NXN_MOUSE
ID NXN_MOUSE Reviewed; 435 AA.
AC P97346; Q5H8T6; Q5H8U0; Q99KF3;
DT 29-APR-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1997, sequence version 1.
DT 03-AUG-2022, entry version 167.
DE RecName: Full=Nucleoredoxin;
DE EC=1.8.1.8;
DE AltName: Full=Protein Red-1;
GN Name=Nxn; Synonyms=Gn25;
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 [GENOMIC DNA], CATALYTIC ACTIVITY, SUBCELLULAR
RP LOCATION, TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RC STRAIN=C57BL/6J; TISSUE=Skin;
RX PubMed=9119370; DOI=10.1006/geno.1996.4493;
RA Kurooka H., Kato K., Minoguchi S., Takahashi Y., Ikeda J.-E., Habu S.,
RA Osawa N., Buchberg A.M., Moriwaki K., Shisa H., Honjo T.;
RT "Cloning and characterization of the nucleoredoxin gene that encodes a
RT novel nuclear protein related to thioredoxin.";
RL Genomics 39:331-339(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1).
RC STRAIN=C3H/HeJ, CTS, NOD, and NSY; TISSUE=Kidney, and Liver;
RX PubMed=15670764; DOI=10.1016/j.bbrc.2004.12.149;
RA Babaya N., Ikegami H., Fujisawa T., Nojima K., Itoi-Babaya M., Inoue K.,
RA Ohno T., Shibata M., Ogihara T.;
RT "Susceptibility to streptozotocin-induced diabetes is mapped to mouse
RT chromosome 11.";
RL Biochem. Biophys. Res. Commun. 328:158-164(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=C57BL/6J; TISSUE=Sympathetic ganglion;
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC STRAIN=Czech II; TISSUE=Mammary tumor, and Olfactory epithelium;
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 [6]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=10903915; DOI=10.1006/bbrc.2000.3106;
RA Hirota K., Matsui M., Murata M., Takashima Y., Cheng F.S., Itoh T.,
RA Fukuda K., Yodoi J.;
RT "Nucleoredoxin, glutaredoxin, and thioredoxin differentially regulate NF-
RT kappaB, AP-1, and CREB activation in HEK293 cells.";
RL Biochem. Biophys. Res. Commun. 274:177-182(2000).
RN [7]
RP FUNCTION, IDENTIFICATION IN A COMPLEX WITH PHOSPHATASE 2A, AND INTERACTION
RP WITH PPP2CA.
RX PubMed=16764867; DOI=10.1016/j.febslet.2006.04.101;
RA Lechward K., Sugajska E., de Baere I., Goris J., Hemmings B.A.,
RA Zolnierowicz S.;
RT "Interaction of nucleoredoxin with protein phosphatase 2A.";
RL FEBS Lett. 580:3631-3637(2006).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY, FUNCTION, INTERACTION WITH DVL1,
RP SUBCELLULAR LOCATION, AND MUTAGENESIS OF CYS-205 AND CYS-208.
RX PubMed=16604061; DOI=10.1038/ncb1405;
RA Funato Y., Michiue T., Asashima M., Miki H.;
RT "The thioredoxin-related redox-regulating protein nucleoredoxin inhibits
RT Wnt-beta-catenin signalling through dishevelled.";
RL Nat. Cell Biol. 8:501-508(2006).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Lung, 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, AND DISRUPTION PHENOTYPE.
RX PubMed=20970343; DOI=10.1016/j.cub.2010.09.065;
RA Funato Y., Terabayashi T., Sakamoto R., Okuzaki D., Ichise H., Nojima H.,
RA Yoshida N., Miki H.;
RT "Nucleoredoxin sustains Wnt/beta-catenin signaling by retaining a pool of
RT inactive dishevelled protein.";
RL Curr. Biol. 20:1945-1952(2010).
CC -!- FUNCTION: Functions as a redox-dependent negative regulator of the Wnt
CC signaling pathway, possibly by preventing ubiquitination of DVL3 by the
CC BCR(KLHL12) complex. May also function as a transcriptional regulator
CC act as a regulator of protein phosphatase 2A (PP2A).
