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Q96P20 (NALP3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 146. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
NACHT, LRR and PYD domains-containing protein 3
Alternative name(s):
Angiotensin/vasopressin receptor AII/AVP-like
Caterpiller protein 1.1
Short name=CLR1.1
Cold autoinflammatory syndrome 1 protein
Cryopyrin
PYRIN-containing APAF1-like protein 1
Gene names
Name:NLRP3
Synonyms:C1orf7, CIAS1, NALP3, PYPAF1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length1036 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

May function as an inducer of apoptosis. Interacts selectively with ASC and this complex may function as an upstream activator of NF-kappa-B signaling. Inhibits TNF-alpha induced activation and nuclear translocation of RELA/NF-KB p65. Also inhibits transcriptional activity of RELA. Activates caspase-1 in response to a number of triggers including bacterial or viral infection which leads to processing and release of IL1B and IL18. Ref.3 Ref.4

Subunit structure

Part of the NALP3 inflammasome complex which is involved in activation of caspase-1 and caspase-5, leading to processing of IL1B and IL18. Interacts with PYCARD/ASC, PML (isoform PML-1) EIF2AK2/PKR and MEFV. Ref.3 Ref.11 Ref.12 Ref.15 Ref.16 Ref.17

Subcellular location

Cytoplasm Ref.3 Ref.4 Ref.13.

Tissue specificity

Expressed in blood leukocytes. Strongly expressed in polymorphonuclear cells and osteoblasts. Undetectable or expressed at a lower magnitude in B- and T-lymphoblasts, respectively. High level of expression detected in chondrocytes. Detected in non-keratinizing epithelia of oropharynx, esophagus and ectocervix and in the urothelial layer of the bladder. Ref.3 Ref.13 Ref.14 Ref.19

Induction

By TNF. Ref.4

Post-translational modification

The disulfide bond in the DAPIN domain may play a role in inflammation activation by reactive oxygen species.

Involvement in disease

Familial cold autoinflammatory syndrome 1 (FCAS1) [MIM:120100]: 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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.1 Ref.2 Ref.18 Ref.21 Ref.23 Ref.26

Muckle-Wells syndrome (MWS) [MIM:191900]: 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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.1 Ref.2 Ref.18 Ref.23

Chronic infantile neurologic cutaneous and articular syndrome (CINCA) [MIM:607115]: Rare congenital inflammatory disorder characterized by a triad of neonatal onset of cutaneous symptoms, chronic meningitis, and joint manifestations with recurrent fever and inflammation.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.19 Ref.20 Ref.22 Ref.23 Ref.24 Ref.25

Sequence similarities

Belongs to the NLRP family.

Contains 1 DAPIN domain.

Contains 9 LRR (leucine-rich) repeats.

Contains 1 NACHT domain.

Sequence caution

The sequence AAC39910.1 differs from that shown. Reason: Frameshift at positions 893, 918 and 926.

The sequence AAL12497.1 differs from that shown. Reason: Erroneous initiation.

The sequence AAL12498.1 differs from that shown. Reason: Erroneous initiation.

The sequence AAL33908.1 differs from that shown. Reason: Erroneous initiation.

The sequence AAL65136.1 differs from that shown. Reason: Erroneous initiation.

The sequence AAQ98889.1 differs from that shown. Reason: Erroneous initiation.

The sequence BAD92128.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

The sequence BAG37494.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

The sequence CAI17155.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
   Biological processApoptosis
   Cellular componentCytoplasm
   Coding sequence diversityAlternative splicing
   DiseaseAmyloidosis
Deafness
Disease mutation
   DomainLeucine-rich repeat
Repeat
   LigandATP-binding
Nucleotide-binding
   PTMDisulfide bond
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processNLRP3 inflammasome complex assembly

