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Protein

NACHT, LRR and PYD domains-containing protein 12

Gene

NLRP12

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi217 – 224ATP8

GO - Molecular functioni

GO - Biological processi

  • activation of cysteine-type endopeptidase activity involved in apoptotic process Source: UniProtKB
  • cellular response to cytokine stimulus Source: Ensembl
  • dendritic cell migration Source: Ensembl
  • negative regulation of cytokine secretion Source: HGNC
  • negative regulation of ERK1 and ERK2 cascade Source: Ensembl
  • negative regulation of I-kappaB kinase/NF-kappaB signaling Source: HGNC
  • negative regulation of inflammatory response Source: BHF-UCL
  • negative regulation of interleukin-1 secretion Source: HGNC
  • negative regulation of interleukin-6 biosynthetic process Source: HGNC
  • negative regulation of NF-kappaB transcription factor activity Source: BHF-UCL
  • negative regulation of NIK/NF-kappaB signaling Source: Ensembl
  • negative regulation of protein autophosphorylation Source: HGNC
  • negative regulation of signal transduction Source: HGNC
  • negative regulation of Toll signaling pathway Source: HGNC
  • positive regulation of inflammatory response Source: UniProtKB
  • positive regulation of interleukin-1 beta secretion Source: UniProtKB
  • positive regulation of MHC class I biosynthetic process Source: MGI
  • regulation of cysteine-type endopeptidase activity involved in apoptotic process Source: MGI
  • regulation of I-kappaB kinase/NF-kappaB signaling Source: MGI
  • regulation of interleukin-18 biosynthetic process Source: UniProtKB
  • release of cytoplasmic sequestered NF-kappaB Source: UniProtKB
  • signal transduction Source: UniProtKB
Complete GO annotation...

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

BioCyciZFISH:ENSG00000142405-MONOMER.

Names & Taxonomyi

Protein namesi
Recommended 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 namesi
Name:NLRP12
Synonyms:NALP12, PYPAF7, RNO
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 19

Organism-specific databases

HGNCiHGNC:22938. NLRP12.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Involvement in diseasei

Familial cold autoinflammatory syndrome 2 (FCAS2)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA 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.
See also OMIM:611762

Organism-specific databases

DisGeNETi91662.
MalaCardsiNLRP12.
MIMi611762. phenotype.
OpenTargetsiENSG00000142405.
Orphaneti247868. NLRP12-associated hereditary periodic fever syndrome.
PharmGKBiPA162397866.

Polymorphism and mutation databases

DMDMi34223733.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000808991 – 1061NACHT, LRR and PYD domains-containing protein 12Add BLAST1061

Proteomic databases

PaxDbiP59046.
PeptideAtlasiP59046.
PRIDEiP59046.

PTM databases

iPTMnetiP59046.
PhosphoSitePlusiP59046.

Expressioni

Tissue specificityi

Detected only in peripheral blood leukocytes, predominantly in eosinophils and granulocytes, and at lower levels in monocytes.1 Publication

Inductioni

By nitric oxide and DMSO in HL-60 cells, an acute myeloid leukemia cell line.1 Publication

Gene expression databases

BgeeiENSG00000142405.
CleanExiHS_NLRP12.
ExpressionAtlasiP59046. baseline and differential.
GenevisibleiP59046. HS.

Organism-specific databases

HPAiHPA042981.

Interactioni

Subunit structurei

Binds to ASC with its pyrin domain. Interacts with FAF1 UBA domain via its pyrin domain.1 Publication

Protein-protein interaction databases

BioGridi124861. 6 interactors.
IntActiP59046. 24 interactors.
MINTiMINT-237788.
STRINGi9606.ENSP00000319377.

Structurei

Secondary structure

11061
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi10 – 17Combined sources8
Helixi22 – 35Combined sources14
Turni37 – 40Combined sources4
Helixi45 – 48Combined sources4
Helixi53 – 64Combined sources12
Helixi66 – 77Combined sources12
Turni78 – 81Combined sources4
Helixi83 – 90Combined sources8
Beta strandi95 – 98Combined sources4

