NLRC4_MOUSE
ID NLRC4_MOUSE Reviewed; 1024 AA.
AC Q3UP24; Q3TAU8;
DT 31-OCT-2012, integrated into UniProtKB/Swiss-Prot.
DT 11-OCT-2005, sequence version 1.
DT 03-AUG-2022, entry version 131.
DE RecName: Full=NLR family CARD domain-containing protein 4;
DE AltName: Full=Caspase recruitment domain-containing protein 12;
DE AltName: Full=Ice protease-activating factor;
DE Short=Ipaf;
GN Name=Nlrc4; Synonyms=Card12, Ipaf;
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 MRNA].
RC STRAIN=C57BL/6J, and NOD; TISSUE=Spleen;
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 [2]
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 [3]
RP DISRUPTION PHENOTYPE.
RX PubMed=16717117; DOI=10.1084/jem.20060206;
RA Lara-Tejero M., Sutterwala F.S., Ogura Y., Grant E.P., Bertin J.,
RA Coyle A.J., Flavell R.A., Galan J.E.;
RT "Role of the caspase-1 inflammasome in Salmonella typhimurium
RT pathogenesis.";
RL J. Exp. Med. 203:1407-1412(2006).
RN [4]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=15190255; DOI=10.1038/nature02664;
RA Mariathasan S., Newton K., Monack D.M., Vucic D., French D.M., Lee W.P.,
RA Roose-Girma M., Erickson S., Dixit V.M.;
RT "Differential activation of the inflammasome by caspase-1 adaptors ASC and
RT Ipaf.";
RL Nature 430:213-218(2004).
RN [5]
RP FUNCTION.
RX PubMed=16648853; DOI=10.1038/ni1344;
RA Miao E.A., Alpuche-Aranda C.M., Dors M., Clark A.E., Bader M.W.,
RA Miller S.I., Aderem A.;
RT "Cytoplasmic flagellin activates caspase-1 and secretion of interleukin
RT 1beta via Ipaf.";
RL Nat. Immunol. 7:569-575(2006).
RN [6]
RP FUNCTION.
RX PubMed=16648852; DOI=10.1038/ni1346;
RA Franchi L., Amer A., Body-Malapel M., Kanneganti T.D., Ozoren N.,
RA Jagirdar R., Inohara N., Vandenabeele P., Bertin J., Coyle A., Grant E.P.,
RA Nunez G.;
RT "Cytosolic flagellin requires Ipaf for activation of caspase-1 and
RT interleukin 1beta in salmonella-infected macrophages.";
RL Nat. Immunol. 7:576-582(2006).
RN [7]
RP FUNCTION.
RX PubMed=18070936; DOI=10.1084/jem.20071239;
RA Sutterwala F.S., Mijares L.A., Li L., Ogura Y., Kazmierczak B.I.,
RA Flavell R.A.;
RT "Immune recognition of Pseudomonas aeruginosa mediated by the IPAF/NLRC4
RT inflammasome.";
RL J. Exp. Med. 204:3235-3245(2007).
RN [8]
RP FUNCTION.
RX PubMed=19343209; DOI=10.1371/journal.ppat.1000361;
RA Akhter A., Gavrilin M.A., Frantz L., Washington S., Ditty C., Limoli D.,
RA Day C., Sarkar A., Newland C., Butchar J., Marsh C.B., Wewers M.D.,
RA Tridandapani S., Kanneganti T.D., Amer A.O.;
RT "Caspase-7 activation by the Nlrc4/Ipaf inflammasome restricts Legionella
RT infection.";
RL PLoS Pathog. 5:E1000361-E1000361(2009).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Spleen;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [10]
RP SUBUNIT.
RX PubMed=21147462; DOI=10.1016/j.chom.2010.11.007;
RA Broz P., von Moltke J., Jones J.W., Vance R.E., Monack D.M.;
RT "Differential requirement for Caspase-1 autoproteolysis in pathogen-induced
RT cell death and cytokine processing.";
RL Cell Host Microbe 8:471-483(2010).
RN [11]
RP FUNCTION.
RX PubMed=20603313; DOI=10.1084/jem.20100257;
RA Broz P., Newton K., Lamkanfi M., Mariathasan S., Dixit V.M., Monack D.M.;
RT "Redundant roles for inflammasome receptors NLRP3 and NLRC4 in host defense
RT against Salmonella.";
RL J. Exp. Med. 207:1745-1755(2010).
RN [12]
RP FUNCTION.
