NLRC4_HUMAN
ID NLRC4_HUMAN Reviewed; 1024 AA.
AC Q9NPP4; A8K9F8; B2RBQ3; B3KTF0; D6W580; Q96J81; Q96J82; Q96J83;
DT 31-JAN-2002, integrated into UniProtKB/Swiss-Prot.
DT 31-JAN-2002, sequence version 2.
DT 03-AUG-2022, entry version 190.
DE RecName: Full=NLR family CARD domain-containing protein 4;
DE AltName: Full=CARD, LRR, and NACHT-containing protein;
DE Short=CED-4-like protein Clan {ECO:0000303|PubMed:11472070};
DE AltName: Full=Caspase recruitment domain-containing protein 12 {ECO:0000303|PubMed:11374873};
DE AltName: Full=Ice protease-activating factor {ECO:0000303|PubMed:11390368};
DE Short=Ipaf {ECO:0000303|PubMed:11390368};
GN Name=NLRC4;
GN Synonyms=CARD12 {ECO:0000303|PubMed:11374873},
GN CLAN {ECO:0000303|PubMed:11472070}, CLAN1,
GN IPAF {ECO:0000303|PubMed:11390368}; ORFNames=UNQ6189/PRO20215;
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=11374873; DOI=10.1006/bbrc.2001.4928;
RA Geddes B.J., Wang L., Huang W.-J., Lavellee M., Manji G.A., Brown M.,
RA Jurman M., Cao J., Morgenstern J., Merriam S., Glucksmann M.A.,
RA DiStefano P.S., Bertin J.;
RT "Human CARD12 is a novel CED4/Apaf-1 family member that induces
RT apoptosis.";
RL Biochem. Biophys. Res. Commun. 284:77-82(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2; 3 AND 4).
RC TISSUE=Lung;
RX PubMed=11472070; DOI=10.1006/geno.2001.6579;
RA Damiano J.S., Stehlik C., Pio F., Godzik A., Reed J.C.;
RT "CLAN, a novel human CED-4-like gene.";
RL Genomics 75:77-83(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND SUBCELLULAR LOCATION.
RC TISSUE=Leukocyte;
RX PubMed=11390368; DOI=10.1074/jbc.c100250200;
RA Poyet J.-L., Srinivasula S.M., Tnani M., Razmara M., Fernandes-Alnemri T.,
RA Alnemri E.S.;
RT "Identification of Ipaf, a human caspase-1-activating protein related to
RT Apaf-1.";
RL J. Biol. Chem. 276:28309-28313(2001).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA Gingras M., Qiu J., Margolin J.F.;
RT "Differential expression of the caspase recruitment domain protein 12
RT (CARD12) during monocytic differentiation.";
RL Submitted (MAY-2001) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RX PubMed=12975309; DOI=10.1101/gr.1293003;
RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J.,
RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P.,
RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A.,
RA Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D.,
RA Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L.,
RA Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C.,
RA Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J.,
RA Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.;
RT "The secreted protein discovery initiative (SPDI), a large-scale effort to
RT identify novel human secreted and transmembrane proteins: a bioinformatics
RT assessment.";
RL Genome Res. 13:2265-2270(2003).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Thymus, and Uterus;
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 [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.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 (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain, Lung, and Testis;
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 [10]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 586-1024 (ISOFORM 1).
RG The European IMAGE consortium;
RL Submitted (JUL-2000) to the EMBL/GenBank/DDBJ databases.
RN [11]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=15107016; DOI=10.1042/bj20031506;
RA Damiano J.S., Oliveira V., Welsh K., Reed J.C.;
RT "Heterotypic interactions among NACHT domains: implications for regulation
RT of innate immune responses.";
RL Biochem. J. 381:213-219(2004).
RN [12]
RP INTERACTION WITH EIF2AK2.
RX PubMed=22801494; DOI=10.1038/nature11290;
RA Lu B., Nakamura T., Inouye K., Li J., Tang Y., Lundbaeck P.,
RA Valdes-Ferrer S.I., Olofsson P.S., Kalb T., Roth J., Zou Y.,
RA Erlandsson-Harris H., Yang H., Ting J.P., Wang H., Andersson U.,
RA Antoine D.J., Chavan S.S., Hotamisligil G.S., Tracey K.J.;
RT "Novel role of PKR in inflammasome activation and HMGB1 release.";
RL Nature 488:670-674(2012).
