Q3UP24

EV
Gene name
Nlrc4 (Card12, Ipaf)
Protein name
NLR family CARD domain-containing protein 4
Names
Caspase recruitment domain-containing protein 12, Ice protease-activating factor, Ipaf
Species
Mus musculus (Mouse)
KEGG Pathway
mmu:268973
EC number
Protein Class
NLR FAMILY CARD DOMAIN-CONTAINING PROTEIN 4 (PTHR47688)

Descriptions

Nucleotide-binding and oligomerization domain-like receptor (NLR) proteins oligomerize into multiprotein complexes termed inflammasomes when activated. NLRs constitute a crucial component of the cytosolic immunosurveillance system of mammals by detecting the signature components of pathogens and consequently triggering immune responses. The adenosine diphosphate-mediated interaction between the central nucleotide-binding domain (NBD) and the winged-helix domain (WHD) is critical for stabilizing the closed conformation. In addition, the helical domain HD2 repressively contacts a conserved and functionally important α-helix of the NBD. The C-terminal leucine-rich repeat (LRR) domain is positioned to sterically occlude one side of the NBD domain and consequently sequester NLRC4 in monomeric state. Disruption of ADP-mediated NBD-WHD or NBD-HD2/NBD-LRR interactions resulted in constitutive activation of NLRC4.

Autoinhibitory domains (AIDs)

356-463 (WHD) EV

Target domain

95-298 (Nucleotide-binding domain, NBD)

Relief mechanism

Others

Assay

Structural analysis, Deletion assay

464-580 (HD2) EV

Target domain

95-298 (Nucleotide-binding domain, NBD)

Relief mechanism

Others

Assay

Structural analysis, Deletion assay, Mutagenesis experiment

581-1024 (LRR) EV

Target domain

95-298 (Nucleotide-binding domain, NBD)

Relief mechanism

Ligand binding

Assay

Structural analysis, Deletion assay

Accessory elements

No accessory elements

References

Autoinhibited structure

Activated structure

5 structures for Q3UP24

Entry ID Method Resolution Chain Position Source
3JBL EM 450 A A/B/C/D/E/F/G/H/I/J/K 93-1024 PDB
4KXF X-ray 320 A B/D/F/H/K/L/N/P 1-1024 PDB
5AJ2 EM 4000 A PDB
6B5B EM 520 A B/C 1-1024 PDB
AF-Q3UP24-F1 Predicted AlphaFoldDB

22 variants for Q3UP24

Variant ID(s) Position Change Description Diseaes Association Provenance
rs260110611 30 L>S No Ensembl
rs50842374 99 N>S No Ensembl
rs242419320 206 R>S No Ensembl
rs224088761 295 A>V No Ensembl
rs218687347 348 Q>H No Ensembl
rs236103197 351 R>K No Ensembl
rs49937915 385 D>N No Ensembl
rs231646020 387 A>T No Ensembl
rs238764373 628 E>K No Ensembl
rs255864832 639 P>S No Ensembl
rs108159529 670 N>S No Ensembl
rs250835686 737 G>D No Ensembl
rs29502769 756 I>V No Ensembl
rs46190029 782 N>S No Ensembl
rs224857287 788 R>Q No Ensembl
rs264573917 796 L>F No Ensembl
rs108684273 799 T>I No Ensembl
rs233690887 819 S>P No Ensembl
rs108575465 908 G>R No Ensembl
rs50053453 920 R>G No Ensembl
rs50575999 948 C>R No Ensembl
rs51771173 1013 S>N No Ensembl

No associated diseases with Q3UP24

3 regional properties for Q3UP24

Type Name Position InterPro Accession
domain CARD domain 1 - 88 IPR001315
domain NACHT nucleoside triphosphatase 163 - 311 IPR007111
domain NLRC4, helical domain 465 - 579 IPR040535

Functions

Description
EC Number
Subcellular Localization
  • Cytoplasm, cytosol
  • Inflammasome
PANTHER Family PTHR47688 NLR FAMILY CARD DOMAIN-CONTAINING PROTEIN 4
PANTHER Subfamily PTHR47688:SF1 NLR FAMILY CARD DOMAIN-CONTAINING PROTEIN 4
PANTHER Protein Class
PANTHER Pathway Category No pathway information available

2 GO annotations of cellular component

Name Definition
cytosol The part of the cytoplasm that does not contain organelles but which does contain other particulate matter, such as protein complexes.
IPAF inflammasome complex An inflammasome complex that consists of three components, IPAF, NAIP and caspase-1, and includes among its functions the sensing of flagellin derived from Legionella pneumophila, Salmonella typhimurium, Pseudomonas aeruginosa and Shigella flexneri.

