NLRC4_RAT
ID NLRC4_RAT Reviewed; 1023 AA.
AC F1M649;
DT 31-OCT-2012, integrated into UniProtKB/Swiss-Prot.
DT 31-OCT-2012, sequence version 2.
DT 03-AUG-2022, entry version 76.
DE RecName: Full=NLR family CARD domain-containing protein 4;
DE AltName: Full=Ice protease-activating factor;
DE Short=Ipaf;
GN Name=Nlrc4; Synonyms=Ipaf;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway;
RX PubMed=15057822; DOI=10.1038/nature02426;
RA Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
RA Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
RA Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
RA Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
RA Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
RA Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
RA Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D.,
RA Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L.,
RA Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D.,
RA Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M.,
RA Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C.,
RA Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J.,
RA Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H.,
RA Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X.,
RA Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q.,
RA Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P.,
RA Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A.,
RA Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C.,
RA Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
RA Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J.,
RA Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F.,
RA Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A.,
RA Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A.,
RA Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J.,
RA Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E.,
RA Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
RA Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C.,
RA Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L.,
RA Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W.,
RA Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y.,
RA Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V.,
RA Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M.,
RA Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S.,
RA Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B.,
RA Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R.,
RA Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J.,
RA Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D.,
RA Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S.,
RA Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S.,
RA Mockrin S., Collins F.S.;
RT "Genome sequence of the Brown Norway rat yields insights into mammalian
RT evolution.";
RL Nature 428:493-521(2004).
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. {ECO:0000250|UniProtKB:Q3UP24}.
CC -!- SUBUNIT: Homooligomer; homooligomerizes following activation of Naip
CC proteins by pathogenic proteins such as S.typhimurium (Salmonella)
CC flagellin or PrgJ. Component of the NLRC4 inflammasome, at least
CC composed of NLRC4, caspase-1 (CASP1) and some NAIP family member (By
CC similarity). Interacts with EIF2AK2/PKR (By similarity).
CC {ECO:0000250|UniProtKB:Q3UP24, ECO:0000250|UniProtKB:Q9NPP4}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol
CC {ECO:0000250|UniProtKB:Q3UP24}.
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}.
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DR RefSeq; NP_001296361.1; NM_001309432.1.
DR RefSeq; XP_008762713.1; XM_008764491.2.
DR AlphaFoldDB; F1M649; -.
DR SMR; F1M649; -.
DR STRING; 10116.ENSRNOP00000007655; -.
DR PaxDb; F1M649; -.
DR PRIDE; F1M649; -.
DR Ensembl; ENSRNOT00000007655; ENSRNOP00000007655; ENSRNOG00000005810.
DR GeneID; 298784; -.
DR KEGG; rno:298784; -.
DR UCSC; RGD:1309831; rat.
DR CTD; 58484; -.
DR RGD; 1309831; Nlrc4.
DR eggNOG; ENOG502QWRJ; Eukaryota.
DR GeneTree; ENSGT00940000161744; -.
DR HOGENOM; CLU_011683_0_0_1; -.
DR InParanoid; F1M649; -.
DR OMA; LRLCIKR; -.
DR OrthoDB; 137566at2759; -.
DR PRO; PR:F1M649; -.
DR Proteomes; UP000002494; Chromosome 6.
DR Bgee; ENSRNOG00000005810; Expressed in duodenum and 14 other tissues.
DR GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IEA:Ensembl.
DR GO; GO:0072557; C:IPAF inflammasome complex; ISS:UniProtKB.
DR GO; GO:0005524; F:ATP binding; ISO:RGD.
DR GO; GO:0089720; F:caspase binding; ISO:RGD.
DR GO; GO:0061133; F:endopeptidase activator activity; ISO:RGD.
DR GO; GO:0042802; F:identical protein binding; ISO:RGD.
DR GO; GO:0042803; F:protein homodimerization activity; ISO:RGD.
DR GO; GO:0097202; P:activation of cysteine-type endopeptidase activity; ISO:RGD.
DR GO; GO:0006919; P:activation of cysteine-type endopeptidase activity involved in apoptotic process; ISO:RGD.
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; ISS:UniProtKB.
DR GO; GO:0016045; P:detection of bacterium; ISS:UniProtKB.
DR GO; GO:0006954; P:inflammatory response; ISS:UniProtKB.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:0043065; P:positive regulation of apoptotic process; ISO:RGD.