RX PubMed=20133635; DOI=10.1073/pnas.0913087107;
RA Miao E.A., Mao D.P., Yudkovsky N., Bonneau R., Lorang C.G., Warren S.E.,
RA Leaf I.A., Aderem A.;
RT "Innate immune detection of the type III secretion apparatus through the
RT NLRC4 inflammasome.";
RL Proc. Natl. Acad. Sci. U.S.A. 107:3076-3080(2010).
RN [13]
RP FUNCTION, SUBUNIT, SUBCELLULAR LOCATION, AND INTERACTION WITH NAIP2; NAIP5
RP AND NAIP6.
RX PubMed=21874021; DOI=10.1038/nature10394;
RA Kofoed E.M., Vance R.E.;
RT "Innate immune recognition of bacterial ligands by NAIPs determines
RT inflammasome specificity.";
RL Nature 477:592-595(2011).
RN [14]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH NAIP2 AND NAIP5.
RX PubMed=21918512; DOI=10.1038/nature10510;
RA Zhao Y., Yang J., Shi J., Gong Y.N., Lu Q., Xu H., Liu L., Shao F.;
RT "The NLRC4 inflammasome receptors for bacterial flagellin and type III
RT secretion apparatus.";
RL Nature 477:596-600(2011).
RN [15]
RP FUNCTION.
RX PubMed=22174673; DOI=10.1371/journal.ppat.1002379;
RA Tomalka J., Ganesan S., Azodi E., Patel K., Majmudar P., Hall B.A.,
RA Fitzgerald K.A., Hise A.G.;
RT "A novel role for the NLRC4 inflammasome in mucosal defenses against the
RT fungal pathogen Candida albicans.";
RL PLoS Pathog. 7:E1002379-E1002379(2011).
RN [16]
RP FUNCTION.
RX PubMed=22547706; DOI=10.4049/jimmunol.1200195;
RA Cai S., Batra S., Wakamatsu N., Pacher P., Jeyaseelan S.;
RT "NLRC4 inflammasome-mediated production of IL-1beta modulates mucosal
RT immunity in the lung against gram-negative bacterial infection.";
RL J. Immunol. 188:5623-5635(2012).
RN [17]
RP FUNCTION.
RX PubMed=22231517; DOI=10.1038/ni.2195;
RA Kupz A., Guarda G., Gebhardt T., Sander L.E., Short K.R.,
RA Diavatopoulos D.A., Wijburg O.L., Cao H., Waithman J.C., Chen W.,
RA Fernandez-Ruiz D., Whitney P.G., Heath W.R., Curtiss R. III, Tschopp J.,
RA Strugnell R.A., Bedoui S.;
RT "NLRC4 inflammasomes in dendritic cells regulate noncognate effector
RT function by memory CD8(+) T cells.";
RL Nat. Immunol. 13:162-169(2012).
RN [18]
RP FUNCTION, DISRUPTION PHENOTYPE, AND TISSUE SPECIFICITY.
RX PubMed=22484733; DOI=10.1038/ni.2263;
RA Franchi L., Kamada N., Nakamura Y., Burberry A., Kuffa P., Suzuki S.,
RA Shaw M.H., Kim Y.G., Nunez G.;
RT "NLRC4-driven production of IL-1beta discriminates between pathogenic and
RT commensal bacteria and promotes host intestinal defense.";
RL Nat. Immunol. 13:449-456(2012).
RN [19]
RP FUNCTION, SUBCELLULAR LOCATION, PHOSPHORYLATION AT SER-533, AND MUTAGENESIS
RP OF SER-533.
RX PubMed=22885697; DOI=10.1038/nature11429;
RA Qu Y., Misaghi S., Izrael-Tomasevic A., Newton K., Gilmour L.L.,
RA Lamkanfi M., Louie S., Kayagaki N., Liu J., Komuves L., Cupp J.E.,
RA Arnott D., Monack D., Dixit V.M.;
RT "Phosphorylation of NLRC4 is critical for inflammasome activation.";
RL Nature 490:539-542(2012).
RN [20]
RP FUNCTION, AND SUBUNIT.
RX PubMed=29182158; DOI=10.1038/cr.2017.148;
RA Yang X., Yang F., Wang W., Lin G., Hu Z., Han Z., Qi Y., Zhang L., Wang J.,
RA Sui S.F., Chai J.;
RT "Structural basis for specific flagellin recognition by the NLR protein
RT NAIP5.";
RL Cell Res. 28:35-47(2018).
RN [21]
RP X-RAY CRYSTALLOGRAPHY (3.2 ANGSTROMS) OF 93-1024 IN COMPLEX WITH ADP, NBD
RP DOMAIN, WHD DOMAIN, LRR REPEATS, PHOSPHORYLATION AT SER-533, AND
RP MUTAGENESIS OF HIS-443.
