Q8K3Z0 (NOD2_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Nucleotide-binding oligomerization domain-containing protein 2

Alternative name(s):
Caspase recruitment domain-containing protein 15

Gene names

Name:	Nod2
Synonyms:	Card15

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	1020 AA.
Sequence status	Complete.
Protein existence	Evidence at transcript level

General annotation (Comments)

Function	Induces NF-kappa-B via RICK (CARDIAK, RIP2) and IKK-gamma. Confers responsiveness to intracellular bacterial lipopolysaccharides (LPS) By similarity.
Subunit structure	Binds to RICK by CARD-CARD interaction. Interacts with ATG16L1 By similarity.
Subcellular location	Cytoplasm By similarity.
Domain	The ATG16L1-binding motif mediates interaction with ATG16L1 By similarity.
Sequence similarities	Contains 2 CARD domains. Contains 10 LRR (leucine-rich) repeats. Contains 1 NACHT domain.
Sequence caution	The sequence AAH44774.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Cellular component	Cytoplasm
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Leucine-rich repeat Repeat
Ligand	ATP-binding Nucleotide-binding
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	activation of MAPK activity involved in innate immune response Inferred from direct assay PubMed 21156799. Source: BHF-UCL cellular response to peptidoglycan Inferred from mutant phenotype PubMed 16949315. Source: MGI cytokine production involved in immune response Inferred from sequence or structural similarity. Source: UniProtKB defense response to Gram-positive bacterium Inferred from mutant phenotype PubMed 15692051PubMed 18261938PubMed 19139201. Source: MGI detection of bacterium Inferred from sequence or structural similarity. Source: HGNC detection of muramyl dipeptide Inferred from sequence or structural similarity. Source: HGNC immunoglobulin production involved in immunoglobulin mediated immune response Inferred from mutant phenotype PubMed 15692051. Source: MGI inflammatory response Traceable author statement PubMed 15967716. Source: HGNC innate immune response in mucosa Inferred from mutant phenotype PubMed 15692051. Source: MGI intracellular signal transduction Inferred from sequence or structural similarity. Source: UniProtKB macrophage inflammatory protein-1 alpha production Inferred from mutant phenotype PubMed 19139201. Source: MGI negative regulation of NF-kappaB transcription factor activity Inferred from mutant phenotype PubMed 15220916. Source: MGI negative regulation of T cell mediated immunity Inferred from mutant phenotype PubMed 16949315. Source: MGI negative regulation of growth of symbiont in host Inferred from mutant phenotype PubMed 19139201. Source: MGI negative regulation of inflammatory response to antigenic stimulus Inferred from mutant phenotype PubMed 16949315. Source: MGI negative regulation of interferon-gamma production Inferred from mutant phenotype PubMed 15220916PubMed 19139201. Source: MGI negative regulation of interleukin-12 production Inferred from direct assay PubMed 15220916. Source: MGI negative regulation of interleukin-18 production Inferred from mutant phenotype PubMed 15220916. Source: MGI negative regulation of interleukin-2 production Inferred from mutant phenotype PubMed 19139201. Source: MGI negative regulation of macrophage apoptotic process Inferred from direct assay PubMed 21156799. Source: BHF-UCL negative regulation of toll-like receptor 2 signaling pathway Inferred from mutant phenotype PubMed 15220916. Source: MGI negative regulation of tumor necrosis factor production Inferred from mutant phenotype PubMed 19139201. Source: MGI positive regulation of ERK1 and ERK2 cascade Inferred from direct assay PubMed 21156799. Source: BHF-UCL positive regulation of I-kappaB kinase/NF-kappaB cascade Inferred from sequence or structural similarity. Source: HGNC