Q9C000 (NALP1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:	NLRP1
Synonyms:	CARD7, DEFCAP, KIAA0926, NAC, NALP1

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	1473 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Able to form cytoplasmic structures termed death effector filaments. Enhances APAF1 and cytochrome c-dependent activation of pro-caspase-9 and consecutive apoptosis. Stimulates apoptosis through activation of caspase-3. Involved in activation of caspase-1 and caspase-5 as part of the NALP1 inflammasome complex which leads to processing and release of IL1B and IL18. Binds ATP. Ref.7 Ref.9 Ref.11
Subunit structure	Interacts strongly with caspase-2, weakly with caspase-9 and with APAF1 in a cytochrome c-inducible way, leading to the formation of an apoptosome. This interaction may be ATP-dependent. Part of the NALP1 inflammasome complex which is involved in activation of caspase-1 and caspase-5, leading to processing of IL1B and IL18. The complex is activated by bacterial muramyl dipeptide which triggers ATP-binding and oligomerization of NALP1. Interacts with EIF2AK2/PKR. Ref.4 Ref.7
Subcellular location	Cytoplasm. Nucleus Ref.10.
Tissue specificity	Widely expressed. Isoform 1 and isoform 2 are expressed in peripheral blood leukocytes and chronic myelogenous leukemia cell line K-562, followed by thymus, spleen and heart. Also detected in brain, lung, placenta, small intestine, colon, kidney, liver, muscle, testis and epithelial cells. Absent from hematopoietic progenitor cells but expressed upon differentiation of cells into granulocytes and, to a lesser extent, monocytes. In peripheral blood cells, highest levels are found in T-lymphocytes, granulocytes and monocytes. Expression is significantly increased in bone marrow blast cells of some acute leukemia patients but not in solid tumors. Ref.8 Ref.10
Involvement in disease	Vitiligo (VTLG) [MIM:193200]: A pigmentary disorder of the skin and mucous membranes. It is characterized by circumscribed depigmented macules and patches, commonly on extensor aspects of extremities, on the face or neck and in skin folds. Vitiligo is a progressive disorder in which some or all of the melanocytes in the affected skin are selectively destroyed. It is a multifactorial disorder with a complex etiology probably including autoimmune mechanisms, and is associated with an elevated risk of other autoimmune diseases. Note: Disease susceptibility is associated with variations affecting the gene represented in this entry. Ref.14 Vitiligo-associated multiple autoimmune disease 1 (VAMAS1) [MIM:606579]: A disorder characterized by the association of vitiligo with several autoimmune and autoinflammatory diseases including autoimmune thyroid disease, rheumatoid arthritis and systemic lupus erythematosus. Note: Disease susceptibility is associated with variations affecting the gene represented in this entry. Ref.14
Sequence similarities	Belongs to the NLRP family. Contains 1 CARD domain. Contains 1 DAPIN domain. Contains 6 LRR (leucine-rich) repeats. Contains 1 NACHT domain.
Sequence caution	The sequence BAA76770.2 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Biological process	Apoptosis
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Leucine-rich repeat Repeat
Ligand	ATP-binding Nucleotide-binding
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	defense response to bacterium Inferred from sequence or structural similarity. Source: BHF-UCL induction of apoptosis Non-traceable author statement Ref.3. Source: UniProtKB innate immune response Traceable author statement. Source: Reactome neuron apoptotic process Inferred from direct assay Ref.9. Source: HGNC nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway Traceable author statement. Source: Reactome positive regulation of interleukin-1 beta secretion Inferred from sequence or structural similarity. Source: BHF-UCL regulation of inflammatory response Inferred by curator Ref.9. Source: BHF-UCL response to muramyl dipeptide Inferred from sequence or structural similarity. Source: BHF-UCL
Cellular_component	NLRP1 inflammasome complex Inferred from direct assay Ref.7. Source: UniProtKB cytosol Traceable author statement. Source: Reactome nucleus Inferred from direct assay Ref.10. Source: BHF-UCL
Molecular_function	ATP binding Inferred from direct assay Ref.9. Source: HGNC cysteine-type endopeptidase activator activity involved in apoptotic process Non-traceable author statement Ref.3. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
BCL2	P10415	12	EBI-1220518,EBI-77694
BCL2L1	Q07817	9	EBI-1220518,EBI-78035
PYCARD	Q9ULZ3	5	EBI-1220518,EBI-751215

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q9C000-1)

Also known as: NAC beta; DEFCAP-L;

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.

