UniProtKB - P59046 (NAL12_HUMAN)
NACHT, LRR and PYD domains-containing protein 12
NLRP12
Functioni
Plays an essential role as an potent mitigator of inflammation (PubMed:30559449).
Primarily expressed in dendritic cells and macrophages, inhibits both canonical and non-canonical NF-kappa-B and ERK activation pathways (PubMed:15489334, PubMed:17947705).
Functions as a negative regulator of NOD2 by targeting it to degradation via the proteasome pathway (PubMed:30559449).
In turn, promotes bacterial tolerance (PubMed:30559449).
Inhibits also the DDX58-mediated immune signaling against RNA viruses by reducing the E3 ubiquitin ligase TRIM25-mediated 'Lys-63'-linked DDX58 activation but enhancing the E3 ubiquitin ligase RNF125-mediated 'Lys-48'-linked DDX58 degradation (PubMed:30902577).
Acts also as a negative regulator of inflammatory response to mitigate obesity and obesity-associated diseases in adipose tissue (By similarity).
By similarity4 PublicationsRegions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Nucleotide bindingi | 217 – 224 | ATP | 8 |
GO - Molecular functioni
- ATP binding Source: UniProtKB-KW
- cysteine-type endopeptidase activator activity involved in apoptotic process Source: UniProtKB
GO - Biological processi
- activation of cysteine-type endopeptidase activity involved in apoptotic process Source: UniProtKB
- cellular response to cytokine stimulus Source: GO_Central
- dendritic cell migration Source: Ensembl
- negative regulation of cytokine production Source: HGNC-UCL
- negative regulation of ERK1 and ERK2 cascade Source: Ensembl
- negative regulation of I-kappaB kinase/NF-kappaB signaling Source: HGNC-UCL
- negative regulation of inflammatory response Source: BHF-UCL
- negative regulation of interleukin-1 production Source: HGNC-UCL
- negative regulation of interleukin-6 production Source: HGNC-UCL
- negative regulation of NF-kappaB transcription factor activity Source: BHF-UCL
- negative regulation of NIK/NF-kappaB signaling Source: UniProtKB
- negative regulation of protein autophosphorylation Source: HGNC-UCL
- negative regulation of signal transduction Source: HGNC-UCL
- negative regulation of Toll signaling pathway Source: HGNC-UCL
- positive regulation of inflammatory response Source: UniProtKB
- positive regulation of interleukin-1 beta production Source: UniProtKB
- positive regulation of MHC class I biosynthetic process Source: MGI
- positive regulation of NIK/NF-kappaB signaling Source: UniProtKB
- 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 production Source: UniProtKB
- signal transduction Source: UniProtKB
Keywordsi
Ligand | ATP-binding, Nucleotide-binding |
Enzyme and pathway databases
PathwayCommonsi | P59046 |
SignaLinki | P59046 |
Names & Taxonomyi
Protein namesi | Recommended name: NACHT, LRR and PYD domains-containing protein 12Alternative name(s): Monarch-1 PYRIN-containing APAF1-like protein 7 Regulated by nitric oxide |
Gene namesi | Name:NLRP12 Synonyms:NALP12, PYPAF7, RNO |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:22938, NLRP12 |
MIMi | 609648, gene |
neXtProti | NX_P59046 |
VEuPathDBi | HostDB:ENSG00000142405 |
Subcellular locationi
Cytoplasm and Cytosol
- Cytoplasm 1 Publication
Other locations
- cytoplasm Source: UniProtKB
Keywords - Cellular componenti
CytoplasmPathology & Biotechi
Involvement in diseasei
Familial cold autoinflammatory syndrome 2 (FCAS2)1 Publication
Organism-specific databases
DisGeNETi | 91662 |
MalaCardsi | NLRP12 |
MIMi | 611762, phenotype |
OpenTargetsi | ENSG00000142405 |
Orphaneti | 247868, NLRP12-associated hereditary periodic fever syndrome |
PharmGKBi | PA162397866 |
Miscellaneous databases
Pharosi | P59046, Tbio |
Genetic variation databases
BioMutai | NLRP12 |
DMDMi | 34223733 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000080899 | 1 – 1061 | NACHT, LRR and PYD domains-containing protein 12Add BLAST | 1061 |
Proteomic databases
MassIVEi | P59046 |
PaxDbi | P59046 |
PeptideAtlasi | P59046 |
PRIDEi | P59046 |
ProteomicsDBi | 2044 57117 [P59046-1] 57118 [P59046-2] 57119 [P59046-3] 57120 [P59046-4] 57121 [P59046-5] |
PTM databases
GlyGeni | P59046, 1 site, 1 O-linked glycan (1 site) |
iPTMneti | P59046 |
PhosphoSitePlusi | P59046 |
Expressioni
Tissue specificityi
Inductioni
Gene expression databases
Bgeei | ENSG00000142405, Expressed in blood and 78 other tissues |
ExpressionAtlasi | P59046, baseline and differential |
Genevisiblei | P59046, HS |
Organism-specific databases
HPAi | ENSG00000142405, Tissue enhanced (bone marrow, lymphoid tissue) |
Interactioni
Subunit structurei
Interacts (via pyrin domain) with ASC.
