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Protein

NACHT, LRR and PYD domains-containing protein 4

Gene

NLRP4

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

May be involved in inflammation and recognition of cytosolic pathogen-associated molecular patterns (PAMPs) not intercepted by membrane-bound receptors. Acts as a negative regulator of the type I interferon signaling pathway by serving as an adapter to promote DTX4-mediated ubiquitination of activated TBK1, and its subsequent degradation. Suppresses NF-kappaB induction by the cytokines TNFA and IL1B, suggesting that it operates at a point of convergence in these two cytokine signaling pathways.2 Publications

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi155 – 162ATPPROSITE-ProRule annotation8

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Biological processi

Inflammatory response

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

BioCyciZFISH:ENSG00000160505-MONOMER.
ReactomeiR-HSA-1606341. IRF3 mediated activation of type 1 IFN.
R-HSA-3134975. Regulation of innate immune responses to cytosolic DNA.
R-HSA-3270619. IRF3-mediated induction of type I IFN.

Names & Taxonomyi

Protein namesi
Recommended name:
NACHT, LRR and PYD domains-containing protein 4
Alternative name(s):
Cancer/testis antigen 58
Short name:
CT58
PAAD and NACHT-containing protein 2
Short name:
PAN2
PYRIN and NACHT-containing protein 2
PYRIN-containing APAF1-like protein 4
Short name:
PYPAF4
Ribonuclease inhibitor 2
Gene namesi
Name:NLRP4
Synonyms:NALP4, PAN2, PYPAF4, RNH2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 19

Organism-specific databases

HGNCiHGNC:22943. NLRP4.

Subcellular locationi

GO - Cellular componenti

  • cytosol Source: Reactome
  • extracellular exosome Source: UniProtKB
Complete GO annotation...

Pathology & Biotechi

Organism-specific databases

DisGeNETi147945.
OpenTargetsiENSG00000160505.
PharmGKBiPA162397947.

Polymorphism and mutation databases

BioMutaiNLRP4.
DMDMi148887404.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000808891 – 994NACHT, LRR and PYD domains-containing protein 4Add BLAST994

Proteomic databases

PaxDbiQ96MN2.
PeptideAtlasiQ96MN2.
PRIDEiQ96MN2.

PTM databases

iPTMnetiQ96MN2.
PhosphoSitePlusiQ96MN2.

Expressioni

Gene expression databases

BgeeiENSG00000160505.
CleanExiHS_NLRP4.
HS_PAN2.
ExpressionAtlasiQ96MN2. baseline and differential.
GenevisibleiQ96MN2. HS.

Organism-specific databases

HPAiHPA042561.

Interactioni

Subunit structurei

Interacts with CHUK/IKKA, inhibiting its kinase activity.1 Publication

Protein-protein interaction databases

BioGridi127102. 6 interactors.
DIPiDIP-60912N.
IntActiQ96MN2. 2 interactors.
STRINGi9606.ENSP00000301295.

Structurei

Secondary structure

1994
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi10 – 15Combined sources6
Helixi20 – 36Combined sources17
Helixi44 – 49Combined sources6
Helixi52 – 78Combined sources27
Helixi82 – 93Combined sources12

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4EWIX-ray2.28A/B1-110[»]
ProteinModelPortaliQ96MN2.
SMRiQ96MN2.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini1 – 94PyrinPROSITE-ProRule annotationAdd BLAST94
Domaini149 – 472NACHTPROSITE-ProRule annotationAdd BLAST324
Repeati637 – 660LRR 1Add BLAST24
Repeati698 – 721LRR 2Add BLAST24
Repeati722 – 745LRR 3Add BLAST24
Repeati750 – 777LRR 4Add BLAST28
Repeati806 – 833LRR 5Add BLAST28
Repeati863 – 886LRR 6Add BLAST24
Repeati920 – 943LRR 7Add BLAST24
Repeati949 – 972LRR 8Add BLAST24

Domaini

The pyrin domain is sufficient for suppression of NF-kappaB activity, it adopts a typical death domain fold, but in contrast to several NLRP family pyrin domains it doesn't bind homotypically to the ASC adapter, which supports the observation that NLRP4 has no effect on IL1B activation.

