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Protein

NACHT, LRR and PYD domains-containing protein 1

Gene

NLRP1

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

Functioni

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).By similarity8 Publications

Miscellaneous

In macrophages and dendritic cells, NLRP1 inflammasome activation of CASP1 and IL1B maturation can be dampened by direct contact with activated effector and memory T-cells. This effect may be mediated by hexameric TNF ligands, such as CD40LG.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei1186Trigger for autolytic processing1 Publication1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi334 – 341ATPPROSITE-ProRule annotation8

GO - Molecular functioni

  • ATP binding Source: HGNC
  • cysteine-type endopeptidase activator activity involved in apoptotic process Source: UniProtKB
  • enzyme binding Source: UniProtKB
  • protein domain specific binding Source: UniProtKB

GO - Biological processi

Keywordsi

Biological processHost-virus interaction, Immunity, Inflammatory response, Innate immunity
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiR-HSA-844455 The NLRP1 inflammasome

Names & Taxonomyi

Protein namesi
Recommended name:
NACHT, LRR and PYD domains-containing protein 1
Alternative name(s):
Caspase recruitment domain-containing protein 7
Death effector filament-forming ced-4-like apoptosis protein
Nucleotide-binding domain and caspase recruitment domain
Gene namesi
Name:NLRP1
Synonyms:CARD7, DEFCAP, KIAA0926, NAC1 Publication, NALP1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 17

Organism-specific databases

EuPathDBiHostDB:ENSG00000091592.15
HGNCiHGNC:14374 NLRP1
MIMi606636 gene
neXtProtiNX_Q9C000

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Inflammasome, Nucleus

Pathology & Biotechi

Involvement in diseasei

Vitiligo-associated multiple autoimmune disease 1 (VAMAS1)1 Publication
Disease susceptibility is associated with variations affecting the gene represented in this entry.
Disease descriptionA disorder characterized by the association of vitiligo with several autoimmune and autoinflammatory diseases including autoimmune thyroid disease, rheumatoid arthritis and systemic lupus erythematosus.
See also OMIM:606579
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_033239155L → H in VAMAS1; associated with disease susceptibility. 2 PublicationsCorresponds to variant dbSNP:rs12150220EnsemblClinVar.1
Palmoplantar carcinoma, multiple self-healing (MSPC)2 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn autosomal dominant disease characterized by keratopathy with neovascularization, bilateral corneal opacification, palmoplantar hyperkeratosis, dyshidrosis, dystrophic nails, and recurrent keratoacanthomas in palmoplantar skin as well as in conjunctival and corneal epithelia. In addition, patients experience a high susceptibility to malignant squamous cell carcinoma.
See also OMIM:615225
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_07879854A → T in MSPC; increased NLRP1-inflammasome complex assembly; altered protein folding. 1 PublicationCorresponds to variant dbSNP:rs1057519492Ensembl.1
Natural variantiVAR_07879966A → V in MSPC; increased NLRP1-inflammasome complex assembly; altered protein folding. 1 PublicationCorresponds to variant dbSNP:rs1057519493Ensembl.1
Natural variantiVAR_06990177M → T in MSPC. 1 PublicationCorresponds to variant dbSNP:rs397514692EnsemblClinVar.1
Natural variantiVAR_078801787 – 843Missing in MSPC; increased NLRP1-inflammasome complex assembly. 1 PublicationAdd BLAST57
Autoinflammation with arthritis and dyskeratosis (AIADK)1 Publication
The disease may be caused by mutations affecting the gene represented in this entry.
Disease descriptionA disorder characterized by recurrent fever, diffuse skin dyskeratosis, autoinflammation, autoimmunity, arthritis and high transitional B-cell level. Inheritance can be autosomal dominant or autosomal recessive.
See also OMIM:617388
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_078800726R → W in AIADK; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs776245016EnsemblClinVar.1
Natural variantiVAR_0788021214P → R in AIADK; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs1057524876Ensembl.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi339 – 340GK → EA: Loss of ATP binding. 1 Publication2
Mutagenesisi340K → L or S: No effect. 1 Publication1
Mutagenesisi1168H → A: Complete loss of autocatalytic processing and of IL1B release. Autocatalytic processing cannot be restored by treatment with hydroxylamine. 1 Publication1
Mutagenesisi1186H → A: Complete loss of autocatalytic processing and of IL1B release. Autocatalytic processing can be restored by treatment with hydroxylamine. 1 Publication1
Mutagenesisi1211S → A: Partial loss of autocatalytic processing and of IL1B release. 1 Publication1
Mutagenesisi1212F → A: Complete loss of autocatalytic processing and of IL1B release. 1 Publication1
Mutagenesisi1213S → A: Complete loss of autocatalytic processing and of IL1B release. Autocatalytic processing cannot be restored by treatment with hydroxylamine. 2 Publications1
Mutagenesisi1213S → C: Complete loss of autocatalytic processing, which can be restored by treatment with hydroxylamine. 1 Publication1
Mutagenesisi1214P → A: Partial loss of autocatalytic processing (50%) and of IL1B release (50%). 1 Publication1
Mutagenesisi1249H → A: Complete loss of autocatalytic processing and IL1B release. Autocatalytic processing cannot be restored by treatment with hydroxylamine. 1 Publication1

