NOD1_MOUSE
ID NOD1_MOUSE Reviewed; 953 AA.
AC Q8BHB0; Q8BUT6;
DT 28-MAR-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 167.
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 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 [LARGE SCALE MRNA].
RC STRAIN=NOD; TISSUE=Cerebellum, and Spleen;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ALA-884.
RC STRAIN=Czech II, and FVB/N; 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 IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Lung;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [4]
RP DISRUPTION PHENOTYPE, FUNCTION, AND TISSUE SPECIFICITY.
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 [5]
RP FUNCTION, SUBCELLULAR LOCATION, AND DISRUPTION PHENOTYPE.
RX PubMed=31201384; DOI=10.1038/s41422-019-0190-3;
RA Zhang Q., Pan Y., Zeng B., Zheng X., Wang H., Shen X., Li H., Jiang Q.,
RA Zhao J., Meng Z.X., Li P., Chen Z., Wei H., Liu Z.;
RT "Intestinal lysozyme liberates Nod1 ligands from microbes to direct insulin
RT trafficking in pancreatic beta cells.";
RL Cell Res. 29:516-532(2019).
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:21715553). Ligand
CC binding triggers oligomerization that facilitates the binding and
CC subsequent activation of the receptor interacting protein-2/RIPK2.
CC RIPK2 subsequently recruits the kinase TAK1 to activate NF-kappa-B and
CC MAPK signaling pathways. Regulates also antiviral response elicited by
CC dsRNA and the expression of RLR pathway members by targeting IFIH1 and
CC TRAF3 to modulate the formation of IFIH1-MAVS and TRAF3-MAVS complexes
CC leading to increased transcription of type I IFNs. Besides recognizing
CC pathogens, participates in surveillance of cellular homeostasis through
CC sensing and binding to the cytosolic metabolite sphingosine-1-phosphate
CC and then initating inflammation process (By similarity). In addition,
CC plays a role in insulin trafficking in beta cells in a cell-autonomous
CC manner. Mechanistically, upon recognizing cognate ligands, NOD1 and
CC RIPK2 localize to insulin vesicles where they recruit RAB1A to direct
CC insulin trafficking through the cytoplasm (PubMed:31201384).
CC {ECO:0000250|UniProtKB:Q9Y239, ECO:0000269|PubMed:21715553,
CC ECO:0000269|PubMed:31201384}.
CC -!- SUBUNIT: Forms homooligomers. Interacts with RIPK2. Interacts with
CC ARHGEF2. Interacts with NLRP10 and recruits it to the cell membrane
CC following invasive bacterial infection. Interacts with RNF34. Interacts
CC with IFIH1; this interaction promotes transcription of antiviral genes
CC and inhibition of viral replication. {ECO:0000250|UniProtKB:Q9Y239}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Cell membrane
CC {ECO:0000250}. Apical cell membrane {ECO:0000250}. Basolateral cell
CC membrane {ECO:0000250}. Note=Detected in the cytoplasm and at the cell
CC membrane. Following bacterial infection, localizes to bacterial entry
CC sites in the cell membrane. Recruited to the basolateral and apical
CC membranes in polarized epithelial cells (By similarity). {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Although ubiquitously expressed, NOD1 levels are
CC more abundant in immune cells, the gastrointestinal tract, and adipose
CC tissue. {ECO:0000269|PubMed:21715553}.
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:0000250|UniProtKB:Q9Y239}.
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 -!- DISRUPTION PHENOTYPE: Deletion mutant mice show a normal glucose
CC tolerance but the level of circulating insulin after glucose infusion
CC was significantly lower than in WT mice (PubMed:31201384). NOD1/NOD2
CC double knockout mice are protected from high-fat diet-induced
CC inflammation, lipid accumulation, and peripheral insulin intolerance
CC (PubMed:21715553). {ECO:0000269|PubMed:21715553,
CC ECO:0000269|PubMed:31201384}.
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; AK082663; BAC38566.1; -; mRNA.
DR EMBL; AK089662; BAC40940.1; -; mRNA.
DR EMBL; BC042670; AAH42670.1; -; mRNA.
DR EMBL; BC043670; AAH43670.1; -; mRNA.
DR CCDS; CCDS20160.1; -.
DR RefSeq; NP_001164478.1; NM_001171007.1.
