NAL12_HUMAN
ID NAL12_HUMAN Reviewed; 1061 AA.
AC P59046; A8MTQ2; B3KTE7; Q8NEU4; Q9BY26;
DT 19-OCT-2002, integrated into UniProtKB/Swiss-Prot.
DT 22-AUG-2003, sequence version 2.
DT 03-AUG-2022, entry version 182.
DE RecName: Full=NACHT, LRR and PYD domains-containing protein 12;
DE AltName: Full=Monarch-1;
DE AltName: Full=PYRIN-containing APAF1-like protein 7;
DE AltName: Full=Regulated by nitric oxide;
GN Name=NLRP12; Synonyms=NALP12, PYPAF7, RNO;
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).
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).
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 [MRNA] (ISOFORMS 1; 2; 3; 4 AND 7).
RC TISSUE=Lymphoma;
RA Williams K.L., Linhoff M.W., Harton J.A., Ting J.P.Y.;
RL Submitted (MAY-2002) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 5), TISSUE SPECIFICITY, ALTERNATIVE
RP SPLICING, AND INDUCTION.
RC TISSUE=Peripheral blood leukocyte;
RX PubMed=11167794; DOI=10.1046/j.1365-2141.2001.02491.x;
RA Shami P.J., Kanai N., Wang L.Y., Vreeke T.M., Parker C.J.;
RT "Identification and characterization of a novel gene that is upregulated in
RT leukaemia cells by nitric oxide.";
RL Br. J. Haematol. 112:138-147(2001).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 6).
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057824; DOI=10.1038/nature02399;
RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E.,
RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A.,
RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S.,
RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A.,
RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J.,
RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M.,
RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W.,
RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V.,
RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D.,
RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I.,
RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L.,
RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A.,
RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M.,
RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J.,
RA Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA Rubin E.M., Lucas S.M.;
RT "The DNA sequence and biology of human chromosome 19.";
RL Nature 428:529-535(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Leukocyte;
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 [9]
RP FUNCTION, AND INTERACTION WITH MAP3K14.
RX PubMed=17237370; DOI=10.4049/jimmunol.178.3.1256;
RA Lich J.D., Williams K.L., Moore C.B., Arthur J.C., Davis B.K., Taxman D.J.,
RA Ting J.P.;
RT "Monarch-1 suppresses non-canonical NF-kappaB activation and p52-dependent
RT chemokine expression in monocytes.";
RL J. Immunol. 178:1256-1260(2007).
RN [10]
RP FUNCTION, AND INTERACTION WITH HSPA8; HSPA1A AND HSP90AA1.
RX PubMed=17947705; DOI=10.4049/jimmunol.179.9.6291;
RA Arthur J.C., Lich J.D., Aziz R.K., Kotb M., Ting J.P.;
RT "Heat shock protein 90 associates with monarch-1 and regulates its ability
RT to promote degradation of NF-kappaB-inducing kinase.";
RL J. Immunol. 179:6291-6296(2007).
RN [11]
RP ATP-BINDING.
RX PubMed=18160710; DOI=10.1128/mcb.01468-07;
RA Ye Z., Lich J.D., Moore C.B., Duncan J.A., Williams K.L., Ting J.P.;
RT "ATP binding by monarch-1/NLRP12 is critical for its inhibitory function.";
RL Mol. Cell. Biol. 28:1841-1850(2008).
RN [12]
RP INVOLVEMENT IN FCAS2.
RX PubMed=18230725; DOI=10.1073/pnas.0708616105;
RA Jeru I., Duquesnoy P., Fernandes-Alnemri T., Cochet E., Yu J.W.,
RA Lackmy-Port-Lis M., Grimprel E., Landman-Parker J., Hentgen V., Marlin S.,
RA McElreavey K., Sarkisian T., Grateau G., Alnemri E.S., Amselem S.;
RT "Mutations in NALP12 cause hereditary periodic fever syndromes.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:1614-1619(2008).
RN [13]
RP FUNCTION, AND INTERACTION WITH NOD2 AND HSP90AA1.