CC {ECO:0000269|PubMed:10903915, ECO:0000269|PubMed:16604061,
CC ECO:0000269|PubMed:16764867, ECO:0000269|PubMed:20970343}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=[protein]-dithiol + NAD(+) = [protein]-disulfide + H(+) +
CC NADH; Xref=Rhea:RHEA:18749, Rhea:RHEA-COMP:10593, Rhea:RHEA-
CC COMP:10594, ChEBI:CHEBI:15378, ChEBI:CHEBI:29950, ChEBI:CHEBI:50058,
CC ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; EC=1.8.1.8;
CC Evidence={ECO:0000269|PubMed:9119370};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=[protein]-dithiol + NADP(+) = [protein]-disulfide + H(+) +
CC NADPH; Xref=Rhea:RHEA:18753, Rhea:RHEA-COMP:10593, Rhea:RHEA-
CC COMP:10594, ChEBI:CHEBI:15378, ChEBI:CHEBI:29950, ChEBI:CHEBI:50058,
CC ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; EC=1.8.1.8;
CC Evidence={ECO:0000269|PubMed:9119370};
CC -!- SUBUNIT: Associates with the phosphatase 2A holoenzyme. Interacts with
CC PPP2CA; the interaction is direct. Interacts with DVL1 (via PDZ
CC domain); the interaction is direct and regulated by oxidative stress.
CC {ECO:0000269|PubMed:16604061, ECO:0000269|PubMed:16764867}.
CC -!- INTERACTION:
CC P97346; P67775: PPP2CA; Xeno; NbExp=2; IntAct=EBI-309684, EBI-712311;
CC P97346; P30153: PPP2R1A; Xeno; NbExp=2; IntAct=EBI-309684, EBI-302388;
CC P97346; Q9UGP8: SEC63; Xeno; NbExp=6; IntAct=EBI-309684, EBI-1045560;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:16604061}.
CC Nucleus {ECO:0000269|PubMed:10903915, ECO:0000269|PubMed:9119370}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P97346-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P97346-2; Sequence=VSP_033396, VSP_033397;
CC -!- TISSUE SPECIFICITY: Widely expressed with higher expression in testis
CC and skin. {ECO:0000269|PubMed:9119370}.
CC -!- DEVELOPMENTAL STAGE: Specifically expressed form 9.5 dpc to 12.5 dpc in
CC limb buds. {ECO:0000269|PubMed:9119370}.
CC -!- DISRUPTION PHENOTYPE: Perinatal lethality, possibly due abnormal
CC cardiovascular development. Osteoblasts show an aberrant activation of
CC the Wnt signaling pathway. {ECO:0000269|PubMed:20970343}.
CC -!- SIMILARITY: Belongs to the nucleoredoxin family. {ECO:0000305}.
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DR EMBL; X92750; CAA63408.1; -; Genomic_DNA.
DR EMBL; AB095441; BAD88798.1; -; mRNA.
DR EMBL; AB095442; BAD88799.1; -; mRNA.
DR EMBL; AB095443; BAD88800.1; -; mRNA.
DR EMBL; AB095444; BAD88801.1; -; mRNA.
DR EMBL; AB096016; BAD88802.1; -; Genomic_DNA.
DR EMBL; AB096017; BAD88803.1; -; Genomic_DNA.
DR EMBL; AB096018; BAD88804.1; -; Genomic_DNA.
DR EMBL; AB096019; BAD88805.1; -; Genomic_DNA.
DR EMBL; AK149075; BAE28730.1; -; mRNA.
DR EMBL; AL663050; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL806529; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC004688; AAH04688.1; -; mRNA.
DR EMBL; BC058244; AAH58244.1; -; mRNA.
DR CCDS; CCDS25064.1; -. [P97346-1]
DR RefSeq; NP_032776.1; NM_008750.5. [P97346-1]
DR AlphaFoldDB; P97346; -.
DR SMR; P97346; -.
DR BioGRID; 201883; 2.
DR IntAct; P97346; 7.
DR MINT; P97346; -.
DR STRING; 10090.ENSMUSP00000021204; -.
DR PhosphoSitePlus; P97346; -.
DR EPD; P97346; -.
DR MaxQB; P97346; -.
DR PaxDb; P97346; -.
DR PeptideAtlas; P97346; -.
DR PRIDE; P97346; -.
DR ProteomicsDB; 293815; -. [P97346-1]
DR ProteomicsDB; 293816; -. [P97346-2]
DR Antibodypedia; 10317; 146 antibodies from 25 providers.
DR DNASU; 18230; -.
DR Ensembl; ENSMUST00000021204; ENSMUSP00000021204; ENSMUSG00000020844. [P97346-1]
DR GeneID; 18230; -.
DR KEGG; mmu:18230; -.
DR UCSC; uc007kfo.2; mouse. [P97346-1]
DR CTD; 64359; -.
DR MGI; MGI:109331; Nxn.
DR VEuPathDB; HostDB:ENSMUSG00000020844; -.