Inferred from electronic annotation. Source: Ensembl

activation of cysteine-type endopeptidase activity involved in apoptotic process

Inferred from electronic annotation. Source: Ensembl

apoptotic process

Non-traceable author statement Ref.19. Source: UniProtKB

cellular response to lipopolysaccharide

Inferred from mutant phenotype Ref.20. Source: BHF-UCL

defense response

Traceable author statement PubMed 15967716. Source: HGNC

defense response to virus

Inferred from electronic annotation. Source: Ensembl

detection of biotic stimulus

Traceable author statement PubMed 15967716. Source: HGNC

inflammatory response

Inferred from mutant phenotype PubMed 12093792. Source: UniProtKB

innate immune response

Traceable author statement. Source: Reactome

interleukin-1 beta production

Inferred from electronic annotation. Source: Ensembl

interleukin-1 secretion

Inferred from electronic annotation. Source: Ensembl

interleukin-18 production

Inferred from electronic annotation. Source: Ensembl

negative regulation of NF-kappaB import into nucleus

Inferred from direct assay Ref.4. Source: HGNC

negative regulation of NF-kappaB transcription factor activity

Inferred from direct assay Ref.4. Source: HGNC

negative regulation of acute inflammatory response

Inferred from mutant phenotype Ref.1. Source: BHF-UCL

negative regulation of inflammatory response

Inferred from mutant phenotype Ref.20PubMed 16531551PubMed 17178985. Source: BHF-UCL

negative regulation of interleukin-1 beta secretion

Inferred from mutant phenotype Ref.20. Source: BHF-UCL

nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway

Traceable author statement. Source: Reactome

positive regulation of NF-kappaB transcription factor activity

Inferred from direct assay PubMed 19158675. Source: UniProtKB

positive regulation of cysteine-type endopeptidase activity involved in apoptotic process

Inferred from direct assay Ref.11. Source: HGNC

positive regulation of interleukin-1 beta secretion

Inferred from direct assay Ref.11. Source: HGNC

protein oligomerization

Traceable author statement PubMed 15967716. Source: HGNC

signal transduction

Non-traceable author statement Ref.3. Source: UniProtKB

   Cellular_componentNLRP3 inflammasome complex

Inferred from direct assay Ref.11. Source: UniProtKB

cytoplasm

Inferred from direct assay Ref.13. Source: BHF-UCL

cytosol

Traceable author statement. Source: Reactome

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

peptidoglycan binding

Traceable author statement PubMed 15967716. Source: HGNC

protein binding

Inferred from physical interaction Ref.15. Source: UniProtKB

Complete GO annotation...

Binary interactions

Alternative products

This entry describes 6 isoforms produced by alternative splicing. [Align] [Select]
Isoform 2 (identifier: 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.
Isoform 1 (identifier: Q96P20-2)

The sequence of this isoform differs from the canonical sequence as follows:
     721-777: Missing.
     836-892: Missing.
Isoform 3 (identifier: Q96P20-3)

The sequence of this isoform differs from the canonical sequence as follows:
     720-1036: Missing.
Isoform 4 (identifier: Q96P20-4)

The sequence of this isoform differs from the canonical sequence as follows:
     721-777: Missing.
Isoform 5 (identifier: Q96P20-5)

The sequence of this isoform differs from the canonical sequence as follows:
     836-892: Missing.
Note: No experimental confirmation available.
Isoform 6 (identifier: Q96P20-6)

The sequence of this isoform differs from the canonical sequence as follows:
     776-796: WLGRCGLSHECCFDISLVLSS → C
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 10361036NACHT, LRR and PYD domains-containing protein 3
PRO_0000080886

Regions

Domain1 – 9393DAPIN
Domain220 – 536317NACHT
Repeat742 – 76221LRR 1
Repeat771 – 79222LRR 2
Repeat799 – 81921LRR 3
Repeat828 – 84922LRR 4
Repeat856 – 87621LRR 5
Repeat885 – 90622LRR 6
Repeat913 – 93321LRR 7
Repeat942 – 96322LRR 8
Repeat970 – 99122LRR 9
Nucleotide binding226 – 2338ATP Potential
Compositional bias690 – 6978Poly-Glu

