Q96P20 · NLRP3_HUMAN
- ProteinNACHT, LRR and PYD domains-containing protein 3
- GeneNLRP3
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids1036 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
In response to pathogens and other damage-associated signals that affect the integrity of membranes, initiates the formation of the inflammasome polymeric complex composed of NLRP3, CASP1 and PYCARD/ASC (PubMed:16407889, PubMed:18403674, PubMed:27432880, PubMed:28847925, PubMed:31189953, PubMed:33231615, PubMed:34133077, PubMed:34341353, PubMed:36142182, PubMed:36442502).
Recruitment of pro-caspase-1 (proCASP1) to the NLRP3 inflammasome promotes caspase-1 (CASP1) activation, which subsequently cleaves and activates inflammatory cytokines IL1B and IL18 and gasdermin-D (GSDMD), promoting cytokine secretion and pyroptosis (PubMed:23582325, PubMed:28847925, PubMed:31189953, PubMed:33231615, PubMed:34133077, PubMed:34341353).
Activation of NLRP3 inflammasome is also required for HMGB1 secretion; stimulating inflammatory responses (PubMed:22801494).
Under resting conditions, ADP-bound NLRP3 is autoinhibited (PubMed:35114687).
NLRP3 activation stimuli include extracellular ATP, nigericin, reactive oxygen species, crystals of monosodium urate or cholesterol, amyloid-beta fibers, environmental or industrial particles and nanoparticles, such as asbestos, silica, aluminum salts, cytosolic dsRNA, etc (PubMed:16407889, PubMed:18403674, PubMed:18604214, PubMed:19414800, PubMed:23871209).
Almost all stimuli trigger intracellular K+ efflux (By similarity).
These stimuli lead to membrane perturbation and activation of NLRP3 (By similarity).
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 and formation of an active inflammasome complex (PubMed:36442502).
Associates with dTGN vesicle membranes by binding to phosphatidylinositol 4-phosphate (PtdIns4P) (PubMed:30487600, PubMed:34554188).
Shows ATPase activity (PubMed:17483456).
During Th2 differentiation, required for optimal IRF4 binding to IL4 promoter and for IRF4-dependent IL4 transcription (By similarity).
Binds to the consensus DNA sequence 5'-GRRGGNRGAG-3' (By similarity).
May also participate in the transcription of IL5, IL13, GATA3, CCR3, CCR4 and MAF (By similarity).
Catalytic activity
- ATP + H2O = ADP + H+ + phosphateThis reaction proceeds in the forward direction.
Activity regulation
Inactive NLRP3 forms homodecameric double-ring cages that hide pyrin domains within NACHT-LRR rings to avoid premature activation (PubMed:35114687).
NLRP3 activation stimuli include extracellular ATP, nigericin, reactive oxygen species, crystals of monosodium urate or cholesterol, amyloid-beta fibers, environmental or industrial particles and nanoparticles, such as asbestos, silica, aluminum salts, cytosolic dsRNA, etc (PubMed:16407889, PubMed:18403674, PubMed:18604214, PubMed:19414800, PubMed:35114687).
Activated upon human coronavirus SARS-CoV-2 infection (PubMed:33231615, PubMed:34133077).
Almost all stimuli trigger intracellular K+ efflux (By similarity).
These stimuli lead to membrane perturbations that induce activation of NLRP3 (By similarity).
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 and recruitment of PYCARD/ASC for the formation of an active inflammasome complex (PubMed:30487600, PubMed:30612879, PubMed:36442502).
NEK7-activated NLRP3 forms a disk-shaped inflammasome (PubMed:36442502).
NLRP3 and PYCARD/ASC interact via their respective pyrin domains; interaction initiates speck formation (nucleation) which greatly enhances further addition of soluble PYCARD/ASC molecules to the speck in a prion-like polymerization process (PubMed:24630722, PubMed:27432880, PubMed:28465465, PubMed:35559676, PubMed:36142182, PubMed:36442502).
Clustered PYCARD/ASC nucleates the formation of CASP1 filaments through the interaction of their respective CARD domains, acting as a platform for CASP1 polymerization and activation (PubMed:24630722).
Active CASP1 then processes IL1B and IL18 precursors, leading to the release of mature cytokines in the extracellular milieu and inflammatory response (PubMed:24630722).
NLRP3 inflammasome assembly is inhibited by IRGM, which impedes NLRP3 oligomerization (PubMed:30612879).
Specifically inhibited by sulfonylurea MCC950 (also named CP-456,773, CRID3), a potent and specific small-molecule inhibitor of the NLRP3 inflammasome that acts by preventing ATP hydrolysis (PubMed:25686105, PubMed:31086327, PubMed:31086329, PubMed:34687713, PubMed:35114687, PubMed:35254907).
Features
Showing features for binding site.
GO annotations
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameNACHT, LRR and PYD domains-containing protein 3
- EC number
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionQ96P20
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
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 (By similarity).
Recruited to dTGN vesicle membranes by binding to phosphatidylinositol 4-phosphate (PtdIns4P) (PubMed:30487600).
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 (PubMed:24952504).
Phagocytosis induces lysosomal damage and inflammasome activation in the recipient cells (PubMed:24952504).
In the Th2 subset of CD4+ helper T-cells, mainly located in the nucleus (By similarity).
Nuclear localization depends upon KPNA2 (By similarity).
In the Th1 subset of CD4+ helper T-cells, mainly cytoplasmic (By similarity).
Keywords
- Cellular component
Disease & Variants
Involvement in disease
Familial cold autoinflammatory syndrome 1 (FCAS1)
- Note
- DescriptionA 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.
- See alsoMIM:120100
Natural variants in FCAS1
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_013227 | 200 | V>M | in FCAS1 and MWS; dbSNP:rs121908147 | |
VAR_014104 | 262 | R>W | in FCAS1 and MWS; spontaneous polymerization into inflammasome speck; dbSNP:rs121908150 | |
VAR_014124 | 307 | L>P | in FCAS1 and MWS; dbSNP:rs180177431 | |
VAR_043685 | 355 | L>P | in FCAS1; dbSNP:rs28937896 | |
VAR_013229 | 441 | A>V | in FCAS1; dbSNP:rs121908146 | |
VAR_043689 | 490 | R>K | in FCAS1; dbSNP:rs145268073 | |
VAR_031853 | 525 | F>C | in FCAS1; dbSNP:rs180177478 | |
VAR_013230 | 629 | E>G | in FCAS1; dbSNP:rs121908148 |
Muckle-Wells syndrome (MWS)
- Note
- DescriptionA 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.
