| IED ID | IndEnz0002006872 |
| Enzyme Type ID | protease006872 |
| Protein Name |
NLR family CARD domain-containing protein 4 Caspase recruitment domain-containing protein 12 Ice protease-activating factor Ipaf |
| Gene Name | Nlrc4 Card12 Ipaf |
| Organism | Mus musculus (Mouse) |
| Taxonomic Lineage | cellular organisms Eukaryota Opisthokonta Metazoa Eumetazoa Bilateria Deuterostomia Chordata Craniata Vertebrata Gnathostomata (jawed vertebrates) Teleostomi Euteleostomi Sarcopterygii Dipnotetrapodomorpha Tetrapoda Amniota Mammalia Theria Eutheria Boreoeutheria Euarchontoglires Glires (Rodents and rabbits) Rodentia Myomorpha (mice and others) Muroidea Muridae Murinae Mus Mus Mus musculus (Mouse) |
| Enzyme Sequence | MNFIRNNRRALIQRMGLTVTKQICDDLFALNVLNNQEANVIYCEPLEQEAARKIIHMTMQKGSAACNLFLKSLENWDYFVYQDLTGQNLSYQVTEEDLNVLAQNLKDLYNSPAFLNFYPLGEDIDIIFNLEKTFTEPIMWKKDHRHHRVEQLTLGSLLEALKSPCLIEGESGKGKSTLLQRIAMLWASGGCRALKGFRLVFFIHLRSARGGLFETLYDQLLNIPDFISKPTFKALLLKLHKEVLFLLDGYNEFHPQNCPEIEALIKENHRFKNMVIVTTTTECLRHIRHVGALTAEVGDMTEDSAKDLIEAVLVPDQVERLWAQIQESRCLRNLMKTPLFVVITCAIQMGRQEFQAHTQTMLFQTFYDLLIQKNSHRYRGGASGDFARSLDYCGDLALEGVFAHKFDFEPEHGSSMNEDVLVTIGLLCKYTAQRLKPTYKFFHKSFQEYTAGRRLSSLLTSKEPEEVSKGNSYLNKMVSISDITSLYGNLLLYTCGSSTEATRAVMRHLAMVYQHGSLQGLSVTKRPLWRQESIQSLRNTTEQDVLKAINVNSFVECGINLFSESMSKSDLSQEFEAFFQGKSLYINSENIPDYLFDFFEYLPNCASALDFVKLDFYERATESQDKAEENVPGVHTEGPSETYIPPRAVSLFFNWKQEFKTLEVTLRDINKLNKQDIKYLGKIFSSATNLRLHIKRCAAMAGRLSSVLRTCKNMHTLMVEASPLTTDDEQYITSVTGLQNLSIHRLHTQQLPGGLIDSLGNLKNLERLILDDIRMNEEDAKNLAEGLRSLKKMRLLHLTHLSDIGEGMDYIVKSLSEESCDLQEMKLVACCLTANSVKVLAQNLHNLIKLSILDISENYLEKDGNEALQELIGRLGVLGELTTLMLPWCWDVHTSLPKLLKQLEGTPGLAKLGLKNWRLRDEEIKSLGEFLEMNPLRDLQQLDLAGHCVSSDGWLYFMNVFENLKQLVFFDFSTEEFLPDAALVRKLSQVLSKLTLLQEVKLTGWEFDDYDISAIKGTFKLVTA |
| Enzyme Length | 1024 |
| Uniprot Accession Number | Q3UP24 |
| Absorption | |
| Active Site | |
| Activity Regulation | |
| Binding Site | BINDING 135; /note="ATP"; /evidence="ECO:0000269|PubMed:23765277, ECO:0007744|PDB:4KXF"; BINDING 443; /note="ATP"; /evidence="ECO:0000269|PubMed:23765277, ECO:0007744|PDB:4KXF" |
| Calcium Binding | |
| catalytic Activity | |
| DNA Binding | |
| EC Number | |
| Enzyme Function | FUNCTION: Key component of inflammasomes that indirectly senses specific proteins from pathogenic bacteria and fungi and responds by assembling an inflammasome complex that promotes caspase-1 activation, cytokine production and macrophage pyroptosis. The NLRC4 inflammasome is activated as part of the innate immune response to a range of intracellular bacteria. It senses pathogenic proteins of the type III secretion system (T3SS) and type IV secretion system (T4SS) such as flagellin and PrgJ-like rod proteins via the Naip proteins (Naip1, Naip2 or Naip5): specific Naip proteins recognize and bind pathogenic proteins, driving assembly and activation of the NLRC4 inflammasome. The NLRC4 inflammasome senses Gram-negative bacteria such as L.pneumophila and P.aeruginosa, enteric pathogens S.typhimurium (Salmonella) and S.flexneri and fungal pathogen C.albicans. In intestine, the NLRC4 inflammasome is able to discriminate between commensal and pathogenic bacteria and specifically drives production of interleukin-1 beta (IL1B) in response to infection by Salmonella or P.aeruginosa. In case of L.pneumophila infection the inflammasome acts by activating caspase-7. {ECO:0000269|PubMed:15190255, ECO:0000269|PubMed:16648852, ECO:0000269|PubMed:16648853, ECO:0000269|PubMed:18070936, ECO:0000269|PubMed:19343209, ECO:0000269|PubMed:20133635, ECO:0000269|PubMed:20603313, ECO:0000269|PubMed:21874021, ECO:0000269|PubMed:21918512, ECO:0000269|PubMed:22174673, ECO:0000269|PubMed:22231517, ECO:0000269|PubMed:22484733, ECO:0000269|PubMed:22547706, ECO:0000269|PubMed:22885697, ECO:0000269|PubMed:29146805, ECO:0000269|PubMed:29182158}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | NP_BIND 172..177; /note="ATP"; /evidence="ECO:0000269|PubMed:23765277, ECO:0007744|PDB:4KXF" |
