Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Thioredoxin

Gene

TXN

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

Functioni

Participates in various redox reactions through the reversible oxidation of its active center dithiol to a disulfide and catalyzes dithiol-disulfide exchange reactions. Plays a role in the reversible S-nitrosylation of cysteine residues in target proteins, and thereby contributes to the response to intracellular nitric oxide. Nitrosylates the active site Cys of CASP3 in response to nitric oxide (NO), and thereby inhibits caspase-3 activity. Induces the FOS/JUN AP-1 DNA-binding activity in ionizing radiation (IR) cells through its oxidation/reduction status and stimulates AP-1 transcriptional activity.
ADF augments the expression of the interleukin-2 receptor TAC (IL2R/P55).

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei26Deprotonates C-terminal active site Cys1
Active sitei32Nucleophile1
Sitei33Contributes to redox potential value1
Sitei34Contributes to redox potential value1
Active sitei35Nucleophile1

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionActivator
Biological processElectron transport, Transcription, Transcription regulation, Transport

Enzyme and pathway databases

ReactomeiR-HSA-2559580 Oxidative Stress Induced Senescence
R-HSA-3299685 Detoxification of Reactive Oxygen Species
R-HSA-499943 Interconversion of nucleotide di- and triphosphates
R-HSA-5628897 TP53 Regulates Metabolic Genes
R-HSA-5676934 Protein repair
R-HSA-844456 The NLRP3 inflammasome
SignaLinkiP10599
SIGNORiP10599

Names & Taxonomyi

Protein namesi
Recommended name:
Thioredoxin
Short name:
Trx
Alternative name(s):
ATL-derived factor
Short name:
ADF
Surface-associated sulphydryl protein
Short name:
SASP
Gene namesi
Name:TXN
Synonyms:TRDX, TRX, TRX1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 9

Organism-specific databases

EuPathDBiHostDB:ENSG00000136810.12
HGNCiHGNC:12435 TXN
MIMi187700 gene
neXtProtiNX_P10599

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

Cytoplasm, Nucleus, Secreted

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi32C → S: Loses its reducing activity, interaction with APEX1 and transcription activation; when associated with S-35. 1 Publication1
Mutagenesisi35C → S: Loses its reducing activity, interaction with APEX1 and transcription activation; when associated with S-32. 1 Publication1
Mutagenesisi60D → N: Loss of pH-dependence of dimerization. 1
Mutagenesisi62C → S: Retains its reducing activity. Retains interaction with APEX1 and transcription activation; when associated with S-69 and S-73. 1 Publication1
Mutagenesisi69C → S: No effect on reducing activity, interaction with APEX1 and on S-nitrosylation of C-73. Retains interaction with APEX1 and transcription activation; when associated with S-62 and S-73. 2 Publications1
Mutagenesisi70E → A: Strongly reduced interaction with CASP3; when associated with A-72. 1 Publication1
Mutagenesisi72K → A: Strongly reduced interaction with CASP3; when associated with A-70. 1 Publication1
Mutagenesisi73C → D: Strongly reduced S-nitrosylation of CASP3. 3 Publications1
Mutagenesisi73C → S: Loss of nitrosylation, and loss of S-nitrosylating activity towards CASP3. Retains interaction with APEX1 and transcription activation; when associated with S-62 and S-69. 3 Publications1
Mutagenesisi73C → S: Retains its reducing activity. 3 Publications1

Organism-specific databases

DisGeNETi7295
OpenTargetsiENSG00000136810
PharmGKBiPA37091

Protein family/group databases

Allergomei3543 Hom s Trx

Chemistry databases

ChEMBLiCHEMBL2010624

Polymorphism and mutation databases

BioMutaiTXN
DMDMi135773

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemoved2 Publications
ChainiPRO_00001200052 – 105ThioredoxinAdd BLAST104

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei3N6-acetyllysineCombined sources1
Modified residuei8N6-succinyllysineBy similarity1
Disulfide bondi32 ↔ 35Redox-activePROSITE-ProRule annotation2 Publications
Modified residuei39N6-acetyllysineCombined sources1
Modified residuei62S-nitrosocysteine1 Publication1
Modified residuei69S-nitrosocysteine1 Publication1
Modified residuei73S-nitrosocysteine; alternate2 Publications1
Disulfide bondi73Interchain; alternate1 Publication
Modified residuei94N6-acetyllysine; alternateBy similarity1
Modified residuei94N6-succinyllysine; alternateBy similarity1