Interacts (via pyrin domain) with FAF1 (via UBA domain) (PubMed:21978668).
Interacts with MAP3K14; this interaction promotes proteasomal degradation of MAP3K14 (PubMed:17237370).
Interacts with NOD2; this interaction promotes degradation of NOD2 through the ubiquitin-proteasome pathway (PubMed:30559449).
Interacts with HSPA1A and HSPA8 (PubMed:17947705).
Interacts with HSP90AA1 (PubMed:17947705, PubMed:30559449).
Interacts with TRIM25; this interaction inhibits DDX58-mediated signaling pathway (PubMed:30902577).
5 PublicationsBinary interactionsi
P59046
Protein-protein interaction databases
BioGRIDi | 124861, 10 interactors |
IntActi | P59046, 76 interactors |
MINTi | P59046 |
STRINGi | 9606.ENSP00000375653 |
Miscellaneous databases
RNActi | P59046, protein |
Structurei
Secondary structure
3D structure databases
BMRBi | P59046 |
SMRi | P59046 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | P59046 |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 1 – 95 | PyrinPROSITE-ProRule annotationAdd BLAST | 95 | |
Domaini | 211 – 528 | NACHTPROSITE-ProRule annotationAdd BLAST | 318 | |
Repeati | 828 – 848 | LRR 1Add BLAST | 21 | |
Repeati | 857 – 878 | LRR 2Add BLAST | 22 | |
Repeati | 885 – 906 | LRR 3Add BLAST | 22 | |
Repeati | 914 – 935 | LRR 4Add BLAST | 22 | |
Repeati | 942 – 962 | LRR 5Add BLAST | 21 | |
Repeati | 971 – 992 | LRR 6Add BLAST | 22 | |
Repeati | 999 – 1020 | LRR 7Add BLAST | 22 | |
Repeati | 1028 – 1049 | LRR 8Add BLAST | 22 |
Sequence similaritiesi
Keywords - Domaini
Leucine-rich repeat, RepeatPhylogenomic databases
eggNOGi | ENOG502QS9E, Eukaryota |
GeneTreei | ENSGT00940000160873 |
InParanoidi | P59046 |
OMAi | PIFCWMA |
OrthoDBi | 114368at2759 |
PhylomeDBi | P59046 |
TreeFami | TF340267 |
Family and domain databases
Gene3Di | 1.10.533.10, 1 hit 3.40.50.300, 1 hit 3.80.10.10, 2 hits |
InterProi | View protein in InterPro IPR004020, DAPIN IPR011029, DEATH-like_dom_sf IPR001611, Leu-rich_rpt IPR032675, LRR_dom_sf IPR029495, NACHT-assoc IPR007111, NACHT_NTPase IPR041267, NLRP_HD2 IPR041075, NOD2_WH IPR027417, P-loop_NTPase |
Pfami | View protein in Pfam PF14484, FISNA, 1 hit PF13516, LRR_6, 5 hits PF05729, NACHT, 1 hit PF17776, NLRC4_HD2, 1 hit PF17779, NOD2_WH, 1 hit PF02758, PYRIN, 1 hit |
SMARTi | View protein in SMART SM01288, FISNA, 1 hit SM01289, PYRIN, 1 hit |
SUPFAMi | SSF47986, SSF47986, 1 hit SSF52540, SSF52540, 1 hit |
PROSITEi | View protein in PROSITE PS50824, DAPIN, 1 hit PS51450, LRR, 5 hits PS50837, NACHT, 1 hit |
s (7+)i Sequence
Sequence statusi: Complete.