| Features | Beta strand (26); Binding site (2); Chain (1); Domain (2); Helix (48); Modified residue (1); Mutagenesis (3); Nucleotide binding (1); Region (2); Repeat (12); Sequence conflict (8); Turn (5) |
| Keywords | 3D-structure;ATP-binding;Apoptosis;Cytoplasm;Immunity;Inflammasome;Inflammatory response;Innate immunity;Leucine-rich repeat;Nucleotide-binding;Phosphoprotein;Reference proteome;Repeat |
| Interact With | P29452; Q9R016; Itself |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:22885697}. Inflammasome {ECO:0000269|PubMed:21874021, ECO:0000269|PubMed:21918512, ECO:0000269|PubMed:26585513}. |
| Modified Residue | MOD_RES 533; /note="Phosphoserine"; /evidence="ECO:0000269|PubMed:22885697, ECO:0000269|PubMed:23765277" |
| Post Translational Modification | PTM: Phosphorylated at Ser-533 following infection of macrophages with S.typhimurium (Salmonella). Phosphorylation is essential for NLRC4 inflammasome function to promote caspase-1 activation and pyroptosis. PRKCD phosphorylates Ser-533 in vitro. {ECO:0000269|PubMed:22885697, ECO:0000269|PubMed:23765277}. |
| Signal Peptide | |
| Structure 3D | Electron microscopy (3); X-ray crystallography (1) |
| Cross Reference PDB | 3JBL; 4KXF; 5AJ2; 6B5B; |
| Mapped Pubmed ID | 14610273; 16230474; 16407890; 16984919; 17087731; 17403772; 17433728; 17452523; 17491021; 17506816; 17548639; 17599094; 17878377; 17935074; 18256184; 18288107; 18490757; 18496530; 18566365; 18624356; 18724372; 18768827; 18799693; 19139171; 19164858; 19222370; 19237518; 19339971; 19362020; 19362023; 19364881; 19587006; 19596994; 19652710; 19684085; 19696895; 19717512; 19720760; 19812205; 19841075; 19918053; 20007575; 20048047; 20333626; 20348425; 20383149; 20385749; 20457908; 20490635; 20495560; 20702413; 20713892; 20722078; 20802146; 20808838; 20974980; 21037094; 21057511; 21072873; 21118981; 21124315; 21267068; 21282416; 21478880; 21487011; 21533069; 21565393; 21683629; 21687424; 21746921; 21771913; 21856950; 21957143; 22002608; 22079982; 22101787; 22241982; 22297845; 22318495; 22331066; 22365665; 22444631; 22461621; 22474394; 22723524; 22902502; 22911706; 23012363; 23024281; 23071280; 23115038; 23209411; 23225887; 23284055; 23297415; 23307811; 23348507; 23355222; 23460746; 23478406; 23509366; 23630357; 23696660; 23763294; 23818043; 23853600; 23887873; 23940371; 23942123; 24043898; 24078693; 24123685; 24157462; 24280936; 24337744; 24453977; 24508233; 24516390; 24555512; 24638169; 24657167; 24798340; 24803432; 24827856; 24919149; 25085021; 25121751; 25166912; 25232720; 25271165; 25385754; 25402425; 25405768; 25422455; 25582856; 25605939; 25687541; 25704009; 25774715; 25775556; 25862092; 25914934; 25959047; 26008898; 26232428; 26320999; 26384545; 26449475; 26516283; 26572062; 26572063; 26635450; 26687278; 26972847; 27011353; 27045008; 27045038; 27114610; 27139490; 27175981; 27270401; 27339979; 27546231; 27617861; 27670879; 27693356; 27706238; 27708283; 27808091; 27846608; 27855208; 27977701; 28032341; 28087670; 28404595; 28410991; 28504273; 28636595; 28684545; 28771586; 28923684; 28961278; 29030458; 29033131; 29133401; 29262324; 29263322; 29321274; 29353059; 29491424; 29576451; 29596938; 29778503; 30279514; 30340040; 30518876; 30982580; 31038471; 31332247; 31420376; 31511697; 31953493; 32041990; 32298652; 32342103; 32758418; 32760056; 32763970; 33074100; 33106673; 33177235; 33178225; 33312172; 33333046; 33535228; 33552083; 34383985; 34678072; |
| Motif | |
| Gene Encoded By | |
| Mass | 116,749 |
| Kinetics | |
| Metal Binding | |
| Rhea ID | |
| Cross Reference Brenda |