RN [13] {ECO:0007744|PDB:6K8J}
RP STRUCTURE BY ELECTRON MICROSCOPY (3.30 ANGSTROMS) OF 1-85.
RX PubMed=33420028; DOI=10.1038/s41467-020-20319-5;
RA Gong Q., Robinson K., Xu C., Huynh P.T., Chong K.H.C., Tan E.Y.J.,
RA Zhang J., Boo Z.Z., Teo D.E.T., Lay K., Zhang Y., Lim J.S.Y., Goh W.I.,
RA Wright G., Zhong F.L., Reversade B., Wu B.;
RT "Structural basis for distinct inflammasome complex assembly by human NLRP1
RT and CARD8.";
RL Nat. Commun. 12:188-188(2021).
RN [14]
RP INVOLVEMENT IN FCAS4, VARIANT FCAS4 PRO-443, CHARACTERIZATION OF VARIANT
RP FCAS4 PRO-443, AND SUBUNIT.
RX PubMed=25385754; DOI=10.1084/jem.20141091;
RA Kitamura A., Sasaki Y., Abe T., Kano H., Yasutomo K.;
RT "An inherited mutation in NLRC4 causes autoinflammation in human and
RT mice.";
RL J. Exp. Med. 211:2385-2396(2014).
RN [15]
RP INVOLVEMENT IN AIFEC, VARIANT AIFEC ALA-341, AND CHARACTERIZATION OF
RP VARIANT AIFEC ALA-341.
RX PubMed=25217960; DOI=10.1038/ng.3066;
RA Romberg N., Al Moussawi K., Nelson-Williams C., Stiegler A.L., Loring E.,
RA Choi M., Overton J., Meffre E., Khokha M.K., Huttner A.J., West B.,
RA Podoltsev N.A., Boggon T.J., Kazmierczak B.I., Lifton R.P.;
RT "Mutation of NLRC4 causes a syndrome of enterocolitis and
RT autoinflammation.";
RL Nat. Genet. 46:1135-1139(2014).
RN [16]
RP VARIANT AIFEC SER-337, AND CHARACTERIZATION OF VARIANT AIFEC SER-337.
RX PubMed=25217959; DOI=10.1038/ng.3089;
RA Canna S.W., de Jesus A.A., Gouni S., Brooks S.R., Marrero B., Liu Y.,
RA DiMattia M.A., Zaal K.J., Sanchez G.A., Kim H., Chapelle D., Plass N.,
RA Huang Y., Villarino A.V., Biancotto A., Fleisher T.A., Duncan J.A.,
RA O'Shea J.J., Benseler S., Grom A., Deng Z., Laxer R.M., Goldbach-Mansky R.;
RT "An activating NLRC4 inflammasome mutation causes autoinflammation with
RT recurrent macrophage activation syndrome.";
RL Nat. Genet. 46:1140-1146(2014).
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 (PubMed:15107016). The
CC NLRC4 inflammasome is activated as part of the innate immune response
CC to a range of intracellular bacteria (By similarity).
CC {ECO:0000250|UniProtKB:Q3UP24, ECO:0000269|PubMed:15107016}.
CC -!- SUBUNIT: Homooligomer; homooligomerizes to induce formation of the
CC NLRC4 inflammasome (PubMed:25385754, PubMed:33420028). Homooligomerizes
CC following activation by pathogenic proteins (By similarity). Component
CC of the NLRC4 inflammasome, at least composed of NLRC4 and caspase-1
CC (CASP1) (By similarity). Some NLRC4 inflammasomes contain PYCARD/ASC,
CC while some others directly contact and activate CASP1
CC (PubMed:25217959). Interacts (via CARD domain) with PYCARD/ASC, pro-
CC caspase-1 (CASP1), NOD2, BCL10 and NALP1 (NAC) by CARD-CARD interaction
CC (PubMed:15107016). Interacts with EIF2AK2/PKR (PubMed:22801494).
CC {ECO:0000250|UniProtKB:Q3UP24, ECO:0000269|PubMed:22801494,
CC ECO:0000269|PubMed:25217959, ECO:0000269|PubMed:33420028}.
CC -!- INTERACTION:
CC Q9NPP4; P29466: CASP1; NbExp=4; IntAct=EBI-1222527, EBI-516667;
CC Q9NPP4; Q9NPP4: NLRC4; NbExp=3; IntAct=EBI-1222527, EBI-1222527;
CC Q9NPP4-1; Q48824: flaA; Xeno; NbExp=3; IntAct=EBI-15944387, EBI-15944232;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:11390368}.
