NAL12_MOUSE
ID NAL12_MOUSE Reviewed; 1054 AA.
AC E9Q5R7; Q3UEM3;
DT 31-OCT-2012, integrated into UniProtKB/Swiss-Prot.
DT 05-APR-2011, sequence version 1.
DT 03-AUG-2022, entry version 87.
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 Short=PYPAF7;
GN Name=Nlrp12; Synonyms=NALP12;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 921-1054.
RC STRAIN=C57BL/6J; TISSUE=Liver;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP FUNCTION, TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE.
RX PubMed=20861349; DOI=10.4049/jimmunol.1002227;
RA Arthur J.C., Lich J.D., Ye Z., Allen I.C., Gris D., Wilson J.E.,
RA Schneider M., Roney K.E., O'Connor B.P., Moore C.B., Morrison A.,
RA Sutterwala F.S., Bertin J., Koller B.H., Liu Z., Ting J.P.;
RT "NLRP12 controls dendritic and myeloid cell migration to affect contact
RT hypersensitivity.";
RL J. Immunol. 185:4515-4519(2010).
RN [4]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=26521018; DOI=10.1186/s12974-015-0414-5;
RA Gharagozloo M., Mahvelati T.M., Imbeault E., Gris P., Zerif E., Bobbala D.,
RA Ilangumaran S., Amrani A., Gris D.;
RT "The nod-like receptor, Nlrp12, plays an anti-inflammatory role in
RT experimental autoimmune encephalomyelitis.";
RL J. Neuroinflamm. 12:198-198(2015).
RN [5]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
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 [6]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=30212649; DOI=10.1016/j.chom.2018.08.009;
RA Truax A.D., Chen L., Tam J.W., Cheng N., Guo H., Koblansky A.A., Chou W.C.,
RA Wilson J.E., Brickey W.J., Petrucelli A., Liu R., Cooper D.E.,
RA Koenigsknecht M.J., Young V.B., Netea M.G., Stienstra R., Sartor R.B.,
RA Montgomery S.A., Coleman R.A., Ting J.P.;
RT "The Inhibitory Innate Immune Sensor NLRP12 Maintains a Threshold against
RT Obesity by Regulating Gut Microbiota Homeostasis.";
RL Cell Host Microbe 24:364-378(2018).
RN [7]
RP DISRUPTION PHENOTYPE.
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).
CC -!- FUNCTION: Plays an essential role as an potent mitigator of
CC inflammation (PubMed:26521018, PubMed:30559449). Primarily expressed in
CC dendritic cells and macrophages, inhibits both canonical and non-
CC canonical NF-kappa-B and ERK activation pathways (PubMed:30559449).
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 (By similarity). Acts also as a negative regulator of
CC inflammatory response to mitigate obesity and obesity-associated
CC diseases in adipose tissue (PubMed:30212649).
CC {ECO:0000250|UniProtKB:P59046, ECO:0000269|PubMed:26521018,
CC ECO:0000269|PubMed:30212649, ECO:0000269|PubMed:30559449}.
CC -!- SUBUNIT: Interacts (via pyrin domain) with ASC. Interacts (via pyrin
CC domain) with FAF1 (via UBA domain) (By similarity). Interacts with
CC MAP3K14; this interaction promotes proteasomal degradation of MAP3K14
CC (By similarity). Interacts with NOD2; this interaction promotes
CC degradation of NOD2 through the ubiquitin-proteasome pathway
CC (PubMed:30559449). Interacts with HSPA1A and HSPA8 (By similarity).
CC Interacts with HSP90AA1 (PubMed:30559449). Interacts with TRIM25; this
CC interaction inhibits DDX58-mediated signaling pathway (By similarity).
CC {ECO:0000250|UniProtKB:P59046, ECO:0000269|PubMed:30559449}.
CC -!- INTERACTION:
CC E9Q5R7; PRO_0000449623 [P0DTD1]: rep; Xeno; NbExp=2; IntAct=EBI-26583426, EBI-25475864;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:P59046}.
CC -!- TISSUE SPECIFICITY: Mainly expressed in dendritic cells (DCs) and
CC neutrophils. {ECO:0000269|PubMed:20861349}.