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2L6ANMR-A1-98[»]
4XHSX-ray1.70A/B10-106[»]
ProteinModelPortaliP59046.
SMRiP59046.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP59046.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini1 – 95PyrinPROSITE-ProRule annotationAdd BLAST95
Domaini211 – 528NACHTPROSITE-ProRule annotationAdd BLAST318
Repeati828 – 848LRR 1Add BLAST21
Repeati857 – 878LRR 2Add BLAST22
Repeati885 – 906LRR 3Add BLAST22
Repeati914 – 935LRR 4Add BLAST22
Repeati942 – 962LRR 5Add BLAST21
Repeati971 – 992LRR 6Add BLAST22
Repeati999 – 1020LRR 7Add BLAST22
Repeati1028 – 1049LRR 8Add BLAST22

Sequence similaritiesi

Belongs to the NLRP family.Curated
Contains 8 LRR (leucine-rich) repeats.Curated
Contains 1 NACHT domain.PROSITE-ProRule annotation
Contains 1 pyrin domain.PROSITE-ProRule annotation

Keywords - Domaini

Leucine-rich repeat, Repeat

Phylogenomic databases

eggNOGiENOG410IE5X. Eukaryota.
ENOG4111H3D. LUCA.
GeneTreeiENSGT00860000133669.
HOGENOMiHOG000294064.
HOVERGENiHBG063656.
InParanoidiP59046.
OMAiQANHNLR.
OrthoDBiEOG091G01CG.
PhylomeDBiP59046.
TreeFamiTF340267.

Family and domain databases

Gene3Di1.10.533.10. 1 hit.
3.40.50.300. 1 hit.
3.80.10.10. 2 hits.
InterProiIPR004020. DAPIN.
IPR011029. DEATH-like_dom.
IPR032675. L_dom-like.
IPR001611. Leu-rich_rpt.
IPR029495. NACHT-assoc.
IPR007111. NACHT_NTPase.
IPR027417. P-loop_NTPase.
[Graphical view]
PfamiPF14484. FISNA. 1 hit.
PF13516. LRR_6. 5 hits.
PF02758. PYRIN. 1 hit.
[Graphical view]
SMARTiSM01288. FISNA. 1 hit.
SM01289. PYRIN. 1 hit.
[Graphical view]
SUPFAMiSSF47986. SSF47986. 1 hit.
SSF52540. SSF52540. 1 hit.
PROSITEiPS50824. DAPIN. 1 hit.
PS51450. LRR. 5 hits.
PS50837. NACHT. 1 hit.
[Graphical view]

Sequences (7)i

Sequence statusi: Complete.

This entry describes 7 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P59046-1) [UniParc]FASTAAdd to basket
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.

« Hide

        10         20         30         40         50
MLRTAGRDGL CRLSTYLEEL EAVELKKFKL YLGTATELGE GKIPWGSMEK
60 70 80 90 100
AGPLEMAQLL ITHFGPEEAW RLALSTFERI NRKDLWERGQ REDLVRDTPP
110 120 130 140 150
GGPSSLGNQS TCLLEVSLVT PRKDPQETYR DYVRRKFRLM EDRNARLGEC
160 170 180 190 200
VNLSHRYTRL LLVKEHSNPM QVQQQLLDTG RGHARTVGHQ ASPIKIETLF
210 220 230 240 250
EPDEERPEPP RTVVMQGAAG IGKSMLAHKV MLDWADGKLF QGRFDYLFYI
260 270 280 290 300
NCREMNQSAT ECSMQDLIFS CWPEPSAPLQ ELIRVPERLL FIIDGFDELK
310 320 330 340 350
PSFHDPQGPW CLCWEEKRPT ELLLNSLIRK KLLPELSLLI TTRPTALEKL
360 370 380 390 400
HRLLEHPRHV EILGFSEAER KEYFYKYFHN AEQAGQVFNY VRDNEPLFTM
410 420 430 440 450
CFVPLVCWVV CTCLQQQLEG GGLLRQTSRT TTAVYMLYLL SLMQPKPGAP
460 470 480 490 500
RLQPPPNQRG LCSLAADGLW NQKILFEEQD LRKHGLDGED VSAFLNMNIF
510 520 530 540 550
QKDINCERYY SFIHLSFQEF FAAMYYILDE GEGGAGPDQD VTRLLTEYAF
560 570 580 590 600
SERSFLALTS RFLFGLLNEE TRSHLEKSLC WKVSPHIKMD LLQWIQSKAQ
610 620 630 640 650
SDGSTLQQGS LEFFSCLYEI QEEEFIQQAL SHFQVIVVSN IASKMEHMVS
660 670 680 690 700
SFCLKRCRSA QVLHLYGATY SADGEDRARC SAGAHTLLVQ LPERTVLLDA
710 720 730 740 750
YSEHLAAALC TNPNLIELSL YRNALGSRGV KLLCQGLRHP NCKLQNLRLK
760 770 780 790 800
RCRISSSACE DLSAALIANK NLTRMDLSGN GVGFPGMMLL CEGLRHPQCR
810 820 830 840 850
LQMIQLRKCQ LESGACQEMA SVLGTNPHLV ELDLTGNALE DLGLRLLCQG
860 870 880 890 900
LRHPVCRLRT LWLKICRLTA AACDELASTL SVNQSLRELD LSLNELGDLG
910 920 930 940 950
VLLLCEGLRH PTCKLQTLRL GICRLGSAAC EGLSVVLQAN HNLRELDLSF
960 970 980 990 1000
NDLGDWGLWL LAEGLQHPAC RLQKLWLDSC GLTAKACENL YFTLGINQTL
1010 1020 1030 1040 1050
TDLYLTNNAL GDTGVRLLCK RLSHPGCKLR VLWLFGMDLN KMTHSRLAAL
1060
RVTKPYLDIG C
Length:1,061
Mass (Da):120,173
Last modified:August 22, 2003 - v2
Checksum:i8C10AFE4907C131B
GO
Isoform 2 (identifier: P59046-2) [UniParc]FASTAAdd to basket
Also known as: II

