Reviewed,
UniProtKB/Swiss-Prot Q9NX02 (NALP2_HUMAN)
Last modified
February 9, 2010.
Version 97.
History...
Clusters with 100%,
90%,
50% identity |
Documents (5) |
Third-party data |
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Names and origin
| Protein names | Recommended name: NACHT, LRR and PYD domains-containing protein 2 Alternative name(s): PYRIN domain and NACHT domain-containing protein 1 PYRIN-containing APAF1-like protein 2 Nucleotide-binding site protein 1 | ||||
| Gene names |
| ||||
| Organism | Homo sapiens (Human) [Complete proteome] | ||||
| Taxonomic identifier | 9606 [NCBI] | ||||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Protein attributes
| Sequence length | 1062 AA. |
| Sequence status | Complete. |
| Protein existence | Evidence at protein level. |
General annotation (Comments)
| Function | Suppresses TNF- and CD40-induced NFKB1 activity at the level of the IKK complex, by inhibiting NFKBIA degradation induced by TNF. When associated with PYCARD, activates CASP1, leading to the secretion of mature proinflammatory cytokine IL1B. May be a component of the inflammasome, a protein complex which also includes PYCARD, CARD8 and CASP1 and whose function would be the activation of proinflammatory caspases. Ref.8 |
| Subunit structure | Interacts with CHUK, IKBKB and IKBKG, as well as with full-length PYCARD and with the DAPIN domain of NAPL1, but not the full-length protein. Ref.8 Ref.7 |
| Subcellular location | |
| Tissue specificity | Expressed at high levels in lung, placenta and thymus and at lower levels in ovary, intestine and brain. Ref.8 |
| Induction | By interferons and lipopolysaccharide (LPS). Ref.8 |
| Domain | The DAPIN domain is necessary and sufficient for suppression of NFKB1 activation induced by TNF and for inducing IL1B secretion in collaboration with caspase-1. It is involved in interaction with PYCARD. When isolated, the NACHT domain is involved in interaction with CARD8. This interaction is not detected for the full-length protein, maybe due to autoinhibition, this inhibition might by relieved by an inducible change in protein folding. |
| 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 BAD92537.1 differs from that shown. Reason: Frameshift at position 769. The sequence BAD92537.1 differs from that shown. Reason: Miscellaneous discrepancy. Erroneous prediction of the initiator methionine. |
Ontologies
| Keywords | |
|---|---|
| Biological process | Apoptosis |
| Cellular component | Cytoplasm |
| Coding sequence diversity | Alternative splicing Polymorphism |
| Domain | Leucine-rich repeat Repeat |
| Ligand | ATP-binding Nucleotide-binding |
| Technical term | Complete proteome |
| Gene Ontology (GO) | |
| Biological process | apoptosis Inferred from electronic annotation. Source: UniProtKB-KW positive regulation of caspase activity Ref.7Inferred from direct assay. Source: HGNC positive regulation of interleukin-1 beta secretion Ref.7Inferred from direct assay. Source: HGNC |
| Cellular component | cytoplasm Ref.7 Inferred from direct assay. Source: HGNC |
| Molecular function | ATP binding Inferred from electronic annotation. Source: UniProtKB-KW Pyrin domain binding Ref.7Inferred from physical interaction. Source: HGNC |
| Complete GO annotation... | |
Alternative products
| This entry describes 4 isoforms produced by alternative splicing. [Align] [Select] | ||||||
| Isoform 1 (identifier: Q9NX02-1) 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 2 (identifier: Q9NX02-2) The sequence of this isoform differs from the canonical sequence as follows: 133-154: Missing. | ||||||
| Isoform 3 (identifier: Q9NX02-3) The sequence of this isoform differs from the canonical sequence as follows: 847-1062: Missing. | ||||||
