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Protein

NACHT, LRR and PYD domains-containing protein 1

Gene

NLRP1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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 similarity7 Publications

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei1186 – 11861Trigger for autocatalytic processing1 Publication

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi334 – 3418ATPPROSITE-ProRule annotation

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

  • activation of cysteine-type endopeptidase activity involved in apoptotic process Source: UniProtKB
  • apoptotic process Source: UniProtKB
  • defense response to bacterium Source: BHF-UCL
  • inflammatory response Source: UniProtKB-KW
  • innate immune response Source: UniProtKB-KW
  • neuron apoptotic process Source: HGNC
  • positive regulation of interleukin-1 beta secretion Source: BHF-UCL
  • regulation of inflammatory response Source: BHF-UCL
  • response to muramyl dipeptide Source: BHF-UCL
Complete GO annotation...

Keywords - Biological processi

Immunity, Inflammatory response, Innate immunity

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiR-HSA-844455. The NLRP1 inflammasome.

Protein family/group databases

MEROPSiS79.A05.

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

HGNCiHGNC:14374. NLRP1.

Subcellular locationi

GO - Cellular componenti

  • cytosol Source: Reactome
  • intracellular Source: UniProtKB
  • NLRP1 inflammasome complex Source: UniProtKB
  • nucleus Source: BHF-UCL
Complete GO annotation...

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)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti155 – 1551L → H in VAMAS1; associated with disease susceptibility. 2 Publications
Corresponds to variant rs12150220 [ dbSNP | Ensembl ].
VAR_033239
Corneal intraepithelial dyskeratosis and ectodermal dysplasia (CIDED)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA disease characterized by keratopathy with neovascularization, bilateral corneal opacification, palmoplantar hyperkeratosis, dyshidrosis, and dystrophic nails.
See also OMIM:615225
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti77 – 771M → T in CIDED. 1 Publication
Corresponds to variant rs397514692 [ dbSNP | Ensembl ].
VAR_069901

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi339 – 3402GK → EA: Loss of ATP binding. 1 Publication
Mutagenesisi340 – 3401K → L or S: No effect. 1 Publication
Mutagenesisi1168 – 11681H → A: Complete loss of autocatalytic processing and of IL1B release. Autocatalytic processing cannot be restored by treatment with hydroxylamine. 1 Publication
Mutagenesisi1186 – 11861H → A: Complete loss of autocatalytic processing and of IL1B release. Autocatalytic processing can be restored by treatment with hydroxylamine. 1 Publication
Mutagenesisi1211 – 12111S → A: Partial loss of autocatalytic processing and of IL1B release. 1 Publication
Mutagenesisi1212 – 12121F → A: Complete loss of autocatalytic processing and of IL1B release. 1 Publication
Mutagenesisi1213 – 12131S → A: Complete loss of autocatalytic processing and of IL1B release. Autocatalytic processing cannot be restored by treatment with hydroxylamine. 2 Publications
Mutagenesisi1213 – 12131S → C: Complete loss of autocatalytic processing, which can be restored by treatment with hydroxylamine. 1 Publication
Mutagenesisi1214 – 12141P → A: Partial loss of autocatalytic processing (50%) and of IL1B release (50%). 1 Publication
Mutagenesisi1249 – 12491H → A: Complete loss of autocatalytic processing and IL1B release. Autocatalytic processing cannot be restored by treatment with hydroxylamine. 1 Publication

Keywords - Diseasei

Disease mutation, Ectodermal dysplasia

Organism-specific databases

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

Chemistry

ChEMBLiCHEMBL1741214.

Polymorphism and mutation databases

BioMutaiNLRP1.
DMDMi17380146.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 14731473NACHT, LRR and PYD domains-containing protein 1PRO_0000096710Add
BLAST

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei1213 – 12142Cleavage; by autocatalysis1 Publication

Proteomic databases

EPDiQ9C000.
PaxDbiQ9C000.
PeptideAtlasiQ9C000.
PRIDEiQ9C000.

PTM databases

iPTMnetiQ9C000.
PhosphoSiteiQ9C000.

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).4 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.
CleanExiHS_NLRP1.
ExpressionAtlasiQ9C000. baseline and differential.
GenevisibleiQ9C000. HS.

Organism-specific databases

HPAiCAB009189.

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

Binary interactionsi

WithEntry#Exp.IntActNotes
BCL2P1041512EBI-1220518,EBI-77694
BCL2L1Q078179EBI-1220518,EBI-78035
PYCARDQ9ULZ35EBI-1220518,EBI-751215

GO - Molecular functioni

  • enzyme binding Source: UniProtKB
  • protein domain specific binding Source: UniProtKB

Protein-protein interaction databases

BioGridi116529. 11 interactions.
DIPiDIP-38407N.
IntActiQ9C000. 9 interactions.
MINTiMINT-150191.
STRINGi9606.ENSP00000460475.

Chemistry

BindingDBiQ9C000.