- See alsoMIM:191900
Natural variants in MWS
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_013227 | 200 | V>M | in FCAS1 and MWS; dbSNP:rs121908147 | |
VAR_014104 | 262 | R>W | in FCAS1 and MWS; spontaneous polymerization into inflammasome speck; dbSNP:rs121908150 | |
VAR_014105 | 305 | D>N | in CINCA and MWS; spontaneous polymerization into inflammasome speck; dbSNP:rs121908153 | |
VAR_014124 | 307 | L>P | in FCAS1 and MWS; dbSNP:rs180177431 | |
VAR_014366 | 350 | T>M | in MWS and CINCA; spontaneous polymerization into inflammasome speck; dbSNP:rs151344629 | |
VAR_013228 | 354 | A>V | in MWS; dbSNP:rs121908149 | |
VAR_014369 | 441 | A>T | in MWS; dbSNP:rs180177430 | |
VAR_014107 | 571 | G>R | in MWS; dbSNP:rs121908151 |
Chronic infantile neurologic cutaneous and articular syndrome (CINCA)
- Note
- DescriptionRare congenital inflammatory disorder characterized by a triad of neonatal onset of cutaneous symptoms, chronic meningitis, and joint manifestations with recurrent fever and inflammation.
- See alsoMIM:607115
Natural variants in CINCA
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_043679 | 174 | I>T | in CINCA; dbSNP:rs180177449 | |
VAR_043680 | 262 | R>L | in CINCA; dbSNP:rs180177442 | |
VAR_043681 | 262 | R>P | in CINCA; dbSNP:rs180177442 | |
VAR_043682 | 266 | L>H | in CINCA; dbSNP:rs180177436 | |
VAR_043683 | 305 | D>G | in CINCA; dbSNP:rs180177447 | |
VAR_014105 | 305 | D>N | in CINCA and MWS; spontaneous polymerization into inflammasome speck; dbSNP:rs121908153 | |
VAR_043684 | 308 | Q>K | in CINCA; dbSNP:rs180177432 | |
VAR_014106 | 311 | F>S | in CINCA; dbSNP:rs121908154 | |
VAR_014366 | 350 | T>M | in MWS and CINCA; spontaneous polymerization into inflammasome speck; dbSNP:rs151344629 | |
VAR_043686 | 356 | E>D | in CINCA; dbSNP:rs180177444 | |
VAR_014367 | 360 | H>R | in CINCA; dbSNP:rs180177434 | |
VAR_043687 | 407 | T>P | in CINCA; dbSNP:rs180177445 | |
VAR_043688 | 438 | T>I | in CINCA; dbSNP:rs180177433 | |
VAR_014368 | 438 | T>N | in CINCA; dbSNP:rs180177433 | |
VAR_043690 | 525 | F>L | in CINCA; dbSNP:rs180177439 | |
VAR_043691 | 572 | Y>C | in CINCA; dbSNP:rs180177438 | |
VAR_014108 | 575 | F>S | in CINCA; dbSNP:rs121908152 | |
VAR_043692 | 634 | L>F | in CINCA; dbSNP:rs180177446 | |
VAR_014370 | 664 | M>T | in CINCA; dbSNP:rs180177435 | |
VAR_023551 | 861 | Y>C | in CINCA; dbSNP:rs180177452 |
Keratoendothelitis fugax hereditaria (KEFH)
- Note
- DescriptionAn 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.
- See alsoMIM:148200
Natural variants in KEFH
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_080490 | 21 | D>H | in KEFH; does not affect ability to homooligomerize into ordered polymers; dbSNP:rs200154873 |
Deafness, autosomal dominant, 34, with or without inflammation (DFNA34)
- Note
- DescriptionA 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.
- See alsoMIM:617772
Natural variants in DFNA34
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_081008 | 920 | R>Q | in DFNA34; uncertain significance; increases inflammatory response; dbSNP:rs1553293095 |
Features
Showing features for mutagenesis, natural variant.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 2-7 | Strongly decreased interaction with MAVS and localization to mitochondria. | ||||
Sequence: Missing | ||||||
Mutagenesis | 5 | Decreased phosphorylation; increased activation of the NLRP3 inflammasome. | ||||
Sequence: S → A | ||||||
Mutagenesis | 5 | Mimics phosphorylation state; decreased activation of the NLRP3 inflammasome. | ||||
Sequence: S → D or E | ||||||
Mutagenesis | 7 | Impaired ability to homooligomerize into ordered polymers. | ||||
Sequence: R → E | ||||||
Mutagenesis | 7-12 | Abolished formation of the NLRP3 inflammasome. | ||||
Sequence: RCKLAR → ACALAA | ||||||
Mutagenesis | 15 | Impaired ability to homooligomerize into ordered polymers. Complete loss of PYCARD/ASC filament nucleation. | ||||
Sequence: E → R | ||||||
Natural variant | VAR_080490 | 21 | in KEFH; does not affect ability to homooligomerize into ordered polymers; dbSNP:rs200154873 | |||
Sequence: D → H | ||||||
Mutagenesis | 22-23 | Loss of PYCARD/ASC-binding. No effect on GBP5-binding. | ||||
Sequence: LK → PA | ||||||
Mutagenesis | 23 | Complete loss of PYCARD/ASC filament nucleation; when associated with E-24. | ||||
Sequence: K → E | ||||||
Mutagenesis | 23-24 | Impaired ability to homooligomerize into ordered polymers. Complete loss of PYCARD/ASC filament nucleation. | ||||
Sequence: KK → EE | ||||||
Mutagenesis | 24 | Complete loss of PYCARD/ASC filament nucleation; when associated with E-23. | ||||
Sequence: K → E | ||||||
Mutagenesis | 27 | Impaired ability to homooligomerize into ordered polymers. Complete loss of PYCARD/ASC filament nucleation. | ||||
Sequence: M → E | ||||||
Mutagenesis | 31 | Impaired ability to homooligomerize into ordered polymers. Decreased PYCARD/ASC filament nucleation. | ||||
Sequence: D → V | ||||||
Mutagenesis | 43 | Impaired ability to homooligomerize into ordered polymers. | ||||
Sequence: R → E | ||||||
Mutagenesis | 43 | Complete loss of PYCARD/ASC filament nucleation. Decreased PYCARD/ASC filament nucleation. | ||||
Sequence: R → W | ||||||
Mutagenesis | 51 | Does not affect ability to homooligomerize into ordered polymers. | ||||
Sequence: H → R | ||||||
Mutagenesis | 52 | Decreased interaction with MAPK4. | ||||
Sequence: V → G | ||||||
Mutagenesis | 64 | Complete loss of PYCARD/ASC filament nucleation. | ||||
