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Protein

Nucleotide-binding oligomerization domain-containing protein 1

Gene

NOD1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Enhances caspase-9-mediated apoptosis. Induces NF-kappa-B activity via RIPK2 and IKK-gamma. Confers responsiveness to intracellular bacterial lipopolysaccharides (LPS). Forms an intracellular sensing system along with ARHGEF2 for the detection of microbial effectors during cell invasion by pathogens. Required for RHOA and RIPK2 dependent NF-kappa-B signaling pathway activation upon S.flexneri cell invasion. Involved not only in sensing peptidoglycan (PGN)-derived muropeptides but also in the activation of NF-kappa-B by Shigella effector proteins IpgB2 and OspB. Recruits NLRP10 to the cell membrane following bacterial infection.4 Publications

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi202 – 209ATPPROSITE-ProRule annotation8

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • CARD domain binding Source: MGI
  • cysteine-type endopeptidase activator activity involved in apoptotic process Source: ProtInc
  • identical protein binding Source: MGI
  • peptidoglycan binding Source: HGNC
  • protein-containing complex binding Source: UniProtKB
  • protein homodimerization activity Source: UniProtKB

GO - Biological processi

Keywordsi

Biological processApoptosis, Immunity, Innate immunity
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiR-HSA-168638 NOD1/2 Signaling Pathway
R-HSA-445989 TAK1 activates NFkB by phosphorylation and activation of IKKs complex
R-HSA-450302 activated TAK1 mediates p38 MAPK activation
R-HSA-450321 JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1
R-HSA-5689896 Ovarian tumor domain proteases
R-HSA-9020702 Interleukin-1 signaling
SignaLinkiQ9Y239
SIGNORiQ9Y239

Names & Taxonomyi

Protein namesi
Recommended name:
Nucleotide-binding oligomerization domain-containing protein 1
Alternative name(s):
Caspase recruitment domain-containing protein 4
Gene namesi
Name:NOD1
Synonyms:CARD4
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 7

Organism-specific databases

EuPathDBiHostDB:ENSG00000106100.10
HGNCiHGNC:16390 NOD1
MIMi605980 gene
neXtProtiNX_Q9Y239

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi41V → A: Abolishes interaction with RIPK2/RICK. 2 Publications1
Mutagenesisi41V → Q: Abolishes caspase-9 activation. 2 Publications1
Mutagenesisi44L → A: Abolishes activation of NF-kappa-B. No effect on interaction with RIPK2. 1 Publication1
Mutagenesisi48D → K: Abolishes activation of NF-kappa-B. No effect on interaction with RIPK2. 1 Publication1
Mutagenesisi53E → K: No effect on activation of NF-kappa-B. Abolishes interaction with RIPK2. 1 Publication1
Mutagenesisi54D → K: Abolishes activation of NF-kappa-B. Abolishes interaction with RIPK2. 1 Publication1
Mutagenesisi56E → K: Abolishes activation of NF-kappa-B. Abolishes interaction with RIPK2. 1 Publication1
Mutagenesisi69R → E: Abolishes activation of NF-kappa-B. Abolishes interaction with RIPK2. 1 Publication1
Mutagenesisi208K → R: Reduces caspase-9 activation. Reduced binding affinity for NLRP10. Does not associate with cell membrane. 3 Publications1
Mutagenesisi287D → A: Reduced binding affinity for NLRP10. 1 Publication1
Mutagenesisi711D → S: Does not associate with cell membrane. 1 Publication1
Mutagenesisi788H → S: No effect on association with cell membrane. 1 Publication1
Mutagenesisi792G → S: Does not associate with cell membrane. 1 Publication1
Mutagenesisi877Q → S: Does not associate with cell membrane. 1 Publication1

Organism-specific databases

DisGeNETi10392
OpenTargetsiENSG00000106100
PharmGKBiPA162398098

Chemistry databases

ChEMBLiCHEMBL1293222
GuidetoPHARMACOLOGYi1762

Polymorphism and mutation databases

BioMutaiNOD1
DMDMi20137579

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001440771 – 953Nucleotide-binding oligomerization domain-containing protein 1Add BLAST953

Post-translational modificationi

Ubiquitinated. 'Lys-48'-linked polyubiquitination by RNF34 promotes proteasomal degradation and thereby negatively regulates NOD1 for instance in NF-kappa-B activition.1 Publication

Keywords - PTMi

Ubl conjugation

Proteomic databases

EPDiQ9Y239
PaxDbiQ9Y239
PeptideAtlasiQ9Y239
PRIDEiQ9Y239
ProteomicsDBi85636

PTM databases

iPTMnetiQ9Y239
PhosphoSitePlusiQ9Y239

Expressioni

Tissue specificityi

Highly expressed in adult heart, skeletal muscle, pancreas, spleen and ovary. Also detected in placenta, lung, liver, kidney, thymus, testis, small intestine and colon.