5 GO annotations of molecular function

Name Definition
ATP binding Binding to ATP, adenosine 5'-triphosphate, a universally important coenzyme and enzyme regulator.
caspase binding Binding to a caspase family protein.
endopeptidase activator activity Binds to and increases the activity of an endopeptidase, any enzyme that hydrolyzes nonterminal peptide bonds in polypeptides.
identical protein binding Binding to an identical protein or proteins.
protein homodimerization activity Binding to an identical protein to form a homodimer.

16 GO annotations of biological process

Name Definition
activation of cysteine-type endopeptidase activity Any process that initiates the activity of the inactive enzyme cysteine-type endopeptidase.
activation of cysteine-type endopeptidase activity involved in apoptotic process Any process that initiates the activity of the inactive enzyme cysteine-type endopeptidase in the context of an apoptotic process.
activation of innate immune response Any process that initiates an innate immune response. Innate immune responses are defense responses mediated by germline encoded components that directly recognize components of potential pathogens. Examples of this process include activation of the hypersensitive response of Arabidopsis thaliana and activation of any NOD or TLR signaling pathway in vertebrate species.
apoptotic process A programmed cell death process which begins when a cell receives an internal (e.g. DNA damage) or external signal (e.g. an extracellular death ligand), and proceeds through a series of biochemical events (signaling pathway phase) which trigger an execution phase. The execution phase is the last step of an apoptotic process, and is typically characterized by rounding-up of the cell, retraction of pseudopodes, reduction of cellular volume (pyknosis), chromatin condensation, nuclear fragmentation (karyorrhexis), plasma membrane blebbing and fragmentation of the cell into apoptotic bodies. When the execution phase is completed, the cell has died.
defense response to bacterium Reactions triggered in response to the presence of a bacterium that act to protect the cell or organism.
detection of bacterium The series of events in which a stimulus from a bacterium is received and converted into a molecular signal.
inflammatory response The immediate defensive reaction (by vertebrate tissue) to infection or injury caused by chemical or physical agents. The process is characterized by local vasodilation, extravasation of plasma into intercellular spaces and accumulation of white blood cells and macrophages.
innate immune response Innate immune responses are defense responses mediated by germline encoded components that directly recognize components of potential pathogens.
positive regulation of apoptotic process Any process that activates or increases the frequency, rate or extent of cell death by apoptotic process.
positive regulation of interleukin-1 beta production Any process that activates or increases the frequency, rate, or extent of interleukin-1 beta production.
positive regulation of NF-kappaB transcription factor activity Any process that activates or increases the frequency, rate or extent of activity of the transcription factor NF-kappaB.
positive regulation of protein processing Any process that increases the rate, frequency or extent of protein maturation by peptide bond cleavage.
protein homooligomerization The process of creating protein oligomers, compounds composed of a small number, usually between three and ten, of identical component monomers. Oligomers may be formed by the polymerization of a number of monomers or the depolymerization of a large protein polymer.
pyroptosis A caspase-1-dependent cell death subroutine that is associated with the generation of pyrogenic mediators such as IL-1beta and IL-18.
regulation of apoptotic process Any process that modulates the occurrence or rate of cell death by apoptotic process.
regulation of cysteine-type endopeptidase activity involved in apoptotic process Any process that modulates the activity of a cysteine-type endopeptidase involved in apoptosis.