Sequence: E → R | ||||||
Mutagenesis | 68 | Does not affect ubiquitination by the SCF(FBXL2) complex. | ||||
Sequence: W → A | ||||||
Mutagenesis | 73 | Decreased ubiquitination by the SCF(FBXL2) complex. | ||||
Sequence: W → A | ||||||
Mutagenesis | 77 | Induces the formation of short but ordered homopolymers. | ||||
Sequence: A → V | ||||||
Mutagenesis | 80 | Impaired ability to homooligomerize into ordered polymers. Decreased PYCARD/ASC filament nucleation. | ||||
Sequence: R → E | ||||||
Mutagenesis | 81 | Impaired ability to homooligomerize into ordered polymers. Decreased PYCARD/ASC filament nucleation. | ||||
Sequence: R → E | ||||||
Mutagenesis | 82 | Complete loss of PYCARD/ASC filament nucleation. | ||||
Sequence: D → R | ||||||
Mutagenesis | 136-143 | Decreased phosphorylation by BTK; when associated with F-168. | ||||
Sequence: YRKKYRKY → FRKKFRKF | ||||||
Mutagenesis | 143 | Decreased ability to activate the NLRP3 inflammasome. | ||||
Sequence: Y → R | ||||||
Mutagenesis | 147 | Impaired ability to activate the NLRP3 inflammasome. | ||||
Sequence: R → E | ||||||
Mutagenesis | 152 | Impaired ability to activate the NLRP3 inflammasome. | ||||
Sequence: E → R | ||||||
Mutagenesis | 155 | Impaired ability to activate the NLRP3 inflammasome. | ||||
Sequence: N → A | ||||||
Mutagenesis | 157 | Impaired ability to activate the NLRP3 inflammasome. | ||||
Sequence: R → E | ||||||
Mutagenesis | 166 | Impaired ability to activate the NLRP3 inflammasome. | ||||
Sequence: K → E | ||||||
Mutagenesis | 168 | Decreased phosphorylation by BTK; when associated with 136-F--F-143. | ||||
Sequence: Y → F | ||||||
Natural variant | VAR_043679 | 174 | in CINCA; dbSNP:rs180177449 | |||
Sequence: I → T | ||||||
Mutagenesis | 176 | Impaired ability to activate the NLRP3 inflammasome. | ||||
Sequence: E → R | ||||||
Mutagenesis | 198 | Abolished phosphorylation by MAPK8/JNK1; decreased activation of the NLRP3 inflammasome. | ||||
Sequence: S → A | ||||||
Mutagenesis | 198 | Mimicks phosphorylation state; increased activation of the NLRP3 inflammasome. | ||||
Sequence: S → D or E | ||||||
Natural variant | VAR_013227 | 200 | in FCAS1 and MWS; dbSNP:rs121908147 | |||
Sequence: V → M | ||||||
Mutagenesis | 213 | Does not affect ability to activate the NLRP3 inflammasome. | ||||
Sequence: D → R | ||||||
Mutagenesis | 228 | Abolished binding to small-inhibitor MCC950 and ability to activate the NLRP3 inflammasome following stimulation with nigericin. | ||||
Sequence: A → Q | ||||||
Mutagenesis | 231-233 | In Walker A mutant; abolished ATPase activity. Reduced ATP-binding leading to decreased activation of the NLRP3 inflammasome. | ||||
Sequence: GKT → AAA | ||||||
Natural variant | VAR_043680 | 262 | in CINCA; dbSNP:rs180177442 | |||
Sequence: R → L | ||||||
Natural variant | VAR_043681 | 262 | in CINCA; dbSNP:rs180177442 | |||
Sequence: R → P | ||||||
Natural variant | VAR_014104 | 262 | in FCAS1 and MWS; spontaneous polymerization into inflammasome speck; dbSNP:rs121908150 | |||
Sequence: R → W | ||||||
Natural variant | VAR_043682 | 266 | in CINCA; dbSNP:rs180177436 | |||
Sequence: L → H | ||||||
Mutagenesis | 302-306 | In Walker B mutant; abolished ATPase activity. Abolished binding to small-inhibitor MCC950. | ||||
Sequence: DGFDE → AGFAA or AGFNA | ||||||
Natural variant | VAR_043683 | 305 | in CINCA; dbSNP:rs180177447 | |||
Sequence: D → G | ||||||
Natural variant | VAR_014105 | 305 | in CINCA and MWS; spontaneous polymerization into inflammasome speck; dbSNP:rs121908153 | |||
Sequence: D → N | ||||||
Natural variant | VAR_014124 | 307 | in FCAS1 and MWS; dbSNP:rs180177431 | |||
Sequence: L → P | ||||||
Natural variant | VAR_043684 | 308 | in CINCA; dbSNP:rs180177432 | |||
Sequence: Q → K | ||||||
Natural variant | VAR_014106 | 311 | in CINCA; dbSNP:rs121908154 | |||
Sequence: F → S | ||||||
Natural variant | VAR_014366 | 350 | in MWS and CINCA; spontaneous polymerization into inflammasome speck; dbSNP:rs151344629 | |||
Sequence: T → M | ||||||
Mutagenesis | 351 | Abolished binding to small-inhibitor MCC950 and ability to activate the NLRP3 inflammasome following stimulation with nigericin. | ||||
Sequence: R → T | ||||||
Natural variant | VAR_013228 | 354 | in MWS; dbSNP:rs121908149 | |||
Sequence: A → V | ||||||
Natural variant | VAR_043685 | 355 | in FCAS1; dbSNP:rs28937896 | |||
Sequence: L → P | ||||||
Natural variant | VAR_043686 | 356 | in CINCA; dbSNP:rs180177444 | |||
Sequence: E → D | ||||||
Mutagenesis | 359 | Does not affect ability to activate the NLRP3 inflammasome. | ||||
Sequence: Q → A or R | ||||||
Mutagenesis | 359 | Decreased interaction with HSPA8/HSC70 and NLRP3 degradation by the chaperone-mediated autophagy pathway. | ||||
Sequence: Q → A | ||||||
Natural variant | VAR_014367 | 360 | in CINCA; dbSNP:rs180177434 | |||
Sequence: H → R | ||||||
Mutagenesis | 364 | Does not affect ability to activate the NLRP3 inflammasome. | ||||
Sequence: H → E | ||||||
Natural variant | VAR_043687 | 407 | in CINCA; dbSNP:rs180177445 | |||
Sequence: T → P | ||||||
Mutagenesis | 424 | Impaired ability to activate the NLRP3 inflammasome. | ||||
Sequence: Q → A | ||||||
Natural variant | VAR_043688 | 438 | in CINCA; dbSNP:rs180177433 | |||
Sequence: T → I | ||||||
Natural variant | VAR_014368 | 438 | in CINCA; dbSNP:rs180177433 | |||
Sequence: T → N | ||||||
Natural variant | VAR_014369 | 441 | in MWS; dbSNP:rs180177430 | |||
