NLRP6_HUMAN
ID NLRP6_HUMAN Reviewed; 892 AA.
AC P59044; A8K9F3; E9PJZ8;
DT 19-OCT-2002, integrated into UniProtKB/Swiss-Prot.
DT 22-SEP-2009, sequence version 2.
DT 03-AUG-2022, entry version 171.
DE RecName: Full=NACHT, LRR and PYD domains-containing protein 6 {ECO:0000305};
DE AltName: Full=Angiotensin II/vasopressin receptor {ECO:0000250|UniProtKB:Q91WS2};
DE AltName: Full=PYRIN-containing APAF1-like protein 5 {ECO:0000303|PubMed:12019269};
GN Name=NLRP6 {ECO:0000303|PubMed:21088234, ECO:0000312|HGNC:HGNC:22944};
GN Synonyms=NALP6 {ECO:0000303|PubMed:12563287},
GN PYPAF5 {ECO:0000303|PubMed:12019269};
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] (ISOFORM 1), AND VARIANTS LEU-163 AND PHE-361.
RX PubMed=12019269; DOI=10.1074/jbc.m203915200;
RA Wang L., Manji G.A., Grenier J.M., Al-Garawi A., Merriam S., Lora J.M.,
RA Geddes B.J., Briskin M., DiStefano P.S., Bertin J.;
RT "PYPAF7, a novel PYRIN-containing Apaf1-like protein that regulates
RT activation of NF-kappa B and caspase-1-dependent cytokine processing.";
RL J. Biol. Chem. 277:29874-29880(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANTS LEU-163 AND PHE-361.
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND VARIANTS LEU-163
RP AND PHE-361.
RC TISSUE=Thymus;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16554811; DOI=10.1038/nature04632;
RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K.,
RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T.,
RA Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G.,
RA Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C.,
RA Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A.,
RA Hattori M., Rogers J., Lander E.S., Sakaki Y.;
RT "Human chromosome 11 DNA sequence and analysis including novel gene
RT identification.";
RL Nature 440:497-500(2006).
RN [5]
RP FUNCTION, INVOLVEMENT IN INFLAMMASOME COMPLEX, SUBCELLULAR LOCATION, AND
RP TISSUE SPECIFICITY.
RX PubMed=12387869; DOI=10.1016/s0014-5793(02)03416-6;
RA Grenier J.M., Wang L., Manji G.A., Huang W.-J., Al-Garawi A., Kelly R.,
RA Carlson A., Merriam S., Lora J.M., Briskin M., DiStefano P.S., Bertin J.;
RT "Functional screening of five PYPAF family members identifies PYPAF5 as a
RT novel regulator of NF-kappaB and caspase-1.";
RL FEBS Lett. 530:73-78(2002).
RN [6]
RP INDUCTION BY ROSIGLITAZONE.
RX PubMed=21088234; DOI=10.1152/ajpgi.00397.2010;
RA Kempster S.L., Belteki G., Forhead A.J., Fowden A.L., Catalano R.D.,
RA Lam B.Y., McFarlane I., Charnock-Jones D.S., Smith G.C.;
RT "Developmental control of the Nlrp6 inflammasome and a substrate, IL-18, in
RT mammalian intestine.";
RL Am. J. Physiol. 300:G253-G263(2011).
RN [7]
RP TISSUE SPECIFICITY.
RX PubMed=21593405; DOI=10.1073/pnas.1100981108;
RA Normand S., Delanoye-Crespin A., Bressenot A., Huot L., Grandjean T.,
RA Peyrin-Biroulet L., Lemoine Y., Hot D., Chamaillard M.;
RT "Nod-like receptor pyrin domain-containing protein 6 (NLRP6) controls
RT epithelial self-renewal and colorectal carcinogenesis upon injury.";
RL Proc. Natl. Acad. Sci. U.S.A. 108:9601-9606(2011).
RN [8]
RP INDUCTION BY CRH AND ROSIGLITAZONE.
RX PubMed=23470617; DOI=10.1053/j.gastro.2013.02.038;
RA Sun Y., Zhang M., Chen C.C., Gillilland M. III, Sun X., El-Zaatari M.,
RA Huffnagle G.B., Young V.B., Zhang J., Hong S.C., Chang Y.M., Gumucio D.L.,
RA Owyang C., Kao J.Y.;
RT "Stress-induced corticotropin-releasing hormone-mediated NLRP6 inflammasome
RT inhibition and transmissible enteritis in mice.";
RL Gastroenterology 144:1478-1487(2013).