The sequence of this isoform differs from the canonical sequence as follows:
     976-1031: Missing.

Show »
Length:1,005
Mass (Da):114,006
Checksum:i79BD8925AA43644F
GO
Isoform 3 (identifier: P59046-3) [UniParc]FASTAAdd to basket
Also known as: III

The sequence of this isoform differs from the canonical sequence as follows:
     862-973: Missing.

Show »
Length:949
Mass (Da):107,913
Checksum:i99995A1C7261D636
GO
Isoform 4 (identifier: P59046-4) [UniParc]FASTAAdd to basket
Also known as: IV

The sequence of this isoform differs from the canonical sequence as follows:
     862-1031: Missing.

Show »
Length:891
Mass (Da):101,504
Checksum:i43093A9B22873A00
GO
Isoform 5 (identifier: P59046-5) [UniParc]FASTAAdd to basket
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.

Show »
Length:287
Mass (Da):31,765
Checksum:iBD3816C3255B2F9E
GO
Isoform 6 (identifier: P59046-6) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     920-976: Missing.

Note: No experimental confirmation available.
Show »
Length:1,004
Mass (Da):113,876
Checksum:i7D7350A83F286749
GO
Isoform 7 (identifier: P59046-7) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     691-691: L → LR

Note: No experimental confirmation.
Show »
Length:1,062
Mass (Da):120,329
Checksum:i0AB81C87F116497F
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti648M → T in BAG53059 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_05362039G → V.Corresponds to variant rs34436714dbSNPEnsembl.1
Natural variantiVAR_053621402F → L.Corresponds to variant rs34971363dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0169081 – 717Missing in isoform 5. 1 PublicationAdd BLAST717
Alternative sequenceiVSP_055193691L → LR in isoform 7. 1 Publication1
Alternative sequenceiVSP_016909718 – 748LSLYR…LQNLR → MSQAWWHTSVSPATQEAKAG GLLQPRRQRLW in isoform 5. 1 PublicationAdd BLAST31
Alternative sequenceiVSP_009879862 – 1031Missing in isoform 4. 1 PublicationAdd BLAST170
Alternative sequenceiVSP_005523862 – 973Missing in isoform 3. 1 PublicationAdd BLAST112
Alternative sequenceiVSP_054622920 – 976Missing in isoform 6. 1 PublicationAdd BLAST57
Alternative sequenceiVSP_016910921 – 977Missing in isoform 5. 1 PublicationAdd BLAST57
Alternative sequenceiVSP_005524976 – 1031Missing in isoform 2. 1 PublicationAdd BLAST56

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
AK095460 mRNA. Translation: BAG53059.1.
AC008753 Genomic DNA. No translation available.
CH471135 Genomic DNA. Translation: EAW72152.1.
BC028069 mRNA. Translation: AAH28069.1.
CCDSiCCDS12864.1. [P59046-1]
CCDS62784.1. [P59046-6]
CCDS62785.1. [P59046-7]
RefSeqiNP_001264055.1. NM_001277126.1. [P59046-7]
NP_001264058.1. NM_001277129.1. [P59046-6]
NP_653288.1. NM_144687.3. [P59046-1]
UniGeneiHs.631573.