Structurei

Secondary structure

1
1473
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi9 – 157Combined sources
Helixi18 – 3114Combined sources
Helixi50 – 6011Combined sources
Helixi63 – 7715Combined sources
Helixi80 – 856Combined sources
Beta strandi88 – 914Combined sources
Helixi794 – 80411Combined sources
Beta strandi812 – 8143Combined sources
Helixi822 – 83312Combined sources
Beta strandi840 – 8434Combined sources
Helixi851 – 86212Combined sources
Beta strandi869 – 8713Combined sources
Helixi878 – 88912Combined sources
Beta strandi898 – 9003Combined sources
Helixi908 – 9103Combined sources
Helixi911 – 92010Combined sources
Beta strandi926 – 9283Combined sources
Beta strandi931 – 9333Combined sources
Helixi935 – 94612Combined sources
Beta strandi955 – 9573Combined sources
Helixi965 – 97713Combined sources
Beta strandi982 – 9843Combined sources
Helixi1381 – 13844Combined sources
Helixi1386 – 13927Combined sources
Helixi1396 – 14038Combined sources
Turni1405 – 14073Combined sources
Helixi1410 – 14178Combined sources
Beta strandi1419 – 14213Combined sources
Helixi1422 – 143312Combined sources
Helixi1438 – 145114Combined sources
Helixi1453 – 146210Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1PN5NMR-A1-93[»]
3KATX-ray3.10A1371-1467[»]
4IFPX-ray1.99A/B/C1379-1462[»]
4IM6X-ray1.65A791-990[»]
DisProtiDP00554.
ProteinModelPortaliQ9C000.
SMRiQ9C000. Positions 1-93, 792-989, 1379-1462.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9C000.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini1 – 9292PyrinPROSITE-ProRule annotationAdd
BLAST
Domaini328 – 637310NACHTPROSITE-ProRule annotationAdd
BLAST
Repeati809 – 83022LRR 1Add
BLAST
Repeati838 – 85821LRR 2Add
BLAST
Repeati866 – 88722LRR 3Add
BLAST
Repeati895 – 91521LRR 4Add
BLAST
Repeati923 – 94422LRR 5Add
BLAST
Repeati950 – 97324LRR 6Add
BLAST
Domaini1374 – 146390CARDPROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni1100 – 1354255FIINDCuratedAdd
BLAST

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
Contains 1 CARD domain.PROSITE-ProRule annotation
Contains 6 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

eggNOGiENOG410JAIN. Eukaryota.
ENOG410YGKV. LUCA.
GeneTreeiENSGT00840000129675.
HOGENOMiHOG000230509.
HOVERGENiHBG052573.
InParanoidiQ9C000.
KOiK12798.
OMAiHPHLIME.
OrthoDBiEOG091G01QH.
PhylomeDBiQ9C000.
TreeFamiTF340267.

Family and domain databases

Gene3Di1.10.533.10. 2 hits.
3.80.10.10. 1 hit.
InterProiIPR001315. CARD.
IPR004020. DAPIN.
IPR011029. DEATH-like_dom.
IPR025307. FIIND_dom.
IPR032675. L_dom-like.
IPR001611. Leu-rich_rpt.
IPR007111. NACHT_NTPase.
IPR033516. NLRP1.
IPR027417. P-loop_NTPase.
[Graphical view]
PANTHERiPTHR24106:SF13. PTHR24106:SF13. 2 hits.
PfamiPF00619. CARD. 1 hit.
PF13553. FIIND. 1 hit.
PF13516. LRR_6. 3 hits.
PF02758. PYRIN. 1 hit.
[Graphical view]
SMARTiSM01289. PYRIN. 1 hit.
[Graphical view]
SUPFAMiSSF47986. SSF47986. 2 hits.
SSF52540. SSF52540. 2 hits.
PROSITEiPS50209. CARD. 1 hit.
PS50824. DAPIN. 1 hit.
PS51450. LRR. 3 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: 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

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)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti287 – 2871P → S in AAH51787 (PubMed:15489334).Curated
Sequence conflicti782 – 7821T → S in AAG15254 (PubMed:11270363).Curated
Sequence conflicti995 – 9951T → I in AAG15254 (PubMed:11270363).Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti77 – 771M → T in CIDED. 1 Publication
Corresponds to variant rs397514692 [ dbSNP | Ensembl ].
VAR_069901
Natural varianti155 – 1551L → H in VAMAS1; associated with disease susceptibility. 2 Publications
Corresponds to variant rs12150220 [ dbSNP | Ensembl ].
VAR_033239
Natural varianti246 – 2461T → S.1 Publication
Corresponds to variant rs11651595 [ dbSNP | Ensembl ].
VAR_024238
Natural varianti404 – 4041R → Q.
Corresponds to variant rs3744718 [ dbSNP | Ensembl ].
VAR_021886
Natural varianti878 – 8781T → M.1 Publication
Corresponds to variant rs11657747 [ dbSNP | Ensembl ].
VAR_033240
Natural varianti1059 – 10591V → M.
Corresponds to variant rs2301582 [ dbSNP | Ensembl ].
VAR_024239
Natural varianti1069 – 10691H → Y.
Corresponds to variant rs9907167 [ dbSNP | Ensembl ].
VAR_033241
Natural varianti1119 – 11191M → V No effect on autocatalytic processing, nor on IL1B release. 2 Publications
Corresponds to variant rs35596958 [ dbSNP | Ensembl ].
VAR_033242
Natural varianti1184 – 11841M → V Increased autocatalytic processing and IL1B release. 3 Publications
Corresponds to variant rs11651270 [ dbSNP | Ensembl ].
VAR_033243
Natural varianti1241 – 12411V → L.1 Publication
Corresponds to variant rs11653832 [ dbSNP | Ensembl ].
VAR_033244
Natural varianti1366 – 13661R → C.1 Publication
Corresponds to variant rs2137722 [ dbSNP | Ensembl ].
VAR_020437