Keywords - Diseasei

Disease mutation, Ectodermal dysplasia

Organism-specific databases

DisGeNETi22861
MalaCardsiNLRP1
MIMi606579 phenotype
615225 phenotype
617388 phenotype
OpenTargetsiENSG00000091592
Orphaneti352662 Corneal intraepithelial dyskeratosis with palmoplantar hyperkeratosis and laryngeal dyskeratosis
3435 Vitiligo
247871 Vitiligo-associated autoimmune disease
PharmGKBiPA162397797

Chemistry databases

ChEMBLiCHEMBL1741214

Polymorphism and mutation databases

BioMutaiNLRP1
DMDMi17380146

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000967101 – 1473NACHT, LRR and PYD domains-containing protein 1Add BLAST1473

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei1212 – 1213Cleavage; by autolysisPROSITE-ProRule annotation1 Publication2

Proteomic databases

EPDiQ9C000
PaxDbiQ9C000
PeptideAtlasiQ9C000
PRIDEiQ9C000
ProteomicsDBi79931
79932 [Q9C000-2]
79933 [Q9C000-3]
79934 [Q9C000-4]

PTM databases

iPTMnetiQ9C000
PhosphoSitePlusiQ9C000

Expressioni

Tissue specificityi

Widely expressed (PubMed:11113115, PubMed:17164409). Abundantly expressed in primary immune cells (isoform 1 and isoform 2), including in neutrophils, monocytes/macrophages, dendritic cells (mostly Langerhans cells), and B- and T-lymphocytes (at protein level) (PubMed:15285719, PubMed:17164409). Strongly expressed in epithelial cells lining the glandular epithelium, such as that of the gastrointestinal tract (stomach, small intestine, colon), the respiratory tract (trachea and bronchi), and the endometrial and endocervical glands, gallbladder, prostate, and breast (at protein level). In testis, expressed in spermatogonia and primary spermatocytes, but not in Sertoli cells (at protein level). In the brain, expressed in neurons, in particular in pyramidal ones and in oligodendrocytes, but not detected in microglia (at protein level) (PubMed:17164409). Expressed in adult and fetal ocular tissues, including in adult and 24-week old fetal choroid, sclera, cornea, and optic nerve, as well as in adult retina and fetal retina/retinal pigment epithelium (PubMed:23349227). Highly expressed in the skin throughout the epidermis and in dermal fibroblasts, in both glabrous skin and plantar skin. It is detected in keratinocytes, but not in melanocytes. Expressed in epidermal appendages such as hair follicles (PubMed:27662089).5 Publications

Developmental stagei

Associated with differentiation in stratified epithelia of the skin, esophagus, intestine, and cervix, as well as in the prostate gland. Undetectable in undifferentiated basal cells, but expressed in differentiated luminal secretory cells (PubMed:11113115). Expressed in differentiated macrophages and granulocytes, but not their precursors (at protein level) (PubMed:11113115, PubMed:15285719). In testis, also associated with cell differentiation, with conflicting results. Expressed in spermatogonia and primary spermatocytes, but not in cells from later differentiation stages, including secondary spermatocytes, spermatids, and spermatozoa (at protein level) (PubMed:17164409). Not detected in spermatocytes, nor spermatids, and strongly expressed in spermatozoa (at protein level) (PubMed:11113115).3 Publications

Inductioni

Up-regulated by ATF4 during endoplasmic reticulum (ER) stress response (PubMed:26086088). Up-regulated in arterial endothelial cells exposed to plasma from patients with peripheral arterial disease, but not to plasma from healthy controls (PubMed:24439873).2 Publications

