NLRC4_BOVIN
ID NLRC4_BOVIN Reviewed; 1017 AA.
AC F1MHT9;
DT 31-OCT-2012, integrated into UniProtKB/Swiss-Prot.
DT 31-OCT-2012, sequence version 3.
DT 03-AUG-2022, entry version 64.
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 Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Hereford;
RX PubMed=19393038; DOI=10.1186/gb-2009-10-4-r42;
RA Zimin A.V., Delcher A.L., Florea L., Kelley D.R., Schatz M.C., Puiu D.,
RA Hanrahan F., Pertea G., Van Tassell C.P., Sonstegard T.S., Marcais G.,
RA Roberts M., Subramanian P., Yorke J.A., Salzberg S.L.;
RT "A whole-genome assembly of the domestic cow, Bos taurus.";
RL Genome Biol. 10:R42.01-R42.10(2009).
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 EMBL; DAAA02030442; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR RefSeq; NP_001179252.2; NM_001192323.2.
DR RefSeq; XP_005212578.1; XM_005212521.3.
DR AlphaFoldDB; F1MHT9; -.
DR SMR; F1MHT9; -.
DR STRING; 9913.ENSBTAP00000010814; -.
DR PaxDb; F1MHT9; -.
DR PRIDE; F1MHT9; -.
DR GeneID; 512480; -.
DR KEGG; bta:512480; -.
DR CTD; 58484; -.
DR eggNOG; ENOG502QWRJ; Eukaryota.
DR InParanoid; F1MHT9; -.
DR OrthoDB; 137566at2759; -.
DR Proteomes; UP000009136; Unplaced.
DR GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR GO; GO:0072557; C:IPAF inflammasome complex; ISS:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
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:0032731; P:positive regulation of interleukin-1 beta production; ISS:UniProtKB.
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; IEA:InterPro.
DR Gene3D; 1.10.533.10; -; 1.
DR Gene3D; 3.40.50.300; -; 1.
DR Gene3D; 3.80.10.10; -; 1.
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..1017
FT /note="NLR family CARD domain-containing protein 4"
FT /id="PRO_0000419974"
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 649..672
FT /note="LRR 2"
FT REPEAT 728..751
FT /note="LRR 3"
FT REPEAT 755..778
FT /note="LRR 4"
FT REPEAT 780..805
FT /note="LRR 5"
FT REPEAT 817..840
FT /note="LRR 6"
FT REPEAT 841..863
FT /note="LRR 7"
FT REPEAT 871..895
FT /note="LRR 8"
FT REPEAT 904..926
FT /note="LRR 9"
FT REPEAT 929..956
FT /note="LRR 10"
FT REPEAT 958..978
FT /note="LRR 11"
FT REPEAT 992..1014
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 1017 AA; 115578 MW; 6D8CA970E844461F CRC64;
MNFIKENSQV LIQRMGMTVI KQILDELFVW NVMNYEEVNV ICGEKFEQDA ARGVIHMILK
KGSEACNLFL KSLEKWNYPL FQELHGLSLF HQMSEEDLDD LAQELKYFYQ SPSFLNFYPL
GEDIDIMFNL KSTFTEPVLW KKDQHHHRLE QLTLSGLLDT LQSPCIIEGE SGKGKSTLLQ
RIAMLWASGE CQALTKFKLV FFLRLSRAQG GLFETLSDQL LDIPDVISKQ TFMARLLKLR
QRVLFLLDGY NEFKAQNCPE IEALIKENHR FKNMVIVTTT TESLRHIRQF GALIAEVGDM
TESSAQALIQ EVLRKEFAED LLLQIQKSRC LRNLMKTPLF VVITCAIQMG KSEFHSHTQT
TLFCTFYDLL INKNRHKRKG LAPSEVTQSL DHCGDLALEG VFSRRFDFEP DDLSNVNEDV
LLTTGLLCKY TAQRFKPKYK FFHQSFQEYT AGRRLSSLLT SGEPAEVTKG NGHLQKMVSI
SDITSKYSNL LLYTCGSSAE ATRTVLKHLS SVYQHGSLLG LSVTKRPLWR QESMQNMKST
TVQEILKAIN INSFTECGIN LFHESISTSS LSKEFEDFFR GKSLYINSEN IPDYLFDFFE
DLPNCASALD FVKLDFYGGA VRDISGNQDQ EFSGTYIPSR AVSLFFNWKQ EFKTLDVTLR
DFCKLSKKDI KYLEKIFSSA TSLRLHIKRC VGMAGSLSSV LSTCKNIHSL IVEASPLTLE
DEQHITSVTN LQTLGVHDLQ IQRLPGGLTD NLGNLKNLMK LILDNIQMNE EDALKLAEGL
TNLKKMCLLR LTHLSDIGEG MDYIVKSLSA EPCDLKEIQL VSCCLSGNAV KTLAQNLHNL
ARLSILDLSE NHLEKDGKEA LQQLIDRLHI LEQLTVLMLP WCGDVRVSLA RLLEQLERVP
QLVKLGLKNW RLTDAEIRIL GVFFEKNPLE NFQQLDLAGN CVSSDGWLAF MSGFENLKEL
VFFDFSTKGL LPDASLVRKL SHVLSKLTFL QEVQLVGWQL DDDDVSVLKG AFKLVIA