RX PubMed=30559449; DOI=10.1038/s41467-018-07750-5;
RA Normand S., Waldschmitt N., Neerincx A., Martinez-Torres R.J., Chauvin C.,
RA Couturier-Maillard A., Boulard O., Cobret L., Awad F., Huot L.,
RA Ribeiro-Ribeiro A., Lautz K., Ruez R., Delacre M., Bondu C., Guilliams M.,
RA Scott C., Segal A., Amselem S., Hot D., Karabina S., Bohn E., Ryffel B.,
RA Poulin L.F., Kufer T.A., Chamaillard M.;
RT "Proteasomal degradation of NOD2 by NLRP12 in monocytes promotes bacterial
RT tolerance and colonization by enteropathogens.";
RL Nat. Commun. 9:5338-5338(2018).
RN [14]
RP FUNCTION, INTERACTION WITH TRIM25, AND SUBCELLULAR LOCATION.
RX PubMed=30902577; DOI=10.1016/j.chom.2019.02.013;
RA Chen S.T., Chen L., Lin D.S., Chen S.Y., Tsao Y.P., Guo H., Li F.J.,
RA Tseng W.T., Tam J.W., Chao C.W., Brickey W.J., Dzhagalov I., Song M.J.,
RA Kang H.R., Jung J.U., Ting J.P.;
RT "NLRP12 Regulates Anti-viral RIG-I Activation via Interaction with
RT TRIM25.";
RL Cell Host Microbe 0:0-0(2019).
RN [15]
RP STRUCTURE BY NMR OF 1-98, AND INTERACTION WITH FAF1.
RX PubMed=21978668; DOI=10.1016/j.jmb.2011.09.024;
RA Pinheiro A.S., Eibl C., Ekman-Vural Z., Schwarzenbacher R., Peti W.;
RT "The NLRP12 pyrin domain: structure, dynamics, and functional insights.";
RL J. Mol. Biol. 413:790-803(2011).
RN [16]
RP X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) OF 9-106.
RX PubMed=28112203; DOI=10.1038/srep40991;
RA Jin T., Chuenchor W., Jiang J., Cheng J., Li Y., Fang K., Huang M.,
RA Smith P., Xiao T.S.;
RT "Design of an expression system to enhance MBP-mediated crystallization.";
RL Sci. Rep. 7:40991-40991(2017).
CC -!- FUNCTION: Plays an essential role as an potent mitigator of
CC inflammation (PubMed:30559449). Primarily expressed in dendritic cells
CC and macrophages, inhibits both canonical and non-canonical NF-kappa-B
CC and ERK activation pathways (PubMed:15489334, PubMed:17947705).
CC Functions as a negative regulator of NOD2 by targeting it to
CC degradation via the proteasome pathway (PubMed:30559449). In turn,
CC promotes bacterial tolerance (PubMed:30559449). Inhibits also the
CC DDX58-mediated immune signaling against RNA viruses by reducing the E3
CC ubiquitin ligase TRIM25-mediated 'Lys-63'-linked DDX58 activation but
CC enhancing the E3 ubiquitin ligase RNF125-mediated 'Lys-48'-linked DDX58
CC degradation (PubMed:30902577). Acts also as a negative regulator of
CC inflammatory response to mitigate obesity and obesity-associated
CC diseases in adipose tissue (By similarity).
CC {ECO:0000250|UniProtKB:E9Q5R7, ECO:0000269|PubMed:15489334,
CC ECO:0000269|PubMed:17947705, ECO:0000269|PubMed:30559449,
CC ECO:0000269|PubMed:30902577}.
CC -!- SUBUNIT: Interacts (via pyrin domain) with ASC. Interacts (via pyrin
CC domain) with FAF1 (via UBA domain) (PubMed:21978668). Interacts with
CC MAP3K14; this interaction promotes proteasomal degradation of MAP3K14
CC (PubMed:17237370). Interacts with NOD2; this interaction promotes
CC degradation of NOD2 through the ubiquitin-proteasome pathway
CC (PubMed:30559449). Interacts with HSPA1A and HSPA8 (PubMed:17947705).
CC Interacts with HSP90AA1 (PubMed:17947705, PubMed:30559449). Interacts
CC with TRIM25; this interaction inhibits DDX58-mediated signaling pathway
CC (PubMed:30902577). {ECO:0000269|PubMed:17237370,
CC ECO:0000269|PubMed:17947705, ECO:0000269|PubMed:21978668,
CC ECO:0000269|PubMed:30559449, ECO:0000269|PubMed:30902577}.
