| IED ID | IndEnz0018001625 |
| Enzyme Type ID | peroxidase001625 |
| Protein Name |
Thioredoxin reductase 1, cytoplasmic TR EC 1.8.1.9 NADPH-dependent thioredoxin reductase Peroxidase TXNRD1 EC 1.11.1.2 Thioredoxin reductase TR1 |
| Gene Name | Txnrd1 Trxr1 |
| Organism | Rattus norvegicus (Rat) |
| Taxonomic Lineage | cellular organisms Eukaryota Opisthokonta Metazoa Eumetazoa Bilateria Deuterostomia Chordata Craniata Vertebrata Gnathostomata (jawed vertebrates) Teleostomi Euteleostomi Sarcopterygii Dipnotetrapodomorpha Tetrapoda Amniota Mammalia Theria Eutheria Boreoeutheria Euarchontoglires Glires (Rodents and rabbits) Rodentia Myomorpha (mice and others) Muroidea Muridae Murinae Rattus Rattus norvegicus (Rat) |
| Enzyme Sequence | MNDSKDAPKSYDFDLIIIGGGSGGLAAAKEAAKFDKKVMVLDFVTPTPLGTRWGLGGTCVNVGCIPKKLMHQAALLGQALKDSRNYGWKLEDTVKHDWEKMTESVQNHIGSLNWGYRVALREKKVVYENAYGKFIGPHKIMATNNKGKEKVYSAERFLIATGERPRYLGIPGDKEYCISSDDLFSLPYCPGKTLVVGASYVALECAGFLAGIGLDVTVMVRSILLRGFDQDMANKIGEHMEEHGIKFIRQFVPTKIEQIEAGTPGRLKVTAKSTNSEETIEDEFNTVLLAVGRDSCTRTIGLETVGVKINEKTGKIPVTDEEQTNVPYIYAIGDILEGKLELTPVAIQAGRLLAQRLYGGSTVKCDYDNVPTTVFTPLEYGCCGLSEEKAVEKFGEENIEVYHSFFWPLEWTVPSRDNNKCYAKVICNLKDNERVVGFHVLGPNAGEVTQGFAAALKCGLTKQQLDSTIGIHPVCAEIFTTLSVTKRSGGDILQSGCUG |
| Enzyme Length | 499 |
| Uniprot Accession Number | O89049 |
| Absorption | |
| Active Site | ACT_SITE 472; /note=Proton acceptor |
| Activity Regulation | |
| Binding Site | BINDING 161; /note=FAD; /evidence=ECO:0007744|PDB:1H6V; BINDING 166; /note=NADP; /evidence=ECO:0007744|PDB:1H6V; BINDING 200; /note=FAD; /evidence=ECO:0000250|UniProtKB:Q16881; BINDING 226; /note=NADP; /evidence=ECO:0007744|PDB:1H6V; BINDING 315; /note=NADP; /evidence=ECO:0000250|UniProtKB:Q16881; BINDING 334; /note=FAD; /evidence=ECO:0007744|PDB:1H6V; BINDING 341; /note=NADP; /evidence=ECO:0007744|PDB:1H6V; BINDING 472; /note=FAD; via carbonyl oxygen; /evidence=ECO:0007744|PDB:1H6V |
| Calcium Binding | |
| catalytic Activity | CATALYTIC ACTIVITY: Reaction=[thioredoxin]-dithiol + NADP(+) = [thioredoxin]-disulfide + H(+) + NADPH; Xref=Rhea:RHEA:20345, Rhea:RHEA-COMP:10698, Rhea:RHEA-COMP:10700, ChEBI:CHEBI:15378, ChEBI:CHEBI:29950, ChEBI:CHEBI:50058, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; EC=1.8.1.9; Evidence={ECO:0000269|PubMed:10849437};PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:20347; Evidence={ECO:0000269|PubMed:10849437}; CATALYTIC ACTIVITY: Reaction=H(+) + H2O2 + NADPH = 2 H2O + NADP(+); Xref=Rhea:RHEA:15173, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:16240, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; EC=1.11.1.2; Evidence={ECO:0000269|PubMed:10849437};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:15174; Evidence={ECO:0000305|PubMed:10849437}; |
| DNA Binding | |
| EC Number | 1.8.1.9; 1.11.1.2 |