Isoform 2 (identifier: Q9C000-2)

Also known as: NAC alpha; DEFCAP-S;

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

Isoform 3 (identifier: Q9C000-3)

Also known as: NAC gamma;

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

Isoform 4 (identifier: Q9C000-4)

Also known as: NAC delta;

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

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 1473

1473

NACHT, LRR and PYD domains-containing protein 1

PRO_0000096710

Regions

Domain

1 – 92

92

DAPIN

Domain

328 – 637

310

NACHT

Repeat

809 – 830

22

LRR 1

Repeat

838 – 858

21

LRR 2

Repeat

866 – 887

22

LRR 3

Repeat

895 – 915

21

LRR 4

Repeat

923 – 944

22

LRR 5

Repeat

950 – 973

24

LRR 6

Domain

1374 – 1463

90

CARD

Nucleotide binding

334 – 341

8

ATP Potential

Natural variations

Alternative sequence

958 – 987

30

Missing in isoform 3 and isoform 4.

VSP_004326

Alternative sequence

1262 – 1305

44

Missing in isoform 2 and isoform 3.

VSP_004327

Natural variant

155

1

L → H Associated with susceptibility to vitiligo and vitiligo-associated autoimmune diseases. Ref.1 Ref.14
Corresponds to variant rs12150220 [ dbSNP | Ensembl ].

VAR_033239

Natural variant

246

1

T → S. Ref.1
Corresponds to variant rs11651595 [ dbSNP | Ensembl ].

VAR_024238

Natural variant

404

1

R → Q.
Corresponds to variant rs3744718 [ dbSNP | Ensembl ].

VAR_021886

Natural variant

878

1

T → M. Ref.1
Corresponds to variant rs11657747 [ dbSNP | Ensembl ].

VAR_033240

Natural variant

1059

1

V → M.
Corresponds to variant rs2301582 [ dbSNP | Ensembl ].

VAR_024239

Natural variant

1069

1

H → Y.
Corresponds to variant rs9907167 [ dbSNP | Ensembl ].

VAR_033241

Natural variant

1119

1

M → V. Ref.1
Corresponds to variant rs35596958 [ dbSNP | Ensembl ].

VAR_033242

Natural variant

1184

1

M → V. Ref.1 Ref.6
Corresponds to variant rs11651270 [ dbSNP | Ensembl ].

VAR_033243

Natural variant

1241

1

V → L. Ref.1
Corresponds to variant rs11653832 [ dbSNP | Ensembl ].

VAR_033244

Natural variant

1366

1

R → C. Ref.1
Corresponds to variant rs2137722 [ dbSNP | Ensembl ].

VAR_020437

Experimental info

Mutagenesis

339 – 340

2

GK → EA: Abolishes binding to ATP. Ref.3 Ref.9

Mutagenesis

340

1

K → L or S: No effect. Ref.3 Ref.9

Sequence conflict

782

1

T → S in AAG15254. Ref.1

Sequence conflict

995

1

T → I in AAG15254. Ref.1

Secondary structure

1

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1473

Helix Strand Turn

Details...

