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Protein

Thioredoxin reductase 1, mitochondrial

Gene

Trxr-1

Organism
Drosophila melanogaster (Fruit fly)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Thioredoxin system is a major player in glutathione metabolism, due to the demonstrated absence of a glutathione reductase. Functionally interacts with the Sod/Cat reactive oxidation species (ROS) defense system and thereby has a role in preadult development and life span. Lack of a glutathione reductase suggests antioxidant defense in Drosophila, and probably in related insects, differs fundamentally from that in other organisms.3 Publications

Catalytic activityi

Thioredoxin + NADP+ = thioredoxin disulfide + NADPH.1 Publication

Cofactori

FADNote: Binds 1 FAD per subunit.

Kineticsi

Measurements were conducted with isoform A unless noted otherwise.

  1. KM=6.5 µM for NADPH (at pH 7.4)7 Publications
  2. KM=1 µM for NADPH (at pH 7.4, 2 mM EDTA, 100 mM KPO4)7 Publications
  3. KM=1 µM for NADPH (isoform B at pH 7.4, 2 mM EDTA, 100 mM KPO4)7 Publications
  4. KM=7.0 µM for dhd (at pH 7.4, 200 µM NADPH, 100 mM KPO4)7 Publications
  5. KM=141 µM for dhd (at pH 7.0, 0.15 mM NADPH, 1 mM EDTA, 1 mg/ml insulin, 50 mM KPO4, 25 degrees Celsius)7 Publications
  6. KM=7 µM for dhd (at pH 7.4, 2 mM EDTA, 100 mM KPO4)7 Publications
  7. KM=19 µM for dhd (isoform B at pH 7.4, 2 mM EDTA, 100 mM KPO4)7 Publications
  8. KM=5.9 µM for Trx-2 (at pH 7.4, 100 µM NADPH, 2 mM EDTA, 100 mM KPO4)7 Publications
  9. KM=310 µM for 5,5'-dithiobis-2-nitrobenzoic acid (DTNB) (at pH 7.4, 100 µM NADPH, 100 mM KPO4)7 Publications
  10. KM=0.17 mM for DTNB (at pH 7.0, 0.2 mM NADPH, 10 mM EDTA, 100 mM KPO4, 25 degrees Celsius)7 Publications
  11. KM=380 µM for DTNB (at pH 7.4, 2 mM EDTA, 100 mM KPO4)7 Publications
  12. KM=410 µM for DTNB (isoform B at pH 7.4, 2 mM EDTA, 100 mM KPO4)7 Publications
  13. KM=675 µM for methylseleninate (100 µM NADPH)7 Publications
  1. Vmax=24.3 µmol/min/mg enzyme toward NADPH (at pH 7.4)7 Publications
  2. Vmax=16 µmol/min/mg enzyme toward Trx-2 (at pH 7.4, 100 µM NADPH, 2 mM EDTA, 100 mM KPO4, 25 degrees Celsius)7 Publications

pH dependencei

Optimum pH is 7.6 for isoform A with Trx-2 and NADPH as substrates.7 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei282FAD1 Publication1
Binding sitei286FAD1 Publication1
Binding sitei302FAD1 Publication1
Binding sitei355NADP1 Publication1
Binding sitei472FAD1 Publication1
Active sitei569Proton acceptor1 Publication1
Binding sitei570FAD1 Publication1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi120 – 126FAD1 Publication7
Nucleotide bindingi143 – 147FAD1 Publication5
Nucleotide bindingi159 – 170FAD1 PublicationAdd BLAST12
Nucleotide bindingi233 – 235FAD1 Publication3
Nucleotide bindingi262 – 266FAD1 Publication5
Nucleotide bindingi322 – 328NADP1 Publication7
Nucleotide bindingi392 – 399FAD1 Publication8
Nucleotide bindingi429 – 432FAD1 Publication4
Nucleotide bindingi438 – 443FAD1 Publication6

GO - Molecular functioni

  • antioxidant activity Source: UniProtKB
  • flavin adenine dinucleotide binding Source: InterPro
  • glutathione-disulfide reductase activity Source: FlyBase
  • protein homodimerization activity Source: FlyBase
  • thioredoxin-disulfide reductase activity Source: UniProtKB

GO - Biological processi

  • cell redox homeostasis Source: UniProtKB
  • cellular response to DNA damage stimulus Source: FlyBase
  • determination of adult lifespan Source: FlyBase
  • neurogenesis Source: FlyBase
  • response to hypoxia Source: FlyBase
  • sensory perception of pain Source: FlyBase
Complete GO annotation...