Gene expression databases

BgeeiENSG00000106100 Expressed in 173 organ(s), highest expression level in left lobe of thyroid gland
CleanExiHS_NOD1
ExpressionAtlasiQ9Y239 baseline and differential
GenevisibleiQ9Y239 HS

Organism-specific databases

HPAiHPA074367

Interactioni

Subunit structurei

Homodimer. Self-associates. Binds to caspase-9 and RIPK2 by CARD-CARD interaction. Interacts with ARHGEF2. Interacts with NLRP10 and recruits it to the cell membrane following invasive bacterial infection. Interacts with RNF34.5 Publications

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi115664, 28 interactors
CORUMiQ9Y239
DIPiDIP-41064N
IntActiQ9Y239, 24 interactors
MINTiQ9Y239
STRINGi9606.ENSP00000222823

Chemistry databases

BindingDBiQ9Y239

Structurei

Secondary structure

1953
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliQ9Y239
SMRiQ9Y239
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9Y239

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini15 – 105CARDPROSITE-ProRule annotationAdd BLAST91
Domaini196 – 531NACHTPROSITE-ProRule annotationAdd BLAST336
Repeati632 – 656LRR 1Add BLAST25
Repeati702 – 725LRR 2Add BLAST24
Repeati727 – 750LRR 3Add BLAST24
Repeati755 – 778LRR 4Add BLAST24
Repeati783 – 806LRR 5Add BLAST24
Repeati839 – 862LRR 6Add BLAST24
Repeati867 – 891LRR 7Add BLAST25
Repeati895 – 918LRR 8Add BLAST24
Repeati923 – 946LRR 9Add BLAST24

Keywords - Domaini

Leucine-rich repeat, Repeat

Phylogenomic databases

eggNOGiKOG4308 Eukaryota
ENOG410ZBX3 LUCA
GeneTreeiENSGT00860000133673
HOGENOMiHOG000070102
HOVERGENiHBG050793
InParanoidiQ9Y239
KOiK08727
OMAiNDYGVRE
OrthoDBiEOG091G0I7O
PhylomeDBiQ9Y239
TreeFamiTF352118

Family and domain databases

Gene3Di3.80.10.10, 2 hits
InterProiView protein in InterPro
IPR001315 CARD
IPR011029 DEATH-like_dom_sf
IPR001611 Leu-rich_rpt
IPR032675 LRR_dom_sf
IPR007111 NACHT_NTPase
PfamiView protein in Pfam
PF00619 CARD, 1 hit
PF13516 LRR_6, 4 hits
PF05729 NACHT, 1 hit
SUPFAMiSSF47986 SSF47986, 1 hit
PROSITEiView protein in PROSITE
PS50209 CARD, 1 hit
PS50837 NACHT, 1 hit

Sequences (2+)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 2 described isoforms and 3 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: Q9Y239-1) [UniParc]FASTAAdd to basket

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.

« Hide
        10         20         30         40         50
MEEQGHSEME IIPSESHPHI QLLKSNRELL VTHIRNTQCL VDNLLKNDYF
60 70 80 90 100
SAEDAEIVCA CPTQPDKVRK ILDLVQSKGE EVSEFFLYLL QQLADAYVDL
110 120 130 140 150
RPWLLEIGFS PSLLTQSKVV VNTDPVSRYT QQLRHHLGRD SKFVLCYAQK
160 170 180 190 200
EELLLEEIYM DTIMELVGFS NESLGSLNSL ACLLDHTTGI LNEQGETIFI
210 220 230 240 250
LGDAGVGKSM LLQRLQSLWA TGRLDAGVKF FFHFRCRMFS CFKESDRLCL
260 270 280 290 300
QDLLFKHYCY PERDPEEVFA FLLRFPHVAL FTFDGLDELH SDLDLSRVPD
310 320 330 340 350
SSCPWEPAHP LVLLANLLSG KLLKGASKLL TARTGIEVPR QFLRKKVLLR
360 370 380 390 400
GFSPSHLRAY ARRMFPERAL QDRLLSQLEA NPNLCSLCSV PLFCWIIFRC
410 420 430 440 450
FQHFRAAFEG SPQLPDCTMT LTDVFLLVTE VHLNRMQPSS LVQRNTRSPV
460 470 480 490 500
ETLHAGRDTL CSLGQVAHRG MEKSLFVFTQ EEVQASGLQE RDMQLGFLRA
510 520 530 540 550
LPELGPGGDQ QSYEFFHLTL QAFFTAFFLV LDDRVGTQEL LRFFQEWMPP
560 570 580 590 600
AGAATTSCYP PFLPFQCLQG SGPAREDLFK NKDHFQFTNL FLCGLLSKAK
610 620 630 640 650
QKLLRHLVPA AALRRKRKAL WAHLFSSLRG YLKSLPRVQV ESFNQVQAMP
660 670 680 690 700
TFIWMLRCIY ETQSQKVGQL AARGICANYL KLTYCNACSA DCSALSFVLH
710 720 730 740 750
HFPKRLALDL DNNNLNDYGV RELQPCFSRL TVLRLSVNQI TDGGVKVLSE
760 770 780 790 800
ELTKYKIVTY LGLYNNQITD VGARYVTKIL DECKGLTHLK LGKNKITSEG
810 820 830 840 850
GKYLALAVKN SKSISEVGMW GNQVGDEGAK AFAEALRNHP SLTTLSLASN
860 870 880 890 900
GISTEGGKSL ARALQQNTSL EILWLTQNEL NDEVAESLAE MLKVNQTLKH
910 920 930 940 950
LWLIQNQITA KGTAQLADAL QSNTGITEIC LNGNLIKPEE AKVYEDEKRI

