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

1-93 (PYRIN domain)

Relief mechanism

Partner binding

Assay

Accessory elements

No accessory elements

Autoinhibited structure

Activated structure

1 structures for A6QLE5

Entry ID Method Resolution Chain Position Source
AF-A6QLE5-F1 Predicted AlphaFoldDB

77 variants for A6QLE5

Variant ID(s) Position Change Description Diseaes Association Provenance
rs433301821 4 V>G No Ensembl
rs453408201 10 L>V No Ensembl
rs473461291 19 D>E No Ensembl
rs441958228 20 I>L No Ensembl
rs462074560 24 K>T No Ensembl
rs475670082 26 K>M No Ensembl
rs797355053 30 E>K No Ensembl
rs444314508 32 Y>H No Ensembl
rs457827892 39 T>P No Ensembl
rs477787397 44 G>V No Ensembl
rs460043403 45 Q>L No Ensembl
rs480269849 46 T>P No Ensembl
rs468910496 72 K>N No Ensembl
rs464788546 89 R>M No Ensembl
rs433338848 89 R>S No Ensembl
rs464788546 89 R>T No Ensembl
rs453444017 92 P>S No Ensembl
rs521994202 98 N>D No Ensembl
rs465916000 132 C>R No Ensembl
rs434529222 136 R>S No Ensembl
rs454521552 137 K>E No Ensembl
rs455677942 144 Q>H No Ensembl
rs209193682 147 K>E No Ensembl
rs468227386 157 V>G No Ensembl
rs436742907 164 T>A No Ensembl
rs437971300 223 G>V No Ensembl
rs456695237 275 S>R No Ensembl
rs476662587 277 C>Y No Ensembl
rs438968294 281 N>T No Ensembl
rs472771549 286 K>Q No Ensembl
rs461374673 326 D>E No Ensembl
rs443602189 364 H>Q No Ensembl
rs445960299 377 E>* No Ensembl
rs466009313 378 Y>N No Ensembl
rs448182859 379 F>C No Ensembl
rs479640480 379 F>I No Ensembl
rs440730015 392 A>S No Ensembl
rs436760990 432 T>A No Ensembl
rs463979002 503 N>T No Ensembl
rs432691582 517 F>V No Ensembl
rs452666968 518 I>L No Ensembl
rs472855607 636 Q>H No Ensembl
rs434953212 650 K>E No Ensembl
rs475070516 667 C>F No Ensembl
rs380251179 674 V>M No Ensembl
rs443735320 678 S>A No Ensembl
rs463801129 681 L>F No Ensembl
rs470963418 684 N>T No Ensembl
rs439567293 688 E>D No Ensembl
rs459545078 691 E>Q No Ensembl
rs479678598 691 E>V No Ensembl
rs448140012 692 E>Q No Ensembl
rs481763189 699 H>Q No Ensembl
rs450492841 703 S>T No Ensembl
rs464017925 704 V>G No Ensembl
rs445157407 723 S>R No Ensembl
rs465311100 725 C>S No Ensembl
rs481420412 757 C>S No Ensembl
rs447466662 764 G>C No Ensembl
rs455420722 775 C>F No Ensembl
rs43571544 780 Q>K No Ensembl
rs444108981 796 V>M No Ensembl
rs471377654 807 D>E No Ensembl
rs457815029 807 D>V No Ensembl
rs439947097 808 F>L No Ensembl
rs460093027 809 G>V No Ensembl
rs797135931 868 G>R No Ensembl
rs800319544 882 Q>K No Ensembl
rs136970780 894 G>S No Ensembl
rs384147601 954 W>* No Ensembl
rs450877647 958 T>S No Ensembl
rs446702063 959 L>H No Ensembl
rs477977729 959 L>V No Ensembl
rs466664273 974 N>H No Ensembl
rs455569088 998 L>Q No Ensembl
rs209843504 1011 R>H No Ensembl
rs465023505 1025 I>T No Ensembl