| Enzyme Function | FUNCTION: Reduces disulfideprotein thioredoxin (Trx) to its dithiol-containing form. Homodimeric flavoprotein involved in the regulation of cellular redox reactions, growth and differentiation. Contains a selenocysteine residue at the C-terminal active site that is essential for catalysis (PubMed:10849437). Also has reductase activity on hydrogen peroxide (H2O2) (PubMed:10849437). {ECO:0000269|PubMed:10849437}. |
| Temperature Dependency | |
| PH Dependency | BIOPHYSICOCHEMICAL PROPERTIES: pH dependence: Optimum pH is 7.5. {ECO:0000269|PubMed:10849437}; |
| Pathway | |
| nucleotide Binding | NP_BIND 18..23; /note=FAD; /evidence=ECO:0007744|PDB:1H6V; NP_BIND 42..43; /note=FAD; /evidence=ECO:0007744|PDB:1H6V; NP_BIND 58..59; /note=FAD; /evidence=ECO:0000250|UniProtKB:Q16881; NP_BIND 63..67; /note=FAD; /evidence=ECO:0007744|PDB:1H6V; NP_BIND 131..132; /note=FAD; /evidence=ECO:0007744|PDB:1H6V; NP_BIND 198..204; /note=NADP; /evidence=ECO:0007744|PDB:1H6V; NP_BIND 221..222; /note=NADP; /evidence=ECO:0007744|PDB:1H6V; NP_BIND 226..228; /note=NADP; /evidence=ECO:0000250|UniProtKB:Q16881; NP_BIND 291..293; /note=NADP; /evidence=ECO:0007744|PDB:1H6V; NP_BIND 341..343; /note=FAD; /evidence=ECO:0007744|PDB:1H6V |
| Features | Active site (1); Beta strand (22); Binding site (8); Chain (1); Cross-link (1); Disulfide bond (1); Erroneous initiation (1); Erroneous termination (1); Helix (18); Modified residue (2); Mutagenesis (2); Non-standard residue (1); Nucleotide binding (10); Sequence conflict (6); Turn (4) |
| Keywords | 3D-structure;Cytoplasm;Direct protein sequencing;Disulfide bond;FAD;Flavoprotein;NADP;Oxidoreductase;Phosphoprotein;Redox-active center;Reference proteome;Selenocysteine;Ubl conjugation |
| Interact With | |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q16881}. |
| Modified Residue | MOD_RES 68; /note=N6-succinyllysine; /evidence=ECO:0000250|UniProtKB:Q9JMH6; MOD_RES 131; /note=Phosphotyrosine; /evidence=ECO:0000250|UniProtKB:Q16881 |
| Post Translational Modification | PTM: ISGylated. {ECO:0000250|UniProtKB:Q16881}. |
| Signal Peptide | |
| Structure 3D | X-ray crystallography (4) |
| Cross Reference PDB | 1H6V; 3EAN; 3EAO; 4KPR; |
| Mapped Pubmed ID | 10512699; 10957643; 12435734; 12574159; 14607844; 15792362; 15879598; 15901730; 16481328; 17023680; 17291446; 17394422; 18382651; 18515646; 19054767; 19128823; 19146949; 19351701; 19409971; 19768707; 19781568; 19833109; 20126492; 20345183; 20393169; 20493230; 20524817; 20536427; 20571744; 20620191; 20810785; 21406454; 21505996; 21903721; 22177986; 22377061; 23629660; 23802942; 24853413; 24984066; 25055978; 25611390; 26252619; 28551108; 32867364; 33649852; 9988709; |
| Motif | |
| Gene Encoded By | |
| Mass | 54,670 |
| Kinetics | BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=3.3 uM for thioredoxin {ECO:0000269|PubMed:10849437}; Note=kcat is 2500 min(-1) with thioredoxin as substrate. {ECO:0000269|PubMed:10849437}; |
| Metal Binding | |
| Rhea ID | RHEA:20345; RHEA:20347; RHEA:15173; RHEA:15174 |
| Cross Reference Brenda | 1.8.1.9; |