Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

NACHT, LRR and PYD domains-containing protein 6

Gene

Nlrp6

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

As the sensor component of the NLRP6 inflammasome, plays a crucial role in innate immunity and inflammation. In response to yet unidentified signals, initiates the formation of the inflammasome polymeric complex, made of NLRP6, PYCARD and CASP1. Recruitment of proCASP1 to the inflammasome promotes its activation and CASP1-catalyzed IL1B and IL18 maturation and secretion in the extracellular milieu. The precise NLRP6 activation stimulus has not been identified yet (By similarity). Essential for gut mucosal self-renewal and proliferation. Maintains intestinal homeostasis and a healthy intestinal microbiota. This function is, at least partially, mediated by IL18, and not IL1B, produced by nonhematopoietic cells. Influences intestinal barrier function and microbial homeostasis through the regulation of goblet cell mucus secretion. Acts by promoting autophagy in goblet cells, an essential step for mucus granule exocytosis. Its role in goblet cell physiology is inflammasome-dependent, but IL1B- and IL18-independent. During systemic bacterial infections, may negatively regulate inflammatory signaling and inhibit the influx of monocytes and neutrophils to the circulation and to the peritoneum. May promote peripheral nerve recovery following injury via an inflammasome-independent mechanism (By similarity).By similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi200 – 2078ATPPROSITE-ProRule annotation

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • peptide binding Source: RGD
  • vasopressin receptor activity Source: UniProtKB

GO - Biological processi

Complete GO annotation...

Keywords - Biological processi

Immunity, Inflammatory response, Innate immunity

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Names & Taxonomyi

Protein namesi
Recommended name:
NACHT, LRR and PYD domains-containing protein 6
Alternative name(s):
Angiotensin II/vasopressin receptor
Non-angiotensin-vasopressin receptor1 Publication
Short name:
Non-AVR1 Publication
PYRIN-containing APAF1-like protein 5-like
Gene namesi
Name:Nlrp6
Synonyms:Nalp6, Navr, Pypaf5
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 1

Organism-specific databases

RGDi708549. Nlrp6.

Subcellular locationi

Isoform 1 :
Isoform 2 :
  • Cytoplasm 1 Publication
  • Cell membrane 1 Publication

  • Note: Predominantly expressed at the cell membrane.

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Inflammasome, Membrane, Nucleus

Pathology & Biotechi

Involvement in diseasei

Defects in Nlrp6 may be a cause of salt-sensitive hypertension.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 881881NACHT, LRR and PYD domains-containing protein 6PRO_0000080894Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei104 – 1041PhosphoserineCombined sources

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiQ63035.
PRIDEiQ63035.

PTM databases

iPTMnetiQ63035.
PhosphoSiteiQ63035.

Expressioni

Tissue specificityi

Detected in several tissues (PubMed:7489366). Expressed in renal epithelial cells in medullary thick ascending limb of Henle, as well as in salivary gland apical epithelium (at protein level). Isoform 1 is widely expressed. Isoform 2 is primarily expressed in kidney (at protein level) (PubMed:18413781).2 Publications

Developmental stagei

Strongly up-regulated in the intestine in late gestation.1 Publication

Gene expression databases

BgeeiENSRNOG00000014685.

Interactioni

Subunit structurei

Sensor component of NLRP6 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. The core of NLRP6 inflammasomes consists of a signal sensor component (NLRP6), an adapter (ASC/PYCARD), which recruits an effector proinflammatory caspase (CASP1). Within the complex, NLRP6 and PYCARD interact via their respective pyrin domains. This interaction initiates speck formation (nucleation) which greatly enhances further addition of soluble PYCARD molecules to the speck in a prion-like polymerization process. NLRP6 localizes at the end of each PYCARD filament. Clustered PYCARD nucleates the formation of CASP1 filaments through the interaction of their respective CARD domains, acting as a platform for CASP1 polymerization. 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 this complex, the sensor protein is sub-stoichiometric to PYCARD, and PYCARD is further substoichiometric to CASP1, suggesting amplifications of signal transduction from the sensor, via the adapter, to the effector.By similarity

Structurei

3D structure databases

ProteinModelPortaliQ63035.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini1 – 129129PyrinPROSITE-ProRule annotationAdd
BLAST
Domaini194 – 510317NACHTPROSITE-ProRule annotationAdd
BLAST
Repeati459 – 48426LRR 1Add
BLAST
Repeati637 – 66024LRR 2Add
BLAST
Repeati749 – 77224LRR 3Add
BLAST
Repeati839 – 86325LRR 4Add
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi590 – 63142Asp/Glu-richAdd
BLAST
Compositional biasi682 – 6898Poly-Lys

Sequence similaritiesi

Belongs to the NLRP family.Curated
Contains 4 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

eggNOGiENOG410IIC5. Eukaryota.
ENOG41115SU. LUCA.
GeneTreeiENSGT00840000129675.
HOGENOMiHOG000169726.
HOVERGENiHBG108172.
InParanoidiQ63035.
OMAiFRDERKA.
OrthoDBiEOG091G01CG.

Family and domain databases

Gene3Di1.10.533.10. 1 hit.
3.80.10.10. 1 hit.
InterProiIPR004020. DAPIN.
IPR011029. DEATH-like_dom.
IPR032675. L_dom-like.
IPR007111. NACHT_NTPase.
IPR027417. P-loop_NTPase.
[Graphical view]
PfamiPF02758. PYRIN. 1 hit.
[Graphical view]
SMARTiSM01289. PYRIN. 1 hit.
[Graphical view]
SUPFAMiSSF47986. SSF47986. 1 hit.
SSF52540. SSF52540. 1 hit.
PROSITEiPS50824. DAPIN. 1 hit.
PS50837. NACHT. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative promoter usage. AlignAdd to basket

Isoform 1 (identifier: Q63035-1) [UniParc]FASTAAdd to basket
Also known as: Non-Avr, Navr1 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
MDAAGASCSS SEAVARELLL AALQDLSQEQ LKRFRHKLRD APLDGRSIPW
60 70 80 90 100
GRLEHSDAVD LTDKLIEFYA PEPAVDVTRK ILKKADIRDV SLRLKEQQLQ
110 120 130 140 150
RLGSSSALLT VSEYKKKYRE HVLRQHAKVK ERNARSVKIN KRFTKLLIAP
160 170 180 190 200
GSGAGEDELL GTSGEPEPER ARRSDTHTFN RLFRGNDDEG PRPLTVVLQG
210 220 230 240 250
PAGIGKTMAA KKILYDWAGG KLYHSQVDFA FFMPCGELLE RPGTRSLADL
260 270 280 290 300
ILEQCPDRTA PVRRILAQPH RLLFILDGAD ELPTLAAPEA TPCRDPFEAT
310 320 330 340 350
SGLRVLSGLL SQELLPSARL LVTSRNATLG RLQGRLCSPQ CAEVRGFSDK
360 370 380 390 400
DKKKYFFKFF RDERKAERAY RFVKENETLY ALCFVPFVCW IVCTVLLQQM
410 420 430 440 450
ELGRDLSRTS KTTTSVYLLF ITSMLKSAGT NGPRVQGELR MLCRLAREGI
460 470 480 490 500
LKHQAQFSEK DLERLKLQGS QVQTMFLSKK ELPGVLETVV TYQFIDQSFQ
510 520 530 540 550
EFLAALSYLL DAEGAPGNSA GSVQMLVNSD AGLRGHLALT TRFLFGLLST
560 570 580 590 600
ERIRDIGNHF GCVVPGRVKQ DTLRWVQGQS QPKVATVGAE KKDELKDEEA
610 620 630 640 650
EEEEEEEEEE EEELNFGLEL LYCLYETQED DFVRQALSSL PEMVLERVRL
660 670 680 690 700
TRMDLEVLSY CVQCCPDGQA LRLVSCGLVA AKEKKKKKKS FMNRLKGSQS
710 720 730 740 750
TGKQPPASLL RPLCEAMITQ QCGLSILTLS HCKLPDAVCR DLSEALKVAP
760 770 780 790 800
SLRELGLLQN RLTEAGLRLL SQGLAWPKCK VQTLRIQMPG LQEVIHYLVI
810 820 830 840 850
VLQQSPVLTT LDLSGCQLPG TVVEPLCSAL KHPKCGLKTL SLTSVELTEN
860 870 880
PLRELQAVKT LKPDLAIIHS KLGTHPQPLK G
Length:881
Mass (Da):98,324
Last modified:November 11, 2015 - v4
Checksum:iA7F36BD7667DF7ED
GO
Isoform 2 (identifier: Q63035-2) [UniParc]FASTAAdd to basket
Also known as: Avr1 Publication

The sequence of this isoform differs from the canonical sequence as follows:
     1-423: Missing.

Show »
Length:458
Mass (Da):50,764
Checksum:iE6CAFB07FA55E714
GO

Sequence cautioni

The sequence AAA03623 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti317 – 3171S → A in ABG66707 (PubMed:18413781).Curated
Sequence conflicti468 – 4681Q → KLQ in AAA03623 (PubMed:7489366).Curated
Sequence conflicti527 – 5271V → L in ABG66707 (PubMed:18413781).Curated
Sequence conflicti527 – 5271V → L in AAA03623 (PubMed:7489366).Curated
Sequence conflicti613 – 6131Missing in ABG66707 (PubMed:18413781).Curated
Sequence conflicti613 – 6131Missing in AAA03623 (PubMed:7489366).Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti518 – 5181N → S in salt-sensitive hypertension. 1 Publication
Natural varianti562 – 5621C → R in salt-sensitive hypertension. 1 Publication

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 423423Missing in isoform 2. 1 PublicationVSP_042302Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
DQ631800 mRNA. Translation: ABG66707.1.
AABR07006017 Genomic DNA. No translation available.
AABR07006018 Genomic DNA. No translation available.
M85183 mRNA. Translation: AAA03623.1. Different initiation.
PIRiS27880.
RefSeqiNP_599202.2. NM_134375.3.
UniGeneiRn.9669.

Genome annotation databases

EnsembliENSRNOT00000019808; ENSRNOP00000019808; ENSRNOG00000014685. [Q63035-1]
ENSRNOT00000050551; ENSRNOP00000044415; ENSRNOG00000045677. [Q63035-1]
GeneIDi171390.
KEGGirno:171390.
UCSCiRGD:708549. rat. [Q63035-1]

Keywords - Coding sequence diversityi

Alternative promoter usage, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
DQ631800 mRNA. Translation: ABG66707.1.
AABR07006017 Genomic DNA. No translation available.
AABR07006018 Genomic DNA. No translation available.
M85183 mRNA. Translation: AAA03623.1. Different initiation.
PIRiS27880.
RefSeqiNP_599202.2. NM_134375.3.
UniGeneiRn.9669.

3D structure databases

ProteinModelPortaliQ63035.
ModBaseiSearch...
MobiDBiSearch...

PTM databases

iPTMnetiQ63035.
PhosphoSiteiQ63035.

Proteomic databases

PaxDbiQ63035.
PRIDEiQ63035.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000019808; ENSRNOP00000019808; ENSRNOG00000014685. [Q63035-1]
ENSRNOT00000050551; ENSRNOP00000044415; ENSRNOG00000045677. [Q63035-1]
GeneIDi171390.
KEGGirno:171390.
UCSCiRGD:708549. rat. [Q63035-1]

Organism-specific databases

CTDi171389.
RGDi708549. Nlrp6.

Phylogenomic databases

eggNOGiENOG410IIC5. Eukaryota.
ENOG41115SU. LUCA.
GeneTreeiENSGT00840000129675.
HOGENOMiHOG000169726.
HOVERGENiHBG108172.
InParanoidiQ63035.
OMAiFRDERKA.
OrthoDBiEOG091G01CG.

Miscellaneous databases

PROiQ63035.

Gene expression databases

BgeeiENSRNOG00000014685.

Family and domain databases

Gene3Di1.10.533.10. 1 hit.
3.80.10.10. 1 hit.
InterProiIPR004020. DAPIN.
IPR011029. DEATH-like_dom.
IPR032675. L_dom-like.
IPR007111. NACHT_NTPase.
IPR027417. P-loop_NTPase.
[Graphical view]
PfamiPF02758. PYRIN. 1 hit.
[Graphical view]
SMARTiSM01289. PYRIN. 1 hit.
[Graphical view]
SUPFAMiSSF47986. SSF47986. 1 hit.
SSF52540. SSF52540. 1 hit.
PROSITEiPS50824. DAPIN. 1 hit.
PS50837. NACHT. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiNLRP6_RAT
AccessioniPrimary (citable) accession number: Q63035
Secondary accession number(s): A5X5C9, D3ZYC0, F1LSH2
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 28, 2003
Last sequence update: November 11, 2015
Last modified: September 7, 2016
This is version 126 of the entry and version 4 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. 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.