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Q8WX94 (NALP7_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 111. 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·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 7
Alternative name(s):
Nucleotide-binding oligomerization domain protein 12
PYRIN-containing APAF1-like protein 3
Gene names
Name:NLRP7
Synonyms:NALP7, NOD12, PYPAF3
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length980 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Inhibits CASP1/caspase-1-dependent IL1B secretion. Ref.6

Subunit structure

Directly interacts with CASP1 and IL1B. Ref.6

Tissue specificity

Expressed in numerous tissues including uterus and ovary, with low levels in heart and brain. Not detected in skeletal muscle. Ref.6 Ref.8

Induction

By bacterial lipopolysaccharides (LPS) and IL1B/interleukin-1 beta in peripheral blood mononuclear cells.

Involvement in disease

Hydatidiform mole, recurrent, 1 (HYDM1) [MIM:231090]: A disorder characterized by excessive trophoblast development that produces a growing mass of tissue inside the uterus at the beginning of a pregnancy. It leads to abnormal pregnancies with no embryo, and cystic degeneration of the chorionic villi.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.8 Ref.9

Sequence similarities

Belongs to the NLRP family.

Contains 1 DAPIN domain.

Contains 9 LRR (leucine-rich) repeats.

Contains 1 NACHT domain.

Ontologies

Keywords
   Coding sequence diversityAlternative splicing
Polymorphism
   DiseaseDisease mutation
   DomainLeucine-rich repeat
Repeat
   LigandATP-binding
Nucleotide-binding
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q8WX94-1)

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: Q8WX94-2)

The sequence of this isoform differs from the canonical sequence as follows:
     644-671: Missing.
     938-938: L → LWSCSLMPFYCQHLGSALLSNQKLETLDLGQNHLWKSGIIKLFGVLRQRTGSLKILRL
Note: No experimental confirmation available.
Isoform 3 (identifier: Q8WX94-3)

The sequence of this isoform differs from the canonical sequence as follows:
     938-938: L → LWSCSLMPFYCQHLGSALLSNQKLETLDLGQNHLWKSGIIKLFGVLRQRTGSLKILRL
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 980980NACHT, LRR and PYD domains-containing protein 7
PRO_0000080895

Regions

Domain1 – 9393DAPIN
Domain172 – 491320NACHT
Repeat614 – 63825LRR 1
Repeat674 – 69724LRR 2
Repeat760 – 78425LRR 3
Repeat788 – 81023LRR 4
Repeat817 – 84024LRR 5
Repeat845 – 86824LRR 6
Repeat874 – 89724LRR 7
Repeat902 – 92827LRR 8
Repeat933 – 95725LRR 9
Nucleotide binding178 – 1858ATP Potential

Natural variations

Alternative sequence644 – 67128Missing in isoform 2.
VSP_016906
Alternative sequence9381L → LWSCSLMPFYCQHLGSALLS NQKLETLDLGQNHLWKSGII KLFGVLRQRTGSLKILRL in isoform 2 and isoform 3.
VSP_016907
Natural variant3191V → I.
Corresponds to variant rs775882 [ dbSNP | Ensembl ].
VAR_026710
Natural variant3981L → R in HYDM1. Ref.9
VAR_059035
Natural variant4871G → E.
Corresponds to variant rs775881 [ dbSNP | Ensembl ].
VAR_060103
Natural variant6511P → S in HYDM1. Ref.9
VAR_059036
Natural variant6931R → P in HYDM1. Ref.8 Ref.9
VAR_026711
Natural variant6931R → Q in HYDM1. Ref.9
VAR_059037
Natural variant6931R → W in HYDM1. Ref.8 Ref.9
VAR_026712
Natural variant7161P → A in HYDM1. Ref.9
VAR_059038
Natural variant7211R → W in HYDM1. Ref.9
VAR_059039
Natural variant7611C → Y in HYDM1. Ref.9
VAR_059040
Natural variant9131N → S in HYDM1. Ref.8 Ref.9
Corresponds to variant rs104895503 [ dbSNP | Ensembl ].
VAR_026713
Natural variant9711T → A.
Corresponds to variant rs7256020 [ dbSNP | Ensembl ].
VAR_026714

Experimental info

Sequence conflict310 – 3112QL → RI in AAI09126. Ref.4
Sequence conflict4811A → T in AAI09126. Ref.4

Secondary structure

................ 980
Helix Strand Turn

Details...

