UniProtKB - Q9NNW7 (TRXR2_HUMAN)
Protein
Thioredoxin reductase 2, mitochondrial
Gene
TXNRD2
Organism
Homo sapiens (Human)
Status
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
- EC:1.8.1.9
Cofactori
FADUniRule annotationCurated
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Active sitei | 497 | Proton acceptorBy similarity | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Nucleotide bindingi | 41 – 70 | FADBy similarityAdd BLAST | 30 |
GO - Molecular functioni
- flavin adenine dinucleotide binding Source: InterPro
- thioredoxin-disulfide reductase activity Source: UniProtKB
GO - Biological processi
- cell redox homeostasis Source: UniProtKB
- cellular response to oxidative stress Source: Reactome
- response to oxygen radical Source: UniProtKB
Keywordsi
Molecular function | Oxidoreductase |
Ligand | FAD, Flavoprotein, NADP |
Enzyme and pathway databases
BRENDAi | 1.8.1.9, 2681 |
PathwayCommonsi | Q9NNW7 |
Reactomei | R-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 |
Organismi | Homo sapiens (Human)Imported |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:18155, TXNRD2 |
MIMi | 606448, gene |
neXtProti | NX_Q9NNW7 |
VEuPathDBi | HostDB:ENSG00000184470.20 |
Subcellular locationi
Mitochondrion
- Mitochondrion 1 Publication
Cytosol
- cytosol Source: HPA
Mitochondrion
- mitochondrial matrix Source: Reactome
- mitochondrion Source: UniProtKB
Other locations
- cytoplasm Source: GO_Central
Keywords - Cellular componenti
MitochondrionPathology & Biotechi
Involvement in diseasei
Glucocorticoid deficiency 5 (GCCD5)1 Publication
The disease may be caused by variants 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.
Related information in OMIMFeature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_080529 | 447 – 524 | Missing in GCCD5; the mutant protein is undetectable in patient cells. 1 PublicationAdd BLAST | 78 |
Keywords - Diseasei
Disease variantOrganism-specific databases
DisGeNETi | 10587 |
MalaCardsi | TXNRD2 |
MIMi | 617825, phenotype |
OpenTargetsi | ENSG00000184470 |
Orphaneti | 361, Familial glucocorticoid deficiency 154, Familial isolated dilated cardiomyopathy |
PharmGKBi | PA38302 |
Miscellaneous databases
Pharosi | Q9NNW7, Tbio |
Chemistry databases
ChEMBLi | CHEMBL2403 |
DrugBanki | DB05428, Motexafin gadolinium |
Genetic variation databases
BioMutai | TXNRD2 |
DMDMi | 182705230 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Transit peptidei | 1 – 36 | MitochondrionSequence analysisAdd BLAST | 36 | |
ChainiPRO_0000030288 | 37 – 524 | Thioredoxin reductase 2, mitochondrialAdd BLAST | 488 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Disulfide bondi | 86 ↔ 91 | Redox-activeBy similarity | ||
Modified residuei | 175 | N6-succinyllysineBy similarity | 1 | |
Modified residuei | 329 | N6-succinyllysineBy similarity | 1 | |
Cross-linki | 522 ↔ 523 | Cysteinyl-selenocysteine (Cys-Sec)By similarity |
Keywords - PTMi
Disulfide bondProteomic databases
EPDi | Q9NNW7 |
jPOSTi | Q9NNW7 |
MassIVEi | Q9NNW7 |
MaxQBi | Q9NNW7 |
PaxDbi | Q9NNW7 |
PeptideAtlasi | Q9NNW7 |
PRIDEi | Q9NNW7 |
ProteomicsDBi | 81857 [Q9NNW7-1] 81858 [Q9NNW7-2] 81859 [Q9NNW7-3] 81860 [Q9NNW7-4] |
PTM databases
iPTMneti | Q9NNW7 |
PhosphoSitePlusi | Q9NNW7 |
SwissPalmi | Q9NNW7 |
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
Bgeei | ENSG00000184470, Expressed in right lobe of liver and 222 other tissues |
ExpressionAtlasi | Q9NNW7, baseline and differential |
Organism-specific databases
HPAi | ENSG00000184470, Low tissue specificity |
Interactioni
Subunit structurei
Homodimer.