Helix

9 – 15

7

Helix

18 – 31

14

Helix

50 – 60

11

Helix

63 – 77

15

Helix

80 – 85

6

Beta strand

88 – 91

4

Helix

1380 – 1384

5

Helix

1386 – 1390

5

Helix

1396 – 1403

8

Turn

1404 – 1407

4

Helix

1410 – 1418

9

Helix

1422 – 1431

10

Helix

1432 – 1435

4

Helix

1440 – 1451

12

Helix

1453 – 1461

9

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (NAC beta) (DEFCAP-L) [UniParc]. Last modified June 1, 2001. Version 1. Checksum: 438F0DCE45C2562D	FASTA	1,473	165,866
	10 20 30 40 50 60 MAGGAWGRLA CYLEFLKKEE LKEFQLLLAN KAHSRSSSGE TPAQPEKTSG MEVASYLVAQ 70 80 90 100 110 120 YGEQRAWDLA LHTWEQMGLR SLCAQAQEGA GHSPSFPYSP SEPHLGSPSQ PTSTAVLMPW 130 140 150 160 170 180 IHELPAGCTQ GSERRVLRQL PDTSGRRWRE ISASLLYQAL PSSPDHESPS QESPNAPTST 190 200 210 220 230 240 AVLGSWGSPP QPSLAPREQE APGTQWPLDE TSGIYYTEIR EREREKSEKG RPPWAAVVGT 250 260 270 280 290 300 PPQAHTSLQP HHHPWEPSVR ESLCSTWPWK NEDFNQKFTQ LLLLQRPHPR SQDPLVKRSW 310 320 330 340 350 360 PDYVEENRGH LIEIRDLFGP GLDTQEPRIV ILQGAAGIGK STLARQVKEA WGRGQLYGDR 370 380 390 400 410 420 FQHVFYFSCR ELAQSKVVSL AELIGKDGTA TPAPIRQILS RPERLLFILD GVDEPGWVLQ 430 440 450 460 470 480 EPSSELCLHW SQPQPADALL GSLLGKTILP EASFLITART TALQNLIPSL EQARWVEVLG 490 500 510 520 530 540 FSESSRKEYF YRYFTDERQA IRAFRLVKSN KELWALCLVP WVSWLACTCL MQQMKRKEKL 550 560 570 580 590 600 TLTSKTTTTL CLHYLAQALQ AQPLGPQLRD LCSLAAEGIW QKKTLFSPDD LRKHGLDGAI 610 620 630 640 650 660 ISTFLKMGIL QEHPIPLSYS FIHLCFQEFF AAMSYVLEDE KGRGKHSNCI IDLEKTLEAY 670 680 690 700 710 720 GIHGLFGAST TRFLLGLLSD EGEREMENIF HCRLSQGRNL MQWVPSLQLL LQPHSLESLH 730 740 750 760 770 780 CLYETRNKTF LTQVMAHFEE MGMCVETDME LLVCTFCIKF SRHVKKLQLI EGRQHRSTWS 790 800 810 820 830 840 PTMVVLFRWV PVTDAYWQIL FSVLKVTRNL KELDLSGNSL SHSAVKSLCK TLRRPRCLLE 850 860 870 880 890 900 TLRLAGCGLT AEDCKDLAFG LRANQTLTEL DLSFNVLTDA GAKHLCQRLR QPSCKLQRLQ 910 920 930 940 950 960 LVSCGLTSDC CQDLASVLSA SPSLKELDLQ QNNLDDVGVR LLCEGLRHPA CKLIRLGLDQ 970 980 990 1000 1010 1020 TTLSDEMRQE LRALEQEKPQ LLIFSRRKPS VMTPTEGLDT GEMSNSTSSL KRQRLGSERA 1030 1040 1050 1060 1070 1080 ASHVAQANLK LLDVSKIFPI AEIAEESSPE VVPVELLCVP SPASQGDLHT KPLGTDDDFW 1090 1100 1110 1120 1130 1140 GPTGPVATEV VDKEKNLYRV HFPVAGSYRW PNTGLCFVMR EAVTVEIEFC VWDQFLGEIN 1150 1160 1170 1180 1190 1200 PQHSWMVAGP LLDIKAEPGA VEAVHLPHFV ALQGGHVDTS LFQMAHFKEE GMLLEKPARV 1210 1220 1230 1240 1250 1260 ELHHIVLENP SFSPLGVLLK MIHNALRFIP VTSVVLLYHR VHPEEVTFHL YLIPSDCSIR 1270 1280 1290 1300 1310 1320 KAIDDLEMKF QFVRIHKPPP LTPLYMGCRY TVSGSGSGML EILPKELELC YRSPGEDQLF 1330 1340 1350 1360 1370 1380 SEFYVGHLGS GIRLQVKDKK DETLVWEALV KPGDLMPATT LIPPARIAVP SPLDAPQLLH 1390 1400 1410 1420 1430 1440 FVDQYREQLI ARVTSVEVVL DKLHGQVLSQ EQYERVLAEN TRPSQMRKLF SLSQSWDRKC 1450 1460 1470 KDGLYQALKE THPHLIMELW EKGSKKGLLP LSS
	Isoform 2 (NAC alpha) (DEFCAP-S) [UniParc]. Checksum: 6C5CBE8FD2819435	FASTA	1,429	160,946
