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Protein

Thioredoxin reductase 2, mitochondrial

Gene

TXNRD2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Involved in the control of reactive oxygen species levels and the regulation of mitochondrial redox homeostasis (PubMed:24601690). Maintains thioredoxin in a reduced state. May play a role in redox-regulated cell signaling.1 Publication

Miscellaneous

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

Catalytic activityi

Thioredoxin + NADP+ = thioredoxin disulfide + NADPH.

Cofactori

FADUniRule annotationCurated

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei497Proton acceptorBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi41 – 70FADBy similarityAdd BLAST30

GO - Molecular functioni

GO - Biological processi

  • cell redox homeostasis Source: UniProtKB
  • cellular response to oxidative stress Source: Reactome
  • response to oxygen radical Source: UniProtKB

Keywordsi

Molecular functionOxidoreductase
LigandFAD, Flavoprotein, NADP

Enzyme and pathway databases

BRENDAi1.8.1.9 2681
ReactomeiR-HSA-3299685 Detoxification of Reactive Oxygen Species

Names & Taxonomyi

Protein namesi
Recommended name:
Thioredoxin reductase 2, mitochondrial (EC:1.8.1.9)
Alternative name(s):
Selenoprotein Z
Short name:
SelZ
TR-beta
Thioredoxin reductase TR3
Gene namesi
Name:TXNRD2
Synonyms:KIAA1652, TRXR2
OrganismiHomo sapiens (Human)Imported
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 22

Organism-specific databases

EuPathDBiHostDB:ENSG00000184470.20
HGNCiHGNC:18155 TXNRD2
MIMi606448 gene
neXtProtiNX_Q9NNW7

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Mitochondrion

Pathology & Biotechi

Involvement in diseasei

Glucocorticoid deficiency 5 (GCCD5)1 Publication
The disease may be caused by mutations affecting the gene represented in this entry.
Disease descriptionA form of glucocorticoid deficiency, a rare autosomal recessive disorder characterized by resistance to ACTH action on the adrenal cortex, adrenal insufficiency and an inability of the adrenal cortex to produce cortisol. It usually presents in the neonatal period or in early childhood with episodes of hypoglycemia and other symptoms related to cortisol deficiency, including failure to thrive, recurrent illnesses or infections, convulsions, and shock. In a small number of patients hypoglycemia can be sufficiently severe and persistent that it leads to serious long-term neurological damage or death. The diagnosis is readily confirmed with a low plasma cortisol measurement in the presence of an elevated ACTH level, and normal aldosterone and plasma renin measurements.
See also OMIM:617825
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_080529447 – 524Missing in GCCD5; the mutant protein is undetectable in patient cells. 1 PublicationAdd BLAST78

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi10587
MalaCardsiTXNRD2
MIMi617825 phenotype
OpenTargetsiENSG00000184470
Orphaneti361 Familial glucocorticoid deficiency
154 Familial isolated dilated cardiomyopathy
PharmGKBiPA38302

Chemistry databases

ChEMBLiCHEMBL2403
DrugBankiDB05428 motexafin gadolinium

Polymorphism and mutation databases

BioMutaiTXNRD2
DMDMi182705230

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Transit peptidei1 – 36MitochondrionSequence analysisAdd BLAST36
ChainiPRO_000003028837 – 524Thioredoxin reductase 2, mitochondrialAdd BLAST488

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi86 ↔ 91Redox-activeBy similarity
Modified residuei175N6-succinyllysineBy similarity1
Modified residuei329N6-succinyllysineBy similarity1
Cross-linki522 ↔ 523Cysteinyl-selenocysteine (Cys-Sec)By similarity

Keywords - PTMi

Disulfide bond

Proteomic databases

EPDiQ9NNW7
MaxQBiQ9NNW7
PaxDbiQ9NNW7
PeptideAtlasiQ9NNW7
PRIDEiQ9NNW7
ProteomicsDBi81857
81858 [Q9NNW7-2]
81859 [Q9NNW7-3]
81860 [Q9NNW7-4]

PTM databases

iPTMnetiQ9NNW7
PhosphoSitePlusiQ9NNW7
SwissPalmiQ9NNW7

Expressioni

Tissue specificityi

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 PubMed:10608886, high levels in kidney, whereas according to PubMed:9923614, levels are low. High expression is observed in the adrenal cortex (PubMed:24601690).4 Publications