Amino acid modifications

Disulfide bond8 ↔ 108Redox-active Ref.17

Natural variations

Alternative sequence720 – 1036317Missing in isoform 3.
VSP_005519
Alternative sequence721 – 77757Missing in isoform 1 and isoform 4.
VSP_005520
Alternative sequence776 – 79621WLGRC…LVLSS → C in isoform 6.
VSP_053714
Alternative sequence836 – 89257Missing in isoform 1 and isoform 5.
VSP_005521
Natural variant1741I → T in CINCA. Ref.25
VAR_043679
Natural variant2001V → M in FCAS1 and MWS. Ref.1 Ref.2 Ref.18 Ref.23
Corresponds to variant rs121908147 [ dbSNP | Ensembl ].
VAR_013227
Natural variant2621R → L in CINCA. Ref.24
VAR_043680
Natural variant2621R → P in CINCA. Ref.24
VAR_043681
Natural variant2621R → W in FCAS1 and MWS. Ref.2 Ref.18
VAR_014104
Natural variant2661L → H in CINCA. Ref.20
VAR_043682
Natural variant3051D → G in CINCA. Ref.24
VAR_043683
Natural variant3051D → N in CINCA and MWS. Ref.18 Ref.19 Ref.20 Ref.23 Ref.24
VAR_014105
Natural variant3071L → P in FCAS1 and MWS. Ref.2 Ref.23
VAR_014124
Natural variant3081Q → L in CINCA. Ref.19
VAR_043684
Natural variant3111F → S in CINCA. Ref.19 Ref.24
VAR_014106
Natural variant3501T → M in MWS and CINCA. Ref.18 Ref.23 Ref.24
VAR_014366
Natural variant3541A → V in MWS. Ref.1
VAR_013228
Natural variant3551L → P in FCAS1. Ref.21
Corresponds to variant rs28937896 [ dbSNP | Ensembl ].
VAR_043685
Natural variant3561E → D in CINCA. Ref.24
VAR_043686
Natural variant3601H → R in CINCA. Ref.19
VAR_014367
Natural variant4071T → P in CINCA. Ref.24
VAR_043687
Natural variant4381T → I in CINCA. Ref.24
VAR_043688
Natural variant4381T → N in CINCA. Ref.19
VAR_014368
Natural variant4411A → T in MWS. Ref.18
VAR_014369
Natural variant4411A → V in FCAS1. Ref.1
VAR_013229
Natural variant4901R → K in FCAS1. Ref.23
Corresponds to variant rs145268073 [ dbSNP | Ensembl ].
VAR_043689
Natural variant5251F → C in FCAS1. Ref.26
VAR_031853
Natural variant5251F → L in CINCA. Ref.20
VAR_043690
Natural variant5711G → R in MWS. Ref.18
VAR_014107
Natural variant5721Y → C in CINCA. Ref.20 Ref.24
VAR_043691
Natural variant5751F → S in CINCA. Ref.19
VAR_014108
Natural variant6291E → G in FCAS1. Ref.1
VAR_013230
Natural variant6341L → F in CINCA. Ref.24
VAR_043692
Natural variant6641M → T in CINCA. Ref.19
VAR_014370
Natural variant7051Q → K. Ref.21
Corresponds to variant rs35829419 [ dbSNP | Ensembl ].
VAR_043693
Natural variant8611Y → C in CINCA. Ref.22
VAR_023551

Experimental info

Sequence conflict1671R → L in AAL78632. Ref.2
Sequence conflict1671R → L in AAM14669. Ref.2
Sequence conflict1671R → L in AAL14640. Ref.2
Sequence conflict3231Q → H in AAL78632. Ref.2
Sequence conflict3231Q → H in AAM14669. Ref.2
Sequence conflict3231Q → H in AAL14640. Ref.2
Sequence conflict4391T → S in AAC39910. Ref.10
Sequence conflict5231M → V in BAG37494. Ref.5
Sequence conflict5991K → M in AAC39910. Ref.10
Sequence conflict6171K → N in AAL78632. Ref.2
Sequence conflict6171K → N in AAM14669. Ref.2
Sequence conflict6171K → N in AAL14640. Ref.2
Sequence conflict622 – 6232QI → HD in AAC39910. Ref.10

Secondary structure

............... 1036
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 2 [UniParc].

Last modified November 3, 2009. Version 3.
Checksum: 4C1DFB2B5B283CE8

FASTA1,036118,173
        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 

« Hide

Isoform 1 [UniParc].

Checksum: 8680FA0F4259B6F8
Show »

FASTA922105,975
Isoform 3 [UniParc].

Checksum: 0BF2090304B74886
Show »

FASTA71983,533
Isoform 4 [UniParc].

Checksum: DB355ECE3BF0A226
Show »

FASTA979111,884
Isoform 5 [UniParc].