Sequence similaritiesi

Belongs to the NLRP family.Curated
Contains 8 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

eggNOGiKOG4308. Eukaryota.
ENOG410ZBX3. LUCA.
GeneTreeiENSGT00860000133669.
HOGENOMiHOG000294064.
HOVERGENiHBG063656.
InParanoidiQ96MN2.
OMAiTGYTKTY.
OrthoDBiEOG091G01CG.
PhylomeDBiQ96MN2.

Family and domain databases

Gene3Di1.10.533.10. 1 hit.
3.40.50.300. 3 hits.
3.80.10.10. 1 hit.
InterProiIPR004020. DAPIN.
IPR011029. DEATH-like_dom.
IPR032675. L_dom-like.
IPR001611. Leu-rich_rpt.
IPR007111. NACHT_NTPase.
IPR027417. P-loop_NTPase.
[Graphical view]
PfamiPF13516. LRR_6. 3 hits.
PF02758. PYRIN. 1 hit.
[Graphical view]
SMARTiSM01289. PYRIN. 1 hit.
[Graphical view]
SUPFAMiSSF47986. SSF47986. 1 hit.
SSF52540. SSF52540. 2 hits.
PROSITEiPS50824. DAPIN. 1 hit.
PS50837. NACHT. 1 hit.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Note: Experimental confirmation may be lacking for some isoforms.
Isoform 1 (identifier: Q96MN2-1) [UniParc]FASTAAdd to basket

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
MAASFFSDFG LMWYLEELKK EEFRKFKEHL KQMTLQLELK QIPWTEVKKA
60 70 80 90 100
SREELANLLI KHYEEQQAWN ITLRIFQKMD RKDLCMKVMR ERTGYTKTYQ
110 120 130 140 150
AHAKQKFSRL WSSKSVTEIH LYFEEEVKQE ECDHLDRLFA PKEAGKQPRT
160 170 180 190 200
VIIQGPQGIG KTTLLMKLMM AWSDNKIFRD RFLYTFYFCC RELRELPPTS
210 220 230 240 250
LADLISREWP DPAAPITEIV SQPERLLFVI DSFEELQGGL NEPDSDLCGD
260 270 280 290 300
LMEKRPVQVL LSSLLRKKML PEASLLIAIK PVCPKELRDQ VTISEIYQPR
310 320 330 340 350
GFNESDRLVY FCCFFKDPKR AMEAFNLVRE SEQLFSICQI PLLCWILCTS
360 370 380 390 400
LKQEMQKGKD LALTCQSTTS VYSSFVFNLF TPEGAEGPTP QTQHQLKALC
410 420 430 440 450
SLAAEGMWTD TFEFCEDDLR RNGVVDADIP ALLGTKILLK YGERESSYVF
460 470 480 490 500
LHVCIQEFCA ALFYLLKSHL DHPHPAVRCV QELLVANFEK ARRAHWIFLG
510 520 530 540 550
CFLTGLLNKK EQEKLDAFFG FQLSQEIKQQ IHQCLKSLGE RGNPQGQVDS
560 570 580 590 600
LAIFYCLFEM QDPAFVKQAV NLLQEANFHI IDNVDLVVSA YCLKYCSSLR
610 620 630 640 650
KLCFSVQNVF KKEDEHSSTS DYSLICWHHI CSVLTTSGHL RELQVQDSTL
660 670 680 690 700
SESTFVTWCN QLRHPSCRLQ KLGINNVSFS GQSVLLFEVL FYQPDLKYLS
710 720 730 740 750
FTLTKLSRDD IRSLCDALNY PAGNVKELAL VNCHLSPIDC EVLAGLLTNN
760 770 780 790 800
KKLTYLNVSC NQLDTGVPLL CEALCSPDTV LVYLMLAFCH LSEQCCEYIS
810 820 830 840 850
EMLLRNKSVR YLDLSANVLK DEGLKTLCEA LKHPDCCLDS LCLVKCFITA
860 870 880 890 900
AGCEDLASAL ISNQNLKILQ IGCNEIGDVG VQLLCRALTH TDCRLEILGL
910 920 930 940 950
EECGLTSTCC KDLASVLTCS KTLQQLNLTL NTLDHTGVVV LCEALRHPEC
960 970 980 990
ALQVLGLRKT DFDEETQALL TAEEERNPNL TITDDCDTIT RVEI
Length:994
Mass (Da):113,415
Last modified:June 12, 2007 - v3
Checksum:iC2DDA1239274B2D1
GO
Isoform 2 (identifier: Q96MN2-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-435: Missing.
     731-786: Missing.