positive regulation of JNK cascade Inferred from direct assay PubMed 18261938. Source: MGI positive regulation of NF-kappaB transcription factor activity Inferred from sequence or structural similarity. Source: HGNC positive regulation of Notch signaling pathway Inferred from direct assay PubMed 21156799. Source: BHF-UCL positive regulation of biosynthetic process of antibacterial peptides active against Gram-positive bacteria Inferred from mutant phenotype PubMed 15692051. Source: MGI positive regulation of dendritic cell antigen processing and presentation Inferred from mutant phenotype PubMed 20008287. Source: BHF-UCL positive regulation of epithelial cell proliferation Inferred from mutant phenotype PubMed 18855982. Source: BHF-UCL positive regulation of humoral immune response mediated by circulating immunoglobulin Inferred from mutant phenotype PubMed 15692051. Source: MGI positive regulation of interleukin-1 beta secretion Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of interleukin-10 production Inferred from mutant phenotype PubMed 21156799. Source: BHF-UCL positive regulation of interleukin-12 production Inferred from direct assay PubMed 15220916. Source: MGI positive regulation of interleukin-17 production Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of interleukin-6 production Inferred from direct assay PubMed 18261938. Source: MGI positive regulation of nitric-oxide synthase biosynthetic process Inferred from mutant phenotype PubMed 21156799. Source: BHF-UCL positive regulation of peptidyl-tyrosine phosphorylation Inferred from mutant phenotype PubMed 15692051. Source: MGI positive regulation of phagocytosis Inferred from mutant phenotype PubMed 19139201. Source: MGI positive regulation of phosphatidylinositol 3-kinase activity Inferred from mutant phenotype PubMed 21156799. Source: BHF-UCL positive regulation of prostaglandin-E synthase activity Inferred from direct assay PubMed 21156799. Source: BHF-UCL positive regulation of prostaglandin-endoperoxide synthase activity Inferred from direct assay PubMed 21156799. Source: BHF-UCL positive regulation of protein ubiquitination Inferred from direct assay PubMed 15620648. Source: UniProtKB positive regulation of tumor necrosis factor production Inferred from direct assay PubMed 18261938. Source: MGI positive regulation of type 2 immune response Inferred from sequence or structural similarity. Source: BHF-UCL protein oligomerization Traceable author statement PubMed 15967716. Source: HGNC regulation of neutrophil chemotaxis Inferred from mutant phenotype PubMed 19139201. Source: MGI response to exogenous dsRNA Inferred from mutant phenotype PubMed 15692051. Source: MGI response to lipopolysaccharide Inferred from mutant phenotype PubMed 14560001PubMed 15692051. Source: MGI
Cellular_component	cell surface Inferred from sequence or structural similarity. Source: UniProtKB cytosol Inferred from sequence or structural similarity. Source: HGNC plasma membrane Inferred from sequence or structural similarity. Source: HGNC vesicle Inferred from sequence or structural similarity. Source: HGNC
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW CARD domain binding Inferred from sequence or structural similarity. Source: HGNC endodeoxyribonuclease activity, producing 5'-phosphomonoesters Inferred from electronic annotation. Source: InterPro muramyl dipeptide binding Inferred from sequence or structural similarity. Source: HGNC peptidoglycan binding Inferred from sequence or structural similarity. Source: HGNC protein kinase binding Inferred from sequence or structural similarity. Source: HGNC
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q8K3Z0-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: Q8K3Z0-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-7: Missing.
     195-195: E → EGYSLCRSRCDRGFTLICLFCIL

