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Protein

Nucleoredoxin

Gene

Nxn

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Functions as a redox-dependent negative regulator of the Wnt signaling pathway, possibly by preventing ubiquitination of DVL3 by the BCR(KLHL12) complex. May also function as a transcriptional regulator act as a regulator of protein phosphatase 2A (PP2A).4 Publications

Catalytic activityi

Protein dithiol + NAD(P)+ = protein disulfide + NAD(P)H.1 Publication

GO - Molecular functioni

GO - Biological processi

  • cardiovascular system development Source: UniProtKB
  • cell differentiation Source: UniProtKB-KW
  • cellular oxidant detoxification Source: GOC
  • negative regulation of protein ubiquitination Source: UniProtKB
  • negative regulation of Wnt signaling pathway Source: UniProtKB
  • Wnt signaling pathway Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Developmental protein, Oxidoreductase

Keywords - Biological processi

Differentiation, Wnt signaling pathway

Keywords - Ligandi

NAD

Names & Taxonomyi

Protein namesi
Recommended name:
Nucleoredoxin (EC:1.8.1.8)
Alternative name(s):
Protein Red-1
Gene namesi
Name:Nxn
Synonyms:Gn25
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 11

Organism-specific databases

MGIiMGI:109331. Nxn.

Subcellular locationi

GO - Cellular componenti

  • cytosol Source: UniProtKB-SubCell
  • nucleus Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Disruption phenotypei

Perinatal lethality, possibly due abnormal cardiovascular development. Osteoblasts show an aberrant activation of the Wnt signaling pathway.1 Publication

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi205 – 2051C → S: Loss of function and interaction with DVL1; when associated with S-208. 1 Publication
Mutagenesisi208 – 2081C → S: Loss of function and interaction with DVL1; when associated with S-205. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methionineiRemovedBy similarity
Chaini2 – 435434NucleoredoxinPRO_0000332934Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei2 – 21N-acetylserineBy similarity

Keywords - PTMi

Acetylation

Proteomic databases

EPDiP97346.
MaxQBiP97346.
PaxDbiP97346.
PRIDEiP97346.

PTM databases

PhosphoSiteiP97346.

Expressioni

Tissue specificityi

Widely expressed with higher expression in testis and skin.1 Publication

Developmental stagei

Specifically expressed form E9.5 to E12.5 in limb buds.1 Publication

Gene expression databases

BgeeiP97346.
GenevisibleiP97346. MM.

Interactioni

Subunit structurei

Associates with the phosphatase 2A holoenzyme. Interacts with PPP2CA; the interaction is direct. Interacts with DVL1 (via PDZ domain); the interaction is direct and regulated by oxidative stress.2 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
PPP2CAP677752EBI-309684,EBI-712311From a different organism.
PPP2R1AP301532EBI-309684,EBI-302388From a different organism.
SEC63Q9UGP86EBI-309684,EBI-1045560From a different organism.

Protein-protein interaction databases

BioGridi201883. 1 interaction.
IntActiP97346. 7 interactions.
MINTiMINT-2634582.
STRINGi10090.ENSMUSP00000021204.

Structurei

3D structure databases

ProteinModelPortaliP97346.
SMRiP97346. Positions 11-165, 196-296.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini167 – 314148ThioredoxinPROSITE-ProRule annotationAdd
BLAST

Sequence similaritiesi

Belongs to the nucleoredoxin family.Curated
Contains 1 thioredoxin domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG2501. Eukaryota.
ENOG410ZIWC. LUCA.
GeneTreeiENSGT00530000063279.
HOGENOMiHOG000007309.
HOVERGENiHBG053461.
InParanoidiP97346.
KOiK17609.
OMAiGHMITRQ.
OrthoDBiEOG70W3G2.
PhylomeDBiP97346.
TreeFamiTF331873.

Family and domain databases

Gene3Di3.40.30.10. 2 hits.
InterProiIPR012336. Thioredoxin-like_fold.
[Graphical view]
PfamiPF13905. Thioredoxin_8. 2 hits.
[Graphical view]
SUPFAMiSSF52833. SSF52833. 3 hits.
PROSITEiPS51352. THIOREDOXIN_2. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

