D4A523

SS
Gene name
Nlrp3
Protein name
NACHT, LRR and PYD domains-containing protein 3
Names
Cold autoinflammatory syndrome 1 protein homolog, Cryopyrin, Mast cell maturation-associated-inducible protein 1, PYRIN-containing APAF1-like protein 1
Species
Rattus norvegicus (Rat)
KEGG Pathway
rno:287362
EC number
Protein Class

Descriptions

PYPAF1 (PYRIN-containing Apaf1-like protein 1) is a novel PYRIN-containing signaling protein that belongs to the nucleotide-binding site/leucine-rich repeat (NBS/LRR) family of signaling proteins. C-terminal leucine-rich repeats (LRRs) may function as a negative regulator of PYPAF1 activity. PYPAF1 and ASC function to regulate the activation of NF-B.

Autoinhibitory domains (AIDs)

741-990 (Leucine-rich repeats) SS

Target domain

1-93 (PYRIN domain)

Relief mechanism

Partner binding

Assay

Accessory elements

No accessory elements

References

Autoinhibited structure

Activated structure

1 structures for D4A523

Entry ID Method Resolution Chain Position Source
AF-D4A523-F1 Predicted AlphaFoldDB

1 variants for D4A523

Variant ID(s) Position Change Description Diseaes Association Provenance
rs106539953 213 H>R No Ensembl

No associated diseases with D4A523

10 regional properties for D4A523

Type Name Position InterPro Accession
repeat Leucine-rich repeat 738 - 761 IPR001611-1
repeat Leucine-rich repeat 796 - 818 IPR001611-2
repeat Leucine-rich repeat 852 - 875 IPR001611-3
repeat Leucine-rich repeat 909 - 932 IPR001611-4
repeat Leucine-rich repeat 966 - 990 IPR001611-5
domain DAPIN domain 1 - 93 IPR004020
domain NACHT nucleoside triphosphatase 218 - 417 IPR007111
domain NACHT-associated domain 137 - 208 IPR029495
domain NOD2, winged helix domain 463 - 518 IPR041075
domain NACHT, LRR and PYD domains-containing protein, helical domain HD2 520 - 644 IPR041267

Functions

Description
EC Number
Subcellular Localization
  • Cytoplasm, cytosol
  • Inflammasome
  • Cytoplasm, cytoskeleton, microtubule organizing center
  • Golgi apparatus membrane
  • Endoplasmic reticulum
  • Mitochondrion
  • Secreted
  • Nucleus
  • In macrophages, under resting conditions, mainly located in the cytosol and on membranes of various organelles, such as endoplasmic reticulum, mitochondria and Golgi: forms an inactive double-ring cage that is primarily localized on membranes
  • Upon activation, NLRP3 is transported to microtubule organizing center (MTOC), where it is unlocked by NEK7, leading to its relocalization to dispersed trans-Golgi network (dTGN) vesicle membranes for the formation of an active inflammasome complex
  • Recruited to dTGN vesicle membranes by binding to phosphatidylinositol 4-phosphate (PtdIns4P)
  • After the induction of pyroptosis, inflammasome specks are released into the extracellular space where they can further promote IL1B processing and where they can be engulfed by macrophages
  • Phagocytosis induces lysosomal damage and inflammasome activation in the recipient cells
  • In the Th2 subset of CD4(+) helper T-cells, mainly located in the nucleus
  • Nuclear localization depends upon KPNA2
  • In the Th1 subset of CD4(+) helper T-cells, mainly cytoplasmic
PANTHER Family
PANTHER Subfamily
PANTHER Protein Class
PANTHER Pathway Category No pathway information available

