Thioredoxin reductase 1, cytoplasmic

Details

Name
Thioredoxin reductase 1, cytoplasmic
Synonyms
  • 1.8.1.9
  • Gene associated with retinoic and IFN-induced mortality 12 protein
  • Gene associated with retinoic and interferon-induced mortality 12 protein
  • GRIM-12
  • GRIM12
  • KDRF
  • KM-102-derived reductase-like factor
  • Thioredoxin reductase TR1
  • TR
Gene Name
TXNRD1
Organism
Humans
Amino acid sequence
>lcl|BSEQ0037154|Thioredoxin reductase 1, cytoplasmic
MGCAEGKAVAAAAPTELQTKGKNGDGRRRSAKDHHPGKTLPENPAGFTSTATADSRALLQ
AYIDGHSVVIFSRSTCTRCTEVKKLFKSLCVPYFVLELDQTEDGRALEGTLSELAAETDL
PVVFVKQRKIGGHGPTLKAYQEGRLQKLLKMNGPEDLPKSYDYDLIIIGGGSGGLAAAKE
AAQYGKKVMVLDFVTPTPLGTRWGLGGTCVNVGCIPKKLMHQAALLGQALQDSRNYGWKV
EETVKHDWDRMIEAVQNHIGSLNWGYRVALREKKVVYENAYGQFIGPHRIKATNNKGKEK
IYSAERFLIATGERPRYLGIPGDKEYCISSDDLFSLPYCPGKTLVVGASYVALECAGFLA
GIGLDVTVMVRSILLRGFDQDMANKIGEHMEEHGIKFIRQFVPIKVEQIEAGTPGRLRVV
AQSTNSEEIIEGEYNTVMLAIGRDACTRKIGLETVGVKINEKTGKIPVTDEEQTNVPYIY
AIGDILEDKVELTPVAIQAGRLLAQRLYAGSTVKCDYENVPTTVFTPLEYGACGLSEEKA
VEKFGEENIEVYHSYFWPLEWTIPSRDNNKCYAKIICNTKDNERVVGFHVLGPNAGEVTQ
GFAAALKCGLTKKQLDSTIGIHPVCAEVFTTLSVTKRSGASILQAGCUG
Number of residues
649
Molecular Weight
70905.58
Theoretical pI
6.43
GO Classification
Functions
electron carrier activity / flavin adenine dinucleotide binding / protein disulfide oxidoreductase activity / thioredoxin-disulfide reductase activity
Processes
cell proliferation / cell redox homeostasis / cellular lipid metabolic process / gene expression / mesoderm formation / nucleobase-containing small molecule interconversion / nucleobase-containing small molecule metabolic process / response to reactive oxygen species / signal transduction / small molecule metabolic process / transcription initiation from RNA polymerase II promoter
Components
cytosol / extracellular exosome / mitochondrion / nucleus
General Function
Thioredoxin-disulfide reductase activity
Specific Function
Isoform 1 may possess glutaredoxin activity as well as thioredoxin reductase activity and induces actin and tubulin polymerization, leading to formation of cell membrane protrusions. Isoform 4 enhances the transcriptional activity of estrogen receptors alpha and beta while isoform 5 enhances the transcriptional activity of the beta receptor only. Isoform 5 also mediates cell death induced by a combination of interferon-beta and retinoic acid.
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Cytoplasm
Gene sequence
>lcl|BSEQ0020576|Thioredoxin reductase 1, cytoplasmic (TXNRD1)
ATGGGCTGCGCCGAGGGCAAGGCAGTGGCGGCGGCCGCCCCAACGGAGCTGCAGACGAAA
GGCAAGAACGGCGATGGCCGCCGTAGGTCAGCTAAAGATCATCACCCTGGTAAAACTTTG
CCAGAGAACCCAGCAGGATTCACCAGCACGGCCACTGCAGACTCCAGAGCCCTGCTTCAG
GCCTATATAGATGGTCACTCTGTGGTCATCTTCAGTAGGTCCACATGCACACGCTGTACT
GAGGTAAAGAAGTTATTTAAATCTCTGTGTGTTCCTTATTTTGTGCTTGAACTTGATCAA
ACAGAGGACGGTCGGGCCCTGGAAGGAACGCTCTCGGAATTGGCCGCGGAAACCGATCTG
CCCGTTGTGTTTGTGAAACAGAGAAAGATAGGCGGCCATGGTCCAACCTTGAAGGCTTAT
CAGGAGGGCAGACTTCAAAAGCTACTAAAAATGAACGGCCCTGAAGATCTTCCCAAGTCC
TATGACTATGACCTTATCATCATTGGAGGTGGCTCAGGAGGTCTGGCAGCTGCTAAGGAG
GCAGCCCAATATGGCAAGAAGGTGATGGTCCTGGACTTTGTCACTCCCACCCCTCTTGGA
ACTAGATGGGGTCTCGGAGGAACATGTGTGAATGTGGGTTGCATACCTAAAAAACTGATG
CATCAAGCAGCTTTGTTAGGACAAGCCCTGCAAGACTCTCGAAATTATGGATGGAAAGTC
GAGGAGACAGTTAAGCATGATTGGGACAGAATGATAGAAGCTGTACAGAATCACATTGGC
TCTTTGAATTGGGGCTACCGAGTAGCTCTGCGGGAGAAAAAAGTCGTCTATGAGAATGCT
TATGGGCAATTTATTGGTCCTCACAGGATTAAGGCAACAAATAATAAAGGCAAAGAAAAA
ATTTATTCAGCAGAGAGATTTCTCATTGCCACTGGTGAAAGACCACGTTACTTGGGCATC
CCTGGTGACAAAGAATACTGCATCAGCAGTGATGATCTTTTCTCCTTGCCTTACTGCCCG
GGTAAGACCCTGGTTGTTGGAGCATCCTATGTCGCTTTGGAGTGCGCTGGATTTCTTGCT
GGTATTGGTTTAGACGTCACTGTTATGGTTAGGTCCATTCTTCTTAGAGGATTTGACCAG
GACATGGCCAACAAAATTGGTGAACACATGGAAGAACATGGCATCAAGTTTATAAGACAG
TTCGTACCAATTAAAGTTGAACAAATTGAAGCAGGGACACCAGGCCGACTCAGAGTAGTA
GCTCAGTCCACCAATAGTGAGGAAATCATTGAAGGAGAATATAATACGGTGATGCTGGCA
ATAGGAAGAGATGCTTGCACAAGAAAAATTGGCTTAGAAACCGTAGGGGTGAAGATAAAT
GAAAAGACTGGAAAAATACCTGTCACAGATGAAGAACAGACCAATGTGCCTTACATCTAT
GCCATTGGCGATATATTGGAGGATAAGGTGGAGCTCACCCCAGTTGCAATCCAGGCAGGA
AGATTGCTGGCTCAGAGGCTCTATGCAGGTTCCACTGTCAAGTGTGACTATGAAAATGTT
CCAACCACTGTATTTACTCCTTTGGAATATGGTGCTTGTGGCCTTTCTGAGGAGAAAGCT
GTGGAGAAGTTTGGGGAAGAAAATATTGAGGTTTACCATAGTTACTTTTGGCCATTGGAA
TGGACGATTCCGTCAAGAGATAACAACAAATGTTATGCAAAAATAATCTGTAATACTAAA
GACAATGAACGTGTTGTGGGCTTTCACGTACTGGGTCCAAATGCTGGAGAAGTTACACAA
GGCTTTGCAGCTGCGCTCAAATGTGGACTGACCAAAAAGCAGCTGGACAGCACAATTGGA
ATCCACCCTGTCTGTGCAGAGGTATTCACAACATTGTCTGTGACCAAGCGCTCTGGGGCA
AGCATCCTCCAGGCTGGCTGCTGAGGTTAA
Chromosome Location
12
Locus
12q23-q24.1
External Identifiers
ResourceLink
UniProtKB IDQ16881
UniProtKB Entry NameTRXR1_HUMAN
GenBank Protein ID1237038
GenBank Gene IDX91247
GenAtlas IDTXNRD1
HGNC IDHGNC:12437
General References
  1. Gasdaska PY, Gasdaska JR, Cochran S, Powis G: Cloning and sequencing of a human thioredoxin reductase. FEBS Lett. 1995 Oct 2;373(1):5-9. [Article]
  2. Koishi R, Kawashima I, Yoshimura C, Sugawara M, Serizawa N: Cloning and characterization of a novel oxidoreductase KDRF from a human bone marrow-derived stromal cell line KM-102. J Biol Chem. 1997 Jan 24;272(4):2570-7. [Article]
  3. Hofmann ER, Boyanapalli M, Lindner DJ, Weihua X, Hassel BA, Jagus R, Gutierrez PL, Kalvakolanu DV: Thioredoxin reductase mediates cell death effects of the combination of beta interferon and retinoic acid. Mol Cell Biol. 1998 Nov;18(11):6493-504. [Article]
  4. Rundlof AK, Janard M, Miranda-Vizuete A, Arner ES: Evidence for intriguingly complex transcription of human thioredoxin reductase 1. Free Radic Biol Med. 2004 Mar 1;36(5):641-56. [Article]
