CNPY3_MOUSE
ID CNPY3_MOUSE Reviewed; 276 AA.
AC Q9DAU1; Q571I0; Q8BUS5; Q8BUV5; Q8C0C5;
DT 15-JAN-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 132.
DE RecName: Full=Protein canopy homolog 3;
DE AltName: Full=Protein associated with Tlr4;
DE AltName: Full=Trinucleotide repeat-containing gene 5 protein;
DE Flags: Precursor;
GN Name=Cnpy3; Synonyms=Prat4a, Tnrc5;
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 [MRNA] (ISOFORM 1).
RC TISSUE=Embryonic carcinoma;
RX PubMed=12511604; DOI=10.1210/me.2002-0192;
RA Glozak M.A., Li Y., Reuille R., Kim K.H., Vo M.N., Rogers M.B.;
RT "Trapping and characterization of novel retinoid response elements.";
RL Mol. Endocrinol. 17:27-41(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC STRAIN=C57BL/6J;
RC TISSUE=Cerebellum, Embryonic stem cell, Fetal head, Kidney, Lung, Ovary,
RC and Placenta;
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=FVB/N; TISSUE=Kidney;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 35-276 (ISOFORM 1).
RC TISSUE=Spleen;
RX PubMed=15449545; DOI=10.1093/dnares/11.2.127;
RA Okazaki N., Kikuno R., Ohara R., Inamoto S., Koseki H., Hiraoka S.,
RA Saga Y., Kitamura H., Nakagawa T., Nagase T., Ohara O., Koga H.;
RT "Prediction of the coding sequences of mouse homologues of FLJ genes: the
RT complete nucleotide sequences of 110 mouse FLJ-homologous cDNAs identified
RT by screening of terminal sequences of cDNA clones randomly sampled from
RT size-fractionated libraries.";
RL DNA Res. 11:127-135(2004).
RN [5]
RP INTERACTION WITH TLR4.
RX PubMed=16338228; DOI=10.1016/j.bbrc.2005.11.123;
RA Konno K., Wakabayashi Y., Akashi-Takamura S., Ishii T., Kobayashi M.,
RA Takahashi K., Kusumoto Y., Saitoh S., Yoshizawa Y., Miyake K.;
RT "A molecule that is associated with Toll-like receptor 4 and regulates its
RT cell surface expression.";
RL Biochem. Biophys. Res. Commun. 339:1076-1082(2006).
RN [6]
RP FUNCTION, AND INTERACTION WITH TLR4.
RX PubMed=16849487; DOI=10.4049/jimmunol.177.3.1772;
RA Wakabayashi Y., Kobayashi M., Akashi-Takamura S., Tanimura N., Konno K.,
RA Takahashi K., Ishii T., Mizutani T., Iba H., Kouro T., Takaki S.,
RA Takatsu K., Oda Y., Ishihama Y., Saitoh S., Miyake K.;
RT "A protein associated with toll-like receptor 4 (PRAT4A) regulates cell
RT surface expression of TLR4.";
RL J. Immunol. 177:1772-1779(2006).
RN [7]
RP FUNCTION, INTERACTION WITH TLR1 AND TLR9, SUBCELLULAR LOCATION, AND
RP DISRUPTION PHENOTYPE.
RX PubMed=17998391; DOI=10.1084/jem.20071132;
RA Takahashi K., Shibata T., Akashi-Takamura S., Kiyokawa T., Wakabayashi Y.,
RA Tanimura N., Kobayashi T., Matsumoto F., Fukui R., Kouro T., Nagai Y.,
RA Takatsu K., Saitoh S., Miyake K.;
RT "A protein associated with Toll-like receptor (TLR) 4 (PRAT4A) is required
RT for TLR-dependent immune responses.";
RL J. Exp. Med. 204:2963-2976(2007).
RN [8]
RP INTERACTION WITH TLR2; TLR4 AND TLR9, AND MUTAGENESIS OF ARG-95; MET-145
RP AND SER-231.
RX PubMed=18780723; DOI=10.1093/intimm/dxn098;
RA Kiyokawa T., Akashi-Takamura S., Shibata T., Matsumoto F., Nishitani C.,
RA Kuroki Y., Seto Y., Miyake K.;
RT "A single base mutation in the PRAT4A gene reveals differential interaction
RT of PRAT4A with Toll-like receptors.";
RL Int. Immunol. 20:1407-1415(2008).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [10]
RP FUNCTION, INTERACTION WITH HSP90B1 AND TLR9, SUBCELLULAR LOCATION, AND
RP MUTAGENESIS OF MET-145.
RX PubMed=20865800; DOI=10.1038/ncomms1070;
RA Liu B., Yang Y., Qiu Z., Staron M., Hong F., Li Y., Wu S., Li Y., Hao B.,
RA Bona R., Han D., Li Z.;
RT "Folding of Toll-like receptors by the HSP90 paralogue gp96 requires a
RT substrate-specific cochaperone.";
RL Nat. Commun. 1:79-79(2010).
RN [11]
RP ERRATUM OF PUBMED:20865800.
RA Liu B., Yang Y., Qiu Z., Staron M., Hong F., Li Y., Wu S., Li Y., Hao B.,
RA Bona R., Han D., Li Z.;
RL Nat. Commun. 3:653-653(2012).
RN [12]
RP DISRUPTION PHENOTYPE.
RX PubMed=29394991; DOI=10.1016/j.ajhg.2018.01.004;
RA Mutoh H., Kato M., Akita T., Shibata T., Wakamoto H., Ikeda H., Kitaura H.,
RA Aoto K., Nakashima M., Wang T., Ohba C., Miyatake S., Miyake N., Kakita A.,
RA Miyake K., Fukuda A., Matsumoto N., Saitsu H.;
RT "Biallelic Variants in CNPY3, Encoding an Endoplasmic Reticulum Chaperone,
RT Cause Early-Onset Epileptic Encephalopathy.";
RL Am. J. Hum. Genet. 102:321-329(2018).
CC -!- FUNCTION: Toll-like receptor (TLR)-specific co-chaperone for HSP90B1.
CC Required for proper TLR folding, except that of TLR3, and hence
CC controls TLR exit from the endoplasmic reticulum. Consequently,
CC required for both innate and adaptive immune responses.
CC {ECO:0000269|PubMed:16849487, ECO:0000269|PubMed:17998391,
CC ECO:0000269|PubMed:20865800}.
CC -!- SUBUNIT: Interacts with HSP90B1; this interaction is disrupted in the
CC presence of ATP. Interacts with TLR1, TLR2, TLR4 and TLR9. Strongest
CC interaction with TLR4. {ECO:0000269|PubMed:16338228,
CC ECO:0000269|PubMed:16849487, ECO:0000269|PubMed:17998391,
CC ECO:0000269|PubMed:18780723, ECO:0000269|PubMed:20865800}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum
CC {ECO:0000269|PubMed:17998391, ECO:0000269|PubMed:20865800}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9DAU1-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9DAU1-2; Sequence=VSP_030134;
CC -!- DISRUPTION PHENOTYPE: The birth rate of knockout mice on a C57BL/6
CC background is very low (approximately 10% of pups). The animals appear
CC normal, but their growth after birth is severely retarded. Half of them
CC die by the end of the weaning period. Mutant mice have profoundly
CC impaired T-helper type 1 lymphocyte (Th1)-mediated responses
CC (PubMed:17998391). On a BALB/c background, under resting conditions,
CC they show spastic or dystonic features and, during the open field test,
CC they exhibit hyperactivity and anxiety. Their resting
CC electroencephalography show enhanced activity in the fast beta
CC frequency band (20-35 Hz). They do not show any apparent structural
CC brain anomaly (PubMed:29394991). {ECO:0000269|PubMed:17998391,
CC ECO:0000269|PubMed:29394991}.
CC -!- SIMILARITY: Belongs to the canopy family. {ECO:0000305}.
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DR EMBL; AF361644; AAK52494.1; -; mRNA.
DR EMBL; AK005532; BAB24103.1; -; mRNA.
DR EMBL; AK031742; BAC27534.1; -; mRNA.
DR EMBL; AK049358; BAC33707.1; -; mRNA.
DR EMBL; AK082340; BAC38471.1; -; mRNA.
DR EMBL; AK082749; BAC38599.1; -; mRNA.
DR EMBL; AK085617; BAC39489.1; -; mRNA.
DR EMBL; AK086940; BAC39769.1; -; mRNA.
DR EMBL; AK143428; BAE25373.1; -; mRNA.
DR EMBL; BC013549; AAH13549.1; -; mRNA.
DR EMBL; AK220209; BAD90134.1; -; mRNA.
DR CCDS; CCDS28839.1; -. [Q9DAU1-1]
DR RefSeq; NP_001292917.1; NM_001305988.1.
DR RefSeq; NP_001292918.1; NM_001305989.1. [Q9DAU1-2]
DR RefSeq; NP_001292919.1; NM_001305990.1. [Q9DAU1-2]
DR RefSeq; NP_082341.1; NM_028065.4. [Q9DAU1-1]
DR RefSeq; XP_017173143.1; XM_017317654.1.
DR AlphaFoldDB; Q9DAU1; -.
DR CORUM; Q9DAU1; -.
DR STRING; 10090.ENSMUSP00000050309; -.
DR GlyConnect; 2619; 3 N-Linked glycans (1 site).
DR GlyGen; Q9DAU1; 1 site, 3 N-linked glycans (1 site).
DR iPTMnet; Q9DAU1; -.
DR PhosphoSitePlus; Q9DAU1; -.
DR EPD; Q9DAU1; -.
DR jPOST; Q9DAU1; -.
DR MaxQB; Q9DAU1; -.
DR PaxDb; Q9DAU1; -.
DR PeptideAtlas; Q9DAU1; -.
DR PRIDE; Q9DAU1; -.
DR ProteomicsDB; 283656; -. [Q9DAU1-1]
DR ProteomicsDB; 283657; -. [Q9DAU1-2]
DR Antibodypedia; 16108; 183 antibodies from 30 providers.
DR DNASU; 72029; -.
DR Ensembl; ENSMUST00000059844; ENSMUSP00000050309; ENSMUSG00000023973. [Q9DAU1-1]
DR GeneID; 72029; -.
DR KEGG; mmu:72029; -.
DR UCSC; uc008cuf.2; mouse. [Q9DAU1-1]
DR CTD; 10695; -.
DR MGI; MGI:1919279; Cnpy3.
DR VEuPathDB; HostDB:ENSMUSG00000023973; -.
DR eggNOG; KOG4052; Eukaryota.
DR GeneTree; ENSGT00390000014072; -.
DR HOGENOM; CLU_078068_0_0_1; -.
DR InParanoid; Q9DAU1; -.
DR OMA; DKACLDE; -.
DR OrthoDB; 1412562at2759; -.
DR PhylomeDB; Q9DAU1; -.
DR TreeFam; TF318951; -.
DR Reactome; R-MMU-1679131; Trafficking and processing of endosomal TLR.
DR BioGRID-ORCS; 72029; 3 hits in 58 CRISPR screens.
DR ChiTaRS; Cnpy3; mouse.
DR PRO; PR:Q9DAU1; -.
DR Proteomes; UP000000589; Chromosome 17.
DR RNAct; Q9DAU1; protein.
DR Bgee; ENSMUSG00000023973; Expressed in humerus cartilage element and 235 other tissues.
DR ExpressionAtlas; Q9DAU1; baseline and differential.
DR Genevisible; Q9DAU1; MM.
DR GO; GO:0005783; C:endoplasmic reticulum; IEA:UniProtKB-SubCell.
DR GO; GO:0005102; F:signaling receptor binding; IPI:MGI.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR InterPro; IPR021852; DUF3456.
DR Pfam; PF11938; DUF3456; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Chaperone; Coiled coil; Disulfide bond;
KW Endoplasmic reticulum; Glycoprotein; Immunity; Innate immunity;
KW Reference proteome; Signal.
FT SIGNAL 1..26
FT /evidence="ECO:0000255"
FT CHAIN 27..276
FT /note="Protein canopy homolog 3"
FT /id="PRO_0000313781"
FT DOMAIN 47..269
FT /note="Saposin B-type"
FT REGION 218..276
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 153..179
FT /evidence="ECO:0000255"
FT COMPBIAS 246..264
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 153
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 49..206
FT /evidence="ECO:0000250"
FT DISULFID 52..194
FT /evidence="ECO:0000250"
FT DISULFID 104..166
FT /evidence="ECO:0000250"
FT VAR_SEQ 1..125
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_030134"
FT MUTAGEN 95
FT /note="R->L: Does not affect association with TLR2, TLR4
FT and TLR9; does not affect cell-surface expression of TLR2,
FT TLR4 and TLR9; does not affect responses of TLR2, TLR4 and
FT TLR9."
FT /evidence="ECO:0000269|PubMed:18780723"
FT MUTAGEN 145
FT /note="M->K: Loss of HSP90B1-binding. Impairs association
FT with TLR2 and TLR4; does not impair association with TLR9;
FT partially affects responses of TLR2 and TLR4; affects
FT responses of TLR9; does not affect cell-surface expression
FT of TLR2; affects cell-surface expression of TLR4 and TLR9."
FT /evidence="ECO:0000269|PubMed:18780723,
FT ECO:0000269|PubMed:20865800"
FT MUTAGEN 231
FT /note="S->I: Does not affect association with TLR2, TLR4
FT and TLR9; does not affect cell-surface expression of TLR2,
FT TLR4 and TLR9; does not affect responses of TLR2, TLR4 and
FT TLR9."
FT /evidence="ECO:0000269|PubMed:18780723"
FT CONFLICT 256
FT /note="A -> AE (in Ref. 4; BAD90134)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 276 AA; 30538 MW; 7C69F60BA3BE1745 CRC64;
MESMSELAPR CLLFPLLLLL PLLLLPAPKL GPSPAGAEET DWVRLPSKCE VCKYVAVELK
SAFEETGKTK EVIDTGYGIL DGKGSGVKYT KSDLRLIEVT ETICKRLLDY SLHKERTGSN
RFAKGMSETF ETLHNLVHKG VKVVMDIPYE LWNETSAEVA DLKKQCDVLV EEFEEVIEDW
YRNHQEEDLT EFLCANHVLK GKDTSCLAER WSGKKGDIAS LGGKKSKKKR SGVKGSSSGS
SKQRKELGGL GEDANAEEEE GVQKASPLPH SPPDEL