7 GO annotations of cellular component

Name Definition
cytoplasm The contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures.
endoplasmic reticulum The irregular network of unit membranes, visible only by electron microscopy, that occurs in the cytoplasm of many eukaryotic cells. The membranes form a complex meshwork of tubular channels, which are often expanded into slitlike cavities called cisternae. The ER takes two forms, rough (or granular), with ribosomes adhering to the outer surface, and smooth (with no ribosomes attached).
extracellular region The space external to the outermost structure of a cell. For cells without external protective or external encapsulating structures this refers to space outside of the plasma membrane. This term covers the host cell environment outside an intracellular parasite.
Golgi membrane The lipid bilayer surrounding any of the compartments of the Golgi apparatus.
inflammasome complex A cytosolic protein complex that is capable of activating caspase-1.
NLRP3 inflammasome complex An inflammasome complex that consists of three components, NLRP3 (NALP3), PYCARD and caspase-1. It is activated upon exposure to whole pathogens, as well as a number of structurally diverse pathogen- and danger-associated molecular patterns (PAMPs and DAMPs) and environmental irritants. Whole pathogens demonstrated to activate the NLRP3 inflammasome complex include the fungi Candida albicans and Saccharomyces cerevisiae, bacteria that produce pore-forming toxins, including Listeria monocytogenes and Staphylococcus aureus, and viruses such as Sendai virus, adenovirus, and influenza virus.
nucleus A membrane-bounded organelle of eukaryotic cells in which chromosomes are housed and replicated. In most cells, the nucleus contains all of the cell's chromosomes except the organellar chromosomes, and is the site of RNA synthesis and processing. In some species, or in specialized cell types, RNA metabolism or DNA replication may be absent.

4 GO annotations of molecular function

Name Definition
ATP binding Binding to ATP, adenosine 5'-triphosphate, a universally important coenzyme and enzyme regulator.
DNA-binding transcription factor binding Binding to a DNA-binding transcription factor, a protein that interacts with a specific DNA sequence (sometimes referred to as a motif) within the regulatory region of a gene to modulate transcription.
identical protein binding Binding to an identical protein or proteins.
sequence-specific DNA binding Binding to DNA of a specific nucleotide composition, e.g. GC-rich DNA binding, or with a specific sequence motif or type of DNA e.g. promotor binding or rDNA binding.

30 GO annotations of biological process

Name Definition
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.
acute inflammatory response Inflammation which comprises a rapid, short-lived, relatively uniform response to acute injury or antigenic challenge and is characterized by accumulations of fluid, plasma proteins, and granulocytic leukocytes. An acute inflammatory response occurs within a matter of minutes or hours, and either resolves within a few days or becomes a chronic inflammatory response.
cellular response to lipopolysaccharide Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a lipopolysaccharide stimulus; lipopolysaccharide is a major component of the cell wall of gram-negative bacteria.
cellular response to peptidoglycan Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a peptidoglycan stimulus. Peptidoglycan is a bacterial cell wall macromolecule.
defense response to Gram-positive bacterium Reactions triggered in response to the presence of a Gram-positive bacterium that act to protect the cell or organism.
defense response to virus Reactions triggered in response to the presence of a virus that act to protect the cell or organism.
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.
leukocyte migration involved in inflammatory response The movement of a leukocyte within or between different tissues and organs of the body contributing to an inflammatory response.
negative regulation of acute inflammatory response Any process that stops, prevents, or reduces the frequency, rate, or extent of an acute inflammatory response.
negative regulation of inflammatory response Any process that stops, prevents, or reduces the frequency, rate or extent of the inflammatory response.
negative regulation of interleukin-1 beta production Any process that stops, prevents, or reduces the frequency, rate, or extent of interleukin-1 beta production.
negative regulation of NF-kappaB transcription factor activity Any process that stops, prevents, or reduces the frequency, rate or extent of the activity of the transcription factor NF-kappaB.
negative regulation of NIK/NF-kappaB signaling Any process that stops, prevents or reduces the frequency, rate or extent of NIK/NF-kappaB signaling.
NLRP3 inflammasome complex assembly The aggregation, arrangement and bonding together of a set of components to form the NLRP3 inflammasome complex, occurring at the level of an individual cell.
positive regulation of cysteine-type endopeptidase activity involved in apoptotic process Any process that activates or increases the activity of a cysteine-type endopeptidase involved in the apoptotic process.
positive regulation of cytokine production involved in immune response Any process that activates or increases the frequency, rate, or extent of cytokine production that contributes to an immune response.
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 interleukin-13 production Any process that activates or increases the frequency, rate, or extent of interleukin-13 production.
positive regulation of interleukin-4 production Any process that activates or increases the frequency, rate, or extent of interleukin-4 production.
positive regulation of interleukin-5 production Any process that activates or increases the frequency, rate, or extent of interleukin-5 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 T-helper 17 cell differentiation Any process that activates or increases the frequency, rate or extent of T-helper 17 cell differentiation.
positive regulation of T-helper 2 cell cytokine production Any process that activates or increases the frequency, rate or extent of T-helper 2 cell cytokine production.
positive regulation of T-helper 2 cell differentiation Any process that activates or increases the frequency, rate or extent of T-helper 2 cell differentiation.
positive regulation of transcription by RNA polymerase II Any process that activates or increases the frequency, rate or extent of transcription from an RNA polymerase II promoter.
positive regulation of type 2 immune response Any process that activates or increases the frequency, rate, or extent of a type 2 immune response.
regulation of inflammatory response Any process that modulates the frequency, rate or extent of the inflammatory response, the immediate defensive reaction (by vertebrate tissue) to infection or injury caused by chemical or physical agents.
response to ethanol Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of an ethanol stimulus.
response to organic cyclic compound Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of an organic cyclic compound stimulus.