Checksum: 8E46F79B1A816B5E
Show »

FASTA979112,263
Isoform 6 [UniParc].

Checksum: CE6980B309C3322D
Show »

FASTA1,016115,968

References

« Hide 'large scale' references
[1]"Mutation of a new gene encoding a putative pyrin-like protein causes familial cold autoinflammatory syndrome and Muckle-Wells syndrome."
Hoffman H.M., Mueller J.L., Broide D.H., Wanderer A.A., Kolodner R.D.
Nat. Genet. 29:301-305(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS 1 AND 2), VARIANTS FCAS1 MET-200; VAL-441 AND GLY-629, VARIANT MWS VAL-354.
[2]"Association of mutations in the NALP3/CIAS1/PYPAF1 gene with a broad phenotype including recurrent fever, cold sensitivity, sensorineural deafness, and AA amyloidosis."
Aganna E., Martinon F., Hawkins P.N., Ross J.B., Swan D.C., Booth D.R., Lachmann H.J., Gaudet R., Woo P., Feighery C., Cotter F.E., Thome M., Hitman G.A., Tschopp J., McDermott M.F.
Arthritis Rheum. 46:2445-2452(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2 AND 3), VARIANT MWS MET-200, VARIANTS FCAS1/MWS TRP-262 AND PRO-307.
[3]"PYPAF1: a PYRIN-containing APAF1-like protein that assembles with ASC and activates NF-kB."
Manji G.A., Wang L., Geddes B.J., Brown M., Merriam S., Al-Garawi A., Mak S., Lora J.M., Briskin M., Jurman M., Cao J., DiStefano P.S., Bertin J.
J. Biol. Chem. 277:11570-11575(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION, INTERACTION WITH PYCARD/ASC, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[4]"CIAS1/cryopyrin/PYPAF1/NALP3/CATERPILLER 1.1 is an inducible inflammatory mediator with NF-kappa B suppressive properties."
O'Connor W. Jr., Harton J.A., Zhu X., Linhoff M.W., Ting J.-P.
J. Immunol. 171:6329-6333(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2 AND 4), FUNCTION, SUBCELLULAR LOCATION, INDUCTION BY TNF.
[5]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Brain.
[6]Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S., Ohara O., Nagase T., Kikuno R.F.
Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 5).
Tissue: Brain.
[7]"The DNA sequence and biological annotation of human chromosome 1."
Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. expand/collapse author list , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.
Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[9]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2; 4 AND 6).
Tissue: Colon.
[10]"Cloning and functional analysis of cDNAs with open reading frames for 300 previously undefined genes expressed in CD34+ hematopoietic stem/progenitor cells."
Zhang Q.-H., Ye M., Wu X.-Y., Ren S.-X., Zhao M., Zhao C.-J., Fu G., Shen Y., Fan H.-Y., Lu G., Zhong M., Xu X.-R., Han Z.-G., Zhang J.-W., Tao J., Huang Q.-H., Zhou J., Hu G.-X. expand/collapse author list , Gu J., Chen S.-J., Chen Z.
Genome Res. 10:1546-1560(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 393-1036 (ISOFORM 1).
Tissue: Umbilical cord blood.
[11]"NALP3 forms an IL-1beta-processing inflammasome with increased activity in Muckle-Wells autoinflammatory disorder."
Agostini L., Martinon F., Burns K., McDermott M.F., Hawkins P.N., Tschopp J.
Immunity 20:319-325(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION IN NALP3 INFLAMMASOME COMPLEX.
[12]"The SPRY domain of Pyrin, mutated in familial Mediterranean fever patients, interacts with inflammasome components and inhibits proIL-1beta processing."
Papin S., Cuenin S., Agostini L., Martinon F., Werner S., Beer H.D., Grutter C., Grutter M., Tschopp J.
Cell Death Differ. 14:1457-1466(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH MEFV.
[13]"Inflammasome components NALP 1 and 3 Show distinct but separate Expression profiles in human tissues suggesting a site-specific role in the inflammatory response."
Kummer J.A., Broekhuizen R., Everett H., Agostini L., Kuijk L., Martinon F., van Bruggen R., Tschopp J.
J. Histochem. Cytochem. 55:443-452(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[14]"Osteoblasts express NLRP3, a nucleotide-binding domain and leucine-rich repeat region containing receptor implicated in bacterially induced cell death."
McCall S.H., Sahraei M., Young A.B., Worley C.S., Duncan J.A., Ting J.P., Marriott I.
J. Bone Miner. Res. 23:30-40(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY.
[15]"Novel role of PKR in inflammasome activation and HMGB1 release."
Lu B., Nakamura T., Inouye K., Li J., Tang Y., Lundbaeck P., Valdes-Ferrer S.I., Olofsson P.S., Kalb T., Roth J., Zou Y., Erlandsson-Harris H., Yang H., Ting J.P., Wang H., Andersson U., Antoine D.J., Chavan S.S., Hotamisligil G.S., Tracey K.J.
Nature 488:670-674(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH EIF2AK2.