Keywords - Molecular functioni

Oxidoreductase

Keywords - Ligandi

FAD, Flavoprotein, NADP, Nucleotide-binding

Enzyme and pathway databases

BRENDAi1.8.1.9. 1994.
ReactomeiR-DME-3299685. Detoxification of Reactive Oxygen Species.

Names & Taxonomyi

Protein namesi
Recommended name:
Thioredoxin reductase 1, mitochondrial (EC:1.8.1.9)
Short name:
TrxR-1
Gene namesi
Name:Trxr-1
Synonyms:GR
ORF Names:CG2151
OrganismiDrosophila melanogaster (Fruit fly)
Taxonomic identifieri7227 [NCBI]
Taxonomic lineageiEukaryotaMetazoaEcdysozoaArthropodaHexapodaInsectaPterygotaNeopteraEndopterygotaDipteraBrachyceraMuscomorphaEphydroideaDrosophilidaeDrosophilaSophophora
Proteomesi
  • UP000000803 Componenti: Chromosome X

Organism-specific databases

FlyBaseiFBgn0020653. Trxr-1.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • cytosol Source: FlyBase
  • microtubule associated complex Source: FlyBase
  • mitochondrion Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Mitochondrion

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi569H → Q: Almost complete loss of TrX reduction. 1 Publication1
Mutagenesisi574E → A: Reduced Trx reduction. 1 Publication1
Mutagenesisi574E → Q: Reduced Trx reduction. 1 Publication1
Mutagenesisi594C → S: Loss of Trx reduction. 1 Publication1
Mutagenesisi595C → S: Loss of Trx reduction. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_0000030291? – 596Thioredoxin reductase 1, mitochondrial
Transit peptidei1 – ?MitochondrionSequence analysis

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi162 ↔ 167Redox-active1 Publication
Disulfide bondi594 ↔ 595Redox-active1 Publication

Keywords - PTMi

Disulfide bond

Proteomic databases

PaxDbiP91938.
PRIDEiP91938.

Expressioni

Tissue specificityi

During embryogenesis, expression is seen in germ cell progenitors, developing midgut, hindgut and proventriculus.1 Publication

Developmental stagei

Expressed both maternally and zygotically during all stages of development, highest expression during adult stages.2 Publications

Gene expression databases

BgeeiFBgn0020653.
GenevisibleiP91938. DM.

Interactioni

Subunit structurei

Homodimer.1 Publication

GO - Molecular functioni

  • protein homodimerization activity Source: FlyBase

Protein-protein interaction databases

BioGridi58221. 32 interactors.
DIPiDIP-19145N.
IntActiP91938. 12 interactors.
MINTiMINT-916376.
STRINGi7227.FBpp0071116.