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 1020	1020	Nucleotide-binding oligomerization domain-containing protein 2		PRO_0000144091
Regions
	Domain	6 – 104	99	CARD 1
	Domain	106 – 200	95	CARD 2
	Domain	273 – 600	328	NACHT
	Repeat	685 – 709	25	LRR 1
	Repeat	726 – 749	24	LRR 2
	Repeat	766 – 792	27	LRR 3
	Repeat	794 – 817	24	LRR 4
	Repeat	822 – 845	24	LRR 5
	Repeat	850 – 873	24	LRR 6
	Repeat	906 – 929	24	LRR 7
	Repeat	934 – 962	29	LRR 8
	Repeat	963 – 985	23	LRR 9
	Repeat	1005 – 1019	15	LRR 10
	Motif	43 – 57	15	ATG16L1-binding motif
Natural variations
	Alternative sequence	1 – 7	7	Missing in isoform 2.		VSP_007069
	Alternative sequence	195	1	E → EGYSLCRSRCDRGFTLICLF CIL in isoform 2.		VSP_007070
	Natural variant	212	1	T → A in strain: NMRI. Ref.2
	Natural variant	240	1	Q → R in strain: NMRI. Ref.2
	Natural variant	422	1	L → C in strain: NMRI; requires 2 nucleotide substitutions. Ref.2
	Natural variant	485	1	G → V in strain: NMRI. Ref.2
	Natural variant	603	1	V → A in strain: NMRI. Ref.2
	Natural variant	675	1	V → I in strain: NMRI. Ref.2
	Natural variant	925	1	E → Q in strain: NMRI. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified October 1, 2002. Version 1. Checksum: 25504905ECF70FBB	FASTA	1,020	113,562
	10 20 30 40 50 60 MRSSCCDMCS QEEFQAQRSQ LVALLISGSL EGFESILDWL LSWDVLSRED YEGLSLPGQP 70 80 90 100 110 120 LSHSARRLLD TVWNKGVWGC QKLLEAVQEA QANSHTFELY GSWDTHSLHP TRDLQSHRPA 130 140 150 160 170 180 IVRRLYNHVE AMLELAREGG FLSQYECEEI RLPIFTSSQR ARRLLDLAAV KANGLAAFLL 190 200 210 220 230 240 QHVRELPAPL PLPYEAAECQ KFISKLRTMV LTQSRFLSTY DGSENLCLED IYTENILELQ 250 260 270 280 290 300 TEVGTAGALQ KSPAILGLED LFDTHGHLNR DADTILVVGE AGSGKSTLLQ RLHLLWATGR 310 320 330 340 350 360 SFQEFLFIFP FSCRQLQCVA KPLSLRTLLF EHCCWPDVAQ DDVFQFLLDH PDRVLLTFDG 370 380 390 400 410 420 LDEFKFRFTD RERHCSPIDP TSVQTLLFNL LQGNLLKNAC KVLTSRPDAV SALLRKFVRT 430 440 450 460 470 480 ELQLKGFSEE GIQLYLRKHH REPGVADRLI QLIQATSALH GLCHLPVFSW MVSRCHRELL 490 500 510 520 530 540 LQNRGFPTTS TDMYLLILQH FLLHASPPDS SPLGLGPGLL QSRLSTLLHL GHLALRGLAM 550 560 570 580 590 600 SCYVFSAQQL QAAQVDSDDI SLGFLVRAQS SVPGSKAPLE FLHITFQCFF AAFYLAVSAD 610 620 630 640 650 660 TSVASLKHLF SCGRLGSSLL GRLLPNLCIQ GSRVKKGSEA ALLQKAEPHN LQITAAFLAG 670 680 690 700 710 720 LLSQQHRDLL AACQVSERVL LQRQARARSC LAHSLREHFH SIPPAVPGET KSMHAMPGFI 730 740 750 760 770 780 WLIRSLYEMQ EEQLAQEAVR RLDIGHLKLT FCRVGPAECA ALAFVLQHLQ RPVALQLDYN 790 800 810 820 830 840 SVGDVGVEQL RPCLGVCTAL YLRDNNISDR GARTLVECAL RCEQLQKLAL FNNKLTDACA 850 860 870 880 890 900 CSMAKLLAHK QNFLSLRVGN NHITAAGAEV LAQGLKSNTS LKFLGFWGNS VGDKGTQALA 910 920 930 940 950 960 EVVADHQNLK WLSLVGNNIG SMGAEALALM LEKNKSLEEL CLEENHICDE GVYSLAEGLK 970 980 990 1000 1010 1020 RNSTLKFLKL SNNGITYRGA EALLQALSRN SAILEVWLRG NTFSLEEIQT LSSRDARLLL
	Isoform 2 [UniParc]. Checksum: 7F0E533DC98068FD	FASTA	1,035	115,301
