General information | DisProt: | DP00554 | Name: | NACHT, LRR and PYD domains-containing protein 1 [Isoform 1 (NAC beta)(DEFCAP-L)] | Synonym(s): | NALP1_HUMAN
Death effector filament-forming ced-4-like apoptosis protein
Nucleotide-binding domain and caspase recruitment domain
Caspase recruitment domain-containing protein 7
| First appeared in release: | Release 4.0 (06/23/2008) | UniProt: | Q9C000-1 | UniGene: | Hs.652273 | SwissProt: | NALP1_HUMAN | TrEMBL: | | NCBI (GI): | 17380146 | Source organism: | Homo sapiens (Human) | Sequence length: | 1473 | Percent disordered: | 1% | Homologues: | |
Native sequence |
10 20 30 40 50 60 | | | | | | MAGGAWGRLA CYLEFLKKEE LKEFQLLLAN KAHSRSSSGE TPAQPEKTSG MEVASYLVAQ - 60 YGEQRAWDLA LHTWEQMGLR SLCAQAQEGA GHSPSFPYSP SEPHLGSPSQ PTSTAVLMPW - 120 IHELPAGCTQ GSERRVLRQL PDTSGRRWRE ISASLLYQAL PSSPDHESPS QESPNAPTST - 180 AVLGSWGSPP QPSLAPREQE APGTQWPLDE TSGIYYTEIR EREREKSEKG RPPWAAVVGT - 240 PPQAHTSLQP HHHPWEPSVR ESLCSTWPWK NEDFNQKFTQ LLLLQRPHPR SQDPLVKRSW - 300 PDYVEENRGH LIEIRDLFGP GLDTQEPRIV ILQGAAGIGK STLARQVKEA WGRGQLYGDR - 360 FQHVFYFSCR ELAQSKVVSL AELIGKDGTA TPAPIRQILS RPERLLFILD GVDEPGWVLQ - 420 EPSSELCLHW SQPQPADALL GSLLGKTILP EASFLITART TALQNLIPSL EQARWVEVLG - 480 FSESSRKEYF YRYFTDERQA IRAFRLVKSN KELWALCLVP WVSWLACTCL MQQMKRKEKL - 540 TLTSKTTTTL CLHYLAQALQ AQPLGPQLRD LCSLAAEGIW QKKTLFSPDD LRKHGLDGAI - 600 ISTFLKMGIL QEHPIPLSYS FIHLCFQEFF AAMSYVLEDE KGRGKHSNCI IDLEKTLEAY - 660 GIHGLFGAST TRFLLGLLSD EGEREMENIF HCRLSQGRNL MQWVPSLQLL LQPHSLESLH - 720 CLYETRNKTF LTQVMAHFEE MGMCVETDME LLVCTFCIKF SRHVKKLQLI EGRQHRSTWS - 780 PTMVVLFRWV PVTDAYWQIL FSVLKVTRNL KELDLSGNSL SHSAVKSLCK TLRRPRCLLE - 840 TLRLAGCGLT AEDCKDLAFG LRANQTLTEL DLSFNVLTDA GAKHLCQRLR QPSCKLQRLQ - 900 LVSCGLTSDC CQDLASVLSA SPSLKELDLQ QNNLDDVGVR LLCEGLRHPA CKLIRLGLDQ - 960 TTLSDEMRQE LRALEQEKPQ LLIFSRRKPS VMTPTEGLDT GEMSNSTSSL KRQRLGSERA - 1020 ASHVAQANLK LLDVSKIFPI AEIAEESSPE VVPVELLCVP SPASQGDLHT KPLGTDDDFW - 1080 GPTGPVATEV VDKEKNLYRV HFPVAGSYRW PNTGLCFVMR EAVTVEIEFC VWDQFLGEIN - 1140 PQHSWMVAGP LLDIKAEPGA VEAVHLPHFV ALQGGHVDTS LFQMAHFKEE GMLLEKPARV - 1200 ELHHIVLENP SFSPLGVLLK MIHNALRFIP VTSVVLLYHR VHPEEVTFHL YLIPSDCSIR - 1260 KAIDDLEMKF QFVRIHKPPP LTPLYMGCRY TVSGSGSGML EILPKELELC YRSPGEDQLF - 1320 SEFYVGHLGS GIRLQVKDKK DETLVWEALV KPGDLMPATT LIPPARIAVP SPLDAPQLLH - 1380 FVDQYREQLI ARVTSVEVVL DKLHGQVLSQ EQYERVLAEN TRPSQMRKLF SLSQSWDRKC - 1440 KDGLYQALKE THPHLIMELW EKGSKKGLLP LSS
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Functional narrative |
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. NALP 1 PYD is involved in the innate immune response and part of the development of inflammasomes. Disordered loop between alpha helices two and four is unique to this PYD protein and could explain the possible correlation with familial Mediterranean fever.
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Map of ordered and disordered regions |
Note: 'Mouse' over a region to see the start and stop residues. Click on a region to see detailed information.
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Region 1 | Type: | Disordered | Name: | | Location: | 31 - 50 | Length: | 20 | Region sequence: |
KAHSRSSSGETPAQPEKTSG | Modification type: | Native
| PDB: | | Structural/functional type: | Function arises via a disorder to order transition | Functional classes: | Modification site
Molecular assembly
| Functional subclasses: | Apoptosis Regulation
Protein-protein binding
| Detection methods:
- Nuclear magnetic resonance (NMR) (293 K; pH: 6.5; CHAPS 1 mM; D2O 5 %; DTT 20 mM; EDTA 0.01 mM; H2O 95 %; Na2HPO4 50 mM; NaCl 50 mM; NaN3 0.02 %)
| References:
- S . Hiller, A . Kohl, F . Fiorito, T . Herrmann, G . Wider, J . Tschopp, M . Grütter, K . Wüthrich. "NMR structure of the apoptosis- and inflammation-related NALP1 pyrin domain." Structure. 2003; 11(10): 1199-1205. PubMed: 14527388
| Comments:
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References |
- Eberstadt M, Huang B, Olejniczak ET, Fesik SW. "The lymphoproliferation mutation in Fas locally unfolds the Fas death domain." Nat Struct Biol. 1997; 4(12): 983-5. PubMed: 9406545
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Comments |
NALP1 PYD lacks the third alpha helix, which is unique to it's topology and could explain its effect on FMF, innate immune response, and inflammasome creation.
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