CC -!- INTERACTION:
CC P59046; P08631: HCK; NbExp=4; IntAct=EBI-6374637, EBI-346340;
CC P59046; Q9Y228: TRAF3IP3; NbExp=2; IntAct=EBI-6374637, EBI-765817;
CC P59046; PRO_0000449623 [P0DTD1]: rep; Xeno; NbExp=3; IntAct=EBI-6374637, EBI-25475864;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:30902577}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=7;
CC Name=1; Synonyms=I;
CC IsoId=P59046-1; Sequence=Displayed;
CC Name=2; Synonyms=II;
CC IsoId=P59046-2; Sequence=VSP_005524;
CC Name=3; Synonyms=III;
CC IsoId=P59046-3; Sequence=VSP_005523;
CC Name=4; Synonyms=IV;
CC IsoId=P59046-4; Sequence=VSP_009879;
CC Name=5; Synonyms=rno-2;
CC IsoId=P59046-5; Sequence=VSP_016908, VSP_016909, VSP_016910;
CC Name=6;
CC IsoId=P59046-6; Sequence=VSP_054622;
CC Name=7;
CC IsoId=P59046-7; Sequence=VSP_055193;
CC -!- TISSUE SPECIFICITY: Detected only in peripheral blood leukocytes,
CC predominantly in eosinophils and granulocytes, and at lower levels in
CC monocytes. {ECO:0000269|PubMed:11167794}.
CC -!- INDUCTION: By nitric oxide and DMSO in HL-60 cells, an acute myeloid
CC leukemia cell line. {ECO:0000269|PubMed:11167794}.
CC -!- DISEASE: Familial cold autoinflammatory syndrome 2 (FCAS2)
CC [MIM:611762]: A rare autosomal dominant systemic inflammatory disease
CC characterized by recurrent episodes of maculopapular rash associated
CC with arthralgias, myalgias, fever and chills, swelling of the
CC extremities, and conjunctivitis after generalized exposure to cold.
CC {ECO:0000269|PubMed:18230725}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the NLRP family. {ECO:0000305}.
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DR EMBL; AY095146; AAM18227.1; -; mRNA.
DR EMBL; AY154467; AAO18163.1; -; mRNA.
DR EMBL; AY116204; AAM75142.1; -; mRNA.
DR EMBL; AY116205; AAM75143.1; -; mRNA.
DR EMBL; AY116206; AAM75144.1; -; mRNA.
DR EMBL; AY116207; AAM75145.1; -; mRNA.
DR EMBL; AF231021; AAK14942.1; -; mRNA.
DR EMBL; AK095460; BAG53059.1; -; mRNA.
DR EMBL; AC008753; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471135; EAW72152.1; -; Genomic_DNA.
DR EMBL; BC028069; AAH28069.1; -; mRNA.
DR CCDS; CCDS12864.1; -. [P59046-1]
DR CCDS; CCDS62784.1; -. [P59046-6]
DR CCDS; CCDS62785.1; -. [P59046-7]
DR RefSeq; NP_001264055.1; NM_001277126.1. [P59046-7]
DR RefSeq; NP_001264058.1; NM_001277129.1. [P59046-6]
DR RefSeq; NP_653288.1; NM_144687.3. [P59046-1]
DR PDB; 2L6A; NMR; -; A=1-98.
DR PDB; 4XHS; X-ray; 1.70 A; A/B=10-106.
DR PDB; 5H7N; X-ray; 1.85 A; A/B=9-106.
DR PDBsum; 2L6A; -.
DR PDBsum; 4XHS; -.
DR PDBsum; 5H7N; -.
DR AlphaFoldDB; P59046; -.
DR BMRB; P59046; -.
DR SMR; P59046; -.
DR BioGRID; 124861; 10.
DR IntAct; P59046; 76.
DR MINT; P59046; -.
DR STRING; 9606.ENSP00000375653; -.
DR GlyGen; P59046; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P59046; -.
DR PhosphoSitePlus; P59046; -.
DR BioMuta; NLRP12; -.
DR DMDM; 34223733; -.
DR PaxDb; P59046; -.