Gene expression databases

BgeeiENSG00000184470 Expressed in 210 organ(s), highest expression level in right lobe of liver
ExpressionAtlasiQ9NNW7 baseline and differential

Organism-specific databases

HPAiCAB002007
HPA003323

Interactioni

Subunit structurei

Homodimer.By similarity

Protein-protein interaction databases

BioGridi115836, 19 interactors
IntActiQ9NNW7, 2 interactors
MINTiQ9NNW7
STRINGi9606.ENSP00000383365

Chemistry databases

BindingDBiQ9NNW7

Structurei

3D structure databases

ProteinModelPortaliQ9NNW7
SMRiQ9NNW7
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Keywords - Domaini

Redox-active center, Transit peptide

Phylogenomic databases

eggNOGiKOG0405 Eukaryota
COG1249 LUCA
GeneTreeiENSGT00390000007578
HOVERGENiHBG004959
InParanoidiQ9NNW7
KOiK22182
OMAiGLECACF
OrthoDBiEOG091G03IU
PhylomeDBiQ9NNW7
TreeFamiTF314782

Family and domain databases

Gene3Di3.30.390.30, 1 hit
3.50.50.60, 2 hits
InterProiView protein in InterPro
IPR036188 FAD/NAD-bd_sf
IPR023753 FAD/NAD-binding_dom
IPR016156 FAD/NAD-linked_Rdtase_dimer_sf
IPR001100 Pyr_nuc-diS_OxRdtase
IPR004099 Pyr_nucl-diS_OxRdtase_dimer
IPR012999 Pyr_OxRdtase_I_AS
IPR006338 Thioredoxin/glutathione_Rdtase
PfamiView protein in Pfam
PF07992 Pyr_redox_2, 1 hit
PF02852 Pyr_redox_dim, 1 hit
PIRSFiPIRSF000350 Mercury_reductase_MerA, 1 hit
SUPFAMiSSF51905 SSF51905, 1 hit
SSF55424 SSF55424, 1 hit
TIGRFAMsiTIGR01438 TGR, 1 hit
PROSITEiView protein in PROSITE
PS00076 PYRIDINE_REDOX_1, 1 hit

Sequences (4+)i

Sequence statusi: Complete.

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

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 4 described isoforms and 11 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: Q9NNW7-1) [UniParc]FASTAAdd to basket
Also known as: AlphaCurated

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
MAAMAVALRG LGGRFRWRTQ AVAGGVRGAA RGAAAGQRDY DLLVVGGGSG
60 70 80 90 100
GLACAKEAAQ LGRKVAVVDY VEPSPQGTRW GLGGTCVNVG CIPKKLMHQA
110 120 130 140 150
ALLGGLIQDA PNYGWEVAQP VPHDWRKMAE AVQNHVKSLN WGHRVQLQDR
160 170 180 190 200
KVKYFNIKAS FVDEHTVCGV AKGGKEILLS ADHIIIATGG RPRYPTHIEG
210 220 230 240 250
ALEYGITSDD IFWLKESPGK TLVVGASYVA LECAGFLTGI GLDTTIMMRS
260 270 280 290 300
IPLRGFDQQM SSMVIEHMAS HGTRFLRGCA PSRVRRLPDG QLQVTWEDST
310 320 330 340 350
TGKEDTGTFD TVLWAIGRVP DTRSLNLEKA GVDTSPDTQK ILVDSREATS
360 370 380 390 400
VPHIYAIGDV VEGRPELTPI AIMAGRLLVQ RLFGGSSDLM DYDNVPTTVF
410 420 430 440 450
TPLEYGCVGL SEEEAVARHG QEHVEVYHAH YKPLEFTVAG RDASQCYVKM
460 470 480 490 500
VCLREPPQLV LGLHFLGPNA GEVTQGFALG IKCGASYAQV MRTVGIHPTC
510 520
SEEVVKLRIS KRSGLDPTVT GCUG
Length:524
Mass (Da):56,507
Last modified:February 26, 2008 - v3
Checksum:iB575A185A2183DAC
GO
Isoform 2 (identifier: Q9NNW7-2) [UniParc]FASTAAdd to basket
Also known as: BetaCurated

The sequence of this isoform differs from the canonical sequence as follows:
     1-30: MAAMAVALRGLGGRFRWRTQAVAGGVRGAA → MEDQ

Show »
Length:498
Mass (Da):53,970
Checksum:i7B255499E2F1881E
GO
Isoform 3 (identifier: Q9NNW7-3) [UniParc]FASTAAdd to basket
Also known as: SelZf2

The sequence of this isoform differs from the canonical sequence as follows:
     1-96: Missing.

