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Q9NNW7 (TRXR2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 140. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Thioredoxin reductase 2, mitochondrial

EC=1.8.1.9
Alternative name(s):
Selenoprotein Z
Short name=SelZ
TR-beta
Thioredoxin reductase TR3
Gene names
Name:TXNRD2
Synonyms:KIAA1652, TRXR2
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length524 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Maintains thioredoxin in a reduced state. Implicated in the defenses against oxidative stress. May play a role in redox-regulated cell signaling.

Catalytic activity

Thioredoxin + NADP+ = thioredoxin disulfide + NADPH.

Cofactor

FAD By similarity.

Subunit structure

Homodimer. UniProtKB P38816

Subcellular location

Mitochondrion Ref.2 Ref.3.

Tissue specificity

Highly expressed in the prostate, ovary, liver, testis, uterus, colon and small intestine. Intermediate levels in brain, skeletal muscle, heart and spleen. Low levels in placenta, pancreas, thymus and peripheral blood leukocytes. According to Ref.5, high levels in kidney, whereas according to Ref.2, levels are low. Ref.2 Ref.3 Ref.5

Miscellaneous

The active site is a redox-active disulfide bond. The selenocysteine residue is essential for enzymatic activity By similarity. UniProtKB Q9Z0J5

Sequence similarities

Belongs to the class-I pyridine nucleotide-disulfide oxidoreductase family.

Sequence caution

The sequence AAD25167.1 differs from that shown. Reason: Erroneous initiation.

The sequence AAG47635.1 differs from that shown. Reason: Erroneous termination at position 523. Translated as Sec.

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q9NNW7-1)

Also known as: Alpha;

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: Q9NNW7-2)

Also known as: Beta;

The sequence of this isoform differs from the canonical sequence as follows:
     1-30: MAAMAVALRGLGGRFRWRTQAVAGGVRGAA → MEDQ
Isoform 3 (identifier: Q9NNW7-3)

Also known as: SelZf2;

The sequence of this isoform differs from the canonical sequence as follows:
     1-96: Missing.
Isoform 4 (identifier: Q9NNW7-4)

Also known as: SelZf1;

The sequence of this isoform differs from the canonical sequence as follows:
     1-247: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Transit peptide1 – 3636Mitochondrion Potential
Chain37 – 524488Thioredoxin reductase 2, mitochondrial
PRO_0000030288

Regions

Nucleotide binding41 – 7030FAD By similarity

Sites

Active site4971Proton acceptor By similarity

Amino acid modifications

Non-standard residue5231Selenocysteine
Modified residue1751N6-succinyllysine By similarity
Modified residue3291N6-succinyllysine By similarity
Disulfide bond86 ↔ 91Redox-active By similarity UniProtKB P00390
Cross-link522 ↔ 523Cysteinyl-selenocysteine (Cys-Sec) By similarity

Natural variations

Alternative sequence1 – 247247Missing in isoform 4.
VSP_008306
Alternative sequence1 – 9696Missing in isoform 3.
VSP_008305
Alternative sequence1 – 3030MAAMA…VRGAA → MEDQ in isoform 2.
VSP_008304
Natural variant141R → L.
Corresponds to variant rs45593642 [ dbSNP | Ensembl ].
VAR_051777
Natural variant661A → S. Ref.2 Ref.6 Ref.8
Corresponds to variant rs5748469 [ dbSNP | Ensembl ].
VAR_051778
Natural variant2991S → R.
Corresponds to variant rs5992495 [ dbSNP | Ensembl ].
VAR_051779
Natural variant3701I → T. Ref.4 Ref.5 Ref.6
Corresponds to variant rs1139793 [ dbSNP | Ensembl ].
VAR_051780

Experimental info

Sequence conflict331Missing in AAG47635. Ref.6
Sequence conflict2851R → K in AAG47635. Ref.6

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (Alpha) [UniParc].