Structurei

Secondary structure

1596
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi114 – 120Combined sources7
Helixi124 – 135Combined sources12
Beta strandi140 – 143Combined sources4
Turni150 – 152Combined sources3
Helixi161 – 165Combined sources5
Helixi167 – 188Combined sources22
Helixi201 – 225Combined sources25
Beta strandi229 – 231Combined sources3
Beta strandi233 – 239Combined sources7
Beta strandi242 – 246Combined sources5
Beta strandi252 – 261Combined sources10
Beta strandi265 – 267Combined sources3
Helixi275 – 278Combined sources4
Helixi282 – 285Combined sources4
Beta strandi294 – 298Combined sources5
Helixi302 – 313Combined sources12
Beta strandi317 – 324Combined sources8
Helixi332 – 344Combined sources13
Beta strandi349 – 351Combined sources3
Beta strandi353 – 360Combined sources8
Beta strandi366 – 372Combined sources7
Turni373 – 375Combined sources3
Beta strandi378 – 388Combined sources11
Beta strandi392 – 394Combined sources3
Helixi397 – 399Combined sources3
Helixi401 – 403Combined sources3
Beta strandi409 – 413Combined sources5
Beta strandi426 – 428Combined sources3
Helixi430 – 432Combined sources3
Helixi440 – 455Combined sources16
Beta strandi469 – 471Combined sources3
Beta strandi473 – 481Combined sources9
Helixi484 – 491Combined sources8
Helixi493 – 495Combined sources3
Beta strandi496 – 502Combined sources7
Helixi506 – 508Combined sources3
Turni509 – 512Combined sources4
Beta strandi519 – 527Combined sources9
Beta strandi531 – 539Combined sources9
Helixi542 – 554Combined sources13
Helixi559 – 563Combined sources5
Helixi573 – 578Combined sources6
Turni583 – 585Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2NVKX-ray2.40X111-593[»]
3DGHX-ray1.75A/B111-588[»]
3DH9X-ray2.25A/B111-591[»]
ProteinModelPortaliP91938.
SMRiP91938.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP91938.

Family & Domainsi

Sequence similaritiesi

Keywords - Domaini

Redox-active center, Transit peptide

Phylogenomic databases

eggNOGiKOG0405. Eukaryota.
COG1249. LUCA.
GeneTreeiENSGT00390000007578.
InParanoidiP91938.
KOiK00384.
OMAiEIEVFHG.
OrthoDBiEOG091G03IU.
PhylomeDBiP91938.

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 and alternative initiation. AlignAdd to basket

Isoform B (identifier: P91938-1) [UniParc]FASTAAdd to basket
Also known as: Mito

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
MNLCNSRFSV TFVRQCSTIL TSPSAGIIQN RGSLTTKVPH WISSSLSCAH
60 70 80 90 100
HTFQRTMNLT GQRGSRDSTG ATGGNAPAGS GAGAPPPFQH PHCDRAAMYA
110 120 130 140 150
QPVRKMSTKG GSYDYDLIVI GGGSAGLACA KEAVLNGARV ACLDFVKPTP
160 170 180 190 200
TLGTKWGVGG TCVNVGCIPK KLMHQASLLG EAVHEAAAYG WNVDEKIKPD
210 220 230 240 250
WHKLVQSVQN HIKSVNWVTR VDLRDKKVEY INGLGSFVDS HTLLAKLKSG
260 270 280 290 300
ERTITAQTFV IAVGGRPRYP DIPGAVEYGI TSDDLFSLDR EPGKTLVVGA
310 320 330 340 350
GYIGLECAGF LKGLGYEPTV MVRSIVLRGF DQQMAELVAA SMEERGIPFL
360 370 380 390 400
RKTVPLSVEK QDDGKLLVKY KNVETGEEAE DVYDTVLWAI GRKGLVDDLN
410 420 430 440 450
LPNAGVTVQK DKIPVDSQEA TNVANIYAVG DIIYGKPELT PVAVLAGRLL
460 470 480 490 500
ARRLYGGSTQ RMDYKDVATT VFTPLEYACV GLSEEDAVKQ FGADEIEVFH
510 520 530 540 550
GYYKPTEFFI PQKSVRYCYL KAVAERHGDQ RVYGLHYIGP VAGEVIQGFA
560 570 580 590
AALKSGLTIN TLINTVGIHP TTAEEFTRLA ITKRSGLDPT PASCCS
Note: Can partially substitute for the cytoplasmic enzyme activity.
Length:596
Mass (Da):64,322
Last modified:January 27, 2003 - v2
Checksum:i8DA6FC08CF6A7292
GO
Isoform A (identifier: P91938-2) [UniParc]FASTAAdd to basket
Also known as: Cyto