RN [9]
RP FUNCTION.
RX PubMed=30392956; DOI=10.1016/j.cell.2018.09.047;
RA Hara H., Seregin S.S., Yang D., Fukase K., Chamaillard M., Alnemri E.S.,
RA Inohara N., Chen G.Y., Nunez G.;
RT "The NLRP6 inflammasome recognizes lipoteichoic acid and regulates Gram-
RT positive pathogen infection.";
RL Cell 175:1651-1664(2018).
RN [10]
RP FUNCTION, SUBUNIT, AND SUBCELLULAR LOCATION.
RX PubMed=31932628; DOI=10.1038/s41598-019-57043-0;
RA Leng F., Yin H., Qin S., Zhang K., Guan Y., Fang R., Wang H., Li G.,
RA Jiang Z., Sun F., Wang D.C., Xie C.;
RT "NLRP6 self-assembles into a linear molecular platform following LPS
RT binding and ATP stimulation.";
RL Sci. Rep. 10:198-198(2020).
RN [11]
RP FUNCTION, SUBCELLULAR LOCATION, DOMAIN, INTERACTION WITH PYCARD, AND
RP MUTAGENESIS OF 352-LYS--LYS-356.
RX PubMed=34678144; DOI=10.1016/j.cell.2021.09.032;
RA Shen C., Li R., Negro R., Cheng J., Vora S.M., Fu T.M., Wang A., He K.,
RA Andreeva L., Gao P., Tian Z., Flavell R.A., Zhu S., Wu H.;
RT "Phase separation drives RNA virus-induced activation of the NLRP6
RT inflammasome.";
RL Cell 184:5759-5774(2021).
RN [12]
RP FUNCTION, AND INTERACTION WITH DHX15.
RX PubMed=34161762; DOI=10.1016/j.celrep.2021.109205;
RA Xing J., Zhou X., Fang M., Zhang E., Minze L.J., Zhang Z.;
RT "DHX15 is required to control RNA virus-induced intestinal inflammation.";
RL Cell Rep. 35:109205-109205(2021).
RN [13]
RP FUNCTION.
RX PubMed=33377178; DOI=10.1111/iej.13469;
RA Tian X.X., Li R., Liu C., Liu F., Yang L.J., Wang S.P., Wang C.L.;
RT "NLRP6-caspase 4 inflammasome activation in response to cariogenic
RT bacterial lipoteichoic acid in human dental pulp inflammation.";
RL Int. Endod. J. 54:916-925(2021).
RN [14] {ECO:0007744|PDB:6NCV, ECO:0007744|PDB:6NDJ}
RP X-RAY CRYSTALLOGRAPHY (2.27 ANGSTROMS) OF 14-106, FUNCTION, SUBCELLULAR
RP LOCATION, SUBUNIT, AND MUTAGENESIS OF LEU-21; LEU-23; 27-GLU-GLU-28;
RP HIS-39; ARG-42; TRP-53; PHE-71 AND ARG-87.
RX PubMed=30674671; DOI=10.1073/pnas.1817221116;
RA Shen C., Lu A., Xie W.J., Ruan J., Negro R., Egelman E.H., Fu T.M., Wu H.;
RT "Molecular mechanism for NLRP6 inflammasome assembly and activation.";
RL Proc. Natl. Acad. Sci. U.S.A. 116:2052-2057(2019).
RN [15]
RP VARIANT VAL-713.
RX PubMed=26282398; DOI=10.1186/s13023-015-0316-8;
RA Dahmani M., Ammar-Khodja F., Bonnet C., Lefevre G.M., Hardelin J.P.,
RA Ibrahim H., Mallek Z., Petit C.;
RT "EPS8L2 is a new causal gene for childhood onset autosomal recessive
RT progressive hearing loss.";
RL Orphanet J. Rare Dis. 10:96-96(2015).