	10 20 30 40 50 60 MCSQEEFQAQ RSQLVALLIS GSLEGFESIL DWLLSWDVLS REDYEGLSLP GQPLSHSARR 70 80 90 100 110 120 LLDTVWNKGV WGCQKLLEAV QEAQANSHTF ELYGSWDTHS LHPTRDLQSH RPAIVRRLYN 130 140 150 160 170 180 HVEAMLELAR EGGFLSQYEC EEIRLPIFTS SQRARRLLDL AAVKANGLAA FLLQHVRELP 190 200 210 220 230 240 APLPLPYEGY SLCRSRCDRG FTLICLFCIL AAECQKFISK LRTMVLTQSR FLSTYDGSEN 250 260 270 280 290 300 LCLEDIYTEN ILELQTEVGT AGALQKSPAI LGLEDLFDTH GHLNRDADTI LVVGEAGSGK 310 320 330 340 350 360 STLLQRLHLL WATGRSFQEF LFIFPFSCRQ LQCVAKPLSL RTLLFEHCCW PDVAQDDVFQ 370 380 390 400 410 420 FLLDHPDRVL LTFDGLDEFK FRFTDRERHC SPIDPTSVQT LLFNLLQGNL LKNACKVLTS 430 440 450 460 470 480 RPDAVSALLR KFVRTELQLK GFSEEGIQLY LRKHHREPGV ADRLIQLIQA TSALHGLCHL 490 500 510 520 530 540 PVFSWMVSRC HRELLLQNRG FPTTSTDMYL LILQHFLLHA SPPDSSPLGL GPGLLQSRLS 550 560 570 580 590 600 TLLHLGHLAL RGLAMSCYVF SAQQLQAAQV DSDDISLGFL VRAQSSVPGS KAPLEFLHIT 610 620 630 640 650 660 FQCFFAAFYL AVSADTSVAS LKHLFSCGRL GSSLLGRLLP NLCIQGSRVK KGSEAALLQK 670 680 690 700 710 720 AEPHNLQITA AFLAGLLSQQ HRDLLAACQV SERVLLQRQA RARSCLAHSL REHFHSIPPA 730 740 750 760 770 780 VPGETKSMHA MPGFIWLIRS LYEMQEEQLA QEAVRRLDIG HLKLTFCRVG PAECAALAFV 790 800 810 820 830 840 LQHLQRPVAL QLDYNSVGDV GVEQLRPCLG VCTALYLRDN NISDRGARTL VECALRCEQL 850 860 870 880 890 900 QKLALFNNKL TDACACSMAK LLAHKQNFLS LRVGNNHITA AGAEVLAQGL KSNTSLKFLG 910 920 930 940 950 960 FWGNSVGDKG TQALAEVVAD HQNLKWLSLV GNNIGSMGAE ALALMLEKNK SLEELCLEEN 970 980 990 1000 1010 1020 HICDEGVYSL AEGLKRNSTL KFLKLSNNGI TYRGAEALLQ ALSRNSAILE VWLRGNTFSL 1030 EEIQTLSSRD ARLLL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning, sequencing and expression analysis of the mouse Nod2/Card15 gene." Iwanaga Y., Davey M.P., Martin T.M., Planck S.R., DePriest M.L., Baugh M.M., Suing C.M., Rosenbaum J.T. Inflamm. Res. 52:272-276(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Strain: BALB/c. Tissue: Monocyte.
[2]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), VARIANTS ALA-212; ARG-240; CYS-422; VAL-485; ALA-603; ILE-675 AND GLN-925. Strain: NMRI. Tissue: Mammary cancer.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF520774 mRNA. Translation: AAM76073.1. BC044774 mRNA. Translation: AAH44774.1. Different initiation.
IPI	IPI00223373. IPI00230403.
UniGene	Mm.222633.
3D structure databases
ProteinModelPortal	Q8K3Z0.
SMR	Q8K3Z0. Positions 747-1004.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-46115N.
PTM databases
PhosphoSite	Q8K3Z0.
Proteomic databases
PRIDE	Q8K3Z0.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000054324; ENSMUSP00000050538; ENSMUSG00000055994. ENSMUST00000109634; ENSMUSP00000105262; ENSMUSG00000055994.
UCSC	uc009mrq.1. mouse.
Organism-specific databases
MGI	MGI:2429397. Nod2.
Phylogenomic databases
eggNOG	NOG248107.
GeneTree	ENSGT00660000095240.
HOGENOM	HOG000113814.
HOVERGEN	HBG050792.
OMA	QYECDEI.
Enzyme and pathway databases
Reactome	REACT_107772. Immune System.
Gene expression databases
ArrayExpress	Q8K3Z0.
Bgee	Q8K3Z0.
Genevestigator	Q8K3Z0.
Family and domain databases
Gene3D	1.10.533.10. 2 hits.
InterPro	IPR001315. CARD. IPR011029. DEATH-like_dom. IPR018228. DNase_TatD-rel_CS. IPR007111. NACHT_NTPase. IPR027417. P-loop_NTPase. [Graphical view]
Pfam	PF00619. CARD. 2 hits. [Graphical view]
SUPFAM	SSF47986. DEATH_like. 2 hits. SSF52540. SSF52540. 1 hit.
PROSITE	PS50209. CARD. 2 hits. PS50837. NACHT. 1 hit. [Graphical view]
ProtoNet	Search...
Other
SOURCE	Search...

Entry information

Entry name

NOD2_MOUSE

Accession

Primary (citable) accession number: Q8K3Z0

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 28, 2003
Last sequence update:	October 1, 2002
Last modified:	May 29, 2013
This is version 101 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program