Genome annotation databases

EnsembliENST00000324134; ENSP00000319377; ENSG00000142405. [P59046-1]
ENST00000391773; ENSP00000375653; ENSG00000142405. [P59046-7]
ENST00000391775; ENSP00000375655; ENSG00000142405. [P59046-6]
GeneIDi91662.
KEGGihsa:91662.
UCSCiuc002qch.6. human. [P59046-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
AK095460 mRNA. Translation: BAG53059.1.
AC008753 Genomic DNA. No translation available.
CH471135 Genomic DNA. Translation: EAW72152.1.
BC028069 mRNA. Translation: AAH28069.1.
CCDSiCCDS12864.1. [P59046-1]
CCDS62784.1. [P59046-6]
CCDS62785.1. [P59046-7]
RefSeqiNP_001264055.1. NM_001277126.1. [P59046-7]
NP_001264058.1. NM_001277129.1. [P59046-6]
NP_653288.1. NM_144687.3. [P59046-1]
UniGeneiHs.631573.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2L6ANMR-A1-98[»]
4XHSX-ray1.70A/B10-106[»]
ProteinModelPortaliP59046.
SMRiP59046.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi124861. 6 interactors.
IntActiP59046. 24 interactors.
MINTiMINT-237788.
STRINGi9606.ENSP00000319377.

PTM databases

iPTMnetiP59046.
PhosphoSitePlusiP59046.

Polymorphism and mutation databases

DMDMi34223733.

Proteomic databases

PaxDbiP59046.
PeptideAtlasiP59046.
PRIDEiP59046.

Protocols and materials databases

DNASUi91662.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000324134; ENSP00000319377; ENSG00000142405. [P59046-1]
ENST00000391773; ENSP00000375653; ENSG00000142405. [P59046-7]
ENST00000391775; ENSP00000375655; ENSG00000142405. [P59046-6]
GeneIDi91662.
KEGGihsa:91662.
UCSCiuc002qch.6. human. [P59046-1]

Organism-specific databases

CTDi91662.
DisGeNETi91662.
GeneCardsiNLRP12.
HGNCiHGNC:22938. NLRP12.
HPAiHPA042981.
MalaCardsiNLRP12.
MIMi609648. gene.
611762. phenotype.
neXtProtiNX_P59046.
OpenTargetsiENSG00000142405.
Orphaneti247868. NLRP12-associated hereditary periodic fever syndrome.
PharmGKBiPA162397866.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IE5X. Eukaryota.
ENOG4111H3D. LUCA.
GeneTreeiENSGT00860000133669.
HOGENOMiHOG000294064.
HOVERGENiHBG063656.
InParanoidiP59046.
OMAiQANHNLR.
OrthoDBiEOG091G01CG.
PhylomeDBiP59046.
TreeFamiTF340267.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000142405-MONOMER.

Miscellaneous databases

EvolutionaryTraceiP59046.
GeneWikiiNLRP12.
GenomeRNAii91662.
PROiP59046.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000142405.
CleanExiHS_NLRP12.
ExpressionAtlasiP59046. baseline and differential.
GenevisibleiP59046. HS.

Family and domain databases

Gene3Di1.10.533.10. 1 hit.
3.40.50.300. 1 hit.
3.80.10.10. 2 hits.
InterProiIPR004020. DAPIN.
IPR011029. DEATH-like_dom.
IPR032675. L_dom-like.
IPR001611. Leu-rich_rpt.
IPR029495. NACHT-assoc.
IPR007111. NACHT_NTPase.
IPR027417. P-loop_NTPase.
[Graphical view]
PfamiPF14484. FISNA. 1 hit.
PF13516. LRR_6. 5 hits.
PF02758. PYRIN. 1 hit.
[Graphical view]
SMARTiSM01288. FISNA. 1 hit.
SM01289. PYRIN. 1 hit.
[Graphical view]
SUPFAMiSSF47986. SSF47986. 1 hit.
SSF52540. SSF52540. 1 hit.
PROSITEiPS50824. DAPIN. 1 hit.
PS51450. LRR. 5 hits.
PS50837. NACHT. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiNAL12_HUMAN
AccessioniPrimary (citable) accession number: P59046
Secondary accession number(s): A8MTQ2
, B3KTE7, Q8NEU4, Q9BY26
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 19, 2002
Last sequence update: August 22, 2003
Last modified: November 30, 2016
This is version 145 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 19
    Human chromosome 19: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.