NAL10_HUMAN
ID NAL10_HUMAN Reviewed; 655 AA.
AC Q86W26; Q2M3C4; Q6JGT0;
DT 13-APR-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2003, sequence version 1.
DT 03-AUG-2022, entry version 148.
DE RecName: Full=NACHT, LRR and PYD domains-containing protein 10;
DE AltName: Full=Nucleotide-binding oligomerization domain protein 8;
GN Name=NLRP10; Synonyms=NALP10, NOD8, PYNOD;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=12563287; DOI=10.1038/nrm1019;
RA Tschopp J., Martinon F., Burns K.;
RT "NALPs: a novel protein family involved in inflammation.";
RL Nat. Rev. Mol. Cell Biol. 4:95-104(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, OLIGOMERIZATION, INTERACTION WITH
RP PYCARD; CASP1 AND IL1B, AND TISSUE SPECIFICITY.
RC TISSUE=Heart;
RX PubMed=15096476; DOI=10.1093/intimm/dxh081;
RA Wang Y., Hasegawa M., Imamura R., Kinoshita T., Kondo C., Konaka K.,
RA Suda T.;
RT "PYNOD, a novel Apaf-1/CED4-like protein is an inhibitor of ASC and
RT caspase-1.";
RL Int. Immunol. 16:777-786(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=12766759; DOI=10.1038/nri1086;
RA Inohara N., Nunez G.;
RT "NODs: intracellular proteins involved in inflammation and apoptosis.";
RL Nat. Rev. Immunol. 3:371-382(2003).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 [5]
RP FUNCTION.
RX PubMed=20393137; DOI=10.4049/jimmunol.0900779;
RA Imamura R., Wang Y., Kinoshita T., Suzuki M., Noda T., Sagara J.,
RA Taniguchi S., Okamoto H., Suda T.;
RT "Anti-inflammatory activity of PYNOD and its mechanism in humans and
RT mice.";
RL J. Immunol. 184:5874-5884(2010).
RN [6]
RP FUNCTION, INTERACTION WITH IKBKG; NOD1; NR2C2 AND RIPK2, SUBCELLULAR
RP LOCATION, TISSUE SPECIFICITY, AND MUTAGENESIS OF LYS-179 AND ASP-252.
RX PubMed=22672233; DOI=10.1111/j.1462-5822.2012.01822.x;
RA Lautz K., Damm A., Menning M., Wenger J., Adam A.C., Zigrino P.,
RA Kremmer E., Kufer T.A.;
RT "NLRP10 enhances Shigella-induced pro-inflammatory responses.";
RL Cell. Microbiol. 14:1568-1583(2012).
RN [7]
RP FUNCTION, AND INDUCTION.
RX PubMed=28766990; DOI=10.1177/1753425917722610;
RA Lee S.J., Choi B.K.;
RT "Involvement of NLRP10 in IL-1alpha induction of oral epithelial cells by
RT periodontal pathogens.";
RL Inn. Immun. 23:569-577(2017).
RN [8]
RP PRELIMINARY STRUCTURE BY NMR OF 1-100.
RX PubMed=22618865; DOI=10.1007/s12104-012-9396-8;
RA Su M.Y., Chang C.I., Chang C.F.;
RT "(1)H, (13)C and (15)N resonance assignments of the pyrin domain from human
RT PYNOD.";
RL Biomol. NMR. Assign. 7:141-143(2013).
RN [9]
RP STRUCTURE BY NMR OF 1-100, FUNCTION, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=23861819; DOI=10.1371/journal.pone.0067843;
RA Su M.Y., Kuo C.I., Chang C.F., Chang C.I.;
RT "Three-dimensional structure of human NLRP10/PYNOD pyrin domain reveals a
RT homotypic interaction site distinct from its mouse homologue.";
RL PLoS ONE 8:E67843-E67843(2013).