This entry describes 7 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 7 described isoforms and 2 potential isoforms that are computationally mapped.Show allAlign All
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
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
Computationally mapped potential isoform sequencesi
There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketA0A0C4DH17 | A0A0C4DH17_HUMAN | NACHT, LRR and PYD domains-containi... | NLRP12 | 1,006 | Annotation score: | ||
A0A0C4DFY3 | A0A0C4DFY3_HUMAN | NACHT, LRR and PYD domains-containi... | NLRP12 | 892 | Annotation score: |
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 648 | M → T in BAG53059 (PubMed:14702039).Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_053620 | 39 | G → V. Corresponds to variant dbSNP:rs34436714EnsemblClinVar. | 1 | |
Natural variantiVAR_053621 | 402 | F → L. Corresponds to variant dbSNP:rs34971363EnsemblClinVar. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_016908 | 1 – 717 | Missing in isoform 5. 1 PublicationAdd BLAST | 717 | |
Alternative sequenceiVSP_055193 | 691 | L → LR in isoform 7. 1 Publication | 1 | |
Alternative sequenceiVSP_016909 | 718 – 748 | LSLYR…LQNLR → MSQAWWHTSVSPATQEAKAG GLLQPRRQRLW in isoform 5. 1 PublicationAdd BLAST | 31 | |
Alternative sequenceiVSP_009879 | 862 – 1031 | Missing in isoform 4. 1 PublicationAdd BLAST | 170 | |
Alternative sequenceiVSP_005523 | 862 – 973 | Missing in isoform 3. 1 PublicationAdd BLAST | 112 | |
Alternative sequenceiVSP_054622 | 920 – 976 | Missing in isoform 6. 1 PublicationAdd BLAST | 57 | |
Alternative sequenceiVSP_016910 | 921 – 977 | Missing in isoform 5. 1 PublicationAdd BLAST | 57 | |
Alternative sequenceiVSP_005524 | 976 – 1031 | Missing in isoform 2. 1 PublicationAdd BLAST | 56 |
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 |
CCDSi | CCDS12864.1 [P59046-1] CCDS62784.1 [P59046-6] CCDS62785.1 [P59046-7] |
RefSeqi | NP_001264055.1, NM_001277126.1 [P59046-7] NP_001264058.1, NM_001277129.1 [P59046-6] NP_653288.1, NM_144687.3 [P59046-1] |
Genome annotation databases
Ensembli | ENST00000324134; ENSP00000319377; ENSG00000142405 ENST00000391773; ENSP00000375653; ENSG00000142405 [P59046-7] ENST00000391775; ENSP00000375655; ENSG00000142405 [P59046-6] |
GeneIDi | 91662 |
KEGGi | hsa:91662 |
MANE-Selecti | ENST00000324134.11; ENSP00000319377.6; NM_144687.4; NP_653288.1 |
UCSCi | uc002qch.6, human [P59046-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
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 |
CCDSi | CCDS12864.1 [P59046-1] CCDS62784.1 [P59046-6] CCDS62785.1 [P59046-7] |
RefSeqi | NP_001264055.1, NM_001277126.1 [P59046-7] NP_001264058.1, NM_001277129.1 [P59046-6] NP_653288.1, NM_144687.3 [P59046-1] |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
2L6A | NMR | - | A | 1-98 | [»] | |
4XHS | X-ray | 1.70 | A/B | 10-106 | [»] | |
5H7N | X-ray | 1.85 | A/B | 9-106 | [»] | |
BMRBi | P59046 | |||||
SMRi | P59046 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 124861, 10 interactors |
IntActi | P59046, 76 interactors |
MINTi | P59046 |
STRINGi | 9606.ENSP00000375653 |
PTM databases
GlyGeni | P59046, 1 site, 1 O-linked glycan (1 site) |
iPTMneti | P59046 |
PhosphoSitePlusi | P59046 |
Genetic variation databases
BioMutai | NLRP12 |