Sequence: A → T | ||||||
Natural variant | VAR_013229 | 441 | in FCAS1; dbSNP:rs121908146 | |||
Sequence: A → V | ||||||
Natural variant | VAR_043689 | 490 | in FCAS1; dbSNP:rs145268073 | |||
Sequence: R → K | ||||||
Mutagenesis | 509 | Impaired ability to activate the NLRP3 inflammasome. | ||||
Sequence: Q → A | ||||||
Natural variant | VAR_031853 | 525 | in FCAS1; dbSNP:rs180177478 | |||
Sequence: F → C | ||||||
Natural variant | VAR_043690 | 525 | in CINCA; dbSNP:rs180177439 | |||
Sequence: F → L | ||||||
Natural variant | VAR_014107 | 571 | in MWS; dbSNP:rs121908151 | |||
Sequence: G → R | ||||||
Natural variant | VAR_043691 | 572 | in CINCA; dbSNP:rs180177438 | |||
Sequence: Y → C | ||||||
Natural variant | VAR_014108 | 575 | in CINCA; dbSNP:rs121908152 | |||
Sequence: F → S | ||||||
Mutagenesis | 578 | Abolished binding to small-inhibitor MCC950 and ability to activate the NLRP3 inflammasome following stimulation with nigericin. | ||||
Sequence: R → A | ||||||
Mutagenesis | 603 | Decreased interaction with HSPA8/HSC70 and NLRP3 degradation by the chaperone-mediated autophagy pathway. | ||||
Sequence: Q → A | ||||||
Mutagenesis | 619-621 | Does not affect autoinhibition of the protein. | ||||
Sequence: KKL → EEA | ||||||
Natural variant | VAR_013230 | 629 | in FCAS1; dbSNP:rs121908148 | |||
Sequence: E → G | ||||||
Natural variant | VAR_043692 | 634 | in CINCA; dbSNP:rs180177446 | |||
Sequence: L → F | ||||||
Mutagenesis | 638-640 | Strongly decreased ability to activate the NLRP3 inflammasome. | ||||
Sequence: QEE → RRR | ||||||
Natural variant | VAR_014370 | 664 | in CINCA; dbSNP:rs180177435 | |||
Sequence: M → T | ||||||
Mutagenesis | 689 | Abolished ubiquitination by the SCF(FBXL2) complex. | ||||
Sequence: K → R | ||||||
Mutagenesis | 689-698 | Loss of autoinhibition of the protein. | ||||
Sequence: Missing | ||||||
Natural variant | VAR_043693 | 705 | in dbSNP:rs35829419 | |||
Sequence: Q → K | ||||||
Mutagenesis | 707 | Decreased ability to activate the NLRP3 inflammasome. | ||||
Sequence: V → R | ||||||
Mutagenesis | 735 | Does not affect activation of the NLRP3 inflammasome. | ||||
Sequence: S → A | ||||||
Mutagenesis | 745 | Abolished ability to activate the NLRP3 inflammasome. | ||||
Sequence: E → R | ||||||
Mutagenesis | 750 | Abolished ability to activate the NLRP3 inflammasome. | ||||
Sequence: D → R | ||||||
Mutagenesis | 788 | Slightly decreased ability to activate the NLRP3 inflammasome; when associated with E-813. | ||||
Sequence: F → E | ||||||
Mutagenesis | 788-789 | Slightly impaired autoinhibition of the protein; when associated with A-831. | ||||
Sequence: FD → AR | ||||||
Mutagenesis | 789 | Slightly decreased ability to activate the NLRP3 inflammasome; when associated with D-816. | ||||
Sequence: D → R | ||||||
Mutagenesis | 798 | Decreased interaction with HSPA8/HSC70 and NLRP3 degradation by the chaperone-mediated autophagy pathway. | ||||
Sequence: Q → A | ||||||
Mutagenesis | 802 | Abolished ability to activate the NLRP3 inflammasome. | ||||
Sequence: E → R | ||||||
Mutagenesis | 806 | Abolished phosphorylation by CSNK1A1; increased activation of the NLRP3 inflammasome. | ||||
Sequence: S → A | ||||||
Mutagenesis | 806 | Mimics phosphorylation state; decreased activation of the NLRP3 inflammasome. | ||||
Sequence: S → D or E | ||||||
Mutagenesis | 813 | Slightly decreased ability to activate the NLRP3 inflammasome; when associated with E-788. | ||||
Sequence: F → E | ||||||
Mutagenesis | 816 | Slightly decreased ability to activate the NLRP3 inflammasome; when associated with R-789. | ||||
Sequence: R → D | ||||||
Mutagenesis | 831 | Slightly impaired autoinhibition of the protein; when associated with 788-A-R-789. | ||||
Sequence: K → A | ||||||
Mutagenesis | 833 | Does not affect ability to activate the NLRP3 inflammasome. | ||||
Sequence: W → G | ||||||
Mutagenesis | 837 | Abolished palmitoylation by ZDHHC5; when associated with S-838. | ||||
Sequence: C → S | ||||||
Mutagenesis | 837 | Partially affected palmitoylation by ZDHHC5, about 50% loss of interaction with NEK7. | ||||
Sequence: C → S | ||||||
Mutagenesis | 838 | Abolished palmitoylation by ZDHHC5; when associated with S-837. | ||||
Sequence: C → S | ||||||
Mutagenesis | 838 | Partially affected palmitoylation by ZDHHC5, about 50% loss of interaction with NEK7. | ||||
Sequence: C → S | ||||||
Mutagenesis | 844 | Abolished palmitoylation by ZDHHC12, preventing degradation by the chaperone-mediated autophagy pathway. | ||||
Sequence: C → A | ||||||
Natural variant | VAR_023551 | 861 | in CINCA; dbSNP:rs180177452 | |||
Sequence: Y → C | ||||||
Mutagenesis | 861 | Abolished phosphorylation. | ||||
Sequence: Y → F | ||||||
Mutagenesis | 864 | Decreased ability to activate the NLRP3 inflammasome. | ||||
Sequence: E → R | ||||||
Mutagenesis | 918 | Decreased ability to activate the NLRP3 inflammasome. | ||||
Sequence: Y → G | ||||||
Natural variant | VAR_081008 | 920 | in DFNA34; uncertain significance; increases inflammatory response; dbSNP:rs1553293095 | |||
Sequence: R → Q | ||||||
Mutagenesis | 995 | Decreased interaction with HSPA8/HSC70 and NLRP3 degradation by the chaperone-mediated autophagy pathway. | ||||
Sequence: Q → A | ||||||
Mutagenesis | 1035 | Does not affect activation of the NLRP3 inflammasome. | ||||
Sequence: S → A |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 34 variants from UniProt as well as other sources including ClinVar and dbSNP.