Note: Incomplete sequence.
Show »
Length:503
Mass (Da):56,764
Checksum:i8DC99CE33DE2F9A9
GO
Isoform 3 (identifier: Q96MN2-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-93: MAASFFSDFG...LCMKVMRERT → MQECLTLWVFSPLALTDS

Show »
Length:919
Mass (Da):103,968
Checksum:i99DFA4C1AC473A5D
GO

Sequence cautioni

The sequence AAL88672 differs from that shown. Reason: Erroneous termination at position 41. Translated as Gln.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti55L → P in AAL88672 (Ref. 4) Curated1
Sequence conflicti99Y → H in AAL88672 (Ref. 4) Curated1
Sequence conflicti177I → T in AAL88672 (Ref. 4) Curated1
Sequence conflicti209W → R in AAL88672 (Ref. 4) Curated1
Sequence conflicti296I → V in AAL88672 (Ref. 4) Curated1
Sequence conflicti720Y → C in AAL88672 (Ref. 4) Curated1
Sequence conflicti957L → P in AAL88672 (Ref. 4) Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_024179144A → T.5 PublicationsCorresponds to variant rs441827dbSNPEnsembl.1
Natural variantiVAR_024827383E → D.1 PublicationCorresponds to variant rs17857373dbSNPEnsembl.1
Natural variantiVAR_024828390P → Q.1 PublicationCorresponds to variant rs17857374dbSNPEnsembl.1
Natural variantiVAR_032764708R → H.Corresponds to variant rs12462372dbSNPEnsembl.1
Natural variantiVAR_024829774L → M.1 PublicationCorresponds to variant rs17854614dbSNPEnsembl.1
Natural variantiVAR_020007925Q → L.1 PublicationCorresponds to variant rs302453dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0440061 – 435Missing in isoform 2. 1 PublicationAdd BLAST435
Alternative sequenceiVSP_0039161 – 93MAASF…MRERT → MQECLTLWVFSPLALTDS in isoform 3. 1 PublicationAdd BLAST93
Alternative sequenceiVSP_044007731 – 786Missing in isoform 2. 1 PublicationAdd BLAST56

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF442488 mRNA. Translation: AAL35293.1.
AY072792 mRNA. Translation: AAL68396.1.
AF479747 mRNA. Translation: AAL87104.1.
AF482706 mRNA. Translation: AAL88672.1. Sequence problems.
AK056688 mRNA. Translation: BAB71254.1.
BC016443 mRNA. Translation: AAH16443.1.
BC050326 mRNA. Translation: AAH50326.1.
CCDSiCCDS12936.1. [Q96MN2-1]
RefSeqiNP_604393.2. NM_134444.4. [Q96MN2-1]
UniGeneiHs.631533.