DR PeptideAtlas; P59046; -.
DR PRIDE; P59046; -.
DR ProteomicsDB; 2044; -.
DR ProteomicsDB; 57117; -. [P59046-1]
DR ProteomicsDB; 57118; -. [P59046-2]
DR ProteomicsDB; 57119; -. [P59046-3]
DR ProteomicsDB; 57120; -. [P59046-4]
DR ProteomicsDB; 57121; -. [P59046-5]
DR Antibodypedia; 32741; 325 antibodies from 35 providers.
DR DNASU; 91662; -.
DR Ensembl; ENST00000324134.11; ENSP00000319377.6; ENSG00000142405.22. [P59046-1]
DR Ensembl; ENST00000391773.6; ENSP00000375653.1; ENSG00000142405.22. [P59046-7]
DR Ensembl; ENST00000391775.7; ENSP00000375655.3; ENSG00000142405.22. [P59046-6]
DR GeneID; 91662; -.
DR KEGG; hsa:91662; -.
DR MANE-Select; ENST00000324134.11; ENSP00000319377.6; NM_144687.4; NP_653288.1.
DR UCSC; uc002qch.6; human. [P59046-1]
DR CTD; 91662; -.
DR DisGeNET; 91662; -.
DR GeneCards; NLRP12; -.
DR HGNC; HGNC:22938; NLRP12.
DR HPA; ENSG00000142405; Tissue enhanced (bone marrow, lymphoid tissue).
DR MalaCards; NLRP12; -.
DR MIM; 609648; gene.
DR MIM; 611762; phenotype.
DR neXtProt; NX_P59046; -.
DR OpenTargets; ENSG00000142405; -.
DR Orphanet; 247868; NLRP12-associated hereditary periodic fever syndrome.
DR PharmGKB; PA162397866; -.
DR VEuPathDB; HostDB:ENSG00000142405; -.
DR eggNOG; ENOG502QS9E; Eukaryota.
DR GeneTree; ENSGT00940000160873; -.
DR InParanoid; P59046; -.
DR OMA; TTAVYMF; -.
DR OrthoDB; 114368at2759; -.
DR PhylomeDB; P59046; -.
DR TreeFam; TF340267; -.
DR PathwayCommons; P59046; -.
DR Reactome; R-HSA-9705671; SARS-CoV-2 activates/modulates innate and adaptive immune responses.
DR SignaLink; P59046; -.
DR BioGRID-ORCS; 91662; 13 hits in 1065 CRISPR screens.
DR ChiTaRS; NLRP12; human.
DR EvolutionaryTrace; P59046; -.
DR GeneWiki; NLRP12; -.
DR GenomeRNAi; 91662; -.
DR Pharos; P59046; Tbio.
DR PRO; PR:P59046; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; P59046; protein.
DR Bgee; ENSG00000142405; Expressed in blood and 87 other tissues.
DR ExpressionAtlas; P59046; baseline and differential.
DR Genevisible; P59046; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0008656; F:cysteine-type endopeptidase activator activity involved in apoptotic process; NAS:UniProtKB.
DR GO; GO:0006919; P:activation of cysteine-type endopeptidase activity involved in apoptotic process; NAS:UniProtKB.
DR GO; GO:0071345; P:cellular response to cytokine stimulus; IBA:GO_Central.
DR GO; GO:0036336; P:dendritic cell migration; IEA:Ensembl.
DR GO; GO:0070371; P:ERK1 and ERK2 cascade; IEA:Ensembl.
DR GO; GO:0001818; P:negative regulation of cytokine production; IDA:HGNC-UCL.
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; IDA:HGNC-UCL.
DR GO; GO:0050728; P:negative regulation of inflammatory response; IMP:BHF-UCL.
DR GO; GO:0032692; P:negative regulation of interleukin-1 production; IDA:HGNC-UCL.
DR GO; GO:0032715; P:negative regulation of interleukin-6 production; IDA:HGNC-UCL.
DR GO; GO:0032088; P:negative regulation of NF-kappaB transcription factor activity; IDA:BHF-UCL.
DR GO; GO:1901223; P:negative regulation of NIK/NF-kappaB signaling; IDA:UniProtKB.
DR GO; GO:0031953; P:negative regulation of protein autophosphorylation; IDA:HGNC-UCL.