Keywords
- Disease
Organism-specific databases
Miscellaneous
Chemistry
Genetic variation databases
PTM/Processing
Features
Showing features for chain, modified residue, disulfide bond, cross-link, lipidation.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000080886 | 1-1036 | NACHT, LRR and PYD domains-containing protein 3 | |||
Sequence: MKMASTRCKLARYLEDLEDVDLKKFKMHLEDYPPQKGCIPLPRGQTEKADHVDLATLMIDFNGEEKAWAMAVWIFAAINRRDLYEKAKRDEPKWGSDNARVSNPTVICQEDSIEEEWMGLLEYLSRISICKMKKDYRKKYRKYVRSRFQCIEDRNARLGESVSLNKRYTRLRLIKEHRSQQEREQELLAIGKTKTCESPVSPIKMELLFDPDDEHSEPVHTVVFQGAAGIGKTILARKMMLDWASGTLYQDRFDYLFYIHCREVSLVTQRSLGDLIMSCCPDPNPPIHKIVRKPSRILFLMDGFDELQGAFDEHIGPLCTDWQKAERGDILLSSLIRKKLLPEASLLITTRPVALEKLQHLLDHPRHVEILGFSEAKRKEYFFKYFSDEAQARAAFSLIQENEVLFTMCFIPLVCWIVCTGLKQQMESGKSLAQTSKTTTAVYVFFLSSLLQPRGGSQEHGLCAHLWGLCSLAADGIWNQKILFEESDLRNHGLQKADVSAFLRMNLFQKEVDCEKFYSFIHMTFQEFFAAMYYLLEEEKEGRTNVPGSRLKLPSRDVTVLLENYGKFEKGYLIFVVRFLFGLVNQERTSYLEKKLSCKISQQIRLELLKWIEVKAKAKKLQIQPSQLELFYCLYEMQEEDFVQRAMDYFPKIEINLSTRMDHMVSSFCIENCHRVESLSLGFLHNMPKEEEEEEKEGRHLDMVQCVLPSSSHAACSHGLVNSHLTSSFCRGLFSVLSTSQSLTELDLSDNSLGDPGMRVLCETLQHPGCNIRRLWLGRCGLSHECCFDISLVLSSNQKLVELDLSDNALGDFGIRLLCVGLKHLLCNLKKLWLVSCCLTSACCQDLASVLSTSHSLTRLYVGENALGDSGVAILCEKAKNPQCNLQKLGLVNSGLTSVCCSALSSVLSTNQNLTHLYLRGNTLGDKGIKLLCEGLLHPDCKLQVLELDNCNLTSHCCWDLSTLLTSSQSLRKLSLGNNDLGDLGVMMFCEVLKQQSCLLQNLGLSEMYFNYETKSALETLQEEKPELTVVFEPSW | ||||||
Modified residue | 5 | Phosphoserine | ||||
Sequence: S | ||||||
Disulfide bond | 8↔108 | Redox-active | ||||
Sequence: CKLARYLEDLEDVDLKKFKMHLEDYPPQKGCIPLPRGQTEKADHVDLATLMIDFNGEEKAWAMAVWIFAAINRRDLYEKAKRDEPKWGSDNARVSNPTVIC | ||||||
Modified residue | 13 | Phosphotyrosine | ||||
Sequence: Y | ||||||
Modified residue | 136 | Phosphotyrosine; by BTK | ||||
Sequence: Y | ||||||
Modified residue | 140 | Phosphotyrosine; by BTK | ||||
Sequence: Y | ||||||
Modified residue | 143 | Phosphotyrosine; by BTK | ||||
Sequence: Y | ||||||
Modified residue | 161 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 163 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 168 | Phosphotyrosine; by BTK | ||||
Sequence: Y | ||||||
Modified residue | 198 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 198 | Phosphoserine; by MAPK8 | ||||
Sequence: S | ||||||
Modified residue | 201 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 295 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 334 | Phosphoserine | ||||
Sequence: S | ||||||
Cross-link | 689 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) | ||||
Sequence: K | ||||||
Modified residue | 728 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 735 | Phosphoserine; by CSNK1A1 | ||||
Sequence: S | ||||||
Modified residue | 806 | Phosphoserine; by CSNK1A1 | ||||
Sequence: S | ||||||
Lipidation | 837 | S-palmitoyl cysteine | ||||
Sequence: C | ||||||
Lipidation | 838 | S-palmitoyl cysteine | ||||
Sequence: C | ||||||
Lipidation | 844 | S-palmitoyl cysteine | ||||
Sequence: C | ||||||
Modified residue | 861 | Phosphotyrosine | ||||
Sequence: Y | ||||||
Cross-link | 878 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) | ||||
Sequence: K | ||||||
Cross-link | 927 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) | ||||
Sequence: K | ||||||
Cross-link | 973 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) | ||||
Sequence: K | ||||||
Modified residue | 975 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 1035 | Phosphoserine; by CSNK1A1 | ||||
Sequence: S |
Post-translational modification
Phosphorylation at Ser-806 by CSNK1A1 prevents inflammasome activation by preventing NEK7 recruitment (PubMed:34615873).