DR RefSeq; NP_766317.1; NM_172729.3.
DR AlphaFoldDB; Q8BHB0; -.
DR SMR; Q8BHB0; -.
DR BioGRID; 223435; 4.
DR DIP; DIP-59535N; -.
DR IntAct; Q8BHB0; 1.
DR STRING; 10090.ENSMUSP00000055747; -.
DR iPTMnet; Q8BHB0; -.
DR PhosphoSitePlus; Q8BHB0; -.
DR MaxQB; Q8BHB0; -.
DR PaxDb; Q8BHB0; -.
DR PRIDE; Q8BHB0; -.
DR ProteomicsDB; 295502; -.
DR Antibodypedia; 26181; 414 antibodies from 37 providers.
DR Ensembl; ENSMUST00000060655; ENSMUSP00000055747; ENSMUSG00000038058.
DR Ensembl; ENSMUST00000168172; ENSMUSP00000130487; ENSMUSG00000038058.
DR GeneID; 107607; -.
DR KEGG; mmu:107607; -.
DR UCSC; uc009caf.2; mouse.
DR CTD; 10392; -.
DR MGI; MGI:1341839; Nod1.
DR VEuPathDB; HostDB:ENSMUSG00000038058; -.
DR eggNOG; KOG4308; Eukaryota.
DR GeneTree; ENSGT00940000157845; -.
DR HOGENOM; CLU_011291_1_0_1; -.
DR InParanoid; Q8BHB0; -.
DR OMA; SYEFFHI; -.
DR OrthoDB; 88836at2759; -.
DR PhylomeDB; Q8BHB0; -.
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 BioGRID-ORCS; 107607; 2 hits in 72 CRISPR screens.
DR ChiTaRS; Nod1; mouse.
DR PRO; PR:Q8BHB0; -.
DR Proteomes; UP000000589; Chromosome 6.
DR RNAct; Q8BHB0; protein.
DR Bgee; ENSMUSG00000038058; Expressed in mesenteric lymph node and 171 other tissues.
DR ExpressionAtlas; Q8BHB0; baseline and differential.
DR Genevisible; Q8BHB0; MM.
DR GO; GO:0046658; C:anchored component of plasma membrane; ISO:MGI.
DR GO; GO:0016324; C:apical plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016323; C:basolateral plasma membrane; ISS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0045335; C:phagocytic vesicle; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0050700; F:CARD domain binding; ISO:MGI.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0038187; F:pattern recognition receptor activity; ISO:MGI.
DR GO; GO:0042803; F:protein homodimerization activity; ISO:MGI.
DR GO; GO:0044877; F:protein-containing complex binding; ISO:MGI.
DR GO; GO:0006919; P:activation of cysteine-type endopeptidase activity involved in apoptotic process; ISO:MGI.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0071225; P:cellular response to muramyl dipeptide; ISO:MGI.
DR GO; GO:0042742; P:defense response to bacterium; ISS:HGNC-UCL.
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:0070371; P:ERK1 and ERK2 cascade; IDA:MGI.
DR GO; GO:0007249; P:I-kappaB kinase/NF-kappaB signaling; IDA:MGI.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:0035556; P:intracellular signal transduction; ISS:HGNC-UCL.
DR GO; GO:0007254; P:JNK cascade; IDA:MGI.
DR GO; GO:0002221; P:pattern recognition receptor signaling pathway; ISO:MGI.
DR GO; GO:0010942; P:positive regulation of cell death; ISO:MGI.
DR GO; GO:0043280; P:positive regulation of cysteine-type endopeptidase activity involved in apoptotic process; ISO:MGI.
DR GO; GO:0002606; P:positive regulation of dendritic cell antigen processing and presentation; IMP:BHF-UCL.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IDA:MGI.
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; ISO:MGI.
DR GO; GO:0032755; P:positive regulation of interleukin-6 production; IMP:MGI.
DR GO; GO:0032757; P:positive regulation of interleukin-8 production; ISS:HGNC-UCL.
DR GO; GO:0046330; P:positive regulation of JNK cascade; IDA:MGI.
DR GO; GO:0060907; P:positive regulation of macrophage cytokine production; IMP:MGI.
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; ISO:MGI.
