Q96P20
EV
Gene name |
NLRP3 |
Protein name |
NACHT, LRR and PYD domains-containing protein 3 |
Names |
Angiotensin/vasopressin receptor AII/AVP-like, Caterpiller protein 1.1, CLR1.1, Cold-induced autoinflammatory syndrome 1 protein, Cryopyrin, PYRIN-containing APAF1-like protein 1 |
Species |
Homo sapiens (Human) |
KEGG Pathway |
hsa:114548 |
EC number |
|
Protein Class |
NACHT, LRR AND PYD DOMAINS-CONTAINING PROTEIN 12 (PTHR45690) |
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)
Target domain |
1-90 (PYRIN domain) |
Relief mechanism |
Partner binding |
Assay |
Deletion assay |
Accessory elements
No accessory elements
Autoinhibited structure
Activated structure
17 structures for Q96P20
| Entry ID | Method | Resolution | Chain | Position | Source |
|---|---|---|---|---|---|
| 2NAQ | NMR | - | A | 3-93 | PDB |
| 3QF2 | X-ray | 170 A | A/B | 3-112 | PDB |
| 6NPY | EM | 380 A | A | 3-1036 | PDB |
| 7ALV | X-ray | 283 A | A | 131-679 | PDB |
| 7PZC | EM | 390 A | A/B/C/D/E/F/G/H/I/J | 1-1036 | PDB |
| 7PZD | EM | 360 A | G/H/I/J/K/L/M/N/O/P/Q/R/S/T/U/V/W/X | 3-110 | PDB |
| 7VTP | EM | 323 A | A/B/C/D/E/F | 130-1036 | PDB |
| 7ZGU | EM | 340 A | A/B/C/D/E/F | 126-1036 | PDB |
| 8EJ4 | EM | 340 A | A/B/C/D/E/F/G/H/I | 133-1004 | PDB |
| 8ERT | EM | 330 A | A/B/C/D/E/F/G/H/I/J/K/L/M/N/O/P/Q/R/S/T/U/V/W | 1-95 | PDB |
| 8ETR | EM | 350 A | A | 134-676 | PDB |
| 8RI2 | X-ray | 280 A | A | 131-679 | PDB |
| 8SWF | EM | 339 A | A/B/C/D/E/F/G/H | 130-1036 | PDB |
| 8SWK | EM | 432 A | A/B/C/D/E/F | 133-1036 | PDB |
| 8SXN | EM | 404 A | C/D | 133-1036 | PDB |
| 8WSM | X-ray | 270 A | A | 131-679 | PDB |
| AF-Q96P20-F1 | Predicted | AlphaFoldDB |
No variants for Q96P20
| Variant ID(s) | Position | Change | Description | Diseaes Association | Provenance |
|---|---|---|---|---|---|
| No variants for Q96P20 | |||||
5 associated diseases with Q96P20
[MIM: 120100]: Familial cold autoinflammatory syndrome 1 (FCAS1)
A rare autosomal dominant systemic inflammatory disease characterized by recurrent episodes of maculopapular rash associated with arthralgias, myalgias, fever and chills, swelling of the extremities, and conjunctivitis after generalized exposure to cold. Rarely, some patients may also develop late-onset renal amyloidosis. {ECO:0000269|PubMed:11687797, ECO:0000269|PubMed:11992256, ECO:0000269|PubMed:12355493, ECO:0000269|PubMed:12522564, ECO:0000269|PubMed:15593220, ECO:0000269|PubMed:17284928, ECO:0000269|PubMed:24952504}. Note=The disease is caused by variants affecting the gene represented in this entry.
[MIM: 191900]: Muckle-Wells syndrome (MWS)
A hereditary periodic fever syndrome characterized by fever, chronic recurrent urticaria, arthralgias, progressive sensorineural deafness, and reactive renal amyloidosis. The disease may be severe if generalized reactive amyloidosis occurs. {ECO:0000269|PubMed:11687797, ECO:0000269|PubMed:11992256, ECO:0000269|PubMed:12355493, ECO:0000269|PubMed:15593220, ECO:0000269|PubMed:24952504}. Note=The disease is caused by variants affecting the gene represented in this entry.
