Q86W26 (NAL10_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
NACHT, LRR and PYD domains-containing protein 10

Alternative name(s):
Nucleotide-binding oligomerization domain protein 8

Gene names

Name:	NLRP10
Synonyms:	NALP10, NOD8, PYNOD

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	655 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Inhibits autoprocessing of CASP1, CASP1-dependent IL1B secretion, PYCARD aggregation and PYCARD-mediated apoptosis but not apoptosis induced by FAS or BID. Displays anti-inflammatory activity. Plays a role in adaptive immunity through control of dendritic cell-mediated transport of antigen to the lymph nodes from peripheral sites. Required for immunity against C.albicans infection. Involved in the innate immune response by contributing to proinflammatory cytokine release in response to invasive bacterial infection. Ref.2 Ref.5 Ref.6
Subunit structure	Oligomerizes. Interacts with PYCARD, CASP1 and IL1B. Also interacts with NOD1 and components of the NOD1 signaling pathway including RIPK2, NR2C2/TAK1 and IKBKG/NEMO. Ref.2 Ref.6
Subcellular location	Cytoplasm. Cell membrane. Note: Cytoplasmic protein which is recruited to the cell membrane by NOD1 following invasive bacterial infection. Ref.6
Tissue specificity	Highly expressed in basal and suprabasal epidermal cell layers with lower levels in dermal fibroblast cells (at protein level). Widely expressed with highest levels in heart, brain and skeletal muscle. Also expressed in liver, colon, dermis and epidermis. Little expression detected in myeloid cells or peripheral blood mononuclear cells. Ref.2 Ref.6
Domain	The DAPIN and ATP-binding domains are required to elicit cytokine release following bacterial infection. The NACHT domain is required for inhibition of CASP1 autoprocessing.
Sequence similarities	Belongs to the NLRP family. Contains 1 DAPIN domain. Contains 1 NACHT domain.
Caution	Despite its official name, does not contain LRR repeats.

Ontologies

Keywords
Biological process	Adaptive immunity Immunity Innate immunity
Cellular component	Cell membrane Cytoplasm Membrane
Ligand	ATP-binding Nucleotide-binding
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	defense response to Gram-negative bacterium Inferred from mutant phenotype Ref.6. Source: UniProtKB defense response to fungus Inferred from sequence or structural similarity. Source: UniProtKB dendritic cell migration Inferred from sequence or structural similarity. Source: UniProtKB helper T cell enhancement of adaptive immune response Inferred from sequence or structural similarity. Source: UniProtKB innate immune response Inferred from electronic annotation. Source: UniProtKB-KW positive regulation of T-helper 1 type immune response Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of T-helper 17 type immune response Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of interleukin-6 secretion Inferred from mutant phenotype Ref.6. Source: UniProtKB positive regulation of interleukin-8 secretion Inferred from mutant phenotype Ref.6. Source: UniProtKB
Cellular_component	cytoplasm Inferred from direct assay Ref.6. Source: UniProtKB extrinsic to plasma membrane Inferred from direct assay Ref.6. Source: UniProtKB
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 655	655	NACHT, LRR and PYD domains-containing protein 10		PRO_0000080896
Regions
	Domain	1 – 96	96	DAPIN
	Domain	167 – 484	318	NACHT
	Nucleotide binding	173 – 180	8	ATP Potential
Experimental info
	Mutagenesis	179	1	K → A: Reduced release of IL8 following invasive bacterial infection. Ref.6
	Mutagenesis	252	1	D → A: Reduced release of IL8 following invasive bacterial infection. Ref.6

Sequences

	Sequence		Length	Mass (Da)
	Q86W26 [UniParc]. Last modified June 1, 2003. Version 1. Checksum: 0A4E5936864F4B5D	FASTA	655	75,032
	10 20 30 40 50 60 MAMAKARKPR EALLWALSDL EENDFKKLKF YLRDMTLSEG QPPLARGELE GLIPVDLAEL 70 80 90 100 110 120 LISKYGEKEA VKVVLKGLKV MNLLELVDQL SHICLHDYRE VYREHVRCLE EWQEAGVNGR 130 140 150 160 170 180 YNQVLLVAKP SSESPESLAC PFPEQELESV TVEALFDSGE KPSLAPSLVV LQGSAGTGKT 190 200 210 220 230 240 TLARKMVLDW ATGTLYPGRF DYVFYVSCKE VVLLLESKLE QLLFWCCGDN QAPVTEILRQ 250 260 270 280 290 300 PERLLFILDG FDELQRPFEE KLKKRGLSPK ESLLHLLIRR HTLPTCSLLI TTRPLALRNL 310 320 330 340 350 360 EPLLKQARHV HILGFSEEER ARYFSSYFTD EKQADRAFDI VQKNDILYKA CQVPGICWVV 370 380 390 400 410 420 CSWLQGQMER GKVVLETPRN STDIFMAYVS TFLPPDDDGG CSELSRHRVL RSLCSLAAEG 430 440 450 460 470 480 IQHQRFLFEE AELRKHNLDG PRLAAFLSSN DYQLGLAIKK FYSFRHISFQ DFFHAMSYLV 490 500 510 520 530 540 KEDQSRLGKE SRREVQRLLE VKEQEGNDEM TLTMQFLLDI SKKDSFSNLE LKFCFRISPC 550 560 570 580 590 600 LAQDLKHFKE QMESMKHNRT WDLEFSLYEA KIKNLVKGIQ MNNVSFKIKH SNEKKSQSQN 610 620 630 640 650 LFSVKSSLSH GPKEEQKCPS VHGQKEGKDN IAGTQKEAST GKGRGTEETP KNTYI

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"NALPs: a novel protein family involved in inflammation." Tschopp J., Martinon F., Burns K. Nat. Rev. Mol. Cell Biol. 4:95-104(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"PYNOD, a novel Apaf-1/CED4-like protein is an inhibitor of ASC and caspase-1." Wang Y., Hasegawa M., Imamura R., Kinoshita T., Kondo C., Konaka K., Suda T. Int. Immunol. 16:777-786(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, OLIGOMERIZATION, INTERACTION WITH PYCARD; CASP1 AND IL1B, TISSUE SPECIFICITY. Tissue: Heart.
[3]	"NODs: intracellular proteins involved in inflammation and apoptosis." Inohara N., Nunez G. Nat. Rev. Immunol. 3:371-382(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[4]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[5]	"Anti-inflammatory activity of PYNOD and its mechanism in humans and mice." Imamura R., Wang Y., Kinoshita T., Suzuki M., Noda T., Sagara J., Taniguchi S., Okamoto H., Suda T. J. Immunol. 184:5874-5884(2010) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[6]	"NLRP10 enhances Shigella-induced pro-inflammatory responses." Lautz K., Damm A., Menning M., Wenger J., Adam A.C., Zigrino P., Kremmer E., Kufer T.A. Cell. Microbiol. 14:1568-1583(2012) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH IKBKG; NOD1; NR2C2 AND RIPK2, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, MUTAGENESIS OF LYS-179 AND ASP-252.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AY154465 mRNA. Translation: AAO18161.1. AY489192 mRNA. Translation: AAS67384.1. BK001110 mRNA. Translation: DAA01243.1. BC104957 mRNA. Translation: AAI04958.1.
IPI	IPI00328970.
RefSeq	NP_789791.1. NM_176821.3.
UniGene	Hs.449636.
3D structure databases
ProteinModelPortal	Q86W26.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000327763.
PTM databases
PhosphoSite	Q86W26.
Polymorphism databases
DMDM	46396380.
Proteomic databases
PaxDb	Q86W26.
PRIDE	Q86W26.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000328600; ENSP00000327763; ENSG00000182261.
GeneID	338322.
KEGG	hsa:338322.
UCSC	uc001mfv.1. human.
Organism-specific databases
CTD	338322.
GeneCards	GC11M007980.
HGNC	HGNC:21464. NLRP10.
HPA	HPA039498. HPA040101.
MIM	609662. gene.
neXtProt	NX_Q86W26.
PharmGKB	PA162397832.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG145856.
HOGENOM	HOG000113728.
HOVERGEN	HBG052572.
InParanoid	Q86W26.
OMA	FFHAMSY.
OrthoDB	EOG48D0V0.
PhylomeDB	Q86W26.
Gene expression databases
ArrayExpress	Q86W26.
Bgee	Q86W26.
CleanEx	HS_NLRP10.
Genevestigator	Q86W26.
GermOnline	ENSG00000182261. Homo sapiens.
Family and domain databases
Gene3D	1.10.533.10. 1 hit.
InterPro	IPR004020. DAPIN. IPR011029. DEATH-like_dom. IPR007111. NACHT_NTPase. [Graphical view]
Pfam	PF02758. PYRIN. 1 hit. [Graphical view]
SUPFAM	SSF47986. DEATH_like. 1 hit.
PROSITE	PS50824. DAPIN. 1 hit. PS50837. NACHT. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	338322.
NextBio	96929.
SOURCE	Search...

Entry information

Entry name

NAL10_HUMAN

Accession

Primary (citable) accession number: Q86W26
Secondary accession number(s): Q2M3C4, Q6JGT0

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 13, 2004
Last sequence update:	June 1, 2003
Last modified:	May 1, 2013
This is version 80 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.