DR eggNOG; KOG2501; Eukaryota.
DR GeneTree; ENSGT00940000161894; -.
DR HOGENOM; CLU_019626_2_1_1; -.
DR InParanoid; P97346; -.
DR OMA; EMITRQG; -.
DR OrthoDB; 1350271at2759; -.
DR PhylomeDB; P97346; -.
DR TreeFam; TF331873; -.
DR BioGRID-ORCS; 18230; 1 hit in 71 CRISPR screens.
DR ChiTaRS; Nxn; mouse.
DR PRO; PR:P97346; -.
DR Proteomes; UP000000589; Chromosome 11.
DR RNAct; P97346; protein.
DR Bgee; ENSMUSG00000020844; Expressed in spermatocyte and 214 other tissues.
DR Genevisible; P97346; MM.
DR GO; GO:0005829; C:cytosol; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0004791; F:thioredoxin-disulfide reductase activity; IDA:MGI.
DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR GO; GO:0072359; P:circulatory system development; IMP:UniProtKB.
DR GO; GO:0001701; P:in utero embryonic development; IMP:MGI.
DR GO; GO:0031397; P:negative regulation of protein ubiquitination; IMP:UniProtKB.
DR GO; GO:0030178; P:negative regulation of Wnt signaling pathway; IMP:UniProtKB.
DR GO; GO:0016055; P:Wnt signaling pathway; ISO:MGI.
DR CDD; cd03071; PDI_b'_NRX; 1.
DR CDD; cd03009; TryX_like_TryX_NRX; 1.
DR InterPro; IPR041861; NRX_PDI_b.
DR InterPro; IPR012336; Thioredoxin-like_fold.
DR InterPro; IPR036249; Thioredoxin-like_sf.
DR InterPro; IPR013766; Thioredoxin_domain.
DR InterPro; IPR045870; TryX_NRX_thioredoxin_dom.
DR Pfam; PF13905; Thioredoxin_8; 2.
DR SUPFAM; SSF52833; SSF52833; 3.
DR PROSITE; PS51352; THIOREDOXIN_2; 1.
PE 1: Evidence at protein level;
KW Acetylation; Alternative splicing; Cytoplasm; Developmental protein;
KW Differentiation; NAD; Nucleus; Oxidoreductase; Reference proteome;
KW Wnt signaling pathway.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:Q6DKJ4"
FT CHAIN 2..435
FT /note="Nucleoredoxin"
FT /id="PRO_0000332934"
FT DOMAIN 167..314
FT /note="Thioredoxin"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00691"
FT MOD_RES 2
FT /note="N-acetylserine"
FT /evidence="ECO:0000250|UniProtKB:Q6DKJ4"
FT VAR_SEQ 362..391
FT /note="KEEEAPLLFFVAGEDDMTDSLRDYTNLPEA -> SAHHSGHVSPGQVRDGCR
FT RDHPSHCGDFCE (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_033396"
FT VAR_SEQ 392..435
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_033397"
FT MUTAGEN 205
FT /note="C->S: Loss of function and interaction with DVL1;
FT when associated with S-208."
FT /evidence="ECO:0000269|PubMed:16604061"
FT MUTAGEN 208
FT /note="C->S: Loss of function and interaction with DVL1;
FT when associated with S-205."
FT /evidence="ECO:0000269|PubMed:16604061"
SQ SEQUENCE 435 AA; 48344 MW; C2AE7A65A5AB7843 CRC64;
MSGFLEELLG DKLVTGGGEE VDVHSLGARG IALLGLYFGC SLSAPCAQLS ASLAAFYGRL
RGDAAAGPGA GAGAGAAAEP EPRHRLEIVF VSSDQDQRQW QDFVRDMPWL ALPYKEKHRK
LKLWNKYRVS NIPSLIFLDA TTGKVVCRNG LLVIRDDPEG LEFPWGPKPF REVIAGPLLR
NNGQSLESSS LEGSHVGVYF SAHWCPPCRS LTRVLVESYR KIKEAGQEFE IIFVSADRSE
ESFKQYFSEM PWLAVPYTDE ARRSRLNRLY GIQGIPTLIV LDPQGEVITR QGRVEVLNDE
DCREFPWHPK PVLELSDSNA VQLNEGPCLV LFVDSEDDGE SEAAKQLIQP IAEKIIAKYK
AKEEEAPLLF FVAGEDDMTD SLRDYTNLPE AAPLLTILDM SARAKYVMDV EEITPAIVET
FVNDFLAEKL KPEPI