Show »
Length:428
Mass (Da):46,841
Checksum:iCA7963D57A19ADAB
GO
Isoform 4 (identifier: Q9NNW7-4) [UniParc]FASTAAdd to basket
Also known as: SelZf1

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

Show »
Length:277
Mass (Da):30,291
Checksum:i80F3E412BF2738F3
GO

Computationally mapped potential isoform sequencesi

There are 11 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
D3YTF8D3YTF8_HUMAN
Thioredoxin reductase 2, mitochondr...
TXNRD2
501Annotation score:
A0A182DWF3A0A182DWF3_HUMAN
Thioredoxin reductase 2, mitochondr...
TXNRD2
523Annotation score:
A0A182DWF2A0A182DWF2_HUMAN
Thioredoxin reductase 2, mitochondr...
TXNRD2
494Annotation score:
A0A096LPK7A0A096LPK7_HUMAN
Thioredoxin reductase 2, mitochondr...
TXNRD2
463Annotation score:
A0A096LPB7A0A096LPB7_HUMAN
Thioredoxin reductase 2, mitochondr...
TXNRD2
180Annotation score:
A0A096LP96A0A096LP96_HUMAN
Thioredoxin reductase 2, mitochondr...
TXNRD2
212Annotation score:
A0A096LPH4A0A096LPH4_HUMAN
Thioredoxin reductase 2, mitochondr...
TXNRD2
165Annotation score:
A0A0U1RQX0A0A0U1RQX0_HUMAN
Thioredoxin reductase 2, mitochondr...
TXNRD2
362Annotation score:
E7EWK1E7EWK1_HUMAN
Thioredoxin reductase 2, mitochondr...
TXNRD2
338Annotation score:
A0A096LPD9A0A096LPD9_HUMAN
Thioredoxin reductase 2, mitochondr...
TXNRD2
306Annotation score:
There is more potential isoformShow all

Sequence cautioni

The sequence AAD25167 differs from that shown. Reason: Erroneous initiation.Curated
The sequence AAG47635 differs from that shown. Reason: Erroneous termination at position 523. Translated as Sec.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti33Missing in AAG47635 (Ref. 6) Curated1
Sequence conflicti285R → K in AAG47635 (Ref. 6) Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_05177714R → L. Corresponds to variant dbSNP:rs45593642Ensembl.1
Natural variantiVAR_05177866A → S4 PublicationsCorresponds to variant dbSNP:rs5748469EnsemblClinVar.1
Natural variantiVAR_051779299S → R1 PublicationCorresponds to variant dbSNP:rs5992495EnsemblClinVar.1
Natural variantiVAR_051780370I → T4 PublicationsCorresponds to variant dbSNP:rs1139793EnsemblClinVar.1
Natural variantiVAR_080529447 – 524Missing in GCCD5; the mutant protein is undetectable in patient cells. 1 PublicationAdd BLAST78

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0083061 – 247Missing in isoform 4. 1 PublicationAdd BLAST247
Alternative sequenceiVSP_0083051 – 96Missing in isoform 3. 1 PublicationAdd BLAST96
Alternative sequenceiVSP_0083041 – 30MAAMA…VRGAA → MEDQ in isoform 2. CuratedAdd BLAST30

Non-standard residue

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Non-standard residuei523Selenocysteine1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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
CCDSiCCDS42981.1 [Q9NNW7-1]
CCDS86998.1 [Q9NNW7-3]
RefSeqiNP_006431.2, NM_006440.4 [Q9NNW7-1]
UniGeneiHs.443430

Genome annotation databases

EnsembliENST00000400521; ENSP00000383365; ENSG00000184470 [Q9NNW7-1]
ENST00000542719; ENSP00000485128; ENSG00000184470 [Q9NNW7-3]
GeneIDi10587
KEGGihsa:10587

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism, Selenocysteine

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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
CCDSiCCDS42981.1 [Q9NNW7-1]
CCDS86998.1 [Q9NNW7-3]
RefSeqiNP_006431.2, NM_006440.4 [Q9NNW7-1]
UniGeneiHs.443430