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 966966Missing in isoform 7. 1 PublicationVSP_053801Add
BLAST
Alternative sequencei1 – 734734Missing in isoform 6. 1 PublicationVSP_053802Add
BLAST
Alternative sequencei958 – 98730Missing in isoform 3 and isoform 4. 1 PublicationVSP_004326Add
BLAST
Alternative sequencei1044 – 10441A → AGKSH in isoform 5 and isoform 7. 2 PublicationsVSP_053803
Alternative sequencei1262 – 130544Missing in isoform 2 and isoform 3. 5 PublicationsVSP_004327Add
BLAST
Alternative sequencei1354 – 137118DLMPA…IAVPS → RNTSQPWNLRCNRDARRY in isoform 5 and isoform 7. 2 PublicationsVSP_053804Add
BLAST
Alternative sequencei1372 – 1473102Missing in isoform 5 and isoform 7. 2 PublicationsVSP_053805Add
BLAST

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]
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

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
EntryMethodResolution (Å)ChainPositionsPDBsum
1PN5NMR-A1-93[»]
3KATX-ray3.10A1371-1467[»]
4IFPX-ray1.99A/B/C1379-1462[»]
4IM6X-ray1.65A791-990[»]
DisProtiDP00554.
ProteinModelPortaliQ9C000.
SMRiQ9C000. Positions 1-93, 792-989, 1379-1462.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi116529. 11 interactions.
DIPiDIP-38407N.
IntActiQ9C000. 9 interactions.
MINTiMINT-150191.
STRINGi9606.ENSP00000460475.

Chemistry

BindingDBiQ9C000.
ChEMBLiCHEMBL1741214.

Protein family/group databases

MEROPSiS79.A05.

PTM databases

iPTMnetiQ9C000.
PhosphoSiteiQ9C000.

Polymorphism and mutation databases

BioMutaiNLRP1.
DMDMi17380146.

Proteomic databases

EPDiQ9C000.
PaxDbiQ9C000.
PeptideAtlasiQ9C000.
PRIDEiQ9C000.

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]
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.
GeneCardsiNLRP1.
HGNCiHGNC:14374. NLRP1.
HPAiCAB009189.
MalaCardsiNLRP1.
MIMi606579. phenotype.
606636. gene.
615225. phenotype.
neXtProtiNX_Q9C000.
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.
GeneTreeiENSGT00840000129675.
HOGENOMiHOG000230509.
HOVERGENiHBG052573.
InParanoidiQ9C000.
KOiK12798.
OMAiHPHLIME.
OrthoDBiEOG091G01QH.
PhylomeDBiQ9C000.
TreeFamiTF340267.

Enzyme and pathway databases

ReactomeiR-HSA-844455. The NLRP1 inflammasome.

Miscellaneous databases

EvolutionaryTraceiQ9C000.
GeneWikiiNLRP1.
GenomeRNAii22861.
PROiQ9C000.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000091592.
CleanExiHS_NLRP1.
ExpressionAtlasiQ9C000. baseline and differential.
GenevisibleiQ9C000. HS.

Family and domain databases

Gene3Di1.10.533.10. 2 hits.
3.80.10.10. 1 hit.
InterProiIPR001315. CARD.
IPR004020. DAPIN.
IPR011029. DEATH-like_dom.
IPR025307. FIIND_dom.
IPR032675. L_dom-like.
IPR001611. Leu-rich_rpt.
IPR007111. NACHT_NTPase.
IPR033516. NLRP1.
IPR027417. P-loop_NTPase.
[Graphical view]
PANTHERiPTHR24106:SF13. PTHR24106:SF13. 2 hits.
PfamiPF00619. CARD. 1 hit.
PF13553. FIIND. 1 hit.
PF13516. LRR_6. 3 hits.
PF02758. PYRIN. 1 hit.
[Graphical view]
SMARTiSM01289. PYRIN. 1 hit.
[Graphical view]
SUPFAMiSSF47986. SSF47986. 2 hits.
SSF52540. SSF52540. 2 hits.
PROSITEiPS50209. CARD. 1 hit.
PS50824. DAPIN. 1 hit.
PS51450. LRR. 3 hits.
PS50837. NACHT. 1 hit.
[Graphical view]
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 historyi
Integrated into UniProtKB/Swiss-Prot: October 18, 2001
Last sequence update: June 1, 2001
Last modified: September 7, 2016
This is version 175 of the entry and version 1 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

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

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 17
    Human chromosome 17: 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.