The sequence of this isoform differs from the canonical sequence as follows:
     1-105: Missing.
     106-110: MSTKG → MAPVQ

Note: Unable to compensate for the loss of the mitochondrial enzyme activity.
Show »
Length:491
Mass (Da):53,223
Checksum:iE40B8AA667768E87
GO
Isoform C (identifier: P91938-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-88: Missing.
     89-110: QHPHCDRAAMYAQPVRKMSTKG → MLKYMICAIVVGAKKSTSSKYN

Show »
Length:508
Mass (Da):55,114
Checksum:iF34F360FD31FA197
GO
Isoform D (identifier: P91938-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-105: Missing.

Note: Produced by alternative initiation at Met-106 of isoform B.
Show »
Length:491
Mass (Da):53,201
Checksum:i567BE40B2DA226DF
GO

Sequence cautioni

The sequence AAK93067 differs from that shown. Chimeric cDNA. Chimeric cDNA originating from chromosomes X and 3.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti88F → L in AAK93067 (PubMed:12537569).Curated1
Sequence conflicti134V → S in AAB48441 (PubMed:9056265).Curated1
Sequence conflicti151Missing in AAB48441 (PubMed:9056265).Curated1
Sequence conflicti189 – 190Missing in AAB48441 (PubMed:9056265).Curated2
Sequence conflicti195E → D in AAB48441 (PubMed:9056265).Curated1
Sequence conflicti195E → D in AAK93067 (PubMed:12537569).Curated1
Sequence conflicti203 – 207KLVQS → RLCAV in AAB48441 (PubMed:9056265).Curated5
Sequence conflicti213 – 216KSVN → SRH in AAB48441 (PubMed:9056265).Curated4
Sequence conflicti220R → V in AAB48441 (PubMed:9056265).Curated1
Sequence conflicti239 – 247DSHTLLAKL → TRTHCCPSM in AAB48441 (PubMed:9056265).Curated9
Sequence conflicti264Missing in AAB48441 (PubMed:9056265).Curated1
Sequence conflicti276 – 280VEYGI → AEIGT in AAB48441 (PubMed:9056265).Curated5
Sequence conflicti292Missing in AAB48441 (PubMed:9056265).Curated1
Sequence conflicti317 – 318EP → G in AAB48441 (PubMed:9056265).Curated2
Sequence conflicti351 – 386RKTVP…VYDTV → ADVDRCREADDAAAREYRLT QIRFTTSHHR in AAB48441 (PubMed:9056265).CuratedAdd BLAST36
Sequence conflicti379A → S in AAK93067 (PubMed:12537569).Curated1
Sequence conflicti396 – 398VDD → CDS in AAB48441 (PubMed:9056265).Curated3
Sequence conflicti403 – 406NAGV → MPAL in AAB48441 (PubMed:9056265).Curated4
Sequence conflicti424 – 425AN → PH in AAB48441 (PubMed:9056265).Curated2
Sequence conflicti455Y → F in AAB48441 (PubMed:9056265).Curated1
Sequence conflicti461R → S in AAB48441 (PubMed:9056265).Curated1
Sequence conflicti473 – 483TPLEYACVGLS → SWSTSASGLA in AAB48441 (PubMed:9056265).CuratedAdd BLAST11
Sequence conflicti488 – 495VKQFGADE → SSSSEPR in AAB48441 (PubMed:9056265).Curated8
Sequence conflicti559 – 560IN → L in AAB48441 (PubMed:9056265).Curated2
Sequence conflicti583K → KP in AAB48441 (PubMed:9056265).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0055721 – 105Missing in isoform A and isoform D. 3 PublicationsAdd BLAST105
Alternative sequenceiVSP_0055711 – 88Missing in isoform C. 1 PublicationAdd BLAST88
Alternative sequenceiVSP_00557389 – 110QHPHC…MSTKG → MLKYMICAIVVGAKKSTSSK YN in isoform C. 1 PublicationAdd BLAST22
Alternative sequenceiVSP_005574106 – 110MSTKG → MAPVQ in isoform A. 3 Publications5

