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Protein

Nucleoredoxin

Gene

NXN

Organism
Homo sapiens (Human)
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) (By similarity).By similarity

Catalytic activityi

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

GO - Molecular functioni

  1. protein-disulfide reductase activity Source: UniProtKB-EC
  2. thioredoxin-disulfide reductase activity Source: Ensembl

GO - Biological processi

  1. cardiovascular system development Source: UniProtKB
  2. cell differentiation Source: UniProtKB-KW
  3. negative regulation of protein ubiquitination Source: UniProtKB
  4. negative regulation of Wnt signaling pathway Source: UniProtKB
  5. 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)
Gene namesi
Name:NXN
Synonyms:NRX
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 17

Organism-specific databases

HGNCiHGNC:18008. NXN.

Subcellular locationi

Cytoplasmcytosol By similarity. Nucleus By similarity

GO - Cellular componenti

  1. cytosol Source: UniProtKB-SubCell
  2. nucleus Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA31863.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methioninei1 – 11Removed1 Publication
Chaini2 – 435434NucleoredoxinPRO_0000332933Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei2 – 21N-acetylserine1 Publication

Keywords - PTMi

Acetylation

Proteomic databases

MaxQBiQ6DKJ4.
PaxDbiQ6DKJ4.
PeptideAtlasiQ6DKJ4.
PRIDEiQ6DKJ4.

PTM databases

PhosphoSiteiQ6DKJ4.

Expressioni

Gene expression databases

BgeeiQ6DKJ4.
CleanExiHS_NXN.
ExpressionAtlasiQ6DKJ4. baseline and differential.
GenevestigatoriQ6DKJ4.

Organism-specific databases

HPAiHPA022850.
HPA023566.

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 (By similarity).By similarity

Protein-protein interaction databases

BioGridi122144. 7 interactions.
IntActiQ6DKJ4. 2 interactions.
MINTiMINT-4898529.
STRINGi9606.ENSP00000337443.

Structurei

3D structure databases

ProteinModelPortaliQ6DKJ4.
SMRiQ6DKJ4. Positions 2-165, 196-296.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini167 – 321155ThioredoxinPROSITE-ProRule annotationAdd
BLAST

Sequence similaritiesi

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

Phylogenomic databases

eggNOGiNOG273116.
GeneTreeiENSGT00530000063279.
HOGENOMiHOG000007309.
HOVERGENiHBG053461.
InParanoidiQ6DKJ4.
KOiK17609.
OMAiCRNFTPK.
OrthoDBiEOG70W3G2.
PhylomeDBiQ6DKJ4.
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 (3)i

Sequence statusi: Complete.

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

This entry describes 3 isoformsi produced by alternative splicing. Align

Isoform 1 (identifier: Q6DKJ4-1) [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 EKLVTGGGEE VDVHSLGARG ISLLGLYFGC SLSAPCAQLS
60 70 80 90 100
ASLAAFYGRL RGDAAAGPGP GAGAGAAAEP EPRRRLEIVF VSSDQDQRQW
110 120 130 140 150
QDFVRDMPWL ALPYKEKHRK LKLWNKYRIS NIPSLIFLDA TTGKVVCRNG
160 170 180 190 200
LLVIRDDPEG LEFPWGPKPF REVIAGPLLR NNGQSLESSS LEGSHVGVYF
210 220 230 240 250
SAHWCPPCRS LTRVLVESYR KIKEAGQNFE IIFVSADRSE ESFKQYFSEM
260 270 280 290 300
PWLAVPYTDE ARRSRLNRLY GIQGIPTLIM LDPQGEVITR QGRVEVLNDE
310 320 330 340 350
DCREFPWHPK PVLELSDSNA AQLNEGPCLV LFVDSEDDGE SEAAKQLIQP
360 370 380 390 400
IAEKIIAKYK AKEEEAPLLF FVAGEDDMTD SLRDYTNLPE AAPLLTILDM
410 420 430
SARAKYVMDV EEITPAIVEA FVNDFLAEKL KPEPI
Length:435
Mass (Da):48,392
Last modified:April 29, 2008 - v2
Checksum:iB67927F001BE4E5B
GO
Isoform 2 (identifier: Q6DKJ4-2) [UniParc]FASTAAdd to Basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-113: Missing.
     114-120: YKEKHRK → MQELRNS
     275-290: IPTLIMLDPQGEVITR → RRSRPRLRVAPGNLLT
     291-435: Missing.

Note: No experimental confirmation available.

Show »
Length:177
Mass (Da):20,328
Checksum:iD36156E815E83ACF
GO
Isoform 3 (identifier: Q6DKJ4-3) [UniParc]FASTAAdd to Basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-108: Missing.
     109-120: WLALPYKEKHRK → MADVSLHRNPAT

Show »
Length:327
Mass (Da):36,871
Checksum:iA9343547616F7A95
GO

Sequence cautioni

The sequence BAB14171.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence BAB55122.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti124 – 1241W → K in BAB55122. (PubMed:14702039)Curated
Sequence conflicti165 – 1651W → K in BAB14171. (PubMed:14702039)Curated
Sequence conflicti372 – 3721V → I in AAH73845. (PubMed:15489334)Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 113113Missing in isoform 2. 1 PublicationVSP_033392Add
BLAST
Alternative sequencei1 – 108108Missing in isoform 3. 1 PublicationVSP_042792Add
BLAST
Alternative sequencei109 – 12012WLALP…EKHRK → MADVSLHRNPAT in isoform 3. 1 PublicationVSP_042793Add
BLAST
Alternative sequencei114 – 1207YKEKHRK → MQELRNS in isoform 2. 1 PublicationVSP_033393
Alternative sequencei275 – 29016IPTLI…EVITR → RRSRPRLRVAPGNLLT in isoform 2. 1 PublicationVSP_033394Add
BLAST
Alternative sequencei291 – 435145Missing in isoform 2. 1 PublicationVSP_033395Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK022676 mRNA. Translation: BAB14171.1. Different initiation.
AK027451 mRNA. Translation: BAB55122.1. Different initiation.
AK302073 mRNA. Translation: BAG63462.1.
AC015884 Genomic DNA. No translation available.
AC036164 Genomic DNA. No translation available.
AC087392 Genomic DNA. No translation available.
CH471108 Genomic DNA. Translation: EAW90640.1.
CH471108 Genomic DNA. Translation: EAW90641.1.
BC009327 mRNA. Translation: AAH09327.2.
BC063828 mRNA. Translation: AAH63828.1.
BC073845 mRNA. Translation: AAH73845.1.
BC104634 mRNA. Translation: AAI04635.1.
CCDSiCCDS10998.1. [Q6DKJ4-1]
CCDS56013.1. [Q6DKJ4-3]
RefSeqiNP_001192248.1. NM_001205319.1. [Q6DKJ4-3]
NP_071908.2. NM_022463.4. [Q6DKJ4-1]
UniGeneiHs.527989.

Genome annotation databases

EnsembliENST00000336868; ENSP00000337443; ENSG00000167693. [Q6DKJ4-1]
ENST00000537628; ENSP00000446446; ENSG00000167693.
ENST00000575801; ENSP00000461038; ENSG00000167693. [Q6DKJ4-3]
GeneIDi64359.
KEGGihsa:64359.
UCSCiuc002fsa.3. human. [Q6DKJ4-1]
uc010vqe.2. human. [Q6DKJ4-3]

Polymorphism databases

DMDMi187471109.

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK022676 mRNA. Translation: BAB14171.1. Different initiation.
AK027451 mRNA. Translation: BAB55122.1. Different initiation.
AK302073 mRNA. Translation: BAG63462.1.
AC015884 Genomic DNA. No translation available.
AC036164 Genomic DNA. No translation available.
AC087392 Genomic DNA. No translation available.
CH471108 Genomic DNA. Translation: EAW90640.1.
CH471108 Genomic DNA. Translation: EAW90641.1.
BC009327 mRNA. Translation: AAH09327.2.
BC063828 mRNA. Translation: AAH63828.1.
BC073845 mRNA. Translation: AAH73845.1.
BC104634 mRNA. Translation: AAI04635.1.
CCDSiCCDS10998.1. [Q6DKJ4-1]
CCDS56013.1. [Q6DKJ4-3]
RefSeqiNP_001192248.1. NM_001205319.1. [Q6DKJ4-3]
NP_071908.2. NM_022463.4. [Q6DKJ4-1]
UniGeneiHs.527989.

3D structure databases

ProteinModelPortaliQ6DKJ4.
SMRiQ6DKJ4. Positions 2-165, 196-296.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi122144. 7 interactions.
IntActiQ6DKJ4. 2 interactions.
MINTiMINT-4898529.
STRINGi9606.ENSP00000337443.

PTM databases

PhosphoSiteiQ6DKJ4.

Polymorphism databases

DMDMi187471109.

Proteomic databases

MaxQBiQ6DKJ4.
PaxDbiQ6DKJ4.
PeptideAtlasiQ6DKJ4.
PRIDEiQ6DKJ4.

Protocols and materials databases

DNASUi64359.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000336868; ENSP00000337443; ENSG00000167693. [Q6DKJ4-1]
ENST00000537628; ENSP00000446446; ENSG00000167693.
ENST00000575801; ENSP00000461038; ENSG00000167693. [Q6DKJ4-3]
GeneIDi64359.
KEGGihsa:64359.
UCSCiuc002fsa.3. human. [Q6DKJ4-1]
uc010vqe.2. human. [Q6DKJ4-3]

Organism-specific databases

CTDi64359.
GeneCardsiGC17M000702.
H-InvDBHIX0013394.
HGNCiHGNC:18008. NXN.
HPAiHPA022850.
HPA023566.
MIMi612895. gene.
neXtProtiNX_Q6DKJ4.
PharmGKBiPA31863.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG273116.
GeneTreeiENSGT00530000063279.
HOGENOMiHOG000007309.
HOVERGENiHBG053461.
InParanoidiQ6DKJ4.
KOiK17609.
OMAiCRNFTPK.
OrthoDBiEOG70W3G2.
PhylomeDBiQ6DKJ4.
TreeFamiTF331873.

Miscellaneous databases

ChiTaRSiNXN. human.
GenomeRNAii64359.
NextBioi66291.
PROiQ6DKJ4.
SOURCEiSearch...

Gene expression databases

BgeeiQ6DKJ4.
CleanExiHS_NXN.
ExpressionAtlasiQ6DKJ4. baseline and differential.
GenevestigatoriQ6DKJ4.

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. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
    Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
    , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
    Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3), NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 124-435 (ISOFORM 1).
    Tissue: Teratocarcinoma and Testis.
  2. "DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage."
    Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R., Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A., Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J., Chang J.L.
    , Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J., DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S., Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E., Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K., LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J., Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A., Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D., Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A., Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.
    Nature 440:1045-1049(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  3. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  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] (ISOFORM 2), PARTIAL NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3), NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 171-435 (ISOFORM 1).
    Tissue: Brain, Liver, Lung and Uterus.
  5. Cited for: IDENTIFICATION IN A COMPLEX WITH PHOSPHATASE 2A.
  6. "Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
    Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.
    Anal. Chem. 81:4493-4501(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS], CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS].
  7. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].

Entry informationi

Entry nameiNXN_HUMAN
AccessioniPrimary (citable) accession number: Q6DKJ4
Secondary accession number(s): B4DXQ0
, D3DTH2, Q3SWW6, Q6P3U6, Q7L4C6, Q9H9Q1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 29, 2008
Last sequence update: April 29, 2008
Last modified: January 7, 2015
This is version 96 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 17
    Human chromosome 17: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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 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.