CC Cytoplasm, cytosol {ECO:0000250|UniProtKB:Q3UP24}. Inflammasome
CC {ECO:0000269|PubMed:15107016, ECO:0000269|PubMed:33420028}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1; Synonyms=CLANA;
CC IsoId=Q9NPP4-1; Sequence=Displayed;
CC Name=2; Synonyms=CLANB;
CC IsoId=Q9NPP4-2; Sequence=VSP_000784;
CC Name=3; Synonyms=CLANC;
CC IsoId=Q9NPP4-3; Sequence=VSP_000785, VSP_000786;
CC Name=4; Synonyms=CLAND;
CC IsoId=Q9NPP4-4; Sequence=VSP_000787, VSP_000788;
CC -!- TISSUE SPECIFICITY: Isoform 2 is expressed ubiquitously, although
CC highly expressed in lung and spleen. Isoform 1 is highly expressed in
CC lung, followed by leukocytes especially monocytes, lymph node, colon,
CC brain, prostate, placenta, spleen, bone marrow and fetal liver. Isoform
CC 4 is only detected in brain.
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. {ECO:0000250|UniProtKB:Q3UP24}.
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:0000250|UniProtKB:Q3UP24}.
CC -!- DISEASE: Autoinflammation with infantile enterocolitis (AIFEC)
CC [MIM:616050]: An autosomal dominant disorder characterized by neonatal-
CC onset enterocolitis, periodic fever, and fatal or near-fatal episodes
CC of autoinflammation. Affected individuals tend to have poor overall
CC growth and gastrointestinal symptoms in infancy, recurrent febrile
CC episodes with splenomegaly, and sometimes hematologic disturbances,
CC arthralgias, or myalgias. {ECO:0000269|PubMed:25217959,
CC ECO:0000269|PubMed:25217960}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Familial cold autoinflammatory syndrome 4 (FCAS4)
CC [MIM:616115]: A form of autoinflammatory syndrome, a rare autosomal
CC dominant systemic disease characterized by recurrent episodes of
CC maculopapular rash associated with arthralgias, myalgias, fever and
CC chills, swelling of the extremities, and conjunctivitis after
CC generalized exposure to cold. {ECO:0000269|PubMed:25385754}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/NLRC4ID43189ch2p22.html";
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DR EMBL; AY032589; AAK38730.1; -; mRNA.
DR EMBL; AY027787; AAK14776.1; -; mRNA.
DR EMBL; AY027788; AAK14777.1; -; mRNA.
DR EMBL; AY027789; AAK14778.1; -; mRNA.
DR EMBL; AY027790; AAK14779.1; -; mRNA.
DR EMBL; AY035391; AAK59843.1; -; mRNA.
DR EMBL; AF376061; AAK53443.1; -; mRNA.
DR EMBL; AY358152; AAQ88519.1; -; mRNA.
DR EMBL; AK095467; BAG53062.1; -; mRNA.
DR EMBL; AK292673; BAF85362.1; -; mRNA.
DR EMBL; AK314762; BAG37300.1; -; mRNA.
DR EMBL; AL121653; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471053; EAX00452.1; -; Genomic_DNA.
DR EMBL; CH471053; EAX00453.1; -; Genomic_DNA.
DR EMBL; CH471053; EAX00454.1; -; Genomic_DNA.
DR EMBL; CH471053; EAX00455.1; -; Genomic_DNA.
DR EMBL; BC031555; AAH31555.1; -; mRNA.
DR EMBL; AL389934; CAB97523.1; -; mRNA.
DR CCDS; CCDS33174.1; -. [Q9NPP4-1]
DR CCDS; CCDS77400.1; -. [Q9NPP4-2]
DR RefSeq; NP_001186067.1; NM_001199138.1. [Q9NPP4-1]
DR RefSeq; NP_001186068.1; NM_001199139.1. [Q9NPP4-1]
DR RefSeq; NP_001289433.1; NM_001302504.1. [Q9NPP4-2]
DR RefSeq; NP_067032.3; NM_021209.4. [Q9NPP4-1]
DR PDB; 6K8J; EM; 3.30 A; A/B/C/D/E/F/G/H/I/J/K/L=1-85.