CC -!- FUNCTION: Acts as the sensor component of the NLRP6 inflammasome, which
CC mediates inflammasome activation in response to various pathogen-
CC associated signals, leading to maturation and secretion of IL1B and
CC IL18 (PubMed:30392956, PubMed:34678144). Inflammasomes are
CC supramolecular complexes that assemble in the cytosol in response to
CC pathogens and other damage-associated signals and play critical roles
CC in innate immunity and inflammation (PubMed:30674671). Acts as a
CC recognition receptor (PRR): recognizes and binds specific pathogens and
CC other damage-associated signals, such as lipoteichoic acid (LTA), a
CC cell-wall component of Gram-positive bacteria, or double stranded RNA
CC (dsRNA) (PubMed:30392956, PubMed:34678144, PubMed:33377178). May also
CC recognize and bind lipopolysaccharide (LPS), a major component of the
CC outer membrane of Gram-negative bacteria; however, LPS is probably not
CC a major activator of the NLRP6 inflammasome (PubMed:31932628,
CC PubMed:34678144). Following LTA- or dsRNA-binding, NLRP6 undergoes
CC liquid-liquid phase separation (LLPS), enhancing multivalent
CC interactions, an essential step for the formation of the NLRP6
CC inflammasome polymeric complex (PubMed:34678144). The NLRP6
CC inflammasome acts by promoting recruitment of effector pro-inflammatory
CC caspases (CASP1 and/or CASP4) that catalyze maturation and secretion of
CC IL1B and IL18 in the extracellular milieu (PubMed:30674671,
CC PubMed:12387869, PubMed:30392956, PubMed:34678144). The NLRP6
CC inflammasome plays a central role in the maintenance of epithelial
CC integrity and host defense against microbial infections in the
CC intestine (PubMed:30392956). Required to restrict infection against
CC Gram-positive bacteria by recognizing lipoteichoic acid (LTA), leading
CC to recruitment of CASP4 and CASP1, and subsequent maturation and
CC secretion of IL1B and IL18 (PubMed:30392956, PubMed:33377178). Involved
CC in intestinal antiviral innate immunity together with DHX15: recognizes
CC and binds viral dsRNA to restrict infection by enteric viruses through
CC the interferon pathway and GSDMD-dependent release of IL18
CC (PubMed:34678144, PubMed:34161762). Required to prevent infection by
CC the apicomplexan parasite Cryptosporidium in enterocytes by promoting
CC GSDMD-dependent release of IL18 (By similarity). The NLRP6 inflammasome
CC may also regulate the gut microbiota composition by acting as a sensor
CC of microbiota-associated metabolites to form a PYCARD/ASC-dependent
CC inflammasome for downstream IL18 release and secretion of antimicrobial
CC peptides (By similarity). Essential for gut mucosal self-renewal and
CC proliferation (By similarity). Regulate mucus secretion in an
CC inflammasome- and autophagy-dependent manner to prevent invasion by
CC enteric bacteria, (By similarity). During systemic bacterial
CC infections, the NLRP6 inflammasome negatively regulates neutrophil
CC recruitment and neutrophil extracellular traps (NETs) formation (By
CC similarity). May promote peripheral nerve recovery following injury via
CC an inflammasome-independent mechanism (By similarity).
CC {ECO:0000250|UniProtKB:Q91WS2, ECO:0000269|PubMed:12387869,
CC ECO:0000269|PubMed:30392956, ECO:0000269|PubMed:30674671,
CC ECO:0000269|PubMed:31932628, ECO:0000269|PubMed:33377178,
CC ECO:0000269|PubMed:34161762, ECO:0000269|PubMed:34678144}.
CC -!- SUBUNIT: Homomultimer; forms the NLRP6 inflammasome polymeric complex,
CC a filament composed of homopolymers in response to pathogens and other
CC damage-associated signals (PubMed:31932628, PubMed:34678144,
CC PubMed:30674671). The core of NLRP6 inflammasomes consists of a signal
CC sensor component (NLRP6), an adapter (PYCARD/ASC), which recruits
CC effector pro-inflammatory caspases (CASP1 and CASP4) (PubMed:34678144,
CC PubMed:30674671). Interacts (via pyrin domain) with PYCARD/ASC (via
CC pyrin domain); interaction takes place following NLRP6 activation and
CC formation of liquid-liquid phase separation (LLPS), initiating
CC nucleation which greatly enhances further addition of soluble
CC PYCARD/ASC molecules to the speck in a prion-like polymerization
CC process (PubMed:34678144, PubMed:30674671). Clustered PYCARD/ASC
CC nucleates the formation of CASP1 (or possibly CASP4) filaments through
CC the interaction of their respective CARD domains, acting as a platform
CC for CASP1 polymerization (PubMed:34678144). CASP1 filament formation
CC increases local enzyme concentration, resulting in trans-autocleavage
CC and activation (PubMed:34678144). Active CASP1 then processes IL1B and
CC IL18 precursors, leading to the release of mature cytokines in the
CC extracellular milieu and inflammatory response (PubMed:34678144).