[16]"Selective inhibition of the NLRP3 inflammasome by targeting to promyelocytic leukemia protein in mouse and human."
Lo Y.H., Huang Y.W., Wu Y.H., Tsai C.S., Lin Y.C., Mo S.T., Kuo W.C., Chuang Y.T., Jiang S.T., Shih H.M., Lai M.Z.
Blood 121:3185-3194(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH PML.
[17]"Crystal structure of NALP3 protein pyrin domain (PYD) and its implications in inflammasome assembly."
Bae J.Y., Park H.H.
J. Biol. Chem. 286:39528-39536(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 3-112, SUBUNIT, DISULFIDE BOND.
[18]"New mutations of CIAS1 that are responsible for Muckle-Wells syndrome and familial cold urticaria: a novel mutation underlies both syndromes."
Dode C., Le Du N., Cuisset L., Letourneur F., Berthelot J.-M., Vaudour G., Meyrier A., Watts R.A., Scott D.G.I., Nicholls A., Granel B., Frances C., Garcier F., Edery P., Boulinguez S., Domergues J.-P., Delpech M., Grateau G.
Am. J. Hum. Genet. 70:1498-1506(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT FCAS1 MET-200, VARIANTS MWS ASN-305; MET-350; THR-441 AND ARG-571, VARIANT FCAS/MWS TRP-262.
[19]"Chronic infantile neurological cutaneous and articular syndrome is caused by mutations in CIAS1, a gene highly expressed in polymorphonuclear cells and chondrocytes."
Feldmann J., Prieur A.-M., Quartier P., Berquin P., Certain S., Cortis E., Teillac-Hamel D., Fischer A., de Saint Basile G.
Am. J. Hum. Genet. 71:198-203(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS CINCA ASN-305; LEU-308; SER-311; ARG-360; ASN-438; SER-575 AND THR-664, TISSUE SPECIFICITY.
[20]"De novo CIAS1 mutations, cytokine activation, and evidence for genetic heterogeneity in patients with neonatal-onset multisystem inflammatory disease (NOMID): a new member of the expanding family of pyrin-associated autoinflammatory diseases."
Aksentijevich I., Nowak M., Mallah M., Chae J.J., Watford W.T., Hofmann S.R., Stein L., Russo R., Goldsmith D., Dent P., Rosenberg H.F., Austin F., Remmers E.F., Balow J.E. Jr., Rosenzweig S., Komarow H., Shoham N.G., Wood G. expand/collapse author list , Jones J., Mangra N., Carrero H., Adams B.S., Moore T.L., Schikler K., Hoffman H., Lovell D.J., Lipnick R., Barron K., O'Shea J.J., Kastner D.L., Goldbach-Mansky R.
Arthritis Rheum. 46:3340-3348(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS CINCA HIS-266; ASN-305; LEU-525 AND CYS-572.
[21]"Fine structure mapping of CIAS1: identification of an ancestral haplotype and a common FCAS mutation, L353P."
Hoffman H.M., Gregory S.G., Mueller J.L., Tresierras M., Broide D.H., Wanderer A.A., Kolodner R.D.
Hum. Genet. 112:209-216(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT FCAS1 PRO-355, VARIANT LYS-705.
[22]"Variant chronic infantile neurologic, cutaneous, articular syndrome due to a mutation within the leucine-rich repeat domain of CIAS1."
Frenkel J., van Kempen M.J., Kuis W., van Amstel H.K.
Arthritis Rheum. 50:2719-2720(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT CINCA CYS-861.
[23]"Clinical and genetic heterogeneity among Spanish patients with recurrent autoinflammatory syndromes associated with the CIAS1/PYPAF1/NALP3 gene."
Arostegui J.I., Aldea A., Modesto C., Rua M.J., Argueelles F., Gonzalez-Ensenat M.A., Ramos E., Rius J., Plaza S., Vives J., Yaguee J.
Arthritis Rheum. 50:4045-4050(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS FCAS1 MET-200; PRO-307 AND LYS-490, VARIANT CINCA ASN-305, VARIANT MWS MET-350.
[24]"Molecular basis of the spectral expression of CIAS1 mutations associated with phagocytic cell-mediated autoinflammatory disorders CINCA/NOMID, MWS, and FCU."
Neven B., Callebaut I., Prieur A.-M., Feldmann J., Bodemer C., Lepore L., Derfalvi B., Benjaponpitak S., Vesely R., Sauvain M.J., Oertle S., Allen R., Morgan G., Borkhardt A., Hill C., Gardner-Medwin J., Fischer A., de Saint Basile G.
Blood 103:2809-2815(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS CINCA LEU-262; PRO-262; ASN-305; GLY-305; SER-311; MET-350; ASP-356; PRO-407; ILE-438; CYS-572 AND PHE-634.
[25]"A novel CIAS1 mutation and plasma/cerebrospinal fluid cytokine profile in a German patient with neonatal-onset multisystem inflammatory disease responsive to methotrexate therapy."
Stojanov S., Weiss M., Lohse P., Belohradsky B.H.
Pediatrics 114:E124-E127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT CINCA THR-174.
[26]"A novel missense mutation in CIAS1 encoding the pyrin-like protein, cryopyrin, causes familial cold autoinflammatory syndrome in a family of Ethiopian origin."
Shalev S.A., Sprecher E., Indelman M., Hujirat Y., Bergman R., Rottem M.
Int. Arch. Allergy Immunol. 143:190-193(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT FCAS1 CYS-525.
+Additional computationally mapped references.