Gene expression databases

BgeeiENSG00000091592 Expressed in 205 organ(s), highest expression level in pituitary gland
CleanExiHS_NLRP1
ExpressionAtlasiQ9C000 baseline and differential
GenevisibleiQ9C000 HS

Organism-specific databases

HPAiCAB009189
HPA064431

Interactioni

Subunit structurei

Sensor component of NLRP1 inflammasomes. Inflammasomes are supramolecular complexes that assemble in the cytosol in response to pathogens and other damage-associated signals and play critical roles in innate immunity and inflammation. Classical inflammasomes consist of a signal sensor component, an adapter (ASC/PYCARD), which recruits an effector proinflammatory caspase (CASP1 and CASP5). This interaction initiates speck formation (nucleation) which greatly enhances further addition of soluble PYCARD molecules to the speck in a prion-like polymerization process. CASP1 filament formation increases local enzyme concentration, resulting in trans-autocleavage and activation. Active CASP1 then processes IL1B and IL18 precursors, leading to the release of mature cytokines in the extracellular milieu and inflammatory response. In NLRP1 inflammasome, the role of PYCARD is not clear. Following activation, NLRP1 can directly interact with CASP1 (possibly through CARD domain) to form a functional inflammasome, although the presence of PYCARD increases CASP1 activity (PubMed:17418785, PubMed:17349957). In a different experimental system, neither CASP1-binding, NLRP1 inflammasome speck formation, nor IL1B release were observed in the absence of PYCARD (PubMed:22665479, PubMed:12191486). Hence PYCARD may not be necessary for NLRP1 and CASP1 interaction, but is required for speck formation and full inflammasome activity (By similarity). Homomer (PubMed:17349957). Interacts (via LRR repeats) with BCL2 and BCL2L1 (via the loop between motifs BH4 and BH3); these interactions reduce NLRP1 inflammasome-induced CASP1 activation and IL1B release, possibly by impairing NLRP1 interaction with PYCARD (PubMed:17418785). Interacts with NOD2; this interaction is enhanced in the presence of muramyl dipeptide (MDP) and increases IL1B release (PubMed:18511561). Interacts with EIF2AK2/PKR; this interaction requires EIF2AK2 activity, is accompanied by EIF2AK2 autophosphorylation and promotes inflammasome assembly in response to danger-associated signals (By similarity). Interacts with MEFV; this interaction targets NLRP1 to degradation by autophagy, hence preventing excessive IL1B- and IL18-mediated inflammation (PubMed:17431422, PubMed:26347139).By similarity7 Publications
(Microbial infection) Interacts with vaccinia virus protein F1 (PubMed:16439990).1 Publication

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi116529, 13 interactors
CORUMiQ9C000
DIPiDIP-38407N
IntActiQ9C000, 11 interactors
STRINGi9606.ENSP00000460475

Chemistry databases

BindingDBiQ9C000

Structurei

Secondary structure

11473
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

DisProtiDP00554
ProteinModelPortaliQ9C000
SMRiQ9C000
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9C000

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini1 – 92PyrinPROSITE-ProRule annotationAdd BLAST92
Domaini328 – 637NACHTPROSITE-ProRule annotationAdd BLAST310
Repeati809 – 830LRR 1Add BLAST22
Repeati838 – 858LRR 2Add BLAST21
Repeati866 – 887LRR 3Add BLAST22
Repeati895 – 915LRR 4Add BLAST21
Repeati923 – 944LRR 5Add BLAST22
Repeati950 – 973LRR 6Add BLAST24
Domaini1079 – 1364FIINDPROSITE-ProRule annotationAdd BLAST286
Domaini1374 – 1463CARDPROSITE-ProRule annotationAdd BLAST90

Domaini

The CARD domain, rather than the pyrin domain, is involved in the interaction with PYCARD, CASP1 and CASP5.3 Publications
The leucine-rich repeat (LRR) domain may be involved in autoinhibition in the absence of activating signal, possibly through intramolecular interaction with the NACHT domain.By similarity2 Publications
The FIIND (domain with function to find) region is involved in homomerization, but not in CASP1-binding (By similarity). Autocatalytic cleavage in this region occurs constitutively, prior to activation signals, and is required for inflammasome activity (IL1B release), possibly by facilitating CASP1 binding. Both N- and C-terminal fragments remain associated (PubMed:22665479, PubMed:22087307).By similarity2 Publications