DR PDB; 6MKS; EM; 3.40 A; A/B/C/D/E/F/G/H/I/J/K/L/M/N/O/P/Q/R/S/T/U/V/W/X/Y/Z/a/b/c/d=1-96.
DR PDB; 6N1I; EM; 3.58 A; A/B/C/D/E/F/G/H/I/J/K/L/M/N/O/P=1-85.
DR PDBsum; 6K8J; -.
DR PDBsum; 6MKS; -.
DR PDBsum; 6N1I; -.
DR AlphaFoldDB; Q9NPP4; -.
DR SMR; Q9NPP4; -.
DR BioGRID; 121814; 15.
DR ComplexPortal; CPX-4144; NLRC4 inflammasome.
DR DIP; DIP-38428N; -.
DR IntAct; Q9NPP4; 8.
DR STRING; 9606.ENSP00000385090; -.
DR ChEMBL; CHEMBL4630857; -.
DR iPTMnet; Q9NPP4; -.
DR PhosphoSitePlus; Q9NPP4; -.
DR BioMuta; NLRC4; -.
DR DMDM; 20138032; -.
DR jPOST; Q9NPP4; -.
DR MassIVE; Q9NPP4; -.
DR PaxDb; Q9NPP4; -.
DR PeptideAtlas; Q9NPP4; -.
DR PRIDE; Q9NPP4; -.
DR ProteomicsDB; 82036; -. [Q9NPP4-1]
DR ProteomicsDB; 82037; -. [Q9NPP4-2]
DR ProteomicsDB; 82038; -. [Q9NPP4-3]
DR ProteomicsDB; 82039; -. [Q9NPP4-4]
DR Antibodypedia; 14265; 344 antibodies from 36 providers.
DR DNASU; 58484; -.
DR Ensembl; ENST00000342905.10; ENSP00000339666.6; ENSG00000091106.19. [Q9NPP4-2]
DR Ensembl; ENST00000360906.9; ENSP00000354159.5; ENSG00000091106.19. [Q9NPP4-1]
DR Ensembl; ENST00000402280.6; ENSP00000385428.1; ENSG00000091106.19. [Q9NPP4-1]
DR GeneID; 58484; -.
DR KEGG; hsa:58484; -.
DR MANE-Select; ENST00000402280.6; ENSP00000385428.1; NM_001199138.2; NP_001186067.1.
DR UCSC; uc002roi.4; human. [Q9NPP4-1]
DR CTD; 58484; -.
DR DisGeNET; 58484; -.
DR GeneCards; NLRC4; -.
DR HGNC; HGNC:16412; NLRC4.
DR HPA; ENSG00000091106; Tissue enhanced (bone marrow, lung, lymphoid tissue).
DR MalaCards; NLRC4; -.
DR MIM; 606831; gene.
DR MIM; 616050; phenotype.
DR MIM; 616115; phenotype.
DR neXtProt; NX_Q9NPP4; -.
DR OpenTargets; ENSG00000091106; -.
DR Orphanet; 576349; NLRC4-related familial cold autoinflammatory syndrome.
DR Orphanet; 436166; Periodic fever-infantile enterocolitis-autoinflammatory syndrome.
DR PharmGKB; PA162397671; -.
DR VEuPathDB; HostDB:ENSG00000091106; -.
DR eggNOG; ENOG502QWRJ; Eukaryota.
DR GeneTree; ENSGT00940000161744; -.
DR HOGENOM; CLU_011683_0_0_1; -.
DR InParanoid; Q9NPP4; -.
DR OMA; LRLCIKR; -.
DR OrthoDB; 137566at2759; -.
DR PhylomeDB; Q9NPP4; -.
DR TreeFam; TF336864; -.
DR PathwayCommons; Q9NPP4; -.
DR Reactome; R-HSA-6803207; TP53 Regulates Transcription of Caspase Activators and Caspases.
DR Reactome; R-HSA-844623; The IPAF inflammasome.
DR SignaLink; Q9NPP4; -.
DR SIGNOR; Q9NPP4; -.
DR BioGRID-ORCS; 58484; 11 hits in 1067 CRISPR screens.
DR GeneWiki; NLRC4; -.
DR GenomeRNAi; 58484; -.
DR Pharos; Q9NPP4; Tbio.
DR PRO; PR:Q9NPP4; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; Q9NPP4; protein.
DR Bgee; ENSG00000091106; Expressed in monocyte and 102 other tissues.
DR ExpressionAtlas; Q9NPP4; baseline and differential.