Web resources

INFEVERS

Repertory of FMF and hereditary autoinflammatory disorders mutations

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF410477 mRNA. Translation: AAL33908.1. Different initiation.
AF427617 mRNA. Translation: AAL33911.1.
AY051117 expand/collapse EMBL AC list , AY051112, AY051113, AY051114, AY051115, AY051116, AY056059, AY056060 Genomic DNA. Translation: AAL12497.1. Different initiation.
AY051117 expand/collapse EMBL AC list , AY051112, AY051113, AY051114, AY051115, AY051116 Genomic DNA. Translation: AAL12498.1. Different initiation.
AF468522 mRNA. Translation: AAL78632.1.
AF420469 mRNA. Translation: AAL65136.1. Different initiation.
AY092033 mRNA. Translation: AAM14669.1.
AF418985 mRNA. Translation: AAL14640.2.
AY422168 mRNA. Translation: AAQ98889.1. Different initiation.
AK314998 mRNA. Translation: BAG37494.1. Different initiation.
AB208891 mRNA. Translation: BAD92128.1. Different initiation.
AL606804, AC104335 Genomic DNA. Translation: CAI17153.1.
AL606804, AC104335 Genomic DNA. Translation: CAI17154.1.
AL606804, AC104335 Genomic DNA. Translation: CAI17155.1. Different initiation.
CH471148 Genomic DNA. Translation: EAW77184.1.
BC117211 mRNA. Translation: AAI17212.1.
BC143359 mRNA. Translation: AAI43360.1.
BC143362 mRNA. Translation: AAI43363.1.
BC143363 mRNA. Translation: AAI43364.1.
AF054176 mRNA. Translation: AAC39910.1. Frameshift.
CCDSCCDS1632.1. [Q96P20-1]
CCDS1633.1. [Q96P20-2]
CCDS44346.1. [Q96P20-5]
CCDS44347.1. [Q96P20-4]
RefSeqNP_001073289.1. NM_001079821.2. [Q96P20-1]
NP_001120933.1. NM_001127461.2. [Q96P20-5]
NP_001120934.1. NM_001127462.2. [Q96P20-4]
NP_001230062.1. NM_001243133.1.
NP_004886.3. NM_004895.4. [Q96P20-1]
NP_899632.1. NM_183395.2. [Q96P20-2]
XP_005273093.1. XM_005273036.1. [Q96P20-1]
XP_005273094.1. XM_005273037.1. [Q96P20-1]
XP_005273095.1. XM_005273038.1. [Q96P20-4]
XP_006711796.1. XM_006711733.1. [Q96P20-1]
UniGeneHs.159483.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
3QF2X-ray1.70A/B3-112[»]
ProteinModelPortalQ96P20.
SMRQ96P20. Positions 5-110, 223-531, 666-1031.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid125319. 4 interactions.
DIPDIP-41153N.
IntActQ96P20. 3 interactions.
MINTMINT-230535.

