Q6DKJ4 (NXN_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Nucleoredoxin
EC=1.8.1.8

Gene names

Name:	NXN
Synonyms:	NRX

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	435 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	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.
Catalytic activity	Protein dithiol + NAD(P)+ = protein disulfide + NAD(P)H.
Subunit structure	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. Ref.5
Subcellular location	Cytoplasm › cytosol By similarity. Nucleus By similarity.
Sequence similarities	Belongs to the nucleoredoxin family. Contains 1 thioredoxin domain.
Sequence caution	The sequence BAB14171.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended. The sequence BAB55122.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

Ontologies

Keywords
Biological process	Differentiation Wnt signaling pathway
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Alternative splicing
Ligand	NAD
Molecular function	Developmental protein Oxidoreductase
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	Wnt receptor signaling pathway Inferred from electronic annotation. Source: UniProtKB-KW cardiovascular system development Inferred from sequence or structural similarity. Source: UniProtKB cell differentiation Inferred from electronic annotation. Source: UniProtKB-KW negative regulation of Wnt receptor signaling pathway Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of protein ubiquitination Inferred from sequence or structural similarity. Source: UniProtKB
Cellular_component	cytosol Inferred from electronic annotation. Source: UniProtKB-SubCell nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	protein-disulfide reductase activity Inferred from electronic annotation. Source: EC thioredoxin-disulfide reductase activity Inferred from electronic annotation. Source: Compara
Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q6DKJ4-1)

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.

Isoform 2 (identifier: Q6DKJ4-2)

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.

Isoform 3 (identifier: Q6DKJ4-3)

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

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 435	435	Nucleoredoxin		PRO_0000332933
Regions
	Domain	167 – 321	155	Thioredoxin
Natural variations
	Alternative sequence	1 – 113	113	Missing in isoform 2.		VSP_033392
	Alternative sequence	1 – 108	108	Missing in isoform 3.		VSP_042792
	Alternative sequence	109 – 120	12	WLALP…EKHRK → MADVSLHRNPAT in isoform 3.		VSP_042793
	Alternative sequence	114 – 120	7	YKEKHRK → MQELRNS in isoform 2.		VSP_033393
	Alternative sequence	275 – 290	16	IPTLI…EVITR → RRSRPRLRVAPGNLLT in isoform 2.		VSP_033394
	Alternative sequence	291 – 435	145	Missing in isoform 2.		VSP_033395
Experimental info
	Sequence conflict	124	1	W → K in BAB55122. Ref.1
	Sequence conflict	165	1	W → K in BAB14171. Ref.1
	Sequence conflict	372	1	V → I in AAH73845. Ref.4

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified April 29, 2008. Version 2. Checksum: B67927F001BE4E5B	FASTA	435	48,392
	10 20 30 40 50 60 MSGFLEELLG EKLVTGGGEE VDVHSLGARG ISLLGLYFGC SLSAPCAQLS ASLAAFYGRL 70 80 90 100 110 120 RGDAAAGPGP GAGAGAAAEP EPRRRLEIVF VSSDQDQRQW QDFVRDMPWL ALPYKEKHRK 130 140 150 160 170 180 LKLWNKYRIS NIPSLIFLDA TTGKVVCRNG LLVIRDDPEG LEFPWGPKPF REVIAGPLLR 190 200 210 220 230 240 NNGQSLESSS LEGSHVGVYF SAHWCPPCRS LTRVLVESYR KIKEAGQNFE IIFVSADRSE 250 260 270 280 290 300 ESFKQYFSEM PWLAVPYTDE ARRSRLNRLY GIQGIPTLIM LDPQGEVITR QGRVEVLNDE 310 320 330 340 350 360 DCREFPWHPK PVLELSDSNA AQLNEGPCLV LFVDSEDDGE SEAAKQLIQP IAEKIIAKYK 370 380 390 400 410 420 AKEEEAPLLF FVAGEDDMTD SLRDYTNLPE AAPLLTILDM SARAKYVMDV EEITPAIVEA 430 FVNDFLAEKL KPEPI
	Isoform 2 [UniParc]. Checksum: D36156E815E83ACF	FASTA	177	20,328
	10 20 30 40 50 60 MQELRNSLKL WNKYRISNIP SLIFLDATTG KVVCRNGLLV IRDDPEGLEF PWGPKPFREV 70 80 90 100 110 120 IAGPLLRNNG QSLESSSLEG SHVGVYFSAH WCPPCRSLTR VLVESYRKIK EAGQNFEIIF 130 140 150 160 170 VSADRSEESF KQYFSEMPWL AVPYTDEARR SRLNRLYGIQ GRRSRPRLRV APGNLLT
	Isoform 3 [UniParc]. Checksum: A9343547616F7A95	FASTA	327	36,871
	10 20 30 40 50 60 MADVSLHRNP ATLKLWNKYR ISNIPSLIFL DATTGKVVCR NGLLVIRDDP EGLEFPWGPK 70 80 90 100 110 120 PFREVIAGPL LRNNGQSLES SSLEGSHVGV YFSAHWCPPC RSLTRVLVES YRKIKEAGQN 130 140 150 160 170 180 FEIIFVSADR SEESFKQYFS EMPWLAVPYT DEARRSRLNR LYGIQGIPTL IMLDPQGEVI 190 200 210 220 230 240 TRQGRVEVLN DEDCREFPWH PKPVLELSDS NAAQLNEGPC LVLFVDSEDD GESEAAKQLI 250 260 270 280 290 300 QPIAEKIIAK YKAKEEEAPL LFFVAGEDDM TDSLRDYTNL PEAAPLLTIL DMSARAKYVM 310 320 DVEEITPAIV EAFVNDFLAE KLKPEPI

References

	« Hide 'large scale' referencesShow 'large scale' references »
[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]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases 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]	"Interaction of nucleoredoxin with protein phosphatase 2A." Lechward K., Sugajska E., de Baere I., Goris J., Hemmings B.A., Zolnierowicz S. FEBS Lett. 580:3631-3637(2006) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION IN A COMPLEX WITH PHOSPHATASE 2A.
[6]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	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.
IPI	IPI00304267. IPI00651743.
RefSeq	NP_001192248.1. NM_001205319.1. NP_071908.2. NM_022463.4.
UniGene	Hs.527989.
3D structure databases
HSSP	HSSP built from PDB template 1O73 based on UniProtKB O77404.
ProteinModelPortal	Q6DKJ4.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q6DKJ4. 1 interaction.
STRING	9606.ENSP00000337443.
PTM databases
PhosphoSite	Q6DKJ4.
Polymorphism databases
DMDM	187471109.
Proteomic databases
PaxDb	Q6DKJ4.
PeptideAtlas	Q6DKJ4.
PRIDE	Q6DKJ4.
Protocols and materials databases
DNASU	64359.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000336868; ENSP00000337443; ENSG00000167693. ENST00000537628; ENSP00000446446; ENSG00000167693. ENST00000575801; ENSP00000461038; ENSG00000167693.
GeneID	64359.
KEGG	hsa:64359.
UCSC	uc002fsa.3. human. uc002fsb.1. human.
Organism-specific databases
CTD	64359.
GeneCards	GC17M000702.
H-InvDB	HIX0013394.
HGNC	HGNC:18008. NXN.
HPA	HPA022850. HPA023566.
MIM	612895. gene.
neXtProt	NX_Q6DKJ4.
PharmGKB	PA31863.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG273116.
HOGENOM	HOG000007309.
HOVERGEN	HBG053461.
InParanoid	Q6DKJ4.
OMA	FVSSDQD.
OrthoDB	EOG4CVG71.
PhylomeDB	Q6DKJ4.
Gene expression databases
ArrayExpress	Q6DKJ4.
Bgee	Q6DKJ4.
CleanEx	HS_NXN.
Genevestigator	Q6DKJ4.
Family and domain databases
Gene3D	3.40.30.10. 2 hits.
InterPro	IPR012336. Thioredoxin-like_fold. [Graphical view]
SUPFAM	SSF52833. Thiordxn-like_fd. 3 hits.
PROSITE	PS00194. THIOREDOXIN_1. False negative. PS51352. THIOREDOXIN_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	NXN. human.
GenomeRNAi	64359.
NextBio	66291.
SOURCE	Search...

Entry information

Entry name

NXN_HUMAN

Accession

Primary (citable) accession number: Q6DKJ4
Secondary accession number(s): B4DXQ0 , D3DTH2, Q3SWW6, Q6P3U6, Q7L4C6, Q9H9Q1

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 29, 2008
Last sequence update:	April 29, 2008
Last modified:	May 1, 2013
This is version 82 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.