Post-translational modificationi

In the fully reduced protein, both Cys-69 and Cys-73 are nitrosylated in response to nitric oxide (NO). When two disulfide bonds are present in the protein, only Cys-73 is nitrosylated. Cys-73 can serve as donor for nitrosylation of target proteins.4 Publications
In case of infection, ubiquitinated by S.typhimurium protein slrP, leading to its degradation.1 Publication

Keywords - PTMi

Acetylation, Disulfide bond, S-nitrosylation, Ubl conjugation

Proteomic databases

EPDiP10599
MaxQBiP10599
PaxDbiP10599
PeptideAtlasiP10599
PRIDEiP10599
ProteomicsDBi12706
52616
TopDownProteomicsiP10599-1 [P10599-1]
P10599-2 [P10599-2]

2D gel databases

DOSAC-COBS-2DPAGEiP10599
REPRODUCTION-2DPAGEiIPI00216298
SWISS-2DPAGEiP10599

PTM databases

CarbonylDBiP10599
iPTMnetiP10599
PhosphoSitePlusiP10599
SwissPalmiP10599

Expressioni

Inductioni

Up-regulated by ionizing radiation.1 Publication

Gene expression databases

BgeeiENSG00000136810 Expressed in 233 organ(s), highest expression level in mouth mucosa
CleanExiHS_TXN
ExpressionAtlasiP10599 baseline and differential
GenevisibleiP10599 HS

Organism-specific databases

HPAiCAB008678
HPA047478
HPA055752

Interactioni

Subunit structurei

Homodimer; disulfide-linked. Interacts with TXNIP through the redox-active site. Interacts with MAP3K5 and CASP3. In case of infection, interacts with S.typhimurium protein slrP. Interacts with APEX1; the interaction stimulates the FOS/JUN AP-1 DNA-binding activity in a redox-dependent manner.5 Publications

Binary interactionsi

Protein-protein interaction databases

BioGridi113146, 128 interactors
DIPiDIP-6129N
IntActiP10599, 64 interactors
MINTiP10599
STRINGi9606.ENSP00000363641

Chemistry databases

BindingDBiP10599

Structurei

Secondary structure

1105
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliP10599
SMRiP10599
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP10599

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini2 – 105ThioredoxinPROSITE-ProRule annotationAdd BLAST104

Sequence similaritiesi

Belongs to the thioredoxin family.Curated

Keywords - Domaini

Redox-active center

Phylogenomic databases

eggNOGiKOG0907 Eukaryota
COG0526 LUCA
GeneTreeiENSGT00530000063008
HOGENOMiHOG000292977
HOVERGENiHBG009243
InParanoidiP10599
KOiK03671
OMAiSKYAFQE
OrthoDBiEOG091G01FG
PhylomeDBiP10599
TreeFamiTF318932

Family and domain databases

InterProiView protein in InterPro
IPR005746 Thioredoxin
IPR036249 Thioredoxin-like_sf
IPR017937 Thioredoxin_CS
IPR013766 Thioredoxin_domain
PANTHERiPTHR10438 PTHR10438, 1 hit
PfamiView protein in Pfam
PF00085 Thioredoxin, 1 hit
PIRSFiPIRSF000077 Thioredoxin, 1 hit
SUPFAMiSSF52833 SSF52833, 1 hit
PROSITEiView protein in PROSITE
PS00194 THIOREDOXIN_1, 1 hit
PS51352 THIOREDOXIN_2, 1 hit

Sequences (2)i

Sequence statusi: Complete.

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

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket
Isoform 1 (identifier: P10599-1) [UniParc]FASTAAdd to basket

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
MVKQIESKTA FQEALDAAGD KLVVVDFSAT WCGPCKMIKP FFHSLSEKYS
60 70 80 90 100
NVIFLEVDVD DCQDVASECE VKCMPTFQFF KKGQKVGEFS GANKEKLEAT

INELV
Length:105
Mass (Da):11,737
Last modified:January 23, 2007 - v3
Checksum:i256F4E3C8A187693
GO
Isoform 2 (identifier: P10599-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     44-63: Missing.

