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

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: 187.49   (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: 187.49   (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 Data Bank (5)

1 – 5 of 5

PDB Structure Id	Ligand	Method	Resolution (Å)	M.W. (kDa)	Pub Year	Title

PDB Structure Id	M.W.	Resolution	Pub Year

Pathways (8)

Reactome (5)

KEGG (1)

PathwayCommons (1)

WikiPathways (1)

Immune System (R-HSA-168256)

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Items per page:

5

1 – 5 of 5

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

Gene Ontology Terms (22)

Functions (4)

Components (6)

Processes (12)

Items per page:

10

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

Protein-Protein Interactions (68)

Explore Interacting Targets

1 – 10 of 68

• See Interactions on String-DB

CASP1

Tchem

Family: Enzyme

Novelty: 0.00043112

Score: 0.994

Data Source: STRINGDB

CASP5

Tchem

Family: Enzyme

Novelty: 0.00907686

Score: 0.987

Data Source: STRINGDB

AIM2

Tbio

Novelty: 0.00325294

Score: 0.984

Data Source: STRINGDB

NLRC4

Tbio

Novelty: 0.00275422

Score: 0.977

Data Source: STRINGDB

BCL2L1

Tchem

Novelty: 0.00021916

Score: 0.971

Data Source: Reactome,STRINGDB

PYCARD

Tbio

Novelty: 0.00561282

Score: 0.941

Data Source: STRINGDB

BCL2

Tclin

Novelty: 0.00566111

Score: 0.938

Data Source: Reactome,STRINGDB

NLRP3

Tchem

Novelty: 0.00042021

Score: 0.922

Data Source: STRINGDB

NLRP9

Tbio

Novelty: 0.11321656

Score: 0.917

Data Source: STRINGDB

DHX33

Tbio

Family: Enzyme

Novelty: 0.1007315

Score: 0.915

Data Source: STRINGDB

Publication Statistics

PubMed Score  187.49

PubMed score by year

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PubTator Score  120

PubTator score by year

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Amino Acid Sequence

Residue Counts

Sequence

MAGGAWGRLACYLEFLKKEELKEFQLLLANKAHSRSSSGETPAQPEKTSGMEVASYLVAQYGEQRAWDLA

1-70

LHTWEQMGLRSLCAQAQEGAGHSPSFPYSPSEPHLGSPSQPTSTAVLMPWIHELPAGCTQGSERRVLRQL

70-140

PDTSGRRWREISASLLYQALPSSPDHESPSQESPNAPTSTAVLGSWGSPPQPSLAPREQEAPGTQWPLDE

140-210

TSGIYYTEIREREREKSEKGRPPWAAVVGTPPQAHTSLQPHHHPWEPSVRESLCSTWPWKNEDFNQKFTQ

210-280

LLLLQRPHPRSQDPLVKRSWPDYVEENRGHLIEIRDLFGPGLDTQEPRIVILQGAAGIGKSTLARQVKEA

280-350

WGRGQLYGDRFQHVFYFSCRELAQSKVVSLAELIGKDGTATPAPIRQILSRPERLLFILDGVDEPGWVLQ

350-420

EPSSELCLHWSQPQPADALLGSLLGKTILPEASFLITARTTALQNLIPSLEQARWVEVLGFSESSRKEYF

420-490

YRYFTDERQAIRAFRLVKSNKELWALCLVPWVSWLACTCLMQQMKRKEKLTLTSKTTTTLCLHYLAQALQ

490-560

AQPLGPQLRDLCSLAAEGIWQKKTLFSPDDLRKHGLDGAIISTFLKMGILQEHPIPLSYSFIHLCFQEFF

560-630