CC Interacts with DHX15 (PubMed:34161762). {ECO:0000269|PubMed:30674671,
CC ECO:0000269|PubMed:31932628, ECO:0000269|PubMed:34161762,
CC ECO:0000269|PubMed:34678144}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:12387869,
CC ECO:0000269|PubMed:31932628}. Inflammasome
CC {ECO:0000269|PubMed:12387869, ECO:0000269|PubMed:30674671,
CC ECO:0000269|PubMed:31932628, ECO:0000269|PubMed:34678144}. Cell
CC membrane {ECO:0000250|UniProtKB:Q63035}. Nucleus membrane
CC {ECO:0000250|UniProtKB:Q63035}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P59044-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P59044-2; Sequence=VSP_054400;
CC -!- TISSUE SPECIFICITY: Expressed in peripheral blood leukocytes,
CC predominantly in granulocytes and, at lower levels, in CD4(+) and
CC CD8(+) T-cells (PubMed:12387869). Expressed in colonic myofibroblasts
CC (at protein level) (PubMed:21593405). {ECO:0000269|PubMed:12387869,
CC ECO:0000269|PubMed:21593405}.
CC -!- INDUCTION: Up-regulated by rosiglitazone, a PPARG agonist, in Caco2 and
CC HCT116 colorectal carcinoma cells (PubMed:21088234, PubMed:23470617).
CC Down-regulated by CRH (at protein level) (PubMed:23470617).
CC {ECO:0000269|PubMed:21088234, ECO:0000269|PubMed:23470617}.
CC -!- DOMAIN: The poly-Lys disordered region (352-356) mediates the formation
CC of liquid-liquid phase separation (LLPS), an essential step for
CC nucleation and formation of the NLRP6 inflammasome complex.
CC {ECO:0000269|PubMed:34678144}.
CC -!- PTM: Polyubiquitinated with 'Lys-63'-linked chains, promoting the
CC interaction with PYCARD/ASC and formation of the NLRP6 inflammasome.
CC Deubiquitination by CYLD decreases the interaction with PYCARD/ASC.
CC {ECO:0000250|UniProtKB:Q91WS2}.
CC -!- SIMILARITY: Belongs to the NLRP family. {ECO:0000305}.
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DR EMBL; AF479748; AAL87105.1; -; mRNA.
DR EMBL; AY154461; AAO18157.1; -; mRNA.
DR EMBL; AK292668; BAF85357.1; -; mRNA.
DR EMBL; AC136475; -; NOT_ANNOTATED_CDS; mRNA.
DR CCDS; CCDS60680.1; -. [P59044-2]
DR CCDS; CCDS7693.1; -. [P59044-1]
DR RefSeq; NP_001263629.1; NM_001276700.1. [P59044-2]
DR RefSeq; NP_612202.2; NM_138329.2. [P59044-1]
DR PDB; 6NCV; EM; 3.70 A; A/B/C/D/E/F/G/H/I/J/K/L/M/N/O/P/Q/R/S/T/V=1-106.
DR PDB; 6NDJ; X-ray; 2.27 A; A/B=14-106.
DR PDBsum; 6NCV; -.
DR PDBsum; 6NDJ; -.
DR AlphaFoldDB; P59044; -.
DR SMR; P59044; -.
DR BioGRID; 128114; 3.
DR STRING; 9606.ENSP00000309767; -.
DR iPTMnet; P59044; -.
DR PhosphoSitePlus; P59044; -.
DR BioMuta; NLRP6; -.
DR DMDM; 259016285; -.