DR GO; GO:0051000; P:positive regulation of nitric-oxide synthase activity; ISO:MGI.
DR GO; GO:0032874; P:positive regulation of stress-activated MAPK cascade; IDA:MGI.
DR GO; GO:0032760; P:positive regulation of tumor necrosis factor production; IMP:MGI.
DR GO; GO:1904417; P:positive regulation of xenophagy; IMP:MGI.
DR GO; GO:0042981; P:regulation of apoptotic process; IEA:InterPro.
DR GO; GO:0051403; P:stress-activated MAPK cascade; IDA:MGI.
DR GO; GO:0098792; P:xenophagy; IMP:MGI.
DR Gene3D; 1.10.533.10; -; 1.
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; 5.
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 Apoptosis; ATP-binding; Cell membrane; Cytoplasm; Immunity;
KW Innate immunity; Leucine-rich repeat; Lipoprotein; Membrane;
KW Nucleotide-binding; Palmitate; Reference proteome; Repeat; Ubl conjugation.
FT CHAIN 1..953
FT /note="Nucleotide-binding oligomerization domain-containing
FT protein 1"
FT /id="PRO_0000144078"
FT DOMAIN 15..107
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 702..725
FT /note="LRR 1"
FT REPEAT 727..750
FT /note="LRR 2"
FT REPEAT 755..778
FT /note="LRR 3"
FT REPEAT 783..806
FT /note="LRR 4"
FT REPEAT 839..862
FT /note="LRR 5"
FT REPEAT 867..890
FT /note="LRR 6"
FT REPEAT 895..918
FT /note="LRR 7"
FT REPEAT 923..946
FT /note="LRR 8"
FT BINDING 202..209
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00136"
FT VARIANT 884
FT /note="S -> A (in strain: Czech II)"
FT /evidence="ECO:0000269|PubMed:15489334"
SQ SEQUENCE 953 AA; 107740 MW; 39C639621CEB1A58 CRC64;
MEEHGHHEME GTPLGCHSHI KLLKINREHL VTNIRNTQCL VDNLLENGYF SAEDAEIVCA
CPTKPDKVRK ILDLVQSKGE EVSEFFLYVL QQLEDAYVDL RLWLSEIGFS PSQLIRTKTI
VNTDPVSRYT QQLRHQLGRD SKFMLCYAQK EDLLLEETYM DTLMELVGFN NENLGSLGGL
DCLLDHSTGV LNEHGETVFV FGDAGVGKSM LLQRLQSLWA SGRLTSTAKF FFHFRCRMFS
CFKESDMLSL QDLLFKHFCY PEQDPEEVFS FLLRFPHTAL FTFDGLDELH SDFDLSRVPD
SCCPWEPAHP LVLLANLLSG RLLKGAGKLL TARTGVEVPR QLLRKKVLLR GFSPSHLRAY
ARRMFPERTA QEHLLQQLDA NPNLCSLCGV PLFCWIIFRC FQHFQTVFEG SSSQLPDCAV
TLTDVFLLVT EVHLNRPQPS SLVQRNTRSP AETLRAGWRT LHALGEVAHR GTDKSLFVFG
QEEVQASKLQ EGDLQLGFLR ALPDVGPEQG QSYEFFHLTL QAFFTAFFLV ADDKVSTREL
LRFFREWTSP GEATSSSCHS SFFSFQCLGG RSRLGPDPFR NKDHFQFTNL FLCGLLAKAR
QKLLRQLVPK AILRRKRKAL WAHLFASLRS YLKSLPRVQS GGFNQVHAMP TFLWMLRCIY
ETQSQKVGRL AARGISADYL KLAFCNACSA DCSALSFVLH HFHRQLALDL DNNNLNDYGV
QELQPCFSRL TVIRLSVNQI TDTGVKVLCE ELTKYKIVTF LGLYNNQITD IGARYVAQIL
DECRGLKHLK LGKNRITSEG GKCVALAVKN STSIVDVGMW GNQIGDEGAK AFAEALKDHP
SLTTLSLAFN GISPEGGKSL AQALKQNTTL TVIWLTKNEL NDESAECFAE MLRVNQTLRH
LWLIQNRITA KGTAQLARAL QKNTAITEIC LNGNLIKPEE AKVFENEKRI ICF
