Skip Header

Contribute Send feedback
Read comments (0) or add your own

Reviewed, UniProtKB/Swiss-Prot Q9NX02 (NALP2_HUMAN)

Last modified February 9, 2010. Version 97. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Alternative products · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

Names and origin

Protein namesRecommended 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
Name: NLRP2
Synonyms: NALP2, NBS1, PAN1, PYPAF2
OrganismHomo sapiens (Human) [Complete proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length1062 AA.
Sequence statusComplete.
Protein existenceEvidence 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

Cytoplasm Ref.8 Ref.7.

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 processApoptosis
   Cellular componentCytoplasm
   Coding sequence diversityAlternative splicing
Polymorphism
   DomainLeucine-rich repeat
Repeat
   LigandATP-binding
Nucleotide-binding
   Technical termComplete proteome
Gene Ontology (GO)
   Biological processapoptosis

Inferred from electronic annotation. Source: UniProtKB-KW

positive regulation of caspase activity Ref.7

Inferred from direct assay. Source: HGNC

positive regulation of interleukin-1 beta secretion Ref.7

Inferred from direct assay. Source: HGNC

   Cellular componentcytoplasm Ref.7

Inferred from direct assay. Source: HGNC

   Molecular functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

Pyrin domain binding Ref.7

Inferred 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 keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 10621062NACHT, LRR and PYD domains-containing protein 2
PRO_0000080888

Regions

Domain1 – 9494DAPIN
Domain207 – 526320NACHT
Repeat467 – 49125LRR 1
Repeat622 – 64524LRR 2
Repeat754 – 77724LRR 3
Repeat810 – 83223LRR 4
Repeat839 – 86224LRR 5
Repeat867 – 89024LRR 6
Repeat924 – 94724LRR 7
Repeat981 – 100525LRR 8
Repeat1010 – 103324LRR 9
Nucleotide binding213 – 2208ATP Potential
Compositional bias518 – 5236Poly-Glu

Natural variations

Alternative sequence109 – 13224Missing in isoform 4.
VSP_017085
Alternative sequence133 – 15422Missing in isoform 2.
VSP_005522
Alternative sequence847 – 1062216Missing in isoform 3.
VSP_017086
Natural variant2211T → M: dbSNP rs17699678.
VAR_053616
Natural variant3021E → Q: dbSNP rs3745904.
VAR_053617
Natural variant3641R → K: dbSNP rs4306647.
VAR_025011
Natural variant8841G → R: dbSNP rs59779270.
VAR_062140
Natural variant10521A → E: dbSNP rs1043673. Ref.6
VAR_020006

Experimental info

Sequence conflict11M → V in AAG15253. Ref.1
Sequence conflict351L → P in AAG15253. Ref.1
Sequence conflict581I → V in AAH39269. Ref.6
Sequence conflict1751W → C in BAD96973. Ref.5
Sequence conflict1751W → C in BAD96989. Ref.5
Sequence conflict3041I → S in BAB15293. Ref.4
Sequence conflict5291T → A in BAD92537. Ref.5
Sequence conflict9801Missing in AAG15253. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified October 1, 2000. Version 1.
Checksum: 4DBB0F6E9C2BC8A7

FASTA1,062120,515
        10         20         30         40         50         60 
MVSSAQMGFN LQALLEQLSQ DELSKFKYLI TTFSLAHELQ KIPHKEVDKA DGKQLVEILT 

        70         80         90        100        110        120 
THCDSYWVEM ASLQVFEKMH RMDLSERAKD EVREAALKSF NKRKPLSLGI TRKERPPLDV 

       130        140        150        160        170        180 
DEMLERFKTE AQAFTETKGN VICLGKEVFK GKKPDKDNRC RYILKTKFRE MWKSWPGDSK 

       190        200        210        220        230        240 
EVQVMAERYK MLIPFSNPRV LPGPFSYTVV LYGPAGLGKT TLAQKLMLDW AEDNLIHKFK 

       250        260        270        280        290        300 
YAFYLSCREL SRLGPCSFAE LVFRDWPELQ DDIPHILAQA RKILFVIDGF DELGAAPGAL 

       310        320        330        340        350        360 
IEDICGDWEK KKPVPVLLGS LLNRVMLPKA ALLVTTRPRA LRDLRILAEE PIYIRVEGFL 

       370        380        390        400        410        420 
EEDRRAYFLR HFGDEDQAMR AFELMRSNAA LFQLGSAPAV CWIVCTTLKL QMEKGEDPVP 

       430        440        450        460        470        480 
TCLTRTGLFL RFLCSRFPQG AQLRGALRTL SLLAAQGLWA QTSVLHREDL ERLGVQESDL 