RX PubMed=23765277; DOI=10.1126/science.1236381;
RA Hu Z., Yan C., Liu P., Huang Z., Ma R., Zhang C., Wang R., Zhang Y.,
RA Martinon F., Miao D., Deng H., Wang J., Chang J., Chai J.;
RT "Crystal structure of NLRC4 reveals its autoinhibition mechanism.";
RL Science 341:172-175(2013).
RN [22] {ECO:0007744|PDB:3JBL}
RP STRUCTURE BY ELECTRON MICROSCOPY (4.50 ANGSTROMS) OF 93-1024, AND SUBUNIT.
RX PubMed=26449474; DOI=10.1126/science.aac5789;
RA Zhang L., Chen S., Ruan J., Wu J., Tong A.B., Yin Q., Li Y., David L.,
RA Lu A., Wang W.L., Marks C., Ouyang Q., Zhang X., Mao Y., Wu H.;
RT "Cryo-EM structure of the activated NAIP2-NLRC4 inflammasome reveals
RT nucleated polymerization.";
RL Science 350:404-409(2015).
RN [23] {ECO:0007744|PDB:5AJ2}
RP STRUCTURE BY ELECTRON MICROSCOPY (40.00 ANGSTROMS), SUBUNIT, AND
RP SUBCELLULAR LOCATION.
RX PubMed=26585513; DOI=10.1016/j.str.2015.10.001;
RA Diebolder C.A., Halff E.F., Koster A.J., Huizinga E.G., Koning R.I.;
RT "Cryoelectron Tomography of the NAIP5/NLRC4 Inflammasome: Implications for
RT NLR Activation.";
RL Structure 23:2349-2357(2015).
RN [24] {ECO:0007744|PDB:6B5B}
RP STRUCTURE BY ELECTRON MICROSCOPY (5.20 ANGSTROMS), FUNCTION, AND SUBUNIT.
RX PubMed=29146805; DOI=10.1126/science.aao1140;
RA Tenthorey J.L., Haloupek N., Lopez-Blanco J.R., Grob P., Adamson E.,
RA Hartenian E., Lind N.A., Bourgeois N.M., Chacon P., Nogales E., Vance R.E.;
RT "The structural basis of flagellin detection by NAIP5: A strategy to limit
RT pathogen immune evasion.";
RL Science 358:888-893(2017).
CC -!- FUNCTION: Key component of inflammasomes that indirectly senses
CC specific proteins from pathogenic bacteria and fungi and responds by
CC assembling an inflammasome complex that promotes caspase-1 activation,
CC cytokine production and macrophage pyroptosis. The NLRC4 inflammasome
CC is activated as part of the innate immune response to a range of
CC intracellular bacteria. It senses pathogenic proteins of the type III
CC secretion system (T3SS) and type IV secretion system (T4SS) such as
CC flagellin and PrgJ-like rod proteins via the Naip proteins (Naip1,
CC Naip2 or Naip5): specific Naip proteins recognize and bind pathogenic
CC proteins, driving assembly and activation of the NLRC4 inflammasome.
CC The NLRC4 inflammasome senses Gram-negative bacteria such as
CC L.pneumophila and P.aeruginosa, enteric pathogens S.typhimurium
CC (Salmonella) and S.flexneri and fungal pathogen C.albicans. In
CC intestine, the NLRC4 inflammasome is able to discriminate between
CC commensal and pathogenic bacteria and specifically drives production of
CC interleukin-1 beta (IL1B) in response to infection by Salmonella or
CC P.aeruginosa. In case of L.pneumophila infection the inflammasome acts
CC by activating caspase-7. {ECO:0000269|PubMed:15190255,
CC ECO:0000269|PubMed:16648852, ECO:0000269|PubMed:16648853,
CC ECO:0000269|PubMed:18070936, ECO:0000269|PubMed:19343209,
CC ECO:0000269|PubMed:20133635, ECO:0000269|PubMed:20603313,
CC ECO:0000269|PubMed:21874021, ECO:0000269|PubMed:21918512,
CC ECO:0000269|PubMed:22174673, ECO:0000269|PubMed:22231517,
CC ECO:0000269|PubMed:22484733, ECO:0000269|PubMed:22547706,
CC ECO:0000269|PubMed:22885697, ECO:0000269|PubMed:29146805,
CC ECO:0000269|PubMed:29182158}.
CC -!- SUBUNIT: Homooligomer; homooligomerizes following activation of Naip
CC proteins by pathogenic proteins such as S.typhimurium (Salmonella)
CC flagellin or PrgJ (PubMed:23765277, PubMed:26449474, PubMed:26585513,
CC PubMed:29146805). Component of the NLRC4 inflammasome, at least
CC composed of NLRC4, caspase-1 (CASP1) and some NAIP protein (Naip, Naip2
CC or Naip5) (PubMed:21874021, PubMed:21918512, PubMed:26585513).
CC Interacts with Naip5 and Naip6; following Naip5 and Naip6 engagement by
CC Salmonella flagellin (PubMed:21874021, PubMed:21918512,
CC PubMed:29182158, PubMed:29146805). Interacts with Naip2; following
CC Naip2 engagement by Salmonella PrgJ (PubMed:21874021, PubMed:21918512,
CC PubMed:26449474). The inflammasome is a huge complex that contains
CC multiple copies of NLRC4 and a single Naip protein chain
CC (PubMed:26449474, PubMed:29146805). Some NLRC4 inflammasomes contain
CC PYCARD/ASC, while some others directly contact and activate CASP1
CC (PubMed:21147462). Interacts with EIF2AK2/PKR (By similarity).
CC {ECO:0000250|UniProtKB:Q9NPP4, ECO:0000269|PubMed:21147462,
CC ECO:0000269|PubMed:21874021, ECO:0000269|PubMed:21918512,
CC ECO:0000269|PubMed:23765277, ECO:0000269|PubMed:26449474,
CC ECO:0000269|PubMed:26585513, ECO:0000269|PubMed:29146805}.
CC -!- INTERACTION:
CC Q3UP24; P29452: Casp1; NbExp=2; IntAct=EBI-16006652, EBI-489700;
CC Q3UP24; Q9R016: Naip5; NbExp=18; IntAct=EBI-16006652, EBI-15944130;
CC Q3UP24; Q3UP24: Nlrc4; NbExp=4; IntAct=EBI-16006652, EBI-16006652;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:22885697}.
CC Inflammasome {ECO:0000269|PubMed:21874021, ECO:0000269|PubMed:21918512,
CC ECO:0000269|PubMed:26585513}.
CC -!- TISSUE SPECIFICITY: Expressed by intestinal mononuclear phagocytes.
CC {ECO:0000269|PubMed:22484733}.
CC -!- DOMAIN: In an autoinhibited form the C-terminal leucine-rich repeat
CC (LRR) domain is positioned to sterically occlude one side of the NBD
CC domain and consequently sequester NLRC4 in a monomeric state. An ADP-
CC mediated interaction between the NBD and the WHD also contributes to
CC the autoinhibition (PubMed:23765277). {ECO:0000269|PubMed:23765277}.
CC -!- PTM: Phosphorylated at Ser-533 following infection of macrophages with
CC S.typhimurium (Salmonella). Phosphorylation is essential for NLRC4
CC inflammasome function to promote caspase-1 activation and pyroptosis.
CC PRKCD phosphorylates Ser-533 in vitro. {ECO:0000269|PubMed:22885697,
CC ECO:0000269|PubMed:23765277}.
CC -!- DISRUPTION PHENOTYPE: Mice show defects in inflammasome function in
CC response to S.typhimurium (Salmonella) infection. Differences are
CC however observed depending on the strain background: in a C57BL/6J
CC strain background, no striking differences are observed compared to
CC wild-type mice following Salmonella infection. While in a BALB/c strain
CC background, mice are highly susceptible to orogastric but not
CC intraperitoneal infection with Salmonella: enhanced lethality is
CC preceded by impaired expression of endothelial adhesion molecules,
CC lower neutrophil recruitment and poor intestinal pathogen clearance.
CC {ECO:0000269|PubMed:15190255, ECO:0000269|PubMed:16717117,
CC ECO:0000269|PubMed:22484733}.
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DR EMBL; AK143864; BAE25573.1; -; mRNA.
DR EMBL; AK171624; BAE42570.1; -; mRNA.
DR EMBL; CT033749; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS37692.1; -.
DR RefSeq; NP_001028539.1; NM_001033367.3.
DR RefSeq; XP_006524409.1; XM_006524346.3.
DR RefSeq; XP_017172979.1; XM_017317490.1.
DR RefSeq; XP_017172980.1; XM_017317491.1.
DR PDB; 3JBL; EM; 4.50 A; A/B/C/D/E/F/G/H/I/J/K=93-1024.
DR PDB; 4KXF; X-ray; 3.20 A; B/D/F/H/K/L/N/P=1-1024.
DR PDB; 5AJ2; EM; 40.00 A; A=1-355, B=356-580, C=580-1024.
DR PDB; 6B5B; EM; 5.20 A; B/C=1-1024.
DR PDBsum; 3JBL; -.
DR PDBsum; 4KXF; -.
DR PDBsum; 5AJ2; -.