CC -!- FUNCTION: Inhibits autoprocessing of CASP1, CASP1-dependent IL1B
CC secretion, PYCARD aggregation and PYCARD-mediated apoptosis but not
CC apoptosis induced by FAS or BID (PubMed:15096476). Displays anti-
CC inflammatory activity (PubMed:20393137). Required for immunity against
CC C.albicans infection (By similarity). Involved in the innate immune
CC response by contributing to pro-inflammatory cytokine release in
CC response to invasive bacterial infection (PubMed:22672233). Contributes
CC to T-cell-mediated inflammatory responses in the skin (By similarity).
CC Plays a role in protection against periodontitis through its
CC involvement in induction of IL1A via ERK activation in oral epithelial
CC cells infected with periodontal pathogens (PubMed:28766990). Exhibits
CC both ATPase and GTPase activities (PubMed:23861819).
CC {ECO:0000250|UniProtKB:Q8CCN1, ECO:0000269|PubMed:15096476,
CC ECO:0000269|PubMed:20393137, ECO:0000269|PubMed:22672233,
CC ECO:0000269|PubMed:23861819}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=169.3 uM for ATP {ECO:0000269|PubMed:23861819};
CC KM=295.6 uM for GTP {ECO:0000269|PubMed:23861819};
CC -!- SUBUNIT: Oligomerizes (PubMed:15096476). Interacts with PYCARD
CC (PubMed:15096476). Also interacts with CASP1 and IL1B
CC (PubMed:15096476). Interacts with NOD1 and components of the NOD1
CC signaling pathway including RIPK2, NR2C2/TAK1 and IKBKG/NEMO
CC (PubMed:22672233). {ECO:0000269|PubMed:15096476,
CC ECO:0000269|PubMed:22672233}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:22672233}. Cell
CC membrane {ECO:0000269|PubMed:22672233}; Peripheral membrane protein
CC {ECO:0000305}. Note=Cytoplasmic protein which is recruited to the cell
CC membrane by NOD1 following invasive bacterial infection.
CC {ECO:0000269|PubMed:22672233}.
CC -!- TISSUE SPECIFICITY: Highly expressed in basal and suprabasal epidermal
CC cell layers with lower levels in dermal fibroblast cells (at protein
CC level) (PubMed:22672233). Widely expressed with highest levels in
CC heart, brain and skeletal muscle (PubMed:15096476). Also expressed in
CC liver, colon, dermis and epidermis (PubMed:15096476). Little expression
CC detected in myeloid cells or peripheral blood mononuclear cells
CC (PubMed:15096476). {ECO:0000269|PubMed:15096476,
CC ECO:0000269|PubMed:22672233}.
CC -!- INDUCTION: By infection with the periodontal pathogens T.forsythia and
CC F.nucleatum (at protein level). {ECO:0000269|PubMed:28766990}.
CC -!- DOMAIN: The pyrin and ATP-binding domains are required to elicit
CC cytokine release following bacterial infection.
CC -!- DOMAIN: The NACHT domain is required for inhibition of CASP1
CC autoprocessing.
CC -!- SIMILARITY: Belongs to the NLRP family. {ECO:0000305}.
CC -!- CAUTION: Despite its official name, does not contain LRR repeats.
CC {ECO:0000305}.
CC -!- CAUTION: Was originally thought to play a role in adaptive immunity
CC through control of dendritic cell-mediated antigen transport to lymph
CC nodes from peripheral sites. However, this was later shown to be
CC dependent on DOCK8. {ECO:0000250|UniProtKB:Q8CCN1}.
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; AY154465; AAO18161.1; -; mRNA.
DR EMBL; AY489192; AAS67384.1; -; mRNA.
DR EMBL; BK001110; DAA01243.1; -; mRNA.
DR EMBL; BC104957; AAI04958.1; -; mRNA.
DR CCDS; CCDS7784.1; -.
DR RefSeq; NP_789791.1; NM_176821.3.
DR RefSeq; XP_011518345.1; XM_011520043.2.
DR PDB; 2M5V; NMR; -; A=1-100.
DR PDBsum; 2M5V; -.
DR AlphaFoldDB; Q86W26; -.
DR BMRB; Q86W26; -.
DR SMR; Q86W26; -.
DR BioGRID; 130709; 13.
DR IntAct; Q86W26; 3.
DR STRING; 9606.ENSP00000327763; -.
DR iPTMnet; Q86W26; -.