Sequence similaritiesi

Belongs to the NLRP family.Curated

Keywords - Domaini

Leucine-rich repeat, Repeat

Phylogenomic databases

eggNOGiENOG410JAIN Eukaryota
ENOG410YGKV LUCA
GeneTreeiENSGT00900000140813
HOGENOMiHOG000230509
HOVERGENiHBG052573
InParanoidiQ9C000
KOiK12798
OMAiLIMELWE
OrthoDBiEOG091G01QH
PhylomeDBiQ9C000
TreeFamiTF340267

Family and domain databases

CDDicd08330 CARD_ASC_NALP1, 1 hit
Gene3Di3.80.10.10, 1 hit
InterProiView protein in InterPro
IPR001315 CARD
IPR033516 CARD8/ASC/NALP1_CARD
IPR004020 DAPIN
IPR011029 DEATH-like_dom_sf
IPR025307 FIIND_dom
IPR001611 Leu-rich_rpt
IPR032675 LRR_dom_sf
IPR007111 NACHT_NTPase
IPR027417 P-loop_NTPase
PfamiView protein in Pfam
PF00619 CARD, 1 hit
PF13553 FIIND, 1 hit
PF13516 LRR_6, 3 hits
PF05729 NACHT, 1 hit
PF02758 PYRIN, 1 hit
SMARTiView protein in SMART
SM01289 PYRIN, 1 hit
SUPFAMiSSF47986 SSF47986, 2 hits
SSF52540 SSF52540, 2 hits
PROSITEiView protein in PROSITE
PS50209 CARD, 1 hit
PS50824 DAPIN, 1 hit
PS51830 FIIND, 1 hit
PS51450 LRR, 3 hits
PS50837 NACHT, 1 hit

Sequences (7+)i

Sequence statusi: Complete.

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

This entry has 7 described isoforms and 2 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: Q9C000-1) [UniParc]FASTAAdd to basket
Also known as: NAC beta, DEFCAP-L, NALP1-L1 Publication