22 homologous proteins in AiPD

UniProt AC Gene Name Protein Name Species Evidence Code
F1MHT9 NLRC4 NLR family CARD domain-containing protein 4 Bos taurus (Bovine) SS
Q9NPP4 NLRC4 NLR family CARD domain-containing protein 4 Homo sapiens (Human) SS
F1M649 Nlrc4 NLR family CARD domain-containing protein 4 Rattus norvegicus (Rat) SS
Q9LRR4 RPPL1 Putative disease resistance RPP13-like protein 1 Arabidopsis thaliana (Mouse-ear cress) PR
Q8W3K3 At1g58400 Putative disease resistance protein At1g58400 Arabidopsis thaliana (Mouse-ear cress) PR
Q39214 RPM1 Disease resistance protein RPM1 Arabidopsis thaliana (Mouse-ear cress) PR
Q9FJB5 RPP8L3 Disease resistance RPP8-like protein 3 Arabidopsis thaliana (Mouse-ear cress) PR
Q9T048 At4g27190 Disease resistance protein At4g27190 Arabidopsis thaliana (Mouse-ear cress) PR
Q9XIF0 At1g59780 Putative disease resistance protein At1g59780 Arabidopsis thaliana (Mouse-ear cress) PR
O22727 At1g61190 Probable disease resistance protein At1g61190 Arabidopsis thaliana (Mouse-ear cress) PR
P0C8S1 RPP8L2 Probable disease resistance RPP8-like protein 2 Arabidopsis thaliana (Mouse-ear cress) PR
Q9C646 RXW24L Probable disease resistance protein RXW24L Arabidopsis thaliana (Mouse-ear cress) PR
O64790 At1g61300 Probable disease resistance protein At1g61300 Arabidopsis thaliana (Mouse-ear cress) PR
Q9FKZ0 At5g66910 Probable disease resistance protein At5g66910 Arabidopsis thaliana (Mouse-ear cress) PR
P60838 SUMM2 Disease resistance protein SUMM2 Arabidopsis thaliana (Mouse-ear cress) PR
F4J339 RPP1 Probable disease resistance protein RPP1 Arabidopsis thaliana (Mouse-ear cress) PR
Q38834 RPP13L4 Disease resistance RPP13-like protein 4 Arabidopsis thaliana (Mouse-ear cress) PR
O64973 RPS5 Disease resistance protein RPS5 Arabidopsis thaliana (Mouse-ear cress) PR
Q940K0 UNI Disease resistance protein UNI Arabidopsis thaliana (Mouse-ear cress) PR
O64789 At1g61310 Probable disease resistance protein At1g61310 Arabidopsis thaliana (Mouse-ear cress) PR
Q9XGM3 RPS4 Disease resistance protein RPS4 Arabidopsis thaliana (Mouse-ear cress) PR
O23317 At4g14610 Probable disease resistance protein At4g14610 Arabidopsis thaliana (Mouse-ear cress) PR
10 20 30 40 50 60
MNFIRNNRRA LIQRMGLTVT KQICDDLFAL NVLNNQEANV IYCEPLEQEA ARKIIHMTMQ
70 80 90 100 110 120
KGSAACNLFL KSLENWDYFV YQDLTGQNLS YQVTEEDLNV LAQNLKDLYN SPAFLNFYPL
130 140 150 160 170 180
GEDIDIIFNL EKTFTEPIMW KKDHRHHRVE QLTLGSLLEA LKSPCLIEGE SGKGKSTLLQ
190 200 210 220 230 240
RIAMLWASGG CRALKGFRLV FFIHLRSARG GLFETLYDQL LNIPDFISKP TFKALLLKLH
250 260 270 280 290 300
KEVLFLLDGY NEFHPQNCPE IEALIKENHR FKNMVIVTTT TECLRHIRHV GALTAEVGDM
310 320 330 340 350 360
TEDSAKDLIE AVLVPDQVER LWAQIQESRC LRNLMKTPLF VVITCAIQMG RQEFQAHTQT
370 380 390 400 410 420
MLFQTFYDLL IQKNSHRYRG GASGDFARSL DYCGDLALEG VFAHKFDFEP EHGSSMNEDV
430 440 450 460 470 480
LVTIGLLCKY TAQRLKPTYK FFHKSFQEYT AGRRLSSLLT SKEPEEVSKG NSYLNKMVSI
490 500 510 520 530 540
SDITSLYGNL LLYTCGSSTE ATRAVMRHLA MVYQHGSLQG LSVTKRPLWR QESIQSLRNT
550 560 570 580 590 600
TEQDVLKAIN VNSFVECGIN LFSESMSKSD LSQEFEAFFQ GKSLYINSEN IPDYLFDFFE
610 620 630 640 650 660
YLPNCASALD FVKLDFYERA TESQDKAEEN VPGVHTEGPS ETYIPPRAVS LFFNWKQEFK
670 680 690 700 710 720
TLEVTLRDIN KLNKQDIKYL GKIFSSATNL RLHIKRCAAM AGRLSSVLRT CKNMHTLMVE
730 740 750 760 770 780
ASPLTTDDEQ YITSVTGLQN LSIHRLHTQQ LPGGLIDSLG NLKNLERLIL DDIRMNEEDA
790 800 810 820 830 840
KNLAEGLRSL KKMRLLHLTH LSDIGEGMDY IVKSLSEESC DLQEMKLVAC CLTANSVKVL
850 860 870 880 890 900
AQNLHNLIKL SILDISENYL EKDGNEALQE LIGRLGVLGE LTTLMLPWCW DVHTSLPKLL
910 920 930 940 950 960
KQLEGTPGLA KLGLKNWRLR DEEIKSLGEF LEMNPLRDLQ QLDLAGHCVS SDGWLYFMNV
970 980 990 1000 1010 1020
FENLKQLVFF DFSTEEFLPD AALVRKLSQV LSKLTLLQEV KLTGWEFDDY DISAIKGTFK
LVTA