DR PhosphoSitePlus; Q86W26; -.
DR BioMuta; NLRP10; -.
DR DMDM; 46396380; -.
DR jPOST; Q86W26; -.
DR MassIVE; Q86W26; -.
DR PaxDb; Q86W26; -.
DR PeptideAtlas; Q86W26; -.
DR PRIDE; Q86W26; -.
DR ProteomicsDB; 70105; -.
DR Antibodypedia; 42324; 207 antibodies from 30 providers.
DR DNASU; 338322; -.
DR Ensembl; ENST00000328600.3; ENSP00000327763.2; ENSG00000182261.5.
DR Ensembl; ENST00000612291.2; ENSP00000478480.1; ENSG00000276780.2.
DR Ensembl; ENST00000625327.2; ENSP00000486762.1; ENSG00000281166.2.
DR Ensembl; ENST00000691676.1; ENSP00000509542.1; ENSG00000182261.5.
DR GeneID; 338322; -.
DR KEGG; hsa:338322; -.
DR MANE-Select; ENST00000691676.1; ENSP00000509542.1; NM_001391958.1; NP_001378887.1.
DR UCSC; uc001mfv.2; human.
DR CTD; 338322; -.
DR DisGeNET; 338322; -.
DR GeneCards; NLRP10; -.
DR HGNC; HGNC:21464; NLRP10.
DR HPA; ENSG00000182261; Group enriched (breast, skin).
DR MIM; 609662; gene.
DR neXtProt; NX_Q86W26; -.
DR OpenTargets; ENSG00000182261; -.
DR PharmGKB; PA162397832; -.
DR VEuPathDB; HostDB:ENSG00000182261; -.
DR eggNOG; ENOG502RT64; Eukaryota.
DR GeneTree; ENSGT00940000159520; -.
DR HOGENOM; CLU_002274_2_3_1; -.
DR InParanoid; Q86W26; -.
DR OMA; VLYKACQ; -.
DR OrthoDB; 114368at2759; -.
DR PhylomeDB; Q86W26; -.
DR PathwayCommons; Q86W26; -.
DR SignaLink; Q86W26; -.
DR BioGRID-ORCS; 338322; 14 hits in 1070 CRISPR screens.
DR GeneWiki; NLRP10; -.
DR GenomeRNAi; 338322; -.
DR Pharos; Q86W26; Tbio.
DR PRO; PR:Q86W26; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; Q86W26; protein.
DR Bgee; ENSG00000182261; Expressed in skin of leg and 22 other tissues.
DR ExpressionAtlas; Q86W26; baseline and differential.
DR Genevisible; Q86W26; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0019897; C:extrinsic component of plasma membrane; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0016887; F:ATP hydrolysis activity; IDA:UniProtKB.
DR GO; GO:0003924; F:GTPase activity; IDA:UniProtKB.
DR GO; GO:0002250; P:adaptive immune response; IEA:UniProtKB-KW.
DR GO; GO:0050832; P:defense response to fungus; ISS:UniProtKB.
DR GO; GO:0050829; P:defense response to Gram-negative bacterium; IMP:UniProtKB.
DR GO; GO:0006954; P:inflammatory response; IEA:UniProtKB-KW.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:1900426; P:positive regulation of defense response to bacterium; IMP:UniProtKB.
DR GO; GO:0050729; P:positive regulation of inflammatory response; ISS:UniProtKB.
DR GO; GO:0032730; P:positive regulation of interleukin-1 alpha production; IMP:UniProtKB.
DR GO; GO:0032755; P:positive regulation of interleukin-6 production; IMP:UniProtKB.
DR GO; GO:0032757; P:positive regulation of interleukin-8 production; IMP:UniProtKB.
DR GO; GO:0002827; P:positive regulation of T-helper 1 type immune response; ISS:UniProtKB.
DR GO; GO:2000318; P:positive regulation of T-helper 17 type immune response; ISS:UniProtKB.
DR GO; GO:0050727; P:regulation of inflammatory response; IBA:GO_Central.
DR Gene3D; 1.10.533.10; -; 1.
DR Gene3D; 3.40.50.300; -; 1.