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
MAGGAWGRLA CYLEFLKKEE LKEFQLLLAN KAHSRSSSGE TPAQPEKTSG
60 70 80 90 100
MEVASYLVAQ YGEQRAWDLA LHTWEQMGLR SLCAQAQEGA GHSPSFPYSP
110 120 130 140 150
SEPHLGSPSQ PTSTAVLMPW IHELPAGCTQ GSERRVLRQL PDTSGRRWRE
160 170 180 190 200
ISASLLYQAL PSSPDHESPS QESPNAPTST AVLGSWGSPP QPSLAPREQE
210 220 230 240 250
APGTQWPLDE TSGIYYTEIR EREREKSEKG RPPWAAVVGT PPQAHTSLQP
260 270 280 290 300
HHHPWEPSVR ESLCSTWPWK NEDFNQKFTQ LLLLQRPHPR SQDPLVKRSW
310 320 330 340 350
PDYVEENRGH LIEIRDLFGP GLDTQEPRIV ILQGAAGIGK STLARQVKEA
360 370 380 390 400
WGRGQLYGDR FQHVFYFSCR ELAQSKVVSL AELIGKDGTA TPAPIRQILS
410 420 430 440 450
RPERLLFILD GVDEPGWVLQ EPSSELCLHW SQPQPADALL GSLLGKTILP
460 470 480 490 500
EASFLITART TALQNLIPSL EQARWVEVLG FSESSRKEYF YRYFTDERQA
510 520 530 540 550
IRAFRLVKSN KELWALCLVP WVSWLACTCL MQQMKRKEKL TLTSKTTTTL
560 570 580 590 600
CLHYLAQALQ AQPLGPQLRD LCSLAAEGIW QKKTLFSPDD LRKHGLDGAI
610 620 630 640 650
ISTFLKMGIL QEHPIPLSYS FIHLCFQEFF AAMSYVLEDE KGRGKHSNCI
660 670 680 690 700
IDLEKTLEAY GIHGLFGAST TRFLLGLLSD EGEREMENIF HCRLSQGRNL
710 720 730 740 750
MQWVPSLQLL LQPHSLESLH CLYETRNKTF LTQVMAHFEE MGMCVETDME
760 770 780 790 800
LLVCTFCIKF SRHVKKLQLI EGRQHRSTWS PTMVVLFRWV PVTDAYWQIL
810 820 830 840 850
FSVLKVTRNL KELDLSGNSL SHSAVKSLCK TLRRPRCLLE TLRLAGCGLT
860 870 880 890 900
AEDCKDLAFG LRANQTLTEL DLSFNVLTDA GAKHLCQRLR QPSCKLQRLQ
910 920 930 940 950
LVSCGLTSDC CQDLASVLSA SPSLKELDLQ QNNLDDVGVR LLCEGLRHPA
960 970 980 990 1000
CKLIRLGLDQ TTLSDEMRQE LRALEQEKPQ LLIFSRRKPS VMTPTEGLDT
1010 1020 1030 1040 1050
GEMSNSTSSL KRQRLGSERA ASHVAQANLK LLDVSKIFPI AEIAEESSPE
1060 1070 1080 1090 1100
VVPVELLCVP SPASQGDLHT KPLGTDDDFW GPTGPVATEV VDKEKNLYRV
1110 1120 1130 1140 1150
HFPVAGSYRW PNTGLCFVMR EAVTVEIEFC VWDQFLGEIN PQHSWMVAGP
1160 1170 1180 1190 1200
LLDIKAEPGA VEAVHLPHFV ALQGGHVDTS LFQMAHFKEE GMLLEKPARV
1210 1220 1230 1240 1250
ELHHIVLENP SFSPLGVLLK MIHNALRFIP VTSVVLLYHR VHPEEVTFHL
1260 1270 1280 1290 1300
YLIPSDCSIR KAIDDLEMKF QFVRIHKPPP LTPLYMGCRY TVSGSGSGML
1310 1320 1330 1340 1350
EILPKELELC YRSPGEDQLF SEFYVGHLGS GIRLQVKDKK DETLVWEALV
1360 1370 1380 1390 1400
KPGDLMPATT LIPPARIAVP SPLDAPQLLH FVDQYREQLI ARVTSVEVVL
1410 1420 1430 1440 1450
DKLHGQVLSQ EQYERVLAEN TRPSQMRKLF SLSQSWDRKC KDGLYQALKE
1460 1470
THPHLIMELW EKGSKKGLLP LSS
Length:1,473
Mass (Da):165,866
Last modified:June 1, 2001 - v1
Checksum:i438F0DCE45C2562D
GO
Isoform 2 (identifier: Q9C000-2) [UniParc]FASTAAdd to basket
Also known as: NAC alpha, DEFCAP-S, NALP1-S1 Publication, NLRP1deltaEx14

The sequence of this isoform differs from the canonical sequence as follows:
     1262-1305: Missing.

Show »
Length:1,429
Mass (Da):160,946
Checksum:i6C5CBE8FD2819435
GO
Isoform 3 (identifier: Q9C000-3) [UniParc]FASTAAdd to basket
Also known as: NAC gamma

The sequence of this isoform differs from the canonical sequence as follows:
     958-987: Missing.
     1262-1305: Missing.

Show »
Length:1,399
Mass (Da):157,319
Checksum:i59C172B75766F38F
GO
Isoform 4 (identifier: Q9C000-4) [UniParc]FASTAAdd to basket
Also known as: NAC delta

The sequence of this isoform differs from the canonical sequence as follows:
     958-987: Missing.

Show »
Length:1,443
Mass (Da):162,239
Checksum:iC30E9BE9EC82FE96
GO
Isoform 5 (identifier: Q9C000-5) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1044-1044: A → AGKSH
     1354-1371: DLMPATTLIPPARIAVPS → RNTSQPWNLRCNRDARRY
     1372-1473: Missing.

Show »
Length:1,375
Mass (Da):154,881
Checksum:iBC6844DC6B4FDB0A
GO
Isoform 6 (identifier: Q9C000-6) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-734: Missing.

Show »
Length:739
Mass (Da):83,100
Checksum:i41E23E686642323B
GO
Isoform 7 (identifier: Q9C000-7) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-966: Missing.
     1044-1044: A → AGKSH
     1354-1371: DLMPATTLIPPARIAVPS → RNTSQPWNLRCNRDARRY
     1372-1473: Missing.