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

Isoform 1 (identifier: P97346-1) [UniParc]FASTAAdd to basket

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
MSGFLEELLG DKLVTGGGEE VDVHSLGARG IALLGLYFGC SLSAPCAQLS
60 70 80 90 100
ASLAAFYGRL RGDAAAGPGA GAGAGAAAEP EPRHRLEIVF VSSDQDQRQW
110 120 130 140 150
QDFVRDMPWL ALPYKEKHRK LKLWNKYRVS NIPSLIFLDA TTGKVVCRNG
160 170 180 190 200
LLVIRDDPEG LEFPWGPKPF REVIAGPLLR NNGQSLESSS LEGSHVGVYF
210 220 230 240 250
SAHWCPPCRS LTRVLVESYR KIKEAGQEFE IIFVSADRSE ESFKQYFSEM
260 270 280 290 300
PWLAVPYTDE ARRSRLNRLY GIQGIPTLIV LDPQGEVITR QGRVEVLNDE
310 320 330 340 350
DCREFPWHPK PVLELSDSNA VQLNEGPCLV LFVDSEDDGE SEAAKQLIQP
360 370 380 390 400
IAEKIIAKYK AKEEEAPLLF FVAGEDDMTD SLRDYTNLPE AAPLLTILDM
410 420 430
SARAKYVMDV EEITPAIVET FVNDFLAEKL KPEPI
Length:435
Mass (Da):48,344
Last modified:May 1, 1997 - v1
Checksum:iC2AE7A65A5AB7843
GO
Isoform 2 (identifier: P97346-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     362-391: KEEEAPLLFFVAGEDDMTDSLRDYTNLPEA → SAHHSGHVSPGQVRDGCRRDHPSHCGDFCE
     392-435: Missing.

Show »
Length:391
Mass (Da):43,284
Checksum:i604032723E77EBA7
GO

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei362 – 39130KEEEA…NLPEA → SAHHSGHVSPGQVRDGCRRD HPSHCGDFCE in isoform 2. 1 PublicationVSP_033396Add
BLAST
Alternative sequencei392 – 43544Missing in isoform 2. 1 PublicationVSP_033397Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X92750 Genomic DNA. Translation: CAA63408.1.
AB095441 mRNA. Translation: BAD88798.1.
AB095442 mRNA. Translation: BAD88799.1.
AB095443 mRNA. Translation: BAD88800.1.
AB095444 mRNA. Translation: BAD88801.1.
AB096016 Genomic DNA. Translation: BAD88802.1.
AB096017 Genomic DNA. Translation: BAD88803.1.
AB096018 Genomic DNA. Translation: BAD88804.1.
AB096019 Genomic DNA. Translation: BAD88805.1.
AK149075 mRNA. Translation: BAE28730.1.
AL806529, AL663050 Genomic DNA. Translation: CAI24674.1.
AL663050, AL806529 Genomic DNA. Translation: CAI25856.1.
BC004688 mRNA. Translation: AAH04688.1.
BC058244 mRNA. Translation: AAH58244.1.
CCDSiCCDS25064.1. [P97346-1]
RefSeqiNP_032776.1. NM_008750.5. [P97346-1]
UniGeneiMm.27915.

Genome annotation databases

EnsembliENSMUST00000021204; ENSMUSP00000021204; ENSMUSG00000020844. [P97346-1]
GeneIDi18230.
KEGGimmu:18230.
UCSCiuc007kfo.2. mouse. [P97346-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X92750 Genomic DNA. Translation: CAA63408.1.
AB095441 mRNA. Translation: BAD88798.1.
AB095442 mRNA. Translation: BAD88799.1.
AB095443 mRNA. Translation: BAD88800.1.
AB095444 mRNA. Translation: BAD88801.1.
AB096016 Genomic DNA. Translation: BAD88802.1.
AB096017 Genomic DNA. Translation: BAD88803.1.
AB096018 Genomic DNA. Translation: BAD88804.1.
AB096019 Genomic DNA. Translation: BAD88805.1.
AK149075 mRNA. Translation: BAE28730.1.
AL806529, AL663050 Genomic DNA. Translation: CAI24674.1.
AL663050, AL806529 Genomic DNA. Translation: CAI25856.1.
BC004688 mRNA. Translation: AAH04688.1.
BC058244 mRNA. Translation: AAH58244.1.
CCDSiCCDS25064.1. [P97346-1]
RefSeqiNP_032776.1. NM_008750.5. [P97346-1]
UniGeneiMm.27915.

3D structure databases

ProteinModelPortaliP97346.
SMRiP97346. Positions 11-165, 196-296.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi201883. 1 interaction.
IntActiP97346. 7 interactions.
MINTiMINT-2634582.
STRINGi10090.ENSMUSP00000021204.

PTM databases

PhosphoSiteiP97346.

Proteomic databases

EPDiP97346.
MaxQBiP97346.
PaxDbiP97346.
PRIDEiP97346.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000021204; ENSMUSP00000021204; ENSMUSG00000020844. [P97346-1]
GeneIDi18230.
KEGGimmu:18230.
UCSCiuc007kfo.2. mouse. [P97346-1]

Organism-specific databases

CTDi64359.
MGIiMGI:109331. Nxn.

Phylogenomic databases

eggNOGiKOG2501. Eukaryota.
ENOG410ZIWC. LUCA.
GeneTreeiENSGT00530000063279.
HOGENOMiHOG000007309.
HOVERGENiHBG053461.
InParanoidiP97346.
KOiK17609.
OMAiGHMITRQ.
OrthoDBiEOG70W3G2.
PhylomeDBiP97346.
TreeFamiTF331873.

Miscellaneous databases

ChiTaRSiNxn. mouse.
NextBioi293664.
PROiP97346.
SOURCEiSearch...

Gene expression databases

BgeeiP97346.
GenevisibleiP97346. MM.

Family and domain databases

Gene3Di3.40.30.10. 2 hits.
InterProiIPR012336. Thioredoxin-like_fold.
[Graphical view]
PfamiPF13905. Thioredoxin_8. 2 hits.
[Graphical view]
SUPFAMiSSF52833. SSF52833. 3 hits.
PROSITEiPS51352. THIOREDOXIN_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Cloning and characterization of the nucleoredoxin gene that encodes a novel nuclear protein related to thioredoxin."
    Kurooka H., Kato K., Minoguchi S., Takahashi Y., Ikeda J.-E., Habu S., Osawa N., Buchberg A.M., Moriwaki K., Shisa H., Honjo T.
    Genomics 39:331-339(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE.
    Strain: C57BL/6J.
    Tissue: Skin.
  2. "Susceptibility to streptozotocin-induced diabetes is mapped to mouse chromosome 11."
    Babaya N., Ikegami H., Fujisawa T., Nojima K., Itoi-Babaya M., Inoue K., Ohno T., Shibata M., Ogihara T.
    Biochem. Biophys. Res. Commun. 328:158-164(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1).
    Strain: C3H/HeJ, CTS, NOD and NSY.
    Tissue: Kidney and Liver.
  3. "The transcriptional landscape of the mammalian genome."
    Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
    , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
    Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
    Strain: C57BL/6J.
    Tissue: Sympathetic ganglion.
  4. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: C57BL/6J.
  5. "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] (ISOFORMS 1 AND 2).
    Strain: Czech II.
    Tissue: Mammary tumor and Olfactory epithelium.
  6. "Nucleoredoxin, glutaredoxin, and thioredoxin differentially regulate NF-kappaB, AP-1, and CREB activation in HEK293 cells."
    Hirota K., Matsui M., Murata M., Takashima Y., Cheng F.S., Itoh T., Fukuda K., Yodoi J.
    Biochem. Biophys. Res. Commun. 274:177-182(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, SUBCELLULAR LOCATION.
  7. Cited for: FUNCTION, IDENTIFICATION IN A COMPLEX WITH PHOSPHATASE 2A, INTERACTION WITH PPP2CA.
  8. "The thioredoxin-related redox-regulating protein nucleoredoxin inhibits Wnt-beta-catenin signalling through dishevelled."
    Funato Y., Michiue T., Asashima M., Miki H.
    Nat. Cell Biol. 8:501-508(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: IDENTIFICATION BY MASS SPECTROMETRY, FUNCTION, INTERACTION WITH DVL1, SUBCELLULAR LOCATION, MUTAGENESIS OF CYS-205 AND CYS-208.
  9. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Brain, Lung, Spleen and Testis.
  10. "Nucleoredoxin sustains Wnt/beta-catenin signaling by retaining a pool of inactive dishevelled protein."
    Funato Y., Terabayashi T., Sakamoto R., Okuzaki D., Ichise H., Nojima H., Yoshida N., Miki H.
    Curr. Biol. 20:1945-1952(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, DISRUPTION PHENOTYPE.

Entry informationi

Entry nameiNXN_MOUSE
AccessioniPrimary (citable) accession number: P97346
Secondary accession number(s): Q5H8T6, Q5H8U0, Q99KF3
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 29, 2008
Last sequence update: May 1, 1997
Last modified: March 16, 2016
This is version 132 of the entry and version 1 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. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. 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.