CC -!- DISRUPTION PHENOTYPE: NLRP12-deficient mice exhibit attenuated
CC inflammatory responses due to significantly reduced capacity of
CC dendritic cells to migrate to draining lymph nodes (PubMed:20861349).
CC They also gained significantly more weight and a greater percentage of
CC body fat than wild-type mice (PubMed:30212649). NLRP12-deficient mice
CC also exhibit enhanced disease in a mouse model of multiple sclerosis
CC (PubMed:26521018). During viral infection, augments host response with
CC greater type I interferon production and DDX58 protein
CC (PubMed:30902577). {ECO:0000269|PubMed:20861349,
CC ECO:0000269|PubMed:26521018, ECO:0000269|PubMed:30212649,
CC ECO:0000269|PubMed:30902577}.
CC -!- SIMILARITY: Belongs to the NLRP family. {ECO:0000305}.
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; CAAA01093162; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CAAA01093166; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CAAA01193276; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AK149454; BAE28888.1; -; mRNA.
DR CCDS; CCDS51963.1; -.
DR RefSeq; NP_001028603.1; NM_001033431.1.
DR AlphaFoldDB; E9Q5R7; -.
DR SMR; E9Q5R7; -.
DR BioGRID; 237541; 1.
DR IntAct; E9Q5R7; 1.
DR STRING; 10090.ENSMUSP00000104293; -.
DR PhosphoSitePlus; E9Q5R7; -.
DR MaxQB; E9Q5R7; -.
DR PaxDb; E9Q5R7; -.
DR PRIDE; E9Q5R7; -.
DR ProteomicsDB; 286146; -.
DR Antibodypedia; 32741; 325 antibodies from 35 providers.
DR DNASU; 378425; -.
DR Ensembl; ENSMUST00000108653; ENSMUSP00000104293; ENSMUSG00000078817.
DR GeneID; 378425; -.
DR KEGG; mmu:378425; -.
DR UCSC; uc009eul.2; mouse.
DR CTD; 91662; -.
DR MGI; MGI:2676630; Nlrp12.
DR VEuPathDB; HostDB:ENSMUSG00000078817; -.
DR eggNOG; ENOG502SBIG; Eukaryota.
DR GeneTree; ENSGT00940000160873; -.
DR HOGENOM; CLU_002274_2_0_1; -.
DR InParanoid; E9Q5R7; -.
DR OMA; TTAVYMF; -.
DR OrthoDB; 114368at2759; -.
DR PhylomeDB; E9Q5R7; -.
DR BioGRID-ORCS; 378425; 4 hits in 74 CRISPR screens.
DR ChiTaRS; Nlrp12; mouse.
DR PRO; PR:E9Q5R7; -.
DR Proteomes; UP000000589; Chromosome 7.
DR RNAct; E9Q5R7; protein.
DR Bgee; ENSMUSG00000078817; Expressed in granulocyte and 10 other tissues.
DR Genevisible; E9Q5R7; MM.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0071345; P:cellular response to cytokine stimulus; IMP:MGI.
DR GO; GO:0036336; P:dendritic cell migration; IMP:MGI.
DR GO; GO:0070371; P:ERK1 and ERK2 cascade; IMP:MGI.
DR GO; GO:0001818; P:negative regulation of cytokine production; ISO:MGI.
DR GO; GO:0070373; P:negative regulation of ERK1 and ERK2 cascade; IMP:MGI.
DR GO; GO:0043124; P:negative regulation of I-kappaB kinase/NF-kappaB signaling; ISO:MGI.
DR GO; GO:0050728; P:negative regulation of inflammatory response; IMP:UniProtKB.
DR GO; GO:0032692; P:negative regulation of interleukin-1 production; ISO:MGI.
DR GO; GO:0032715; P:negative regulation of interleukin-6 production; ISO:MGI.
DR GO; GO:0032088; P:negative regulation of NF-kappaB transcription factor activity; ISO:MGI.
DR GO; GO:1901223; P:negative regulation of NIK/NF-kappaB signaling; IMP:MGI.
DR GO; GO:0031953; P:negative regulation of protein autophosphorylation; ISO:MGI.
DR GO; GO:0009968; P:negative regulation of signal transduction; ISO:MGI.