       490        500        510        520        530        540 
RLFLDGDILR QDRVSKGCYS FIHLSFQQFL TALFYTLEKE EEEDRDGHTW DIGDVQKLLS 

       550        560        570        580        590        600 
GVERLRNPDL IQAGYYSFGL ANEKRAKELE ATFGCRMSPD IKQELLRCDI SCKGGHSTVT 

       610        620        630        640        650        660 
DLQELLGCLY ESQEEELVKE VMAQFKEISL HLNAVDVVPS SFCVKHCRNL QKMSLQVIKE 

       670        680        690        700        710        720 
NLPENVTASE SDAEVERSQD DQHMLPFWTD LCSIFGSNKD LMGLAINDSF LSASLVRILC 

       730        740        750        760        770        780 
EQIASDTCHL QRVVFKNISP ADAHRNLCLA LRGHKTVTYL TLQGNDQDDM FPALCEVLRH 

       790        800        810        820        830        840 
PECNLRYLGL VSCSATTQQW ADLSLALEVN QSLTCVNLSD NELLDEGAKL LYTTLRHPKC 

       850        860        870        880        890        900 
FLQRLSLENC HLTEANCKDL AAVLVVSREL THLCLAKNPI GNTGVKFLCE GLRYPECKLQ 

       910        920        930        940        950        960 
TLVLWNCDIT SDGCCDLTKL LQEKSSLLCL DLGLNHIGVK GMKFLCEALR KPLCNLRCLW 

       970        980        990       1000       1010       1020 
LWGCSIPPFS CEDLCSALSC NQSLVTLDLG QNPLGSSGVK MLFETLTCSS GTLRTLRLKI 

      1030       1040       1050       1060 
DDFNDELNKL LEEIEEKNPQ LIIDTEKHHP WAERPSSHDF MI 

« Hide

Isoform 2.

Checksum: 0FF49C18762CEDB4
Show »

FASTA1,040118,138
Isoform 3.

Checksum: 22DD3265062DC0CB
Show »

FASTA84696,383
Isoform 4.

Checksum: AA066954D53827F2
Show »

FASTA1,038117,674

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. 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: 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.
IPIIPI00016480.
IPI00218560.
IPI00719706.
IPI00719715.
RefSeqNP_060322.1.
UniGeneHs.369279

3D structure databases

SMRQ9NX02. Positions 10-92, 208-370, 693-1043.
ModBaseSearch...

Protein-protein interaction databases

STRINGQ9NX02.

Proteomic databases

PeptideAtlasQ9NX02.
PRIDEQ9NX02.

Genome annotation databases

EnsemblENST00000263437; ENSP00000263437; ENSG00000022556; Homo sapiens. [Genome view]
ENST00000448584; ENSP00000409370; ENSG00000022556; Homo sapiens. [Genome view]
GeneID55655.
KEGGhsa:55655.
UCSCuc002qij.1. human.
uc010esn.1. human.
uc010esp.1. human.

Organism-specific databases

CTD55655.
GeneCardsGC19P060170.
H-InvDBHIX0015449.
HIX0057240.
HGNCHGNC:22948. NLRP2.
HPAHPA020765.
MIM609364. gene.
GenAtlasSearch...

Phylogenomic databases

eggNOGprNOG06002.
HOVERGENQ9NX02.
InParanoidQ9NX02.
OMARPSSHDF.
OrthoDBEOG9QJV6C.
PhylomeDBQ9NX02.

Gene expression databases

ArrayExpressQ9NX02.
BgeeQ9NX02.
CleanExHS_NLRP2.
GenevestigatorQ9NX02.
GermOnlineENSG00000022556. Homo sapiens.

Family and domain databases

InterProIPR011029. DEATH-like.
IPR007111. NACHT_NTPase.
IPR004020. Pyrin.
[Graphical view]
Gene3DG3DSA:1.10.533.10. DEATH_like. 1 hit.
PfamPF02758. PAAD_DAPIN. 1 hit.
[Graphical view]
PROSITEPS50824. DAPIN. 1 hit.
PS50837. NACHT. 1 hit.
[Graphical view]
ProtoNetSearch...

Other Resources

NextBio60371.
SOURCESearch...

Entry information

Entry nameNALP2_HUMAN
AccessionPrimary (citable) accession number: Q9NX02
Secondary accession number(s): Q53FL5 expand/collapse secondary AC list , Q59G09, Q8IXT0, Q9BVN5, Q9H6G6, Q9HAV9, Q9NWK3
Entry history
Integrated into UniProtKB/Swiss-Prot: October 18, 2001
Last sequence update: October 1, 2000
Last modified: February 9, 2010
This is version 97 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)
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

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

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Alternative products · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents