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Protein

Thioredoxin reductase 2, mitochondrial

Gene

TXNRD2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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

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: InterPro
  • response to oxygen radical Source: UniProtKB
  • response to reactive oxygen species Source: Reactome
Complete GO annotation...

Keywords - Molecular functioni

Oxidoreductase

Keywords - Ligandi

FAD, Flavoprotein, NADP

Enzyme and pathway databases

BioCyciZFISH:HS00001-MONOMER.
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

HGNCiHGNC:18155. TXNRD2.

Subcellular locationi

GO - Cellular componenti

  • mitochondrial matrix Source: Reactome
  • mitochondrion Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Mitochondrion

Pathology & Biotechi

Organism-specific databases

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

Chemistry databases

ChEMBLiCHEMBL2403.

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.

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.3 Publications

Gene expression databases

BgeeiENSG00000184470.
ExpressionAtlasiQ9NNW7. baseline and differential.

Organism-specific databases

HPAiHPA003323.

Interactioni

Subunit structurei

Homodimer.By similarity

Protein-protein interaction databases

BioGridi115836. 16 interactors.
IntActiQ9NNW7. 1 interactor.
STRINGi9606.ENSP00000383365.

Chemistry databases

BindingDBiQ9NNW7.

Structurei

3D structure databases

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

Family & Domainsi

Sequence similaritiesi

Keywords - Domaini

Redox-active center, Transit peptide

Phylogenomic databases

eggNOGiKOG0405. Eukaryota.
COG1249. LUCA.
GeneTreeiENSGT00390000007578.
HOVERGENiHBG004959.
InParanoidiQ9NNW7.
KOiK00384.
OMAiGLHFTGP.
OrthoDBiEOG091G03IU.
PhylomeDBiQ9NNW7.
TreeFamiTF314782.

Family and domain databases

Gene3Di3.30.390.30. 1 hit.
3.50.50.60. 2 hits.
InterProiIPR023753. FAD/NAD-binding_dom.
IPR016156. FAD/NAD-linked_Rdtase_dimer.
IPR004099. Pyr_nucl-diS_OxRdtase_dimer.
IPR012999. Pyr_OxRdtase_I_AS.
IPR006338. Thioredoxin/glutathione_Rdtase.
[Graphical view]
PfamiPF07992. Pyr_redox_2. 1 hit.
PF02852. Pyr_redox_dim. 1 hit.
[Graphical view]
SUPFAMiSSF51905. SSF51905. 1 hit.
SSF55424. SSF55424. 1 hit.
TIGRFAMsiTIGR01438. TGR. 1 hit.
PROSITEiPS00076. PYRIDINE_REDOX_1. 1 hit.
[Graphical view]

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

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

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 rs45593642dbSNPEnsembl.1
Natural variantiVAR_05177866A → S.3 PublicationsCorresponds to variant rs5748469dbSNPEnsembl.1
Natural variantiVAR_051779299S → R.Corresponds to variant rs5992495dbSNPEnsembl.1
Natural variantiVAR_051780370I → T.3 PublicationsCorresponds to variant rs1139793dbSNPEnsembl.1

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]
RefSeqiNP_001269441.1. NM_001282512.1.
NP_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

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]
RefSeqiNP_001269441.1. NM_001282512.1.
NP_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.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi115836. 16 interactors.
IntActiQ9NNW7. 1 interactor.
STRINGi9606.ENSP00000383365.

Chemistry databases

BindingDBiQ9NNW7.
ChEMBLiCHEMBL2403.

PTM databases

iPTMnetiQ9NNW7.
PhosphoSitePlusiQ9NNW7.
SwissPalmiQ9NNW7.

Polymorphism and mutation databases

BioMutaiTXNRD2.
DMDMi182705230.

Proteomic databases

EPDiQ9NNW7.
MaxQBiQ9NNW7.
PaxDbiQ9NNW7.
PeptideAtlasiQ9NNW7.
PRIDEiQ9NNW7.

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.
GeneCardsiTXNRD2.
H-InvDBHIX0016244.
HGNCiHGNC:18155. TXNRD2.
HPAiHPA003323.
MalaCardsiTXNRD2.
MIMi606448. gene.
neXtProtiNX_Q9NNW7.
OpenTargetsiENSG00000184470.
Orphaneti361. Familial glucocorticoid deficiency.
154. Familial isolated dilated cardiomyopathy.
PharmGKBiPA38302.
HUGEiSearch...
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0405. Eukaryota.
COG1249. LUCA.
GeneTreeiENSGT00390000007578.
HOVERGENiHBG004959.
InParanoidiQ9NNW7.
KOiK00384.
OMAiGLHFTGP.
OrthoDBiEOG091G03IU.
PhylomeDBiQ9NNW7.
TreeFamiTF314782.

Enzyme and pathway databases

BioCyciZFISH:HS00001-MONOMER.
BRENDAi1.8.1.9. 2681.
ReactomeiR-HSA-3299685. Detoxification of Reactive Oxygen Species.

Miscellaneous databases

ChiTaRSiTXNRD2. human.
GenomeRNAii10587.
PROiQ9NNW7.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000184470.
ExpressionAtlasiQ9NNW7. baseline and differential.

Family and domain databases

Gene3Di3.30.390.30. 1 hit.
3.50.50.60. 2 hits.
InterProiIPR023753. FAD/NAD-binding_dom.
IPR016156. FAD/NAD-linked_Rdtase_dimer.
IPR004099. Pyr_nucl-diS_OxRdtase_dimer.
IPR012999. Pyr_OxRdtase_I_AS.
IPR006338. Thioredoxin/glutathione_Rdtase.
[Graphical view]
PfamiPF07992. Pyr_redox_2. 1 hit.
PF02852. Pyr_redox_dim. 1 hit.
[Graphical view]
SUPFAMiSSF51905. SSF51905. 1 hit.
SSF55424. SSF55424. 1 hit.
TIGRFAMsiTIGR01438. TGR. 1 hit.
PROSITEiPS00076. PYRIDINE_REDOX_1. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiTRXR2_HUMAN
AccessioniPrimary (citable) accession number: Q9NNW7
Secondary accession number(s): O95840
, Q96IJ2, Q9H2Z5, Q9NZV3, Q9NZV4, Q9P2Y0, Q9P2Y1, Q9UQU8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: September 19, 2003
Last sequence update: February 26, 2008
Last modified: November 2, 2016
This is version 164 of the entry and version 3 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

Miscellaneous

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

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 22
    Human chromosome 22: entries, gene names and cross-references to MIM
  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. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. 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.