Phosphorylation at Ser-5 in the pyrin domain inhibits homomultimerization of NLRP3 and activation of the NLRP3 inflammasome: dephosphorylation by protein phosphatase 2A (PP2A) promotes assembly of the NLRP3 inflammasome (PubMed:28465465).
Phosphorylation at Ser-295 by PKD/PRKD1 promotes NLRP3 inflammasome assembly (By similarity).
Phosphorylation by ERK1/MAPK3 promotes NLRP3 inflammasome assembly (PubMed:24623131).
Phosphorylation by BTK (at Tyr-136, Tyr-140, Tyr-143 and Tyr-168) in the region that mediates binding to phosphatidylinositol phosphate, promotes relocalization of NLRP3 and assembly of the NLRP3 inflammasome (PubMed:34554188).
Phosphorylation at Tyr-861 inhibits NLRP3 inflammasome assembly: dephosphorylation by PTPN22 promotes inflammasome activation (PubMed:27043286).
Ubiquitination does not lead to degradation, but inhibits inflammasome activation (By similarity).
Deubiquitination is catalyzed by BRCC3 and associated with NLRP3 activation and inflammasome assembly (By similarity).
This process can be induced by the activation of Toll-like receptors (by LPS), through a non-transcriptional pathway dependent on the mitochondrial production of reactive oxygen species, and by ATP (By similarity).
Ubiquitinated by TRIM31 via 'Lys-48'-linked ubiquitination, leading to its degradation by the proteasome (PubMed:27929086).
Ubiquitinated at Lys-689 by the SCF(FBXL2) complex, leading to its degradation by the proteasome (PubMed:26037928).
Ubiquitinated by TRIM35 via 'lys-48' and 'Lys-63'-linked ubiquitination leading to inhibition of NLRP3 inflammasome activation (PubMed:34512673).
Following palmitoylation, HSPA8/HSC70 recognizes and binds the KFERQ-like motifs on NLRP3 and promotes NLRP3 recruitment to lysosomes, where it is degraded via the chaperone-mediated autophagy pathway in a LAMP2-dependent process (PubMed:36586411).
Palmitoylation by ZDHHC5 enhances its binding to NEK7 leading to inflammasome assembly and activation (PubMed:38092000).
Depalmitoylated by ABHD17A (PubMed:38092000).
IRGM promotes NLRP3 recruitment to autophagosome membranes, promoting its SQSTM1/p62-dependent autophagy-dependent degradation (PubMed:30612879).
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Also expressed in dendritic cells, B- and T-cells (at protein level) (PubMed:11786556, PubMed:17164409).
Expressed in LPS-treated granulocytes, but not in resting cells (at protein level) (PubMed:17164409).
Expression in monocytes is very weak (at protein level) (PubMed:17164409).
Expressed in stratified non-keratinizing squamous epithelium, including oral, esophageal and ectocervical mucosa and in the Hassall's corpuscles in the thymus. Also, detected in the stratified epithelium covering the bladder and ureter (transitional mucosa) (at protein level) (PubMed:17164409).
Expressed in lung epithelial cells (at protein level) (PubMed:23229815).
Expressed in chondrocytes (PubMed:12032915).
Expressed at low levels in resting osteoblasts (PubMed:17907925).
Induction
Up-regulated in osteoblasts after exposure to invasive, but not invasion-defective, strains of Salmonella typhimurium (at protein level) (PubMed:17907925).
In macrophages, up-regulated by endocannabinoid anandamide/AEA (PubMed:23955712).
Gene expression databases
Interaction
Subunit
The core of NLRP3 inflammasomes consists of a signal sensor component (NLRP3), an adapter (PYCARD/ASC), which recruits an effector pro-inflammatory caspase (CASP1 and, possibly, CASP4 and CASP5) (PubMed:11786556, PubMed:15030775, PubMed:21880711).
Homodecamer; inactive NLRP3 forms homodecameric double-ring cages that hide pyrin domains within NACHT-LRR rings to avoid premature activation (PubMed:35114687, PubMed:35254907).
Interacts (via pyrin domain) with PYCARD/ASC (via pyrin domain); interaction is direct (PubMed:11786556, PubMed:27432880, PubMed:34341353, PubMed:35559676, PubMed:36142182, PubMed:36442502).
Interacts (via LRR repeat domain) with NEK7 (via N-terminus); the interaction is required for the formation of the complex NLRP3:PYCARD, oligomerization of PYCARD/ASC and activation of CASP1 (PubMed:31189953, PubMed:36442502, PubMed:38092000).
Interacts (via LRR repeat domain) with NR4A1/Nur77 (via N-terminus); the interaction is direct, requires activation of NR4A1 by its ligands NBRE-containing dsDNA and lipopolysaccharide, and stimulates the association of NLRP3 with NEK7 for non-canonical NLRP3 inflammasome activation (By similarity).
Interacts with CARD8; leading to inhibit formation of the NLRP3 inflammasome (PubMed:24517500).
Interacts with MEFV; this interaction targets NLRP3 to degradation by autophagy, hence preventing excessive IL1B- and IL18-mediated inflammation (PubMed:17431422, PubMed:26347139).
Interacts with EIF2AK2/PKR; this interaction requires EIF2AK2 activity, is accompanied by EIF2AK2 autophosphorylation and promotes inflammasome assembly in response to specific stimuli (PubMed:22801494).
Interacts with GBP5 (via DAPIN domain); this interaction promotes inflammasome assembly in response to microbial and soluble, but not crystalline, agents (PubMed:22461501).
Interacts with PML (isoform PML-1) (via the leucine-rich repeat (LRR) domain); PML-mediated increase in NLRP3 inflammasome activation does not depend upon this interaction (PubMed:23430110).
Interacts (via NACHT domain) with DHX33 (via DEAH box); NLRP3 activation in presence of cytosolic dsRNA is mediated by DHX33 (PubMed:23871209).
Interacts (via NACHT and LRR domains) with ARRB2; this interaction is direct and inducible by polyunsaturated fatty acids (PUFAs) (PubMed:23809162).
Interacts with PYDC5 (PubMed:24531343).
Interacts (via NACHT domain) with DDX3X under both LPS-primed and inflammasome-activating conditions (By similarity).