Show »
Length:409
Mass (Da):46,068
Checksum:i07CC5FACF3EB7236
GO

Computationally mapped potential isoform sequencesi

There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
I3L2G5I3L2G5_HUMAN
NACHT, LRR and PYD domains-containi...
NLRP1
1,429Annotation score:
I3L0S2I3L0S2_HUMAN
NACHT, LRR and PYD domains-containi...
NLRP1
35Annotation score:

Sequence cautioni

The sequence BAA76770 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated
The sequence BAB15469 differs from that shown. Reason: Frameshift at position 1241.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti287P → S in AAH51787 (PubMed:15489334).Curated1
Sequence conflicti782T → S in AAG15254 (PubMed:11270363).Curated1
Sequence conflicti995T → I in AAG15254 (PubMed:11270363).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_07879854A → T in MSPC; increased NLRP1-inflammasome complex assembly; altered protein folding. 1 PublicationCorresponds to variant dbSNP:rs1057519492Ensembl.1
Natural variantiVAR_07879966A → V in MSPC; increased NLRP1-inflammasome complex assembly; altered protein folding. 1 PublicationCorresponds to variant dbSNP:rs1057519493Ensembl.1
Natural variantiVAR_06990177M → T in MSPC. 1 PublicationCorresponds to variant dbSNP:rs397514692EnsemblClinVar.1
Natural variantiVAR_033239155L → H in VAMAS1; associated with disease susceptibility. 2 PublicationsCorresponds to variant dbSNP:rs12150220EnsemblClinVar.1
Natural variantiVAR_024238246T → S1 PublicationCorresponds to variant dbSNP:rs11651595Ensembl.1
Natural variantiVAR_021886404R → Q. Corresponds to variant dbSNP:rs3744718Ensembl.1
Natural variantiVAR_078800726R → W in AIADK; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs776245016EnsemblClinVar.1
Natural variantiVAR_078801787 – 843Missing in MSPC; increased NLRP1-inflammasome complex assembly. 1 PublicationAdd BLAST57
Natural variantiVAR_033240878T → M1 PublicationCorresponds to variant dbSNP:rs11657747Ensembl.1
Natural variantiVAR_0242391059V → M. Corresponds to variant dbSNP:rs2301582Ensembl.1
Natural variantiVAR_0332411069H → Y. Corresponds to variant dbSNP:rs9907167Ensembl.1
Natural variantiVAR_0332421119M → V No effect on autocatalytic processing, nor on IL1B release. 2 PublicationsCorresponds to variant dbSNP:rs35596958Ensembl.1
Natural variantiVAR_0332431184M → V Increased autocatalytic processing and IL1B release. 3 PublicationsCorresponds to variant dbSNP:rs11651270Ensembl.1
Natural variantiVAR_0788021214P → R in AIADK; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs1057524876Ensembl.1
Natural variantiVAR_0332441241V → L1 PublicationCorresponds to variant dbSNP:rs11653832Ensembl.1
Natural variantiVAR_0204371366R → C1 PublicationCorresponds to variant dbSNP:rs2137722Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0538011 – 966Missing in isoform 7. 1 PublicationAdd BLAST966
Alternative sequenceiVSP_0538021 – 734Missing in isoform 6. 1 PublicationAdd BLAST734
Alternative sequenceiVSP_004326958 – 987Missing in isoform 3 and isoform 4. 1 PublicationAdd BLAST30
Alternative sequenceiVSP_0538031044A → AGKSH in isoform 5 and isoform 7. 2 Publications1
Alternative sequenceiVSP_0043271262 – 1305Missing in isoform 2 and isoform 3. 5 PublicationsAdd BLAST44
Alternative sequenceiVSP_0538041354 – 1371DLMPA…IAVPS → RNTSQPWNLRCNRDARRY in isoform 5 and isoform 7. 2 PublicationsAdd BLAST18
Alternative sequenceiVSP_0538051372 – 1473Missing in isoform 5 and isoform 7. 2 PublicationsAdd BLAST102