	10 20 30 40 50 60 MAGGAWGRLA CYLEFLKKEE LKEFQLLLAN KAHSRSSSGE TPAQPEKTSG MEVASYLVAQ 70 80 90 100 110 120 YGEQRAWDLA LHTWEQMGLR SLCAQAQEGA GHSPSFPYSP SEPHLGSPSQ PTSTAVLMPW 130 140 150 160 170 180 IHELPAGCTQ GSERRVLRQL PDTSGRRWRE ISASLLYQAL PSSPDHESPS QESPNAPTST 190 200 210 220 230 240 AVLGSWGSPP QPSLAPREQE APGTQWPLDE TSGIYYTEIR EREREKSEKG RPPWAAVVGT 250 260 270 280 290 300 PPQAHTSLQP HHHPWEPSVR ESLCSTWPWK NEDFNQKFTQ LLLLQRPHPR SQDPLVKRSW 310 320 330 340 350 360 PDYVEENRGH LIEIRDLFGP GLDTQEPRIV ILQGAAGIGK STLARQVKEA WGRGQLYGDR 370 380 390 400 410 420 FQHVFYFSCR ELAQSKVVSL AELIGKDGTA TPAPIRQILS RPERLLFILD GVDEPGWVLQ 430 440 450 460 470 480 EPSSELCLHW SQPQPADALL GSLLGKTILP EASFLITART TALQNLIPSL EQARWVEVLG 490 500 510 520 530 540 FSESSRKEYF YRYFTDERQA IRAFRLVKSN KELWALCLVP WVSWLACTCL MQQMKRKEKL 550 560 570 580 590 600 TLTSKTTTTL CLHYLAQALQ AQPLGPQLRD LCSLAAEGIW QKKTLFSPDD LRKHGLDGAI 610 620 630 640 650 660 ISTFLKMGIL QEHPIPLSYS FIHLCFQEFF AAMSYVLEDE KGRGKHSNCI IDLEKTLEAY 670 680 690 700 710 720 GIHGLFGAST TRFLLGLLSD EGEREMENIF HCRLSQGRNL MQWVPSLQLL LQPHSLESLH 730 740 750 760 770 780 CLYETRNKTF LTQVMAHFEE MGMCVETDME LLVCTFCIKF SRHVKKLQLI EGRQHRSTWS 790 800 810 820 830 840 PTMVVLFRWV PVTDAYWQIL FSVLKVTRNL KELDLSGNSL SHSAVKSLCK TLRRPRCLLE 850 860 870 880 890 900 TLRLAGCGLT AEDCKDLAFG LRANQTLTEL DLSFNVLTDA GAKHLCQRLR QPSCKLQRLQ 910 920 930 940 950 960 LVSCGLTSDC CQDLASVLSA SPSLKELDLQ QNNLDDVGVR LLCEGLRHPA CKLIRLGLDQ 970 980 990 1000 1010 1020 TTLSDEMRQE LRALEQEKPQ LLIFSRRKPS VMTPTEGLDT GEMSNSTSSL KRQRLGSERA 1030 1040 1050 1060 1070 1080 ASHVAQANLK LLDVSKIFPI AEIAEESSPE VVPVELLCVP SPASQGDLHT KPLGTDDDFW 1090 1100 1110 1120 1130 1140 GPTGPVATEV VDKEKNLYRV HFPVAGSYRW PNTGLCFVMR EAVTVEIEFC VWDQFLGEIN 1150 1160 1170 1180 1190 1200 PQHSWMVAGP LLDIKAEPGA VEAVHLPHFV ALQGGHVDTS LFQMAHFKEE GMLLEKPARV 1210 1220 1230 1240 1250 1260 ELHHIVLENP SFSPLGVLLK MIHNALRFIP VTSVVLLYHR VHPEEVTFHL YLIPSDCSIR 1270 1280 1290 1300 1310 1320 KELELCYRSP GEDQLFSEFY VGHLGSGIRL QVKDKKDETL VWEALVKPGD LMPATTLIPP 1330 1340 1350 1360 1370 1380 ARIAVPSPLD APQLLHFVDQ YREQLIARVT SVEVVLDKLH GQVLSQEQYE RVLAENTRPS 1390 1400 1410 1420 QMRKLFSLSQ SWDRKCKDGL YQALKETHPH LIMELWEKGS KKGLLPLSS
	Isoform 3 (NAC gamma) [UniParc]. Checksum: 59C172B75766F38F	FASTA	1,399	157,319
	10 20 30 40 50 60 MAGGAWGRLA CYLEFLKKEE LKEFQLLLAN KAHSRSSSGE TPAQPEKTSG MEVASYLVAQ 70 80 90 100 110 120 YGEQRAWDLA LHTWEQMGLR SLCAQAQEGA GHSPSFPYSP SEPHLGSPSQ PTSTAVLMPW 130 140 150 160 170 180 IHELPAGCTQ GSERRVLRQL PDTSGRRWRE ISASLLYQAL PSSPDHESPS QESPNAPTST 190 200 210 220 230 240 AVLGSWGSPP QPSLAPREQE APGTQWPLDE TSGIYYTEIR EREREKSEKG RPPWAAVVGT 250 260 270 280 290 300 PPQAHTSLQP HHHPWEPSVR ESLCSTWPWK NEDFNQKFTQ LLLLQRPHPR SQDPLVKRSW 310 320 330 340 350 360 PDYVEENRGH LIEIRDLFGP GLDTQEPRIV ILQGAAGIGK STLARQVKEA WGRGQLYGDR 370 380 390 400 410 420 FQHVFYFSCR ELAQSKVVSL AELIGKDGTA