NAL10_MOUSE
ID NAL10_MOUSE Reviewed; 673 AA.
AC Q8CCN1;
DT 13-APR-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 147.
DE RecName: Full=NACHT, LRR and PYD domains-containing protein 10;
GN Name=Nlrp10; Synonyms=Nalp10, Pynod;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Olfactory bulb;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP INTERACTION WITH CASP1 AND IL1B.
RC TISSUE=Heart;
RX PubMed=15096476; DOI=10.1093/intimm/dxh081;
RA Wang Y., Hasegawa M., Imamura R., Kinoshita T., Kondo C., Konaka K.,
RA Suda T.;
RT "PYNOD, a novel Apaf-1/CED4-like protein is an inhibitor of ASC and
RT caspase-1.";
RL Int. Immunol. 16:777-786(2004).
RN [3]
RP TISSUE SPECIFICITY.
RX PubMed=20393137; DOI=10.4049/jimmunol.0900779;
RA Imamura R., Wang Y., Kinoshita T., Suzuki M., Noda T., Sagara J.,
RA Taniguchi S., Okamoto H., Suda T.;
RT "Anti-inflammatory activity of PYNOD and its mechanism in humans and
RT mice.";
RL J. Immunol. 184:5874-5884(2010).
RN [4]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=23071280; DOI=10.4049/jimmunol.1201715;
RA Joly S., Eisenbarth S.C., Olivier A.K., Williams A., Kaplan D.H.,
RA Cassel S.L., Flavell R.A., Sutterwala F.S.;
RT "Nlrp10 is essential for protective antifungal adaptive immunity against
RT Candida albicans.";
RL J. Immunol. 189:4713-4717(2012).
RN [5]
RP DISRUPTION PHENOTYPE.
RX PubMed=22538615; DOI=10.1038/nature11012;
RA Eisenbarth S.C., Williams A., Colegio O.R., Meng H., Strowig T.,
RA Rongvaux A., Henao-Mejia J., Thaiss C.A., Joly S., Gonzalez D.G., Xu L.,
RA Zenewicz L.A., Haberman A.M., Elinav E., Kleinstein S.H., Sutterwala F.S.,
RA Flavell R.A.;
RT "NLRP10 is a NOD-like receptor essential to initiate adaptive immunity by
RT dendritic cells.";
RL Nature 484:510-513(2012).
RN [6]
RP ERRATUM OF PUBMED:22538615.
RX PubMed=26605525; DOI=10.1038/nature16074;
RA Eisenbarth S.C., Williams A., Colegio O.R., Meng H., Strowig T.,
RA Rongvaux A., Henao-Mejia J., Thaiss C.A., Joly S., Gonzalez D.G., Xu L.,
RA Zenewicz L.A., Haberman A.M., Elinav E., Kleinstein S.H., Sutterwala F.S.,
RA Flavell R.A.;
RL Nature 530:504-504(2016).
RN [7]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=27221772; DOI=10.1002/eji.201646401;
RA Damm A., Giebeler N., Zamek J., Zigrino P., Kufer T.A.;
RT "Epidermal NLRP10 contributes to contact hypersensitivity responses in
RT mice.";
RL Eur. J. Immunol. 46:1959-1969(2016).
RN [8]
RP STRUCTURE BY NMR OF 1-102.
RG RIKEN structural genomics initiative (RSGI);
RT "Solution structure of the pyrin/paad-dapin domain in mouse NALP10 (NACHT,
RT leucine rich repeat and PYD containing 10).";
RL Submitted (OCT-2006) to the PDB data bank.
CC -!- FUNCTION: Inhibits autoprocessing of CASP1, CASP1-dependent IL1B
CC secretion, PYCARD aggregation and PYCARD-mediated apoptosis but not
CC apoptosis induced by FAS or BID (By similarity). Displays anti-
CC inflammatory activity (By similarity). Required for immunity against
CC C.albicans infection (PubMed:23071280). Involved in the innate immune
CC response by contributing to pro-inflammatory cytokine release in
CC response to invasive bacterial infection (By similarity). Contributes
CC to T-cell-mediated inflammatory responses in the skin
CC (PubMed:27221772). Plays a role in protection against periodontitis
CC through its involvement in induction of IL1A via ERK activation in oral
CC epithelial cells infected with periodontal pathogens (By similarity).
CC Exhibits both ATPase and GTPase activities (By similarity).
CC {ECO:0000250|UniProtKB:Q86W26, ECO:0000269|PubMed:23071280,
CC ECO:0000269|PubMed:27221772}.
CC -!- SUBUNIT: Oligomerizes (By similarity). Interacts with PYCARD (By
CC similarity). Also interacts with CASP1 and IL1B (PubMed:15096476).
CC Interacts with NOD1 and components of the NOD1 signaling pathway
CC including RIPK2, NR2C2/TAK1 and IKBKG/NEMO (By similarity).