DR Genevisible; Q9NPP4; HS.
DR GO; GO:0005737; C:cytoplasm; IC:ComplexPortal.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0061702; C:inflammasome complex; IC:ComplexPortal.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR GO; GO:0072557; C:IPAF inflammasome complex; ISS:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IDA:HGNC-UCL.
DR GO; GO:0089720; F:caspase binding; IPI:ARUK-UCL.
DR GO; GO:0061133; F:endopeptidase activator activity; IGI:ARUK-UCL.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0000287; F:magnesium ion binding; TAS:HGNC-UCL.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:HGNC-UCL.
DR GO; GO:0097202; P:activation of cysteine-type endopeptidase activity; IMP:CACAO.
DR GO; GO:0006919; P:activation of cysteine-type endopeptidase activity involved in apoptotic process; IDA:HGNC-UCL.
DR GO; GO:0002218; P:activation of innate immune response; ISS:UniProtKB.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0042742; P:defense response to bacterium; IDA:HGNC-UCL.
DR GO; GO:0016045; P:detection of bacterium; IDA:HGNC-UCL.
DR GO; GO:0046456; P:icosanoid biosynthetic process; IC:ComplexPortal.
DR GO; GO:0006954; P:inflammatory response; ISS:UniProtKB.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:0002221; P:pattern recognition receptor signaling pathway; IC:ComplexPortal.
DR GO; GO:0043065; P:positive regulation of apoptotic process; IDA:UniProtKB.
DR GO; GO:0050729; P:positive regulation of inflammatory response; IC:ComplexPortal.
DR GO; GO:0032731; P:positive regulation of interleukin-1 beta production; IGI:HGNC-UCL.
DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; IDA:UniProtKB.
DR GO; GO:0010954; P:positive regulation of protein processing; IGI:ARUK-UCL.
DR GO; GO:0051260; P:protein homooligomerization; ISS:UniProtKB.
DR GO; GO:0070269; P:pyroptosis; ISS:UniProtKB.
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; Alternative splicing; Apoptosis; ATP-binding; Cytoplasm;
KW Disease variant; Immunity; Inflammasome; Inflammatory response;
KW Innate immunity; Leucine-rich repeat; Nucleotide-binding; Phosphoprotein;
KW Reference proteome; Repeat.
FT CHAIN 1..1024
FT /note="NLR family CARD domain-containing protein 4"
FT /id="PRO_0000144087"
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 REPEAT 656..679
FT /note="LRR 2"
FT REPEAT 735..758
FT /note="LRR 3"
FT REPEAT 762..785
FT /note="LRR 4"
FT REPEAT 787..812
FT /note="LRR 5"
FT REPEAT 824..847
FT /note="LRR 6"
FT REPEAT 848..870
FT /note="LRR 7"
FT REPEAT 878..902
FT /note="LRR 8"
FT REPEAT 911..933
FT /note="LRR 9"
FT REPEAT 936..963
FT /note="LRR 10"
FT REPEAT 965..985
FT /note="LRR 11"
FT REPEAT 999..1021
FT /note="LRR 12"
FT REGION 95..298
FT /note="Nucleotide-binding domain (NBD)"
FT /evidence="ECO:0000250"
FT REGION 356..463
FT /note="Winged-helix domain (WHD)"
FT /evidence="ECO:0000250"
FT BINDING 169..176
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00136"
FT MOD_RES 533
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q3UP24"
FT VAR_SEQ 89..753
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:11472070"
FT /id="VSP_000784"
FT VAR_SEQ 90..92