[MIM: 607115]: Chronic infantile neurologic cutaneous and articular syndrome (CINCA)
Rare congenital inflammatory disorder characterized by a triad of neonatal onset of cutaneous symptoms, chronic meningitis, and joint manifestations with recurrent fever and inflammation. {ECO:0000269|PubMed:12032915, ECO:0000269|PubMed:12483741, ECO:0000269|PubMed:14630794, ECO:0000269|PubMed:15231984, ECO:0000269|PubMed:15334500, ECO:0000269|PubMed:15593220, ECO:0000269|PubMed:24952504}. Note=The disease is caused by variants affecting the gene represented in this entry.
[MIM: 148200]: Keratoendothelitis fugax hereditaria (KEFH)
An autosomal dominant corneal disease that periodically, and fleetingly, affects the corneal endothelium, stroma, and vision, eventually leading to central corneal stromal opacities in some patients. The disease is characterized by unilateral attacks of ocular pain, pericorneal injection, and photophobia. The acute symptoms vanish in 1-2 days but vision remains blurry for several weeks. The attacks start at the age of 3-12 years and can affect either eye. They generally decrease in frequency and get milder with age. {ECO:0000269|PubMed:29366613}. Note=The disease is caused by variants affecting the gene represented in this entry.
[MIM: 617772]: Deafness, autosomal dominant, 34, with or without inflammation (DFNA34)
A form of sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information. DFNA34 is a postlingual, slowly progressive form with variable severity and variable additional features. Some DFNA34 patients have autoinflammatory manifestations. {ECO:0000269|PubMed:28847925}. Note=The disease may be caused by variants affecting the gene represented in this entry.
Without disease ID
- A rare autosomal dominant systemic inflammatory disease characterized by recurrent episodes of maculopapular rash associated with arthralgias, myalgias, fever and chills, swelling of the extremities, and conjunctivitis after generalized exposure to cold. Rarely, some patients may also develop late-onset renal amyloidosis. {ECO:0000269|PubMed:11687797, ECO:0000269|PubMed:11992256, ECO:0000269|PubMed:12355493, ECO:0000269|PubMed:12522564, ECO:0000269|PubMed:15593220, ECO:0000269|PubMed:17284928, ECO:0000269|PubMed:24952504}. Note=The disease is caused by variants affecting the gene represented in this entry.
- A hereditary periodic fever syndrome characterized by fever, chronic recurrent urticaria, arthralgias, progressive sensorineural deafness, and reactive renal amyloidosis. The disease may be severe if generalized reactive amyloidosis occurs. {ECO:0000269|PubMed:11687797, ECO:0000269|PubMed:11992256, ECO:0000269|PubMed:12355493, ECO:0000269|PubMed:15593220, ECO:0000269|PubMed:24952504}. Note=The disease is caused by variants affecting the gene represented in this entry.
- Rare congenital inflammatory disorder characterized by a triad of neonatal onset of cutaneous symptoms, chronic meningitis, and joint manifestations with recurrent fever and inflammation. {ECO:0000269|PubMed:12032915, ECO:0000269|PubMed:12483741, ECO:0000269|PubMed:14630794, ECO:0000269|PubMed:15231984, ECO:0000269|PubMed:15334500, ECO:0000269|PubMed:15593220, ECO:0000269|PubMed:24952504}. Note=The disease is caused by variants affecting the gene represented in this entry.
- An autosomal dominant corneal disease that periodically, and fleetingly, affects the corneal endothelium, stroma, and vision, eventually leading to central corneal stromal opacities in some patients. The disease is characterized by unilateral attacks of ocular pain, pericorneal injection, and photophobia. The acute symptoms vanish in 1-2 days but vision remains blurry for several weeks. The attacks start at the age of 3-12 years and can affect either eye. They generally decrease in frequency and get milder with age. {ECO:0000269|PubMed:29366613}. Note=The disease is caused by variants affecting the gene represented in this entry.