Chemistry

ChEMBLCHEMBL1741208.

PTM databases

PhosphoSiteQ96P20.

Polymorphism databases

DMDM262527566.

Proteomic databases

PaxDbQ96P20.
PRIDEQ96P20.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000336119; ENSP00000337383; ENSG00000162711. [Q96P20-1]
ENST00000348069; ENSP00000294752; ENSG00000162711. [Q96P20-2]
ENST00000366496; ENSP00000355452; ENSG00000162711. [Q96P20-5]
ENST00000366497; ENSP00000355453; ENSG00000162711. [Q96P20-5]
ENST00000391827; ENSP00000375703; ENSG00000162711. [Q96P20-4]
ENST00000391828; ENSP00000375704; ENSG00000162711. [Q96P20-1]
GeneID114548.
KEGGhsa:114548.
UCSCuc001icr.3. human. [Q96P20-1]
uc001ics.3. human. [Q96P20-5]
uc001icv.3. human. [Q96P20-2]
uc001icw.3. human. [Q96P20-4]

Organism-specific databases

CTD114548.
GeneCardsGC01P247579.
HGNCHGNC:16400. NLRP3.
HPACAB009190.
HPA012878.
HPA017374.
MIM120100. phenotype.
191900. phenotype.
606416. gene.
607115. phenotype.
neXtProtNX_Q96P20.
Orphanet93365. CINCA syndrome with NLRP3 mutations.
47045. Familial cold urticaria.
575. Muckle-Wells syndrome.
PharmGKBPA26512.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG82860.
HOVERGENHBG063656.
InParanoidQ96P20.
KOK12800.
OMAQRAMDYF.
OrthoDBEOG7P5T07.
PhylomeDBQ96P20.
TreeFamTF340267.

Enzyme and pathway databases

ReactomeREACT_6900. Immune System.

Gene expression databases

ArrayExpressQ96P20.
BgeeQ96P20.
GenevestigatorQ96P20.

Family and domain databases

Gene3D1.10.533.10. 1 hit.
InterProIPR004020. DAPIN.
IPR011029. DEATH-like_dom.
IPR003590. Leu-rich_rpt_RNase_inh_sub-typ.
IPR007111. NACHT_NTPase.
IPR029495. NATCH-assoc.
IPR027417. P-loop_NTPase.
[Graphical view]
PfamPF14484. FISNA. 1 hit.
PF02758. PYRIN. 1 hit.
[Graphical view]
SMARTSM00368. LRR_RI. 3 hits.
[Graphical view]
SUPFAMSSF47986. SSF47986. 1 hit.
SSF52540. SSF52540. 2 hits.
PROSITEPS50824. DAPIN. 1 hit.
PS50837. NACHT. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiNALP3.
GenomeRNAi114548.
NextBio35481188.
PROQ96P20.
SOURCESearch...

Entry information

Entry nameNALP3_HUMAN
AccessionPrimary (citable) accession number: Q96P20
Secondary accession number(s): B2RC97 expand/collapse secondary AC list , B7ZKS9, B7ZKT2, B7ZKT3, O75434, Q17RS2, Q59H68, Q5JQS8, Q5JQS9, Q6TG35, Q8TCW0, Q8TEU9, Q8WXH9
Entry history
Integrated into UniProtKB/Swiss-Prot: May 2, 2002
Last sequence update: November 3, 2009
Last modified: July 9, 2014
This is version 146 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 1

Human chromosome 1: entries, gene names and cross-references to MIM