ICF
Length:953
Mass (Da):107,691
Last modified:November 1, 1999 - v1
Checksum:i0A9DF5FC6487E21A
GO
Isoform 2 (identifier: Q9Y239-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     195-249: GETIFILGDA...SCFKESDRLC → AASRKVTGCV...AWTSCTRTWT
     250-953: Missing.

Note: No experimental confirmation available.
Show »
Length:249
Mass (Da):27,949
Checksum:i9387E0E72FA907A6
GO

Computationally mapped potential isoform sequencesi

There are 3 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
G3XAL1G3XAL1_HUMAN
Caspase recruitment domain family, ...
NOD1 CARD4, hCG_39138
779Annotation score:
A0A1B0GX71A0A1B0GX71_HUMAN
Nucleotide-binding oligomerization ...
NOD1
59Annotation score:
C9J8X8C9J8X8_HUMAN
Nucleotide-binding oligomerization ...
NOD1
45Annotation score:

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_020371266E → K. Corresponds to variant dbSNP:rs2075820Ensembl.1
Natural variantiVAR_053624372D → N. Corresponds to variant dbSNP:rs5743342Ensembl.1
Natural variantiVAR_053625447R → H1 PublicationCorresponds to variant dbSNP:rs2975634Ensembl.1
Natural variantiVAR_053626605R → W. Corresponds to variant dbSNP:rs5743345Ensembl.1
Natural variantiVAR_053627610A → T. Corresponds to variant dbSNP:rs5743346Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_055825195 – 249GETIF…SDRLC → AASRKVTGCVCRTCSSSTTA TQSGTPRRCLPSCCASPTWP SSPSMAWTSCTRTWT in isoform 2. 1 PublicationAdd BLAST55
Alternative sequenceiVSP_055826250 – 953Missing in isoform 2. 1 PublicationAdd BLAST704

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF126484 mRNA Translation: AAD29125.1
AF149774 Genomic DNA Translation: AAD43922.1
AF113925 mRNA Translation: AAD28350.1
AK300367 mRNA Translation: BAG62105.1
AC005154 Genomic DNA No translation available.
AC006027 Genomic DNA Translation: AAS46897.1
BC040339 mRNA Translation: AAH40339.1
CCDSiCCDS5427.1 [Q9Y239-1]
RefSeqiNP_006083.1, NM_006092.2 [Q9Y239-1]
XP_005249625.1, XM_005249568.1 [Q9Y239-1]
XP_005249629.1, XM_005249572.1 [Q9Y239-1]
XP_006715696.1, XM_006715633.2 [Q9Y239-1]
XP_011513381.1, XM_011515079.1 [Q9Y239-1]
XP_011513382.1, XM_011515080.2 [Q9Y239-1]
XP_011513383.1, XM_011515081.2 [Q9Y239-1]
UniGeneiHs.405153
Hs.738731