TPAPIRQILS RPERLLFILD GVDEPGWVLQ 430 440 450 460 470 480 EPSSELCLHW SQPQPADALL GSLLGKTILP EASFLITART TALQNLIPSL EQARWVEVLG 490 500 510 520 530 540 FSESSRKEYF YRYFTDERQA IRAFRLVKSN KELWALCLVP WVSWLACTCL MQQMKRKEKL 550 560 570 580 590 600 TLTSKTTTTL CLHYLAQALQ AQPLGPQLRD LCSLAAEGIW QKKTLFSPDD LRKHGLDGAI 610 620 630 640 650 660 ISTFLKMGIL QEHPIPLSYS FIHLCFQEFF AAMSYVLEDE KGRGKHSNCI IDLEKTLEAY 670 680 690 700 710 720 GIHGLFGAST TRFLLGLLSD EGEREMENIF HCRLSQGRNL MQWVPSLQLL LQPHSLESLH 730 740 750 760 770 780 CLYETRNKTF LTQVMAHFEE MGMCVETDME LLVCTFCIKF SRHVKKLQLI EGRQHRSTWS 790 800 810 820 830 840 PTMVVLFRWV PVTDAYWQIL FSVLKVTRNL KELDLSGNSL SHSAVKSLCK TLRRPRCLLE 850 860 870 880 890 900 TLRLAGCGLT AEDCKDLAFG LRANQTLTEL DLSFNVLTDA GAKHLCQRLR QPSCKLQRLQ 910 920 930 940 950 960 LVSCGLTSDC CQDLASVLSA SPSLKELDLQ QNNLDDVGVR LLCEGLRHPA CKLIRLGKPS 970 980 990 1000 1010 1020 VMTPTEGLDT GEMSNSTSSL KRQRLGSERA ASHVAQANLK LLDVSKIFPI AEIAEESSPE 1030 1040 1050 1060 1070 1080 VVPVELLCVP SPASQGDLHT KPLGTDDDFW GPTGPVATEV VDKEKNLYRV HFPVAGSYRW 1090 1100 1110 1120 1130 1140 PNTGLCFVMR EAVTVEIEFC VWDQFLGEIN PQHSWMVAGP LLDIKAEPGA VEAVHLPHFV 1150 1160 1170 1180 1190 1200 ALQGGHVDTS LFQMAHFKEE GMLLEKPARV ELHHIVLENP SFSPLGVLLK MIHNALRFIP 1210 1220 1230 1240 1250 1260 VTSVVLLYHR VHPEEVTFHL YLIPSDCSIR KELELCYRSP GEDQLFSEFY VGHLGSGIRL 1270 1280 1290 1300 1310 1320 QVKDKKDETL VWEALVKPGD LMPATTLIPP ARIAVPSPLD APQLLHFVDQ YREQLIARVT 1330 1340 1350 1360 1370 1380 SVEVVLDKLH GQVLSQEQYE RVLAENTRPS QMRKLFSLSQ SWDRKCKDGL YQALKETHPH 1390 LIMELWEKGS KKGLLPLSS
	Isoform 4 (NAC delta) [UniParc]. Checksum: C30E9BE9EC82FE96	FASTA	1,443	162,239
	10 20 30 40 50 60 MAGGAWGRLA CYLEFLKKEE LKEFQLLLAN KAHSRSSSGE TPAQPEKTSG MEVASYLVAQ 70 80 90 100 110 120 YGEQRAWDLA LHTWEQMGLR SLCAQAQEGA GHSPSFPYSP SEPHLGSPSQ PTSTAVLMPW 130 140 150 160 170 180 IHELPAGCTQ GSERRVLRQL PDTSGRRWRE ISASLLYQAL PSSPDHESPS QESPNAPTST 190 200 210 220 230 240 AVLGSWGSPP QPSLAPREQE APGTQWPLDE TSGIYYTEIR EREREKSEKG RPPWAAVVGT 250 260 270 280 290 300 PPQAHTSLQP HHHPWEPSVR ESLCSTWPWK NEDFNQKFTQ LLLLQRPHPR SQDPLVKRSW 310 320 330 340 350 360 PDYVEENRGH LIEIRDLFGP GLDTQEPRIV ILQGAAGIGK STLARQVKEA WGRGQLYGDR 370 380 390 400 410 420 FQHVFYFSCR ELAQSKVVSL AELIGKDGTA TPAPIRQILS RPERLLFILD GVDEPGWVLQ 430 440 450 460 470 480 EPSSELCLHW SQPQPADALL GSLLGKTILP EASFLITART TALQNLIPSL EQARWVEVLG 490 500 510 520 530 540 FSESSRKEYF YRYFTDERQA IRAFRLVKSN KELWALCLVP WVSWLACTCL MQQMKRKEKL 550 560 570 580 590 600 TLTSKTTTTL CLHYLAQALQ AQPLGPQLRD LCSLAAEGIW QKKTLFSPDD LRKHGLDGAI 610 620 630 640 650 660 ISTFLKMGIL QEHPIPLSYS FIHLCFQEFF AAMSYVLEDE KGRGKHSNCI IDLEKTLEAY 670 680 690 700 710 720 GIHGLFGAST TRFLLGLLSD EGEREMENIF HCRLSQGRNL MQWVPSLQLL LQPHSLESLH 730 740 750 760 770 780 CLYETRNKTF LTQVMAHFEE MGMCVETDME LLVCTFCIKF SRHVKKLQLI EGRQHRSTWS 790 800 810 820 830 840 PTMVVLFRWV PVTDAYWQIL FSVLKVTRNL KELDLSGNSL