DR MassIVE; P59044; -.
DR PaxDb; P59044; -.
DR PeptideAtlas; P59044; -.
DR PRIDE; P59044; -.
DR ProteomicsDB; 21300; -.
DR ProteomicsDB; 57113; -. [P59044-1]
DR Antibodypedia; 58845; 238 antibodies from 29 providers.
DR DNASU; 171389; -.
DR Ensembl; ENST00000312165.5; ENSP00000309767.4; ENSG00000174885.13. [P59044-1]
DR Ensembl; ENST00000534750.6; ENSP00000433617.1; ENSG00000174885.13. [P59044-2]
DR GeneID; 171389; -.
DR KEGG; hsa:171389; -.
DR MANE-Select; ENST00000534750.6; ENSP00000433617.1; NM_001276700.2; NP_001263629.1. [P59044-2]
DR UCSC; uc010qvs.4; human. [P59044-1]
DR CTD; 171389; -.
DR DisGeNET; 171389; -.
DR GeneCards; NLRP6; -.
DR HGNC; HGNC:22944; NLRP6.
DR HPA; ENSG00000174885; Tissue enriched (intestine).
DR MIM; 609650; gene.
DR neXtProt; NX_P59044; -.
DR OpenTargets; ENSG00000174885; -.
DR PharmGKB; PA162398002; -.
DR VEuPathDB; HostDB:ENSG00000174885; -.
DR eggNOG; ENOG502SANB; Eukaryota.
DR GeneTree; ENSGT00940000162758; -.
DR HOGENOM; CLU_002274_2_2_1; -.
DR InParanoid; P59044; -.
DR OMA; QCRVQKL; -.
DR OrthoDB; 114368at2759; -.
DR PhylomeDB; P59044; -.
DR PathwayCommons; P59044; -.
DR BioGRID-ORCS; 171389; 8 hits in 1074 CRISPR screens.
DR GeneWiki; NLRP6; -.
DR GenomeRNAi; 171389; -.
DR Pharos; P59044; Tbio.
DR PRO; PR:P59044; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; P59044; protein.
DR Bgee; ENSG00000174885; Expressed in small intestine Peyer's patch and 75 other tissues.
DR Genevisible; P59044; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0061702; C:inflammasome complex; IBA:GO_Central.
DR GO; GO:0140738; C:NLRP6 inflammasome complex; IDA:UniProtKB.
DR GO; GO:0043228; C:non-membrane-bounded organelle; IDA:UniProtKB.
DR GO; GO:0031965; C:nuclear membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0003725; F:double-stranded RNA binding; IDA:UniProtKB.
DR GO; GO:0001530; F:lipopolysaccharide binding; IDA:UniProtKB.
DR GO; GO:0070891; F:lipoteichoic acid binding; IDA:UniProtKB.
DR GO; GO:0140693; F:molecular condensate scaffold activity; IDA:UniProtKB.
DR GO; GO:0038187; F:pattern recognition receptor activity; IDA:UniProtKB.
DR GO; GO:0042277; F:peptide binding; IBA:GO_Central.
DR GO; GO:0005000; F:vasopressin receptor activity; ISS:UniProtKB.
DR GO; GO:0097202; P:activation of cysteine-type endopeptidase activity; IEA:Ensembl.
DR GO; GO:0002526; P:acute inflammatory response; IBA:GO_Central.
DR GO; GO:0002438; P:acute inflammatory response to antigenic stimulus; IEA:Ensembl.
DR GO; GO:0140374; P:antiviral innate immune response; IDA:UniProtKB.
DR GO; GO:0050830; P:defense response to Gram-positive bacterium; IDA:UniProtKB.
DR GO; GO:0051607; P:defense response to virus; IDA:UniProtKB.
DR GO; GO:0048874; P:host-mediated regulation of intestinal microbiota composition; IEA:Ensembl.
DR GO; GO:0070266; P:necroptotic process; IEA:Ensembl.
DR GO; GO:0070373; P:negative regulation of ERK1 and ERK2 cascade; IEA:Ensembl.
DR GO; GO:0043124; P:negative regulation of I-kappaB kinase/NF-kappaB signaling; IEA:Ensembl.
DR GO; GO:0002862; P:negative regulation of inflammatory response to antigenic stimulus; IEA:Ensembl.