DR PDBsum; 6B5B; -.
DR AlphaFoldDB; Q3UP24; -.
DR SMR; Q3UP24; -.
DR IntAct; Q3UP24; 9.
DR STRING; 10090.ENSMUSP00000059637; -.
DR ChEMBL; CHEMBL4295841; -.
DR iPTMnet; Q3UP24; -.
DR PhosphoSitePlus; Q3UP24; -.
DR MaxQB; Q3UP24; -.
DR PaxDb; Q3UP24; -.
DR PeptideAtlas; Q3UP24; -.
DR PRIDE; Q3UP24; -.
DR ProteomicsDB; 293579; -.
DR Antibodypedia; 14265; 344 antibodies from 36 providers.
DR DNASU; 268973; -.
DR Ensembl; ENSMUST00000052124; ENSMUSP00000059637; ENSMUSG00000039193.
DR GeneID; 268973; -.
DR KEGG; mmu:268973; -.
DR UCSC; uc008doc.1; mouse.
DR CTD; 58484; -.
DR MGI; MGI:3036243; Nlrc4.
DR VEuPathDB; HostDB:ENSMUSG00000039193; -.
DR eggNOG; ENOG502QWRJ; Eukaryota.
DR GeneTree; ENSGT00940000161744; -.
DR HOGENOM; CLU_011683_0_0_1; -.
DR InParanoid; Q3UP24; -.
DR OMA; VETHYHQ; -.
DR OrthoDB; 137566at2759; -.
DR PhylomeDB; Q3UP24; -.
DR TreeFam; TF336864; -.
DR BioGRID-ORCS; 268973; 2 hits in 72 CRISPR screens.
DR ChiTaRS; Nlrc4; mouse.
DR PRO; PR:Q3UP24; -.
DR Proteomes; UP000000589; Chromosome 17.
DR RNAct; Q3UP24; protein.
DR Bgee; ENSMUSG00000039193; Expressed in jejunum and 34 other tissues.
DR ExpressionAtlas; Q3UP24; baseline and differential.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; ISO:MGI.
DR GO; GO:0072557; C:IPAF inflammasome complex; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; ISS:HGNC-UCL.
DR GO; GO:0089720; F:caspase binding; ISO:MGI.
DR GO; GO:0061133; F:endopeptidase activator activity; ISO:MGI.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0042803; F:protein homodimerization activity; ISS:HGNC-UCL.
DR GO; GO:0097202; P:activation of cysteine-type endopeptidase activity; ISO:MGI.
DR GO; GO:0006919; P:activation of cysteine-type endopeptidase activity involved in apoptotic process; ISS:HGNC-UCL.
DR GO; GO:0002218; P:activation of innate immune response; IMP:UniProtKB.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0042742; P:defense response to bacterium; IMP:UniProtKB.
DR GO; GO:0016045; P:detection of bacterium; IMP:UniProtKB.
DR GO; GO:0006954; P:inflammatory response; IMP:UniProtKB.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:0043065; P:positive regulation of apoptotic process; ISO:MGI.
DR GO; GO:0032731; P:positive regulation of interleukin-1 beta production; IMP:UniProtKB.
DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; ISO:MGI.
DR GO; GO:0010954; P:positive regulation of protein processing; ISO:MGI.
DR GO; GO:0051260; P:protein homooligomerization; IDA:UniProtKB.
DR GO; GO:0070269; P:pyroptosis; IMP:UniProtKB.
DR GO; GO:0042981; P:regulation of apoptotic process; IMP:MGI.
DR GO; GO:0043281; P:regulation of cysteine-type endopeptidase activity involved in apoptotic process; IMP:MGI.
DR Gene3D; 1.10.533.10; -; 1.
DR Gene3D; 3.40.50.300; -; 1.
DR Gene3D; 3.80.10.10; -; 2.
DR InterPro; IPR001315; CARD.
DR InterPro; IPR011029; DEATH-like_dom_sf.
DR InterPro; IPR032675; LRR_dom_sf.
DR InterPro; IPR007111; NACHT_NTPase.
DR InterPro; IPR042220; NLRC4.
DR InterPro; IPR040535; NLRC4_HD.
DR InterPro; IPR027417; P-loop_NTPase.
DR PANTHER; PTHR47688; PTHR47688; 1.
DR Pfam; PF00619; CARD; 1.
DR Pfam; PF05729; NACHT; 1.
DR Pfam; PF17889; NLRC4_HD; 1.
DR SUPFAM; SSF47986; SSF47986; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR PROSITE; PS50209; CARD; 1.
