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P59046 (NAL12_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 117. 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·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
NACHT, LRR and PYD domains-containing protein 12
Alternative name(s):
Monarch-1
PYRIN-containing APAF1-like protein 7
Regulated by nitric oxide
Gene names
Name:NLRP12
Synonyms:NALP12, PYPAF7, RNO
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length1061 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

May mediate activation of CASP1 via ASC and promote activation of NF-kappa-B via IKK.

Subunit structure

Binds to ASC with its DAPIN domain. Interacts with FAF1 UBA domain via its DAPIN domain. Ref.8

Subcellular location

Cytoplasm.

Tissue specificity

Detected only in peripheral blood leukocytes, predominantly in eosinophils and granulocytes, and at lower levels in monocytes. Ref.4

Induction

By nitric oxide and DMSO in HL-60 cells, an acute myeloid leukemia cell line. Ref.4

Involvement in disease

Familial cold autoinflammatory syndrome 2 (FCAS2) [MIM:611762]: 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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.7

Sequence similarities

Belongs to the NLRP family.

Contains 1 DAPIN domain.

Contains 8 LRR (leucine-rich) repeats.

Contains 1 NACHT domain.

Ontologies

Keywords
   Cellular componentCytoplasm
   Coding sequence diversityAlternative splicing
Polymorphism
   DomainLeucine-rich repeat
Repeat
   LigandATP-binding
Nucleotide-binding
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processactivation of cysteine-type endopeptidase activity involved in apoptotic process

Non-traceable author statement Ref.1. Source: UniProtKB

cellular response to cytokine stimulus

Inferred from electronic annotation. Source: Ensembl

dendritic cell migration

Inferred from electronic annotation. Source: Ensembl

negative regulation of ERK1 and ERK2 cascade

Inferred from electronic annotation. Source: Ensembl

negative regulation of I-kappaB kinase/NF-kappaB signaling

Inferred from direct assay PubMed 16203735. Source: HGNC

negative regulation of NF-kappaB transcription factor activity

Inferred from direct assay Ref.7. Source: BHF-UCL

negative regulation of NIK/NF-kappaB signaling

Inferred from electronic annotation. Source: Ensembl

negative regulation of Toll signaling pathway

Inferred from direct assay PubMed 16203735. Source: HGNC

negative regulation of cytokine secretion

Inferred from direct assay PubMed 16203735. Source: HGNC

negative regulation of inflammatory response

Inferred from mutant phenotype Ref.7. Source: BHF-UCL

negative regulation of interleukin-1 secretion

Inferred from direct assay PubMed 16203735. Source: HGNC

negative regulation of interleukin-6 biosynthetic process

Inferred from direct assay PubMed 16203735. Source: HGNC

negative regulation of protein autophosphorylation

Inferred from direct assay PubMed 16203735. Source: HGNC

negative regulation of signal transduction

Inferred from direct assay PubMed 16203735. Source: HGNC

positive regulation of inflammatory response

Non-traceable author statement Ref.1. Source: UniProtKB

positive regulation of interleukin-1 beta secretion

Non-traceable author statement Ref.1. Source: UniProtKB

regulation of interleukin-18 biosynthetic process

Non-traceable author statement Ref.1. Source: UniProtKB

release of cytoplasmic sequestered NF-kappaB

Inferred from direct assay Ref.1. Source: UniProtKB

signal transduction

Non-traceable author statement Ref.1. Source: UniProtKB

   Cellular_componentcytoplasm

Inferred from direct assay Ref.1. Source: UniProtKB

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

cysteine-type endopeptidase activator activity involved in apoptotic process

Non-traceable author statement Ref.1. Source: UniProtKB

Complete GO annotation...

Alternative products

This entry describes 5 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P59046-1)

Also known as: I;

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: P59046-2)

Also known as: II;

The sequence of this isoform differs from the canonical sequence as follows:
     976-1031: Missing.
Isoform 3 (identifier: P59046-3)

Also known as: III;

The sequence of this isoform differs from the canonical sequence as follows:
     862-973: Missing.
Isoform 4 (identifier: P59046-4)

Also known as: IV;

The sequence of this isoform differs from the canonical sequence as follows:
     862-1031: Missing.
Isoform 5 (identifier: P59046-5)

Also known as: rno-2;

The sequence of this isoform differs from the canonical sequence as follows:
     1-717: Missing.
     718-748: LSLYRNALGSRGVKLLCQGLRHPNCKLQNLR → MSQAWWHTSVSPATQEAKAGGLLQPRRQRLW
     921-977: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 10611061NACHT, LRR and PYD domains-containing protein 12
PRO_0000080899

Regions

Domain1 – 9595DAPIN
Domain211 – 528318NACHT
Repeat828 – 84821LRR 1
Repeat857 – 87822LRR 2
Repeat885 – 90622LRR 3
Repeat914 – 93522LRR 4
Repeat942 – 96221LRR 5
Repeat971 – 99222LRR 6
Repeat999 – 102022LRR 7
Repeat1028 – 104922LRR 8
Nucleotide binding217 – 2248ATP