SHSAVKSLCK TLRRPRCLLE 850 860 870 880 890 900 TLRLAGCGLT AEDCKDLAFG LRANQTLTEL DLSFNVLTDA GAKHLCQRLR QPSCKLQRLQ 910 920 930 940 950 960 LVSCGLTSDC CQDLASVLSA SPSLKELDLQ QNNLDDVGVR LLCEGLRHPA CKLIRLGKPS 970 980 990 1000 1010 1020 VMTPTEGLDT GEMSNSTSSL KRQRLGSERA ASHVAQANLK LLDVSKIFPI AEIAEESSPE 1030 1040 1050 1060 1070 1080 VVPVELLCVP SPASQGDLHT KPLGTDDDFW GPTGPVATEV VDKEKNLYRV HFPVAGSYRW 1090 1100 1110 1120 1130 1140 PNTGLCFVMR EAVTVEIEFC VWDQFLGEIN PQHSWMVAGP LLDIKAEPGA VEAVHLPHFV 1150 1160 1170 1180 1190 1200 ALQGGHVDTS LFQMAHFKEE GMLLEKPARV ELHHIVLENP SFSPLGVLLK MIHNALRFIP 1210 1220 1230 1240 1250 1260 VTSVVLLYHR VHPEEVTFHL YLIPSDCSIR KAIDDLEMKF QFVRIHKPPP LTPLYMGCRY 1270 1280 1290 1300 1310 1320 TVSGSGSGML EILPKELELC YRSPGEDQLF SEFYVGHLGS GIRLQVKDKK DETLVWEALV 1330 1340 1350 1360 1370 1380 KPGDLMPATT LIPPARIAVP SPLDAPQLLH FVDQYREQLI ARVTSVEVVL DKLHGQVLSQ 1390 1400 1410 1420 1430 1440 EQYERVLAEN TRPSQMRKLF SLSQSWDRKC KDGLYQALKE THPHLIMELW EKGSKKGLLP LSS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The PYRIN domain: a novel motif found in apoptosis and inflammation proteins." Bertin J., DiStefano P.S. Cell Death Differ. 7:1273-1274(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), VARIANTS HIS-155; SER-246; MET-878; VAL-1119; VAL-1184; LEU-1241 AND CYS-1366.
[2]	"The pyrin domain: a possible member of the death domain-fold family implicated in apoptosis and inflammation." Martinon F., Hofmann K., Tschopp J. Curr. Biol. 11:R118-R120(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
[3]	"Molecular cloning and characterization of DEFCAP-L and -S, two isoforms of a novel member of the mammalian Ced-4 family of apoptosis proteins." Hlaing T., Guo R.-F., Dilley K.A., Loussia J.M., Morrish T.A., Shi M.M., Vincenz C., Ward P.A. J. Biol. Chem. 276:9230-9238(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), MUTAGENESIS OF LYS-340. Tissue: Erythroleukemia.
[4]	"A novel enhancer of the Apaf1 apoptosome involved in cytochrome c-dependent caspase activation and apoptosis." Chu Z.-L., Pio F., Xie Z., Welsh K., Krajewska M., Krajewski S., Godzik A., Reed J.C. J. Biol. Chem. 276:9239-9245(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2; 3 AND 4), INTERACTION WITH CASP2 AND CASP9. Tissue: T-cell.
[5]	"Prediction of the coding sequences of unidentified human genes. XIII. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro." Nagase T., Ishikawa K., Suyama M., Kikuno R., Hirosawa M., Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O. DNA Res. 6:63-70(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Brain.
[6]	"The full-ORF clone resource of the German cDNA consortium." Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I. BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 282-1473 (ISOFORM 1), VARIANT VAL-1184. Tissue: Uterus.