DR PROSITE; PS50837; NACHT; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Apoptosis; ATP-binding; Cytoplasm; Immunity; Inflammasome;
KW Inflammatory response; Innate immunity; Leucine-rich repeat;
KW Nucleotide-binding; Phosphoprotein; Reference proteome; Repeat.
FT CHAIN 1..1024
FT /note="NLR family CARD domain-containing protein 4"
FT /id="PRO_0000419975"
FT DOMAIN 1..88
FT /note="CARD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00046"
FT DOMAIN 163..476
FT /note="NACHT"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00136"
FT REPEAT 578..598
FT /note="LRR 1"
FT /evidence="ECO:0000269|PubMed:23765277"
FT REPEAT 656..679
FT /note="LRR 2"
FT /evidence="ECO:0000269|PubMed:23765277"
FT REPEAT 735..758
FT /note="LRR 3"
FT /evidence="ECO:0000269|PubMed:23765277"
FT REPEAT 762..785
FT /note="LRR 4"
FT /evidence="ECO:0000269|PubMed:23765277"
FT REPEAT 787..812
FT /note="LRR 5"
FT /evidence="ECO:0000269|PubMed:23765277"
FT REPEAT 824..847
FT /note="LRR 6"
FT /evidence="ECO:0000269|PubMed:23765277"
FT REPEAT 848..870
FT /note="LRR 7"
FT /evidence="ECO:0000269|PubMed:23765277"
FT REPEAT 878..902
FT /note="LRR 8"
FT /evidence="ECO:0000269|PubMed:23765277"
FT REPEAT 911..933
FT /note="LRR 9"
FT /evidence="ECO:0000269|PubMed:23765277"
FT REPEAT 936..963
FT /note="LRR 10"
FT /evidence="ECO:0000269|PubMed:23765277"
FT REPEAT 965..985
FT /note="LRR 11"
FT /evidence="ECO:0000269|PubMed:23765277"
FT REPEAT 999..1021
FT /note="LRR 12"
FT /evidence="ECO:0000269|PubMed:23765277"
FT REGION 95..298
FT /note="Nucleotide-binding domain (NBD)"
FT REGION 356..463
FT /note="Winged-helix domain (WHD)"
FT BINDING 135
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:23765277,
FT ECO:0007744|PDB:4KXF"
FT BINDING 172..177
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:23765277,
FT ECO:0007744|PDB:4KXF"
FT BINDING 443
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:23765277,
FT ECO:0007744|PDB:4KXF"
FT MOD_RES 533
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:22885697,
FT ECO:0000269|PubMed:23765277"
FT MUTAGEN 443
FT /note="H->L: Constitutively active."
FT /evidence="ECO:0000269|PubMed:23765277"
FT MUTAGEN 533
FT /note="S->A: Abolishes phosphorylation and prevents
FT activation of caspase-1 and pyroptosis in response to
FT S.typhimurium."
FT /evidence="ECO:0000269|PubMed:22885697"
FT MUTAGEN 533
FT /note="S->D: Mimics phosphorylation; causes rapid
FT macrophage pyroptosis without infection."
FT /evidence="ECO:0000269|PubMed:22885697"
FT CONFLICT 99
FT /note="N -> S (in Ref. 1; BAE42570)"
FT /evidence="ECO:0000305"
FT CONFLICT 385
FT /note="D -> N (in Ref. 1; BAE42570)"
FT /evidence="ECO:0000305"
FT CONFLICT 515
FT /note="H -> Y (in Ref. 1; BAE42570)"
FT /evidence="ECO:0000305"
FT CONFLICT 670
FT /note="N -> S (in Ref. 1; BAE42570)"
FT /evidence="ECO:0000305"
FT CONFLICT 756
FT /note="I -> V (in Ref. 1; BAE42570)"