- A form of sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information. DFNA34 is a postlingual, slowly progressive form with variable severity and variable additional features. Some DFNA34 patients have autoinflammatory manifestations. {ECO:0000269|PubMed:28847925}. Note=The disease may be caused by variants affecting the gene represented in this entry.
10 regional properties for Q96P20
| Type | Name | Position | InterPro Accession |
|---|---|---|---|
| repeat | Leucine-rich repeat | 740 - 762 | IPR001611-1 |
| repeat | Leucine-rich repeat | 796 - 819 | IPR001611-2 |
| repeat | Leucine-rich repeat | 854 - 872 | IPR001611-3 |
| repeat | Leucine-rich repeat | 910 - 933 | IPR001611-4 |
| repeat | Leucine-rich repeat | 968 - 990 | IPR001611-5 |
| domain | DAPIN domain | 1 - 93 | IPR004020 |
| domain | NACHT nucleoside triphosphatase | 220 - 536 | IPR007111 |
| domain | NACHT-associated domain | 139 - 210 | IPR029495 |
| domain | NOD2, winged helix domain | 466 - 520 | IPR041075 |
| domain | NACHT, LRR and PYD domains-containing protein, helical domain HD2 | 522 - 645 | IPR041267 |
Functions
| Description | ||
|---|---|---|
| EC Number | ||
| Subcellular Localization |
|
|
| PANTHER Family | PTHR45690 | NACHT, LRR AND PYD DOMAINS-CONTAINING PROTEIN 12 |
| PANTHER Subfamily | PTHR45690:SF19 | NACHT, LRR AND PYD DOMAINS-CONTAINING PROTEIN 3 |
| PANTHER Protein Class | defense/immunity protein | |
| 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. |
| cytosol | The part of the cytoplasm that does not contain organelles but which does contain other particulate matter, such as protein complexes. |
| 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. |
| 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. |
5 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. |
| peptidoglycan binding | Interacting selectively and non-covalently, in a non-covalent manner, with peptidoglycan, any of a class of glycoconjugates found in bacterial cell walls. |
| 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. |
22 GO annotations of biological process
| Name | Definition |
|---|---|
| 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. |
| 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 virus | 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 stimulus from a virus. |
| defense response | Reactions, triggered in response to the presence of a foreign body or the occurrence of an injury, which result in restriction of damage to the organism attacked or prevention/recovery from the infection caused by the attack. |
| detection of biotic stimulus | The series of events in which a biotic stimulus, one caused or produced by a living organism, 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. |
| 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 interleukin-1 beta production | Any process that activates or increases the frequency, rate, or extent of interleukin-1 beta 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 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 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. |