[7]	"The inflammasome: a molecular platform triggering activation of inflammatory caspases and processing of proIL-beta." Martinon F., Burns K., Tschopp J. Mol. Cell 10:417-426(2002) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, IDENTIFICATION IN NALP1 INFLAMMASOME COMPLEX.
[8]	"NALP1 is a transcriptional target for cAMP-response-element-binding protein (CREB) in myeloid leukaemia cells." Sanz C., Calasanz M.J., Andreu E., Richard C., Prosper F., Fernandez-Luna J.L. Biochem. J. 384:281-286(2004) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY.
[9]	"Expression of NALP1 in cerebellar granule neurons stimulates apoptosis." Liu F., Lo C.F., Ning X., Kajkowski E.M., Jin M., Chiriac C., Gonzales C., Naureckiene S., Lock Y.-W., Pong K., Zaleska M.M., Jacobsen J.S., Silverman S., Ozenberger B.A. Cell. Signal. 16:1013-1021(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, MUTAGENESIS OF 339-GLY-LYS-340.
[10]	"Inflammasome components NALP 1 and 3 Show distinct but separate Expression profiles in human tissues suggesting a site-specific role in the inflammatory response." Kummer J.A., Broekhuizen R., Everett H., Agostini L., Kuijk L., Martinon F., van Bruggen R., Tschopp J. J. Histochem. Cytochem. 55:443-452(2007) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[11]	"Reconstituted NALP1 inflammasome reveals two-step mechanism of caspase-1 activation." Faustin B., Lartigue L., Bruey J.-M., Luciano F., Sergienko E., Bailly-Maitre B., Volkmann N., Hanein D., Rouiller I., Reed J.C. Mol. Cell 25:713-724(2007) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[12]	"Novel role of PKR in inflammasome activation and HMGB1 release." Lu B., Nakamura T., Inouye K., Li J., Tang Y., Lundbaeck P., Valdes-Ferrer S.I., Olofsson P.S., Kalb T., Roth J., Zou Y., Erlandsson-Harris H., Yang H., Ting J.P., Wang H., Andersson U., Antoine D.J., Chavan S.S., Hotamisligil G.S., Tracey K.J. Nature 488:670-674(2012) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH EIF2AK2.
[13]	"NMR structure of the apoptosis- and inflammation-related NALP1 pyrin domain." Hiller S., Kohl A., Fiorito F., Herrmann T., Wider G., Tschopp J., Gruetter M.G., Wuethrich K. Structure 11:1199-1205(2003) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF 1-93.
[14]	"NALP1 in vitiligo-associated multiple autoimmune disease." Jin Y., Mailloux C.M., Gowan K., Riccardi S.L., LaBerge G., Bennett D.C., Fain P.R., Spritz R.A. N. Engl. J. Med. 356:1216-1225(2007) [PubMed] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN SUSCEPTIBILITY TO VITILIGO AND VITILIGO-ASSOCIATED AUTOIMMUNE DISEASES, VARIANT HIS-155.
[15]	"Northeast structural genomics consortium target HR3486E." Northeast structural genomics consortium (NESG) Submitted (OCT-2009) to the PDB data bank Cited for: X-RAY CRYSTALLOGRAPHY (3.1 ANGSTROMS) OF 1371-1467.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