DR InterPro; IPR004020; DAPIN.
DR InterPro; IPR011029; DEATH-like_dom_sf.
DR InterPro; IPR007111; NACHT_NTPase.
DR InterPro; IPR041075; NOD2_WH.
DR InterPro; IPR027417; P-loop_NTPase.
DR Pfam; PF05729; NACHT; 1.
DR Pfam; PF17779; NOD2_WH; 1.
DR Pfam; PF02758; PYRIN; 1.
DR SMART; SM01289; PYRIN; 1.
DR SUPFAM; SSF47986; SSF47986; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR PROSITE; PS50824; DAPIN; 1.
DR PROSITE; PS50837; NACHT; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Adaptive immunity; ATP-binding; Cell membrane; Cytoplasm;
KW Immunity; Inflammatory response; Innate immunity; Membrane;
KW Nucleotide-binding; Reference proteome.
FT CHAIN 1..655
FT /note="NACHT, LRR and PYD domains-containing protein 10"
FT /id="PRO_0000080896"
FT DOMAIN 1..96
FT /note="Pyrin"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00061"
FT DOMAIN 167..484
FT /note="NACHT"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00136"
FT REGION 597..655
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 610..632
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 633..655
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 173..180
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00136"
FT MUTAGEN 179
FT /note="K->A: Reduced release of IL8 following invasive
FT bacterial infection."
FT /evidence="ECO:0000269|PubMed:22672233"
FT MUTAGEN 252
FT /note="D->A: Reduced release of IL8 following invasive
FT bacterial infection."
FT /evidence="ECO:0000269|PubMed:22672233"
FT HELIX 9..19
FT /evidence="ECO:0007829|PDB:2M5V"
FT HELIX 22..36
FT /evidence="ECO:0007829|PDB:2M5V"
FT HELIX 46..48
FT /evidence="ECO:0007829|PDB:2M5V"
FT TURN 49..51
FT /evidence="ECO:0007829|PDB:2M5V"
FT HELIX 54..64
FT /evidence="ECO:0007829|PDB:2M5V"
FT HELIX 67..79
FT /evidence="ECO:0007829|PDB:2M5V"
FT TURN 80..82
FT /evidence="ECO:0007829|PDB:2M5V"
FT HELIX 84..93
FT /evidence="ECO:0007829|PDB:2M5V"
FT HELIX 96..98
FT /evidence="ECO:0007829|PDB:2M5V"
SQ SEQUENCE 655 AA; 75032 MW; 0A4E5936864F4B5D CRC64;
MAMAKARKPR EALLWALSDL EENDFKKLKF YLRDMTLSEG QPPLARGELE GLIPVDLAEL
LISKYGEKEA VKVVLKGLKV MNLLELVDQL SHICLHDYRE VYREHVRCLE EWQEAGVNGR
YNQVLLVAKP SSESPESLAC PFPEQELESV TVEALFDSGE KPSLAPSLVV LQGSAGTGKT
TLARKMVLDW ATGTLYPGRF DYVFYVSCKE VVLLLESKLE QLLFWCCGDN QAPVTEILRQ
PERLLFILDG FDELQRPFEE KLKKRGLSPK ESLLHLLIRR HTLPTCSLLI TTRPLALRNL
EPLLKQARHV HILGFSEEER ARYFSSYFTD EKQADRAFDI VQKNDILYKA CQVPGICWVV
CSWLQGQMER GKVVLETPRN STDIFMAYVS TFLPPDDDGG CSELSRHRVL RSLCSLAAEG
IQHQRFLFEE AELRKHNLDG PRLAAFLSSN DYQLGLAIKK FYSFRHISFQ DFFHAMSYLV
KEDQSRLGKE SRREVQRLLE VKEQEGNDEM TLTMQFLLDI SKKDSFSNLE LKFCFRISPC
LAQDLKHFKE QMESMKHNRT WDLEFSLYEA KIKNLVKGIQ MNNVSFKIKH SNEKKSQSQN
LFSVKSSLSH GPKEEQKCPS VHGQKEGKDN IAGTQKEAST GKGRGTEETP KNTYI