DR GO; GO:0045751; P:negative regulation of Toll signaling pathway; ISO:MGI.
DR GO; GO:0038061; P:NIK/NF-kappaB signaling; IMP:MGI.
DR GO; GO:0045345; P:positive regulation of MHC class I biosynthetic process; ISO:MGI.
DR GO; GO:1901224; P:positive regulation of NIK/NF-kappaB signaling; ISO:MGI.
DR GO; GO:0043281; P:regulation of cysteine-type endopeptidase activity involved in apoptotic process; ISO:MGI.
DR GO; GO:0043122; P:regulation of I-kappaB kinase/NF-kappaB signaling; ISO:MGI.
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 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; 6.
DR PROSITE; PS50837; NACHT; 1.
PE 1: Evidence at protein level;
KW ATP-binding; Cytoplasm; Leucine-rich repeat; Nucleotide-binding;
KW Reference proteome; Repeat.
FT CHAIN 1..1054
FT /note="NACHT, LRR and PYD domains-containing protein 12"
FT /id="PRO_0000419758"
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 821..841
FT /note="LRR 1"
FT REPEAT 850..871
FT /note="LRR 2"
FT REPEAT 878..899
FT /note="LRR 3"
FT REPEAT 907..928
FT /note="LRR 4"
FT REPEAT 935..955
FT /note="LRR 5"
FT REPEAT 964..985
FT /note="LRR 6"
FT REPEAT 992..1013
FT /note="LRR 7"
FT REPEAT 1021..1042
FT /note="LRR 8"
FT BINDING 217..224
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00136"
SQ SEQUENCE 1054 AA; 119319 MW; 3F17BEA78BA38621 CRC64;
MLPSTARDGL YRLSTYLEEL EAGELKKFKL FLGIAEDLSQ DKIPWGRMEK AGPLEMAQLM
VAHMGTREAW LLALSTFQRI HRKDLWERGQ GEDLVRVTPN NGLCLFESQS ACPLDVSPNA
PRKDLQTTYK DYVRRKFQLM EDRNARLGEC VNLSNRYTRL LLVKEHSNPI WTQQKFVDVE
WERSRTRRHQ TSPIQMETLF EPDEERPEPP HTVVLQGAAG MGKSMLAHKV MLDWADGRLF
QGRFDYVFYI SCRELNRSHT QCSVQDLISS CWPERGISLE DLMQAPDRLL FIIDGFDKLH
PSFHDAQGPW CLCWEEKQPT EVLLGSLIRR LLLPQVSLLI TTRPCALEKL HGLLEHPRHV
EILGFSEEAR KEYFYRYFHN TGQASRVLSF LMDYEPLFTM CFVPMVSWVV CTCLKQQLES
GELLRQTPRT TTAVYMFYLL SLMQPKPGTP TFKVPANQRG LVSLAAEGLW NQKILFDEQD
LGKHGLDGAD VSTFLNVNIF QKGIKCEKFY SFIHLSFQEF FAAMYCALNG REAVRRALAE
YGFSERNFLA LTVHFLFGLL NEEMRCYLER NLGWSISPQV KEEVLAWIQN KAGSEGSTLQ
HGSLELLSCL YEVQEEDFIQ QALSHFQVVV VRSISTKMEH MVCSFCARYC RSTEVLHLHG
SAYSTGMEDD PPEPSGVQTQ STYLQERNML PDVYSAYLSA AVCTNSNLIE LALYRNALGS
QGVRLLCQGL RHASCKLQNL RLKRCQISGS ACQDLAAAVI ANRNLIRLDL SDNSIGVPGL
ELLCEGLQHP RCRLQMIQLR KCLLEAAAGR SLASVLSNNS YLVELDLTGN PLEDSGLKLL
CQGLRHPVCR LRTLWLKICH LGQASCEDLA STLKMNQSLL ELDLGLNDLG DSGVLLLCEG
LSHPDCKLQT LRLGICRLGS VACVGIASVL QVNTCLQELD LSFNDLGDRG LQLLGEGLRH
QTCRLQKLWL DNCGLTSKAC EDLSSILGIS QTLHELYLTN NALGDTGVCL LCKRLRHPGC
KLRVLWLFGM DLNKKTHRRM AALRVTKPYL DIGC
