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Protein

NACHT, LRR and PYD domains-containing protein 10

Gene

NLRP10

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Inhibits autoprocessing of CASP1, CASP1-dependent IL1B secretion, PYCARD aggregation and PYCARD-mediated apoptosis but not apoptosis induced by FAS or BID (PubMed:15096476). Displays anti-inflammatory activity (PubMed:20393137). Required for immunity against C.albicans infection (By similarity). Involved in the innate immune response by contributing to proinflammatory cytokine release in response to invasive bacterial infection (PubMed:22672233). Contributes to T-cell-mediated inflammatory responses in the skin (By similarity). Plays a role in protection against periodontitis through its involvement in induction of IL1A via ERK activation in oral epithelial cells infected with periodontal pathogens (PubMed:28766990). Exhibits both ATPase and GTPase activities (PubMed:23861819).By similarity4 Publications

Kineticsi

  1. KM=169.3 µM for ATP1 Publication
  2. KM=295.6 µM for GTP1 Publication

    Regions

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Nucleotide bindingi173 – 180ATPPROSITE-ProRule annotation8

    GO - Molecular functioni

    GO - Biological processi

    Keywordsi

    Biological processAdaptive immunity, Immunity, Inflammatory response, Innate immunity
    LigandATP-binding, Nucleotide-binding

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    NACHT, LRR and PYD domains-containing protein 10
    Alternative name(s):
    Nucleotide-binding oligomerization domain protein 8
    Gene namesi
    Name:NLRP10
    Synonyms:NALP10, NOD8, PYNOD
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    Proteomesi
    • UP000005640 Componenti: Chromosome 11

    Organism-specific databases

    EuPathDBiHostDB:ENSG00000182261.3.
    HGNCiHGNC:21464. NLRP10.

    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
    Mutagenesisi179K → A: Reduced release of IL8 following invasive bacterial infection. 1 Publication1
    Mutagenesisi252D → A: Reduced release of IL8 following invasive bacterial infection. 1 Publication1

    Organism-specific databases

    DisGeNETi338322.
    OpenTargetsiENSG00000182261.
    PharmGKBiPA162397832.

    Polymorphism and mutation databases

    BioMutaiNLRP10.
    DMDMi46396380.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    ChainiPRO_00000808961 – 655NACHT, LRR and PYD domains-containing protein 10Add BLAST655

    Proteomic databases

    PaxDbiQ86W26.
    PeptideAtlasiQ86W26.
    PRIDEiQ86W26.

    PTM databases

    iPTMnetiQ86W26.
    PhosphoSitePlusiQ86W26.

    Expressioni

    Tissue specificityi

    Highly expressed in basal and suprabasal epidermal cell layers with lower levels in dermal fibroblast cells (at protein level) (PubMed:22672233). Widely expressed with highest levels in heart, brain and skeletal muscle (PubMed:15096476). Also expressed in liver, colon, dermis and epidermis (PubMed:15096476). Little expression detected in myeloid cells or peripheral blood mononuclear cells (PubMed:15096476).2 Publications

    Inductioni

    By infection with the periodontal pathogens T.forsythia and F.nucleatum (at protein level).1 Publication

    Gene expression databases

    BgeeiENSG00000182261.
    CleanExiHS_NLRP10.
    ExpressionAtlasiQ86W26. baseline and differential.
    GenevisibleiQ86W26. HS.

    Organism-specific databases

    HPAiHPA039498.
    HPA040101.

    Interactioni

    Subunit structurei

    Oligomerizes (PubMed:15096476). Interacts with PYCARD (PubMed:15096476). Also interacts with CASP1 and IL1B (PubMed:15096476). Interacts with NOD1 and components of the NOD1 signaling pathway including RIPK2, NR2C2/TAK1 and IKBKG/NEMO (PubMed:22672233).2 Publications

    Protein-protein interaction databases

    BioGridi130709. 7 interactors.
    STRINGi9606.ENSP00000327763.

    Structurei

    Secondary structure

    1655
    Legend: HelixTurnBeta strandPDB Structure known for this area
    Show more details
    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Helixi9 – 19Combined sources11
    Helixi22 – 36Combined sources15
    Helixi46 – 48Combined sources3
    Turni49 – 51Combined sources3
    Helixi54 – 64Combined sources11
    Helixi67 – 79Combined sources13
    Turni80 – 82Combined sources3
    Helixi84 – 93Combined sources10
    Helixi96 – 98Combined sources3

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    PDB entryMethodResolution (Å)ChainPositionsPDBsum
    2M5VNMR-A1-100[»]
    ProteinModelPortaliQ86W26.
    SMRiQ86W26.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Domaini1 – 96PyrinPROSITE-ProRule annotationAdd BLAST96
    Domaini167 – 484NACHTPROSITE-ProRule annotationAdd BLAST318

    Domaini

    The pyrin and ATP-binding domains are required to elicit cytokine release following bacterial infection.
    The NACHT domain is required for inhibition of CASP1 autoprocessing.