Genome annotation databases

EnsembliENST00000301295; ENSP00000301295; ENSG00000160505. [Q96MN2-1]
ENST00000587891; ENSP00000465463; ENSG00000160505. [Q96MN2-3]
GeneIDi147945.
KEGGihsa:147945.
UCSCiuc002qmd.5. human. [Q96MN2-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF442488 mRNA. Translation: AAL35293.1.
AY072792 mRNA. Translation: AAL68396.1.
AF479747 mRNA. Translation: AAL87104.1.
AF482706 mRNA. Translation: AAL88672.1. Sequence problems.
AK056688 mRNA. Translation: BAB71254.1.
BC016443 mRNA. Translation: AAH16443.1.
BC050326 mRNA. Translation: AAH50326.1.
CCDSiCCDS12936.1. [Q96MN2-1]
RefSeqiNP_604393.2. NM_134444.4. [Q96MN2-1]
UniGeneiHs.631533.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4EWIX-ray2.28A/B1-110[»]
ProteinModelPortaliQ96MN2.
SMRiQ96MN2.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi127102. 6 interactors.
DIPiDIP-60912N.
IntActiQ96MN2. 2 interactors.
STRINGi9606.ENSP00000301295.

PTM databases

iPTMnetiQ96MN2.
PhosphoSitePlusiQ96MN2.

Polymorphism and mutation databases

BioMutaiNLRP4.
DMDMi148887404.

Proteomic databases

PaxDbiQ96MN2.
PeptideAtlasiQ96MN2.
PRIDEiQ96MN2.

Protocols and materials databases

DNASUi147945.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000301295; ENSP00000301295; ENSG00000160505. [Q96MN2-1]
ENST00000587891; ENSP00000465463; ENSG00000160505. [Q96MN2-3]
GeneIDi147945.
KEGGihsa:147945.
UCSCiuc002qmd.5. human. [Q96MN2-1]

Organism-specific databases

CTDi147945.
DisGeNETi147945.
GeneCardsiNLRP4.
H-InvDBHIX0015485.
HGNCiHGNC:22943. NLRP4.
HPAiHPA042561.
MIMi609645. gene.
neXtProtiNX_Q96MN2.
OpenTargetsiENSG00000160505.
PharmGKBiPA162397947.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG4308. Eukaryota.
ENOG410ZBX3. LUCA.
GeneTreeiENSGT00860000133669.
HOGENOMiHOG000294064.
HOVERGENiHBG063656.
InParanoidiQ96MN2.
OMAiTGYTKTY.
OrthoDBiEOG091G01CG.
PhylomeDBiQ96MN2.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000160505-MONOMER.
ReactomeiR-HSA-1606341. IRF3 mediated activation of type 1 IFN.
R-HSA-3134975. Regulation of innate immune responses to cytosolic DNA.
R-HSA-3270619. IRF3-mediated induction of type I IFN.

Miscellaneous databases

ChiTaRSiNLRP4. human.
GeneWikiiNLRP4.
GenomeRNAii147945.
PROiQ96MN2.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000160505.
CleanExiHS_NLRP4.
HS_PAN2.
ExpressionAtlasiQ96MN2. baseline and differential.
GenevisibleiQ96MN2. HS.

Family and domain databases

Gene3Di1.10.533.10. 1 hit.
3.40.50.300. 3 hits.
3.80.10.10. 1 hit.
InterProiIPR004020. DAPIN.
IPR011029. DEATH-like_dom.
IPR032675. L_dom-like.
IPR001611. Leu-rich_rpt.
IPR007111. NACHT_NTPase.
IPR027417. P-loop_NTPase.
[Graphical view]
PfamiPF13516. LRR_6. 3 hits.
PF02758. PYRIN. 1 hit.
[Graphical view]
SMARTiSM01289. PYRIN. 1 hit.
[Graphical view]
SUPFAMiSSF47986. SSF47986. 1 hit.
SSF52540. SSF52540. 2 hits.
PROSITEiPS50824. DAPIN. 1 hit.
PS50837. NACHT. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiNALP4_HUMAN
AccessioniPrimary (citable) accession number: Q96MN2
Secondary accession number(s): Q86W87, Q96AY6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 2, 2002
Last sequence update: June 12, 2007
Last modified: November 30, 2016
This is version 149 of the entry and version 3 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

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 19
    Human chromosome 19: 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.