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U81995 mRNA. Translation: AAB48441.1.
AF301145 mRNA. Translation: AAG25640.1.
AF301144 mRNA. Translation: AAG25639.1.
AE014298 Genomic DNA. Translation: AAF46354.1.
AE014298 Genomic DNA. Translation: AAF46355.2.
AE014298 Genomic DNA. Translation: AAN09228.1.
BT003266 mRNA. Translation: AAO25023.1.
BT025070 mRNA. Translation: ABE73241.1.
AY051643 mRNA. Translation: AAK93067.1. Sequence problems.
RefSeqiNP_511082.2. NM_078527.3. [P91938-2]
NP_727251.1. NM_167149.2. [P91938-1]
NP_727252.1. NM_167150.2. [P91938-3]
UniGeneiDm.20991.

Genome annotation databases

EnsemblMetazoaiFBtr0071168; FBpp0071116; FBgn0020653. [P91938-1]
GeneIDi31760.
KEGGidme:Dmel_CG2151.

Keywords - Coding sequence diversityi

Alternative initiation, Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U81995 mRNA. Translation: AAB48441.1.
AF301145 mRNA. Translation: AAG25640.1.
AF301144 mRNA. Translation: AAG25639.1.
AE014298 Genomic DNA. Translation: AAF46354.1.
AE014298 Genomic DNA. Translation: AAF46355.2.
AE014298 Genomic DNA. Translation: AAN09228.1.
BT003266 mRNA. Translation: AAO25023.1.
BT025070 mRNA. Translation: ABE73241.1.
AY051643 mRNA. Translation: AAK93067.1. Sequence problems.
RefSeqiNP_511082.2. NM_078527.3. [P91938-2]
NP_727251.1. NM_167149.2. [P91938-1]
NP_727252.1. NM_167150.2. [P91938-3]
UniGeneiDm.20991.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2NVKX-ray2.40X111-593[»]
3DGHX-ray1.75A/B111-588[»]
3DH9X-ray2.25A/B111-591[»]
ProteinModelPortaliP91938.
SMRiP91938.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi58221. 32 interactors.
DIPiDIP-19145N.
IntActiP91938. 12 interactors.
MINTiMINT-916376.
STRINGi7227.FBpp0071116.

Proteomic databases

PaxDbiP91938.
PRIDEiP91938.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsemblMetazoaiFBtr0071168; FBpp0071116; FBgn0020653. [P91938-1]
GeneIDi31760.
KEGGidme:Dmel_CG2151.

Organism-specific databases

CTDi31760.
FlyBaseiFBgn0020653. Trxr-1.

Phylogenomic databases

eggNOGiKOG0405. Eukaryota.
COG1249. LUCA.
GeneTreeiENSGT00390000007578.
InParanoidiP91938.
KOiK00384.
OMAiEIEVFHG.
OrthoDBiEOG091G03IU.
PhylomeDBiP91938.

Enzyme and pathway databases

BRENDAi1.8.1.9. 1994.
ReactomeiR-DME-3299685. Detoxification of Reactive Oxygen Species.

Miscellaneous databases

ChiTaRSiTrxr-1. fly.
EvolutionaryTraceiP91938.
GenomeRNAii31760.
PROiP91938.

Gene expression databases

BgeeiFBgn0020653.
GenevisibleiP91938. DM.

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 nameiTRXR1_DROME
AccessioniPrimary (citable) accession number: P91938
Secondary accession number(s): Q1RKZ0
, Q53YG2, Q961E3, Q9W3H2, Q9W3H3
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: January 27, 2003
Last modified: November 2, 2016
This is version 169 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programDrosophila annotation project

Miscellaneousi

Miscellaneous

The active site is a redox-active disulfide bond.

Caution

Was originally thought to be a glutathione reductase.1 Publication

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Drosophila
    Drosophila: entries, gene names and cross-references to FlyBase
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. 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.