Last modified February 26, 2008. Version 3.
Checksum: B575A185A2183DAC

FASTA52456,507
        10         20         30         40         50         60 
MAAMAVALRG LGGRFRWRTQ AVAGGVRGAA RGAAAGQRDY DLLVVGGGSG GLACAKEAAQ 

        70         80         90        100        110        120 
LGRKVAVVDY VEPSPQGTRW GLGGTCVNVG CIPKKLMHQA ALLGGLIQDA PNYGWEVAQP 

       130        140        150        160        170        180 
VPHDWRKMAE AVQNHVKSLN WGHRVQLQDR KVKYFNIKAS FVDEHTVCGV AKGGKEILLS 

       190        200        210        220        230        240 
ADHIIIATGG RPRYPTHIEG ALEYGITSDD IFWLKESPGK TLVVGASYVA LECAGFLTGI 

       250        260        270        280        290        300 
GLDTTIMMRS IPLRGFDQQM SSMVIEHMAS HGTRFLRGCA PSRVRRLPDG QLQVTWEDST 

       310        320        330        340        350        360 
TGKEDTGTFD TVLWAIGRVP DTRSLNLEKA GVDTSPDTQK ILVDSREATS VPHIYAIGDV 

       370        380        390        400        410        420 
VEGRPELTPI AIMAGRLLVQ RLFGGSSDLM DYDNVPTTVF TPLEYGCVGL SEEEAVARHG 

       430        440        450        460        470        480 
QEHVEVYHAH YKPLEFTVAG RDASQCYVKM VCLREPPQLV LGLHFLGPNA GEVTQGFALG 

       490        500        510        520 
IKCGASYAQV MRTVGIHPTC SEEVVKLRIS KRSGLDPTVT GCUG 

« Hide

Isoform 2 (Beta) [UniParc].

Checksum: 7B255499E2F1881E
Show »

FASTA49853,970
Isoform 3 (SelZf2) [UniParc].

Checksum: CA7963D57A19ADAB
Show »

FASTA42846,841
Isoform 4 (SelZf1) [UniParc].

Checksum: 80F3E412BF2738F3
Show »