FT /note="FHQ -> LTA (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:11472070"
FT /id="VSP_000787"
FT VAR_SEQ 93..1024
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:11472070"
FT /id="VSP_000788"
FT VAR_SEQ 155..156
FT /note="NG -> VL (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:11472070"
FT /id="VSP_000785"
FT VAR_SEQ 157..1024
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:11472070"
FT /id="VSP_000786"
FT VARIANT 337
FT /note="T -> S (in AIFEC; results in a gain of function
FT mutation with constitutive activation of caspase-1;
FT dbSNP:rs587777840)"
FT /evidence="ECO:0000269|PubMed:25217959"
FT /id="VAR_072484"
FT VARIANT 341
FT /note="V -> A (in AIFEC; results in a gain of function
FT mutation with constitutive activation of caspase-1;
FT dbSNP:rs587781260)"
FT /evidence="ECO:0000269|PubMed:25217960"
FT /id="VAR_072485"
FT VARIANT 443
FT /note="H -> P (in FCAS4; the mutation increases
FT oligomerization of the NLRC4 protein; results in
FT hyperactivation of caspase-1 with an increase in IL1B
FT protein secretion; dbSNP:rs606231460)"
FT /evidence="ECO:0000269|PubMed:25385754"
FT /id="VAR_072645"
FT CONFLICT 39
FT /note="N -> D (in Ref. 6; BAF85362)"
FT /evidence="ECO:0000305"
FT CONFLICT 138
FT /note="V -> I (in Ref. 2; AAK14776)"
FT /evidence="ECO:0000305"
FT CONFLICT 393
FT /note="C -> R (in Ref. 2; AAK14776)"
FT /evidence="ECO:0000305"
FT CONFLICT 420
FT /note="V -> A (in Ref. 4; AAK53443)"
FT /evidence="ECO:0000305"
FT CONFLICT 678
FT /note="R -> T (in Ref. 1; AAK38730)"
FT /evidence="ECO:0000305"
FT CONFLICT 791
FT /note="K -> E (in Ref. 6; BAG53062)"
FT /evidence="ECO:0000305"
FT HELIX 2..11
FT /evidence="ECO:0007829|PDB:6K8J"
FT HELIX 17..29
FT /evidence="ECO:0007829|PDB:6K8J"
FT HELIX 35..41
FT /evidence="ECO:0007829|PDB:6K8J"
FT HELIX 47..58
FT /evidence="ECO:0007829|PDB:6K8J"
FT HELIX 64..75
FT /evidence="ECO:0007829|PDB:6K8J"
FT HELIX 78..84
FT /evidence="ECO:0007829|PDB:6K8J"
SQ SEQUENCE 1024 AA; 116159 MW; 49378DBB54938E0F CRC64;
MNFIKDNSRA LIQRMGMTVI KQITDDLFVW NVLNREEVNI ICCEKVEQDA ARGIIHMILK
KGSESCNLFL KSLKEWNYPL FQDLNGQSLF HQTSEGDLDD LAQDLKDLYH TPSFLNFYPL
GEDIDIIFNL KSTFTEPVLW RKDQHHHRVE QLTLNGLLQA LQSPCIIEGE SGKGKSTLLQ
RIAMLWGSGK CKALTKFKFV FFLRLSRAQG GLFETLCDQL LDIPGTIRKQ TFMAMLLKLR
QRVLFLLDGY NEFKPQNCPE IEALIKENHR FKNMVIVTTT TECLRHIRQF GALTAEVGDM
TEDSAQALIR EVLIKELAEG LLLQIQKSRC LRNLMKTPLF VVITCAIQMG ESEFHSHTQT
TLFHTFYDLL IQKNKHKHKG VAASDFIRSL DHCGDLALEG VFSHKFDFEL QDVSSVNEDV
LLTTGLLCKY TAQRFKPKYK FFHKSFQEYT AGRRLSSLLT SHEPEEVTKG NGYLQKMVSI
SDITSTYSSL LRYTCGSSVE ATRAVMKHLA AVYQHGCLLG LSIAKRPLWR QESLQSVKNT
TEQEILKAIN INSFVECGIH LYQESTSKSA LSQEFEAFFQ GKSLYINSGN IPDYLFDFFE
HLPNCASALD FIKLDFYGGA MASWEKAAED TGGIHMEEAP ETYIPSRAVS LFFNWKQEFR
TLEVTLRDFS KLNKQDIRYL GKIFSSATSL RLQIKRCAGV AGSLSLVLST CKNIYSLMVE
ASPLTIEDER HITSVTNLKT LSIHDLQNQR LPGGLTDSLG NLKNLTKLIM DNIKMNEEDA
IKLAEGLKNL KKMCLFHLTH LSDIGEGMDY IVKSLSSEPC DLEEIQLVSC CLSANAVKIL
AQNLHNLVKL SILDLSENYL EKDGNEALHE LIDRMNVLEQ LTALMLPWGC DVQGSLSSLL
KHLEEVPQLV KLGLKNWRLT DTEIRILGAF FGKNPLKNFQ QLNLAGNRVS SDGWLAFMGV
FENLKQLVFF DFSTKEFLPD PALVRKLSQV LSKLTFLQEA RLVGWQFDDD DLSVITGAFK
LVTA