CC {ECO:0000250|UniProtKB:Q86W26, ECO:0000269|PubMed:15096476}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q86W26}. Cell
CC membrane {ECO:0000250|UniProtKB:Q86W26}; Peripheral membrane protein
CC {ECO:0000305}. Note=Cytoplasmic protein which is recruited to the cell
CC membrane by NOD1 following invasive bacterial infection.
CC {ECO:0000250|UniProtKB:Q86W26}.
CC -!- TISSUE SPECIFICITY: Expressed in skin, tongue, heart, colon and several
CC cell lines of hematopoietic and myocytic origin but not in kidney,
CC skeletal muscle, spleen, liver, lung, thymus, brain or small intestine
CC (at protein level). {ECO:0000269|PubMed:20393137}.
CC -!- DOMAIN: The pyrin and ATP-binding domains are required to elicit
CC cytokine release following bacterial infection. {ECO:0000250}.
CC -!- DOMAIN: The NACHT domain is required for inhibition of CASP1
CC autoprocessing. {ECO:0000250}.
CC -!- DISRUPTION PHENOTYPE: High susceptibility to systemic infection by
CC C.albicans with 100% mortality by day 16 post-infection
CC (PubMed:23071280). Does not alter Nlrp3 inflammasome activity and up-
CC regulates Gdpd3 expression (PubMed:22538615). Does not impair skin
CC repair after wounding (PubMed:27221772). Also does not impair the
CC irritant contact dermatitis response following treatment with the
CC irritant croton oil (PubMed:27221772). Significantly reduced
CC inflammation in dinitrofluorobenzene-induced contact hypersensitivity
CC response with reduced numbers of CD3(+), CD8(+) and CD4(+) T cells
CC (PubMed:27221772). {ECO:0000269|PubMed:22538615,
CC ECO:0000269|PubMed:23071280, ECO:0000269|PubMed:27221772}.
CC -!- SIMILARITY: Belongs to the NLRP family. {ECO:0000305}.
CC -!- CAUTION: Despite its official name, does not contain LRR repeats.
CC {ECO:0000305}.
CC -!- CAUTION: Was originally thought to play a role in adaptive immunity
CC through control of dendritic cell-mediated antigen transport to lymph
CC nodes from peripheral sites (PubMed:22538615). However, this was later
CC shown to be dependent on DOCK8 (PubMed:26605525).
CC {ECO:0000303|PubMed:22538615, ECO:0000303|PubMed:26605525}.
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DR EMBL; AK032446; BAC27872.1; -; mRNA.
DR CCDS; CCDS21730.1; -.
DR RefSeq; NP_780741.1; NM_175532.3.
DR PDB; 2DO9; NMR; -; A=1-102.
DR PDBsum; 2DO9; -.
DR AlphaFoldDB; Q8CCN1; -.
DR SMR; Q8CCN1; -.
DR BioGRID; 232621; 1.
DR STRING; 10090.ENSMUSP00000050252; -.
DR iPTMnet; Q8CCN1; -.
DR PhosphoSitePlus; Q8CCN1; -.
DR PaxDb; Q8CCN1; -.
DR PRIDE; Q8CCN1; -.
DR ProteomicsDB; 287604; -.
DR Antibodypedia; 42324; 207 antibodies from 30 providers.
DR DNASU; 244202; -.
DR Ensembl; ENSMUST00000055745; ENSMUSP00000050252; ENSMUSG00000049709.
DR GeneID; 244202; -.
DR KEGG; mmu:244202; -.
DR UCSC; uc009jdb.1; mouse.
DR CTD; 338322; -.
DR MGI; MGI:2444084; Nlrp10.
DR VEuPathDB; HostDB:ENSMUSG00000049709; -.
DR eggNOG; ENOG502QTJW; Eukaryota.
DR GeneTree; ENSGT00940000159520; -.
DR HOGENOM; CLU_002274_2_3_1; -.
DR InParanoid; Q8CCN1; -.
DR OMA; VLYKACQ; -.
DR OrthoDB; 114368at2759; -.
DR PhylomeDB; Q8CCN1; -.
DR BioGRID-ORCS; 244202; 3 hits in 73 CRISPR screens.
DR ChiTaRS; Nlrp10; mouse.
DR EvolutionaryTrace; Q8CCN1; -.
DR PRO; PR:Q8CCN1; -.
DR Proteomes; UP000000589; Chromosome 7.
DR RNAct; Q8CCN1; protein.
DR Bgee; ENSMUSG00000049709; Expressed in interventricular septum and 54 other tissues.
DR ExpressionAtlas; Q8CCN1; baseline and differential.
DR Genevisible; Q8CCN1; MM.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0019897; C:extrinsic component of plasma membrane; ISS:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0016887; F:ATP hydrolysis activity; ISS:UniProtKB.
DR GO; GO:0003924; F:GTPase activity; ISS:UniProtKB.
DR GO; GO:0002250; P:adaptive immune response; IEA:UniProtKB-KW.
DR GO; GO:0050832; P:defense response to fungus; IMP:UniProtKB.
DR GO; GO:0050829; P:defense response to Gram-negative bacterium; ISS:UniProtKB.
DR GO; GO:0006954; P:inflammatory response; IEA:UniProtKB-KW.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:1900426; P:positive regulation of defense response to bacterium; ISS:UniProtKB.
DR GO; GO:0050729; P:positive regulation of inflammatory response; IMP:UniProtKB.
DR GO; GO:0032730; P:positive regulation of interleukin-1 alpha production; ISS:UniProtKB.
DR GO; GO:0032755; P:positive regulation of interleukin-6 production; ISS:UniProtKB.
DR GO; GO:0032757; P:positive regulation of interleukin-8 production; ISS:UniProtKB.
DR GO; GO:0002827; P:positive regulation of T-helper 1 type immune response; IMP:UniProtKB.
DR GO; GO:2000318; P:positive regulation of T-helper 17 type immune response; IMP:UniProtKB.
DR GO; GO:0050727; P:regulation of inflammatory response; IBA:GO_Central.
DR Gene3D; 1.10.533.10; -; 1.
DR Gene3D; 3.40.50.300; -; 1.
DR InterPro; IPR004020; DAPIN.
DR InterPro; IPR011029; DEATH-like_dom_sf.
DR InterPro; IPR007111; NACHT_NTPase.
DR InterPro; IPR041075; NOD2_WH.
DR InterPro; IPR027417; P-loop_NTPase.
DR Pfam; PF05729; NACHT; 1.
DR Pfam; PF17779; NOD2_WH; 1.
DR Pfam; PF02758; PYRIN; 1.
DR SMART; SM01289; PYRIN; 1.
DR SUPFAM; SSF47986; SSF47986; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR PROSITE; PS50824; DAPIN; 1.
DR PROSITE; PS50837; NACHT; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Adaptive immunity; ATP-binding; Cell membrane; Cytoplasm;
KW Immunity; Inflammatory response; Innate immunity; Membrane;
KW Nucleotide-binding; Reference proteome.
FT CHAIN 1..673
FT /note="NACHT, LRR and PYD domains-containing protein 10"
FT /id="PRO_0000080897"
FT DOMAIN 1..92
FT /note="Pyrin"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00061"
FT DOMAIN 163..469
FT /note="NACHT"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00136"
FT REGION 578..673
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 584..603
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 604..646
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 655..673
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 169..176
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00136"
FT HELIX 9..19
FT /evidence="ECO:0007829|PDB:2DO9"
FT HELIX 22..36
FT /evidence="ECO:0007829|PDB:2DO9"
FT STRAND 42..44
FT /evidence="ECO:0007829|PDB:2DO9"
FT TURN 45..47
FT /evidence="ECO:0007829|PDB:2DO9"
FT HELIX 52..60
FT /evidence="ECO:0007829|PDB:2DO9"
FT HELIX 63..77
FT /evidence="ECO:0007829|PDB:2DO9"
FT HELIX 80..88
FT /evidence="ECO:0007829|PDB:2DO9"
FT STRAND 97..99
FT /evidence="ECO:0007829|PDB:2DO9"
SQ SEQUENCE 673 AA; 76367 MW; EE773C592BEC7054 CRC64;
MALARANSPQ EALLWALNDL EENSFKTLKF HLRDVTQFHL ARGELESLSQ VDLASKLISM
YGAQEAVRVV SRSLLAMNLM ELVDYLNQVC LNDYREIYRE HVRCLEERQD WGVNSSHNKL
LLMATSSSGG RRSPSCSDLE QELDPVDVET LFAPEAESYS TPPIVVMQGS AGTGKTTLVK
KLVQDWSKGK LYPGQFDYVF YVSCREVVLL PKCDLPNLIC WCCGDDQAPV TEILRQPGRL
LFILDGYDEL QKSSRAECVL HILMRRREVP CSLLITTRPP ALQSLEPMLG ERRHVLVLGF
SEEERETYFS SCFTDKEQLK NALEFVQNNA VLYKACQVPG ICWVVCSWLK KKMARGQEVS
ETPSNSTDIF TAYVSTFLPT DGNGDSSELT RHKVLKSLCS LAAEGMRHQR LLFEEEVLRK
HGLDGPSLTA FLNCIDYRAG LGIKKFYSFR HISFQEFFYA MSFLVKEDQS QQGEATHKEV
AKLVDPENHE EVTLSLQFLF DMLKTEGTLS LGLKFCFRIA PSVRQDLKHF KEQIEAIKYK
RSWDLEFSLY DSKIKKLTQG IQMKDVILNV QHLDEKKSDK KKSVSVTSSF SSGKVQSPFL
GNDKSTRKQK KASNGKSRGA EEPAPGVRNR RLASREKGHM EMNDKEDGGV EEQEDEEGQT
LKKDGEMIDK MNG