FASTA27730,291

References

« Hide 'large scale' references
[1]"Redox regulation of cell signaling by selenocysteine in mammalian thioredoxin reductases."
Sun Q.-A., Wu Y., Zappacosta F., Jeang K.-T., Lee B.J., Hatfield D.L., Gladyshev V.N.
J. Biol. Chem. 274:24522-24530(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]"Cloning, sequencing and functional expression of a novel human thioredoxin reductase."
Gasdaska P.Y., Berggren M.M., Berry M.J., Powis G.
FEBS Lett. 442:105-111(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, VARIANT SER-66.
Tissue: Fetal heart and Placenta.
[3]"Human mitochondrial thioredoxin reductase: cDNA cloning, expression and genomic organization."
Miranda-Vizuete A., Damdimopoulos A.E., Pedrajas J.R., Gustafsson J.-A., Spyrou G.
Eur. J. Biochem. 261:405-412(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
Tissue: Adrenal gland and Testis.
[4]Toji S., Yano M., Tamai K.
Submitted (NOV-1998) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE (ISOFORMS 1 AND 2), VARIANT THR-370.
[5]"Novel selenoproteins identified in silico and in vivo by using a conserved RNA structural motif."
Lescure A., Gautheret D., Carbon P., Krol A.
J. Biol. Chem. 274:38147-38154(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 3 AND 4), ALTERNATIVE SPLICING, TISSUE SPECIFICITY, VARIANT THR-370.
Tissue: Cervix carcinoma.
[6]Kim J.-R., Lee Y.H., Lee S.-R., Kim B.H., Rhee S.G., Kim J.H.
Submitted (NOV-1999) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE (ISOFORM 1), VARIANTS SER-66 AND THR-370.
[7]"The DNA sequence of human chromosome 22."
Dunham I., Hunt A.R., Collins J.E., Bruskiewich R., Beare D.M., Clamp M., Smink L.J., Ainscough R., Almeida J.P., Babbage A.K., Bagguley C., Bailey J., Barlow K.F., Bates K.N., Beasley O.P., Bird C.P., Blakey S.E., Bridgeman A.M. expand/collapse author list , Buck D., Burgess J., Burrill W.D., Burton J., Carder C., Carter N.P., Chen Y., Clark G., Clegg S.M., Cobley V.E., Cole C.G., Collier R.E., Connor R., Conroy D., Corby N.R., Coville G.J., Cox A.V., Davis J., Dawson E., Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M., Ellington A.G., Evans K.L., Fey J.M., Fleming K., French L., Garner A.A., Gilbert J.G.R., Goward M.E., Grafham D.V., Griffiths M.N.D., Hall C., Hall R.E., Hall-Tamlyn G., Heathcott R.W., Ho S., Holmes S., Hunt S.E., Jones M.C., Kershaw J., Kimberley A.M., King A., Laird G.K., Langford C.F., Leversha M.A., Lloyd C., Lloyd D.M., Martyn I.D., Mashreghi-Mohammadi M., Matthews L.H., Mccann O.T., Mcclay J., Mclaren S., McMurray A.A., Milne S.A., Mortimore B.J., Odell C.N., Pavitt R., Pearce A.V., Pearson D., Phillimore B.J.C.T., Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y., Rogers L., Ross M.T., Scott C.E., Sehra H.K., Skuce C.D., Smalley S., Smith M.L., Soderlund C., Spragon L., Steward C.A., Sulston J.E., Swann R.M., Vaudin M., Wall M., Wallis J.M., Whiteley M.N., Willey D.L., Williams L., Williams S.A., Williamson H., Wilmer T.E., Wilming L., Wright C.L., Hubbard T., Bentley D.R., Beck S., Rogers J., Shimizu N., Minoshima S., Kawasaki K., Sasaki T., Asakawa S., Kudoh J., Shintani A., Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S., Roe B.A., Chen F., Chu L., Crabtree J., Deschamps S., Do A., Do T., Dorman A., Fang F., Fu Y., Hu P., Hua A., Kenton S., Lai H., Lao H.I., Lewis J., Lewis S., Lin S.-P., Loh P., Malaj E., Nguyen T., Pan H., Phan S., Qi S., Qian Y., Ray L., Ren Q., Shaull S., Sloan D., Song L., Wang Q., Wang Y., Wang Z., White J., Willingham D., Wu H., Yao Z., Zhan M., Zhang G., Chissoe S., Murray J., Miller N., Minx P., Fulton R., Johnson D., Bemis G., Bentley D., Bradshaw H., Bourne S., Cordes M., Du Z., Fulton L., Goela D., Graves T., Hawkins J., Hinds K., Kemp K., Latreille P., Layman D., Ozersky P., Rohlfing T., Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K., Nelson J., Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R., Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S., Budarf M.L., McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E., Edelmann L., Kim U.J., Shizuya H., Simon M.I., Dumanski J.P., Peyrard M., Kedra D., Seroussi E., Fransson I., Tapia I., Bruder C.E., O'Brien K.P., Wilkinson P., Bodenteich A., Hartman K., Hu X., Khan A.S., Lane L., Tilahun Y., Wright H.
Nature 402:489-495(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]"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] OF 40-524, VARIANT SER-66.
Tissue: Skin.
[9]"Heterogeneity within animal thioredoxin reductases: evidence for alternative first exon splicing."
Sun Q.-A., Zappacosta F., Factor V.M., Wirth P.J., Hatfield D.L., Gladyshev V.N.
J. Biol. Chem. 276:3106-3114(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: ALTERNATIVE SPLICING.
[10]"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
AF171054 mRNA. Translation: AAD51324.1.
AF106697 mRNA. Translation: AAD19597.1.
AF044212 mRNA. Translation: AAD25167.1. Different initiation.
AB019694 mRNA. Translation: BAA77601.2.
AB019695 mRNA. Translation: BAA77602.2.
AF166126 mRNA. Translation: AAF21431.1.
AF166127 mRNA. Translation: AAF21432.1.
AF201385 mRNA. Translation: AAG47635.1. Sequence problems.
AC000078 Genomic DNA. No translation available.
AC000080 Genomic DNA. No translation available.
AC000090 Genomic DNA. No translation available.
BC007489 mRNA. Translation: AAH07489.3.
CCDSCCDS42981.1. [Q9NNW7-1]
RefSeqNP_001269441.1. NM_001282512.1.
NP_006431.2. NM_006440.4. [Q9NNW7-1]
UniGeneHs.443430.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1W1Emodel-A/B36-524[»]
ProteinModelPortalQ9NNW7.
SMRQ9NNW7. Positions 37-518.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid115836. 8 interactions.

Chemistry

BindingDBQ9NNW7.
ChEMBLCHEMBL2403.

PTM databases

PhosphoSiteQ9NNW7.

Polymorphism databases

DMDM182705230.

Proteomic databases

MaxQBQ9NNW7.
PaxDbQ9NNW7.
PRIDEQ9NNW7.

Protocols and materials databases

DNASU10587.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000400521; ENSP00000383365; ENSG00000184470. [Q9NNW7-1]
GeneID10587.
KEGGhsa:10587.
UCSCuc002zqq.1. human. [Q9NNW7-4]
uc021wlj.1. human. [Q9NNW7-1]

Organism-specific databases

CTD10587.
GeneCardsGC22M019863.
H-InvDBHIX0016244.
HGNCHGNC:18155. TXNRD2.
HPACAB002007.
HPA003323.
MIM606448. gene.
neXtProtNX_Q9NNW7.
Orphanet154. Familial isolated dilated cardiomyopathy.
PharmGKBPA38302.
HUGESearch...
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG1249.
HOVERGENHBG004959.
InParanoidQ9NNW7.
KOK00384.
OMAHFTGPNA.
PhylomeDBQ9NNW7.
TreeFamTF314782.

Enzyme and pathway databases

ReactomeREACT_120956. Cellular responses to stress.

Gene expression databases

ArrayExpressQ9NNW7.
BgeeQ9NNW7.
GenevestigatorQ9NNW7.

Family and domain databases

Gene3D3.30.390.30. 1 hit.
InterProIPR016156. FAD/NAD-linked_Rdtase_dimer.
IPR013027. FAD_pyr_nucl-diS_OxRdtase.
IPR004099. Pyr_nucl-diS_OxRdtase_dimer.
IPR023753. Pyr_nucl-diS_OxRdtase_FAD/NAD.
IPR012999. Pyr_OxRdtase_I_AS.
IPR001327. Pyr_OxRdtase_NAD-bd_dom.
IPR006338. Thioredoxin/glutathione_Rdtase.
[Graphical view]
PfamPF00070. Pyr_redox. 1 hit.
PF07992. Pyr_redox_2. 1 hit.
PF02852. Pyr_redox_dim. 1 hit.
[Graphical view]
PRINTSPR00368. FADPNR.
SUPFAMSSF55424. SSF55424. 1 hit.
TIGRFAMsTIGR01438. TGR. 1 hit.
PROSITEPS00076. PYRIDINE_REDOX_1. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSTXNRD2. human.
GenomeRNAi10587.
NextBio40203.
PROQ9NNW7.
SOURCESearch...

Entry information

Entry nameTRXR2_HUMAN
AccessionPrimary (citable) accession number: Q9NNW7
Secondary accession number(s): O95840 expand/collapse secondary AC list , Q96IJ2, Q9H2Z5, Q9NZV3, Q9NZV4, Q9P2Y0, Q9P2Y1, Q9UQU8
Entry history
Integrated into UniProtKB/Swiss-Prot: September 19, 2003
Last sequence update: February 26, 2008
Last modified: July 9, 2014
This is version 140 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 22

Human chromosome 22: entries, gene names and cross-references to MIM