No associated diseases with A6QLE5

10 regional properties for A6QLE5

Type Name Position InterPro Accession
repeat Leucine-rich repeat 737 - 756 IPR001611-1
repeat Leucine-rich repeat 791 - 814 IPR001611-2
repeat Leucine-rich repeat 848 - 867 IPR001611-3
repeat Leucine-rich repeat 905 - 928 IPR001611-4
repeat Leucine-rich repeat 962 - 985 IPR001611-5
domain DAPIN domain 1 - 93 IPR004020
domain NACHT nucleoside triphosphatase 217 - 533 IPR007111
domain NACHT-associated domain 134 - 207 IPR029495
domain NOD2, winged helix domain 462 - 517 IPR041075
domain NACHT, LRR and PYD domains-containing protein, helical domain HD2 519 - 643 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

5 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.
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.

3 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.
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.

9 GO annotations of biological process

Name Definition
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 NIK/NF-kappaB signaling Any process that stops, prevents or reduces the frequency, rate or extent of NIK/NF-kappaB signaling.
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-4 production Any process that activates or increases the frequency, rate, or extent of interleukin-4 production.
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.

5 homologous proteins in AiPD

UniProt AC Gene Name Protein Name Species Evidence Code
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
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
MRMVSVRCKL ARYLEDLEDI DFKKFKMHLE DYPSQKGCTS IPRGQTEKAD HVDLATLMID
70 80 90 100 110 120
FNGEEKAWAM AKWIFAAINR RDLYEKAKRE EPEWENANIS VLSQEESLEE EWMGLLGYLS
130 140 150 160 170 180
RISICRKKKD YCKKYRKYVR SKFQCIKDRN ARLGESVNLN KRFTRLRLIK EHRSQQEREH
190 200 210 220 230 240
ELLAIGRTWA KIQDSPVSSV NLELLFDPED QHSEPVHTVV FQGAAGIGKT ILARKIMLDW
250 260 270 280 290 300
ASEKLYQDRF DYLFYIHCRE VSLGTQRSLG DLIASCCPGP NPPIGKIVSK PSRILFLMDG
310 320 330 340 350 360
FDELQGAFDE HTEALCTNWR KVERGDILLS SLIRKRLLPE ASLLITTRPV ALEKLQHLLG
370 380 390 400 410 420
QARHVEILGF SEARRKEYFL KYFSDEQQAR EAFRLIQENE ILFTMCFIPL VCWIVCTGLK
430 440 450 460 470 480
QQMDSGKSLA RTSKTTTAVY IFFLSSLLQS QGGSQENHNS ATLWGLCSLA ADGIWNQKIL
490 500 510 520 530 540
FQECDLRNHG LQKADVSAFL RMNLFQKEVD CEKFYSFIHM TFQEFFAAMY YLLEEDNHGE
550 560 570 580 590 600
MRNTPQACSK LPNRDVKVLL ENYGKFEKGY LIFVVRFLFG LINQERTSYL EKKLSCKISQ
610 620 630 640 650 660
KIRLELLKWI EAKANAKTLQ IEPSQLELFY CLYEMQEEDF VQRAMSHFPK IEIKLSTRMD
670 680 690 700 710 720
HVVSSFCIEN CRHVESLSLR LLHNSPKEEE EEEEVRHSHM DRSVLSDFEV AYSQGLVNYL
730 740 750 760 770 780
TSSICRGIFS VLSNNWNLTE LNLSGNTLGD PGMNVLCETL QQPGCNIRRL WLGQCCLSHQ
790 800 810 820 830 840
CCFNISSVLS NNQKLVELDL SHNALGDFGI RLLCVGLRHL FCNLKKLWLV SCCLTSASCE
850 860 870 880 890 900
DLASVLSTNH SLTRLYLGEN ALGDSGVGIL CEKVKNPHCN LQKLGLVNSG LTSGCCPALS
910 920 930 940 950 960
SVLSTNQNLT HLYLQGNALG DMGVKLLCEG LLHRNCKLQV LELDNCSLTS HCCWDLSTLL
970 980 990 1000 1010 1020
TSNQSLRKLC LGNNDLGDLG VMLLCEVLKQ QGCLLKSLRL CEMYFNYDTK RALETLQEEK
1030
PELTIVFEPS R