DR GO; GO:0032689; P:negative regulation of interferon-gamma production; IEA:Ensembl.
DR GO; GO:0034122; P:negative regulation of toll-like receptor signaling pathway; IEA:Ensembl.
DR GO; GO:0070946; P:neutrophil-mediated killing of gram-positive bacterium; IEA:Ensembl.
DR GO; GO:0140739; P:NLRP6 inflammasome complex assembly; IDA:UniProtKB.
DR GO; GO:0050729; P:positive regulation of inflammatory response; IDA:UniProtKB.
DR GO; GO:2000494; P:positive regulation of interleukin-18-mediated signaling pathway; IDA:UniProtKB.
DR GO; GO:0051260; P:protein homooligomerization; IDA:UniProtKB.
DR GO; GO:0070269; P:pyroptosis; IEA:Ensembl.
DR GO; GO:0010506; P:regulation of autophagy; IEA:Ensembl.
DR GO; GO:0050727; P:regulation of inflammatory response; ISS:UniProtKB.
DR GO; GO:0070255; P:regulation of mucus secretion; IEA:Ensembl.
DR GO; GO:0009617; P:response to bacterium; IBA:GO_Central.
DR GO; GO:0042060; P:wound healing; IEA:Ensembl.
DR Gene3D; 1.10.533.10; -; 1.
DR Gene3D; 3.40.50.300; -; 1.
DR Gene3D; 3.80.10.10; -; 1.
DR InterPro; IPR004020; DAPIN.
DR InterPro; IPR011029; DEATH-like_dom_sf.
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; PF05729; NACHT; 1.
DR Pfam; PF17776; NLRC4_HD2; 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; Alternative splicing; ATP-binding; Cell membrane; Cytoplasm;
KW Immunity; Inflammasome; Inflammatory response; Innate immunity;
KW Leucine-rich repeat; Membrane; Nucleotide-binding; Nucleus;
KW Reference proteome; Repeat; Ubl conjugation.
FT CHAIN 1..892
FT /note="NACHT, LRR and PYD domains-containing protein 6"
FT /id="PRO_0000080892"
FT DOMAIN 1..103
FT /note="Pyrin"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00061"
FT DOMAIN 196..513
FT /note="NACHT"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00136"
FT REPEAT 462..487
FT /note="LRR 1"
FT /evidence="ECO:0000255"
FT REPEAT 727..747
FT /note="LRR 2"
FT /evidence="ECO:0000255"
FT REPEAT 755..778
FT /note="LRR 3"
FT /evidence="ECO:0000255"
FT REPEAT 811..834
FT /note="LRR 4"
FT /evidence="ECO:0000255"
FT REPEAT 845..868
FT /note="LRR 5"
FT /evidence="ECO:0000255"
FT REGION 158..181
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 352..356
FT /note="Disordered"
FT /evidence="ECO:0000269|PubMed:34678144"
FT REGION 590..614
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 166..181
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 202..209
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00136"
FT VAR_SEQ 702
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_054400"
FT VARIANT 163
FT /note="M -> L (in dbSNP:rs6421985)"
FT /evidence="ECO:0000269|PubMed:12019269,
FT ECO:0000269|PubMed:12563287, ECO:0000269|PubMed:14702039"
FT /id="VAR_058968"
FT VARIANT 361
FT /note="Y -> F (in dbSNP:rs7482965)"
FT /evidence="ECO:0000269|PubMed:12019269,
FT ECO:0000269|PubMed:12563287, ECO:0000269|PubMed:14702039"
FT /id="VAR_058969"
FT VARIANT 713
FT /note="A -> V (in dbSNP:rs966612159)"
FT /evidence="ECO:0000269|PubMed:26282398"
FT /id="VAR_079497"
FT MUTAGEN 21
FT /note="L->R: Decreased formation of an inflammasome
FT filament."
FT /evidence="ECO:0000269|PubMed:30674671"
FT MUTAGEN 23
FT /note="L->R: Decreased formation of an inflammasome
FT filament. Decreased ability to promote PYCARD/ASC
FT polymerization."
FT /evidence="ECO:0000269|PubMed:30674671"
FT MUTAGEN 27..28
FT /note="EE->RR: Abolished formation of an inflammasome
FT filament."