Interacts with IRF4 (via the LRR domain); this interaction is direct and is required for optimal IRF4 binding to IL4 promoter and efficient IL4 transactivation during differentiation of Th2 helper T-cells (By similarity).
Interacts with MAVS; promoting localization to mitochondria and activation of the NLRP3 inflammasome (PubMed:23582325).
Interacts with MARK4; promoting localization of NLRP3 to the microtubule organizing center (MTOC) (PubMed:28656979).
Interacts with TRIM50; this interaction promotes also NLRP3 oligomerization and subsequent inflammasome activation (By similarity).
Interacts with IRGM; preventing NLRP3 inflammasome assembly and promoting NLRP3 degradation (PubMed:30612879).
Interacts (via KFERQ-like motifs) with HSPA8/HSC70; promoting NLRP3 degradation by the chaperone-mediated autophagy pathway (PubMed:36586411).
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
XENO | Q96P20 | 8b Q80H93 | 7 | EBI-6253230, EBI-25492924 | |
BINARY | Q96P20 | CALR P27797 | 3 | EBI-6253230, EBI-1049597 | |
BINARY | Q96P20 | DLST P36957 | 3 | EBI-6253230, EBI-351007 | |
BINARY | Q96P20 | EIF2AK2 P19525 | 6 | EBI-6253230, EBI-640775 | |
BINARY | Q96P20 | MAVS Q7Z434 | 4 | EBI-6253230, EBI-995373 | |
XENO | Q96P20 | N P0DTC9 | 18 | EBI-6253230, EBI-25475856 | |
BINARY | Q96P20 | NEK7 Q8TDX7 | 4 | EBI-6253230, EBI-1055945 | |
XENO | Q96P20 | Nek7 Q9ES74 | 2 | EBI-6253230, EBI-16193749 | |
BINARY | Q96P20 | NLRP3 Q96P20 | 2 | EBI-6253230, EBI-6253230 | |
BINARY | Q96P20 | PYCARD Q9ULZ3 | 26 | EBI-6253230, EBI-751215 | |
BINARY | Q96P20-1 | NEK7 Q8TDX7-1 | 6 | EBI-14029575, EBI-16193799 |
Protein-protein interaction databases
Chemistry
Miscellaneous
Structure
Family & Domains
Features
Showing features for domain, region, motif, repeat.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Domain | 1-93 | Pyrin | ||||
Sequence: MKMASTRCKLARYLEDLEDVDLKKFKMHLEDYPPQKGCIPLPRGQTEKADHVDLATLMIDFNGEEKAWAMAVWIFAAINRRDLYEKAKRDEPK | ||||||
Region | 131-134 | Required for binding to phosphatidylinositol 4-phosphate (PtdIns4P) | ||||
Sequence: KMKK | ||||||
Domain | 140-210 | FISNA | ||||
Sequence: YRKYVRSRFQCIEDRNARLGESVSLNKRYTRLRLIKEHRSQQEREQELLAIGKTKTCESPVSPIKMELLFD | ||||||
Domain | 220-536 | NACHT | ||||
Sequence: HTVVFQGAAGIGKTILARKMMLDWASGTLYQDRFDYLFYIHCREVSLVTQRSLGDLIMSCCPDPNPPIHKIVRKPSRILFLMDGFDELQGAFDEHIGPLCTDWQKAERGDILLSSLIRKKLLPEASLLITTRPVALEKLQHLLDHPRHVEILGFSEAKRKEYFFKYFSDEAQARAAFSLIQENEVLFTMCFIPLVCWIVCTGLKQQMESGKSLAQTSKTTTAVYVFFLSSLLQPRGGSQEHGLCAHLWGLCSLAADGIWNQKILFEESDLRNHGLQKADVSAFLRMNLFQKEVDCEKFYSFIHMTFQEFFAAMYYLL | ||||||
Motif | 355-359 | KFERQ-like motif 1 | ||||
Sequence: LEKLQ | ||||||
Motif | 603-607 | KFERQ-like motif 2 | ||||
Sequence: QIRLE | ||||||
Repeat | 742-762 | LRR 1 | ||||
Sequence: SLTELDLSDNSLGDPGMRVLC | ||||||
Repeat | 771-792 | LRR 2 | ||||
Sequence: NIRRLWLGRCGLSHECCFDISL | ||||||
Motif | 798-802 | KFERQ-like motif 3 | ||||
Sequence: QKLVE | ||||||
Repeat | 799-819 | LRR 3 | ||||
Sequence: KLVELDLSDNALGDFGIRLLC | ||||||
Repeat | 828-849 | LRR 4 | ||||
Sequence: NLKKLWLVSCCLTSACCQDLAS | ||||||
Repeat | 856-876 | LRR 5 | ||||
Sequence: SLTRLYVGENALGDSGVAILC | ||||||
Repeat | 885-906 | LRR 6 | ||||
Sequence: NLQKLGLVNSGLTSVCCSALSS | ||||||
Repeat | 913-933 | LRR 7 | ||||
Sequence: NLTHLYLRGNTLGDKGIKLLC | ||||||
Repeat | 942-963 | LRR 8 | ||||
Sequence: KLQVLELDNCNLTSHCCWDLST | ||||||
Repeat | 970-991 | LRR 9 | ||||
Sequence: SLRKLSLGNNDLGDLGVMMFCE | ||||||
Motif | 991-995 | KFERQ-like motif 4 | ||||
Sequence: EVLKQ |
Domain
It becomes ordered in its key regions during activation to stabilize the active NACHT conformation and mediate most interactions in the NLRP3 disk (PubMed:36442502).
Sequence similarities
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence & Isoforms
- Sequence statusComplete
This entry describes 6 isoforms produced by Alternative splicing.