AAMSYVLEDEKGRGKHSNCIIDLEKTLEAYGIHGLFGASTTRFLLGLLSDEGEREMENIFHCRLSQGRNL

630-700

MQWVPSLQLLLQPHSLESLHCLYETRNKTFLTQVMAHFEEMGMCVETDMELLVCTFCIKFSRHVKKLQLI

700-770

EGRQHRSTWSPTMVVLFRWVPVTDAYWQILFSVLKVTRNLKELDLSGNSLSHSAVKSLCKTLRRPRCLLE

770-840

TLRLAGCGLTAEDCKDLAFGLRANQTLTELDLSFNVLTDAGAKHLCQRLRQPSCKLQRLQLVSCGLTSDC

840-910

CQDLASVLSASPSLKELDLQQNNLDDVGVRLLCEGLRHPACKLIRLGLDQTTLSDEMRQELRALEQEKPQ

910-980

LLIFSRRKPSVMTPTEGLDTGEMSNSTSSLKRQRLGSERAASHVAQANLKLLDVSKIFPIAEIAEESSPE

980-1050

VVPVELLCVPSPASQGDLHTKPLGTDDDFWGPTGPVATEVVDKEKNLYRVHFPVAGSYRWPNTGLCFVMR

1050-1120

EAVTVEIEFCVWDQFLGEINPQHSWMVAGPLLDIKAEPGAVEAVHLPHFVALQGGHVDTSLFQMAHFKEE

1120-1190

GMLLEKPARVELHHIVLENPSFSPLGVLLKMIHNALRFIPVTSVVLLYHRVHPEEVTFHLYLIPSDCSIR

1190-1260

KAIDDLEMKFQFVRIHKPPPLTPLYMGCRYTVSGSGSGMLEILPKELELCYRSPGEDQLFSEFYVGHLGS

1260-1330

GIRLQVKDKKDETLVWEALVKPGDLMPATTLIPPARIAVPSPLDAPQLLHFVDQYREQLIARVTSVEVVL

1330-1400

DKLHGQVLSQEQYERVLAENTRPSQMRKLFSLSQSWDRKCKDGLYQALKETHPHLIMELWEKGSKKGLLP

1400-1470

LSS

1470-1473

MAGGAWGRLACYLEFLKKEELKEFQLLLANKAHSRSSSGETPAQPEKTSGMEVASYLVAQYGEQRAWDLALHTWEQMGLRSLCAQAQEGAGHSPSFPYSPSEPHLGSPSQPTSTAVLMPWIHELPAGCTQGSERRVLRQLPDTSGRRWREISASLLYQALPSSPDHESPSQESPNAPTSTAVLGSWGSPPQPSLAPREQEAPGTQWPLDETSGIYYTEIREREREKSEKGRPPWAAVVGTPPQAHTSLQPHHHPWEPSVRESLCSTWPWKNEDFNQKFTQLLLLQRPHPRSQDPLVKRSWPDYVEENRGHLIEIRDLFGPGLDTQEPRIVILQGAAGIGKSTLARQVKEAWGRGQLYGDRFQHVFYFSCRELAQSKVVSLAELIGKDGTATPAPIRQILSRPERLLFILDGVDEPGWVLQEPSSELCLHWSQPQPADALLGSLLGKTILPEASFLITARTTALQNLIPSLEQARWVEVLGFSESSRKEYFYRYFTDERQAIRAFRLVKSNKELWALCLVPWVSWLACTCLMQQMKRKEKLTLTSKTTTTLCLHYLAQALQAQPLGPQLRDLCSLAAEGIWQKKTLFSPDDLRKHGLDGAIISTFLKMGILQEHPIPLSYSFIHLCFQEFFAAMSYVLEDEKGRGKHSNCIIDLEKTLEAYGIHGLFGASTTRFLLGLLSDEGEREMENIFHCRLSQGRNLMQWVPSLQLLLQPHSLESLHCLYETRNKTFLTQVMAHFEEMGMCVETDMELLVCTFCIKFSRHVKKLQLIEGRQHRSTWSPTMVVLFRWVPVTDAYWQILFSVLKVTRNLKELDLSGNSLSHSAVKSLCKTLRRPRCLLETLRLAGCGLTAEDCKDLAFGLRANQTLTELDLSFNVLTDAGAKHLCQRLRQPSCKLQRLQLVSCGLTSDCCQDLASVLSASPSLKELDLQQNNLDDVGVRLLCEGLRHPACKLIRLGLDQTTLSDEMRQELRALEQEKPQLLIFSRRKPSVMTPTEGLDTGEMSNSTSSLKRQRLGSERAASHVAQANLKLLDVSKIFPIAEIAEESSPEVVPVELLCVPSPASQGDLHTKPLGTDDDFWGPTGPVATEVVDKEKNLYRVHFPVAGSYRWPNTGLCFVMREAVTVEIEFCVWDQFLGEINPQHSWMVAGPLLDIKAEPGAVEAVHLPHFVALQGGHVDTSLFQMAHFKEEGMLLEKPARVELHHIVLENPSFSPLGVLLKMIHNALRFIPVTSVVLLYHRVHPEEVTFHLYLIPSDCSIRKAIDDLEMKFQFVRIHKPPPLTPLYMGCRYTVSGSGSGMLEILPKELELCYRSPGEDQLFSEFYVGHLGSGIRLQVKDKKDETLVWEALVKPGDLMPATTLIPPARIAVPSPLDAPQLLHFVDQYREQLIARVTSVEVVLDKLHGQVLSQEQYERVLAENTRPSQMRKLFSLSQSWDRKCKDGLYQALKETHPHLIMELWEKGSKKGLLPLSS

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Uniprot Keyword

3D-structure
Alternative splicing
ATP-binding
Complete proteome
Cytoplasm
Direct protein sequencing
Disease mutation
Ectodermal dysplasia
Host-virus interaction
Immunity