Genome annotation databases

EnsembliENST00000222823; ENSP00000222823; ENSG00000106100 [Q9Y239-1]
GeneIDi10392
KEGGihsa:10392
UCSCiuc003tav.4 human [Q9Y239-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF126484 mRNA Translation: AAD29125.1
AF149774 Genomic DNA Translation: AAD43922.1
AF113925 mRNA Translation: AAD28350.1
AK300367 mRNA Translation: BAG62105.1
AC005154 Genomic DNA No translation available.
AC006027 Genomic DNA Translation: AAS46897.1
BC040339 mRNA Translation: AAH40339.1
CCDSiCCDS5427.1 [Q9Y239-1]
RefSeqiNP_006083.1, NM_006092.2 [Q9Y239-1]
XP_005249625.1, XM_005249568.1 [Q9Y239-1]
XP_005249629.1, XM_005249572.1 [Q9Y239-1]
XP_006715696.1, XM_006715633.2 [Q9Y239-1]
XP_011513381.1, XM_011515079.1 [Q9Y239-1]
XP_011513382.1, XM_011515080.2 [Q9Y239-1]
XP_011513383.1, XM_011515081.2 [Q9Y239-1]
UniGeneiHs.405153
Hs.738731

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2B1WNMR-A15-138[»]
2DBDNMR-A17-110[»]
2NSNX-ray2.00A16-108[»]
2NZ7X-ray1.90A/B9-106[»]
4E9MX-ray2.15A/B/C/D/E/F2-138[»]
4JQWX-ray2.90A16-108[»]
ProteinModelPortaliQ9Y239
SMRiQ9Y239
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi115664, 28 interactors
CORUMiQ9Y239
DIPiDIP-41064N
IntActiQ9Y239, 24 interactors
MINTiQ9Y239
STRINGi9606.ENSP00000222823

Chemistry databases

BindingDBiQ9Y239
ChEMBLiCHEMBL1293222
GuidetoPHARMACOLOGYi1762

PTM databases

iPTMnetiQ9Y239
PhosphoSitePlusiQ9Y239

Polymorphism and mutation databases

BioMutaiNOD1
DMDMi20137579

Proteomic databases

EPDiQ9Y239
PaxDbiQ9Y239
PeptideAtlasiQ9Y239
PRIDEiQ9Y239
ProteomicsDBi85636

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000222823; ENSP00000222823; ENSG00000106100 [Q9Y239-1]
GeneIDi10392
KEGGihsa:10392
UCSCiuc003tav.4 human [Q9Y239-1]

Organism-specific databases

CTDi10392
DisGeNETi10392
EuPathDBiHostDB:ENSG00000106100.10
GeneCardsiNOD1
HGNCiHGNC:16390 NOD1
HPAiHPA074367
MIMi605980 gene
neXtProtiNX_Q9Y239
OpenTargetsiENSG00000106100
PharmGKBiPA162398098
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG4308 Eukaryota
ENOG410ZBX3 LUCA
GeneTreeiENSGT00860000133673
HOGENOMiHOG000070102
HOVERGENiHBG050793
InParanoidiQ9Y239
KOiK08727
OMAiNDYGVRE
OrthoDBiEOG091G0I7O
PhylomeDBiQ9Y239
TreeFamiTF352118

Enzyme and pathway databases

ReactomeiR-HSA-168638 NOD1/2 Signaling Pathway
R-HSA-445989 TAK1 activates NFkB by phosphorylation and activation of IKKs complex
R-HSA-450302 activated TAK1 mediates p38 MAPK activation
R-HSA-450321 JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1
R-HSA-5689896 Ovarian tumor domain proteases
R-HSA-9020702 Interleukin-1 signaling
SignaLinkiQ9Y239
SIGNORiQ9Y239

Miscellaneous databases

ChiTaRSiNOD1 human
EvolutionaryTraceiQ9Y239
GeneWikiiNOD1
GenomeRNAii10392
PROiPR:Q9Y239
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000106100 Expressed in 173 organ(s), highest expression level in left lobe of thyroid gland
CleanExiHS_NOD1
ExpressionAtlasiQ9Y239 baseline and differential
GenevisibleiQ9Y239 HS

Family and domain databases

Gene3Di3.80.10.10, 2 hits
InterProiView protein in InterPro
IPR001315 CARD
IPR011029 DEATH-like_dom_sf
IPR001611 Leu-rich_rpt
IPR032675 LRR_dom_sf
IPR007111 NACHT_NTPase
PfamiView protein in Pfam
PF00619 CARD, 1 hit
PF13516 LRR_6, 4 hits
PF05729 NACHT, 1 hit
SUPFAMiSSF47986 SSF47986, 1 hit
PROSITEiView protein in PROSITE
PS50209 CARD, 1 hit
PS50837 NACHT, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiNOD1_HUMAN
AccessioniPrimary (citable) accession number: Q9Y239
Secondary accession number(s): B4DTU3, Q549U4, Q8IWF5
Entry historyiIntegrated into UniProtKB/Swiss-Prot: January 31, 2002
Last sequence update: November 1, 1999
Last modified: November 7, 2018
This is version 187 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  2. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  3. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  4. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  5. Human chromosome 7
    Human chromosome 7: entries, gene names and cross-references to MIM
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