FT /note="CARD 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00046" FT DOMAIN 106..200 FT /note="CARD 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00046" FT DOMAIN 273..600 FT /note="NACHT" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00136" FT REPEAT 685..709 FT /note="LRR 1" FT REPEAT 726..749 FT /note="LRR 2" FT REPEAT 766..792 FT /note="LRR 3" FT REPEAT 794..817 FT /note="LRR 4" FT REPEAT 822..845 FT /note="LRR 5" FT REPEAT 850..873 FT /note="LRR 6" FT REPEAT 906..929 FT /note="LRR 7" FT REPEAT 934..962 FT /note="LRR 8" FT REPEAT 963..985 FT /note="LRR 9" FT REPEAT 1005..1019 FT /note="LRR 10" FT REGION 221..254 FT /note="Required for CARD9 binding" FT /evidence="ECO:0000250|UniProtKB:Q9HC29" FT MOTIF 43..57 FT /note="ATG16L1-binding motif" FT /evidence="ECO:0000250|UniProtKB:Q9HC29" FT BINDING 219 FT /ligand="ADP" FT /ligand_id="ChEBI:CHEBI:456216" FT /evidence="ECO:0000250|UniProtKB:G1T469" FT BINDING 232 FT /ligand="ADP" FT /ligand_id="ChEBI:CHEBI:456216" FT /evidence="ECO:0000250|UniProtKB:G1T469" FT BINDING 233 FT /ligand="ADP" FT /ligand_id="ChEBI:CHEBI:456216" FT /evidence="ECO:0000250|UniProtKB:G1T469" FT BINDING 282 FT /ligand="ADP" FT /ligand_id="ChEBI:CHEBI:456216" FT /evidence="ECO:0000250|UniProtKB:G1T469" FT BINDING 283 FT /ligand="ADP" FT /ligand_id="ChEBI:CHEBI:456216" FT /evidence="ECO:0000250|UniProtKB:G1T469" FT BINDING 284 FT /ligand="ADP" FT /ligand_id="ChEBI:CHEBI:456216" FT /evidence="ECO:0000250|UniProtKB:G1T469" FT BINDING 285 FT /ligand="ADP" FT /ligand_id="ChEBI:CHEBI:456216" FT /evidence="ECO:0000250|UniProtKB:G1T469" FT BINDING 286 FT /ligand="ADP" FT /ligand_id="ChEBI:CHEBI:456216" FT /evidence="ECO:0000250|UniProtKB:G1T469" FT BINDING 287 FT /ligand="ADP" FT /ligand_id="ChEBI:CHEBI:456216" FT /evidence="ECO:0000250|UniProtKB:G1T469" FT BINDING 583 FT /ligand="ADP" FT /ligand_id="ChEBI:CHEBI:456216" FT /evidence="ECO:0000250|UniProtKB:G1T469" FT LIPID 375 FT /note="S-palmitoyl cysteine" FT /evidence="ECO:0000250|UniProtKB:Q9HC29" FT VAR_SEQ 1..7 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_007069" FT VAR_SEQ 195 FT /note="E -> EGYSLCRSRCDRGFTLICLFCIL (in isoform 2)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_007070" FT VARIANT 212 FT /note="T -> A (in strain: NMRI)" FT /evidence="ECO:0000269|PubMed:15489334" FT VARIANT 240 FT /note="Q -> R (in strain: NMRI)" FT /evidence="ECO:0000269|PubMed:15489334" FT VARIANT 422 FT /note="L -> C (in strain: NMRI; requires 2 nucleotide FT substitutions)" FT /evidence="ECO:0000269|PubMed:15489334" FT VARIANT 485 FT /note="G -> V (in strain: NMRI)" FT /evidence="ECO:0000269|PubMed:15489334" FT VARIANT 603 FT /note="V -> A (in strain: NMRI)" FT /evidence="ECO:0000269|PubMed:15489334" FT VARIANT 675 FT /note="V -> I (in strain: NMRI)" FT /evidence="ECO:0000269|PubMed:15489334" FT VARIANT 925 FT /note="E -> Q (in strain: NMRI)" FT /evidence="ECO:0000269|PubMed:15489334" FT MUTAGEN 314 FT /note="R->Q: Mutation that mimics a human variant FT associated with Blau syndrome (BLAUS); knockin mice show FT impaired response to muramyl dipeptide." FT /evidence="ECO:0000269|PubMed:25429073" FT MUTAGEN 987..1020 FT /note="LSRNSAILEVWLRGNTFSLEEIQTLSSRDARLLL->P: Mutation that FT mimics human L1007fsinsC variant; knockin mice show FT elevated NF-kappa-B activation in response to muramyl FT dipeptide and more efficient processing and secretion of FT the cytokine IL1B." FT /evidence="ECO:0000269|PubMed:15692052" SQ SEQUENCE 1020 AA; 113562 MW; 25504905ECF70FBB CRC64; MRSSCCDMCS QEEFQAQRSQ LVALLISGSL EGFESILDWL LSWDVLSRED YEGLSLPGQP LSHSARRLLD TVWNKGVWGC QKLLEAVQEA QANSHTFELY GSWDTHSLHP TRDLQSHRPA IVRRLYNHVE AMLELAREGG FLSQYECEEI RLPIFTSSQR ARRLLDLAAV KANGLAAFLL QHVRELPAPL PLPYEAAECQ KFISKLRTMV LTQSRFLSTY DGSENLCLED IYTENILELQ TEVGTAGALQ KSPAILGLED LFDTHGHLNR DADTILVVGE AGSGKSTLLQ RLHLLWATGR SFQEFLFIFP FSCRQLQCVA KPLSLRTLLF EHCCWPDVAQ DDVFQFLLDH PDRVLLTFDG LDEFKFRFTD RERHCSPIDP TSVQTLLFNL LQGNLLKNAC KVLTSRPDAV SALLRKFVRT ELQLKGFSEE GIQLYLRKHH REPGVADRLI QLIQATSALH GLCHLPVFSW MVSRCHRELL LQNRGFPTTS TDMYLLILQH FLLHASPPDS SPLGLGPGLL QSRLSTLLHL GHLALRGLAM SCYVFSAQQL QAAQVDSDDI SLGFLVRAQS SVPGSKAPLE FLHITFQCFF AAFYLAVSAD TSVASLKHLF SCGRLGSSLL GRLLPNLCIQ GSRVKKGSEA ALLQKAEPHN LQITAAFLAG LLSQQHRDLL AACQVSERVL LQRQARARSC LAHSLREHFH SIPPAVPGET KSMHAMPGFI WLIRSLYEMQ EEQLAQEAVR RLDIGHLKLT FCRVGPAECA ALAFVLQHLQ RPVALQLDYN SVGDVGVEQL RPCLGVCTAL YLRDNNISDR GARTLVECAL RCEQLQKLAL FNNKLTDACA CSMAKLLAHK QNFLSLRVGN NHITAAGAEV LAQGLKSNTS LKFLGFWGNS VGDKGTQALA EVVADHQNLK WLSLVGNNIG SMGAEALALM LEKNKSLEEL CLEENHICDE GVYSLAEGLK RNSTLKFLKL SNNGITYRGA EALLQALSRN SAILEVWLRG NTFSLEEIQT LSSRDARLLL //