Natural variations

Alternative sequence1 – 717717Missing in isoform 5.
VSP_016908
Alternative sequence718 – 74831LSLYR…LQNLR → MSQAWWHTSVSPATQEAKAG GLLQPRRQRLW in isoform 5.
VSP_016909
Alternative sequence862 – 1031170Missing in isoform 4.
VSP_009879
Alternative sequence862 – 973112Missing in isoform 3.
VSP_005523
Alternative sequence921 – 97757Missing in isoform 5.
VSP_016910
Alternative sequence976 – 103156Missing in isoform 2.
VSP_005524
Natural variant391G → V.
Corresponds to variant rs34436714 [ dbSNP | Ensembl ].
VAR_053620
Natural variant4021F → L.
Corresponds to variant rs34971363 [ dbSNP | Ensembl ].
VAR_053621

Experimental info

Sequence conflict6911L → LR in AAM75142. Ref.3
Sequence conflict6911L → LR in AAM75143. Ref.3
Sequence conflict6911L → LR in AAM75144. Ref.3

Secondary structure

.................. 1061
Helix Strand Turn

Details...

Sequences

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

Last modified August 22, 2003. Version 2.
Checksum: 8C10AFE4907C131B

FASTA1,061120,173
        10         20         30         40         50         60 
MLRTAGRDGL CRLSTYLEEL EAVELKKFKL YLGTATELGE GKIPWGSMEK AGPLEMAQLL 

        70         80         90        100        110        120 
ITHFGPEEAW RLALSTFERI NRKDLWERGQ REDLVRDTPP GGPSSLGNQS TCLLEVSLVT 

       130        140        150        160        170        180 
PRKDPQETYR DYVRRKFRLM EDRNARLGEC VNLSHRYTRL LLVKEHSNPM QVQQQLLDTG 

       190        200        210        220        230        240 
RGHARTVGHQ ASPIKIETLF EPDEERPEPP RTVVMQGAAG IGKSMLAHKV MLDWADGKLF 

       250        260        270        280        290        300 
QGRFDYLFYI NCREMNQSAT ECSMQDLIFS CWPEPSAPLQ ELIRVPERLL FIIDGFDELK 

       310        320        330        340        350        360 
PSFHDPQGPW CLCWEEKRPT ELLLNSLIRK KLLPELSLLI TTRPTALEKL HRLLEHPRHV 

       370        380        390        400        410        420 
EILGFSEAER KEYFYKYFHN AEQAGQVFNY VRDNEPLFTM CFVPLVCWVV CTCLQQQLEG 

       430        440        450        460        470        480 
GGLLRQTSRT TTAVYMLYLL SLMQPKPGAP RLQPPPNQRG LCSLAADGLW NQKILFEEQD 

       490        500        510        520        530        540 
LRKHGLDGED VSAFLNMNIF QKDINCERYY SFIHLSFQEF FAAMYYILDE GEGGAGPDQD 

       550        560        570        580        590        600 
VTRLLTEYAF SERSFLALTS RFLFGLLNEE TRSHLEKSLC WKVSPHIKMD LLQWIQSKAQ 

       610        620        630        640        650        660 
SDGSTLQQGS LEFFSCLYEI QEEEFIQQAL SHFQVIVVSN IASKMEHMVS SFCLKRCRSA 

       670        680        690        700        710        720 
QVLHLYGATY SADGEDRARC SAGAHTLLVQ LPERTVLLDA YSEHLAAALC TNPNLIELSL 

       730        740        750        760        770        780 
YRNALGSRGV KLLCQGLRHP NCKLQNLRLK RCRISSSACE DLSAALIANK NLTRMDLSGN 

       790        800        810        820        830        840 
GVGFPGMMLL CEGLRHPQCR LQMIQLRKCQ LESGACQEMA SVLGTNPHLV ELDLTGNALE 

       850        860        870        880        890        900 
DLGLRLLCQG LRHPVCRLRT LWLKICRLTA AACDELASTL SVNQSLRELD LSLNELGDLG 

       910        920        930        940        950        960 
VLLLCEGLRH PTCKLQTLRL GICRLGSAAC EGLSVVLQAN HNLRELDLSF NDLGDWGLWL 

       970        980        990       1000       1010       1020 
LAEGLQHPAC RLQKLWLDSC GLTAKACENL YFTLGINQTL TDLYLTNNAL GDTGVRLLCK 

      1030       1040       1050       1060 
RLSHPGCKLR VLWLFGMDLN KMTHSRLAAL RVTKPYLDIG C 

« Hide

Isoform 2 (II) [UniParc].

Checksum: 79BD8925AA43644F
Show »

FASTA1,005114,006
Isoform 3 (III) [UniParc].

Checksum: 99995A1C7261D636
Show »

FASTA949107,913
Isoform 4 (IV) [UniParc].

Checksum: 43093A9B22873A00
Show »

FASTA891101,504
Isoform 5 (rno-2) [UniParc].