By similarityProtein-protein interaction databases
BioGRIDi | 115836, 44 interactors |
IntActi | Q9NNW7, 7 interactors |
MINTi | Q9NNW7 |
STRINGi | 9606.ENSP00000383365 |
Chemistry databases
BindingDBi | Q9NNW7 |
Miscellaneous databases
RNActi | Q9NNW7, protein |
Family & Domainsi
Sequence similaritiesi
Belongs to the class-I pyridine nucleotide-disulfide oxidoreductase family.Curated
Keywords - Domaini
Redox-active center, Transit peptidePhylogenomic databases
eggNOGi | KOG4716, Eukaryota |
GeneTreei | ENSGT00940000158832 |
InParanoidi | Q9NNW7 |
OMAi | GLECACF |
OrthoDBi | 581771at2759 |
PhylomeDBi | Q9NNW7 |
TreeFami | TF314782 |
Family and domain databases
Gene3Di | 3.30.390.30, 1 hit 3.50.50.60, 2 hits |
InterProi | View 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 |
Pfami | View protein in Pfam PF07992, Pyr_redox_2, 1 hit PF02852, Pyr_redox_dim, 1 hit |
PIRSFi | PIRSF000350, Mercury_reductase_MerA, 1 hit |
SUPFAMi | SSF51905, SSF51905, 1 hit SSF55424, SSF55424, 1 hit |
TIGRFAMsi | TIGR01438, TGR, 1 hit |
PROSITEi | View protein in PROSITE PS00076, PYRIDINE_REDOX_1, 1 hit |
s (4+)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry describes 4 produced by isoformsialternative splicing. AlignAdd to basketThis 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 sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
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
Computationally mapped potential isoform sequencesi
There are 11 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketD3YTF8 | D3YTF8_HUMAN | Thioredoxin-disulfide reductase | TXNRD2 | 501 | Annotation score: | ||
A0A182DWF2 | A0A182DWF2_HUMAN | Thioredoxin-disulfide reductase | TXNRD2 | 494 | Annotation score: | ||
A0A182DWF3 | A0A182DWF3_HUMAN | Thioredoxin-disulfide reductase | TXNRD2 | 523 | Annotation score: | ||
A0A096LPK7 | A0A096LPK7_HUMAN | Thioredoxin-disulfide reductase | TXNRD2 | 463 | Annotation score: | ||
E7EWK1 | E7EWK1_HUMAN | Thioredoxin reductase 2, mitochondr... | TXNRD2 | 338 | Annotation score: | ||
A0A096LPD9 | A0A096LPD9_HUMAN | Thioredoxin reductase 2, mitochondr... | TXNRD2 | 306 | Annotation score: | ||
A0A096LPH4 | A0A096LPH4_HUMAN | Thioredoxin reductase 2, mitochondr... | TXNRD2 | 165 | Annotation score: | ||
A0A096LPB7 | A0A096LPB7_HUMAN | Thioredoxin reductase 2, mitochondr... | TXNRD2 | 180 | Annotation score: | ||
A0A096LP96 | A0A096LP96_HUMAN | Thioredoxin reductase 2, mitochondr... | TXNRD2 | 212 | Annotation score: | ||
A0A0U1RQX0 | A0A0U1RQX0_HUMAN | Thioredoxin reductase 2, mitochondr... | TXNRD2 | 362 | Annotation 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. Truncated C-terminus.Curated
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 33 | Missing in AAG47635 (Ref. 6) Curated | 1 | |
Sequence conflicti | 285 | R → K in AAG47635 (Ref. 6) Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_051777 | 14 | R → L. Corresponds to variant dbSNP:rs45593642Ensembl. | 1 | |
Natural variantiVAR_051778 | 66 | A → S4 PublicationsCorresponds to variant dbSNP:rs5748469EnsemblClinVar. | 1 | |
Natural variantiVAR_051779 | 299 | S → R1 PublicationCorresponds to variant dbSNP:rs5992495EnsemblClinVar. | 1 | |
Natural variantiVAR_051780 | 370 | I → T4 PublicationsCorresponds to variant dbSNP:rs1139793EnsemblClinVar. | 1 | |
Natural variantiVAR_080529 | 447 – 524 | Missing in GCCD5; the mutant protein is undetectable in patient cells. 1 PublicationAdd BLAST | 78 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_008306 | 1 – 247 | Missing in isoform 4. 1 PublicationAdd BLAST | 247 | |
Alternative sequenceiVSP_008305 | 1 – 96 | Missing in isoform 3. 1 PublicationAdd BLAST | 96 | |
Alternative sequenceiVSP_008304 | 1 – 30 | MAAMA…VRGAA → MEDQ in isoform 2. CuratedAdd BLAST | 30 |
Non-standard residue
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Non-standard residuei | 523 | Selenocysteine | 1 |
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 |
CCDSi | CCDS42981.1 [Q9NNW7-1] CCDS86998.1 [Q9NNW7-3] |