DR GO; GO:0009968; P:negative regulation of signal transduction; IDA:HGNC-UCL.
DR GO; GO:0045751; P:negative regulation of Toll signaling pathway; IDA:HGNC-UCL.
DR GO; GO:0038061; P:NIK/NF-kappaB signaling; IEA:Ensembl.
DR GO; GO:0050729; P:positive regulation of inflammatory response; NAS:UniProtKB.
DR GO; GO:0032731; P:positive regulation of interleukin-1 beta production; NAS:UniProtKB.
DR GO; GO:0045345; P:positive regulation of MHC class I biosynthetic process; IDA:MGI.
DR GO; GO:1901224; P:positive regulation of NIK/NF-kappaB signaling; IDA:UniProtKB.
DR GO; GO:0043281; P:regulation of cysteine-type endopeptidase activity involved in apoptotic process; IDA:MGI.
DR GO; GO:0043122; P:regulation of I-kappaB kinase/NF-kappaB signaling; IDA:MGI.
DR GO; GO:0050727; P:regulation of inflammatory response; IBA:GO_Central.
DR GO; GO:0032661; P:regulation of interleukin-18 production; NAS:UniProtKB.
DR GO; GO:0007165; P:signal transduction; NAS:UniProtKB.
DR Gene3D; 1.10.533.10; -; 1.
DR Gene3D; 3.40.50.300; -; 1.
DR Gene3D; 3.80.10.10; -; 2.
DR InterPro; IPR004020; DAPIN.
DR InterPro; IPR011029; DEATH-like_dom_sf.
DR InterPro; IPR001611; Leu-rich_rpt.
DR InterPro; IPR032675; LRR_dom_sf.
DR InterPro; IPR029495; NACHT-assoc.
DR InterPro; IPR007111; NACHT_NTPase.
DR InterPro; IPR041267; NLRP_HD2.
DR InterPro; IPR041075; NOD2_WH.
DR InterPro; IPR027417; P-loop_NTPase.
DR Pfam; PF14484; FISNA; 1.
DR Pfam; PF13516; LRR_6; 5.
DR Pfam; PF05729; NACHT; 1.
DR Pfam; PF17776; NLRC4_HD2; 1.
DR Pfam; PF17779; NOD2_WH; 1.
DR Pfam; PF02758; PYRIN; 1.
DR SMART; SM01288; FISNA; 1.
DR SMART; SM01289; PYRIN; 1.
DR SUPFAM; SSF47986; SSF47986; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR PROSITE; PS50824; DAPIN; 1.
DR PROSITE; PS51450; LRR; 5.
DR PROSITE; PS50837; NACHT; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; ATP-binding; Cytoplasm;
KW Leucine-rich repeat; Nucleotide-binding; Reference proteome; Repeat.
FT CHAIN 1..1061
FT /note="NACHT, LRR and PYD domains-containing protein 12"
FT /id="PRO_0000080899"
FT DOMAIN 1..95
FT /note="Pyrin"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00061"
FT DOMAIN 211..528
FT /note="NACHT"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00136"
FT REPEAT 828..848
FT /note="LRR 1"
FT REPEAT 857..878
FT /note="LRR 2"
FT REPEAT 885..906
FT /note="LRR 3"
FT REPEAT 914..935
FT /note="LRR 4"
FT REPEAT 942..962
FT /note="LRR 5"
FT REPEAT 971..992
FT /note="LRR 6"
FT REPEAT 999..1020
FT /note="LRR 7"
FT REPEAT 1028..1049
FT /note="LRR 8"
FT BINDING 217..224
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT VAR_SEQ 1..717
FT /note="Missing (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:11167794"
FT /id="VSP_016908"