Show »
Length:85
Mass (Da):9,452
Checksum:i3CC6254BD6A1D66F
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti39K → N in AAA74596 (PubMed:3170595).Curated1
Sequence conflicti39K → N in AAF86466 (Ref. 4) Curated1
Sequence conflicti74M → T in AAA74596 (PubMed:3170595).Curated1
Sequence conflicti74M → T in AAF86466 (Ref. 4) Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_04560744 – 63Missing in isoform 2. 1 PublicationAdd BLAST20

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
J04026 mRNA Translation: AAA74596.1
X77584 mRNA Translation: CAA54687.1
X54539, X54540, X54541 Genomic DNA Translation: CAA38410.1
AF276919 mRNA Translation: AAF86466.1
AY004872 mRNA Translation: AAF87085.1
AF313911 mRNA Translation: AAG34699.1
AK289508 mRNA Translation: BAF82197.1
CR407665 mRNA Translation: CAG28593.1
AF548001 Genomic DNA Translation: AAN33187.1
AL158158 Genomic DNA No translation available.
CH471105 Genomic DNA Translation: EAW59059.1
CH471105 Genomic DNA Translation: EAW59060.1
BC003377 mRNA Translation: AAH03377.1
BC054866 mRNA Translation: AAH54866.1
AF065241 mRNA Translation: AAC17430.1
CCDSiCCDS35103.1 [P10599-1]
CCDS59139.1 [P10599-2]
PIRiJH0568
RefSeqiNP_001231867.1, NM_001244938.1 [P10599-2]
NP_003320.2, NM_003329.3 [P10599-1]
UniGeneiHs.435136

Genome annotation databases

EnsembliENST00000374515; ENSP00000363639; ENSG00000136810 [P10599-2]
ENST00000374517; ENSP00000363641; ENSG00000136810 [P10599-1]
GeneIDi7295
KEGGihsa:7295
UCSCiuc004bep.3 human [P10599-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Cross-referencesi

Web resourcesi

NIEHS-SNPs
Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
J04026 mRNA Translation: AAA74596.1
X77584 mRNA Translation: CAA54687.1
X54539, X54540, X54541 Genomic DNA Translation: CAA38410.1
AF276919 mRNA Translation: AAF86466.1
AY004872 mRNA Translation: AAF87085.1
AF313911 mRNA Translation: AAG34699.1
AK289508 mRNA Translation: BAF82197.1
CR407665 mRNA Translation: CAG28593.1
AF548001 Genomic DNA Translation: AAN33187.1
AL158158 Genomic DNA No translation available.
CH471105 Genomic DNA Translation: EAW59059.1
CH471105 Genomic DNA Translation: EAW59060.1
BC003377 mRNA Translation: AAH03377.1
BC054866 mRNA Translation: AAH54866.1
AF065241 mRNA Translation: AAC17430.1
CCDSiCCDS35103.1 [P10599-1]
CCDS59139.1 [P10599-2]
PIRiJH0568
RefSeqiNP_001231867.1, NM_001244938.1 [P10599-2]
NP_003320.2, NM_003329.3 [P10599-1]
UniGeneiHs.435136

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1AIUX-ray2.00A1-105[»]
1AUCX-ray2.10A1-105[»]
1CQGNMR-A1-105[»]
1CQHNMR-A1-105[»]
1ERTX-ray1.70A1-105[»]
1ERUX-ray2.10A1-105[»]
1ERVX-ray1.65A1-105[»]
1ERWX-ray1.80A1-105[»]
1M7TNMR-A1-66[»]
1MDINMR-A1-105[»]
1MDJNMR-A1-105[»]
1MDKNMR-A1-105[»]
1TRSNMR-A1-105[»]
1TRUNMR-A1-105[»]
1TRVNMR-A1-105[»]
1TRWNMR-A1-105[»]
1W1Cmodel-C1-105[»]
1W1Emodel-C1-105[»]
2HSHX-ray1.35A1-105[»]
2HXKX-ray1.65A/B/C1-105[»]
2IFQX-ray1.20A/B/C1-105[»]
2IIYX-ray1.70A1-105[»]
3E3EX-ray2.01A/B1-105[»]
3KD0X-ray1.70A1-105[»]
3M9JX-ray1.10A/B1-105[»]
3M9KX-ray1.50A/B1-105[»]
3QFAX-ray2.20C/D2-105[»]
3QFBX-ray2.60C/D2-105[»]
3TRXNMR-A1-105[»]
4LL1X-ray2.00B/D1-105[»]
4LL4X-ray2.70B/D1-105[»]
4OO4X-ray0.97A/B1-105[»]
4OO5X-ray1.54A1-105[»]
4POKX-ray2.52A/B/C/D1-105[»]
4POLX-ray2.80A/B/C/D1-105[»]
4POMX-ray1.85A/B/C/D1-105[»]
4PUFX-ray3.30C/D1-105[»]
4TRXNMR-A1-105[»]
5DQYX-ray1.40A1-105[»]
ProteinModelPortaliP10599
SMRiP10599
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi113146, 128 interactors
DIPiDIP-6129N
IntActiP10599, 64 interactors
MINTiP10599
STRINGi9606.ENSP00000363641