RefSeqi | NP_006431.2, NM_006440.4 [Q9NNW7-1] |
Genome annotation databases
Ensembli | ENST00000400521; ENSP00000383365; ENSG00000184470 [Q9NNW7-1] ENST00000542719; ENSP00000485128; ENSG00000184470 [Q9NNW7-3] |
GeneIDi | 10587 |
KEGGi | hsa:10587 |
Keywords - Coding sequence diversityi
Alternative splicing, SelenocysteineSimilar 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 |
CCDSi | CCDS42981.1 [Q9NNW7-1] CCDS86998.1 [Q9NNW7-3] |
RefSeqi | NP_006431.2, NM_006440.4 [Q9NNW7-1] |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
1W1E | model | - | A/B | 36-524 | [»] | |
SMRi | Q9NNW7 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 115836, 44 interactors |
IntActi | Q9NNW7, 7 interactors |
MINTi | Q9NNW7 |
STRINGi | 9606.ENSP00000383365 |
Chemistry databases
BindingDBi | Q9NNW7 |
ChEMBLi | CHEMBL2403 |
DrugBanki | DB05428, Motexafin gadolinium |
PTM databases
iPTMneti | Q9NNW7 |
PhosphoSitePlusi | Q9NNW7 |
SwissPalmi | Q9NNW7 |
Genetic variation databases
BioMutai | TXNRD2 |
DMDMi | 182705230 |
Proteomic databases
EPDi | Q9NNW7 |
jPOSTi | Q9NNW7 |
MassIVEi | Q9NNW7 |
MaxQBi | Q9NNW7 |
PaxDbi | Q9NNW7 |
PeptideAtlasi | Q9NNW7 |
PRIDEi | Q9NNW7 |
ProteomicsDBi | 81857 [Q9NNW7-1] 81858 [Q9NNW7-2] 81859 [Q9NNW7-3] 81860 [Q9NNW7-4] |
Protocols and materials databases
Antibodypediai | 230, 244 antibodies |
DNASUi | 10587 |
Genome annotation databases
Ensembli | ENST00000400521; ENSP00000383365; ENSG00000184470 [Q9NNW7-1] ENST00000542719; ENSP00000485128; ENSG00000184470 [Q9NNW7-3] |
GeneIDi | 10587 |
KEGGi | hsa:10587 |
Organism-specific databases
CTDi | 10587 |
DisGeNETi | 10587 |
GeneCardsi | TXNRD2 |
HGNCi | HGNC:18155, TXNRD2 |
HPAi | ENSG00000184470, Low tissue specificity |
MalaCardsi | TXNRD2 |
MIMi | 606448, gene 617825, phenotype |
neXtProti | NX_Q9NNW7 |
OpenTargetsi | ENSG00000184470 |
Orphaneti | 361, Familial glucocorticoid deficiency 154, Familial isolated dilated cardiomyopathy |
PharmGKBi | PA38302 |
VEuPathDBi | HostDB:ENSG00000184470.20 |
HUGEi | Search... |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG4716, Eukaryota |
GeneTreei | ENSGT00940000158832 |
InParanoidi | Q9NNW7 |
OMAi | GLECACF |
OrthoDBi | 581771at2759 |
PhylomeDBi | Q9NNW7 |
TreeFami | TF314782 |
Enzyme and pathway databases
BRENDAi | 1.8.1.9, 2681 |
PathwayCommonsi | Q9NNW7 |
Reactomei | R-HSA-3299685, Detoxification of Reactive Oxygen Species |
Miscellaneous databases
BioGRID-ORCSi | 10587, 16 hits in 879 CRISPR screens |
ChiTaRSi | TXNRD2, human |
GenomeRNAii | 10587 |
Pharosi | Q9NNW7, Tbio |
PROi | PR:Q9NNW7 |
RNActi | Q9NNW7, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000184470, Expressed in right lobe of liver and 222 other tissues |
ExpressionAtlasi | Q9NNW7, baseline and differential |
Family and domain databases
Gene3Di | 3.30.390.30, 1 hit 3.50.50.60, 2 hits |
InterProi | View 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 |
Pfami | View protein in Pfam PF07992, Pyr_redox_2, 1 hit PF02852, Pyr_redox_dim, 1 hit |
PIRSFi | PIRSF000350, Mercury_reductase_MerA, 1 hit |
SUPFAMi | SSF51905, SSF51905, 1 hit SSF55424, SSF55424, 1 hit |
TIGRFAMsi | TIGR01438, TGR, 1 hit |
PROSITEi | View protein in PROSITE PS00076, PYRIDINE_REDOX_1, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | TRXR2_HUMAN | |
Accessioni | Q9NNW7Primary (citable) accession number: Q9NNW7 Secondary accession number(s): O95840 Q9UQU8 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | September 19, 2003 |
Last sequence update: | February 26, 2008 | |
Last modified: | February 10, 2021 | |
This is version 197 of the entry and version 3 of the sequence. See complete history. | ||
Entry statusi | 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. |
Miscellaneousi
Keywords - Technical termi
3D-structure, Reference proteomeDocuments
- Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families - Human chromosome 22
Human chromosome 22: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants