Tbio NLRP1 NACHT, LRR and PYD domains-containing protein 1

Protein Summary

Description

As the sensor component of the NLRP1 inflammasome, plays a crucial role in innate immunity and inflammation. In response to pathogens and other damage-associated signals, initiates the formation of the inflammasome polymeric complex, made of NLRP1, CASP1, and possibly PYCARD. Recruitment of proCASP1 to the inflammasome promotes its activation and CASP1-catalyzed IL1B and IL18 maturation and secretion in the extracellular milieu. Activation of NLRP1 inflammasome is also required for HMGB1 secretion. The active cytokines and HMGB1 stimulate inflammatory responses. Inflammasomes can also induce pyroptosis, an inflammatory form of programmed cell death (PubMed:22665479, PubMed:17418785). May be activated by muramyl dipeptide (MDP), a fragment of bacterial peptidoglycan, in a NOD2-dependent manner (PubMed:18511561). Contrary to its mouse ortholog, not activated by Bacillus anthracis lethal toxin (PubMed:19651869). It is unclear whether isoform 2 is involved in inflammasome formation. It is not cleaved within the FIIND domain, does not assemble into specks, nor promote IL1B release (PubMed:22665479). However, in an vitro cell-free system, it has been shown to be activated by MDP (PubMed:17349957). Binds ATP (PubMed:11113115, PubMed:15212762). This gene encodes a member of the Ced-4 family of apoptosis proteins. Ced-family members contain a caspase recruitment domain (CARD) and are known to be key mediators of programmed cell death. The encoded protein contains a distinct N-terminal pyrin-like motif, which is possibly involved in protein-protein interactions. This protein interacts strongly with caspase 2 and weakly with caspase 9. Overexpression of this gene was demonstrated to induce apoptosis in cells. Multiple alternatively spliced transcript variants encoding distinct isoforms have been found for this gene, but the biological validity of some variants has not been determined. [provided by RefSeq, Jul 2008]

Uniprot Accession IDs

• Q9C000
• E9PE50
• I6L9D9
• Q9BZZ8
• Q9BZZ9
• Q9H5Z7
• Q9H5Z8
• Q9HAV8
• Q9UFT4
• Q9Y2E0

Gene Name

• NLRP1

Ensembl ID

• ENST00000262467
• ENSP00000262467
• ENSG00000091592
• ENST00000269280
• ENSP00000269280
• ENST00000345221
• ENSP00000324366
• ENST00000354411
• ENSP00000346390
• ENST00000544378
• ENSP00000442029
• ENST00000571451
• ENSP00000459661
• ENST00000572272
• ENSP00000460475
• ENST00000577119
• ENSP00000460216
• ENST00000613500
• ENSP00000483359
• ENST00000617618
• ENSP00000478516
• ENST00000619223
• ENSP00000484692

Symbol

• CARD7
• DEFCAP
• KIAA0926
• NAC
• NALP1
• NAC
• MSPC
• AIADK
• CARD7
• CIDED
• NALP1
• SLEV1
• DEFCAP
• PP1044
• VAMAS1
• CLR17.1
• DEFCAP-L/S

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
molecular function	0.95
protein domain	0.92
biological process	0.8
cell type or tissue	0.66
biological term	0.61

Protein Classes

No PANTHER Classes or DTO Classes found

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 237.55   (req: < 5)

Gene RIFs: 88   (req: <= 3)

Antibodies: 228   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 237.55   (req: >= 5)

Gene RIFs: 88   (req: > 3)

Antibodies: 228   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 16

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligand: 0

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 0

Protein Sequence and Structure

Residue Counts

Protein Sequence

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Expression Data (0 Tissues)

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No expression data found

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Target Illumination GWAS Analytics (TIGA)

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GENEVA

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GlyGen

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ARCHS4

ARCHS4 provides access to gene-function predictions based on RNA-seq co-expression, and gene expression levels across cell and tissues.

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Approved Drugs (0)

No approved drugs found

Active Ligands (0)

No active ligands found

Protein-Protein Interactions (68)

Explore Interacting Targets

1 – 10 of 68

• See Interactions on String-DB

CASP1

Tchem

Family:  Enzyme

Novelty:  0.00034643

Score:  0.994

Data Source:  STRINGDB

CASP5

Tchem

Family:  Enzyme

Novelty:  0.00734661

Score:  0.987

Data Source:  STRINGDB

AIM2

Tbio

Novelty:  0.00360474

Score:  0.984

Data Source:  STRINGDB

NLRC4

Tbio

Novelty:  0.0032237

Score:  0.977

Data Source:  STRINGDB

BCL2L1

Tchem

Novelty:  0.00018414

Score:  0.971

Data Source:  Reactome,STRINGDB

PYCARD

Tbio

Novelty:  0.00719985

Score:  0.941

Data Source:  STRINGDB

BCL2

Tclin

Novelty:  0.00608635

Score:  0.938

Data Source:  Reactome,STRINGDB

NLRP3

Tchem

Novelty:  0.00043957

Score:  0.922

Data Source:  STRINGDB

NLRP9

Tbio

Novelty:  0.075833

Score:  0.917

Data Source:  STRINGDB

DHX33

Tbio

Family:  Enzyme

Novelty:  0.07473852

Score:  0.915

Data Source:  STRINGDB

Nearest Tclin Targets

Nearest Tclin calculations are only available for targets with KEGG Pathway annotations.

Pathways (8)

Reactome (5)

KEGG (1)

PathwayCommons (1)

WikiPathways (1)

Immune System (R-HSA-168256)

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Data Source	Name	Explore in Pharos	Explore in Source
Reactome	Immune System	2246 targets	R-HSA-168256
Reactome	Inflammasomes	20 targets	R-HSA-622312
Reactome	Innate Immune System	1188 targets	R-HSA-168249
Reactome	Nucleotide-binding domain, leucine rich repeat containing receptor (NLR) signaling pathways	50 targets	R-HSA-168643
Reactome	The NLRP1 inflammasome	3 targets	R-HSA-844455

Name	Explore in Pharos	Explore in Source
Immune System	2246 targets	R-HSA-168256
Inflammasomes	20 targets	R-HSA-622312
Innate Immune System	1188 targets	R-HSA-168249
Nucleotide-binding domain, leucine rich repeat containing receptor (NLR) signaling pathways	50 targets	R-HSA-168643
The NLRP1 inflammasome	3 targets	R-HSA-844455

Viral Interactions (0)

No viral interactions found

Gene Ontology Terms (22)

Functions (4)

Components (6)

Processes (12)

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1 – 4 of 4

GO Term	Evidence	Assigned by
ATP binding	Inferred from Direct Assay (IDA)	HGNC
enzyme binding	Inferred from Physical Interaction (IPI)	UniProtKB
protein domain specific binding	Inferred from Physical Interaction (IPI)	UniProtKB
cysteine-type endopeptidase activator activity involved in apoptotic process	Non-traceable Author Statement (NAS)	UniProtKB

Disease Associations ()

No disease associations found

GWAS Traits (7)

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1 – 5 of 7

GWAS Trait	EFO ID	Study Count	SNP Count	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
myeloid white cell count	EFO_0007988	1	1	1		78.1
leukocyte count	EFO_0004308	1	1	1		73.9
neutrophil count	EFO_0004833	2	1	2		64.9
body mass index	EFO_0004340	1	1	1		38.8
hip bone size	EFO_0004844	1	1	1		35

• Explore on Target Illumination GWAS Analytics (TIGA)

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5

1 – 5 of 7

GWAS Trait	EFO ID	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
myeloid white cell count	EFO_0007988	1		78.1
leukocyte count	EFO_0004308	1		73.9
neutrophil count	EFO_0004833	2		64.9
body mass index	EFO_0004340	1		38.8
hip bone size	EFO_0004844	1		35

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UniProt Keyword Find Similar Targets

No Header	No Header
3D-structure
Alternative splicing
ATP-binding
Complete proteome
Cytoplasm
Direct protein sequencing
Disease mutation
Ectodermal dysplasia
Host-virus interaction
Immunity

GWAS Trait Find Similar Targets

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age at menopause
body mass index
hip bone size
leukocyte count
migraine disorder
myeloid white cell count
neutrophil count

MGI Phenotype Find Similar Targets

No Header	No Header
cardiovascular system phenotype
cellular phenotype
endocrine/exocrine gland phenotype
growth/size/body region phenotype
hematopoietic system phenotype
homeostasis/metabolism phenotype
immune system phenotype
liver/biliary system phenotype
mortality/aging
nervous system phenotype

IDG Resources

No IDG generated resources found

Orthologs (7)

1 – 5 of 7

Species	Name	Source ID	Gene ID	OMA	EggNOG	Inparanoid
Chimp	NLR family pyrin domain containing 1	VGNC:12556	468451
Mouse	NLR family, pyrin domain containing 1A	MGI:2684861	195046
Mouse	NLR family, pyrin domain containing 1B	MGI:3582959	637515
Dog	NLR family pyrin domain containing 1	VGNC:43845	489449
Horse	NLR family pyrin domain containing 1 [Source:HGNC Symbol;Acc:HGNC:14374]

Species	Name	OMA	EggNOG	Inparanoid
Chimp	NLR family pyrin domain containing 1
Mouse	NLR family, pyrin domain containing 1A
Mouse	NLR family, pyrin domain containing 1B
Dog	NLR family pyrin domain containing 1
Horse	NLR family pyrin domain containing 1 [Source:HGNC Symbol;Acc:HGNC:14374]

Publication Statistics

PubMed Score 237.55

PubMed score by year

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PubTator Score 120.00

PubTator score by year

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Related Publications

Text Mined References (114)

GeneRif Annotations (88)

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PMID	Year	Title