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.
AL117470 mRNA. Translation: CAB55945.1.

IPI

IPI00004551.
IPI00099688.
IPI00328123.
IPI00335800.

PIR

T17255.

RefSeq

NP_001028225.1. NM_001033053.2.
NP_055737.1. NM_014922.4.
NP_127497.1. NM_033004.3.
NP_127499.1. NM_033006.3.
NP_127500.1. NM_033007.3.

UniGene

Hs.652273.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1PN5	NMR	-	A	1-93	[»]
3KAT	X-ray	3.10	A	1371-1467	[»]
4IFP	X-ray	1.99	A/B/C	1379-1462	[»]

ProteinModelPortal

Q9C000.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-38407N.

IntAct

Q9C000. 9 interactions.

MINT

MINT-150191.

Protein family/group databases

MEROPS

S79.002.

PTM databases

PhosphoSite

Q9C000.

Polymorphism databases

DMDM

17380146.

Proteomic databases

PaxDb

Q9C000.

PRIDE

Q9C000.

Protocols and materials databases

DNASU

22861.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000269280; ENSP00000269280; ENSG00000091592.
ENST00000345221; ENSP00000324366; ENSG00000091592.
ENST00000354411; ENSP00000346390; ENSG00000091592.
ENST00000572272; ENSP00000460475; ENSG00000091592.
ENST00000577119; ENSP00000460216; ENSG00000091592.

GeneID

22861.

KEGG

hsa:22861.

UCSC

uc002gch.4. human.
uc002gci.3. human.
uc002gcj.3. human.
uc002gcl.3. human.

Organism-specific databases

CTD

22861.

GeneCards

GC17M005407.

HGNC

HGNC:14374. NLRP1.

HPA

CAB009189.

MIM

193200. phenotype.
606579. phenotype.
606636. gene.

neXtProt

NX_Q9C000.

Orphanet

3435. Vitiligo.

PharmGKB

PA162397797.

HUGE

Search...

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG146295.

HOGENOM

HOG000230509.

HOVERGEN

HBG052573.

InParanoid

Q9C000.

KO

K12798.

OMA

HPHLIME.

Enzyme and pathway databases

Pathway_Interaction_DB

anthraxpathway. Cellular roles of Anthrax toxin.

Reactome

REACT_6900. Immune System.

Gene expression databases

ArrayExpress

Q9C000.

Bgee

Q9C000.

CleanEx

HS_NLRP1.

Genevestigator

Q9C000.

GermOnline

ENSG00000091592. Homo sapiens.

Family and domain databases

Gene3D

1.10.533.10. 2 hits.

InterPro

IPR001315. CARD.
IPR004020. DAPIN.
IPR011029. DEATH-like_dom.
IPR000767. Disease_R.
IPR025307. FIIND_dom.
IPR001611. Leu-rich_rpt.
IPR007111. NACHT_NTPase.
IPR027417. P-loop_NTPase.
[Graphical view]

Pfam

PF00619. CARD. 1 hit.
PF13553. FIIND. 1 hit.
PF02758. PYRIN. 1 hit.
[Graphical view]

PRINTS

PR00364. DISEASERSIST.

SUPFAM

SSF47986. DEATH_like. 2 hits.
SSF52540. SSF52540. 1 hit.

PROSITE

PS50209. CARD. 1 hit.
PS50824. DAPIN. 1 hit.
PS51450. LRR. 3 hits.
PS50837. NACHT. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

Q9C000.

ChEMBL

CHEMBL1741214.

ChiTaRS

NLRP1. human.

EvolutionaryTrace

Q9C000.

GenomeRNAi

22861.

NextBio

43357.

SOURCE

Search...

Entry information

Entry name

NALP1_HUMAN

Accession

Primary (citable) accession number: Q9C000
Secondary accession number(s): Q9BZZ8 , Q9BZZ9, Q9HAV8, Q9UFT4, Q9Y2E0

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 18, 2001
Last sequence update:	June 1, 2001
Last modified:	May 29, 2013
This is version 139 of the entry and version 1 of the sequence. [Complete history]

Entry status

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.