Sequences

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

Last modified March 1, 2002. Version 1.
Checksum: 822AF2FD4338003D

FASTA980111,807
        10         20         30         40         50         60 
MTSPQLEWTL QTLLEQLNED ELKSFKSLLW AFPLEDVLQK TPWSEVEEAD GKKLAEILVN 

        70         80         90        100        110        120 
TSSENWIRNA TVNILEEMNL TELCKMAKAE MMEDGQVQEI DNPELGDAEE DSELAKPGEK 

       130        140        150        160        170        180 
EGWRNSMEKQ SLVWKNTFWQ GDIDNFHDDV TLRNQRFIPF LNPRTPRKLT PYTVVLHGPA 

       190        200        210        220        230        240 
GVGKTTLAKK CMLDWTDCNL SPTLRYAFYL SCKELSRMGP CSFAELISKD WPELQDDIPS 

       250        260        270        280        290        300 
ILAQAQRILF VVDGLDELKV PPGALIQDIC GDWEKKKPVP VLLGSLLKRK MLPRAALLVT 

       310        320        330        340        350        360 
TRPRALRDLQ LLAQQPIYVR VEGFLEEDRR AYFLRHFGDE DQAMRAFELM RSNAALFQLG 

       370        380        390        400        410        420 
SAPAVCWIVC TTLKLQMEKG EDPVPTCLTR TGLFLRFLCS RFPQGAQLRG ALRTLSLLAA 

       430        440        450        460        470        480 
QGLWAQMSVF HREDLERLGV QESDLRLFLD GDILRQDRVS KGCYSFIHLS FQQFLTALFY 

       490        500        510        520        530        540 
ALEKEEGEDR DGHAWDIGDV QKLLSGEERL KNPDLIQVGH FLFGLANEKR AKELEATFGC 

       550        560        570        580        590        600 
RMSPDIKQEL LQCKAHLHAN KPLSVTDLKE VLGCLYESQE EELAKVVVAP FKEISIHLTN 

       610        620        630        640        650        660 
TSEVMHCSFS LKHCQDLQKL SLQVAKGVFL ENYMDFELDI EFERCTYLTI PNWARQDLRS 

       670        680        690        700        710        720 
LRLWTDFCSL FSSNSNLKFL EVKQSFLSDS SVRILCDHVT RSTCHLQKVE IKNVTPDTAY 

       730        740        750        760        770        780 
RDFCLAFIGK KTLTHLTLAG HIEWERTMML MLCDLLRNHK CNLQYLRLGG HCATPEQWAE 

       790        800        810        820        830        840 
FFYVLKANQS LKHLRLSANV LLDEGAMLLY KTMTRPKHFL QMLSLENCRL TEASCKDLAA 

       850        860        870        880        890        900 
VLVVSKKLTH LCLAKNPIGD TGVKFLCEGL SYPDCKLQTL VLQQCSITKL GCRYLSEALQ 

       910        920        930        940        950        960 
EACSLTNLDL SINQIARGLW ILCQALENPN CNLKHLRLKT YETNLEIKKL LEEVKEKNPK 

       970        980 
LTIDCNASGA TAPPCCDFFC 

« Hide

Isoform 2 [UniParc].

Checksum: EB76450B0C05AE24
Show »

FASTA1,009114,845
Isoform 3 [UniParc].

Checksum: BB5642CADF5DA666
Show »

FASTA1,037118,303

References

« Hide 'large scale' references
[1]"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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]"NALPs: a novel protein family involved in inflammation."
Tschopp J., Martinon F., Burns K.
Nat. Rev. Mol. Cell Biol. 4:95-104(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[3]"The DNA sequence and biology of human chromosome 19."
Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., Carrano A.V. expand/collapse author list , Caoile C., Chan Y.M., Christensen M., Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., Rubin E.M., Lucas S.M.
Nature 428:529-535(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]"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] (ISOFORM 3).
[5]"NODs: intracellular proteins involved in inflammation and apoptosis."
Inohara N., Nunez G.
Nat. Rev. Immunol. 3:371-382(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION (ISOFORM 2).
[6]"PYPAF3, a PYRIN-containing APAF-1-like protein, is a feedback regulator of caspase-1-dependent interleukin-1beta secretion."
Kinoshita T., Wang Y., Hasegawa M., Imamura R., Suda T.
J. Biol. Chem. 280:21720-21725(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH CASP1 AND IL1B, TISSUE SPECIFICITY.
[7]"Three-dimensional structure of the NLRP7 pyrin domain: insight into pyrin-pyrin-mediated effector domain signaling in innate immunity."
Pinheiro A.S., Proell M., Eibl C., Page R., Schwarzenbacher R., Peti W.
J. Biol. Chem. 285:27402-27410(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR OF 1-96.
[8]"Mutations in NALP7 cause recurrent hydatidiform moles and reproductive wastage in humans."
Murdoch S., Djuric U., Mazhar B., Seoud M., Khan R., Kuick R., Bagga R., Kircheisen R., Ao A., Ratti B., Hanash S., Rouleau G.A., Slim R.
Nat. Genet. 38:300-302(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS HYDM1 TRP-693; PRO-693 AND SER-913, TISSUE SPECIFICITY.
[9]"Identification of 13 novel NLRP7 mutations in 20 families with recurrent hydatidiform mole; missense mutations cluster in the leucine-rich region."
Wang C.M., Dixon P.H., Decordova S., Hodges M.D., Sebire N.J., Ozalp S., Fallahian M., Sensi A., Ashrafi F., Repiska V., Zhao J., Xiang Y., Savage P.M., Seckl M.J., Fisher R.A.
J. Med. Genet. 46:569-575(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS HYDM1 ARG-398; SER-651; TRP-693; PRO-693; GLN-693; ALA-716; TRP-721; TYR-761 AND SER-913.
+Additional computationally mapped references.

Web resources

INFEVERS

Repertory of FMF and hereditary autoinflammatory disorders mutations

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF464765 mRNA. Translation: AAL69963.1.
AY154462 mRNA. Translation: AAO18158.1.
AC011476 Genomic DNA. No translation available.
BC109125 mRNA. Translation: AAI09126.1.
BK001113 mRNA. Translation: DAA01246.1.
RefSeqNP_001120727.1. NM_001127255.1.
NP_631915.2. NM_139176.3.
NP_996611.2. NM_206828.3.
UniGeneHs.351118.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2KM6NMR-A1-96[»]
ProteinModelPortalQ8WX94.
SMRQ8WX94. Positions 1-96, 603-968.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid128265. 2 interactions.
STRING9606.ENSP00000329568.

PTM databases

PhosphoSiteQ8WX94.

Polymorphism databases

DMDM24212128.

Proteomic databases

PaxDbQ8WX94.
PRIDEQ8WX94.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000328092; ENSP00000329568; ENSG00000167634. [Q8WX94-2]
ENST00000340844; ENSP00000339491; ENSG00000167634. [Q8WX94-1]
ENST00000448121; ENSP00000409137; ENSG00000167634. [Q8WX94-2]
ENST00000570326; ENSP00000461614; ENSG00000262736. [Q8WX94-2]
ENST00000570389; ENSP00000461532; ENSG00000263168. [Q8WX94-1]
ENST00000571114; ENSP00000461064; ENSG00000263168. [Q8WX94-2]
ENST00000571118; ENSP00000459241; ENSG00000263026. [Q8WX94-2]
ENST00000571397; ENSP00000461321; ENSG00000262690. [Q8WX94-2]
ENST00000571769; ENSP00000458231; ENSG00000263026. [Q8WX94-2]
ENST00000572166; ENSP00000459861; ENSG00000262457. [Q8WX94-2]
ENST00000572307; ENSP00000458674; ENSG00000262457. [Q8WX94-2]
ENST00000573987; ENSP00000459596; ENSG00000263068. [Q8WX94-1]
ENST00000575015; ENSP00000461257; ENSG00000262736. [Q8WX94-2]
ENST00000575084; ENSP00000458215; ENSG00000262009. [Q8WX94-1]
ENST00000575121; ENSP00000459698; ENSG00000263168. [Q8WX94-2]
ENST00000575386; ENSP00000460076; ENSG00000262690. [Q8WX94-1]
ENST00000575631; ENSP00000459086; ENSG00000262009. [Q8WX94-2]
ENST00000576007; ENSP00000459959; ENSG00000262736. [Q8WX94-1]
ENST00000576081; ENSP00000458962; ENSG00000262690. [Q8WX94-2]
ENST00000576102; ENSP00000458454; ENSG00000263026. [Q8WX94-1]
ENST00000576609; ENSP00000459548; ENSG00000262457. [Q8WX94-1]
ENST00000576715; ENSP00000458887; ENSG00000262009. [Q8WX94-2]
ENST00000576774; ENSP00000460017; ENSG00000263068. [Q8WX94-2]
ENST00000576855; ENSP00000459718; ENSG00000263068. [Q8WX94-2]
ENST00000585738; ENSP00000468742; ENSG00000263068. [Q8WX94-3]
ENST00000585875; ENSP00000467002; ENSG00000262009. [Q8WX94-1]
ENST00000586225; ENSP00000465333; ENSG00000262690. [Q8WX94-1]
ENST00000586640; ENSP00000465583; ENSG00000263026. [Q8WX94-1]
ENST00000586736; ENSP00000464771; ENSG00000262457. [Q8WX94-3]
ENST00000586781; ENSP00000468204; ENSG00000263168. [Q8WX94-1]
ENST00000587685; ENSP00000466268; ENSG00000263168. [Q8WX94-3]
ENST00000588487; ENSP00000467374; ENSG00000263026. [Q8WX94-3]
ENST00000588588; ENSP00000467625; ENSG00000263068. [Q8WX94-1]
ENST00000588756; ENSP00000467123; ENSG00000167634. [Q8WX94-3]
ENST00000588840; ENSP00000467159; ENSG00000262009. [Q8WX94-3]
ENST00000589207; ENSP00000466553; ENSG00000262736. [Q8WX94-3]
ENST00000589382; ENSP00000468657; ENSG00000262736. [Q8WX94-3]
ENST00000589500; ENSP00000468589; ENSG00000263068. [Q8WX94-3]
ENST00000589909; ENSP00000467009; ENSG00000262690. [Q8WX94-3]
ENST00000590030; ENSP00000465520; ENSG00000167634. [Q8WX94-1]
ENST00000590391; ENSP00000464834; ENSG00000262457. [Q8WX94-1]
ENST00000590894; ENSP00000466043; ENSG00000262009. [Q8WX94-3]
ENST00000591176; ENSP00000465388; ENSG00000262457. [Q8WX94-3]
ENST00000592036; ENSP00000466171; ENSG00000263168. [Q8WX94-3]
ENST00000592784; ENSP00000468706; ENSG00000167634. [Q8WX94-3]
ENST00000592964; ENSP00000467853; ENSG00000263026. [Q8WX94-3]
ENST00000592978; ENSP00000466323; ENSG00000262736. [Q8WX94-1]
ENST00000593150; ENSP00000466209; ENSG00000262690. [Q8WX94-3]
ENST00000603249; ENSP00000474619; ENSG00000270884. [Q8WX94-3]
ENST00000603510; ENSP00000475132; ENSG00000270884. [Q8WX94-2]
ENST00000605016; ENSP00000474665; ENSG00000270884. [Q8WX94-3]
ENST00000605335; ENSP00000474886; ENSG00000270884. [Q8WX94-1]
ENST00000605486; ENSP00000474261; ENSG00000270884. [Q8WX94-1]
ENST00000605774; ENSP00000473807; ENSG00000270884. [Q8WX94-2]
GeneID199713.
KEGGhsa:199713.
UCSCuc002qig.4. human. [Q8WX94-2]
uc002qih.4. human. [Q8WX94-1]
uc002qii.4. human. [Q8WX94-3]

Organism-specific databases

CTD199713.
GeneCardsGC19M055434.
HGNCHGNC:22947. NLRP7.
HPAHPA051382.
MIM231090. phenotype.
609661. gene.
neXtProtNX_Q8WX94.
Orphanet254688. Complete hydatidiform mole.
254693. Partial hydatidiform mole.
PharmGKBPA162398003.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG146691.
HOGENOMHOG000294064.
HOVERGENHBG103856.
PhylomeDBQ8WX94.

Gene expression databases

ArrayExpressQ8WX94.
BgeeQ8WX94.
CleanExHS_NLRP7.
GenevestigatorQ8WX94.

Family and domain databases

Gene3D1.10.533.10. 1 hit.
3.40.50.300. 1 hit.
InterProIPR004020. DAPIN.
IPR011029. DEATH-like_dom.
IPR007111. NACHT_NTPase.
IPR027417. P-loop_NTPase.
[Graphical view]
PfamPF02758. PYRIN. 1 hit.
[Graphical view]
SUPFAMSSF47986. SSF47986. 1 hit.
SSF52540. SSF52540. 2 hits.
PROSITEPS50824. DAPIN. 1 hit.
PS50837. NACHT. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSNLRP7. human.
EvolutionaryTraceQ8WX94.
GeneWikiNLRP7.
GenomeRNAi199713.
NextBio89703.
PROQ8WX94.
SOURCESearch...

Entry information

Entry nameNALP7_HUMAN
AccessionPrimary (citable) accession number: Q8WX94
Secondary accession number(s): E9PE16, Q32MH8, Q7RTR1
Entry history
Integrated into UniProtKB/Swiss-Prot: October 19, 2002
Last sequence update: March 1, 2002
Last modified: April 16, 2014
This is version 111 of the entry and version 1 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 19

Human chromosome 19: entries, gene names and cross-references to MIM