| Note: No experimental confirmation available. | ||||||
| Isoform 4 (identifier: Q9NX02-4) The sequence of this isoform differs from the canonical sequence as follows: 109-132: Missing. | ||||||
| Note: No experimental confirmation available. |
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||
Molecule processing | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Chain | 1 – 1062 | 1062 | NACHT, LRR and PYD domains-containing protein 2 | PRO_0000080888 | |||||
Regions | |||||||||
| Domain | 1 – 94 | 94 | DAPIN | ||||||
| Domain | 207 – 526 | 320 | NACHT | ||||||
| Repeat | 467 – 491 | 25 | LRR 1 | ||||||
| Repeat | 622 – 645 | 24 | LRR 2 | ||||||
| Repeat | 754 – 777 | 24 | LRR 3 | ||||||
| Repeat | 810 – 832 | 23 | LRR 4 | ||||||
| Repeat | 839 – 862 | 24 | LRR 5 | ||||||
| Repeat | 867 – 890 | 24 | LRR 6 | ||||||
| Repeat | 924 – 947 | 24 | LRR 7 | ||||||
| Repeat | 981 – 1005 | 25 | LRR 8 | ||||||
| Repeat | 1010 – 1033 | 24 | LRR 9 | ||||||
| Nucleotide binding | 213 – 220 | 8 | ATP Potential | ||||||
| Compositional bias | 518 – 523 | 6 | Poly-Glu | ||||||
Natural variations | |||||||||
| Alternative sequence | 109 – 132 | 24 | Missing in isoform 4. | VSP_017085 | |||||
| Alternative sequence | 133 – 154 | 22 | Missing in isoform 2. | VSP_005522 | |||||
| Alternative sequence | 847 – 1062 | 216 | Missing in isoform 3. | VSP_017086 | |||||
| Natural variant | 221 | 1 | T → M: dbSNP rs17699678. | VAR_053616 | |||||
| Natural variant | 302 | 1 | E → Q: dbSNP rs3745904. | VAR_053617 | |||||
| Natural variant | 364 | 1 | R → K: dbSNP rs4306647. | VAR_025011 | |||||
| Natural variant | 884 | 1 | G → R: dbSNP rs59779270. | VAR_062140 | |||||
| Natural variant | 1052 | 1 | A → E: dbSNP rs1043673. Ref.6 | VAR_020006 | |||||
Experimental info | |||||||||
| Sequence conflict | 1 | 1 | M → V in AAG15253. Ref.1 | ||||||
| Sequence conflict | 35 | 1 | L → P in AAG15253. Ref.1 | ||||||
| Sequence conflict | 58 | 1 | I → V in AAH39269. Ref.6 | ||||||
| Sequence conflict | 175 | 1 | W → C in BAD96973. Ref.5 | ||||||
| Sequence conflict | 175 | 1 | W → C in BAD96989. Ref.5 | ||||||
| Sequence conflict | 304 | 1 | I → S in BAB15293. Ref.4 | ||||||
| Sequence conflict | 529 | 1 | T → A in BAD92537. Ref.5 | ||||||
| Sequence conflict | 980 | 1 | Missing in AAG15253. Ref.1 | ||||||
Sequences
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References
| « Hide 'large scale' references | |
| [1] | "The PYRIN domain: a novel motif found in apoptosis and inflammation proteins." Bertin J., DiStefano P.S. Cell Death Differ. 7:1273-1274(2000) [PubMed: 11270363] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), VARIANT LYS-364. |
| [2] | "The pyrin domain: a possible member of the death domain-fold family implicated in apoptosis and inflammation." Martinon F., Hofmann K., Tschopp J. Curr. Biol. 11:R118-R120(2001) [PubMed: 11250163] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). |
| [3] | "PYPAF7, a novel PYRIN-containing Apaf1-like protein that regulates activation of NF-kappa B and caspase-1-dependent cytokine processing." Wang L., Manji G.A., Grenier J.M., Al-Garawi A., Merriam S., Lora J.M., Geddes B.J., Briskin M., DiStefano P.S., Bertin J. J. Biol. Chem. 277:29874-29880(2002) [PubMed: 12019269] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). |
| [4] | "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. Sugano S.Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Colon and Kidney epithelium. |
| [5] | Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S. Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 4). Tissue: Brain and Gastric mucosa. |
| [6] | "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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3), VARIANT GLU-1052. Tissue: Lung, Placenta and Testis. |
| [7] | "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: 15030775] [Abstract] Cited for: INTERACTION WITH PYCARD AND CARD8, SUBCELLULAR LOCATION. |
| [8] | "PAN1/NALP2/PYPAF2, an inducible inflammatory mediator that regulates NF-kappaB and caspase-1 activation in macrophages." Bruey J.-M., Bruey-Sedano N., Newman R., Chandler S., Stehlik C., Reed J.C. J. Biol. Chem. 279:51897-51907(2004) [PubMed: 15456791] [Abstract] Cited for: FUNCTION, INTERACTION WITH CHUK; IKBKB; IKBKG AND PYCARD, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, INDUCTION. |
| [9] | Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY. |
Cross-references
Sequence databases | |
|---|---|
| EMBL GenBank DDBJ | AF298547 mRNA. Translation: AAG15253.1. Different initiation. AF310106 mRNA. Translation: AAG30289.1. AF464764 mRNA. Translation: AAL69962.1. AK000517 mRNA. Translation: BAA91223.1. AK025952 mRNA. Translation: BAB15293.1. AK000784 mRNA. Translation: BAA91377.1. Different initiation. AB209300 mRNA. Translation: BAD92537.1. Sequence problems. AK223253 mRNA. Translation: BAD96973.1. AK223269 mRNA. Translation: BAD96989.1. BC001039 mRNA. Translation: AAH01039.1. BC003592 mRNA. Translation: AAH03592.1. BC039269 mRNA. Translation: AAH39269.1. |
| IPI | IPI00016480. IPI00218560. IPI00719706. IPI00719715. |
| RefSeq | NP_060322.1. |
| UniGene | Hs.369279 |
3D structure databases | |
| SMR | Q9NX02. Positions 10-92, 208-370, 693-1043. |
| ModBase | Search... |
Protein-protein interaction databases | |
| STRING | Q9NX02. |
Proteomic databases | |
| PeptideAtlas | Q9NX02. |
| PRIDE | Q9NX02. |
Genome annotation databases | |
| Ensembl | ENST00000263437; ENSP00000263437; ENSG00000022556; Homo sapiens. [Genome view] ENST00000448584; ENSP00000409370; ENSG00000022556; Homo sapiens. [Genome view] |
| GeneID | 55655. |
| KEGG | hsa:55655. |
| UCSC | uc002qij.1. human. uc010esn.1. human. uc010esp.1. human. |
Organism-specific databases | |
| CTD | 55655. |
| GeneCards | GC19P060170. |
| H-InvDB | HIX0015449. HIX0057240. |
| HGNC | HGNC:22948. NLRP2. |
| HPA | HPA020765. |
| MIM | 609364. gene. |
| GenAtlas | Search... |
Phylogenomic databases | |
| eggNOG | prNOG06002. |
| HOVERGEN | Q9NX02. |
| InParanoid | Q9NX02. |
| OMA | RPSSHDF. |
| OrthoDB | EOG9QJV6C. |
| PhylomeDB | Q9NX02. |
Gene expression databases | |
| ArrayExpress | Q9NX02. |
| Bgee | Q9NX02. |
| CleanEx | HS_NLRP2. |
| Genevestigator | Q9NX02. |
| GermOnline | ENSG00000022556. Homo sapiens. |
Family and domain databases | |
| InterPro | IPR011029. DEATH-like. IPR007111. NACHT_NTPase. IPR004020. Pyrin. [Graphical view] |
| Gene3D | G3DSA:1.10.533.10. DEATH_like. 1 hit. |
| Pfam | PF02758. PAAD_DAPIN. 1 hit. [Graphical view] |
| PROSITE | PS50824. DAPIN. 1 hit. PS50837. NACHT. 1 hit. [Graphical view] |
| ProtoNet | Search... |
Other Resources | |
| NextBio | 60371. |
| SOURCE | Search... |
Entry information
| Entry name | NALP2_HUMAN | ||||||||
| Accession | Primary (citable) accession number: Q9NX02 Secondary accession number(s): Q53FL5 Q9NWK3 | ||||||||
| Entry history |
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| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation project | HPI (Human Proteome Initiative) | ||||||||
| Disclaimer | Any 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
| Human chromosome 19 Human chromosome 19: entries, gene names and cross-references to MIM |
| Human entries with polymorphisms or disease mutations List of human entries with polymorphisms or disease mutations |
| Human polymorphisms and disease mutations Index of human polymorphisms and disease mutations |
| MIM cross-references Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot |
| SIMILARITY comments Index of protein domains and families |

Clusters with