Q96P20-1
This isoform has been chosen as the canonical sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
- Name2
- Length1,036
- Mass (Da)118,173
- Last updated2009-11-03 v3
- Checksum4C1DFB2B5B283CE8
Q96P20-2
- Name1
Q96P20-3
- Name3
- Differences from canonical
- 720-1036: Missing
Q96P20-4
- Name4
- Differences from canonical
- 721-777: Missing
Q96P20-5
- Name5
- Differences from canonical
- 836-892: Missing
Q96P20-6
- Name6
- Differences from canonical
- 776-796: WLGRCGLSHECCFDISLVLSS → C
Computationally mapped potential isoform sequences
There are 7 potential isoforms mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
A0A7I2R3P8 | A0A7I2R3P8_HUMAN | NLRP3 | 1034 | ||
A0A2R8YEG7 | A0A2R8YEG7_HUMAN | NLRP3 | 672 | ||
A0A7I2PJH0 | A0A7I2PJH0_HUMAN | NLRP3 | 920 | ||
A0A7I2PMC6 | A0A7I2PMC6_HUMAN | NLRP3 | 977 | ||
A0A7I2PRX0 | A0A7I2PRX0_HUMAN | NLRP3 | 977 | ||
A0A7I2YME5 | A0A7I2YME5_HUMAN | NLRP3 | 1014 | ||
A0A7I2UNQ2 | A0A7I2UNQ2_HUMAN | NLRP3 | 717 |
Sequence caution
Features
Showing features for sequence conflict, alternative sequence.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 167 | in Ref. 2; AAL78632/AAM14669/AAL14640 | ||||
Sequence: R → L | ||||||
Sequence conflict | 323 | in Ref. 2; AAL78632/AAM14669/AAL14640 | ||||
Sequence: Q → H | ||||||
Sequence conflict | 439 | in Ref. 10; AAC39910 | ||||
Sequence: T → S | ||||||
Sequence conflict | 523 | in Ref. 5; BAG37494 | ||||
Sequence: M → V | ||||||
Sequence conflict | 599 | in Ref. 10; AAC39910 | ||||
Sequence: K → M | ||||||
Sequence conflict | 617 | in Ref. 2; AAL78632/AAM14669/AAL14640 | ||||
Sequence: K → N | ||||||
Sequence conflict | 622-623 | in Ref. 10; AAC39910 | ||||
Sequence: QI → HD | ||||||
Alternative sequence | VSP_005519 | 720-1036 | in isoform 3 | |||
Sequence: Missing | ||||||
Alternative sequence | VSP_005520 | 721-777 | in isoform 1 and isoform 4 | |||
Sequence: Missing | ||||||
Alternative sequence | VSP_053714 | 776-796 | in isoform 6 | |||
Sequence: WLGRCGLSHECCFDISLVLSS → C | ||||||
Alternative sequence | VSP_005521 | 836-892 | in isoform 1 and isoform 5 | |||
Sequence: Missing |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AF410477 EMBL· GenBank· DDBJ | AAL33908.1 EMBL· GenBank· DDBJ | mRNA | Different initiation | |
AF427617 EMBL· GenBank· DDBJ | AAL33911.1 EMBL· GenBank· DDBJ | mRNA | ||
AY051117 EMBL· GenBank· DDBJ | AAL12497.1 EMBL· GenBank· DDBJ | Genomic DNA | Different initiation | |
AY051112 EMBL· GenBank· DDBJ | AAL12497.1 EMBL· GenBank· DDBJ | Genomic DNA | Different initiation | |
AY051113 EMBL· GenBank· DDBJ | AAL12497.1 EMBL· GenBank· DDBJ | Genomic DNA | Different initiation | |
AY051114 EMBL· GenBank· DDBJ | AAL12497.1 EMBL· GenBank· DDBJ | Genomic DNA | Different initiation | |
AY051115 EMBL· GenBank· DDBJ | AAL12497.1 EMBL· GenBank· DDBJ | Genomic DNA | Different initiation | |
AY051116 EMBL· GenBank· DDBJ | AAL12497.1 EMBL· GenBank· DDBJ | Genomic DNA | Different initiation | |
AY056059 EMBL· GenBank· DDBJ | AAL12497.1 EMBL· GenBank· DDBJ | Genomic DNA | Different initiation | |
AY056060 EMBL· GenBank· DDBJ | AAL12497.1 EMBL· GenBank· DDBJ | Genomic DNA | Different initiation | |
AY051117 EMBL· GenBank· DDBJ | AAL12498.1 EMBL· GenBank· DDBJ | Genomic DNA | Different initiation | |
AY051112 EMBL· GenBank· DDBJ | AAL12498.1 EMBL· GenBank· DDBJ | Genomic DNA | Different initiation | |
AY051113 EMBL· GenBank· DDBJ | AAL12498.1 EMBL· GenBank· DDBJ | Genomic DNA | Different initiation | |
AY051114 EMBL· GenBank· DDBJ | AAL12498.1 EMBL· GenBank· DDBJ | Genomic DNA | Different initiation | |
AY051115 EMBL· GenBank· DDBJ | AAL12498.1 EMBL· GenBank· DDBJ | Genomic DNA | Different initiation | |
AY051116 EMBL· GenBank· DDBJ | AAL12498.1 EMBL· GenBank· DDBJ | Genomic DNA | Different initiation | |
AF468522 EMBL· GenBank· DDBJ | AAL78632.1 EMBL· GenBank· DDBJ | mRNA | ||
AF420469 EMBL· GenBank· DDBJ | AAL65136.1 EMBL· GenBank· DDBJ | mRNA | Different initiation | |
AY092033 EMBL· GenBank· DDBJ | AAM14669.1 EMBL· GenBank· DDBJ | mRNA | ||
AF418985 EMBL· GenBank· DDBJ | AAL14640.2 EMBL· GenBank· DDBJ | mRNA | ||
AK314998 EMBL· GenBank· DDBJ | BAG37494.1 EMBL· GenBank· DDBJ | mRNA | Different initiation | |
AB208891 EMBL· GenBank· DDBJ | BAD92128.1 EMBL· GenBank· DDBJ | mRNA | Different initiation | |
AC104335 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
AL606804 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
CH471148 EMBL· GenBank· DDBJ | EAW77184.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
CH471148 EMBL· GenBank· DDBJ | EAW77186.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BC117211 EMBL· GenBank· DDBJ | AAI17212.1 EMBL· GenBank· DDBJ | mRNA | ||
BC143359 EMBL· GenBank· DDBJ | AAI43360.1 EMBL· GenBank· DDBJ | mRNA | ||
BC143362 EMBL· GenBank· DDBJ | AAI43363.1 EMBL· GenBank· DDBJ | mRNA | ||
BC143363 EMBL· GenBank· DDBJ | AAI43364.1 EMBL· GenBank· DDBJ | mRNA | ||
AY422168 EMBL· GenBank· DDBJ | AAQ98889.1 EMBL· GenBank· DDBJ | mRNA | ||
AF054176 EMBL· GenBank· DDBJ | AAC39910.1 EMBL· GenBank· DDBJ | mRNA | Frameshift |