| IED ID | IndEnz0018001480 |
| Enzyme Type ID | peroxidase001480 |
| Protein Name |
Thioredoxin reductase 1, cytoplasmic TR EC 1.8.1.9 Gene associated with retinoic and interferon-induced mortality 12 protein GRIM-12 Gene associated with retinoic and IFN-induced mortality 12 protein KM-102-derived reductase-like factor Peroxidase TXNRD1 EC 1.11.1.2 Thioredoxin reductase TR1 |
| Gene Name | TXNRD1 GRIM12 KDRF |
| Organism | Homo sapiens (Human) |
| 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 Primates Haplorrhini Simiiformes Catarrhini Hominoidea (apes) Hominidae (great apes) Homininae Homo Homo sapiens (Human) |
| Enzyme Sequence | MGCAEGKAVAAAAPTELQTKGKNGDGRRRSAKDHHPGKTLPENPAGFTSTATADSRALLQAYIDGHSVVIFSRSTCTRCTEVKKLFKSLCVPYFVLELDQTEDGRALEGTLSELAAETDLPVVFVKQRKIGGHGPTLKAYQEGRLQKLLKMNGPEDLPKSYDYDLIIIGGGSGGLAAAKEAAQYGKKVMVLDFVTPTPLGTRWGLGGTCVNVGCIPKKLMHQAALLGQALQDSRNYGWKVEETVKHDWDRMIEAVQNHIGSLNWGYRVALREKKVVYENAYGQFIGPHRIKATNNKGKEKIYSAERFLIATGERPRYLGIPGDKEYCISSDDLFSLPYCPGKTLVVGASYVALECAGFLAGIGLDVTVMVRSILLRGFDQDMANKIGEHMEEHGIKFIRQFVPIKVEQIEAGTPGRLRVVAQSTNSEEIIEGEYNTVMLAIGRDACTRKIGLETVGVKINEKTGKIPVTDEEQTNVPYIYAIGDILEDKVELTPVAIQAGRLLAQRLYAGSTVKCDYENVPTTVFTPLEYGACGLSEEKAVEKFGEENIEVYHSYFWPLEWTIPSRDNNKCYAKIICNTKDNERVVGFHVLGPNAGEVTQGFAAALKCGLTKKQLDSTIGIHPVCAEVFTTLSVTKRSGASILQAGCUG |
| Enzyme Length | 649 |
| Uniprot Accession Number | Q16881 |
| Absorption | |
| Active Site | ACT_SITE 622; /note=Proton acceptor; /evidence=ECO:0000250 |
| Activity Regulation | |
| Binding Site | BINDING 311; /note="FAD"; /evidence="ECO:0007744|PDB:2J3N"; BINDING 316; /note="NADP"; /evidence="ECO:0000269|PubMed:17512005, ECO:0007744|PDB:2J3N"; BINDING 350; /note="FAD"; /evidence="ECO:0007744|PDB:2ZZ0, ECO:0007744|PDB:2ZZB, ECO:0007744|PDB:3QFA"; BINDING 376; /note="NADP"; /evidence="ECO:0000250|UniProtKB:O89049"; BINDING 465; /note="NADP"; /evidence="ECO:0000269|PubMed:17512005, ECO:0007744|PDB:2J3N"; BINDING 484; /note="FAD"; /evidence="ECO:0000269|PubMed:17512005, ECO:0007744|PDB:2J3N"; BINDING 491; /note="NADP"; /evidence="ECO:0007744|PDB:2J3N"; BINDING 622; /note="FAD; via carbonyl oxygen"; /evidence="ECO:0000269|PubMed:17512005, ECO:0007744|PDB:2J3N" |
| 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:8577704};PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:20347; Evidence={ECO:0000305|PubMed:8577704}; 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 (PubMed:8577704). 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 (Probable). Also has reductase activity on hydrogen peroxide (H2O2) (PubMed:10849437). {ECO:0000269|PubMed:10849437, ECO:0000269|PubMed:8577704, ECO:0000305|PubMed:17512005}.; FUNCTION: [Isoform 1]: Induces actin and tubulin polymerization, leading to formation of cell membrane protrusions. {ECO:0000269|PubMed:18042542, ECO:0000269|PubMed:8577704}.; FUNCTION: [Isoform 4]: Enhances the transcriptional activity of estrogen receptors ESR1 and ESR2. {ECO:0000269|PubMed:15199063}.; FUNCTION: [Isoform 5]: Enhances the transcriptional activity of the estrogen receptor ESR2 only (PubMed:15199063). Mediates cell death induced by a combination of interferon-beta and retinoic acid (PubMed:9774665). {ECO:0000269|PubMed:15199063, ECO:0000269|PubMed:9774665}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | NP_BIND 172..173; /note="FAD"; /evidence="ECO:0000269|PubMed:17512005, ECO:0007744|PDB:2J3N"; NP_BIND 192..193; /note="FAD"; /evidence="ECO:0000269|PubMed:17512005, ECO:0007744|PDB:2J3N"; NP_BIND 208..209; /note="FAD"; /evidence="ECO:0000269|PubMed:17512005, ECO:0007744|PDB:2J3N"; NP_BIND 213..217; /note="FAD"; /evidence="ECO:0000269|PubMed:17512005, ECO:0007744|PDB:2J3N"; NP_BIND 281..282; /note="FAD"; /evidence="ECO:0000269|PubMed:17512005, ECO:0007744|PDB:2J3N"; NP_BIND 348..354; /note="NADP"; /evidence="ECO:0000269|PubMed:17512005, ECO:0007744|PDB:2J3N"; NP_BIND 371..372; /note="NADP"; /evidence="ECO:0000269|PubMed:17512005, ECO:0007744|PDB:2J3N"; NP_BIND 376..378; /note="NADP"; /evidence="ECO:0000269|PubMed:17512005, ECO:0007744|PDB:2J3N"; NP_BIND 442..443; /note="NADP"; /evidence="ECO:0000269|PubMed:17512005, ECO:0007744|PDB:2J3N"; NP_BIND 491..493; /note="FAD"; /evidence="ECO:0000269|PubMed:17512005, ECO:0007744|PDB:2J3N" |
| Features | Active site (1); Alternative sequence (9); Beta strand (24); Binding site (8); Chain (1); Compositional bias (1); Cross-link (1); Disulfide bond (1); Domain (1); Erroneous termination (13); Helix (16); Modified residue (3); Natural variant (1); Non-standard residue (1); Nucleotide binding (10); Region (2); Sequence conflict (15); Turn (8) |
| Keywords | 3D-structure;Acetylation;Alternative splicing;Cytoplasm;Direct protein sequencing;Disulfide bond;Electron transport;FAD;Flavoprotein;NADP;Nucleus;Oxidoreductase;Phosphoprotein;Redox-active center;Reference proteome;Selenocysteine;Transport;Ubl conjugation |
| Interact With | Q03135; P03372; Q92731 |
| Induction | INDUCTION: [Isoform 1]: Induced by estradiol or testosterone in HeLa cells. {ECO:0000269|PubMed:18042542}.; INDUCTION: [Isoform 5]: Induced by a combination of interferon-beta and retinoic acid (at protein level). {ECO:0000269|PubMed:9774665}. |
| Subcellular Location | SUBCELLULAR LOCATION: [Isoform 1]: Cytoplasm {ECO:0000269|PubMed:18042542}.; SUBCELLULAR LOCATION: [Isoform 4]: Cytoplasm {ECO:0000269|PubMed:15199063}. Nucleus {ECO:0000269|PubMed:15199063}.; SUBCELLULAR LOCATION: [Isoform 5]: Cytoplasm {ECO:0000269|PubMed:15199063}. |
| Modified Residue | MOD_RES 218; /note="N6-succinyllysine"; /evidence="ECO:0000250|UniProtKB:Q9JMH6"; MOD_RES 281; /note="Phosphotyrosine"; /evidence="ECO:0007744|PubMed:15592455"; MOD_RES Q16881-5:1; /note="N-acetylmethionine"; /evidence="ECO:0007744|PubMed:19413330, ECO:0007744|PubMed:22223895" |
| Post Translational Modification | PTM: [Isoform 5]: The N-terminus is blocked.; PTM: ISGylated. {ECO:0000305|PubMed:16815975}. |
| Signal Peptide | |
| Structure 3D | X-ray crystallography (7) |
| Cross Reference PDB | 2CFY; 2J3N; 2ZZ0; 2ZZB; 2ZZC; 3QFA; 3QFB; |
| Mapped Pubmed ID | 10455115; 11782468; 11953436; 12214272; 12435734; 12506115; 12574159; 12668662; 12949356; 1321713; 13679440; 15123685; 15183196; 15824742; 15879598; 16169070; 16424062; 16481328; 16750198; 16868544; 16977661; 17234762; 17382897; 17601350; 17634480; 18163424; 18187038; 18267104; 18382651; 18483336; 18977241; 18996185; 19020731; 19059456; 19124506; 19525010; 19555664; 19595745; 19620238; 19654027; 19710929; 19766715; 19820694; 19896490; 20160040; 20460467; 20536427; 20584310; 20711500; 20877624; 20920480; 21172426; 21206984; 21593104; 21750537; 21988832; 22069710; 22977247; 23063346; 23223577; 23413027; 23512591; 24407164; 24583460; 24624337; 24778250; 24853413; 25179160; 25343990; 25391969; 25495870; 25576832; 25592259; 26064428; 26117319; 26184858; 26464515; 26698667; 26743692; 26760912; 26871773; 26898501; 27002142; 27233942; 27346647; 27377780; 27381867; 27667125; 27706680; 28093500; 28218611; 28232204; 28249720; 28471109; 28536696; 28551108; 28653098; 28688915; 28774816; 29117711; 29305108; 29327078; 30561826; 30880248; 31113439; 31176737; 31359011; 31367013; 31601260; 31649256; 31836775; 32142958; 32284348; 32418115; 32596335; 33115246; 33167092; 33345387; 33455417; 34553295; 34673143; 34688818; |
| Motif | |
| Gene Encoded By | |
| Mass | 70,906 |
| Kinetics | BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=2.5 mM for H202 {ECO:0000269|PubMed:10849437}; Note=kcat is 100 min(-1) with H2O2 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; |