FT VAR_SEQ 691
FT /note="L -> LR (in isoform 7)"
FT /evidence="ECO:0000303|Ref.3"
FT /id="VSP_055193"
FT VAR_SEQ 718..748
FT /note="LSLYRNALGSRGVKLLCQGLRHPNCKLQNLR -> MSQAWWHTSVSPATQEA
FT KAGGLLQPRRQRLW (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:11167794"
FT /id="VSP_016909"
FT VAR_SEQ 862..1031
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|Ref.3"
FT /id="VSP_009879"
FT VAR_SEQ 862..973
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|Ref.3"
FT /id="VSP_005523"
FT VAR_SEQ 920..976
FT /note="Missing (in isoform 6)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_054622"
FT VAR_SEQ 921..977
FT /note="Missing (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:11167794"
FT /id="VSP_016910"
FT VAR_SEQ 976..1031
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|Ref.3"
FT /id="VSP_005524"
FT VARIANT 39
FT /note="G -> V (in dbSNP:rs34436714)"
FT /id="VAR_053620"
FT VARIANT 402
FT /note="F -> L (in dbSNP:rs34971363)"
FT /id="VAR_053621"
FT CONFLICT 648
FT /note="M -> T (in Ref. 5; BAG53059)"
FT /evidence="ECO:0000305"
FT HELIX 9..18
FT /evidence="ECO:0007829|PDB:5H7N"
FT HELIX 22..32
FT /evidence="ECO:0007829|PDB:5H7N"
FT TURN 37..40
FT /evidence="ECO:0007829|PDB:2L6A"
FT HELIX 45..49
FT /evidence="ECO:0007829|PDB:5H7N"
FT HELIX 53..64
FT /evidence="ECO:0007829|PDB:5H7N"
FT HELIX 66..79
FT /evidence="ECO:0007829|PDB:5H7N"
FT HELIX 83..92
FT /evidence="ECO:0007829|PDB:5H7N"
FT STRAND 95..98
FT /evidence="ECO:0007829|PDB:2L6A"
SQ SEQUENCE 1061 AA; 120173 MW; 8C10AFE4907C131B CRC64;
MLRTAGRDGL CRLSTYLEEL EAVELKKFKL YLGTATELGE GKIPWGSMEK AGPLEMAQLL
ITHFGPEEAW RLALSTFERI NRKDLWERGQ REDLVRDTPP GGPSSLGNQS TCLLEVSLVT
PRKDPQETYR DYVRRKFRLM EDRNARLGEC VNLSHRYTRL LLVKEHSNPM QVQQQLLDTG
RGHARTVGHQ ASPIKIETLF EPDEERPEPP RTVVMQGAAG IGKSMLAHKV MLDWADGKLF
QGRFDYLFYI NCREMNQSAT ECSMQDLIFS CWPEPSAPLQ ELIRVPERLL FIIDGFDELK
PSFHDPQGPW CLCWEEKRPT ELLLNSLIRK KLLPELSLLI TTRPTALEKL HRLLEHPRHV
EILGFSEAER KEYFYKYFHN AEQAGQVFNY VRDNEPLFTM CFVPLVCWVV CTCLQQQLEG
GGLLRQTSRT TTAVYMLYLL SLMQPKPGAP RLQPPPNQRG LCSLAADGLW NQKILFEEQD
LRKHGLDGED VSAFLNMNIF QKDINCERYY SFIHLSFQEF FAAMYYILDE GEGGAGPDQD
VTRLLTEYAF SERSFLALTS RFLFGLLNEE TRSHLEKSLC WKVSPHIKMD LLQWIQSKAQ
SDGSTLQQGS LEFFSCLYEI QEEEFIQQAL SHFQVIVVSN IASKMEHMVS SFCLKRCRSA
QVLHLYGATY SADGEDRARC SAGAHTLLVQ LPERTVLLDA YSEHLAAALC TNPNLIELSL
YRNALGSRGV KLLCQGLRHP NCKLQNLRLK RCRISSSACE DLSAALIANK NLTRMDLSGN
GVGFPGMMLL CEGLRHPQCR LQMIQLRKCQ LESGACQEMA SVLGTNPHLV ELDLTGNALE
DLGLRLLCQG LRHPVCRLRT LWLKICRLTA AACDELASTL SVNQSLRELD LSLNELGDLG
VLLLCEGLRH PTCKLQTLRL GICRLGSAAC EGLSVVLQAN HNLRELDLSF NDLGDWGLWL
LAEGLQHPAC RLQKLWLDSC GLTAKACENL YFTLGINQTL TDLYLTNNAL GDTGVRLLCK
RLSHPGCKLR VLWLFGMDLN KMTHSRLAAL RVTKPYLDIG C