FT /evidence="ECO:0000305"
FT CONFLICT 782
FT /note="N -> S (in Ref. 1; BAE42570)"
FT /evidence="ECO:0000305"
FT CONFLICT 799
FT /note="T -> I (in Ref. 1; BAE42570)"
FT /evidence="ECO:0000305"
FT CONFLICT 948
FT /note="C -> R (in Ref. 1; BAE42570)"
FT /evidence="ECO:0000305"
FT HELIX 95..109
FT /evidence="ECO:0007829|PDB:4KXF"
FT HELIX 112..115
FT /evidence="ECO:0007829|PDB:4KXF"
FT TURN 130..133
FT /evidence="ECO:0007829|PDB:4KXF"
FT STRAND 139..142
FT /evidence="ECO:0007829|PDB:4KXF"
FT STRAND 148..152
FT /evidence="ECO:0007829|PDB:4KXF"
FT HELIX 154..159
FT /evidence="ECO:0007829|PDB:4KXF"
FT STRAND 163..168
FT /evidence="ECO:0007829|PDB:4KXF"
FT HELIX 175..188
FT /evidence="ECO:0007829|PDB:4KXF"
FT HELIX 193..196
FT /evidence="ECO:0007829|PDB:4KXF"
FT STRAND 198..204
FT /evidence="ECO:0007829|PDB:4KXF"
FT HELIX 205..207
FT /evidence="ECO:0007829|PDB:4KXF"
FT HELIX 212..220
FT /evidence="ECO:0007829|PDB:4KXF"
FT HELIX 229..239
FT /evidence="ECO:0007829|PDB:4KXF"
FT HELIX 240..242
FT /evidence="ECO:0007829|PDB:4KXF"
FT STRAND 243..248
FT /evidence="ECO:0007829|PDB:4KXF"
FT HELIX 250..252
FT /evidence="ECO:0007829|PDB:4KXF"
FT TURN 255..257
FT /evidence="ECO:0007829|PDB:4KXF"
FT HELIX 259..266
FT /evidence="ECO:0007829|PDB:4KXF"
FT TURN 269..271
FT /evidence="ECO:0007829|PDB:4KXF"
FT STRAND 274..278
FT /evidence="ECO:0007829|PDB:4KXF"
FT HELIX 284..287
FT /evidence="ECO:0007829|PDB:4KXF"
FT TURN 288..290
FT /evidence="ECO:0007829|PDB:4KXF"
FT STRAND 292..297
FT /evidence="ECO:0007829|PDB:4KXF"
FT HELIX 302..312
FT /evidence="ECO:0007829|PDB:4KXF"
FT HELIX 315..327
FT /evidence="ECO:0007829|PDB:4KXF"
FT HELIX 329..334
FT /evidence="ECO:0007829|PDB:4KXF"
FT HELIX 338..350
FT /evidence="ECO:0007829|PDB:4KXF"
FT HELIX 359..374
FT /evidence="ECO:0007829|PDB:4KXF"
FT HELIX 375..377
FT /evidence="ECO:0007829|PDB:4KXF"
FT HELIX 386..403
FT /evidence="ECO:0007829|PDB:4KXF"
FT HELIX 416..424
FT /evidence="ECO:0007829|PDB:4KXF"
FT STRAND 426..429
FT /evidence="ECO:0007829|PDB:4KXF"
FT HELIX 444..459
FT /evidence="ECO:0007829|PDB:4KXF"
FT HELIX 464..475
FT /evidence="ECO:0007829|PDB:4KXF"
FT HELIX 480..485
FT /evidence="ECO:0007829|PDB:4KXF"
FT HELIX 488..497
FT /evidence="ECO:0007829|PDB:4KXF"
FT HELIX 499..509
FT /evidence="ECO:0007829|PDB:4KXF"
FT HELIX 519..521
FT /evidence="ECO:0007829|PDB:4KXF"
FT HELIX 534..538
FT /evidence="ECO:0007829|PDB:4KXF"
FT HELIX 542..565
FT /evidence="ECO:0007829|PDB:4KXF"
FT HELIX 572..579
FT /evidence="ECO:0007829|PDB:4KXF"
FT STRAND 583..589
FT /evidence="ECO:0007829|PDB:4KXF"
FT HELIX 593..601
FT /evidence="ECO:0007829|PDB:4KXF"
FT HELIX 603..608
FT /evidence="ECO:0007829|PDB:4KXF"
FT STRAND 609..618
FT /evidence="ECO:0007829|PDB:4KXF"
FT HELIX 646..654
FT /evidence="ECO:0007829|PDB:4KXF"
FT STRAND 659..668
FT /evidence="ECO:0007829|PDB:4KXF"
FT HELIX 674..684
FT /evidence="ECO:0007829|PDB:4KXF"