| signal transduction | The cellular process in which a signal is conveyed to trigger a change in the activity or state of a cell. Signal transduction begins with reception of a signal (e.g. a ligand binding to a receptor or receptor activation by a stimulus such as light), or for signal transduction in the absence of ligand, signal-withdrawal or the activity of a constitutively active receptor. Signal transduction ends with regulation of a downstream cellular process, e.g. regulation of transcription or regulation of a metabolic process. Signal transduction covers signaling from receptors located on the surface of the cell and signaling via molecules located within the cell. For signaling between cells, signal transduction is restricted to events at and within the receiving cell. |
11 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 |
| Q9NX02 | NLRP2 | NACHT, LRR and PYD domains-containing protein 2 | Homo sapiens (Human) | PR |
| Q86W26 | NLRP10 | NACHT, LRR and PYD domains-containing protein 10 | Homo sapiens (Human) | PR |
| P59046 | NLRP12 | NACHT, LRR and PYD domains-containing protein 12 | Homo sapiens (Human) | SS |
| Q9C000 | NLRP1 | NACHT, LRR and PYD domains-containing protein 1 | 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 |
| A1Z198 | Nlrp1b | NACHT, LRR and PYD domains-containing protein 1b allele 2 | Mus musculus (Mouse) | SS |
| Q2LKU9 | Nlrp1a | NACHT, LRR and PYD domains-containing protein 1a | Mus musculus (Mouse) | SS |
| D4A523 | Nlrp3 | NACHT, LRR and PYD domains-containing protein 3 | Rattus norvegicus (Rat) | SS |
| B0FPE9 | NLRP3 | NACHT, LRR and PYD domains-containing protein 3 | Macaca mulatta (Rhesus macaque) | SS |
| 10 | 20 | 30 | 40 | 50 | 60 |
| MKMASTRCKL | ARYLEDLEDV | DLKKFKMHLE | DYPPQKGCIP | LPRGQTEKAD | HVDLATLMID |
| 70 | 80 | 90 | 100 | 110 | 120 |
| FNGEEKAWAM | AVWIFAAINR | RDLYEKAKRD | EPKWGSDNAR | VSNPTVICQE | DSIEEEWMGL |
| 130 | 140 | 150 | 160 | 170 | 180 |
| LEYLSRISIC | KMKKDYRKKY | RKYVRSRFQC | IEDRNARLGE | SVSLNKRYTR | LRLIKEHRSQ |
| 190 | 200 | 210 | 220 | 230 | 240 |
| QEREQELLAI | GKTKTCESPV | SPIKMELLFD | PDDEHSEPVH | TVVFQGAAGI | GKTILARKMM |
| 250 | 260 | 270 | 280 | 290 | 300 |
| LDWASGTLYQ | DRFDYLFYIH | CREVSLVTQR | SLGDLIMSCC | PDPNPPIHKI | VRKPSRILFL |
| 310 | 320 | 330 | 340 | 350 | 360 |
| MDGFDELQGA | FDEHIGPLCT | DWQKAERGDI | LLSSLIRKKL | LPEASLLITT | RPVALEKLQH |
| 370 | 380 | 390 | 400 | 410 | 420 |
| LLDHPRHVEI | LGFSEAKRKE | YFFKYFSDEA | QARAAFSLIQ | ENEVLFTMCF | IPLVCWIVCT |
| 430 | 440 | 450 | 460 | 470 | 480 |
| GLKQQMESGK | SLAQTSKTTT | AVYVFFLSSL | LQPRGGSQEH | GLCAHLWGLC | SLAADGIWNQ |
| 490 | 500 | 510 | 520 | 530 | 540 |
| KILFEESDLR | NHGLQKADVS | AFLRMNLFQK | EVDCEKFYSF | IHMTFQEFFA | AMYYLLEEEK |
| 550 | 560 | 570 | 580 | 590 | 600 |
| EGRTNVPGSR | LKLPSRDVTV | LLENYGKFEK | GYLIFVVRFL | FGLVNQERTS | YLEKKLSCKI |
| 610 | 620 | 630 | 640 | 650 | 660 |
| SQQIRLELLK | WIEVKAKAKK | LQIQPSQLEL | FYCLYEMQEE | DFVQRAMDYF | PKIEINLSTR |
| 670 | 680 | 690 | 700 | 710 | 720 |
| MDHMVSSFCI | ENCHRVESLS | LGFLHNMPKE | EEEEEKEGRH | LDMVQCVLPS | SSHAACSHGL |
| 730 | 740 | 750 | 760 | 770 | 780 |
| VNSHLTSSFC | RGLFSVLSTS | QSLTELDLSD | NSLGDPGMRV | LCETLQHPGC | NIRRLWLGRC |
| 790 | 800 | 810 | 820 | 830 | 840 |
| GLSHECCFDI | SLVLSSNQKL | VELDLSDNAL | GDFGIRLLCV | GLKHLLCNLK | KLWLVSCCLT |
| 850 | 860 | 870 | 880 | 890 | 900 |
| SACCQDLASV | LSTSHSLTRL | YVGENALGDS | GVAILCEKAK | NPQCNLQKLG | LVNSGLTSVC |
| 910 | 920 | 930 | 940 | 950 | 960 |
| CSALSSVLST | NQNLTHLYLR | GNTLGDKGIK | LLCEGLLHPD | CKLQVLELDN | CNLTSHCCWD |
| 970 | 980 | 990 | 1000 | 1010 | 1020 |
| LSTLLTSSQS | LRKLSLGNND | LGDLGVMMFC | EVLKQQSCLL | QNLGLSEMYF | NYETKSALET |
| 1030 | |||||
| LQEEKPELTV | VFEPSW |