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF298548 mRNA Translation: AAG15254.1
AF310105 mRNA Translation: AAG30288.1
AF229059 mRNA Translation: AAK00748.1
AF229060 mRNA Translation: AAK00749.1
AF229061 mRNA Translation: AAK00750.1
AF229062 mRNA Translation: AAK00751.1
AB023143 mRNA Translation: BAA76770.2 Different initiation.
AK026393 mRNA Translation: BAB15469.1 Frameshift.
AK026398 mRNA Translation: BAB15470.1
AC055839 Genomic DNA No translation available.
BC051787 mRNA Translation: AAH51787.1
AL117470 mRNA Translation: CAB55945.1
CCDSiCCDS32537.1 [Q9C000-5]
CCDS42244.1 [Q9C000-4]
CCDS42245.1 [Q9C000-2]
CCDS42246.1 [Q9C000-1]
CCDS58508.1 [Q9C000-3]
PIRiT17255
RefSeqiNP_001028225.1, NM_001033053.2 [Q9C000-5]
NP_055737.1, NM_014922.4 [Q9C000-2]
NP_127497.1, NM_033004.3 [Q9C000-1]
NP_127499.1, NM_033006.3 [Q9C000-4]
NP_127500.1, NM_033007.3 [Q9C000-3]
UniGeneiHs.652273

Genome annotation databases

EnsembliENST00000262467; ENSP00000262467; ENSG00000091592 [Q9C000-5]
ENST00000269280; ENSP00000269280; ENSG00000091592 [Q9C000-2]
ENST00000345221; ENSP00000324366; ENSG00000091592 [Q9C000-2]
ENST00000354411; ENSP00000346390; ENSG00000091592 [Q9C000-4]
ENST00000544378; ENSP00000442029; ENSG00000091592 [Q9C000-5]
ENST00000571451; ENSP00000459661; ENSG00000091592 [Q9C000-2]
ENST00000572272; ENSP00000460475; ENSG00000091592 [Q9C000-1]
ENST00000577119; ENSP00000460216; ENSG00000091592 [Q9C000-3]
ENST00000613500; ENSP00000483359; ENSG00000091592 [Q9C000-5]
ENST00000617618; ENSP00000478516; ENSG00000091592 [Q9C000-1]
ENST00000619223; ENSP00000484692; ENSG00000091592 [Q9C000-4]
GeneIDi22861
KEGGihsa:22861
UCSCiuc002gcg.2 human [Q9C000-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF298548 mRNA Translation: AAG15254.1
AF310105 mRNA Translation: AAG30288.1
AF229059 mRNA Translation: AAK00748.1
AF229060 mRNA Translation: AAK00749.1
AF229061 mRNA Translation: AAK00750.1
AF229062 mRNA Translation: AAK00751.1
AB023143 mRNA Translation: BAA76770.2 Different initiation.
AK026393 mRNA Translation: BAB15469.1 Frameshift.
AK026398 mRNA Translation: BAB15470.1
AC055839 Genomic DNA No translation available.
BC051787 mRNA Translation: AAH51787.1
AL117470 mRNA Translation: CAB55945.1
CCDSiCCDS32537.1 [Q9C000-5]
CCDS42244.1 [Q9C000-4]
CCDS42245.1 [Q9C000-2]
CCDS42246.1 [Q9C000-1]
CCDS58508.1 [Q9C000-3]
PIRiT17255
RefSeqiNP_001028225.1, NM_001033053.2 [Q9C000-5]
NP_055737.1, NM_014922.4 [Q9C000-2]
NP_127497.1, NM_033004.3 [Q9C000-1]
NP_127499.1, NM_033006.3 [Q9C000-4]
NP_127500.1, NM_033007.3 [Q9C000-3]
UniGeneiHs.652273

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1PN5NMR-A1-93[»]
3KATX-ray3.10A1371-1467[»]
4IFPX-ray1.99A/B/C1379-1462[»]
4IM6X-ray1.65A791-990[»]
5Y3SX-ray2.45A/B/C/D790-990[»]
DisProtiDP00554
ProteinModelPortaliQ9C000
SMRiQ9C000
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi116529, 13 interactors
CORUMiQ9C000
DIPiDIP-38407N
IntActiQ9C000, 11 interactors
STRINGi9606.ENSP00000460475

Chemistry databases

BindingDBiQ9C000
ChEMBLiCHEMBL1741214

PTM databases

iPTMnetiQ9C000
PhosphoSitePlusiQ9C000

Polymorphism and mutation databases

BioMutaiNLRP1
DMDMi17380146

Proteomic databases

EPDiQ9C000
PaxDbiQ9C000
PeptideAtlasiQ9C000
PRIDEiQ9C000
ProteomicsDBi79931
79932 [Q9C000-2]
79933 [Q9C000-3]
79934 [Q9C000-4]