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1W1Emodel-A/B36-524[»]
ProteinModelPortaliQ9NNW7
SMRiQ9NNW7
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi115836, 19 interactors
IntActiQ9NNW7, 2 interactors
MINTiQ9NNW7
STRINGi9606.ENSP00000383365

Chemistry databases

BindingDBiQ9NNW7
ChEMBLiCHEMBL2403
DrugBankiDB05428 motexafin gadolinium

PTM databases

iPTMnetiQ9NNW7
PhosphoSitePlusiQ9NNW7
SwissPalmiQ9NNW7

Polymorphism and mutation databases

BioMutaiTXNRD2
DMDMi182705230

Proteomic databases

EPDiQ9NNW7
MaxQBiQ9NNW7
PaxDbiQ9NNW7
PeptideAtlasiQ9NNW7
PRIDEiQ9NNW7
ProteomicsDBi81857
81858 [Q9NNW7-2]
81859 [Q9NNW7-3]
81860 [Q9NNW7-4]

Protocols and materials databases

DNASUi10587
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000400521; ENSP00000383365; ENSG00000184470 [Q9NNW7-1]
ENST00000542719; ENSP00000485128; ENSG00000184470 [Q9NNW7-3]
GeneIDi10587
KEGGihsa:10587

Organism-specific databases

CTDi10587
DisGeNETi10587
EuPathDBiHostDB:ENSG00000184470.20
GeneCardsiTXNRD2
H-InvDBiHIX0016244
HGNCiHGNC:18155 TXNRD2
HPAiCAB002007
HPA003323
MalaCardsiTXNRD2
MIMi606448 gene
617825 phenotype
neXtProtiNX_Q9NNW7
OpenTargetsiENSG00000184470
Orphaneti361 Familial glucocorticoid deficiency
154 Familial isolated dilated cardiomyopathy
PharmGKBiPA38302
HUGEiSearch...
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0405 Eukaryota
COG1249 LUCA
GeneTreeiENSGT00390000007578
HOVERGENiHBG004959
InParanoidiQ9NNW7
KOiK22182
OMAiGLECACF
OrthoDBiEOG091G03IU
PhylomeDBiQ9NNW7
TreeFamiTF314782

Enzyme and pathway databases

BRENDAi1.8.1.9 2681
ReactomeiR-HSA-3299685 Detoxification of Reactive Oxygen Species

Miscellaneous databases

ChiTaRSiTXNRD2 human
GenomeRNAii10587
PROiPR:Q9NNW7
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000184470 Expressed in 210 organ(s), highest expression level in right lobe of liver
ExpressionAtlasiQ9NNW7 baseline and differential

Family and domain databases

Gene3Di3.30.390.30, 1 hit
3.50.50.60, 2 hits
InterProiView protein in InterPro
IPR036188 FAD/NAD-bd_sf
IPR023753 FAD/NAD-binding_dom
IPR016156 FAD/NAD-linked_Rdtase_dimer_sf
IPR001100 Pyr_nuc-diS_OxRdtase
IPR004099 Pyr_nucl-diS_OxRdtase_dimer
IPR012999 Pyr_OxRdtase_I_AS
IPR006338 Thioredoxin/glutathione_Rdtase
PfamiView protein in Pfam
PF07992 Pyr_redox_2, 1 hit
PF02852 Pyr_redox_dim, 1 hit
PIRSFiPIRSF000350 Mercury_reductase_MerA, 1 hit
SUPFAMiSSF51905 SSF51905, 1 hit
SSF55424 SSF55424, 1 hit
TIGRFAMsiTIGR01438 TGR, 1 hit
PROSITEiView protein in PROSITE
PS00076 PYRIDINE_REDOX_1, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiTRXR2_HUMAN
AccessioniPrimary (citable) accession number: Q9NNW7
Secondary accession number(s): O95840
, Q96IJ2, Q9H2Z5, Q9NZV3, Q9NZV4, Q9P2Y0, Q9P2Y1, Q9UQU8
Entry historyiIntegrated into UniProtKB/Swiss-Prot: September 19, 2003
Last sequence update: February 26, 2008
Last modified: November 7, 2018
This is version 180 of the entry and version 3 of the sequence. See 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

3D-structure, Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. Human chromosome 22
    Human chromosome 22: entries, gene names and cross-references to MIM
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
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