    Sequence similaritiesi

    Belongs to the NLRP family.Curated

    Phylogenomic databases

    eggNOGiENOG410IGPF. Eukaryota.
    ENOG410Y19A. LUCA.
    GeneTreeiENSGT00900000140813.
    HOGENOMiHOG000113728.
    HOVERGENiHBG052572.
    InParanoidiQ86W26.
    OMAiDIFMAYV.
    OrthoDBiEOG091G01CG.
    PhylomeDBiQ86W26.

    Family and domain databases

    InterProiView protein in InterPro
    IPR004020. DAPIN.
    IPR011029. DEATH-like_dom.
    IPR007111. NACHT_NTPase.
    IPR027417. P-loop_NTPase.
    PfamiView protein in Pfam
    PF02758. PYRIN. 1 hit.
    SMARTiView protein in SMART
    SM01289. PYRIN. 1 hit.
    SUPFAMiSSF47986. SSF47986. 1 hit.
    SSF52540. SSF52540. 1 hit.
    PROSITEiView protein in PROSITE
    PS50824. DAPIN. 1 hit.
    PS50837. NACHT. 1 hit.

    Sequencei

    Sequence statusi: Complete.

    Q86W26-1 [UniParc]FASTAAdd to basket

    « Hide

            10         20         30         40         50
    MAMAKARKPR EALLWALSDL EENDFKKLKF YLRDMTLSEG QPPLARGELE
    60 70 80 90 100
    GLIPVDLAEL LISKYGEKEA VKVVLKGLKV MNLLELVDQL SHICLHDYRE
    110 120 130 140 150
    VYREHVRCLE EWQEAGVNGR YNQVLLVAKP SSESPESLAC PFPEQELESV
    160 170 180 190 200
    TVEALFDSGE KPSLAPSLVV LQGSAGTGKT TLARKMVLDW ATGTLYPGRF
    210 220 230 240 250
    DYVFYVSCKE VVLLLESKLE QLLFWCCGDN QAPVTEILRQ PERLLFILDG
    260 270 280 290 300
    FDELQRPFEE KLKKRGLSPK ESLLHLLIRR HTLPTCSLLI TTRPLALRNL
    310 320 330 340 350
    EPLLKQARHV HILGFSEEER ARYFSSYFTD EKQADRAFDI VQKNDILYKA
    360 370 380 390 400
    CQVPGICWVV CSWLQGQMER GKVVLETPRN STDIFMAYVS TFLPPDDDGG
    410 420 430 440 450
    CSELSRHRVL RSLCSLAAEG IQHQRFLFEE AELRKHNLDG PRLAAFLSSN
    460 470 480 490 500
    DYQLGLAIKK FYSFRHISFQ DFFHAMSYLV KEDQSRLGKE SRREVQRLLE
    510 520 530 540 550
    VKEQEGNDEM TLTMQFLLDI SKKDSFSNLE LKFCFRISPC LAQDLKHFKE
    560 570 580 590 600
    QMESMKHNRT WDLEFSLYEA KIKNLVKGIQ MNNVSFKIKH SNEKKSQSQN
    610 620 630 640 650
    LFSVKSSLSH GPKEEQKCPS VHGQKEGKDN IAGTQKEAST GKGRGTEETP

    KNTYI
    Length:655
    Mass (Da):75,032
    Last modified:June 1, 2003 - v1
    Checksum:i0A4E5936864F4B5D
    GO

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AY154465 mRNA. Translation: AAO18161.1.
    AY489192 mRNA. Translation: AAS67384.1.
    BK001110 mRNA. Translation: DAA01243.1.
    BC104957 mRNA. Translation: AAI04958.1.
    CCDSiCCDS7784.1.
    RefSeqiNP_789791.1. NM_176821.3.
    XP_011518345.1. XM_011520043.2.
    UniGeneiHs.449636.

    Genome annotation databases

    EnsembliENST00000328600; ENSP00000327763; ENSG00000182261.
    ENST00000612291; ENSP00000478480; ENSG00000276780.
    ENST00000625327; ENSP00000486762; ENSG00000281166.
    GeneIDi338322.
    KEGGihsa:338322.
    UCSCiuc001mfv.2. human.

    Similar proteinsi

    Entry informationi

    Entry nameiNAL10_HUMAN
    AccessioniPrimary (citable) accession number: Q86W26
    Secondary accession number(s): Q2M3C4, Q6JGT0
    Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 13, 2004
    Last sequence update: June 1, 2003
    Last modified: October 25, 2017
    This is version 123 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

    Caution

    Despite its official name, does not contain LRR repeats.Curated
    Was originally thought to play a role in adaptive immunity through control of dendritic cell-mediated antigen transport to lymph nodes from peripheral sites. However, this was later shown to be dependent on DOCK8.By similarity

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. Human chromosome 11
      Human chromosome 11: entries, gene names and cross-references to MIM
    2. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    3. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    4. SIMILARITY comments
      Index of protein domains and families