FT /evidence="ECO:0000269|PubMed:30674671"
FT MUTAGEN 39
FT /note="H->R: Decreased formation of an inflammasome
FT filament. Abolished ability to promote PYCARD/ASC
FT polymerization."
FT /evidence="ECO:0000269|PubMed:30674671"
FT MUTAGEN 42
FT /note="R->E: Abolished formation of an inflammasome
FT filament."
FT /evidence="ECO:0000269|PubMed:30674671"
FT MUTAGEN 53
FT /note="W->E: Abolished formation of an inflammasome
FT filament."
FT /evidence="ECO:0000269|PubMed:30674671"
FT MUTAGEN 53
FT /note="W->F: Does not affect formation of an inflammasome
FT filament."
FT /evidence="ECO:0000269|PubMed:30674671"
FT MUTAGEN 71
FT /note="F->R: Does not prevent formation of an inflammasome
FT filament."
FT /evidence="ECO:0000269|PubMed:30674671"
FT MUTAGEN 87
FT /note="R->D: Does not prevent formation of an inflammasome
FT filament."
FT /evidence="ECO:0000269|PubMed:30674671"
FT MUTAGEN 352..356
FT /note="KDKKK->ADAAA: Impaired formation of liquid-liquid
FT phase separation (LLPS)."
FT /evidence="ECO:0000269|PubMed:34678144"
FT HELIX 14..27
FT /evidence="ECO:0007829|PDB:6NDJ"
FT HELIX 31..41
FT /evidence="ECO:0007829|PDB:6NDJ"
FT HELIX 46..48
FT /evidence="ECO:0007829|PDB:6NDJ"
FT HELIX 56..58
FT /evidence="ECO:0007829|PDB:6NDJ"
FT HELIX 61..72
FT /evidence="ECO:0007829|PDB:6NDJ"
FT HELIX 74..85
FT /evidence="ECO:0007829|PDB:6NDJ"
SQ SEQUENCE 892 AA; 98768 MW; A987FDACE6448C6A CRC64;
MDQPEAPCSS TGPRLAVARE LLLAALEELS QEQLKRFRHK LRDVGPDGRS IPWGRLERAD
AVDLAEQLAQ FYGPEPALEV ARKTLKRADA RDVAAQLQER RLQRLGLGSG TLLSVSEYKK
KYREHVLQLH ARVKERNARS VKITKRFTKL LIAPESAAPE EAMGPAEEPE PGRARRSDTH
TFNRLFRRDE EGRRPLTVVL QGPAGIGKTM AAKKILYDWA AGKLYQGQVD FAFFMPCGEL
LERPGTRSLA DLILDQCPDR GAPVPQMLAQ PQRLLFILDG ADELPALGGP EAAPCTDPFE
AASGARVLGG LLSKALLPTA LLLVTTRAAA PGRLQGRLCS PQCAEVRGFS DKDKKKYFYK
YFRDERRAER AYRFVKENET LFALCFVPFV CWIVCTVLRQ QLELGRDLSR TSKTTTSVYL
LFITSVLSSA PVADGPRLQG DLRNLCRLAR EGVLGRRAQF AEKELEQLEL RGSKVQTLFL
SKKELPGVLE TEVTYQFIDQ SFQEFLAALS YLLEDGGVPR TAAGGVGTLL RGDAQPHSHL
VLTTRFLFGL LSAERMRDIE RHFGCMVSER VKQEALRWVQ GQGQGCPGVA PEVTEGAKGL
EDTEEPEEEE EGEEPNYPLE LLYCLYETQE DAFVRQALCR FPELALQRVR FCRMDVAVLS
YCVRCCPAGQ ALRLISCRLV AAQEKKKKSL GKRLQASLGG GSSSQGTTKQ LPASLLHPLF
QAMTDPLCHL SSLTLSHCKL PDAVCRDLSE ALRAAPALTE LGLLHNRLSE AGLRMLSEGL
AWPQCRVQTV RVQLPDPQRG LQYLVGMLRQ SPALTTLDLS GCQLPAPMVT YLCAVLQHQG
CGLQTLSLAS VELSEQSLQE LQAVKRAKPD LVITHPALDG HPQPPKELIS TF