DMDMi | 34223733 |
Proteomic databases
MassIVEi | P59046 |
PaxDbi | P59046 |
PeptideAtlasi | P59046 |
PRIDEi | P59046 |
ProteomicsDBi | 2044 57117 [P59046-1] 57118 [P59046-2] 57119 [P59046-3] 57120 [P59046-4] 57121 [P59046-5] |
Protocols and materials databases
Antibodypediai | 32741, 323 antibodies from 34 providers |
DNASUi | 91662 |
Genome annotation databases
Ensembli | ENST00000324134; ENSP00000319377; ENSG00000142405 ENST00000391773; ENSP00000375653; ENSG00000142405 [P59046-7] ENST00000391775; ENSP00000375655; ENSG00000142405 [P59046-6] |
GeneIDi | 91662 |
KEGGi | hsa:91662 |
MANE-Selecti | ENST00000324134.11; ENSP00000319377.6; NM_144687.4; NP_653288.1 |
UCSCi | uc002qch.6, human [P59046-1] |
Organism-specific databases
CTDi | 91662 |
DisGeNETi | 91662 |
GeneCardsi | NLRP12 |
HGNCi | HGNC:22938, NLRP12 |
HPAi | ENSG00000142405, Tissue enhanced (bone marrow, lymphoid tissue) |
MalaCardsi | NLRP12 |
MIMi | 609648, gene 611762, phenotype |
neXtProti | NX_P59046 |
OpenTargetsi | ENSG00000142405 |
Orphaneti | 247868, NLRP12-associated hereditary periodic fever syndrome |
PharmGKBi | PA162397866 |
VEuPathDBi | HostDB:ENSG00000142405 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | ENOG502QS9E, Eukaryota |
GeneTreei | ENSGT00940000160873 |
InParanoidi | P59046 |
OMAi | PIFCWMA |
OrthoDBi | 114368at2759 |
PhylomeDBi | P59046 |
TreeFami | TF340267 |
Enzyme and pathway databases
PathwayCommonsi | P59046 |
SignaLinki | P59046 |
Miscellaneous databases
BioGRID-ORCSi | 91662, 8 hits in 1034 CRISPR screens |
ChiTaRSi | NLRP12, human |
EvolutionaryTracei | P59046 |
GeneWikii | NLRP12 |
GenomeRNAii | 91662 |
Pharosi | P59046, Tbio |
PROi | PR:P59046 |
RNActi | P59046, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000142405, Expressed in blood and 78 other tissues |
ExpressionAtlasi | P59046, baseline and differential |
Genevisiblei | P59046, HS |
Family and domain databases
Gene3Di | 1.10.533.10, 1 hit 3.40.50.300, 1 hit 3.80.10.10, 2 hits |
InterProi | View protein in InterPro IPR004020, DAPIN IPR011029, DEATH-like_dom_sf IPR001611, Leu-rich_rpt IPR032675, LRR_dom_sf IPR029495, NACHT-assoc IPR007111, NACHT_NTPase IPR041267, NLRP_HD2 IPR041075, NOD2_WH IPR027417, P-loop_NTPase |
Pfami | View protein in Pfam PF14484, FISNA, 1 hit PF13516, LRR_6, 5 hits PF05729, NACHT, 1 hit PF17776, NLRC4_HD2, 1 hit PF17779, NOD2_WH, 1 hit PF02758, PYRIN, 1 hit |
SMARTi | View protein in SMART SM01288, FISNA, 1 hit SM01289, PYRIN, 1 hit |
SUPFAMi | SSF47986, SSF47986, 1 hit SSF52540, SSF52540, 1 hit |
PROSITEi | View protein in PROSITE PS50824, DAPIN, 1 hit PS51450, LRR, 5 hits PS50837, NACHT, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | NAL12_HUMAN | |
Accessioni | P59046Primary (citable) accession number: P59046 Secondary accession number(s): A8MTQ2 Q9BY26 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | October 19, 2002 |
Last sequence update: | August 22, 2003 | |
Last modified: | February 23, 2022 | |
This is version 180 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
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. |
Miscellaneousi
Keywords - Technical termi
3D-structure, Reference proteomeDocuments
- Human chromosome 19
Human chromosome 19: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families