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  7. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [Article]
  8. Gladyshev VN, Jeang KT, Stadtman TC: Selenocysteine, identified as the penultimate C-terminal residue in human T-cell thioredoxin reductase, corresponds to TGA in the human placental gene. Proc Natl Acad Sci U S A. 1996 Jun 11;93(12):6146-51. [Article]
  9. Tamura T, Stadtman TC: A new selenoprotein from human lung adenocarcinoma cells: purification, properties, and thioredoxin reductase activity. Proc Natl Acad Sci U S A. 1996 Feb 6;93(3):1006-11. [Article]
  10. Su D, Gladyshev VN: Alternative splicing involving the thioredoxin reductase module in mammals: a glutaredoxin-containing thioredoxin reductase 1. Biochemistry. 2004 Sep 28;43(38):12177-88. [Article]
  11. Damdimopoulos AE, Miranda-Vizuete A, Treuter E, Gustafsson JA, Spyrou G: An alternative splicing variant of the selenoprotein thioredoxin reductase is a modulator of estrogen signaling. J Biol Chem. 2004 Sep 10;279(37):38721-9. Epub 2004 Jun 14. [Article]
  12. Rush J, Moritz A, Lee KA, Guo A, Goss VL, Spek EJ, Zhang H, Zha XM, Polakiewicz RD, Comb MJ: Immunoaffinity profiling of tyrosine phosphorylation in cancer cells. Nat Biotechnol. 2005 Jan;23(1):94-101. Epub 2004 Dec 12. [Article]
  13. Wong JJ, Pung YF, Sze NS, Chin KC: HERC5 is an IFN-induced HECT-type E3 protein ligase that mediates type I IFN-induced ISGylation of protein targets. Proc Natl Acad Sci U S A. 2006 Jul 11;103(28):10735-40. Epub 2006 Jun 30. [Article]
  14. Dammeyer P, Damdimopoulos AE, Nordman T, Jimenez A, Miranda-Vizuete A, Arner ES: Induction of cell membrane protrusions by the N-terminal glutaredoxin domain of a rare splice variant of human thioredoxin reductase 1. J Biol Chem. 2008 Feb 1;283(5):2814-21. Epub 2007 Nov 27. [Article]
  15. Gauci S, Helbig AO, Slijper M, Krijgsveld J, Heck AJ, Mohammed S: Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach. Anal Chem. 2009 Jun 1;81(11):4493-501. doi: 10.1021/ac9004309. [Article]
  16. Mayya V, Lundgren DH, Hwang SI, Rezaul K, Wu L, Eng JK, Rodionov V, Han DK: Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions. Sci Signal. 2009 Aug 18;2(84):ra46. doi: 10.1126/scisignal.2000007. [Article]
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  19. Fritz-Wolf K, Urig S, Becker K: The structure of human thioredoxin reductase 1 provides insights into C-terminal rearrangements during catalysis. J Mol Biol. 2007 Jun 29;370(1):116-27. Epub 2007 Apr 24. [Article]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB02338NADPHexperimentalunknownDetails
DB03147Flavin adenine dinucleotideapprovedunknownDetails
DB03566SpermidineexperimentalunknownDetails
DB04106FotemustineinvestigationalunknownDetails
DB05428Motexafin gadoliniuminvestigationalunknownDetails
DB05448PX-12investigationalunknownDetails
DB01169Arsenic trioxideapproved, investigationalyesinhibitorDetails
DB11135Seleniumapproved, investigational, vet_approvednosubstrateDetails
DB11127Selenious acidapproved, investigationalunknownsubstrateDetails
DB00126Ascorbic acidapproved, nutraceuticalunknownsubstrateDetails