5 homologous proteins in AiPD

UniProt AC Gene Name Protein Name Species Evidence Code
A6QLE5 NLRP3 NACHT, LRR and PYD domains-containing protein 3 Bos taurus (Bovine) SS
Q96P20 NLRP3 NACHT, LRR and PYD domains-containing protein 3 Homo sapiens (Human) EV
E9Q5R7 Nlrp12 NACHT, LRR and PYD domains-containing protein 12 Mus musculus (Mouse) SS
Q8R4B8 Nlrp3 NACHT, LRR and PYD domains-containing protein 3 Mus musculus (Mouse) SS
B0FPE9 NLRP3 NACHT, LRR and PYD domains-containing protein 3 Macaca mulatta (Rhesus macaque) SS
10 20 30 40 50 60
MKMMSVRCKL AQYLEDLEDV DLKKFKMHLE DYPPEKGCVP IPRGQMEKAD HLDLATLMID
70 80 90 100 110 120
FNGEEKAWGM AVWIFAAINR RDLWEKAKKD QPEWNDACTS NLSMVCQEDS LEEEWIGLLG
130 140 150 160 170 180
YLSRISICKK KKDYCKIYRR HVRSRFYSIK DRNARLGESV DLNRRYTQLQ LVKEHPSKQE
190 200 210 220 230 240
REHELLTIGR TKMWDRPMSS LKLELLFEPE DEHLEPVHTV VFQGAAGIGK TILARKIMLD
250 260 270 280 290 300
WALGKLFKDK FDYLFFIHCR EVSLRAPKSL ADLIISCWPD PNPPVCKILC KPSRILFLMD
310 320 330 340 350 360
GFDELQGAFD EHIEEVCTDW QKAVRGDILL SSLIRKKLLP KASLLITTRP VALEKLQHLL
370 380 390 400 410 420
DHPRHVEILG FSEAKRKEYF FKYFSNELQA REAFRLIQEN EILFTMCFIP LVCWIVCTGL
430 440 450 460 470 480
KQQMETGKSL AQTSKTTTAV YVFFLSSLLQ SRGGIEEHLF SAYLPGLCSL AADGIWNQKI
490 500 510 520 530 540
LFEECDLRKH GLQKTDVSAF LRMNVFQKEV DCERFYSFSH MTFQEFFAAM YYLLEEEEEG
550 560 570 580 590 600
VTVRKGPEGC SDLLNRDVKV LLENYGKFEK GYLIFVVRFL FGLVNQERTS YLEKKLSCKI
610 620 630 640 650 660
SQQVRLELLK WIEVKAKAKK LQRQPSQLEL FYCLYEMQEE DFVQSAMGHF PKIEINLSTR
670 680 690 700 710 720
MDHVVSSFCI KNCHRVKTLS LGFLHNSPKE EEEEKRGSQP LDQVQCVFPD PHVACSSRLV
730 740 750 760 770 780
NCCLTSSFCR GLFSSLSTNQ SLTELDLSDN TLGDPGMRVL CEALQHPGCN IQRLWLGRCG
790 800 810 820 830 840
LTHQCCFNIS SVLSSSQKLV ELDLSDNALG DFGVRLLCVG LKHLLCNLQK LWLVSCCLTS
850 860 870 880 890 900
ACCQDLALVL SSNHSLTRLY IGENALGDSG VQVLCEKMKD PQCNLQKLGL VNSGLTSLCC
910 920 930 940 950 960
SALTSVLKTN QNLTHLYLRS NALGDMGLKL LCEGLLHPDC KLQMLELDNC SLTSHSCWDL
970 980 990 1000 1010 1020
STILTHNQSL RKLNLSNNDL GDLCVVTLCE VLKQQGCLLQ SLQLGEMYLN CETKRTLEAL
1030
QEEKPELTVV FEISW