Chemistry databases

BindingDBiP10599
ChEMBLiCHEMBL2010624

Protein family/group databases

Allergomei3543 Hom s Trx

PTM databases

CarbonylDBiP10599
iPTMnetiP10599
PhosphoSitePlusiP10599
SwissPalmiP10599

Polymorphism and mutation databases

BioMutaiTXN
DMDMi135773

2D gel databases

DOSAC-COBS-2DPAGEiP10599
REPRODUCTION-2DPAGEiIPI00216298
SWISS-2DPAGEiP10599

Proteomic databases

EPDiP10599
MaxQBiP10599
PaxDbiP10599
PeptideAtlasiP10599
PRIDEiP10599
ProteomicsDBi12706
52616
TopDownProteomicsiP10599-1 [P10599-1]
P10599-2 [P10599-2]

Protocols and materials databases

DNASUi7295
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000374515; ENSP00000363639; ENSG00000136810 [P10599-2]
ENST00000374517; ENSP00000363641; ENSG00000136810 [P10599-1]
GeneIDi7295
KEGGihsa:7295
UCSCiuc004bep.3 human [P10599-1]

Organism-specific databases

CTDi7295
DisGeNETi7295
EuPathDBiHostDB:ENSG00000136810.12
GeneCardsiTXN
HGNCiHGNC:12435 TXN
HPAiCAB008678
HPA047478
HPA055752
MIMi187700 gene
neXtProtiNX_P10599
OpenTargetsiENSG00000136810
PharmGKBiPA37091
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0907 Eukaryota
COG0526 LUCA
GeneTreeiENSGT00530000063008
HOGENOMiHOG000292977
HOVERGENiHBG009243
InParanoidiP10599
KOiK03671
OMAiSKYAFQE
OrthoDBiEOG091G01FG
PhylomeDBiP10599
TreeFamiTF318932

Enzyme and pathway databases

ReactomeiR-HSA-2559580 Oxidative Stress Induced Senescence
R-HSA-3299685 Detoxification of Reactive Oxygen Species
R-HSA-499943 Interconversion of nucleotide di- and triphosphates
R-HSA-5628897 TP53 Regulates Metabolic Genes
R-HSA-5676934 Protein repair
R-HSA-844456 The NLRP3 inflammasome
SignaLinkiP10599
SIGNORiP10599

Miscellaneous databases

ChiTaRSiTXN human
EvolutionaryTraceiP10599
GeneWikiiThioredoxin
GenomeRNAii7295
PROiPR:P10599
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000136810 Expressed in 233 organ(s), highest expression level in mouth mucosa
CleanExiHS_TXN
ExpressionAtlasiP10599 baseline and differential
GenevisibleiP10599 HS

Family and domain databases

InterProiView protein in InterPro
IPR005746 Thioredoxin
IPR036249 Thioredoxin-like_sf
IPR017937 Thioredoxin_CS
IPR013766 Thioredoxin_domain
PANTHERiPTHR10438 PTHR10438, 1 hit
PfamiView protein in Pfam
PF00085 Thioredoxin, 1 hit
PIRSFiPIRSF000077 Thioredoxin, 1 hit
SUPFAMiSSF52833 SSF52833, 1 hit
PROSITEiView protein in PROSITE
PS00194 THIOREDOXIN_1, 1 hit
PS51352 THIOREDOXIN_2, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiTHIO_HUMAN
AccessioniPrimary (citable) accession number: P10599
Secondary accession number(s): B1ALW1
, O60744, Q53X69, Q96KI3, Q9UDG5
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 1, 1989
Last sequence update: January 23, 2007
Last modified: September 12, 2018
This is version 218 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, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 9
    Human chromosome 9: entries, gene names and cross-references to MIM
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. SIMILARITY comments
    Index of protein domains and families
  4. UniProtKB entry view manual
    User manual for the UniProtKB entry view
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

We'd like to inform you that we have updated our Privacy Notice to comply with Europe’s new General Data Protection Regulation (GDPR) that applies since 25 May 2018.

Do not show this banner again