Checksum: BD3816C3255B2F9E
Show »

FASTA28731,765

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]Williams K.L., Linhoff M.W., Harton J.A., Ting J.P.Y.
Submitted (MAY-2002) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2; 3 AND 4).
Tissue: Lymphoma.
[4]"Identification and characterization of a novel gene that is upregulated in leukaemia cells by nitric oxide."
Shami P.J., Kanai N., Wang L.Y., Vreeke T.M., Parker C.J.
Br. J. Haematol. 112:138-147(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 5), TISSUE SPECIFICITY, ALTERNATIVE SPLICING, INDUCTION.
Tissue: Peripheral blood leukocyte.
[5]"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 1).
Tissue: Leukocyte.
[6]"ATP binding by monarch-1/NLRP12 is critical for its inhibitory function."
Ye Z., Lich J.D., Moore C.B., Duncan J.A., Williams K.L., Ting J.P.
Mol. Cell. Biol. 28:1841-1850(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: ATP-BINDING.
[7]"Mutations in NALP12 cause hereditary periodic fever syndromes."
Jeru I., Duquesnoy P., Fernandes-Alnemri T., Cochet E., Yu J.W., Lackmy-Port-Lis M., Grimprel E., Landman-Parker J., Hentgen V., Marlin S., McElreavey K., Sarkisian T., Grateau G., Alnemri E.S., Amselem S.
Proc. Natl. Acad. Sci. U.S.A. 105:1614-1619(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN FCAS2.
[8]"The NLRP12 pyrin domain: structure, dynamics, and functional insights."
Pinheiro A.S., Eibl C., Ekman-Vural Z., Schwarzenbacher R., Peti W.
J. Mol. Biol. 413:790-803(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR OF 1-98, INTERACTION WITH FAF1.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AY095146 mRNA. Translation: AAM18227.1.
AY154467 mRNA. Translation: AAO18163.1.
AY116204 mRNA. Translation: AAM75142.1.
AY116205 mRNA. Translation: AAM75143.1.
AY116206 mRNA. Translation: AAM75144.1.
AY116207 mRNA. Translation: AAM75145.1.
AF231021 mRNA. Translation: AAK14942.1.
BC028069 mRNA. Translation: AAH28069.1.
RefSeqNP_001264055.1. NM_001277126.1.
NP_001264058.1. NM_001277129.1.
NP_653288.1. NM_144687.3.
UniGeneHs.631573.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2L6ANMR-A1-98[»]
ProteinModelPortalP59046.
SMRP59046. Positions 1-98, 643-1059.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid124861. 6 interactions.
IntActP59046. 2 interactions.
MINTMINT-237788.
STRING9606.ENSP00000319377.

PTM databases

PhosphoSiteP59046.

Polymorphism databases

DMDM34223733.

Proteomic databases

PaxDbP59046.
PRIDEP59046.

Protocols and materials databases

DNASU91662.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000324134; ENSP00000319377; ENSG00000142405. [P59046-1]
ENST00000345770; ENSP00000341428; ENSG00000142405.
ENST00000391772; ENSP00000375652; ENSG00000142405.
ENST00000391773; ENSP00000375653; ENSG00000142405.
GeneID91662.
KEGGhsa:91662.
UCSCuc002qch.5. human. [P59046-1]
uc010eqw.4. human. [P59046-5]

Organism-specific databases

CTD91662.
GeneCardsGC19M054296.
HGNCHGNC:22938. NLRP12.
HPAHPA042981.
MIM609648. gene.
611762. phenotype.
neXtProtNX_P59046.
Orphanet247868. NLRP12-associated hereditary periodic fever syndrome.
PharmGKBPA162397866.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG82860.
HOGENOMHOG000294064.
HOVERGENHBG063656.
OrthoDBEOG7P5T07.
PhylomeDBP59046.
TreeFamTF340267.

Gene expression databases

ArrayExpressP59046.
BgeeP59046.
CleanExHS_NLRP12.
GenevestigatorP59046.

Family and domain databases

Gene3D1.10.533.10. 1 hit.
InterProIPR004020. DAPIN.
IPR011029. DEATH-like_dom.
IPR001611. Leu-rich_rpt.
IPR007111. NACHT_NTPase.
IPR027417. P-loop_NTPase.
[Graphical view]
PfamPF02758. PYRIN. 1 hit.
[Graphical view]
SUPFAMSSF47986. SSF47986. 1 hit.
SSF52540. SSF52540. 1 hit.
PROSITEPS50824. DAPIN. 1 hit.
PS51450. LRR. 5 hits.
PS50837. NACHT. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP59046.
GeneWikiNLRP12.
GenomeRNAi91662.
NextBio77368.
PROP59046.
SOURCESearch...

Entry information

Entry nameNAL12_HUMAN
AccessionPrimary (citable) accession number: P59046
Secondary accession number(s): Q8NEU4, Q9BY26
Entry history
Integrated into UniProtKB/Swiss-Prot: October 19, 2002
Last sequence update: August 22, 2003
Last modified: April 16, 2014
This is version 117 of the entry and version 2 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