FT STRAND 687..696
FT /evidence="ECO:0007829|PDB:4KXF"
FT HELIX 703..707
FT /evidence="ECO:0007829|PDB:4KXF"
FT STRAND 712..721
FT /evidence="ECO:0007829|PDB:4KXF"
FT HELIX 726..734
FT /evidence="ECO:0007829|PDB:4KXF"
FT STRAND 740..746
FT /evidence="ECO:0007829|PDB:4KXF"
FT TURN 755..758
FT /evidence="ECO:0007829|PDB:4KXF"
FT STRAND 767..773
FT /evidence="ECO:0007829|PDB:4KXF"
FT HELIX 777..787
FT /evidence="ECO:0007829|PDB:4KXF"
FT STRAND 794..800
FT /evidence="ECO:0007829|PDB:4KXF"
FT HELIX 807..816
FT /evidence="ECO:0007829|PDB:4KXF"
FT STRAND 824..830
FT /evidence="ECO:0007829|PDB:4KXF"
FT HELIX 834..843
FT /evidence="ECO:0007829|PDB:4KXF"
FT HELIX 844..846
FT /evidence="ECO:0007829|PDB:4KXF"
FT STRAND 852..854
FT /evidence="ECO:0007829|PDB:4KXF"
FT HELIX 864..873
FT /evidence="ECO:0007829|PDB:4KXF"
FT HELIX 874..877
FT /evidence="ECO:0007829|PDB:4KXF"
FT STRAND 883..886
FT /evidence="ECO:0007829|PDB:4KXF"
FT HELIX 892..895
FT /evidence="ECO:0007829|PDB:4KXF"
FT HELIX 896..902
FT /evidence="ECO:0007829|PDB:4KXF"
FT HELIX 903..905
FT /evidence="ECO:0007829|PDB:4KXF"
FT STRAND 911..916
FT /evidence="ECO:0007829|PDB:4KXF"
FT HELIX 921..933
FT /evidence="ECO:0007829|PDB:4KXF"
FT STRAND 941..946
FT /evidence="ECO:0007829|PDB:4KXF"
FT HELIX 951..961
FT /evidence="ECO:0007829|PDB:4KXF"
FT STRAND 969..971
FT /evidence="ECO:0007829|PDB:4KXF"
FT STRAND 975..977
FT /evidence="ECO:0007829|PDB:4KXF"
FT HELIX 981..993
FT /evidence="ECO:0007829|PDB:4KXF"
FT STRAND 999..1001
FT /evidence="ECO:0007829|PDB:4KXF"
FT STRAND 1008..1010
FT /evidence="ECO:0007829|PDB:4KXF"
FT HELIX 1012..1015
FT /evidence="ECO:0007829|PDB:4KXF"
FT STRAND 1018..1022
FT /evidence="ECO:0007829|PDB:4KXF"
SQ SEQUENCE 1024 AA; 116749 MW; 15F192E8F00FF017 CRC64;
MNFIRNNRRA LIQRMGLTVT KQICDDLFAL NVLNNQEANV IYCEPLEQEA ARKIIHMTMQ
KGSAACNLFL KSLENWDYFV YQDLTGQNLS YQVTEEDLNV LAQNLKDLYN SPAFLNFYPL
GEDIDIIFNL EKTFTEPIMW KKDHRHHRVE QLTLGSLLEA LKSPCLIEGE SGKGKSTLLQ
RIAMLWASGG CRALKGFRLV FFIHLRSARG GLFETLYDQL LNIPDFISKP TFKALLLKLH
KEVLFLLDGY NEFHPQNCPE IEALIKENHR FKNMVIVTTT TECLRHIRHV GALTAEVGDM
TEDSAKDLIE AVLVPDQVER LWAQIQESRC LRNLMKTPLF VVITCAIQMG RQEFQAHTQT
MLFQTFYDLL IQKNSHRYRG GASGDFARSL DYCGDLALEG VFAHKFDFEP EHGSSMNEDV
LVTIGLLCKY TAQRLKPTYK FFHKSFQEYT AGRRLSSLLT SKEPEEVSKG NSYLNKMVSI
SDITSLYGNL LLYTCGSSTE ATRAVMRHLA MVYQHGSLQG LSVTKRPLWR QESIQSLRNT
TEQDVLKAIN VNSFVECGIN LFSESMSKSD LSQEFEAFFQ GKSLYINSEN IPDYLFDFFE
YLPNCASALD FVKLDFYERA TESQDKAEEN VPGVHTEGPS ETYIPPRAVS LFFNWKQEFK
TLEVTLRDIN KLNKQDIKYL GKIFSSATNL RLHIKRCAAM AGRLSSVLRT CKNMHTLMVE
ASPLTTDDEQ YITSVTGLQN LSIHRLHTQQ LPGGLIDSLG NLKNLERLIL DDIRMNEEDA
KNLAEGLRSL KKMRLLHLTH LSDIGEGMDY IVKSLSEESC DLQEMKLVAC CLTANSVKVL
AQNLHNLIKL SILDISENYL EKDGNEALQE LIGRLGVLGE LTTLMLPWCW DVHTSLPKLL
KQLEGTPGLA KLGLKNWRLR DEEIKSLGEF LEMNPLRDLQ QLDLAGHCVS SDGWLYFMNV
FENLKQLVFF DFSTEEFLPD AALVRKLSQV LSKLTLLQEV KLTGWEFDDY DISAIKGTFK
LVTA