Protocols and materials databases

DNASUi22861
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000262467; ENSP00000262467; ENSG00000091592 [Q9C000-5]
ENST00000269280; ENSP00000269280; ENSG00000091592 [Q9C000-2]
ENST00000345221; ENSP00000324366; ENSG00000091592 [Q9C000-2]
ENST00000354411; ENSP00000346390; ENSG00000091592 [Q9C000-4]
ENST00000544378; ENSP00000442029; ENSG00000091592 [Q9C000-5]
ENST00000571451; ENSP00000459661; ENSG00000091592 [Q9C000-2]
ENST00000572272; ENSP00000460475; ENSG00000091592 [Q9C000-1]
ENST00000577119; ENSP00000460216; ENSG00000091592 [Q9C000-3]
ENST00000613500; ENSP00000483359; ENSG00000091592 [Q9C000-5]
ENST00000617618; ENSP00000478516; ENSG00000091592 [Q9C000-1]
ENST00000619223; ENSP00000484692; ENSG00000091592 [Q9C000-4]
GeneIDi22861
KEGGihsa:22861
UCSCiuc002gcg.2 human [Q9C000-1]

Organism-specific databases

CTDi22861
DisGeNETi22861
EuPathDBiHostDB:ENSG00000091592.15
GeneCardsiNLRP1
HGNCiHGNC:14374 NLRP1
HPAiCAB009189
HPA064431
MalaCardsiNLRP1
MIMi606579 phenotype
606636 gene
615225 phenotype
617388 phenotype
neXtProtiNX_Q9C000
OpenTargetsiENSG00000091592
Orphaneti352662 Corneal intraepithelial dyskeratosis with palmoplantar hyperkeratosis and laryngeal dyskeratosis
3435 Vitiligo
247871 Vitiligo-associated autoimmune disease
PharmGKBiPA162397797
HUGEiSearch...
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410JAIN Eukaryota
ENOG410YGKV LUCA
GeneTreeiENSGT00900000140813
HOGENOMiHOG000230509
HOVERGENiHBG052573
InParanoidiQ9C000
KOiK12798
OMAiLIMELWE
OrthoDBiEOG091G01QH
PhylomeDBiQ9C000
TreeFamiTF340267

Enzyme and pathway databases

ReactomeiR-HSA-844455 The NLRP1 inflammasome

Miscellaneous databases

ChiTaRSiNLRP1 human
EvolutionaryTraceiQ9C000
GeneWikiiNLRP1
GenomeRNAii22861
PROiPR:Q9C000
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000091592 Expressed in 205 organ(s), highest expression level in pituitary gland
CleanExiHS_NLRP1
ExpressionAtlasiQ9C000 baseline and differential
GenevisibleiQ9C000 HS

Family and domain databases

CDDicd08330 CARD_ASC_NALP1, 1 hit
Gene3Di3.80.10.10, 1 hit
InterProiView protein in InterPro
IPR001315 CARD
IPR033516 CARD8/ASC/NALP1_CARD
IPR004020 DAPIN
IPR011029 DEATH-like_dom_sf
IPR025307 FIIND_dom
IPR001611 Leu-rich_rpt
IPR032675 LRR_dom_sf
IPR007111 NACHT_NTPase
IPR027417 P-loop_NTPase
PfamiView protein in Pfam
PF00619 CARD, 1 hit
PF13553 FIIND, 1 hit
PF13516 LRR_6, 3 hits
PF05729 NACHT, 1 hit
PF02758 PYRIN, 1 hit
SMARTiView protein in SMART
SM01289 PYRIN, 1 hit
SUPFAMiSSF47986 SSF47986, 2 hits
SSF52540 SSF52540, 2 hits
PROSITEiView protein in PROSITE
PS50209 CARD, 1 hit
PS50824 DAPIN, 1 hit
PS51830 FIIND, 1 hit
PS51450 LRR, 3 hits
PS50837 NACHT, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiNLRP1_HUMAN
AccessioniPrimary (citable) accession number: Q9C000
Secondary accession number(s): E9PE50
, I6L9D9, Q9BZZ8, Q9BZZ9, Q9H5Z7, Q9H5Z8, Q9HAV8, Q9UFT4, Q9Y2E0
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 18, 2001
Last sequence update: June 1, 2001
Last modified: October 10, 2018
This is version 196 of the entry and version 1 of the sequence. See 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, Direct protein sequencing, Reference proteome

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. SIMILARITY comments
    Index of protein domains and families
  3. Human chromosome 17
    Human chromosome 17: entries, gene names and cross-references to MIM
  4. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  5. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  6. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
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