DR GO; GO:0032731; P:positive regulation of interleukin-1 beta production; ISS:UniProtKB.
DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; ISO:RGD.
DR GO; GO:0010954; P:positive regulation of protein processing; ISO:RGD.
DR GO; GO:0051260; P:protein homooligomerization; ISS:UniProtKB.
DR GO; GO:0070269; P:pyroptosis; ISS:UniProtKB.
DR GO; GO:0042981; P:regulation of apoptotic process; ISO:RGD.
DR GO; GO:0043281; P:regulation of cysteine-type endopeptidase activity involved in apoptotic process; ISO:RGD.
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 3: Inferred from homology;
KW Apoptosis; ATP-binding; Cytoplasm; Immunity; Inflammatory response;
KW Innate immunity; Leucine-rich repeat; Nucleotide-binding; Phosphoprotein;
KW Reference proteome; Repeat.
FT CHAIN 1..1023
FT /note="NLR family CARD domain-containing protein 4"
FT /id="PRO_0000419976"
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 655..678
FT /note="LRR 2"
FT REPEAT 734..757
FT /note="LRR 3"
FT REPEAT 761..784
FT /note="LRR 4"
FT REPEAT 786..811
FT /note="LRR 5"
FT REPEAT 823..846
FT /note="LRR 6"
FT REPEAT 847..869
FT /note="LRR 7"
FT REPEAT 877..901
FT /note="LRR 8"
FT REPEAT 910..932
FT /note="LRR 9"
FT REPEAT 935..962
FT /note="LRR 10"
FT REPEAT 964..984
FT /note="LRR 11"
FT REPEAT 998..1020
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"
SQ SEQUENCE 1023 AA; 116142 MW; A91F740D9D78F327 CRC64;
MNFIKENSQA LIQRMGIVVI KQICDDLFAL NVLNGEEVAI ICSHRVEQDA ARDIVHMILK
KGSAACNLFL KSLENWNYPV YQDLTGHSLF HQNLEEDLDV LAQSLKDLYN SPVFKNFFPL
GEDIDIIFNL QITFTEPVLW RKDHRHHRVE QMTLGSLLEA LKSPCLIEGE SGKGKSTLLQ
KIAMLWASGM CPALNQFKLV FFIRLSSARG GLFETLYDQL VNIPDSISKP TFRALLLKLH
KKVLFLLDAY NEFHPQNCPE IEALVKENHR FKNMVIVTTT TECLRHIRHV GALTVEVGDM
TEDSARVLIR EVLINELAEG LLFQMQESRC LRNLMRTPLF VVITCAIQMG SEEFQAHTQT
MLFQTFYDLL IQKNRRRHSG GTSGDFVRSL DYCGDLALEG VFSHKFDFEL EDVCSMNEDV
LVRTGLLCKY TAQRLRPTYK FFHKSFQEYT AGRRLSSLLK SREPEEVSKG NSYLKKMVSI
SDITSLYGNL LLYTCGSSTE ATRAIMRHLA MVCEHGSLQG LSVTKRPLWR QESIQNLRNT
TEQDVLKAIN VNSFVECGIN LFSESISKSE LSQEFEAFFQ GKSLYINSEN IPDYLFDFFK
YLPNCVSALD FVKLDFYGRA TVSQDKTGEN SSGVHTEGPS TYIPSRAVSL FFNWMQKFKT
LEVTLRDISK LNKQDIKYLG KIFSSASNLK LYIKRCAAVA GRLSSVLRTC KNIHSLMVEA
SPLTTEDEQY ITSVTDLQNL SIHDLHTQRL PGGLADSLGN LKNLLKLILD DIRLNEEDAK
SLAEGLRNLK KMRLLHLTRL SDMGEGMDYI VKSLSEEPCD LQEMKLVDCC LTANSLKILA
QNLHNLVKLS VLDMSENYLE KAGSEALQGL IGRLGVLEQL SALMLPWCWD AYISLPNLLK
QLEGTPGLVK LGLKNWRLRD EEIRSFGEFL EMNPLRDLQQ LDLAGHGVSS DGWLSFMDVF
ENLKQLVFFD FGTEEFLPDA ALVRKLGQVL SKLTLLQEAR LTGWELDDYD ISVIKGTFKL
VTA
